Transfer of communication skills to the workplace: impact of a 38-hour communication skills training program designed for radiotherapy teams.

PubMed

Merckaert, Isabelle; Delevallez, France; Gibon, Anne-Sophie; Liénard, Aurore; Libert, Yves; Delvaux, Nicole; Marchal, Serge; Etienne, Anne-Marie; Bragard, Isabelle; Reynaert, Christine; Slachmuylder, Jean-Louis; Scalliet, Pierre; Van Houtte, Paul; Coucke, Philippe; Razavi, Darius

2015-03-10

This study assessed the efficacy of a 38-hour communication skills training program designed to train a multidisciplinary radiotherapy team. Four radiotherapy teams were randomly assigned to a training program or a waiting list. Assessments were scheduled at baseline and after training for the training group and at baseline and 4 months later for the waiting list group. Assessments included an audio recording of a radiotherapy planning session to assess team members' communication skills and expression of concerns of patients with breast cancer (analyzed with content analysis software) and an adapted European Organisation for Research and Treatment of Cancer satisfaction with care questionnaire completed by patients at the end of radiotherapy. Two hundred thirty-seven radiotherapy planning sessions were recorded. Compared with members of the untrained teams, members of the trained teams acquired, over time, more assessment skills (P = .003) and more supportive skills (P = .050) and provided more setting information (P = .010). Over time, patients interacting with members of the trained teams asked more open questions (P = .022), expressed more emotional words (P = .025), and exhibited a higher satisfaction level regarding nurses' interventions (P = .028). The 38-hour training program facilitated transfer of team member learned communication skills to the clinical practice and improved patients' satisfaction with care. © 2015 by American Society of Clinical Oncology.

National survey of perspectives of palliative radiation therapy: role, barriers, and needs.

PubMed

McCloskey, Susan A; Tao, May Lin; Rose, Christopher M; Fink, Arlene; Amadeo, Alessandra M

2007-01-01

Despite growth of palliative care programs and evidence on the effectiveness of radiotherapy in palliating cancer symptoms, radiotherapy is probably underused in this setting. Radiation and medical oncologists and palliative medicine specialists were surveyed regarding the perceived role of palliative radiotherapy and barriers to its use. The survey was sent electronically to all physician members of the American Society for Therapeutic Radiology and Oncology (ASTRO) and the American Academy of Hospice and Palliative Medicine (AAHPM) and a random sample of American Society of Clinical Oncology (ASCO) members, with known e-mail addresses. Response rates were 27%, 14% and 26% for ASTRO, ASCO, and AAHPM respondents, respectively. Although most felt radiotherapy is an effective and important option for palliation of some common cancer symptoms, referrals for such therapy may be declining. Most agreed that radiation oncologists should be more involved in palliative care; however, multiple barriers were identified, such as poor reimbursement, emotional burden of care, insufficient training/knowledge, and the sense of unwillingness of others to share delivery of such services. Although multiple barriers limit optimal integration, most agree that there should be greater national and professional society efforts to promote the advancement of radiation oncology in the area of palliative care.

Vitamin D protects keratinocytes from deleterious effects of ionizing radiation.

PubMed

Langberg, M; Rotem, C; Fenig, E; Koren, R; Ravid, A

2009-01-01

Radiotherapy can induce severe skin responses that may limit the clinically acceptable radiation dose. The responses include erythema, dry and moist desquamation, erosions and dermal-epidermal blister formation. These effects reflect injury to, and reproductive failure of, epidermal cells and may also be due to dysregulation of the tissue remodelling process caused by excessive proteolytic activity. Calcitriol, the hormonally active vitamin D metabolite, protects keratinocytes from programmed cell death induced by various noxious stimuli. To examine whether calcitriol protects proliferating keratinocytes from the damage inflicted by ionizing radiation under conditions similar to those employed during radiotherapy. Autonomously proliferating HaCaT keratinocytes, used as a model for basal layer keratinocytes, were irradiated using a linear accelerator. Cell death was monitored by vital staining, executioner caspase activation, lactic dehydrogenase release and colony formation assay. Induction of matrix metalloproteinase-9 was assessed by gelatinase activity assay and mRNA determination. Levels of specific proteins were determined by immunoblotting. Treatment with calcitriol inhibited both caspase-dependent and -independent programmed cell death occurring within 48 h of irradiation and increased the colony formation capacity of irradiated cells. These effects may be attributable to inhibition of the c-Jun NH(2)-terminal kinase cascade and to upregulation of the truncated antiapoptotic isoform of p63. Treatment with the hormone also attenuated radiation-induced increase in matrix metalloproteinase-9 protein and mRNA levels. The results of this study suggest that active vitamin D derivatives may attenuate cell death and excessive proteolytic activity in the epidermis due to exposure to ionizing radiation in the course of radiotherapy.

Is it possible to improve communication around radiotherapy delivery: A randomized study to assess the efficacy of team training?

PubMed

Liénard, Aurore; Delevallez, France; Razavi, Darius; Gibon, Anne-Sophie; Libert, Yves; Delvaux, Nicole; Marchal, Serge; Etienne, Anne-Marie; Bragard, Isabelle; Reynaert, Christine; Slachmuylder, Jean-Louis; Durieux, Jean-François; Farvacques, Christine; Scalliet, Pierre; Van Houtte, Paul; Coucke, Philippe; Merckaert, Isabelle

2016-05-01

The aim of this study was to assess the efficacy of a 38-h communication skills training program designed for multidisciplinary radiotherapy teams. Four radiotherapy teams were randomly assigned to a training program or to a waiting list. Assessments were scheduled at baseline (T1) and then after the training was completed or four months later (T2), respectively. Communication around radiotherapy delivery was assessed based on audio recordings of the first and last radiotherapy sessions in order to assess team members' communication skills and the expression of concerns by breast cancer patients (analyzed with content analysis software LaComm). 198 radiotherapy sessions were recorded. During the first radiotherapy sessions, members of the trained teams exhibited more assessment skills (p=0.048), provided more setting information (p<0.001), and used more social words (p=0.019) compared to the members of the untrained teams. During the last radiotherapy session, members of the trained teams used more assessment skills (p=0.004) and patients interacting with members of the trained teams expressed more sadness words (p=0.023). Training of multidisciplinary teams has the potential to transfer skills that affect the short exchanges that take place around radiotherapy delivery. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Seizure control following radiotherapy in patients with diffuse gliomas: a retrospective study

PubMed Central

Rudà, Roberta; Magliola, Umberto; Bertero, Luca; Trevisan, Elisa; Bosa, Chiara; Mantovani, Cristina; Ricardi, Umberto; Castiglione, Anna; Monagheddu, Chiara; Soffietti, Riccardo

2013-01-01

Background Little information is available regarding the effect of conventional radiotherapy on glioma-related seizures. Methods In this retrospective study, we analyzed the seizure response and outcome following conventional radiotherapy in a cohort of 43 patients with glioma (33 grade II, 10 grade III) and medically intractable epilepsy. Results At 3 months after radiotherapy, seizure reduction was significant (≥50% reduction of frequency compared with baseline) in 31/43 patients (72%) of the whole series and in 25/33 patients (76%) with grade II gliomas, whereas at 12 months seizure reduction was significant in 26/34 (76%) and in 19/25 (76%) patients, respectively. Seizure reduction was observed more often among patients displaying an objective tumor response on MRI, but patients with no change on MRI also had a significant seizure reduction. Seizure freedom (Engel class I) was achieved at 12 months in 32% of all patients and in 38% of patients with grade II tumors. Timing of radiotherapy and duration of seizures prior to radiotherapy were significantly associated with seizure reduction. Conclusions This study showed that a high proportion of patients with medically intractable epilepsy from diffuse gliomas derive a significant and durable benefit from radiotherapy in terms of epilepsy control and that this positive effect is not strictly associated with tumor shrinkage as shown on MRI. Radiotherapy at tumor progression seems as effective as early radiotherapy after surgery. Prospective studies must confirm and better characterize the response to radiotherapy. PMID:23897633

Speech-language therapy program for mouth opening in patients with oral and oropharyngeal cancer undergoing adjuvant radiotherapy: a pilot study.

PubMed

Marrafon, Caroline Somera; Matos, Leandro Luongo; Simões-Zenari, Marcia; Cernea, Claudio Roberto; Nemr, Katia

2018-01-01

Purpose Assess the effectiveness of an orofacial myofunctional therapeutic program in patients with oral or oropharyngeal cancer submitted to adjuvant radiotherapy through pre- and post-program comparison of maximum mandibular opening. Methods Prospective study involving five adult patients and five elderly patients postoperatively to oral cavity/oropharynx surgery who were awaiting the beginning of radiotherapy or had undergone fewer than five treatment sessions. The study participants had their maximum jaw opening measured using a sliding caliper at the beginning and end of the program. Two mobility exercises and three mandibular traction exercises were selected and weekly monitored presentially for 10 weeks. Descriptive data and pre- and post-therapy comparative measures were statistically analyzed using the Wilcoxon test. Results Ten patients (two women and eight men) with mean age of 58.4 years, median of 57.0 years, completed the therapeutic program. They presented mean maximum mandibular opening of 31.6 ± 11.7 and 36.4 ± 8.0 mm pre- and post-therapy, respectively (p =0.021). Conclusion The proposed orofacial myofunctional therapeutic program increased the maximum jaw opening of patients referred to adjuvant radiotherapy for oral cavity or oropharynx cancer treatment.

Integer programming for improving radiotherapy treatment efficiency.

PubMed

Lv, Ming; Li, Yi; Kou, Bo; Zhou, Zhili

2017-01-01

Patients received by radiotherapy departments are diverse and may be diagnosed with different cancers. Therefore, they need different radiotherapy treatment plans and thus have different needs for medical resources. This research aims to explore the best method of scheduling the admission of patients receiving radiotherapy so as to reduce patient loss and maximize the usage efficiency of service resources. A mix integer programming (MIP) model integrated with special features of radiotherapy is constructed. The data used here is based on the historical data collected and we propose an exact method to solve the MIP model. Compared with the traditional First Come First Served (FCFS) method, the new method has boosted patient admission as well as the usage of linear accelerators (LINAC) and beds. The integer programming model can be used to describe the complex problem of scheduling radio-receiving patients, to identify the bottleneck resources that hinder patient admission, and to obtain the optimal LINAC-bed radio under the current data conditions. Different management strategies can be implemented by adjusting the settings of the MIP model. The computational results can serve as a reference for the policy-makers in decision making.

Analysis of errors detected in external beam audit dosimetry program at Mexican radiotherapy centers

NASA Astrophysics Data System (ADS)

Álvarez-Romero, José T.; Tovar-Muñoz, Víctor M.

2012-10-01

Presented and analyzed are the causes of deviation observed in the pilot postal dosimetry audit program to verify the absorbed dose to water Dw in external beams of teletherapy 60Co and/or linear accelerators in Mexican radiotherapy centers, during the years 2007-2011.

Genomic and Histopathological Tissue Biomarkers That Predict Radiotherapy Response in Localised Prostate Cancer

PubMed Central

Wilkins, Anna; Dearnaley, David; Somaiah, Navita

2015-01-01

Localised prostate cancer, in particular, intermediate risk disease, has varied survival outcomes that cannot be predicted accurately using current clinical risk factors. External beam radiotherapy (EBRT) is one of the standard curative treatment options for localised disease and its efficacy is related to wide ranging aspects of tumour biology. Histopathological techniques including immunohistochemistry and a variety of genomic assays have been used to identify biomarkers of tumour proliferation, cell cycle checkpoints, hypoxia, DNA repair, apoptosis, and androgen synthesis, which predict response to radiotherapy. Global measures of genomic instability also show exciting capacity to predict survival outcomes following EBRT. There is also an urgent clinical need for biomarkers to predict the radiotherapy fraction sensitivity of different prostate tumours and preclinical studies point to possible candidates. Finally, the increased resolution of next generation sequencing (NGS) is likely to enable yet more precise molecular predictions of radiotherapy response and fraction sensitivity. PMID:26504789

Education and training of medical physics in Iran: The past, the present and the future.

PubMed

Mahdavi, Seyed Rabi; Rasuli, Behrouz; Niroomand-Rad, Azam

2017-04-01

The aim of this study was to investigate the current status of education and training programs in medical physics in Iran. A questionnaire was designed and sent to 274 IAMP (Iranian Association of Medical Physicists) members focusing on these two topics: the educational situation (course syllabus, number of faculty members, number of PhD and MSc students and sub-fields offered in the department) and the professional situation (work experience, workplaces of medical physicists, postgraduate degrees that were granted and the amount of therapy and imaging equipment). Medical physics education in Iran is provided at 14 universities at master and doctorate levels. All medical physics departments offer an MSc program and 6 of them offer a PhD program. Most medical physics faculty (24%) work in the radiotherapy physics sub-specialty. Also, about 95 medical physics students graduate every year. There are six major peer-reviewed Iranian journals that publish medical physics papers in English. In addition, there are 74 radiotherapy machines including Co-60 and LINACs (LINear ACcelerators) across Iran as of 2013. The curriculum of medical physics programs (MSc and PhD) in Iran must be improved to include long-term clinical courses in the four major sub-specialties of radiotherapy, medical imaging, nuclear medicine and radiation protection. It is hoped that clinical medical physicists will go through nationally-accredited exams before assuming independent clinical responsibilities. Moreover, the work situation of the medical physics profession in Iran should be clear and the government authorities must recognize importance of this interdisciplinary field in medicine. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

The role of radiotherapy in the management of POEMS syndrome.

PubMed

Suh, Yang-Gun; Kim, Young-Suk; Suh, Chang-Ok; Kim, Yu Ri; Cheong, June-Won; Kim, Jin Seok; Cho, Jaeho

2014-11-28

POEMS syndrome is a paraneoplastic syndrome caused by an underlying plasma cell proliferative disease. In this study, we examined the treatment outcomes and role of radiotherapy in the management of POEMS syndrome. In total, 33 patients diagnosed with POEMS syndrome were analyzed. These patients presented with osteosclerotic myeloma (OSM, n = 13), Castleman's disease (CD, n = 4), OSM with CD (n = 10), and vascular endothelial growth factor elevation without gross lesions (VEGFe, n = 6), respectively. The patients were treated by radiotherapy alone (n = 4), chemotherapy alone (n = 16), or a combination thereof (n = 9). The clinical response rates of radiotherapy, chemotherapy, and radiotherapy plus chemotherapy were 75%, 69%, and 89%, respectively. In addition, the hematologic response rates were 50%, 69%, and 71%, respectively. Among the six patients with limited multiple lesions who underwent radiotherapy, the clinical symptoms were improved in five patients after radiotherapy. The median progression-free survival (PFS) was 51 months, and the median overall survival (OS) was 65 months. In univariate analysis, the administration of chemotherapy was significantly associated with better PFS (p = 0.007) and OS (p = 0.020). In contrast, underlying VEGFe was a significant factor worsening PFS (p = 0.035) and OS (p = 0.008). Radiotherapy produces a reliable clinical response and is effective in improving POEMS-associated symptoms that are refractory to chemotherapy in selected patients with clustered or limited multiple lesions that can be covered by single radiation field.

A theoretical stochastic control framework for adapting radiotherapy to hypoxia

NASA Astrophysics Data System (ADS)

Saberian, Fatemeh; Ghate, Archis; Kim, Minsun

2016-10-01

Hypoxia, that is, insufficient oxygen partial pressure, is a known cause of reduced radiosensitivity in solid tumors, and especially in head-and-neck tumors. It is thus believed to adversely affect the outcome of fractionated radiotherapy. Oxygen partial pressure varies spatially and temporally over the treatment course and exhibits inter-patient and intra-tumor variation. Emerging advances in non-invasive functional imaging offer the future possibility of adapting radiotherapy plans to this uncertain spatiotemporal evolution of hypoxia over the treatment course. We study the potential benefits of such adaptive planning via a theoretical stochastic control framework using computer-simulated evolution of hypoxia on computer-generated test cases in head-and-neck cancer. The exact solution of the resulting control problem is computationally intractable. We develop an approximation algorithm, called certainty equivalent control, that calls for the solution of a sequence of convex programs over the treatment course; dose-volume constraints are handled using a simple constraint generation method. These convex programs are solved using an interior point algorithm with a logarithmic barrier via Newton’s method and backtracking line search. Convexity of various formulations in this paper is guaranteed by a sufficient condition on radiobiological tumor-response parameters. This condition is expected to hold for head-and-neck tumors and for other similarly responding tumors where the linear dose-response parameter is larger than the quadratic dose-response parameter. We perform numerical experiments on four test cases by using a first-order vector autoregressive process with exponential and rational-quadratic covariance functions from the spatiotemporal statistics literature to simulate the evolution of hypoxia. Our results suggest that dynamic planning could lead to a considerable improvement in the number of tumor cells remaining at the end of the treatment course. Through these simulations, we also gain insights into when and why dynamic planning is likely to yield the largest benefits.

A versatile program for the calculation of linear accelerator room shielding.

PubMed

Hassan, Zeinab El-Taher; Farag, Nehad M; Elshemey, Wael M

2018-03-22

This work aims at designing a computer program to calculate the necessary amount of shielding for a given or proposed linear accelerator room design in radiotherapy. The program (Shield Calculation in Radiotherapy, SCR) has been developed using Microsoft Visual Basic. It applies the treatment room shielding calculations of NCRP report no. 151 to calculate proper shielding thicknesses for a given linear accelerator treatment room design. The program is composed of six main user-friendly interfaces. The first enables the user to upload their choice of treatment room design and to measure the distances required for shielding calculations. The second interface enables the user to calculate the primary barrier thickness in case of three-dimensional conventional radiotherapy (3D-CRT), intensity modulated radiotherapy (IMRT) and total body irradiation (TBI). The third interface calculates the required secondary barrier thickness due to both scattered and leakage radiation. The fourth and fifth interfaces provide a means to calculate the photon dose equivalent for low and high energy radiation, respectively, in door and maze areas. The sixth interface enables the user to calculate the skyshine radiation for photons and neutrons. The SCR program has been successfully validated, precisely reproducing all of the calculated examples presented in NCRP report no. 151 in a simple and fast manner. Moreover, it easily performed the same calculations for a test design that was also calculated manually, and produced the same results. The program includes a new and important feature that is the ability to calculate required treatment room thickness in case of IMRT and TBI. It is characterised by simplicity, precision, data saving, printing and retrieval, in addition to providing a means for uploading and testing any proposed treatment room shielding design. The SCR program provides comprehensive, simple, fast and accurate room shielding calculations in radiotherapy.

Redesigning Radiotherapy Quality Assurance: Opportunities to Develop an Efficient, Evidence-Based System to Support Clinical Trials-Report of the National Cancer Institute Work Group on Radiotherapy Quality Assurance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bekelman, Justin E., E-mail: bekelman@uphs.upenn.edu; Deye, James A.; Vikram, Bhadrasain

2012-07-01

Purpose: In the context of national calls for reorganizing cancer clinical trials, the National Cancer Institute sponsored a 2-day workshop to examine challenges and opportunities for optimizing radiotherapy quality assurance (QA) in clinical trial design. Methods and Materials: Participants reviewed the current processes of clinical trial QA and noted the QA challenges presented by advanced technologies. The lessons learned from the radiotherapy QA programs of recent trials were discussed in detail. Four potential opportunities for optimizing radiotherapy QA were explored, including the use of normal tissue toxicity and tumor control metrics, biomarkers of radiation toxicity, new radiotherapy modalities such asmore » proton beam therapy, and the international harmonization of clinical trial QA. Results: Four recommendations were made: (1) to develop a tiered (and more efficient) system for radiotherapy QA and tailor the intensity of QA to the clinical trial objectives (tiers include general credentialing, trial-specific credentialing, and individual case review); (2) to establish a case QA repository; (3) to develop an evidence base for clinical trial QA and introduce innovative prospective trial designs to evaluate radiotherapy QA in clinical trials; and (4) to explore the feasibility of consolidating clinical trial QA in the United States. Conclusion: Radiotherapy QA can affect clinical trial accrual, cost, outcomes, and generalizability. To achieve maximum benefit, QA programs must become more efficient and evidence-based.« less

Redesigning radiotherapy quality assurance: opportunities to develop an efficient, evidence-based system to support clinical trials--report of the National Cancer Institute Work Group on Radiotherapy Quality Assurance.

PubMed

Bekelman, Justin E; Deye, James A; Vikram, Bhadrasain; Bentzen, Soren M; Bruner, Deborah; Curran, Walter J; Dignam, James; Efstathiou, Jason A; FitzGerald, T J; Hurkmans, Coen; Ibbott, Geoffrey S; Lee, J Jack; Merchant, Thomas E; Michalski, Jeff; Palta, Jatinder R; Simon, Richard; Ten Haken, Randal K; Timmerman, Robert; Tunis, Sean; Coleman, C Norman; Purdy, James

2012-07-01

In the context of national calls for reorganizing cancer clinical trials, the National Cancer Institute sponsored a 2-day workshop to examine challenges and opportunities for optimizing radiotherapy quality assurance (QA) in clinical trial design. Participants reviewed the current processes of clinical trial QA and noted the QA challenges presented by advanced technologies. The lessons learned from the radiotherapy QA programs of recent trials were discussed in detail. Four potential opportunities for optimizing radiotherapy QA were explored, including the use of normal tissue toxicity and tumor control metrics, biomarkers of radiation toxicity, new radiotherapy modalities such as proton beam therapy, and the international harmonization of clinical trial QA. Four recommendations were made: (1) to develop a tiered (and more efficient) system for radiotherapy QA and tailor the intensity of QA to the clinical trial objectives (tiers include general credentialing, trial-specific credentialing, and individual case review); (2) to establish a case QA repository; (3) to develop an evidence base for clinical trial QA and introduce innovative prospective trial designs to evaluate radiotherapy QA in clinical trials; and (4) to explore the feasibility of consolidating clinical trial QA in the United States. Radiotherapy QA can affect clinical trial accrual, cost, outcomes, and generalizability. To achieve maximum benefit, QA programs must become more efficient and evidence-based. Copyright © 2012 Elsevier Inc. All rights reserved.

SU-C-BRD-05: Implementation of Incident Learning in the Safety and Quality Management of Radiotherapy: The Primary Experience in a New Established Program with Advanced Techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, R; Wang, J

2014-06-15

Purpose: To explore the implementation and effectiveness of incident learning for the safety and quality of radiotherapy in a new established radiotherapy program with advanced technology. Methods: Reference to the consensus recommendations by American Association of Physicist in Medicine, an incident learning system was specifically designed for reporting, investigating, and learning of individual radiotherapy incidents in a new established radiotherapy program, with 4D CBCT, Ultrasound guided radiotherapy, VMAT, gated treatment delivered on two new installed linacs. The incidents occurring in external beam radiotherapy from February, 2012 to January, 2014 were reported. Results: A total of 33 reports were analyzed, includingmore » 28 near misses and 5 incidents. Among them, 5 originated in imaging for planning, 25 in planning, 1 in plan transfer, 1 in commissioning and 1 in treatment delivery. Among them, three near misses originated in the safety barrier of the radiotherapy process. In terms of error type, 1 incident was classified as wrong patient, 7 near misses/incidents as wrong site, 6 as wrong laterality, 5 as wrong dose, 7 as wrong prescription, and 7 as suboptimal plan quality. 5 incidents were all classified as grade 1/2 of dosimetric severity, 1 as grade 0, and the other 4 as grade 1 of medical severity. For the causes/contributory factors, negligence, policy not followed, inadequate training, failure to develop an effective plan, and communication contributed to 19, 15, 12, 5 and 3 near misses/incidents, respectively. The average incident rate per 100 patients treated was 0.4; this rate fell to 0.28% in the second year from 0.56% in the first year. The rate of near miss fell to 1.24% from 2.22%. Conclusion: Effective incident learning can reduce the occurrence of near miss/incidents, enhance the culture of safety. Incident learning is an effective proactive method for improving the quality and safety of radiotherapy.« less

Redesigning Radiotherapy Quality Assurance: Opportunities to Develop an Efficient, Evidence-Based System to Support Clinical Trials

PubMed Central

Bekelman, Justin E.; Deye, James A.; Vikram, Bhadrasain; Bentzen, Soren M.; Bruner, Deborah; Curran, Walter J.; Dignam, James; Efstathiou, Jason A.; FitzGerald, T. J.; Hurkmans, Coen; Ibbott, Geoffrey S.; Lee, J. Jack; Merchant, Timothy E.; Michalski, Jeff; Palta, Jatinder R.; Simon, Richard; Ten Haken, Randal K.; Timmerman, Robert; Tunis, Sean; Coleman, C. Norman; Purdy, James

2012-01-01

Background In the context of national calls for reorganizing cancer clinical trials, the National Cancer Institute (NCI) sponsored a two day workshop to examine the challenges and opportunities for optimizing radiotherapy quality assurance (QA) in clinical trial design. Methods Participants reviewed the current processes of clinical trial QA and noted the QA challenges presented by advanced technologies. Lessons learned from the radiotherapy QA programs of recent trials were discussed in detail. Four potential opportunities for optimizing radiotherapy QA were explored, including the use of normal tissue toxicity and tumor control metrics, biomarkers of radiation toxicity, new radiotherapy modalities like proton beam therapy, and the international harmonization of clinical trial QA. Results Four recommendations were made: 1) Develop a tiered (and more efficient) system for radiotherapy QA and tailor intensity of QA to clinical trial objectives. Tiers include (i) general credentialing, (ii) trial specific credentialing, and (iii) individual case review; 2) Establish a case QA repository; 3) Develop an evidence base for clinical trial QA and introduce innovative prospective trial designs to evaluate radiotherapy QA in clinical trials; and 4) Explore the feasibility of consolidating clinical trial QA in the United States. Conclusion Radiotherapy QA may impact clinical trial accrual, cost, outcomes and generalizability. To achieve maximum benefit, QA programs must become more efficient and evidence-based. PMID:22425219

WE-B-BRD-00: MRI for Radiation Oncology

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The use of MRI in radiation therapy is rapidly increasing. Applications vary from the MRI simulator, to the MRI fused with CT, and to the integrated MRI+RT system. Compared with the standard MRI QA, a broader scope of QA features has to be defined in order to maximize the benefits of using MRI in radiation therapy. These QA features include geometric fidelity, image registration, motion management, cross-system alignment, and hardware interference. Advanced MRI techniques require a specific type of QA, as they are being widely used in radiation therapy planning, dose calculations, post-implant dosimetry, and prognoses. A vigorous and adaptivemore » QA program is crucial to defining the responsibility of the entire radiation therapy group and detecting deviations from the performance of high-quality treatment. As a drastic departure from CT simulation, MRI simulation requires changes in the work flow of treatment planning and image guidance. MRI guided radiotherapy platforms are being developed and commercialized to take the advantage of the advance in knowledge, technology and clinical experience. This symposium will from an educational perspective discuss the scope and specific issues related to MRI guided radiotherapy. Learning Objectives: Understand the difference between a standard and a radiotherapy-specific MRI QA program. Understand the effects of MRI artifacts (geometric distortion and motion) on radiotherapy. Understand advanced MRI techniques (ultrashort echo, fast MRI including dynamic MRI and 4DMRI, diffusion, perfusion, and MRS) and related QA. Understand the methods to prepare MRI for treatment planning (electron density assignment, multimodality image registration, segmentation and motion management). Current status of MRI guided treatment platforms. Dr. Jihong Wang has a research grant with Elekta-MRL project. Dr. Ke Sheng receives research grants from Varian Medical systems.« less

Tissue and serum expression of TGM-3 may be prognostic marker in patients of oral squamous cell carcinoma undergoing chemo-radiotherapy.

PubMed

Nayak, Seema; Bhatt, M L B; Goel, Madhu Mati; Gupta, Seema; Mahdi, Abbas Ali; Mishra, Anupam; Mehrotra, Divya

2018-01-01

Radioresistance is one of the main determinants of treatment outcome in oral squamous cell carcinoma (OSCC), but its prediction is difficult. Several authors aimed to establish radioresistant OSCC cell lines to identify genes with altered expression in response to radioresistance. The development of OSCC is a multistep carcinogenic process that includes activation of several oncogenes and inactivation of tumour suppressor genes. TGM-3 is a tumour suppressor gene and contributes to carcinogenesis process. The aim of this study was to estimate serum and tissue expression of TGM-3 and its correlation with clinico-pathological factors and overall survival in patients of OSCC undergoing chemo-radiotherapy. Tissue expression was observed in formalin fixed tissue biopsies of 96 cases of OSCC and 32 healthy controls were subjected to immunohistochemistry (IHC) by using antibody against TGM-3 and serum level was estimated by ELISA method. mRNA expression was determined by using Real-Time PCR. Patients were followed for 2 year for chemo radiotherapy response. In OSCC, 76.70% cases and in controls 90.62% were positive for TGM-3 IHC expression. TGM-3 expression was cytoplasmic and nuclear staining expressed in keratinized layer, stratum granulosum and stratum spinosum in controls and tumour cells. Mean serum TGM-3 in pre chemo-radiotherapy OSCC cases were 1304.83±573.55, post chemo-radiotherapy samples were 1530.64±669.33 and controls were 1869.16±1377.36, but difference was significant in pre chemo-radiotherapy samples as compared to controls (p<0.018). This finding was also confirmed by real- time PCR analysis in which down regulation (-7.92 fold change) of TGM-3 in OSCC as compared to controls. TGM-3 expression was significantly associated with response to chemo-radiotherapy treatment (p<0.007) and overall survival (p<0.015). Patents having higher level of TGM-3 expression have good response to chemo-radiotherapy and also have better overall survival. TGM-3 may serve as a candidate biomarker for responsiveness to chemo-radiotherapy treatment in OSCC patients.

Response to treatment and interval to surgery after preoperative short-course radiotherapy in rectal cancer.

PubMed

García-Cabezas, Sonia; Rodríguez-Liñán, Milagrosa; Otero-Romero, Ana M; Bueno-Serrano, Carmen M; Gómez-Barbadillo, José; Palacios-Eito, Amalia

2016-10-01

Preoperative short-course radiotherapy with immediate surgery improves local control in patients with rectal cancer. Tumor responses are smaller than those described with radiochemotherapy. Preliminary data associate this lower response to the short period until surgery. The aim of this study is to analyze the response to preoperative short-course radiotherapy and its correlation with the interval to surgery especially analyzing patients with mesorectal fascia involvement. A total of 155 patients with locally advanced rectal cancer treated with preoperative radiotherapy (5×5Gy) were retrospectively analyzed. Tumor response in terms of rates of complete pathological response, downstaging, tumor regression grading and status of the circumferential resection margin were quantified. The mean interval from radiotherapy to surgery was 23 days. The rate of complete pathological response was 2.2% and 28% experienced downstaging (stage decreased). No differences between these rates and interval to surgery were detected. Eighty-eight patients had magnetic resonance imaging for staging (in 31 patients the mesorectal fascia was involved).The mean time to surgery in patients with involvement of the fascia and R0 surgery was 27 days and 16 days if R1 (P=.016). The cutoff of 20 days reached the highest probability of achieving a free circumferential resection margin between patients with mesorectal fascia involvement, with no statistically significant differences: RR 3.036 95% CI=(0.691-13.328), P=.06. After preoperative short-course radiotherapy, an interval>20 days enhances the likelihood of achieving a free circumferential resection margin in patients with mesorectal fascia involvement. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Low-Dose Radiotherapy in Indolent Lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rossier, Christine; Schick, Ulrike; Miralbell, Raymond

Purpose: To assess the response rate, duration of response, and overall survival after low-dose involved-field radiotherapy in patients with recurrent low-grade lymphoma or chronic lymphocytic leukemia (CLL). Methods and Materials: Forty-three (24 women, 19 men) consecutive patients with indolent lymphoma or CLL were treated with a total dose of 4 Gy (2 x 2 Gy) using 6- 18-MV photons. The median age was 73 years (range, 39-88). Radiotherapy was given either after (n = 32; 75%) or before (n = 11; 25%) chemotherapy. The median time from diagnosis was 48 months (range, 1-249). The median follow-up period was 20 monthsmore » (range, 1-56). Results: The overall response rate was 90%. Twelve patients (28%) had a complete response, 15 (35%) had a partial response, 11 (26%) had stable disease, and 5 (11%) had progressive disease. The median overall survival for patients with a positive response (complete response/partial response/stable disease) was 41 months; for patients with progressive disease it was 6 months (p = 0.001). The median time to in-field progression was 21 months (range, 0-24), and the median time to out-field progression was 8 months (range, 0-40). The 3-year in-field control was 92% in patients with complete response (median was not reached). The median time to in-field progression was 9 months (range, 0.5-24) in patients with partial response and 6 months (range, 0.6-6) in those with stable disease (p < 0.05). Younger age, positive response to radiotherapy, and no previous chemotherapy were the best factors influencing the outcome. Conclusions: Low-dose involved-field radiotherapy is an effective treatment in the management of patients with recurrent low-grade lymphoma or CLL.« less

Early change in glucose metabolic rate measured using FDG-PET in patients with high-grade glioma predicts response to temozolomide but not temozolomide plus radiotherapy.

PubMed

Charnley, Natalie; West, Catharine M; Barnett, Carolyn M; Brock, Catherine; Bydder, Graeme M; Glaser, Mark; Newlands, Ed S; Swindell, Ric; Matthews, Julian; Price, Pat

2006-10-01

To compare the ability of positron emission tomography (PET) to predict response to temozolomide vs. temozolomide plus radiotherapy. Nineteen patients with high-grade glioma (HGG) were studied. Patients with recurrent glioma received temozolomide 75 mg/m2 daily for 7 weeks (n=8). Newly diagnosed patients received temozolomide 75 mg/m2 daily plus radiotherapy 60 Gy/30 fractions over 6 weeks, followed by six cycles of adjuvant temozolomide 200 mg/m2/day (Days 1-5 q28) starting 1 month after radiotherapy (n=11). [18F]Fluorodeoxyglucose ([18F]FDG) PET scan and magnetic resonance imaging (MRI) were performed at baseline, and 7 and 19 weeks after initiation of temozolomide administration. Changes in glucose metabolic rate (MRGlu) and MRI response were correlated with patient survival. In the temozolomide-alone group, patients who survived>26 vs. or=25%, survived longer than nonresponders with mean survival times of 75 weeks (95% CI, 34-115 vs. 20 weeks (95% CI, 14-26) (p=0.0067). In the small group of patients studied, there was no relationship between MRI response and survival (p=0.52). For patients receiving temozolomide plus radiotherapy, there was no difference in survival between PET responders and nonresponders (p=0.32). Early changes in MRGlu predict response to temozolomide, but not temozolomide plus radiotherapy.

Evaluation of Mediators Associated with the Inflammatory Response in Prostate Cancer Patients Undergoing Radiotherapy

PubMed Central

Bedini, Nice; Cicchetti, Alessandro; Palorini, Federica; Magnani, Tiziana; Zuco, Valentina; Pennati, Marzia; Campi, Elisa; Allavena, Paola; Pesce, Samantha; Villa, Sergio; Avuzzi, Barbara; Morlino, Sara; Visentin, Maria Emanuela; Zaffaroni, Nadia; Valdagni, Riccardo

2018-01-01

A recent “hot topic” in prostate cancer radiotherapy is the observed association between acute/late rectal toxicity and the presence of abdominal surgery before radiotherapy. The exact mechanism is unclear. Our working hypothesis was that a previous surgery may influence plasma level of inflammatory molecules and this might result in enhanced radiosensitivity. We here present results on the feasibility of monitoring the expression of inflammatory molecules during radiotherapy. Plasma levels of a panel of soluble mediators associated with the inflammatory response were measured in prostate cancer patients undergoing radical radiotherapy. We measured 3 cytokines (IL-1b, IL-6, and TNF alpha), 2 chemokines (CCL2 and CXCL8), and the long pentraxin PTX3. 20 patients were enrolled in this feasibility evaluation. All patients were treated with IMRT at 78 Gy. 3/20 patients reported grade 2 acute rectal toxicity, while 4/20 were scored as grade 2 late toxicity. CCL2 was the most interesting marker showing significant increase during and after radiotherapy. CCL2 levels at radiotherapy end could be modelled using linear regression including basal CCL2, age, surgery, hypertension, and use of anticoagulants. The 4 patients with late toxicity had CCL2 values at radiotherapy end above the median value. This trial is registered with ISRCTN64979094. PMID:29682101

Evaluation of Mediators Associated with the Inflammatory Response in Prostate Cancer Patients Undergoing Radiotherapy.

PubMed

Bedini, Nice; Cicchetti, Alessandro; Palorini, Federica; Magnani, Tiziana; Zuco, Valentina; Pennati, Marzia; Campi, Elisa; Allavena, Paola; Pesce, Samantha; Villa, Sergio; Avuzzi, Barbara; Morlino, Sara; Visentin, Maria Emanuela; Zaffaroni, Nadia; Rancati, Tiziana; Valdagni, Riccardo

2018-01-01

A recent "hot topic" in prostate cancer radiotherapy is the observed association between acute/late rectal toxicity and the presence of abdominal surgery before radiotherapy. The exact mechanism is unclear. Our working hypothesis was that a previous surgery may influence plasma level of inflammatory molecules and this might result in enhanced radiosensitivity. We here present results on the feasibility of monitoring the expression of inflammatory molecules during radiotherapy. Plasma levels of a panel of soluble mediators associated with the inflammatory response were measured in prostate cancer patients undergoing radical radiotherapy. We measured 3 cytokines (IL-1b, IL-6, and TNF alpha), 2 chemokines (CCL2 and CXCL8), and the long pentraxin PTX3. 20 patients were enrolled in this feasibility evaluation. All patients were treated with IMRT at 78 Gy. 3/20 patients reported grade 2 acute rectal toxicity, while 4/20 were scored as grade 2 late toxicity. CCL2 was the most interesting marker showing significant increase during and after radiotherapy. CCL2 levels at radiotherapy end could be modelled using linear regression including basal CCL2, age, surgery, hypertension, and use of anticoagulants. The 4 patients with late toxicity had CCL2 values at radiotherapy end above the median value. This trial is registered with ISRCTN64979094.

Radiation-induced immune responses: mechanisms and therapeutic perspectives.

PubMed

Jeong, Hoibin; Bok, Seoyeon; Hong, Beom-Ju; Choi, Hyung-Seok; Ahn, G-One

2016-09-01

Recent advancement in the radiotherapy technology has allowed conformal delivery of high doses of ionizing radiation precisely to the tumors while sparing large volume of the normal tissues, which have led to better clinical responses. Despite this technological advancement many advanced tumors often recur and they do so within the previously irradiated regions. How could tumors recur after receiving such high ablative doses of radiation? In this review, we outlined how radiation can elicit anti-tumor responses by introducing some of the cytokines that can be induced by ionizing radiation. We then discuss how tumor hypoxia, a major limiting factor responsible for failure of radiotherapy, may also negatively impact the anti-tumor responses. In addition, we highlight how there may be other populations of immune cells including regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) that can be recruited to tumors interfering with the anti-tumor immunity. Finally, the impact of irradiation on tumor hypoxia and the immune responses according to different radiotherapy regimen is also delineated. It is indeed an exciting time to see that radiotherapy is being combined with immunotherapy in the clinic and we hope that this review can add an excitement to the field.

It Is Tough and Tiring but It Works--Children's Experiences of Undergoing Radiotherapy.

PubMed

Engvall, Gunn; Ångström-Brännström, Charlotte; Mullaney, Tara; Nilsson, Kristina; Wickart-Johansson, Gun; Svärd, Anna-Maja; Nyholm, Tufve; Lindh, Jack; Lindh, Viveca

2016-01-01

Approximately 300 children ages 0 to 18 are diagnosed with cancer in Sweden every year, and 80 to 90 of them undergo radiotherapy treatment. The aim was to describe children's experiences of preparing for and undergoing radiotherapy, and furthermore to describe children's suggestions for improvement. Thirteen children between the ages of 5 and 15 with various cancer diagnoses were interviewed. Data was analyzed using qualitative content analysis. The findings revealed five categories: positive and negative experiences with hospital stays and practical arrangements; age-appropriate information, communication, and guidance to various degrees; struggle with emotions; use of distraction and other suitable coping strategies; and children's suggestions for improvement during radiotherapy. An overarching theme emerged: "It is tough and tiring but it works". Some key areas were: explanatory visits, the need for information and communication, being afraid, discomfort and suffering, the need for media distraction, dealing with emotions, and the need for support. A systematic, family-centered preparation program could possible help families prepare and individualized distraction during radiotherapy could contribute to reducing distress. Further studies with interventions could clarify successful programs.

Cetuximab in the treatment of head and neck cancer: preliminary results outside clinical trials

PubMed Central

Dequanter, Didier; Shahla, Mohammad; Paulus, Pascal; Lothaire, Phillippe

2010-01-01

Introduction: The purpose of this study was to evaluate the clinical efficacy in our daily practice, outside clinical trials, of cetuximab plus radiotherapy in a majority of treatment-naive patients with locoregionally advanced head and neck squamous cell carcinomas. Methods: A retrospective study was performed to evaluate outcomes in patients who were treated definitively with cetuximab and radiotherapy (ExRT). Patients with stage III or IV, nonmetastatic, measurable squamous cell carcinoma of the head and neck (SCCHN) were eligible. Results: There were 18 males and two females. The median age was 61 years (range from 49 to 87 years old). Concurrent radiotherapy and cetuximab was used, in first line, in 17 patients with locally advanced disease; two patients with recurrent SCCHN, who were intolerant of Cisplatin-based regimens, were treated with radiotherapy combined with weekly cetuximab; and 1 patient received cetuximab and radiotherapy postoperatively. The median time of response was 10 months (range from 2 to 24 months). A partial response was observed in 11 cases; a complete response in nine cases. The occurrence of grade 2–3 skin toxicity was observed in 11 cases. Skin toxicity was clearly correlated with a better response and the duration of the response to the treatment. The use of cetuximab in combination with radiotherapy does not increase the side effects of radiotherapy. At the end of the follow-up, 17 patients died. Conclusion: Cetuximab, with its highly targeted mechanism of action and synergistic activity with current treatment modalities, is a valuable treatment option in head and neck patients. The effect of the epidermal growth factor receptor antagonist occurs without any change in the pattern and the severity of toxicity usually associated with head and neck radiation. Cetuximab seems not to provide the most benefit for patients with oropharyngeal cancers but will in patients with T4 tumors. However, the median duration of local control was less as described in the clinical trials. PMID:21188107

Improved survival and complete response rates in patients with advanced melanoma treated with concurrent ipilimumab and radiotherapy versus ipilimumab alone.

PubMed

Koller, Kristian M; Mackley, Heath B; Liu, Jason; Wagner, Henry; Talamo, Giampaolo; Schell, Todd D; Pameijer, Colette; Neves, Rogerio I; Anderson, Bryan; Kokolus, Kathleen M; Mallon, Carol A; Drabick, Joseph J

2017-01-02

There is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited. We conducted a retrospective analysis to evaluate patients treated with ipilimumab for advanced melanoma at a single institution from May 2011 to June 2015. Patients were grouped into those who had received concurrent radiotherapy while on ipilimumab (Ipi-RT), and those who did not. We then evaluated the treatment response following completion of ipilimumab. A total of 101 patients received ipilimumab in the prespecified time frame. 70 received Ipi-RT and 31 received ipilimumab without concurrent radiotherapy. Median overall survival (OS) was significantly increased in the concurrent Ipi-RT arm at 19 months vs. 10 months for ipilimumab alone (p = 0.01). Median progression free survival (PFS) was marginally increased in the Ipi-RT group compare with the ipilimumab alone group (5 months vs. 3 months, p = 0.20). Rates of complete response (CR) were significantly increased in the Ipi-RT group vs. ipilimumab alone (25.7% vs. 6.5%; p = 0.04), and rates of overall response (OR) in the groups were 37.1% vs. 19.4% (p = 0.11). No increase in toxicities was observed in the Ipi-RT group compare with ipilimumab alone. Prospective trials are needed to further clarify the role of radiotherapy with ipilimumab, but these encouraging preliminary observations suggest that this combination can induce more durable responses to immunotherapy.

Improved survival and complete response rates in patients with advanced melanoma treated with concurrent ipilimumab and radiotherapy versus ipilimumab alone

PubMed Central

Koller, Kristian M.; Mackley, Heath B.; Liu, Jason; Wagner, Henry; Talamo, Giampaolo; Schell, Todd D.; Pameijer, Colette; Neves, Rogerio I.; Anderson, Bryan; Kokolus, Kathleen M.; Mallon, Carol A.; Drabick, Joseph J.

2017-01-01

ABSTRACT There is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited. We conducted a retrospective analysis to evaluate patients treated with ipilimumab for advanced melanoma at a single institution from May 2011 to June 2015. Patients were grouped into those who had received concurrent radiotherapy while on ipilimumab (Ipi-RT), and those who did not. We then evaluated the treatment response following completion of ipilimumab. A total of 101 patients received ipilimumab in the prespecified time frame. 70 received Ipi-RT and 31 received ipilimumab without concurrent radiotherapy. Median overall survival (OS) was significantly increased in the concurrent Ipi-RT arm at 19 months vs. 10 months for ipilimumab alone (p = 0.01). Median progression free survival (PFS) was marginally increased in the Ipi-RT group compare with the ipilimumab alone group (5 months vs. 3 months, p = 0.20). Rates of complete response (CR) were significantly increased in the Ipi-RT group vs. ipilimumab alone (25.7% vs. 6.5%; p = 0.04), and rates of overall response (OR) in the groups were 37.1% vs. 19.4% (p = 0.11). No increase in toxicities was observed in the Ipi-RT group compare with ipilimumab alone. Prospective trials are needed to further clarify the role of radiotherapy with ipilimumab, but these encouraging preliminary observations suggest that this combination can induce more durable responses to immunotherapy. PMID:27905824

Combination of immunotherapy with chemotherapy and radiotherapy in lung cancer: is this the beginning of the end for cancer?

PubMed Central

Lazzari, Chiara; Karachaliou, Niki; Bulotta, Alessandra; Viganó, Mariagrazia; Mirabile, Aurora; Brioschi, Elena; Santarpia, Mariacarmela; Gianni, Luca; Rosell, Rafael; Gregorc, Vanesa

2018-01-01

Immune checkpoint inhibitors have significantly improved overall survival with an acceptable safety profile in a substantial proportion of non-small cell lung cancer (NSCLC) patients. However, not all patients are sensitive to immune checkpoint blockade and, in some cases, programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors accelerate tumor progression. Several combination strategies are under evaluation, including the concomitant or sequential evaluation of chemotherapy or radiotherapy with immunotherapy. The current review provides an overview on the molecular rationale for the investigation of combinatorial approaches with chemotherapy or radiotherapy. Moreover, the results of completed clinical studies will be reported. PMID:29662546

Combination of immunotherapy with chemotherapy and radiotherapy in lung cancer: is this the beginning of the end for cancer?

PubMed

Lazzari, Chiara; Karachaliou, Niki; Bulotta, Alessandra; Viganó, Mariagrazia; Mirabile, Aurora; Brioschi, Elena; Santarpia, Mariacarmela; Gianni, Luca; Rosell, Rafael; Gregorc, Vanesa

2018-01-01

Immune checkpoint inhibitors have significantly improved overall survival with an acceptable safety profile in a substantial proportion of non-small cell lung cancer (NSCLC) patients. However, not all patients are sensitive to immune checkpoint blockade and, in some cases, programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors accelerate tumor progression. Several combination strategies are under evaluation, including the concomitant or sequential evaluation of chemotherapy or radiotherapy with immunotherapy. The current review provides an overview on the molecular rationale for the investigation of combinatorial approaches with chemotherapy or radiotherapy. Moreover, the results of completed clinical studies will be reported.

Can immunostimulatory agents enhance the abscopal effect of radiotherapy?

PubMed

Levy, Antonin; Chargari, Cyrus; Marabelle, Aurelien; Perfettini, Jean-Luc; Magné, Nicolas; Deutsch, Eric

2016-07-01

Ionising radiation (IR) may harm cancer cells through a rare indirect out-of-field phenomenon described as the abscopal effect. Increasing evidence demonstrates that radiotherapy could be capable of generating tumour-specific immune responses. On the other hand, effects of IR also include inhibitory immune signals on the tumour microenvironment. Following these observations, and in the context of newly available immunostimulatory agents in metastatic cancers (anti-cytotoxic T lymphocyte-associated antigen 4 and programmed cell death protein-1 or -ligand 1 [PD1 or PDL-1]), there is a remarkable potential for synergistic combinations of IR with such agents that act through the reactivation of immune surveillance. Here, we present and discuss the pre-clinical and clinical rationale supporting the enhancement of the abscopal effect of IR on the blockade of immune checkpoints and discuss the evolving potential of immunoradiotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

In Silico Simulation of a Clinical Trial Concerning Tumour Response to Radiotherapy

NASA Astrophysics Data System (ADS)

Dionysiou, Dimitra D.; Stamatakos, Georgios S.; Athanaileas, Theodoras E.; Merrychtas, Andreas; Kaklamani, Dimitra; Varvarigou, Theodora; Uzunoglu, Nikolaos

2008-11-01

The aim of this paper is to demonstrate how multilevel tumour growth and response to therapeutic treatment models can be used in order to simulate clinical trials, with the long-term intention of both better designing clinical studies and understanding their outcome based on basic biological science. For this purpose, an already developed computer simulation model of glioblastoma multiforme response to radiotherapy has been used and a clinical study concerning glioblastoma multiforme response to radiotherapy has been simulated. In order to facilitate the simulation of such virtual trials, a toolkit enabling the user-friendly execution of the simulations on grid infrastructures has been designed and developed. The results of the conducted virtual trial are in agreement with the outcome of the real clinical study.

External audit on the clinical practice and medical decision-making at the departments of radiotherapy in Budapest and Vienna.

PubMed

Esik, O; Seitz, W; Lövey, J; Knocke, T H; Gaudi, I; Németh, G; Pötter, R

1999-04-01

To present an example of how to study and analyze the clinical practice and the quality of medical decision-making under daily routine working conditions in a radiotherapy department, with the aims of detecting deficiencies and improving the quality of patient care. Two departments, each with a divisional organization structure and an established internal audit system, the University Clinic of Radiotherapy and Radiobiology in Vienna (Austria), and the Department of Radiotherapy at the National Institute of Oncology in Budapest (Hungary), conducted common external audits. The descriptive parameters of the external audit provided information on the auditing (auditor and serial number of the audit), the cohorts (diagnosis, referring institution, serial number and intention of radiotherapy) and the staff responsible for the treatment (division and physician). During the ongoing external audits, the qualifying parameters were (1) the sound foundation of the indication of radiotherapy, (2) conformity to the institution protocol (3), the adequacy of the choice of radiation equipment, (4) the appropriateness of the treatment plan, and the correspondence of the latter with (5) the simulation and (6) verification films. Various degrees of deviation from the treatment principles were defined and scored on the basis of the concept of Horiot et al. (Horiot JC, Schueren van der E. Johansson KA, Bernier J, Bartelink H. The program of quality assurance of the EORTC radiotherapy group. A historical overview. Radiother. Oncol. 1993,29:81-84), with some modifications. The action was regarded as adequate (score 1) in the event of no deviation or only a small deviation with presumably no alteration of the desired end-result of the treatment. A deviation adversely influencing the result of the therapy was considered a major deviation (score 3). Cases involving a minor deviation (score 2) were those only slightly affecting the therapeutic end-results, with effects between those of cases with scores 1 and 3. Non-performance of the necessary radiotherapeutic procedures was penalized by the highest score of 4. Statistical evaluation was performed with the BMDP software package, using variance analysis. Bimonthly audits (six with a duration of 4-6 h in each institution) were carried out by three auditors from the evaluating departments; they reviewed a total of 452 cases in Department A, and 265 cases in Department B. Despite the comparable staffing and instrumental conditions, a markedly higher number (1.5 times) of new cases were treated in Department A, but with a lower quality of radiotherapy, as adequate values of qualifying parameters (1-6) were more frequent for the cases treated in Department B (85.3%, 94%, 83.4%, 28.3%, 41.9% and 81.1%) than for those in Department A (67%, 83.4%, 87.8%, 26.1%, 33.2% and 17.7%). The responsible division (including staff and instrumentation), the responsible physician and the type of the disease each exerted a highly significant effect on the quality level of the treatment. Statistical analysis revealed a positive influence of the curative (relative to the palliative/symptomatic) intention of the treatment on the level of quality, but the effect of the first radiotherapy (relative to the second or further one) was statistically significant in only one department. At the same time, the quality parameters did not vary with the referring institution, the auditing person or the serial number of the audit. The external audit relating to the provision of radiotherapeutic care proved feasible with the basic conformity and compliance of the staff and resulted in valuable information to take correction measures.

Commercial glass beads as TLDs in radiotherapy produced by different manufacturers

NASA Astrophysics Data System (ADS)

Jafari, S. M.; Bates, N. M.; Jupp, T.; Abdul Sani, S. F.; Nisbet, A.; Bradley, D. A.

2017-08-01

While commercial jewellery glass beads offer the basis of novel radiotherapy TL dosimetry (Jafari et al. 2014a,b,c, 2015a,b), detailed study of TL variation is required for the products from various manufacturers. Investigation is made for glass beads from four manufacturers from four countries: China (Rocaille), Japan (Mill Hill), Indonesia (TOHO™) and Czech Republic (Czech). Sample composition was determined using an energy-dispersive X-ray unit coupled to a scanning electron microscope. Values of mass attenuation coefficient, μ/ρ, as a function of photon energy were then calculated for photons of energy 1 keV to 10 MeV, using the National Institute of Standards and Technology XCOM program. Radiation and energy response were determined using X-rays generated at accelerating potentials from 80 kVp to 6 MV (TPR20/10=0.670). All bead types showed TL to be linear with dose (R2>0.999). Glow curve dosimetric peaks reached a maximum value at 300 °C for the Toho and 290 °C for the Czech and Mill Hill products but was between 200-250 °C for the Rocaille product. Radiation sensitivity following mass normalisation varied within an order of magnitude; Toho samples showed the greatest and Rocaille the least sensitivity. For the Toho, Czech, Rocaille and Mill Hill samples the energy responses at 80 kVp were 5.0, 4.0, 3.6 and 3.3 times that obtained at 6 MV. All four glass bead types offer potential use as TL dosimeters over doses commonly applied in radiotherapy. Energy response variation was <1% at 6 MV but significant variation was found for photon beam energies covering the kV range; careful characterisation is required if use at this range is intended.

A phase 1 dose-escalation study of the oral histone deacetylase inhibitor abexinostat in combination with standard hypofractionated radiotherapy in advanced solid tumors

PubMed Central

Deutsch, Eric; Moyal, Elizabeth Cohen-Jonathan; Gregorc, Vanesa; Zucali, Paolo Andrea; Menard, Jean; Soria, Jean-Charles; Kloos, Ioana; Hsu, Jeff; Luan, Ying; Liu, Emily; Vezan, Remus; Graef, Thorsten; Rivera, Sofia

2017-01-01

Current treatments for advanced solid tumors tend to be only palliative. Although radiotherapy is administered with a curative intent, radioresistance and dose-limiting toxicities pose limitations to treatment. Abexinostat, an oral pan-histone deacetylase inhibitor, demonstrated enhanced sensitivity to radiation in various solid tumor cell lines. We conducted an exploratory, phase 1, dose-escalation study of abexinostat in combination with standard hypofractionated radiotherapy in patients with advanced solid tumors treated in a palliative setting. Among 58 treated patients, the median age was 61.5 years (range, 20-82); 47% of the patients had M1 stage disease, and 95% had received previous chemotherapy alone or chemotherapy in combination with surgery and/or radiotherapy. The recommended phase 2 dose was determined to be 90 mg/m2 (140 mg). Of the 51 patients evaluable for response, best overall response was 8% (1 complete response [CR], 3 partial responses [PRs]), and best loco-regional response was 12% (1 CR and 5 PRs) at a median follow-up of 16 weeks. Of note, patients with target or non-target brain lesions showed encouraging responses, with 1 patient achieving a best loco-regional response of CR. Treatment-emergent grade ≥3 adverse events (AEs) were few, with most common being thrombocytopenia (17%), lymphopenia (12%), and hypokalemia (7%). Six patients (10%) discontinued treatment due to AEs. No grade ≥3 prolongation of the QTc interval was observed, with no treatment discontinuations due to this AE. Oral abexinostat combined with radiotherapy was well tolerated in patients with advanced solid tumors. The combination may have potential for treatment of patients with brain lesions. PMID:28915584

Accuracy requirements and uncertainties in radiotherapy: a report of the International Atomic Energy Agency.

PubMed

van der Merwe, Debbie; Van Dyk, Jacob; Healy, Brendan; Zubizarreta, Eduardo; Izewska, Joanna; Mijnheer, Ben; Meghzifene, Ahmed

2017-01-01

Radiotherapy technology continues to advance and the expectation of improved outcomes requires greater accuracy in various radiotherapy steps. Different factors affect the overall accuracy of dose delivery. Institutional comprehensive quality assurance (QA) programs should ensure that uncertainties are maintained at acceptable levels. The International Atomic Energy Agency has recently developed a report summarizing the accuracy achievable and the suggested action levels, for each step in the radiotherapy process. Overview of the report: The report seeks to promote awareness and encourage quantification of uncertainties in order to promote safer and more effective patient treatments. The radiotherapy process and the radiobiological and clinical frameworks that define the need for accuracy are depicted. Factors that influence uncertainty are described for a range of techniques, technologies and systems. Methodologies for determining and combining uncertainties are presented, and strategies for reducing uncertainties through QA programs are suggested. The role of quality audits in providing international benchmarking of achievable accuracy and realistic action levels is also discussed. The report concludes with nine general recommendations: (1) Radiotherapy should be applied as accurately as reasonably achievable, technical and biological factors being taken into account. (2) For consistency in prescribing, reporting and recording, recommendations of the International Commission on Radiation Units and Measurements should be implemented. (3) Each institution should determine uncertainties for their treatment procedures. Sample data are tabulated for typical clinical scenarios with estimates of the levels of accuracy that are practically achievable and suggested action levels. (4) Independent dosimetry audits should be performed regularly. (5) Comprehensive quality assurance programs should be in place. (6) Professional staff should be appropriately educated and adequate staffing levels should be maintained. (7) For reporting purposes, uncertainties should be presented. (8) Manufacturers should provide training on all equipment. (9) Research should aid in improving the accuracy of radiotherapy. Some example research projects are suggested.

Estimating the costs of intensity-modulated and 3-dimensional conformal radiotherapy in Ontario.

PubMed

Yong, J H E; McGowan, T; Redmond-Misner, R; Beca, J; Warde, P; Gutierrez, E; Hoch, J S

2016-06-01

Radiotherapy is a common treatment for many cancers, but up-to-date estimates of the costs of radiotherapy are lacking. In the present study, we estimated the unit costs of intensity-modulated radiotherapy (imrt) and 3-dimensional conformal radiotherapy (3D-crt) in Ontario. An activity-based costing model was developed to estimate the costs of imrt and 3D-crt in prostate cancer. It included the costs of equipment, staff, and supporting infrastructure. The framework was subsequently adapted to estimate the costs of radiotherapy in breast cancer and head-and-neck cancer. We also tested various scenarios by varying the program maturity and the use of volumetric modulated arc therapy (vmat) alongside imrt. From the perspective of the health care system, treating prostate cancer with imrt and 3D-crt respectively cost $12,834 and $12,453 per patient. The cost of radiotherapy ranged from $5,270 to $14,155 and was sensitive to analytic perspective, radiation technique, and disease site. Cases of head-and-neck cancer were the most costly, being driven by treatment complexity and fractions per treatment. Although imrt was more costly than 3D-crt, its cost will likely decline over time as programs mature and vmat is incorporated. Our costing model can be modified to estimate the costs of 3D-crt and imrt for various disease sites and settings. The results demonstrate the important role of capital costs in studies of radiotherapy cost from a health system perspective, which our model can accommodate. In addition, our study established the need for future analyses of imrt cost to consider how vmat affects time consumption.

It Is Tough and Tiring but It Works—Children’s Experiences of Undergoing Radiotherapy

PubMed Central

Engvall, Gunn; Ångström-Brännström, Charlotte; Mullaney, Tara; Nilsson, Kristina; Wickart-Johansson, Gun; Svärd, Anna-Maja; Nyholm, Tufve; Lindh, Jack; Lindh, Viveca

2016-01-01

Approximately 300 children ages 0 to 18 are diagnosed with cancer in Sweden every year, and 80 to 90 of them undergo radiotherapy treatment. The aim was to describe children’s experiences of preparing for and undergoing radiotherapy, and furthermore to describe children’s suggestions for improvement. Thirteen children between the ages of 5 and 15 with various cancer diagnoses were interviewed. Data was analyzed using qualitative content analysis. The findings revealed five categories: positive and negative experiences with hospital stays and practical arrangements; age-appropriate information, communication, and guidance to various degrees; struggle with emotions; use of distraction and other suitable coping strategies; and children’s suggestions for improvement during radiotherapy. An overarching theme emerged: “It is tough and tiring but it works”. Some key areas were: explanatory visits, the need for information and communication, being afraid, discomfort and suffering, the need for media distraction, dealing with emotions, and the need for support. A systematic, family-centered preparation program could possible help families prepare and individualized distraction during radiotherapy could contribute to reducing distress. Further studies with interventions could clarify successful programs. PMID:27055258

Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy.

PubMed

Grimaldi, Antonio M; Simeone, Ester; Giannarelli, Diana; Muto, Paolo; Falivene, Sara; Borzillo, Valentina; Giugliano, Francesca Maria; Sandomenico, Fabio; Petrillo, Antonella; Curvietto, Marcello; Esposito, Assunta; Paone, Miriam; Palla, Marco; Palmieri, Giuseppe; Caracò, Corrado; Ciliberto, Gennaro; Mozzillo, Nicola; Ascierto, Paolo A

2014-01-01

Cancer radiotherapy (RT) may induce what is referred to as the "abscopal effect," a regression of non-irradiated metastatic lesions distant from the primary tumor site directly subject to irradiation. This clinical response is rare, but has been surmised to be an immune-mediated phenomenon, suggesting that immunotherapy and RT could potentially synergize. Here, we report the outcome of patients with advanced melanoma treated with the immune checkpoint blockade monoclonal antibody antagonist, ipilimumab followed by RT. Patients were selected for enrollment at the National Cancer Institute "Fondazione G.Pascale" through the expanded access program in Italy. Those who experienced disease progression after ipilimumab thus received subsequent RT and were selected for analysis. Among 21 patients, 13 patients (62%) received RT to treat metastases in the brain and 8 received RT directed at extracranial sites. An abscopal response was observed in 11 patients (52%), 9 of whom had partial responses (43%) and 2 had stable disease (10%). The median time from RT to an abscopal response was 1 month (range 1-4). Median overall survival (OS) for all 21 patients was 13 months (range 6-26). Median OS for patients with abscopal responses was extended to 22.4 months (range 2.5-50.3) vs. 8.3 months (range 7.6-9.0) without. A local response to RT was detected in 13 patients (62%) and, of these, 11 patients (85%) had an abscopal response and abscopal effects were only observed among patients exhibiting a local response. These results suggest RT after ipilimumab may lead to abscopal responses in some patients with advanced melanoma correlating with prolonged OS. Our data also suggest that local responses to RT may be predictive of abscopal responses. Further research in larger randomized trials is needed to validate these results.

Oncologists’ Perspectives on Consolidation Radiation Treatment after Chemotherapy for Lymphomas: A Survey Study by the Lymphoma Working Committee of the Turkish Oncology Group (TOG)

PubMed Central

Tanriverdi, Ozgur; Barista, Ibrahim; Paydas, Semra; Nayir, Erdinc; Karakas, Yusuf

2017-01-01

In this study, we aimed to determine the perspectives of medical and radiation oncologists regarding consolidation radiotherapy in patients with a complete response after chemotherapy for Hodgkin’s and non-Hodgkin’s lymphomas. The survey was designed to identify demographic and occupational features of medical and radiation oncologists and their views on application of consolidation radiotherapy in their clinical practices, as based on a five-point Likert scale (never, rarely, sometimes, often, and always). The study covered 263, out of 935, physicians working in the oncology field as either medical or radiation oncologists; the rate of return on the invitations to participate was 28%. The majority of the participants were male radiation oncologists, with a duration of between 5 and 10 years of work as a university hospital official, and the mean age was 38 ± 14 (years). Although the most commonly followed international guidelines were NCCN, among the physicians, the majority of the respondents suggested that the guidelines were unclear regarding recommendations for consolidative radiotherapy. The administered dose for consolidative radiotherapy in lymphoma patients was indicated as 40 Gy by 49% of all the physicians and the most common cause of hesitancy concerning consolidative radiation treatment was the risk of secondary malignancies as a long-term adverse effect (54%). In conclusion, we suggest that medical oncologists could be most active in the treatment of lymphoma through a continuous training program about lymphomas and current national guidelines. PMID:29172293

Does chronomodulated radiotherapy improve pathological response in locally advanced rectal cancer?

PubMed

Squire, Tim; Buchanan, Grant; Rangiah, David; Davis, Ian; Yip, Desmond; Chua, Yu Jo; Rich, Tyvin; Elsaleh, Hany

2017-01-01

The predominant mode of radiation-induced cell death for solid tumours is mitotic catastrophe, which is in part dependent on sublethal damage repair being complete at around 6 h. Circadian variation appears to play a role in normal cellular division, and this could influence tumour response of radiation treatment depending on the time of treatment delivery. We tested the hypothesis that radiation treatment later in the day may improve tumour response and nodal downstaging in rectal cancer patients treated neoadjuvantly with radiation therapy. Recruitment was by retrospective review of 267 rectal cancer patients treated neoadjuvantly in the Department of Radiation Oncology at the Canberra Hospital between January 2010 and November 2015. One hundred and fifty-five patients met the inclusion criteria for which demographic, pathological and imaging data were collected, as well as the time of day patients received treatment with each fraction of radiotherapy. Data analysis was performed using the Statistical Package R with nonparametric methods of significance for all tests set at p < 0.05. Of the 45 female and 110 male patients, the median age was 64. Seventy-three percent had cT3 disease and there was a mean tumour distance from the anal verge of 7 cm. Time to surgical resection following radiotherapy ranged from 4 to 162 days with a median of 50 days, with a complete pathological response seen in 21% of patients. Patients exhibiting a favourable pathological response had smaller median pre- and postradiotherapy tumour size and had a greater change in tumour size following treatment (p < 0.01). Patients who received the majority of their radiotherapy fractions after 12:00 pm were more likely to show a complete or moderate pathological response (p = 0.035) and improved nodal downstaging. There were also more favourable responses amongst patients with longer time to surgical resection postradiotherapy (p < 0.004), although no relationship was seen between response and tumour distance from the anal verge. Females were less likely to exhibit several of the above responses. Neoadjuvant radiotherapy for locally advanced rectal cancer performed later in the day coupled with a longer time period to surgical resection may improve pathological tumour response rates and nodal downstaging. A prospective study in chronomodulated radiotherapy in this disease is warranted.

[Integration of the radiotherapy irradiation planning in the digital workflow].

PubMed

Röhner, F; Schmucker, M; Henne, K; Momm, F; Bruggmoser, G; Grosu, A-L; Frommhold, H; Heinemann, F E

2013-02-01

At the Clinic of Radiotherapy at the University Hospital Freiburg, all relevant workflow is paperless. After implementing the Operating Schedule System (OSS) as a framework, all processes are being implemented into the departmental system MOSAIQ. Designing a digital workflow for radiotherapy irradiation planning is a large challenge, it requires interdisciplinary expertise and therefore the interfaces between the professions also have to be interdisciplinary. For every single step of radiotherapy irradiation planning, distinct responsibilities have to be defined and documented. All aspects of digital storage, backup and long-term availability of data were considered and have already been realized during the OSS project. After an analysis of the complete workflow and the statutory requirements, a detailed project plan was designed. In an interdisciplinary workgroup, problems were discussed and a detailed flowchart was developed. The new functionalities were implemented in a testing environment by the Clinical and Administrative IT Department (CAI). After extensive tests they were integrated into the new modular department system. The Clinic of Radiotherapy succeeded in realizing a completely digital workflow for radiotherapy irradiation planning. During the testing phase, our digital workflow was examined and afterwards was approved by the responsible authority.

Autophagy inhibition radiosensitizes in vitro, yet reduces radioresponses in vivo due to deficient immunogenic signalling

PubMed Central

Ko, A; Kanehisa, A; Martins, I; Senovilla, L; Chargari, C; Dugue, D; Mariño, G; Kepp, O; Michaud, M; Perfettini, J-L; Kroemer, G; Deutsch, E

2014-01-01

Clinical oncology heavily relies on the use of radiotherapy, which often leads to merely transient responses that are followed by local or distant relapse. The molecular mechanisms explaining radioresistance are largely elusive. Here, we identified a dual role of autophagy in the response of cancer cells to ionizing radiation. On one hand, we observed that the depletion of essential autophagy-relevant gene products, such as ATG5 and Beclin 1, increased the sensitivity of human or mouse cancer cell lines to irradiation, both in vitro (where autophagy inhibition increased radiation-induced cell death and decreased clonogenic survival) and in vivo, after transplantation of the cell lines into immunodeficient mice (where autophagy inhibition potentiated the tumour growth-inhibitory effect of radiotherapy). On the other hand, when tumour proficient or deficient for autophagy were implanted in immunocompetent mice, it turned out that defective autophagy reduced the efficacy of radiotherapy. Indeed, radiotherapy elicited an anti-cancer immune response that was dependent on autophagy-induced ATP release from stressed or dying tumour cells and was characterized by dense lymphocyte infiltration of the tumour bed. Intratumoural injection of an ecto-ATPase inhibitor restored the immune infiltration of autophagy-deficient tumours post radiotherapy and improved the growth-inhibitory effect of ionizing irradiation. Altogether, our results reveal that beyond its cytoprotective function, autophagy confers immunogenic properties to tumours, hence amplifying the efficacy of radiotherapy in an immunocompetent context. This has far-reaching implications for the development of pharmacological radiosensitizers. PMID:24037090

SU-F-E-12: Elective International Rotations in Medical Physics Residency Programs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, D; Mundt, A; Einck, J

Purpose: The purpose of this educational program is to motivate talented, intelligent individuals to become stakeholders in the global effort to improve access to radiotherapy. Methods: The need to improve global access to radiotherapy has been clearly established and several organizations are making substantial progress in securing funding and developing plans to achieve this worthwhile goal. The incorporation of elective international rotations in residency programs may provide one possible mechanism to promote and support this future investment. We recently incorporated an elective 1-month international rotation into our CAMPEP accredited Medical Physics residency program, with our first rotation taking place inmore » Vietnam. A unique aspect of this rotation was that it was scheduled collaboratively with our Radiation Oncology residency program such that Radiation Oncology and Medical Physics residents traveled to the same clinic at the same time. Results: We believe the international rotation substantially enhances the educational experience, providing additional benefits to residents by increasing cross-disciplinary learning and offering a shared learning experience. The combined international rotation may also increase benefit to the host institution by modeling positive multidisciplinary working relationships between Radiation Oncologists and Medical Physicists. Our first resident returned with several ideas designed to improve radiotherapy in resource-limited settings – one of which is currently being pursued in collaboration with a vendor. Conclusion: The elective international rotation provides a unique learning experience that has the potential to motivate residents to become stakeholders in the global effort to improve access to radiotherapy. What better way to prepare the next generation of Medical Physicists to meet the challenges of improving global access to radiotherapy than to provide them with training experiences that motivate them to be socially conscious and equip them with the clinical and problem solving skills required to deliver effective treatments in resource limited settings?.« less

Comparison of Thoracic Radiotherapy Efficacy Between Patients With and Without EGFR-mutated Lung Adenocarcinoma.

PubMed

Li, Ming-Hsien; Tsai, Jo-Ting; Ting, Lai-Lei; Lin, Jang-Chun; Liu, Yu-Chang

2018-01-01

To investigate the association between tumor response to thoracic radiotherapy and epidermal growth factor receptor (EGFR) mutation status in patients with lung adenocarcinoma, we collected 48 patients treated between January 2010 and December 2013. Of the 18 patients with EGFR mutation, 15 (83.3%) had a single mutation, and three (16.7%) had double mutation. Different EGFR mutation subtypes exhibited different responses to radiotherapy. The identified double EGFR mutations were associated with reduction of residual tumor burden (RTB) after radiotherapy. In univariate analysis, EGFR mutations in exon 18, 20, and 21 and double EGFR mutation were significant factors predicting RTB. In multivariate analysis, exon 20 mutation was the only significant factor. Patients with EGFR mutation seemed to have longer mean overall survival (OS) compared to the group with wild-type EGFR (31.1 vs. 26.6 months, p=0.49). The median and mean OS in patients with double EGFR mutation vs. wild-type EGFR were 20.1 vs. 16.9 months and 28.9 vs. 26.6 months, respectively. Further studies with larger sample size are warranted to clarify the association of EGFR mutation status with the lung tumor response after radiotherapy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Medical physics in radiotherapy: The importance of preserving clinical responsibilities and expanding the profession's role in research, education, and quality control

PubMed Central

Malicki, Julian

2015-01-01

Medical physicists have long had an integral role in radiotherapy. In recent decades, medical physicists have slowly but surely stepped back from direct clinical responsibilities in planning radiotherapy treatments while medical dosimetrists have assumed more responsibility. In this article, I argue against this gradual withdrawal from routine therapy planning. It is essential that physicists be involved, at least to some extent, in treatment planning and clinical dosimetry for each and every patient; otherwise, physicists can no longer be considered clinical specialists. More importantly, this withdrawal could negatively impact treatment quality and patient safety. Medical physicists must have a sound understanding of human anatomy and physiology in order to be competent partners to radiation oncologists. In addition, they must possess a thorough knowledge of the physics of radiation as it interacts with body tissues, and also understand the limitations of the algorithms used in radiotherapy. Medical physicists should also take the lead in evaluating emerging challenges in quality and safety of radiotherapy. In this sense, the input of physicists in clinical audits and risk assessment is crucial. The way forward is to proactively take the necessary steps to maintain and advance our important role in clinical medicine. PMID:25949219

Physician Expectations of Treatment Outcomes for Patients With Brain Metastases Referred for Whole Brain Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barnes, Elizabeth A., E-mail: toni.barnes@sunnybrook.c; Chow, Edward; Tsao, May N.

2010-01-15

Purpose: Patients with advanced cancer are referred to our Rapid Response Radiotherapy Program for quick access to palliative radiotherapy. The primary objective of this prospective study was to determine the physician expectations of the treatment outcomes for patients with brain metastases referred for whole brain radiotherapy (WBRT). The secondary objectives were to determine the factors influencing the expectations and to examine the accuracy of the physician-estimated patient survival. Methods and Materials: Patients were identified during a 17-month period. The referring physicians were sent a survey by facsimile to be completed and returned before the patient consultation. Information was sought onmore » the patient's disease status, the physician's expectations of WBRT, the estimated patient survival and performance status, and physician demographic data. Results: A total of 137 surveys were sent out, and the overall response rate was 57.7%. The median patient age was 66 years (range, 35-87), 78.5% had multiple brain metastases, 42.3% had a controlled primary tumor, and 62.3% had extracranial disease. WBRT was thought to stabilize neurologic symptoms, improve quality of life, and allow for a Decadron (dexamethasone) taper by >=94.9% of the referring physicians; 87.0% thought WBRT would improve performance status; 77.9% thought it would improve neurologic symptoms; and 40.8% thought it would improve survival. The referring physicians estimated patient survival as a median of 6.0 months; however, the actual survival was a median of 2.5 months, for a median individual difference of 1.9 months (p < .0001). Conclusion: Physicians referring patients with brain metastases for consideration of WBRT are often overly optimistic when estimating the clinical benefit of the treatment and overestimate patient survival. These findings highlight the need for education and additional research in this field.« less

Optical spectroscopy of radiotherapy and photodynamic therapy responses in normal rat skin shows vascular breakdown products

NASA Astrophysics Data System (ADS)

Teles de Andrade, Cintia; Nogueira, Marcelo S.; Kanick, Stephen C.; Marra, Kayla; Gunn, Jason; Andreozzi, Jacqueline; Samkoe, Kimberley S.; Kurachi, Cristina; Pogue, Brian W.

2016-03-01

Photodynamic therapy (PDT) and radiotherapy are non-systemic cancer treatment options with different mechanisms of damage. So combining these techniques has been shown to have some synergy, and can mitigate their limitations such as low PDT light penetration or radiotherapy side effects. The present study monitored the induced tissue changes after PDT, radiotherapy, and a combination protocol in normal rat skin, using an optical spectroscopy system to track the observed biophysical changes. The Wistar rats were treated with one of the protocols: PDT followed by radiotherapy, PDT, radiotherapy and radiotherapy followed by PDT. Reflectance spectra were collected in order to observe the effects of these combined therapies, especially targeting vascular response. From the reflectance, information about oxygen saturation, met-hemoglobin and bilirubin concentration, blood volume fraction (BVF) and vessel radius were extracted from model fitting of the spectra. The rats were monitored for 24 hours after treatment. Results showed that there was no significant variation in the vessel size or BVF after the treatments. However, the PDT caused a significant increase in the met-hemoglobin and bilirubin concentrations, indicating an important blood breakdown. These results may provide an important clue on how the damage establishment takes place, helping to understand the effect of the combination of those techniques in order to verify the existence of a known synergistic effect.

Conventional and conformal technique of external beam radiotherapy in locally advanced cervical cancer: Dose distribution, tumor response, and side effects

NASA Astrophysics Data System (ADS)

Mutrikah, N.; Winarno, H.; Amalia, T.; Djakaria, M.

2017-08-01

The objective of this study was to compare conventional and conformal techniques of external beam radiotherapy (EBRT) in terms of the dose distribution, tumor response, and side effects in the treatment of locally advanced cervical cancer patients. A retrospective cohort study was conducted on cervical cancer patients who underwent EBRT before brachytherapy in the Radiotherapy Department of Cipto Mangunkusumo Hospital. The prescribed dose distribution, tumor response, and acute side effects of EBRT using conventional and conformal techniques were investigated. In total, 51 patients who underwent EBRT using conventional techniques (25 cases using Cobalt-60 and 26 cases using a linear accelerator (LINAC)) and 29 patients who underwent EBRT using conformal techniques were included in the study. The distribution of the prescribed dose in the target had an impact on the patient’s final response to EBRT. The complete response rate of patients to conformal techniques was significantly greater (58%) than that of patients to conventional techniques (42%). No severe acute local side effects were seen in any of the patients (Radiation Therapy Oncology Group (RTOG) grades 3-4). The distribution of the dose and volume to the gastrointestinal tract affected the proportion of mild acute side effects (RTOG grades 1-2). The urinary bladder was significantly greater using conventional techniques (Cobalt-60/LINAC) than using conformal techniques at 72% and 78% compared to 28% and 22%, respectively. The use of conformal techniques in pelvic radiation therapy is suggested in radiotherapy centers with CT simulators and 3D Radiotherapy Treatment Planning Systems (RTPSs) to decrease some uncertainties in radiotherapy planning. The use of AP/PA pelvic radiation techniques with Cobalt-60 should be limited in body thicknesses equal to or less than 18 cm. When using conformal techniques, delineation should be applied in the small bowel, as it is considered a critical organ according to RTOG consensus guidelines.

Impact of involved field radiotherapy in partial response after doxorubicin-based chemotherapy for advanced aggressive non-Hodgkin's lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moser, Elizabeth C.; Kluin-Nelemans, Hanneke C.; Carde, Patrice

2006-11-15

Purpose: Whether salvage therapy in patients with advanced aggressive non-Hodgkin's lymphoma (NHL) in partial remission (PR) should consist of radiotherapy or autologous stem-cell transplantation (ASCT) is debatable. We evaluated the impact of radiotherapy on outcome in PR patients treated in four successive European Organization for Research and Treatment of Cancer trials for aggressive NHL. Patients and Methods: Records of 974 patients (1980-1999) were reviewed regarding initial response, final outcome, and type and timing of salvage treatment. After 8 cycles of doxorubicin-based chemotherapy, 227 NHL patients were in PR and treated: 114 received involved field radiotherapy, 16 ASCT, 93 second-line chemotherapy,more » and 4 were operated. Overall survival (OS) and progression-free survival (PFS) after radiotherapy were estimated (Kaplan-Meier method) and compared with other treatments (log-rank). Impact on survival was evaluated by multivariate analysis (Cox proportional hazards model). Results: The median PFS in PR patients was 4.2 years and 48% remained progression-free at 5 years. Half of the PR patients converted to a complete remission. After conversion, survival was comparable to patients directly in complete remission. Radiotherapy resulted in better OS and PFS compared with other treatments, especially in patients with low to intermediate International Prognostic Index score, bulky disease, or nodal disease only. Correction by multivariate analysis for prognostic factors such as stage, bulky disease, and number of extranodal locations showed that radiotherapy was clearly the most significant factor affecting both OS and PFS. Conclusion: This retrospective analysis demonstrates that radiotherapy can be effective for patients in PR after fully dosed chemotherapy; assessment in a randomized trial (radiotherapy vs. ASCT) is justified.« less

Mechanisms of Invariant Natural Killer T Cell-Mediated Immunoregulation in Cancer

DTIC Science & Technology

2011-05-01

iNKTcells play a major role in regulating the response to treatment with local radiotherapy and CTLA-4 blockade. Preclinical models and clinical trials...and cure rate following treatment with radiotherapy and CTLA-4 blockade, suggesting that iNKT cells can play a major role in regulating the response...represent a small population of cells, their role in shaping the ensuing adaptive response puts them at a critical bridge between the innate and

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hei, Tom K.

This conference grant was proposed to organize and host an international conference at Columbia University in New York to critically assess the cellular and molecular signaling events and tissue response following radiation damage. The conference would also serve as a venue to play tribute to the more than forty years contributions made by Professor Eric J. Hall to the radiation biology field. The goals of the meeting were to examine tumor hypoxia and sensitizer development; recent advances made in clinical radiotherapy; addressed several low dose phenomena, including genomic instability and bystander effects that are important in radiation risk assessment. Studymore » and Results: The symposium was held on October 13th and 14th, 2008 at the Alfred Lerner Hall in the Morningside campus of Columbia University. The symposium, entitled “From Beans to Genes: A Forty Year Odyssey in Radiation Biology” was attended by more than 120 faculty, scientists, clinicians, fellows and students. The symposium, spanned over a day and a half, covered four scientific themes. These included tumor hypoxia and radiosensitizers; low dose radiation response; radiation biology in the practice of radiotherapy, and radiation hazard in space and genetic predisposition to cancer. The program of the symposium is as follow:« less

Establishing and Delivering Quality Radiation Therapy in Resource-Constrained Settings: The Story of Botswana.

PubMed

Efstathiou, Jason A; Heunis, Magda; Karumekayi, Talkmore; Makufa, Remigio; Bvochora-Nsingo, Memory; Gierga, David P; Suneja, Gita; Grover, Surbhi; Kasese, Joseph; Mmalane, Mompati; Moffat, Howard; von Paleske, Alexander; Makhema, Joseph; Dryden-Peterson, Scott

2016-01-01

There is a global cancer crisis, and it is disproportionately affecting resource-constrained settings, especially in low- and middle-income countries (LMICs). Radiotherapy is a critical and cost-effective component of a comprehensive cancer control plan that offers the potential for cure, control, and palliation of disease in greater than 50% of patients with cancer. Globally, LMICs do not have adequate access to quality radiation therapy and this gap is particularly pronounced in sub-Saharan Africa. Although there are numerous challenges in implementing a radiation therapy program in a low-resource setting, providing more equitable global access to radiotherapy is a responsibility and investment worth prioritizing. We outline a systems approach and a series of key questions to direct strategy toward establishing quality radiation services in LMICs, and highlight the story of private-public investment in Botswana from the late 1990s to the present. After assessing the need and defining the value of radiation, we explore core investments required, barriers that need to be overcome, and assets that can be leveraged to establish a radiation program. Considerations addressed include infrastructure; machine choice; quality assurance and patient safety; acquisition, development, and retention of human capital; governmental engagement; public-private partnerships; international collaborations; and the need to critically evaluate the program to foster further growth and sustainability. © 2015 by American Society of Clinical Oncology.

Amifostine reduces side effects and improves complete response rate during radiotherapy: Results of a meta-analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sasse, Andre Deeke; Gontijo de Oliveira Clark, Luciana; Sasse, Emma Chen

Purpose: To evaluate the efficacy of amifostine in diminishing radiotherapy side effects and whether or not it protects the tumor. Methods and Materials: We performed a systematic review and meta-analysis of 14 included randomized controlled trials, comprising 1451 patients, comparing the use of radiotherapy vs. radiotherapy plus amifostine for cancer treatment. Results: The use of amifostine significantly reduced the risk of developing mucositis (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.29-0.48; p < 0.00001), esophagitis (OR, 0.38; CI, 0.26-0.54; p < 0.00001), acute xerostomia (OR, 0.24; CI, 0.15-0.36; p < 0.00001), late xerostomia (OR, 0.33; CI, 0.21-0.51; p

Fractionated external beam radiotherapy of skull base metastases with cranial nerve involvement.

PubMed

Dröge, L H; Hinsche, T; Canis, M; Alt-Epping, B; Hess, C F; Wolff, H A

2014-02-01

Skull base metastases frequently appear in a late stage of various tumor entities and cause pain and neurological disorders which strongly impair patient quality of life. This study retrospectively analyzed fractionated external beam radiotherapy (EBRT) as a palliative treatment approach with special respect to neurological outcome, feasibility and acute toxicity. A total of 30 patients with skull base metastases and cranial nerve disorders underwent EBRT with a mean total dose of 31.6 Gy. Neurological status was assessed before radiotherapy, during radiotherapy and 2 weeks afterwards categorizing orbital, parasellar, middle fossa, jugular foramen and occipital condyle involvement and associated clinical syndromes. Neurological outcome was scored as persistence of symptoms, partial response, good response and complete remission. Treatment-related toxicity and overall survival were assessed. Before EBRT 37 skull base involvement syndromes were determined with 4 patients showing more than 1 syndrome. Of the patients 81.1 % responded to radiotherapy with 10.8 % in complete remission, 48.6 % with good response and 21.6 % with partial response. Grade 1 toxicity of the skin occurred in two patients and grade 1 hematological toxicity in 1 patient under concurrent chemoradiotherapy. Median overall survival was 3.9 months with a median follow-up of 45 months. The use of EBRT for skull base metastases with symptomatic involvement of cranial nerves is marked by good therapeutic success in terms of neurological outcome, high feasibility and low toxicity rates. These findings underline EBRT as the standard therapeutic approach in the palliative setting.

Effects of a Short-Term Dance Movement Therapy Program on Symptoms and Stress in Patients With Breast Cancer Undergoing Radiotherapy: A Randomized, Controlled, Single-Blind Trial.

PubMed

Ho, Rainbow T H; Fong, Ted C T; Cheung, Irene K M; Yip, Paul S F; Luk, Mai-Yee

2016-05-01

Integrated interventions with combined elements of body movement and psychotherapy on treatment-related symptoms in cancer patients are relatively scarce. The aim of the present study is to investigate the effectiveness of dance movement therapy (DMT) on improving treatment-related symptoms in a randomized controlled trial. A total of 139 Chinese patients with breast cancer awaiting adjuvant radiotherapy were randomized to DMT or control group. The intervention included six 1.5-hour DMT sessions provided twice a week over the course of radiotherapy. Self-report measures on perceived stress, anxiety, depression, fatigue, pain, sleep disturbance, and quality of life were completed before and after the three-week program. DMT showed significant effects on buffering the deterioration in perceived stress, pain severity, and pain interference (Cohen d = 0.34-0.36, P < 0.05). No significant intervention effects were found on anxiety, depression, fatigue, sleep disturbance, and quality of life (Cohen d = 0.01-0.20, P > 0.05). The short-term DMT program can counter the anticipated worsening of stress and pain in women with breast cancer during radiotherapy. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Immunotherapy and stereotactic ablative radiotherapy (ISABR): a curative approach?

PubMed

Bernstein, Michael B; Krishnan, Sunil; Hodge, James W; Chang, Joe Y

2016-08-01

Conventional radiotherapy, in addition to its well-established tumoricidal effects, can also activate the host immune system. Radiation therapy modulates tumour phenotypes, enhances antigen presentation and tumour immunogenicity, increases production of cytokines and alters the tumour microenvironment, enabling destruction of the tumour by the immune system. Investigating the combination of radiotherapy with immunotherapeutic agents, which also promote the host antitumour immune response is, therefore, a logical progression. As the spectrum of clinical use of stereotactic radiotherapy continues to broaden, the question arose as to whether the ablative radiation doses used can also stimulate immune responses and, if so, whether we can amplify these effects by combining immunotherapy and stereotactic ablative radiotherapy (SABR). In this Perspectives article, we explore the preclinical and clinical evidence supporting activation of the immune system following SABR. We then examine studies that provide data on the effectiveness of combining these two techniques - immunotherapy and SABR - in an approach that we have termed 'ISABR'. Lastly, we provide general guiding principles for the development of future clinical trials to investigate the efficacy of ISABR in the hope of generating further interest in these exciting developments.

New techniques for assessing response after hypofractionated radiotherapy for lung cancer

PubMed Central

Mattonen, Sarah A.; Huang, Kitty; Ward, Aaron D.; Senan, Suresh

2014-01-01

Hypofractionated radiotherapy (HFRT) is an effective and increasingly-used treatment for early stage non-small cell lung cancer (NSCLC). Stereotactic ablative radiotherapy (SABR) is a form of HFRT and delivers biologically effective doses (BEDs) in excess of 100 Gy10 in 3-8 fractions. Excellent long-term outcomes have been reported; however, response assessment following SABR is complicated as radiation induced lung injury can appear similar to a recurring tumor on CT. Current approaches to scoring treatment responses include Response Evaluation Criteria in Solid Tumors (RECIST) and positron emission tomography (PET), both of which appear to have a limited role in detecting recurrences following SABR. Novel approaches to assess response are required, but new techniques should be easily standardized across centers, cost effective, with sensitivity and specificity that improves on current CT and PET approaches. This review examines potential novel approaches, focusing on the emerging field of quantitative image feature analysis, to distinguish recurrence from fibrosis after SABR. PMID:24688782

Role of Activin A in Immune Response to Breast Cancer

DTIC Science & Technology

2016-12-01

the response to radiotherapy (RT). 2 KEYWORDS Breast cancer, metastasis, transforming growth factor-beta (TGFβ) superfamily, activin- A, radiotherapy... Transforming Growth Factor-beta (TGFβ) and activin A (actA) are members of the TGFβ superfamily with overlapping as well as distinct functions in many...Vaccination C. Vanpouille-Box, S. Formenti, and S. Demaria; Weill Cornell Medical College, New York, NY Purpose/Objective(s): Transforming Growth

Response of melanoma to heat and radiation therapy--a review of the literature and experience from The Prince of Wales Hospital, Sydney.

PubMed

Mameghan, H; Knittel, T

1988-11-07

Our review of the literature indicates that radiotherapy and/or heat therapy can provide local control of recurrent or metastatic melanoma in a large proportion of patients. This has undoubted value in the local palliation of symptoms and, in the absence of disseminated disease, can be curative. At The Prince of Wales Hospital, Sydney, we have studied the response of melanoma lesions to heat and radiation therapy and have assessed the reaction in the adjacent normal skin. Thirty-two melanoma lesions that were measurable in 12 patients received radiotherapy and heat therapy in different combinations and dose schedules (15 lesions received radiotherapy alone, six lesions received heat therapy alone, and 11 lesions received combined radiation and heat therapy). The acute normal skin reaction was compared between lesions that received single modality radiation or heat therapy and those that received the combination of heat and radiation therapy. A moderate or severe reaction developed at six of the 21 sites that were treated by a single modality, and at four of the 11 sites that received combined heat and radiation therapy (P = 0.7), and all healed within a few days. Evaluation of the melanoma response to therapy was possible only in 26 of the 32 lesions that were treated because two patients died soon after therapy and the response of their six lesions was not evaluable. A complete response occurred in 14 (54%) of 26 lesions and a partial response occurred in 10 (38%) of 26 lesions. The objective response by treatment modality was 10 of 15 lesions for radiotherapy, six of six lesions for heat therapy and eight of 11 lesions for both therapies combined. We conclude that radiotherapy and heat therapy, separately or combined, produce acceptably-low damage to normal tissue and highly-satisfactory local control of melanoma.

SU-E-T-275: Radiobiological Evaluation of Intensity Modulated Radiotherapy Treatment for Locally Advanced Head and Neck Squamous Cell Carcinomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rekha Reddy, B.; Ravikumar, M.; Tanvir Pasha, C.R

2014-06-01

Purpose: To evaluate the radiobiological outcome of Intensity Modulated Radiotherapy Treatment (IMRT) for locally advanced head and neck squamous cell carcinomas using HART (Histogram Analysis in Radiation Therapy; J Appl Clin Med Phys 11(1): 137–157, 2010) program and compare with the clinical outcomes. Methods: We have treated 20 patients of stage III and IV HNSCC Oropharynx and hypopharynx with accelerated IMRT technique and concurrent chemotherapy. Delineation of tumor and normal tissues were done using Danish Head and Neck Cancer Group (DAHANCA) contouring guidelines and radiotherapy was delivered to a dose of 70Gy in 35 fractions to the primary and involvedmore » lymph nodes, 63Gy to intermediate risk areas and 56 Gy to lower risk areas, Monday to Saturday, 6 Days/week using 6 MV Photons with an expected overall treatment time of 6 weeks. The TCP and NTCP's were calculated from the dose-volume histogram (DVH) statistics using the Poisson Statistics (PS) and JT Lyman models respectively and the Resultwas correlated with clinical outcomes of the patients with mean follow up of 24 months. Results: Using HART program, the TCP (0.89± 0.01) of primary tumor and the NTCP for parotids (0.20±0.12), spinal cord (0.05±0.01), esophagus (0.30±0.2), mandible (0.35±0.21), Oral cavity (0.37±0.18), Larynx (0.30±0.15) were estimated and correlated with clinical outcome of the patients. Conclusion: Accelerated IMRT with Chemotherapy is a clinical feasible option in the treatment of locally advanced HNSCC with encouraging initial tumour response and acceptable acute toxicities. The correlation between the clinical outcomes and radiobiological model estimated parameters using HART programs are found to be satisfactory.« less

A model to describe potential effects of chemotherapy on critical radiobiological treatments

NASA Astrophysics Data System (ADS)

Rodríguez-Pérez, D.; Desco, M. M.; Antoranz, J. C.

2016-08-01

Although chemo- and radiotherapy can annihilate tumors on their own. they are also used in coadjuvancy: improving local effects of radiotherapy using chemotherapy as a radiosensit.izer. The effects of radiotherapy are well described by current radiobiological models. The goal of this work is to describe a discrete radiotherapy model, that has been previously used describe high radiation dose response as well as unusual radio-responses of some types of tumors (e.g. prostate cancer), to obtain a model of chemo+radiotherapy that can describe how the outcome of their combination is a more efficient removal of the tumor. Our hypothesis is that, although both treatments haven different mechanisms, both affect similar key points of cell metabolism and regulation, that lead to cellular death. Hence, we will consider a discrete model where chemotherapy may affect a fraction of the same targets destroyed by radiotherapy. Although radiotherapy reaches all cells equally, chemotherapy diffuses through a tumor attaining lower concentration in its center and higher in its surface. With our simulations we study the enhanced effect of combined therapy treatment and how it depends on the tissue critical parameters (the parameters of the lion-extensive radiobiological model), the number of “targets” aimed at by chemotherapy, and the concentration and diffusion rate of the drug inside the tumor. The results show that an equivalent, cliemo-radio-dose can be computed that allows the prediction of the lower radiation dose that causes the same effect than a radio-only treatment.

Oncologists’ Perspectives on Consolidation Radiation Treatment after Chemotherapy for Lymphomas: A Survey Study by the Lymphoma Working Committee of the Turkish Oncology Group (TOG)

PubMed

Tanriverdi, Ozgur; Barista, Ibrahim; Paydas, Semra; Nayir, Erdinc; Karakas, Yusuf

2017-11-26

In this study, we aimed to determine the perspectives of medical and radiation oncologists regarding consolidation radiotherapy in patients with a complete response after chemotherapy for Hodgkin’s and non-Hodgkin’s lymphomas. The survey was designed to identify demographic and occupational features of medical and radiation oncologists and their views on application of consolidation radiotherapy in their clinical practices, as based on a five-point Likert scale (never, rarely, sometimes, often, and always). The study covered 263, out of 935, physicians working in the oncology field as either medical or radiation oncologists; the rate of return on the invitations to participate was 28%. The majority of the participants were male radiation oncologists, with a duration of between 5 and 10 years of work as a university hospital official, and the mean age was 38 ± 14 (years). Although the most commonly followed international guidelines were NCCN, among the physicians, the majority of the respondents suggested that the guidelines were unclear regarding recommendations for consolidative radiotherapy. The administered dose for consolidative radiotherapy in lymphoma patients was indicated as 40 Gy by 49% of all the physicians and the most common cause of hesitancy concerning consolidative radiation treatment was the risk of secondary malignancies as a long-term adverse effect (54%). In conclusion, we suggest that medical oncologists could be most active in the treatment of lymphoma through a continuous training program about lymphomas and current national guidelines. Creative Commons Attribution License

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Yexiong, E-mail: yexiong@yahoo.com; Wang Hua; Jin Jing

Purpose: This study aims to evaluate the outcome and pattern of failure in a large cohort of patients with Stage I NK/T-cell lymphoma of the upper aerodigestive tract treated with radiotherapy alone. Methods and Materials: The pathological diagnosis was confirmed using standard criteria. All patients were treated with high-dose extended-field radiotherapy alone. The median dose was 50 Gy. The primary tumor was located in the nasal cavity (n = 80), Waldeyer ring (n = 5), or oral cavity (n = 2). Results: The overall response to radiotherapy was achieved in 85 of 87 (97.7%) patients, with a complete response ratemore » of 95.4% and a partial response rate of 2.3%. The 5-year overall survival, progression-free survival, and local control rates for all patients were 80%, 69%, and 93%, respectively. Twenty patients (23%) had disease progression or relapse. Of these, 15 patients (17%) developed systemic extranodal disseminations, whereas only 4 (5%) patients had local relapse and 4 (5%) patients had lymph node relapse. Conclusions: Our study suggests that high-dose extended-field radiotherapy alone is a curative therapy and shows favorable clinical outcome in patients with Stage I disease. With the high possibility of local control and primary failure of systemic dissemination, the integration of optimal radiotherapy with more effective systematic therapy is warranted to bring additional improvement to the outcome for these patients.« less

Radiochemotherapy in Anal Cancer: cCR, clinical outcomes and quality of life using two different treatment schedules

PubMed Central

Di Santo, Sara; Trignani, Marianna; Neri, Matteo; Milano, Angelo; Innocenti, Paolo; Taraborrelli, Maria; Augurio, Antonietta; Vinciguerra, Annamaria; Di Tommaso, Monica; Ursini, Lucia Anna; Di Pilla, Angelo; Di Nicola, Marta; Genovesi, Domenico

2014-01-01

Aim Main endpoint was a response rate to therapy; secondary endpoints were disease-free survival, overall survival, acute and late toxicities, specially in terms of anorectal and urinary continence. Background Radiochemotherapy for anal cancer achieves a good clinical response, locoregional control, anal function preservation. However, oncologic outcomes can differ using radiotherapy plus fluorouracil and mytomicin vs. cisplatin and fluorouracil. Methods Between 2000 and 2012, 27 anal cancer patients receiving radiotherapy combined with two different radiochemotherapy schedules, fluorouracil and mytomicin (group A) and cisplatin plus fluorouracil (group B). The Kaplan–Meier method was also used to estimate local control, overall survival and disease free survival. Statistical significance between curves was evaluated using the Log-rank test. Results Complete pathological response was found in 85.2% of patients, with higher rates of response in the group A (100% vs. 63.6%, p = 0.039). No significantly difference was found between the two groups for the other endpoints. Low rates of both acute and late toxicities were recorded. Conclusion Radiotherapy plus fluorouracil and mytomicin provide a better complete pathological response than radiotherapy plus cisplatin and fluorouracil and a greater rate of anal sphincter function preservation. Globally, radiochemotherapy of the anal cancer provides excellent clinical outcomes with a good profile of acute and late toxicity, without difference between the two groups studied. PMID:25859401

TOPK modulates tumour-specific radiosensitivity and correlates with recurrence after prostate radiotherapy

PubMed Central

Pirovano, Giacomo; Ashton, Thomas M; Herbert, Katharine J; Bryant, Richard J; Verrill, Clare L; Cerundolo, Lucia; Buffa, Francesca M; Prevo, Remko; Harrap, Iona; Ryan, Anderson J; Macaulay, Valentine; McKenna, William G; Higgins, Geoff S

2017-01-01

Background: Tumour-specific radiosensitising treatments may enhance the efficacy of radiotherapy without exacerbating side effects. In this study we determined the radiation response following depletion or inhibition of TOPK, a mitogen-activated protein kinase kinase family Ser/Thr protein kinase that is upregulated in many cancers. Methods: Radiation response was studied in a wide range of cancer cell lines and normal cells using colony formation assays. The effect on cell cycle progression was assessed and the relationship between TOPK expression and therapeutic efficacy was studied in a cohort of 128 prostate cancer patients treated with radical radiotherapy. Results: TOPK knockdown did not alter radiation response in normal tissues, but significantly enhanced radiosensitivity in cancer cells. This result was recapitulated in TOPK knockout cells and with the TOPK inhibitor, OTS964. TOPK depletion altered the G1/S transition and G2/M arrest in response to radiation. Furthermore, TOPK depletion increased chromosomal aberrations, multinucleation and apoptotic cell death after irradiation. These results suggest a possible role for TOPK in the radiation-induced DNA damage checkpoints. These findings have clinical relevance, as elevated TOPK protein expression was associated with poorer clinical outcomes in prostate cancer patients treated with radical radiotherapy. Conclusions: This study demonstrates that TOPK disruption may cause tumour-specific radiosensitisation in multiple different tumour types. PMID:28677687

TOPK modulates tumour-specific radiosensitivity and correlates with recurrence after prostate radiotherapy.

PubMed

Pirovano, Giacomo; Ashton, Thomas M; Herbert, Katharine J; Bryant, Richard J; Verrill, Clare L; Cerundolo, Lucia; Buffa, Francesca M; Prevo, Remko; Harrap, Iona; Ryan, Anderson J; Macaulay, Valentine; McKenna, William G; Higgins, Geoff S

2017-08-08

Tumour-specific radiosensitising treatments may enhance the efficacy of radiotherapy without exacerbating side effects. In this study we determined the radiation response following depletion or inhibition of TOPK, a mitogen-activated protein kinase kinase family Ser/Thr protein kinase that is upregulated in many cancers. Radiation response was studied in a wide range of cancer cell lines and normal cells using colony formation assays. The effect on cell cycle progression was assessed and the relationship between TOPK expression and therapeutic efficacy was studied in a cohort of 128 prostate cancer patients treated with radical radiotherapy. TOPK knockdown did not alter radiation response in normal tissues, but significantly enhanced radiosensitivity in cancer cells. This result was recapitulated in TOPK knockout cells and with the TOPK inhibitor, OTS964. TOPK depletion altered the G 1 /S transition and G 2 /M arrest in response to radiation. Furthermore, TOPK depletion increased chromosomal aberrations, multinucleation and apoptotic cell death after irradiation. These results suggest a possible role for TOPK in the radiation-induced DNA damage checkpoints. These findings have clinical relevance, as elevated TOPK protein expression was associated with poorer clinical outcomes in prostate cancer patients treated with radical radiotherapy. This study demonstrates that TOPK disruption may cause tumour-specific radiosensitisation in multiple different tumour types.

Vrx: a verify-record system for radiotherapy.

PubMed

Dickof, P; Morris, P; Getz, D

1984-01-01

A system of computer programs has been created to allow the entry of radiotherapy treatment details as defined by the physician, the verification of the machine parameters at every treatment, and the recording of the entire course of treatment. Various utility programs are available to simplify the use and maintenance of the system. The majority of the code is written in FORTRAN-77, the remainder in MACRO-11. The system has been implemented on a PDP 11/60 minicomputer for use with a Mevatron linear accelerator, the implementation required minor hardware changes to the accelerator.

Strategies to tackle the challenges of external beam radiotherapy for liver tumors.

PubMed

Lock, Michael I; Klein, Jonathan; Chung, Hans T; Herman, Joseph M; Kim, Edward Y; Small, William; Mayr, Nina A; Lo, Simon S

2017-05-18

Primary and metastatic liver cancer is an increasingly common and difficult to control disease entity. Radiation offers a non-invasive treatment alternative for these patients who often have few options and a poor prognosis. However, the anatomy and aggressiveness of liver cancer poses significant challenges such as accurate localization at simulation and treatment, management of motion and appropriate selection of dose regimen. This article aims to review the options available and provide information for the practical implementation and/or improvement of liver cancer radiation programs within the context of stereotactic body radiotherapy and image-guided radiotherapy guidelines. Specific patient inclusion and exclusion criteria are presented given the significant toxicity found in certain sub-populations treated with radiation. Indeed, certain sub-populations, such as those with tumor thrombosis or those with larger lesions treated with transarterial chemoembolization, have been shown to have significant improvements in outcome with the addition of radiation and merit special consideration. Implementing a liver radiation program requires three primary challenges to be addressed: (1) immobilization and motion management; (2) localization; and (3) dose regimen and constraint selection. Strategies to deal with motion include simple internal target volume (ITV) expansions, non-gated ITV reduction strategies, breath hold methods, and surrogate marker methods to enable gating or tracking. Localization of the tumor and organs-at-risk are addressed using contrast infusion techniques to take advantage of different normal liver and cancer vascular anatomy, imaging modalities, and margin management. Finally, a dose response has been demonstrated and dose regimens appear to be converging. A more uniform approach to treatment in terms of technique, dose selection and patient selection will allow us to study liver radiation in larger and, hopefully, multicenter randomized studies.

Strategies to tackle the challenges of external beam radiotherapy for liver tumors

PubMed Central

Lock, Michael I; Klein, Jonathan; Chung, Hans T; Herman, Joseph M; Kim, Edward Y; Small, William; Mayr, Nina A; Lo, Simon S

2017-01-01

Primary and metastatic liver cancer is an increasingly common and difficult to control disease entity. Radiation offers a non-invasive treatment alternative for these patients who often have few options and a poor prognosis. However, the anatomy and aggressiveness of liver cancer poses significant challenges such as accurate localization at simulation and treatment, management of motion and appropriate selection of dose regimen. This article aims to review the options available and provide information for the practical implementation and/or improvement of liver cancer radiation programs within the context of stereotactic body radiotherapy and image-guided radiotherapy guidelines. Specific patient inclusion and exclusion criteria are presented given the significant toxicity found in certain sub-populations treated with radiation. Indeed, certain sub-populations, such as those with tumor thrombosis or those with larger lesions treated with transarterial chemoembolization, have been shown to have significant improvements in outcome with the addition of radiation and merit special consideration. Implementing a liver radiation program requires three primary challenges to be addressed: (1) immobilization and motion management; (2) localization; and (3) dose regimen and constraint selection. Strategies to deal with motion include simple internal target volume (ITV) expansions, non-gated ITV reduction strategies, breath hold methods, and surrogate marker methods to enable gating or tracking. Localization of the tumor and organs-at-risk are addressed using contrast infusion techniques to take advantage of different normal liver and cancer vascular anatomy, imaging modalities, and margin management. Finally, a dose response has been demonstrated and dose regimens appear to be converging. A more uniform approach to treatment in terms of technique, dose selection and patient selection will allow us to study liver radiation in larger and, hopefully, multicenter randomized studies. PMID:28588749

Optimisation in radiotherapy. III: Stochastic optimisation algorithms and conclusions.

PubMed

Ebert, M

1997-12-01

This is the final article in a three part examination of optimisation in radiotherapy. Previous articles have established the bases and form of the radiotherapy optimisation problem, and examined certain types of optimisation algorithm, namely, those which perform some form of ordered search of the solution space (mathematical programming), and those which attempt to find the closest feasible solution to the inverse planning problem (deterministic inversion). The current paper examines algorithms which search the space of possible irradiation strategies by stochastic methods. The resulting iterative search methods move about the solution space by sampling random variates, which gradually become more constricted as the algorithm converges upon the optimal solution. This paper also discusses the implementation of optimisation in radiotherapy practice.

A randomized controlled trial of mindfulness-based stress reduction for women with early-stage breast cancer receiving radiotherapy.

PubMed

Henderson, Virginia P; Massion, Ann O; Clemow, Lynn; Hurley, Thomas G; Druker, Susan; Hébert, James R

2013-09-01

To testthe relative effectiveness of a mindfulness-based stress reduction program (MBSR) compared with a nutrition education intervention (NEP) and usual care (UC) in women with newly diagnosed early-stage breast cancer (BrCA)undergoing radiotherapy. Datawere available from a randomized controlled trialof 172 women, 20 to 65 years old, with stage I or II BrCA. Data from women completing the 8-week MBSR program plus 3 additional sessions focuses on special needs associated with BrCA were compared to women receiving attention control NEP and UC. Follow-up was performed at 3 post-intervention points: 4 months, and 1 and 2 years. Standardized, validated self-administered questionnaires were used to assess psychosocial variables. Descriptive analyses compared women by randomization assignment. Regression analyses, incorporating both intention-to-treat and post hoc multivariable approaches, were used to control for potential confounding variables. A subset of 120 women underwent radiotherapy; 77 completed treatment prior to the study, and 40 had radiotherapy during the MBSR intervention. Women who actively received radiotherapy (art) while participating in the MBSR intervention (MBSR-art) experienced a significant (P < .05) improvement in 16 psychosocial variables compared with the NEP-art, UC-art, or both at 4 months. These included health-related, BrCA-specific quality of life and psychosocial coping, which were the primary outcomes, and secondary measures, including meaningfulness, helplessness, cognitive avoidance, depression, paranoid ideation, hostility, anxiety, global severity, anxious preoccupation, and emotional control. MBSR appears to facilitate psychosocial adjustment in BrCA patients receiving radiotherapy, suggesting applicability for MBSR as adjunctive therapy in oncological practice.

Radiotherapy dosimetry using a commercial OSL system.

PubMed

Viamonte, A; da Rosa, L A R; Buckley, L A; Cherpak, A; Cygler, J E

2008-04-01

A commercial optically stimulated luminescence (OSL) system developed for radiation protection dosimetry by Landauer, Inc., the InLight microStar reader, was tested for dosimetry procedures in radiotherapy. The system uses carbon-doped aluminum oxide, Al2O3:C, as a radiation detector material. Using this OSL system, a percent depth dose curve for 60Co gamma radiation was measured in solid water. Field size and SSD dependences of the detector response were also evaluated. The dose response relationship was investigated between 25 and 400 cGy. The decay of the response with time following irradiation and the energy dependence of the Al2O3:C OSL detectors were also measured. The results obtained using OSL dosimeters show good agreement with ionization chamber and diode measurements carried out under the same conditions. Reproducibility studies show that the response of the OSL system to repeated exposures is 2.5% (1sd), indicating a real possibility of applying the Landauer OSL commercial system for radiotherapy dosimetric procedures.

Dose-Effect Relationships for Recurrence of Keloid and Pterygium After Surgery and Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kal, Henk B.; Veen, Ronald E.; Juergenliemk-Schulz, Ina M.

2009-05-01

Purpose: To show radiation dose-response relationships for recurrence of keloid and pterygium after radiotherapy following surgery. Methods and Materials: Using PubMed, we performed a retrospective review of articles reporting incidences and/or dose-response relationships for recurrence of keloid and pterygium after radiotherapy following surgery. The irradiation regimens identified were normalized by use of the linear-quadratic model; biologically effective doses (BEDs) were calculated. Results: For keloid recurrence after radiotherapy following keloid removal, with either teletherapy or brachytherapy, the recurrence rate after having delivered a BED greater than 30 Gy is less than 10%. For pterygium recurrence after bare sclera surgery and {supmore » 90}Sr {beta}-irradiation, a BED of about 30 Gy seems to be sufficient also to reduce the recurrence rate to less than 10%. Conclusions: Most of the doses in the radiotherapy schemes used for prevention of keloid recurrence after surgery are too low. In contrast, the doses applied in most regimens to prevent pterygium recurrence are too high. A scheme with a BED of 30 to 40 Gy seems to be sufficient to prevent recurrences of keloid as well as pterygium.« less

Risk analysis factors for local recurrence in Ewing's sarcoma: when should adjuvant radiotherapy be administered?

PubMed

Albergo, J I; Gaston, C L L; Parry, M C; Laitinen, M K; Jeys, L M; Tillman, R M; Abudu, A T; Grimer, R J

2018-02-01

The aim of this study was to analyse a group of patients with non-metastatic Ewing's sarcoma at presentation and identify prognostic factors affecting the development of local recurrence, in order to assess the role of radiotherapy. A retrospective review of all patients with a Ewing's sarcoma treated between 1980 and 2012 was carried out. Only those treated with chemotherapy followed by surgery and/or radiotherapy were included. Patients were grouped according to site (central or limb) for further analysis of the prognostic factors. A total of 388 patients were included in the study. Of these, 60 (15%) developed local recurrence at a mean median of 27 months (sd 24, range 7 to 150) and the five-year local recurrence-free survival (5yrLRFS) was 83%. For central tumours, the size of the tumour and histological response to chemotherapy were found to be significant factors for local recurrence. For limb tumours, local recurrence was affected by intralesional and marginal resections, but not by the histological response to chemotherapy. Radiotherapy in those with a marginal resection reduced the risk of local recurrence (5yrLRFS: 96% versus 81%, p = 0.044). Local recurrence significantly affects the overall survival in patients with a Ewing's sarcoma. For those with a tumour in a limb, radiotherapy reduced the risk of local recurrence, especially in those with a marginal margin of excision, but the effect in central tumours was less clear. Radiotherapy for those who have had a wide margin of resection does not reduce the risk of local recurrence, regardless of the histological response to chemotherapy. Cite this article: Bone Joint J 2018;100-B: 247-55. ©2018 The British Editorial Society of Bone & Joint Surgery.

Pembrolizumab combined with stereotactic body radiotherapy in a patient with human immunodeficiency virus and advanced non-small cell lung cancer: a case report.

PubMed

Li, Dongqi; He, Chuanchun; Xia, Yaoxiong; Du, Yaxi; Zhang, Jing

2018-04-23

Pembrolizumab has significantly improved outcomes in patients with advanced non-small cell lung cancer. Combining programmed death-1 inhibitor with stereotactic body radiotherapy showed a slight toxicity and good benefits in recent clinical trials. However, patients infected with human immunodeficiency virus were excluded from most trials because it was assumed that their anti-tumor immunity was compromised compared with immunocompetent patients. In June 2016, a 52-year-old Chinese man presented with human immunodeficiency virus and lung adenocarcinoma (T1bN3M1b). From November 2016 to December 2016, systemic chemotherapy and palliative radiotherapy for bone metastasis of femoral neck were carried out, but the tumor progressed. In January 2017, after immunochemistry detection of programmed death-1 and programmed death-ligand 1 expression (both > 50%), pembrolizumab was started. Three weeks after pembrolizumab, we combined stereotactic body radiotherapy for the primary lung tumor. He received no comfort and his CD4 lymphocyte count was stable. Human immunodeficiency virus-ribonucleic acid remained below the limits of detection. In March 2017, after three cycles of pembrolizumab and 5 weeks of stereotactic body radiotherapy therapy, he suddenly presented with palpitations. Emergency computed tomography scanning showed massive pericardial effusion and interstitial pneumonia. So we interrupted the pembrolizumab use and initiated treatment with prednisolone 1 mg/kg; however, the tumor progressed. Then, his CD4 lymphocyte count declined. Finally he died in June 2017 due to dyscrasia. Pembrolizumab combined with SBRT therapy for patients with human immunodeficiency virus infection and non-small cell lung cancer may lead to serious immune-related adverse events and more clinical trials are needed.

Efficiency and prognosis of whole brain irradiation combined with precise radiotherapy on triple-negative breast cancer.

PubMed

Wu, Xinhong; Luo, Bo; Wei, Shaozhong; Luo, Yan; Feng, Yaojun; Xu, Juan; Wei, Wei

2013-11-01

To investigate the treatment efficiency of whole brain irradiation combined with precise radiotherapy on triple-negative (TN) phenotype breast cancer patients with brain metastases and their survival times. A total of 112 metastatic breast cancer patients treated with whole brain irradiation and intensity modulated radiotherapy (IMRT) or 3D conformal radiotherapy (3DCRT) were analyzed. Thirty-seven patients were of TN phenotype. Objective response rates were compared. Survival times were estimated by using the Kaplan-Meier method. Log-rank test was used to compare the survival time difference between the TN and non-TN groups. Potential prognostic factors were determined by using a Cox proportional hazard regression model. The efficiency of radiotherapy treatment on TN and non-TN phenotypes was 96.2% and 97%, respectively. TN phenotype was associated with worse survival times than non-TN phenotype after radiotherapy (6.9 months vs. 17 months) (P < 0.01). On multivariate analysis, good prognosis was associated with non-TN status, lower graded prognosis assessment class, and nonexistence of active extracranial metastases. After whole brain irradiation followed by IMRT or 3DCRT treatment, TN phenotype breast cancer patients with intracranial metastasis had high objective response rates but shorter survival time. With respect to survival in breast cancer patients with intracranial metastasis, the TN phenotype represents a significant adverse prognostic factor.

Neoadjuvant chemotherapy with continuous infusion of cisplatin and 5-fluorouracil, with or without leucovorin, for locally advanced nasopharyngeal carcinoma.

PubMed

Fonseca, E; Cruz, J J; Rodríguez, C A; Gómez-Bernal, A; Martín, G; Sánchez, P; Nieto, A; Soria, P; Vega, M J; Muñoz, A; Pardal, J L

1996-01-01

Cisplatin-based induction chemotherapy has been extensively tested in nasopharyngeal carcinoma for the improvement of local and systemic control and survival of this disease. In this study, we report the results of the treatment with induction chemotherapy in 40 patients with locally advanced carcinoma of the nasopharynx (LANPC) with four courses of cisplatin (P) 25 mg/m2 per day and 5-fluorouracil (F) 1000 mg/m2 per day both in a 4-days continuous infusion, with or without leucovorin (L) 250 mg/m2 per day in 2-hour infusion at the beginning of daily administration of PF, followed by sequential radiotherapy. All except one were in stage IV. The overall response after induction chemotherapy was 93%, with 55% CR and 38% PR. Definitive overall response after radiotherapy was 98%, with 80% CR and 18% PR. At a maximum follow up of 11 years, the overall survival rate is 55%. Induction chemotherapy with continuous infusion of PF with or without leucovorin followed by radiotherapy is a highly active regimen for the treatment of locally advanced nasopharyngeal carcinoma with response and survival rates comparable to other combinations of sequential or simultaneous chemotherapy and radiotherapy.

Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial.

PubMed

Shaverdian, Narek; Lisberg, Aaron E; Bornazyan, Krikor; Veruttipong, Darlene; Goldman, Jonathan W; Formenti, Silvia C; Garon, Edward B; Lee, Percy

2017-07-01

Preclinical studies have found radiotherapy enhances antitumour immune responses. We aimed to assess disease control and pulmonary toxicity in patients who previously received radiotherapy for non-small-cell lung cancer (NSCLC) before receiving pembrolizumab. We assessed patients with advanced NSCLC treated on the phase 1 KEYNOTE-001 trial at a single institution (University of California, Los Angeles, CA, USA). Patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 1 or less, had adequate organ function, and no history of pneumonitis. Patients received pembrolizumab at a dose of either 2 mg/kg of bodyweight or 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks, until disease progression, unacceptable toxicity, or other protocol-defined reasons for discontinuation. Disease response and pulmonary toxicity were prospectively assessed by Immune-related Response Criteria and Common Terminology Criteria for Adverse Events version 4.0. The primary objective of the KEYNOTE-001 trial was to assess the safety, side-effect profile, and antitumour activity of pembrolizumab. For our secondary analysis, patients were divided into subgroups to compare patients who previously received radiotherapy with patients who had not. Our primary objective was to determine whether previous radiotherapy affected progression-free survival, overall survival, and pulmonary toxicity in the intention-to-treat population. The KEYNOTE-001 trial was registered with ClinicalTrials.gov, number NCT01295827. Between May 22, 2012, and July 11, 2014, 98 patients were enrolled and received their first cycle of pembrolizumab. One patient was lost to follow-up. 42 (43%) of 97 patients had previously received any radiotherapy for the treatment of NSCLC before the first cycle of pembrolizumab. 38 (39%) of 97 patients received extracranial radiotherapy and 24 (25%) of 97 patients received thoracic radiotherapy. Median follow-up for surviving patients was 32·5 months (IQR 29·8-34·1). Progression-free survival with pembrolizumab was significantly longer in patients who previously received any radiotherapy than in patients without previous radiotherapy (hazard ratio [HR] 0·56 [95% CI 0·34-0·91], p=0·019; median progression-free survival 4·4 months [95% CI 2·1-8·6] vs 2·1 months [1·6-2·3]) and for patients who previously received extracranial radiotherapy compared with those without previous extracranial radiotherapy (HR 0·50 [0·30-0·84], p=0·0084; median progression-free survival 6·3 months [95% CI 2·1-10·4] vs 2·0 months [1·8-2·1]). Overall survival with pembrolizumab was significantly longer in patients who previously received any radiotherapy than in patients without previous radiotherapy (HR 0·58 [95% CI 0·36-0·94], p=0·026; median overall survival 10·7 months [95% CI 6·5-18·9] vs 5·3 months [2·7-7·7]) and for patients who previously received extracranial radiotherapy compared with those without previous extracranial radiotherapy (0·59 [95% CI 0·36-0·96], p=0·034; median overall survival 11·6 months [95% CI 6·5-20·5] vs 5·3 months [3·0-8·5]). 15 (63%) of 24 patients who had previously received thoracic radiotherapy had any recorded pulmonary toxicity versus 29 (40%) of 73 patients with no previous thoracic radiotherapy. Three (13%) patients with previous thoracic radiotherapy had treatment-related pulmonary toxicity compared with one (1%) of those without; frequency of grade 3 or worse treatment-related pulmonary toxicities was similar (one patient in each group). Our data suggest that previous treatment with radiotherapy in patients with advanced NSCLC results in longer progression-free survival and overall survival with pembrolizumab treatment than that seen in patients who did not have previous radiotherapy, with an acceptable safety profile. Further clinical trials investigating this combination are needed to determine the optimal treatment strategy for patients with advanced NSCLC. US National Institutes of Health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Salvage radiotherapy in prostate cancer patients. Planning, treatment response and prognosis using (11)C-choline PET/CT.

PubMed

García, J R; Cozar, M; Soler, M; Bassa, P; Riera, E; Ferrer, J

2016-01-01

To assess the prognostic value of the therapeutic response by (11)C-choline PET/CT in prostate cancer patients with biochemical recurrence in which (11)C-choline PET/CT indicated radio-guided radiotherapy. The study included 37 patients initially treated with prostatectomy, who were treated due to biochemical recurrence. (11)C-choline PE/CT detected infra-diaphragmatic lymph-node involvement. All were selected for intensity modulated radiation therapy, escalating the dose according to the PET findings. One year after treatment patients underwent PSA and (11)C-choline PET/CT categorizing response (complete/partial/progression). Clinical/biochemical/image monitoring was performed until appearance of second relapse or 36 months in disease-free patients. (11)C-choline PET/CT could detect lymph nodes in all 37 patients. They were 18 (48.6%) of more than a centimetre in size and 19 (51.3%) with no pathological CT morphology: 9 (24.3%) with positive lymph nodes of around one centimetre and 10 (27.0%) only less than a centimetre in size. The response by (11)C-choline PET/CT was categorised one year after radiotherapy: 16 patients (43.2%) complete response; 15 (40.5%) partial response, and 6 (16.2%) progression. The response was concordant between the PSA result and (11)C-choline PET/CT in 32 patients (86.5%), and discordant in five (13.5%). New recurrence was detected in 12 patients (80%) with partial response, and 5 (31.2%) with complete response. The mean time to recurrence was 9 months after partial response, and 18 months after complete response (significant difference, p<.0001). (11)C-choline PET/CT allows the selection of patients with recurrent prostate cancer candidates for radiotherapy and to plan the technique. The evaluation of therapeutic response by (11)C-choline PET/CT has prognostic significance. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Low-Dose Palliative Radiotherapy for Cutaneous B- and T-Cell Lymphomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neelis, Karen J.; Schimmel, Erik C.; Vermeer, Maarten H.

Purpose: To determine the efficacy of low-dose palliative radiotherapy for both low-grade malignant cutaneous B-cell lymphomas (CBCLs) and cutaneous T-cell lymphomas (mycosis fungoides). Methods and Materials: A total of 18 patients with low-grade CBCL (10 primary cutaneous marginal zone B-cell and 8 primary cutaneous follicle center lymphomas) with 44 symptomatic plaques and tumors underwent low-dose (4 Gy in two fractions) local radiotherapy. A total of 31 patients with mycosis fungoides were treated at 82 symptomatic sites, initially with 4 Gy and later with 8 Gy in two fractions. Results: The complete response rate for CBCL lesions was 72%. Of themore » 44 B-cell lymphoma lesions, 13 were re-treated to the same site after a median of 6.3 months because of persistent (n = 8) or recurrent (n = 5) symptomatic disease. Of the mycosis fungoides patients treated with 4 Gy in two fractions (17 lesions), 70% failed to respond. Increasing the dose to 8 Gy in two fractions yielded a complete response rate of 92% (60 of 65 lesions). The patients in whom low-dose radiotherapy failed were retreated with 20 Gy in eight fractions. Conclusion: Our results have demonstrated that low-dose involved-field radiotherapy induces a high response rate in both CBCL and cutaneous T-cell lymphoma lesions without any toxicity. Therefore, this treatment is now our standard palliative treatment. At progression, it is safe and feasible to apply greater radiation doses.« less

Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy

PubMed Central

Grimaldi, Antonio M; Simeone, Ester; Giannarelli, Diana; Muto, Paolo; Falivene, Sara; Borzillo, Valentina; Giugliano, Francesca Maria; Sandomenico, Fabio; Petrillo, Antonella; Curvietto, Marcello; Esposito, Assunta; Paone, Miriam; Palla, Marco; Palmieri, Giuseppe; Caracò, Corrado; Ciliberto, Gennaro; Mozzillo, Nicola; Ascierto, Paolo A

2014-01-01

Cancer radiotherapy (RT) may induce what is referred to as the “abscopal effect,” a regression of non-irradiated metastatic lesions distant from the primary tumor site directly subject to irradiation. This clinical response is rare, but has been surmised to be an immune-mediated phenomenon, suggesting that immunotherapy and RT could potentially synergize. Here, we report the outcome of patients with advanced melanoma treated with the immune checkpoint blockade monoclonal antibody antagonist, ipilimumab followed by RT. Patients were selected for enrollment at the National Cancer Institute “Fondazione G.Pascale” through the expanded access program in Italy. Those who experienced disease progression after ipilimumab thus received subsequent RT and were selected for analysis. Among 21 patients, 13 patients (62%) received RT to treat metastases in the brain and 8 received RT directed at extracranial sites. An abscopal response was observed in 11 patients (52%), 9 of whom had partial responses (43%) and 2 had stable disease (10%). The median time from RT to an abscopal response was 1 month (range 1–4). Median overall survival (OS) for all 21 patients was 13 months (range 6–26). Median OS for patients with abscopal responses was extended to 22.4 months (range 2.5–50.3) vs. 8.3 months (range 7.6–9.0) without. A local response to RT was detected in 13 patients (62%) and, of these, 11 patients (85%) had an abscopal response and abscopal effects were only observed among patients exhibiting a local response. These results suggest RT after ipilimumab may lead to abscopal responses in some patients with advanced melanoma correlating with prolonged OS. Our data also suggest that local responses to RT may be predictive of abscopal responses. Further research in larger randomized trials is needed to validate these results. PMID:25083318

Prediction of lung density changes after radiotherapy by cone beam computed tomography response markers and pre-treatment factors for non-small cell lung cancer patients.

PubMed

Bernchou, Uffe; Hansen, Olfred; Schytte, Tine; Bertelsen, Anders; Hope, Andrew; Moseley, Douglas; Brink, Carsten

2015-10-01

This study investigates the ability of pre-treatment factors and response markers extracted from standard cone-beam computed tomography (CBCT) images to predict the lung density changes induced by radiotherapy for non-small cell lung cancer (NSCLC) patients. Density changes in follow-up computed tomography scans were evaluated for 135 NSCLC patients treated with radiotherapy. Early response markers were obtained by analysing changes in lung density in CBCT images acquired during the treatment course. The ability of pre-treatment factors and CBCT markers to predict lung density changes induced by radiotherapy was investigated. Age and CBCT markers extracted at 10th, 20th, and 30th treatment fraction significantly predicted lung density changes in a multivariable analysis, and a set of response models based on these parameters were established. The correlation coefficient for the models was 0.35, 0.35, and 0.39, when based on the markers obtained at the 10th, 20th, and 30th fraction, respectively. The study indicates that younger patients without lung tissue reactions early into their treatment course may have minimal radiation induced lung density increase at follow-up. Further investigations are needed to examine the ability of the models to identify patients with low risk of symptomatic toxicity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Extensive disease small cell carcinoma of the lung; trial of non-cross resistant chemotherapy and consolidation radiotherapy. [X ray

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dillman, R.O., Taelle, R., Segren, S.; Royston, I.; Koziol, J.

1982-05-15

Twenty-nine patients with extensive disease, small-cell carcinoma of the lung, were treated with two cycles of intensive combination chemotherapy: HexaVAC (hexamethylmelamine, vincristine, Adriamycin, cyclophosphamide). Responders received prophylactic cranial radiation (2000 rad/10 fractions) and non cross resistant chemotherapy via a schedule of alternating cycles of CMV (cyclophosphamide, methotrexate, VP-16-213) and AMV (Adriamycin, methotrexate, VP-16-213). Whenever a complete response was achieved, consolidation radiotherapy was given to the lung primary (4000 rad/20 fractions, split dose) and abdominal metastases (2000 rad/10 fractions) synchronous with CMV therapy. The complete response rate was 14% with HexaVAC, but increased to 38% during CMV/AMV. Total response rate (completemore » and partial) was 59% and median survival was 42 weeks. Prophylactic brain radiation prevented clinical relapse in the brain in all 14 patients who received it. However, consolidation radiotherapy failed to prevent clinical relapse in the lung and/or liver, and therapeutic brain radiation (3000 rad) failed to prevent relapse in that site. The simultaneous administration of radiotherapy and chemotherapy was well-tolerated although two patients with poor performance status died of infectious complications while leukopenic. In spite of the high response rate, durable remissions with prolonged disease free survival were rare. Further evaluation of induction, consolidation, and maintenance modes of therapy are indicated.« less

Hypofractionated radiation therapy for prostate cancer: The McGill University Health Center experience.

PubMed

Barbosa Neto, O; Souhami, L; Faria, S

2015-10-01

In 2002, at the McGill University Health Centre, we began a program of hypofractionated radiotherapy for patients with low risk prostate cancer as an alternative to conventionally fractionated radiotherapy. Our initial hypofractionation regimen was 66 Gy given in 22 fractions, prescribed to the isocenter, delivered with 3D-conformal radiotherapy plan. The clinical target volume was the prostate gland and the planning target volume consisted of the clinical target volume plus a 7-mm margin in all directions. Hormonal therapy was not given to any patient. The long-term results for this group of patients confirmed the feasibility, good tolerance and excellent disease control of the regimen with the extra-benefit of being convenient to both patients and the health system by shortening treatment duration. The outcomes of this approach stimulated us to use hypofractionation in patients with intermediate-risk. Analysis of 100 intermediate-risk patients receiving our hypofractionated radiotherapy regimen (no hormones) shows, at median follow-up of 75 months, 8-year biochemical recurrence free and cancer specific survival rates of 90% and 95%, respectively, with acceptable toxicity. Our technique changed from 3D to intensity modulated radiotherapy with the dose adjusted to 60 Gy in 20 fractions. Lastly, we have expanded the program to high-risk patients where IMRT treatments are given to the pelvic nodes (44 Gy in 20 fractions) with a simultaneous integrated boost delivery to the prostate (60 Gy in the same 20 fractions). Our long-term results have shown that moderate hypofractionated radiotherapy for prostate cancer is safe and provides good tumor control comparable to high-dose conventionally fractionated radiotherapy. This hypofractionated regimen has been routinely used in our institution. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

The treatment of patients with 1-3 brain metastases: is there a place for whole brain radiotherapy alone, yet? A retrospective analysis.

PubMed

Buglione, Michela; Pedretti, Sara; Gipponi, Stefano; Buttolo, Luciano; Panciani, Paolo; Poliani, Pietro Luigi; Liserre, Roberto; Borghetti, Paolo; Pegurri, Ludovica; Costa, Loredana; Triggiani, Luca; Pasinetti, Nadia; Ghirardelli, Paolo; Pandini, Sara; Padovani, Alessandro; Magrini, Stefano Maria

2015-12-01

To evaluate the efficacy of whole brain radiotherapy (WBRT) with or without other treatments in patients (pts) with 1-3 brain metastases (BM). Toxicities and survival of 134 pts treated between 2009 and 2013 with WBRT alone (58 pts), WBRT plus surgery (SUR-WBRT: 42 pts) or WBRT followed by stereotactic or integrated boost radiotherapy (SRT-WBRT: 34 pts) were analyzed. Differences in toxicity (acute and late) incidence and in overall (OS), disease-free (DFS) and disease-specific survival (DSS) were evaluated (χ(2)-test, uni- and multivariate analysis). Pts given intensified treatments (SUR- and SBRT-WBRT) had better 3-month local response compared to WBRT alone group (p < 0.045). Better 1-year local control was evident only in SRT-WBRT pts (p < 0.035). Univariate OS analysis confirmed, as favorable prognostic factors, RPA class I (p < 0.001), GPA class III and IV (p < 0.001), single metastasis (p = 0.045), stable primary disease (p = 0.03), intensified treatment (p = 0.000), systemic therapy after radiotherapy (p = 0.04) and response of metastatic lesions (p = 0.002). At multivariate analysis, OS was better in RPA class I pts (p = 0.002), who had more aggressive radiotherapy treatments (p = 0.001), chemotherapy after radiotherapy (p < 0.001) and response to RT (p = 0.003). Response to radiotherapy (p = 0.002) and BM number (p < 0.001) resulted independently prognostic for DFS. About 60 % of patients had mild acute toxicity (G1), especially headache (51 %) and fatigue (34 %); only 2 patients (2 %) had severe (G3) headache and 5 patients (4 %) severe fatigue (G3) reversible with oral steroids. No differences were evident between the different treatment groups. Among 80 pts followed up with MRI, 12 (15 %) had leukoencephalopathy (equally distributed across subgroups) and 5 (6 %) radionecroses, 4/5 asymptomatic, 5/5 in pts given intensified treatments. This analysis confirms the known prognostic factors for BM, emphasizing the importance of intensified treatments in a population with favorable features.

Characterization of a new MOSFET detector configuration for in vivo skin dosimetry.

PubMed

Scalchi, Paolo; Francescon, Paolo; Rajaguru, Priyadarshini

2005-06-01

The dose released to the patient skin during a radiotherapy treatment is important when the skin is an organ at risk, or on the contrary, is included in the target volume. Since most treatment planning programs do not predict dose within several millimeters of the body surface, it is important to have a method to verify the skin dose for the patient who is undergoing radiotherapy. A special type of metal oxide semiconductors field-effect transistors (MOSFET) was developed to perform in vivo skin dosimetry for radiotherapy treatments. Water-equivalent depth (WED), both manufacturing and sensor reproducibility, dependence on both field size and angulation of the sensor were investigated using 6 MV photon beams. Patient skin dosimetries were performed during 6 MV total body irradiations (TBI). The resulting WEDs ranged from 0.04 and 0.15 mm (0.09 mm on average). The reproducibility of the sensor response, for doses of 50 cGy, was within +/-2% (maximum deviation) and improves with increasing sensitivity or dose level. As to the manufacturing reproducibility, it was found to be +/-0.055 mm. No WED dependence on the field size was verified, but possible variations of this quantity with the field size could be hidden by the assessment uncertainty. The angular dependence, for both phantom-surface and in-air setups, when referred to the mean response, is within +/-27% until 80 degree rotations. The results of the performed patient skin dosimetries showed that, normally, our TBI setup was suitable to give skin the prescribed dose, but, for some cases, interventions were necessary: as a consequence the TBI setup was corrected. The water-equivalent depth is, on average, less than the thinnest thermoluminescent dosimeters (TLD). In addition, when compared with TLDs, the skin MOSFETs have significant advantages, like immediate both readout and reuse, as well as the permanent storage of dose. These sensors are also waterproof. The in vivo dosimetries performed prove the importance of verifying the dose to the skin of the patient undergoing radiotherapy.

[Initial outcome of induction chemotherapy with weekly paclitaxel followed by three-dimensional conformal radiotherapy and concurrent weekly paclitaxel for stage III non-small cell lung cancer].

PubMed

Wang, Wei-Hua; Bao, Yong; Chen, Ming; Zhang, Li; Li, Kai-Xin; Xu, Guang-Chuan; Deng, Xiao-Wu; Lu, Tai-Xiang; Cui, Nian-Ji

2006-10-01

The efficacy of radiotherapy alone on locally advanced non-small cell lung cancer (NSCLC) is poor. Although the combined modality of chemoradiotherapy and dose-escalation of radiotherapy have been the main trends, the optimal modality still remains unknown. This study was to evaluate the toxicity and efficacy of induction chemotherapy (ICT) followed by three-dimensional conformal radiotherapy (3D CRT) and concurrent weekly paclitaxel on unresectable NSCLC. Stage III NSCLC patients with favorable conditions were treated with 2 to 4 cycles of carboplatin (AUC=5-6, d1) combined with paclitaxel (175 mg/m(2), d1), then followed by weekly paclitaxel (40 mg/m(2)) and concurrent 3D CRT within 3-4 weeks. The prescription dose was given as high as possible under the condition that V20 < or =31% and spinal cord dose < or =50 Gy. Thirty-one patients were enrolled. ICT was well tolerated. During the concurrent chemoradiotherapy, the treatment of 3 patients was ended ahead of the schedule because of severe pulmonary and heart toxicities; the treatment of 2 patients was delayed for 7 and 12 days because of fatigue. Myelosuppression was mild (16/31): all were grade 1-2 except 1 was grade 3. Lymphocytopenia was more obvious (29/31, grade 3 in 21). Three patients developed grade 3 radiation-induced esophagitis, and 2 developed grade 3-4 radiation-induced pneumonitis. Two developed grade 3 esophageal stricture. No grade 3-4 pulmonary fibrosis was observed. The overall response rate was 74.1%. The 1-, 2-, 3-year overall survival rates were 74.2%, 41.9%, and 34.6%, respectively, with the median survival time of 18.5 months. The 1-, 2-, 3-year local progression-freely survival rates were 64.5%, 32.3%, and 20.5%, respectively, with the median local progression-freely survival time of 14.3 months. The program of ICT followed by weekly paclitaxel and 3D CRT is accomplished in most of the favorable stage III NSCLC patients. The toxicity is tolerable, and the response rate is inspiriting.

The role of radiotherapy in the management of patients with diffuse low grade glioma: A systematic review and evidence-based clinical practice guideline.

PubMed

Ryken, Timothy C; Parney, Ian; Buatti, John; Kalkanis, Steven N; Olson, Jeffrey J

2015-12-01

(1) What is the optimal role of external beam radiotherapy in the management of adult patients with newly diagnosed low-grade glioma (LGG) in terms of improving outcome (i.e., survival, complications, seizure control or other reported outcomes of interest)? (2) Which radiation strategies (dose, timing, fractionation, stereotactic radiation, brachytherapy, chemotherapy) improve outcomes compared to standard external beam radiation therapy in the initial management of low grade gliomas in adults? (3) Do specific factors (e.g., age, volume, extent of resection, genetic subtype) identify subgroups with better outcomes following radiation therapy than the general population of adults with newly diagnosed low-grade gliomas? These recommendations apply to adults with newly diagnosed diffuse LGG. OUTCOMES IN ADULT PATIENTS WITH NEWLY DIAGNOSED LOW GRADE GLIOMA TREATED WITH RADIOTHERAPY: Level I Radiotherapy is recommended in the management of newly diagnosed low-grade glioma in adults to prolong progression free survival, irrespective of extent of resection. Level II Radiotherapy is recommended in the management of newly diagnosed low grade glioma in adults as an equivalent alternative to observation in preserving cognitive function, irrespective of extent of resection. Level III Radiotherapy is recommended in the management of newly diagnosed low grade glioma in adults to improve seizure control in patients with epilepsy and subtotal resection. Level III Radiotherapy is recommended in the management of newly diagnosed low-grade glioma in adults to prolong overall survival in patients with subtotal resection. Level III Consideration of the risk of radiation induced morbidity, including cognitive decline, imaging abnormalities, metabolic dysfunction and malignant transformation, is recommended when the delivery of radiotherapy is selected in the management of newly diagnosed low-grade glioma in adults. STRATEGIES OF RADIOTHERAPY IN ADULT PATIENTS WITH NEWLY DIAGNOSED LOW GRADE GLIOMA: Level I Lower dose radiotherapy is recommended as an equivalent alternative to higher dose immediate postoperative radiotherapy (45-50.4 vs. 59.4-64.8 Gy) in the management of newly diagnosed low-grade glioma in adults with reduced toxicity. Level III Delaying radiotherapy until recurrence or progression is recommended as an equivalent alternative to immediate postoperative radiotherapy in the management of newly diagnosed low-grade glioma in adults but may result in shorter time to progression. Level III The addition of chemotherapy to radiotherapy is not recommended over whole brain radiotherapy alone in the management of low-grade glioma, as it provides no additional survival benefit. Level III Limited-field radiotherapy is recommended over whole brain radiotherapy in the management of low-grade glioma. Level III Either stereotactic radiosurgery or brachytherapy are recommended as acceptable alternatives to external radiotherapy in selected patients. PROGNOSTIC FACTORS IN ADULT PATIENTS WITH NEWLY DIAGNOSED LOW GRADE GLIOMA TREATED WITH RADIOTHERAPY: Level II It is recommended that age greater than 40 years, astrocytic pathology, diameter greater than 6 cm, tumor crossing the midline and preoperative neurological deficit be considered as negative prognostic indicators when predicting overall survival in adult low grade glioma patients treated with radiotherapy. Level II It is recommended that smaller tumor size, extent of surgical resection and higher mini-mental status exam be considered as positive prognostic indicators when predicting overall survival and progression free survival in patients in adult low grade glioma patients treated with radiotherapy. Level III It is recommended that seizures at presentation, presence of oligodendroglial histological component and 1p19q deletion (along with additional relevant factors-see Table 1) be considered as positive prognostic indicators when predicting response to radiotherapy in adults with low grade gliomas. Level III It is recommended that increasing age, decreasing performance status, decreasing cognition, presence of astrocytic histological component (along with additional relevant factors (see Tables 1, 2) be considered as negative prognostic indicators when predicting response to radiotherapy.

Internet-based computer technology on radiotherapy.

PubMed

Chow, James C L

2017-01-01

Recent rapid development of Internet-based computer technologies has made possible many novel applications in radiation dose delivery. However, translational speed of applying these new technologies in radiotherapy could hardly catch up due to the complex commissioning process and quality assurance protocol. Implementing novel Internet-based technology in radiotherapy requires corresponding design of algorithm and infrastructure of the application, set up of related clinical policies, purchase and development of software and hardware, computer programming and debugging, and national to international collaboration. Although such implementation processes are time consuming, some recent computer advancements in the radiation dose delivery are still noticeable. In this review, we will present the background and concept of some recent Internet-based computer technologies such as cloud computing, big data processing and machine learning, followed by their potential applications in radiotherapy, such as treatment planning and dose delivery. We will also discuss the current progress of these applications and their impacts on radiotherapy. We will explore and evaluate the expected benefits and challenges in implementation as well.

Repeated diffusion MRI reveals earliest time point for stratification of radiotherapy response in brain metastases

NASA Astrophysics Data System (ADS)

Mahmood, Faisal; Johannesen, Helle H.; Geertsen, Poul; Hansen, Rasmus H.

2017-04-01

An imaging biomarker for early prediction of treatment response potentially provides a non-invasive tool for better prognostics and individualized management of the disease. Radiotherapy (RT) response is generally related to changes in gross tumor volume manifesting months later. In this prospective study we investigated the apparent diffusion coefficient (ADC), perfusion fraction and pseudo diffusion coefficient derived from diffusion weighted MRI as potential early biomarkers for radiotherapy response of brain metastases. It was a particular aim to assess the optimal time point for acquiring the DW-MRI scan during the course of treatment, since to our knowledge this important question has not been addressed directly in previous studies. Twenty-nine metastases (N  =  29) from twenty-one patients, treated with whole-brain fractionated external beam RT were analyzed. Patients were scanned with a 1 T MRI system to acquire DW-, T2*W-, T2W- and T1W scans, before start of RT, at each fraction and at follow up two to three months after RT. The DW-MRI parameters were derived using regions of interest based on high b-value images (b  =  800 s mm-2). Both volumetric and RECIST criteria were applied for response evaluation. It was found that in non-responding metastases the mean ADC decreased and in responding metastases it increased. The volume based response proved to be far more consistently predictable by the ADC change found at fraction number 7 and later, compared to the linear response (RECIST). The perfusion fraction and pseudo diffusion coefficient did not show sufficient prognostic value with either response assessment criteria. In conclusion this study shows that the ADC derived using high b-values may be a reliable biomarker for early assessment of radiotherapy response for brain metastases patients. The earliest response stratification can be achieved using two DW-MRI scans, one pre-treatment and one at treatment day 7-9 (equivalent to 21 Gy).

Measuring the inequalities in radiotherapy health resources in Japan: comparison of the Hokkaido-Tohoku and Tokyo districts.

PubMed

Ohba, Hisateru; Narumi, Masakazu; Hosokawa, Yoichiro; Aoki, Masahiko

2010-01-01

The aim of this study was to measure and compare the geographical inequalities in radiotherapy health resources between the Hokkaido-Tohoku and Tokyo districts of Japan. The numbers of radiotherapy facilities, radiologists, and radiological technologists were used to represent radiotherapy health resources. The target areas were 11 prefectures in the Hokkaido-Tohoku and Tokyo districts. The Gini coefficient (GC) was used to measure inequalities in health resources in relation to the population and area of each secondary medical care zone. Correlation analysis was performed to clarify the relation between the GC and the all-cancer mortality rate per 100,000 people. The mean population and area GCs of Yamagata Prefecture were the smallest, whereas the mean population GC of Tokyo and the mean area GC of Hokkaido were the largest. The mean GCs of radiotherapy facilities and radiological technologists were higher in the Tokyo district than in the Hokkaido-Tohoku district. No significant correlation was found between GC and cancer mortality. Geographical inequalities in radiotherapy health resources tended to be larger in the Tokyo district than in the Hokkaido-Tohoku district. It is expected that the radiotherapy system will be substantially improved by the Basic Plan to Promote Cancer Control Programs.

Venetoclax Synergizes with Radiotherapy for Treatment of B-cell Lymphomas.

PubMed

O'Steen, Shyril; Green, Damian J; Gopal, Ajay K; Orozco, Johnnie J; Kenoyer, Aimee L; Lin, Yukang; Wilbur, D Scott; Hamlin, Donald K; Fisher, Darrell R; Hylarides, Mark D; Gooley, Theodore A; Waltman, Amelia; Till, Brian G; Press, Oliver W

2017-07-15

Constitutive B-cell receptor signaling leads to overexpression of the antiapoptotic BCL-2 protein and is implicated in the pathogenesis of many types of B-cell non-Hodgkin lymphoma (B-NHL). The BCL-2 small-molecule inhibitor venetoclax shows promising clinical response rates in several lymphomas, but is not curative as monotherapy. Radiotherapy is a rational candidate for combining with BCL-2 inhibition, as DNA damage caused by radiotherapy increases the activity of pro-apoptotic BCL-2 pathway proteins, and lymphomas are exquisitely sensitive to radiation. We tested B-NHL responses to venetoclax combined with either external beam radiotherapy or radioimmunotherapy (RIT), which joins the selectivity of antibody targeting with the effectiveness of irradiation. We first tested cytotoxicity of cesium-137 irradiation plus venetoclax in 14 B-NHL cell lines representing five lymphoma subtypes. Combination treatment synergistically increased cell death in 10 of 14 lines. Lack of synergy was predicted by resistance to single-agent venetoclax and high BCL-XL expression. We then assessed the efficacy of external beam radiotherapy plus venetoclax in murine xenograft models of mantle cell (MCL), germinal-center diffuse large B-cell (GCB-DLBCL), and activated B-cell (ABC-DLBCL) lymphomas. In each model, external beam radiotherapy plus venetoclax synergistically increased mouse survival time, curing up to 10%. We finally combined venetoclax treatment of MCL and ABC-DLBCL xenografts with a pretargeted RIT (PRIT) system directed against the CD20 antigen. Optimal dosing of PRIT plus venetoclax cured 100% of mice with no detectable toxicity. Venetoclax combined with radiotherapy may be a promising treatment for a wide range of lymphomas Cancer Res; 77(14); 3885-93. ©2017 AACR . ©2017 American Association for Cancer Research.

Effect of increasing radiation dose on pathologic complete response in rectal cancer patients treated with neoadjuvant chemoradiation therapy.

PubMed

Hall, Matthew D; Schultheiss, Timothy E; Smith, David D; Fakih, Marwan G; Wong, Jeffrey Y C; Chen, Yi-Jen

2016-12-01

Neoadjuvant chemoradiation therapy (CRT) increases pathological complete response (pCR) rates compared to radiotherapy alone in patients with stage II-III rectal cancer. Limited evidence addresses whether radiotherapy dose escalation further improves pCR rates. Our purpose is to measure the effects of radiotherapy dose and other factors on post-therapy pathologic tumor (ypT) and nodal stage in rectal cancer patients treated with neoadjuvant CRT followed by mesorectal excision. A non-randomized comparative effectiveness analysis was performed of rectal cancer patients treated in 2000-2013 from the National Oncology Data Alliance™ (NODA), a pooled database of cancer registries from >150 US hospitals. The NODA contains the same data submitted to state cancer registries and SEER combined with validated radiotherapy and chemotherapy records. Eligible patients were treated with neoadjuvant CRT followed by proctectomy and had complete data on treatment start dates, radiotherapy dose, clinical tumor (cT) and ypT stage, and number of positive nodes at surgery (n = 3298 patients). Multivariable logistic regression was used to assess the predictive value of independent variables on achieving a pCR. On multivariable regression, radiotherapy dose, cT stage, and time interval between CRT and surgery were significant predictors of achieving a pCR. After adjusting for the effect of other variates, patients treated with higher radiotherapy doses were also more likely to have negative nodes at surgery and be downstaged from cT3-T4 and/or node positive disease to ypT0-T2N0 after neoadjuvant CRT. Our study suggests that increasing dose significantly improved pCR rates and downstaging in rectal cancer patients treated with neoadjuvant CRT followed by surgery.

Quality of radiotherapy services in post-Soviet countries: An IAEA survey.

PubMed

Rosenblatt, Eduardo; Fidarova, Elena; Ghosh, Sunita; Zubizarreta, Eduardo; Unterkirhere, Olga; Semikoz, Natalia; Sinaika, Valery; Kim, Viktor; Karamyan, Nerses; Isayev, Isa; Akbarov, Kamal; Lomidze, Darejan; Bondareva, Oksana; Tuzlucov, Piotr; Zardodkhonova, Manzura; Tkachev, Sergey; Kislyakova, Marina; Alimov, Jamshid; Pidlubna, Tetiana; Barton, Michael; Mackillop, William

2018-04-25

The quality of radiotherapy services in post-Soviet countries has not yet been studied following a formal methodology. The IAEA conducted a survey using two sets of validated radiation oncology quality indicators (ROIs). Eleven post-Soviet countries were assessed. A coordinator was designated for each country and acted as the liaison between the country and the IAEA. The methodology was a one-time cross-sectional survey using a 58-question tool in Russian. The questionnaire was based on two validated sets of ROIs: for radiotherapy centres, the indicators proposed by Cionini et al., and for data at the country level, the Australasian ROIs. The overall response ratio was 66.3%, but for the Russian Federation, it was 24%. Data were updated on radiotherapy infrastructure and equipment. 256 radiotherapy centres are operating 275 linear accelerators and 337 Cobalt-60 units. 61% of teletherapy machines are older than ten years. Analysis of ROIs revealed significant differences between these countries and radiotherapy practices in the West. Naming, task profile and education programmes of radiotherapy professionals are different than in the West. Most countries need modernization of their radiotherapy infrastructure coupled with adequate staffing numbers and updated education programmes focusing on evidence-based medicine, quality, and safety. Copyright © 2018 Elsevier B.V. All rights reserved.

TU-F-CAMPUS-J-02: Evaluation of Textural Feature Extraction for Radiotherapy Response Assessment of Early Stage Breast Cancer Patients Using Diffusion Weighted MRI and Dynamic Contrast Enhanced MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xie, Y; Wang, C; Horton, J

Purpose: To investigate the feasibility of using classic textural feature extraction in radiotherapy response assessment, we studied a unique cohort of early stage breast cancer patients with paired pre - and post-radiation Diffusion Weighted MRI (DWI-MRI) and Dynamic Contrast Enhanced MRI (DCE-MRI). Methods: 15 female patients from our prospective phase I trial evaluating preoperative radiotherapy were included in this retrospective study. Each patient received a single-fraction radiation treatment, and DWI and DCE scans were conducted before and after the radiotherapy. DWI scans were acquired using a spin-echo EPI sequence with diffusion weighting factors of b = 0 and b =more » 500 mm{sup 2} /s, and the apparent diffusion coefficient (ADC) maps were calculated. DCE-MRI scans were acquired using a T{sub 1}-weighted 3D SPGR sequence with a temporal resolution of about 1 minute. The contrast agent (CA) was intravenously injected with a 0.1 mmol/kg bodyweight dose at 2 ml/s. Two parameters, volume transfer constant (K{sup trans} ) and k{sub ep} were analyzed using the two-compartment Tofts kinetic model. For DCE parametric maps and ADC maps, 33 textural features were generated from the clinical target volume (CTV) in a 3D fashion using the classic gray level co-occurrence matrix (GLCOM) and gray level run length matrix (GLRLM). Wilcoxon signed-rank test was used to determine the significance of each texture feature’s change after the radiotherapy. The significance was set to 0.05 with Bonferroni correction. Results: For ADC maps calculated from DWI-MRI, 24 out of 33 CTV features changed significantly after the radiotherapy. For DCE-MRI pharmacokinetic parameters, all 33 CTV features of K{sup trans} and 33 features of k{sub ep} changed significantly. Conclusion: Initial results indicate that those significantly changed classic texture features are sensitive to radiation-induced changes and can be used for assessment of radiotherapy response in breast cancer.« less

A Comparison of Dose-Response Models for the Parotid Gland in a Large Group of Head-and-Neck Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Houweling, Antonetta C., E-mail: A.Houweling@umcutrecht.n; Philippens, Marielle E.P.; Dijkema, Tim

2010-03-15

Purpose: The dose-response relationship of the parotid gland has been described most frequently using the Lyman-Kutcher-Burman model. However, various other normal tissue complication probability (NTCP) models exist. We evaluated in a large group of patients the value of six NTCP models that describe the parotid gland dose response 1 year after radiotherapy. Methods and Materials: A total of 347 patients with head-and-neck tumors were included in this prospective parotid gland dose-response study. The patients were treated with either conventional radiotherapy or intensity-modulated radiotherapy. Dose-volume histograms for the parotid glands were derived from three-dimensional dose calculations using computed tomography scans. Stimulatedmore » salivary flow rates were measured before and 1 year after radiotherapy. A threshold of 25% of the pretreatment flow rate was used to define a complication. The evaluated models included the Lyman-Kutcher-Burman model, the mean dose model, the relative seriality model, the critical volume model, the parallel functional subunit model, and the dose-threshold model. The goodness of fit (GOF) was determined by the deviance and a Monte Carlo hypothesis test. Ranking of the models was based on Akaike's information criterion (AIC). Results: None of the models was rejected based on the evaluation of the GOF. The mean dose model was ranked as the best model based on the AIC. The TD{sub 50} in these models was approximately 39 Gy. Conclusions: The mean dose model was preferred for describing the dose-response relationship of the parotid gland.« less

Radiobiological concepts for treatment planning of schemes that combines external beam radiotherapy and systemic targeted radiotherapy

NASA Astrophysics Data System (ADS)

Fabián Calderón Marín, Carlos; González González, Joaquín Jorge; Laguardia, Rodolfo Alfonso

2017-09-01

The combination of radiotherapy modalities with external bundles and systemic radiotherapy (CIERT) could be a reliable alternative for patients with multiple lesions or those where treatment planning maybe difficult because organ(s)-at-risk (OARs) constraints. Radiobiological models should have the capacity for predicting the biological irradiation response considering the differences in the temporal pattern of dose delivering in both modalities. Two CIERT scenarios were studied: sequential combination in which one modality is executed following the other one and concurrent combination when both modalities are running simultaneously. Expressions are provided for calculation of the dose-response magnitudes Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP). General results on radiobiological modeling using the linear-quadratic (LQ) model are also discussed. Inter-subject variation of radiosensitivity and volume irradiation effect in CIERT are studied. OARs should be under control during the planning in concurrent CIERT treatment as the administered activity is increased. The formulation presented here may be used for biological evaluation of prescriptions and biological treatment planning of CIERT schemes in clinical situation.

Re-irradiation: outcome, cumulative dose and toxicity in patients retreated with stereotactic radiotherapy in the abdominal or pelvic region.

PubMed

Abusaris, Huda; Hoogeman, M; Nuyttens, Joost J

2012-12-01

The purpose of the present study was to explore the outcome, cumulative dose in tumor and organs at risk and toxicity after extra-cranial stereotactic re-irradiation. Twenty-seven patients were evaluated who had been re-irradiated with stereotactic body radiotherapy (SBRT) after conventional radiotherapy (CRT). The dose summation of the SBRT and CRT plans was done by dose point calculations accounting for fraction size by the linear-quadratic model. Efficacy and toxicity was scored by looking at the reduction in tumor size, pain and bleeding. Symptomatic response was observed in 96% of the patients. The median maximum SBRT dose to the tumor was 90 Gy(3) (range: 42-420 Gy(3)). The median cumulative dose for the rectum, bowel and bladder resulted in 104 Gy(3), 98 Gy(3) and 113 Gy(3), respectively. No grades 5, 4 and 3 acute and late toxicity was observed. re-irradiation to the same region using extra-cranial stereotactic radiotherapy is feasible and resulted in a 96% symptomatic response with low toxicity.

Evolving Clinical Cancer Radiotherapy: Concerns Regarding Normal Tissue Protection and Quality Assurance

PubMed Central

Choi, Won Hoon

2016-01-01

Radiotherapy, which is one of three major cancer treatment methods in modern medicine, has continued to develop for a long period, more than a century. The development of radiotherapy means allowing the administration of higher doses to tumors to improve tumor control rates while minimizing the radiation doses absorbed by surrounding normal tissues through which radiation passes for administration to tumors, thereby reducing or removing the incidence of side effects. Such development of radiotherapy was accomplished by the development of clinical radiation oncology, the development of computers and machine engineering, the introduction of cutting-edge imaging technology, a deepened understanding of biological studies on the effects of radiation on human bodies, and the development of quality assurance (QA) programs in medical physics. The development of radiotherapy over the last two decades has been quite dazzling. Due to continuous improvements in cancer treatment, the average five-year survival rate of cancer patients has been close to 70%. The increases in cancer patients’ complete cure rates and survival periods are making patients’ quality of life during or after treatment a vitally important issue. Radiotherapy is implemented in approximately 1/3 to 2/3s of all cancer patients; and has improved the quality of life of cancer patients in the present age. Over the last century, as a noninvasive treatment, radiotherapy has unceasingly enhanced complete tumor cure rates and the side effects of radiotherapy have been gradually decreasing, resulting in a tremendous improvement in the quality of life of cancer patients. PMID:26908993

Longitudinal diffusion MRI for treatment response assessment: Preliminary experience using an MRI-guided tri-cobalt 60 radiotherapy system.

PubMed

Yang, Yingli; Cao, Minsong; Sheng, Ke; Gao, Yu; Chen, Allen; Kamrava, Mitch; Lee, Percy; Agazaryan, Nzhde; Lamb, James; Thomas, David; Low, Daniel; Hu, Peng

2016-03-01

To demonstrate the preliminary feasibility of a longitudinal diffusion magnetic resonance imaging (MRI) strategy for assessing patient response to radiotherapy at 0.35 T using an MRI-guided radiotherapy system (ViewRay). Six patients (three head and neck cancer, three sarcoma) who underwent fractionated radiotherapy were enrolled in this study. A 2D multislice spin echo single-shot echo planar imaging diffusion pulse sequence was implemented on the ViewRay system and tested in phantom studies. The same pulse sequence was used to acquire longitudinal diffusion data (every 2-5 fractions) on the six patients throughout the entire course of radiotherapy. The reproducibility of the apparent diffusion coefficient (ADC) measurements was assessed using reference regions and the temporal variations of the tumor ADC values were evaluated. In diffusion phantom studies, the ADC values measured on the ViewRay system matched well with reference ADC values with <5% error for a range of ground truth diffusion coefficients of 0.4-1.1 × 10(-3) mm(2)/s. The remote reference regions (i.e., brainstem in head and neck patients) had consistent ADC values throughout the therapy for all three head and neck patients, indicating acceptable reproducibility of the diffusion imaging sequence. The tumor ADC values changed throughout therapy, with the change differing between patients, ranging from a 40% drop in ADC within the first week of therapy to gradually increasing throughout therapy. For larger tumors, intratumoral heterogeneity was observed. For one sarcoma patient, postradiotherapy biopsy showed less than 10% necrosis score, which correlated with the observed 40% decrease in ADC from the fifth fraction to the eighth treatment fraction. This pilot study demonstrated that longitudinal diffusion MRI is feasible using the 0.35 T ViewRay MRI. Larger patient cohort studies are warranted to correlate the longitudinal diffusion measurements to patient outcomes. Such an approach may enable response-guided adaptive radiotherapy.

Capecitabine and Oxaliplatin Before, During, and After Radiotherapy for High-Risk Rectal Cancer.

PubMed

Larsen, Finn Ole; Markussen, Alice; Jensen, Benny V; Fromm, Anne L; Vistisen, Kirsten K; Parner, Vibeke K; Linnemann, Dorte; Hansen, Rasmus H; Johannesen, Helle H; Schou, Jakob V

2017-06-01

To evaluate the effect of capecitabine and oxaliplatin before, during, and after radiotherapy for high-risk rectal cancer. Patients with rectum cancer T4 or T3 involving the mesorectal fascia was included in a prospective phase 2 trial. Liver or lung metastases were accepted if the surgeons found them resectable. The patients received 6 weeks of capecitabine and oxaliplatin before chemoradiotherapy (CRT), continued capecitabine and oxaliplatin during radiotherapy, and received 4 weeks of capecitabine and oxaliplatin after CRT. The patients received radiotherapy as intensity-modulated radiotherapy. Total mesorectal excision was planned 8 weeks after CRT. The patients were evaluated with magnetic resonance imaging (MRI) before start of treatment, after 6 weeks of chemotherapy, and again just before the operation. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-CR29 scoring system was used to evaluate adverse events. Fifty-two patients were enrolled between 2009 and 2012. The treatment was well tolerated, with only one death during treatment. Eighty percent of assessable patients experienced response to chemotherapy alone as evaluated by MRI, which increased to 94% after complete oncologic treatment. Forty-nine patients had a total mesorectal excision performed, all with a R0 resection and with a pathologic complete response of 20% for patients with T3 tumor and 7% for patients with T4 tumor. Five patients had metastases at study entry, while 47 patients had locally advanced rectal cancer without metastases. Of these 47 patients, overall survival and progression-free survival at 5 years was 72% and 62%, respectively, with a median follow-up of 60 months. This aggressive approach with capecitabine and oxaliplatin before, during, and after radiotherapy for high-risk rectal cancer is safe and feasible; it also has an impressive response rate as measured by MRI and a promising 5-year overall survival. Copyright © 2016 Elsevier Inc. All rights reserved.

Tumor volume changes on serial imaging with megavoltage CT for non-small-cell lung cancer during intensity-modulated radiotherapy: how reliable, consistent, and meaningful is the effect?

PubMed

Siker, Malika L; Tomé, Wolfgang A; Mehta, Minesh P

2006-09-01

Adaptive radiotherapy allows treatment plan modification based on data obtained during treatment. Assessing volume changes during treatment is now possible with intratreatment imaging capabilities on radiotherapy devices. This study assesses non-small-cell lung cancer (NSCLC) volume changes during treatment with conformal intensity-modulated radiotherapy by evaluating serial megavoltage computed tomography (MVCT) scans, with a specific emphasis on the frequency, reliability, and meaningfulness of these changes. Megavoltage CTs were retrospectively reviewed for 25 patients treated with the TomoTherapy Hi-Art system at the University of Wisconsin. Twenty-one patients received definitive radiotherapy, 4 with extracranial stereotactic radioablation (60 Gy in five fractions) and 17 on a dose-per-fraction escalation protocol (57-80.5 Gy in 25 fractions). Four patients were treated palliatively (22-30 Gy in 8 to 10 fractions). Gross tumor volumes were contoured on serial MVCTs at weekly intervals. Each patient had 4 to 25 scans, including at least one at the beginning, midway, and one at the end of treatment. At completion of treatment, no patient demonstrated a complete response. Partial response occurred in 3 (12%) and marginal response was noted in 5 (20%). The remaining 17 patients (68%) showed stable disease. The minimum "scorable threshold" for volume discrepancy between scans to account for interscan assessment variability was set at >25% volume change; 10 patients (40%) had >25% tumor regression. None of the patients treated ablatively or palliatively showed tumor regression during treatment. Although gross tumor regression during treatment may be objectively measured using MVCTs, substantial volumetric decrease occurs only in a minority. The clinical significance of this regression is questionable, because there is no way to document histologic tumor clearance, and therefore field reductions during radiotherapy cannot be recommended.

Implementation of Incident Learning in the Safety and Quality Management of Radiotherapy: The Primary Experience in a New Established Program with Advanced Technology

PubMed Central

Yang, Ruijie; Wang, Junjie; Zhang, Xile; Sun, Haitao; Gao, Yang; Liu, Lu; Lin, Lei

2014-01-01

Objective. To explore the implementation of incident learning for quality management of radiotherapy in a new established radiotherapy program. Materials and Methods. With reference to the consensus recommendations by American Association of Physicist in Medicine, an incident learning system was specifically established for reporting, investigating, and learning of individual incidents. The incidents that occurred in external beam radiotherapy from February, 2012, to February, 2014, were reported. Results. A total of 28 near misses and 5 incidents were reported. Among them, 5 originated in imaging for planning, 25 in planning, and 1 in plan transfer, commissioning, and delivery, respectively. One near miss/incident was classified as wrong patient, 7 wrong sites, 6 wrong laterality, and 5 wrong dose. Five reported incidents were all classified as grade 1/2 of dosimetric severity, 1 as grade 0, and the other 4 as grade 1 of medical severity. For the causes/contributory factors, negligence, policy not followed, and inadequate training contributed to 19, 15, and 12 near misses/incidents, respectively. The average incident rate per 100 patients treated was 0.4. Conclusion. Effective implementation of incident learning can reduce the occurrence of near misses/incidents and enhance the culture of safety. PMID:25140309

Phase II study. Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer.

PubMed

Arrieta, Oscar; Blake, Mónika; de la Mata-Moya, María Dolores; Corona, Francisco; Turcott, Jenny; Orta, David; Alexander-Alatorre, Jorge; Gallardo-Rincón, Dolores

2014-05-01

Nitroglycerin, a nitric oxide donor agent, reduces the expression of hypoxia-inducible factor-1α (HIF-1α) and could be a normalizer of the tumor microenvironment. Both factors are associated with chemo-radio-resistance. The aim of this study was to determine the safety profile and efficacy of nitroglycerin administration with chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). This is a phase II trial of locally advanced NSCLC patients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy. A 25-mg NTG patch was administered to the patients for 5 days (1 day before and 4 days after chemotherapy induction and consolidation) and all day during chemo-radiotherapy. VEGF plasmatic level was determined before and after two cycles of chemotherapy. Thirty-five patients were enrolled in this trial. Sixty-three percent of patients achieved an overall response after induction of chemotherapy, and 75% achieved an overall response after chemo-radiotherapy. The median progression-free survival was 13.5 months (95% CI, 8.8-18.2), and the median overall survival was 26.9 months (95% CI, 15.3-38.5). Reduction of VEGF level was associated with better OS. The toxicity profile related to nitroglycerin included headache (20%) and hypotension (2.9%). The addition of nitroglycerin to induction chemotherapy and concurrent chemoradiotherapy in patients with locally advanced NSCLC has an acceptable toxicity profile and supports the possibility to add nitroglycerin to chemotherapy and radiotherapy. A randomized trial is warranted to confirm these findings. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Hyperfractionated Accelerated Radiotherapy (HART) for Anaplastic Thyroid Carcinoma: Toxicity and Survival Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dandekar, Prasad; Harmer, Clive; Barbachano, Yolanda

2009-06-01

Purpose: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers, and the current protocol of hyperfractionated accelerated radiotherapy was initiated to improve survival while limiting toxicities. Methods and Materials: All patients with ATC from 1991 to 2002 were accrued and received megavoltage radiotherapy from the mastoid processes to the carina up to 60 Gy in twice-daily fractions of 1.8 and 2 Gy, 6 hours apart. Results: Thirty-one patients were accrued with a median age of 69 years, and 55% were women. Debulking was performed in 26%, and total thyroidectomy, in 6%, whereas 68% received radical radiotherapy alone. Localmore » control data were available for 27 patients: 22% had a complete response, 26% had a partial response, 15% showed progressive disease, and 37% showed static disease. Median overall survival for all 31 patients was 70 days (95% confidence interval, 40-99). There was no significant difference in median survival between patients younger (70 days) and older than 70 years (42 days), between men (70 days) and women (49days), and between patients receiving postoperative radiotherapy (77 days) and radical radiotherapy alone (35 days). Grade III or higher skin erythema was seen in 56% patients; desquamation in 21%; dysphagia in 74%; and esophagitis in 79%. Conclusion: The current protocol failed to offer a significant survival benefit, was associated with severe toxicities, and thus was discontinued. There is a suggestion that younger patients with operable disease have longer survival, but this would require a larger study to confirm it.« less

Palliative Radiotherapy in the Local Management of Stage IVB Esophageal Cancer: Factors Affecting Swallowing and Survival.

PubMed

Suzuki, Gen; Yamazaki, Hideya; Aibe, Norihiro; Masui, Koji; Tatekawa, Kotoha; Sasaki, Naomi; Kimoto, Takuya; Nishimura, Takeshi; Nakashima, Akihiro; Takenaka, Tadashi; Fujiwara, Hitoshi; Ishikawa, Takeshi; Yamada, Kei

2017-06-01

To clarify the role of external-beam radiotherapy in the local management of state IVB esophageal cancer. We reviewed records of 31 patients with histopathologically-proven squamous cell carcinoma who underwent radiotherapy for their primary lesion. The change in dysphagia score from before to after treatment was assessed. Nutritional support-free survival (NSFS) was also evaluated. The median overall survival was 6 months. The overall rate of improvement in dysphagia score was 73% (23/31). The median NSFS was 5 months. Age at presentation <67 years, tumor location in the middle thoracic esophagus, and tumor length <7 cm were associated with significant improvement in swallowing scores. Responders to radiotherapy had significantly longer NSFS than non-responders (p=0.04). Palliative radiotherapy in the local management of stage IVB esophageal cancer is an effective treatment option for dysphagia. Factors highly associated with improvement of swallowing are age, tumor location, and tumor length. Response to radiotherapy is the most important factor in improving NSFS. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

PET imaging in adaptive radiotherapy of gastrointestinal tumours.

PubMed

Bulens, Philippe; Thomas, Melissa; Deroose, Christophe M; Haustermans, Karin

2018-06-04

Radiotherapy is the standard of care in the multimodality treatment of a variety of gastrointestinal (GI) tumours, such as oesophageal cancer, gastric cancer, rectal cancer and anal cancer. Additionally, radiotherapy has served as an alternative for surgery in patients with liver cancer, cancer of the biliary tract and pancreatic cancer. Positron-emission tomography (PET), generally in combination with computed tomography (CT), has an established role in the diagnosis, response assessment and (re-)staging of several GI tumours. However, the additional value of PET in adaptive radiotherapy, i.e. during the radiation treatment course and in the delineation process, is still unclear. When performed during radiotherapy, PET aims at assessing treatment-induced variations in functional tumour volumes to reduce the radiation target volume. Moreover, in the radiation treatment planning, tumour delineation could be more accurate by incorporating PET to identify the metabolic tumour volume. This review focuses on the additional value of PET for adaptive radiotherapy protocols as well as for the target volume adaptation for individualised treatment strategies in oesophageal, gastric, pancreatic, liver, biliary tract, rectal and anal neoplasms.

GPU-based High-Performance Computing for Radiation Therapy

PubMed Central

Jia, Xun; Ziegenhein, Peter; Jiang, Steve B.

2014-01-01

Recent developments in radiotherapy therapy demand high computation powers to solve challenging problems in a timely fashion in a clinical environment. Graphics processing unit (GPU), as an emerging high-performance computing platform, has been introduced to radiotherapy. It is particularly attractive due to its high computational power, small size, and low cost for facility deployment and maintenance. Over the past a few years, GPU-based high-performance computing in radiotherapy has experienced rapid developments. A tremendous amount of studies have been conducted, in which large acceleration factors compared with the conventional CPU platform have been observed. In this article, we will first give a brief introduction to the GPU hardware structure and programming model. We will then review the current applications of GPU in major imaging-related and therapy-related problems encountered in radiotherapy. A comparison of GPU with other platforms will also be presented. PMID:24486639

Durable treatment response of relapsing CNS plasmacytoma using intrathecal chemotherapy, radiotherapy, and Daratumumab.

PubMed

Elhassadi, Ezzat; Murphy, Maurice; Hacking, Dayle; Farrell, Michael

2018-04-01

CNS myelomatous involvement is a rare complication of multiple myeloma with dismal outcome. This disease's optimal treatment is unclear. Combined approach of systemic therapy, radiotherapy, and intrathecal injections chemotherapy should be considered and autologous stem cell transplant consolidation is offered to eligible patients. The role of Daratumumab in this disease deserves further evaluation.

High dose chemoradiation for unresectable hilar cholangiocarcinomas using intensity modulated external beam radiotherapy: a single tertiary care centre experience

PubMed Central

Mehta, Shaesta; Kalyani, Nikhil; Chaudhari, Suresh; Dharia, Tejas; Shetty, Nitin; Chopra, Supriya; Goel, Mahesh; Kulkarni, Suyash; Shrivastava, Shyam Kishore

2017-01-01

Background We present results of patients diagnosed with unresectable hilar cholangiocarcinomas treated with high dose radiotherapy and concurrent chemotherapy. Methods From Aug 2005 to Dec 2012, 68 consecutive patients were treated. Fifty patients (group 1) presenting to us with obstructive jaundice were planned for endobiliary brachytherapy (EBBT 14 Gy) followed external beam radiotherapy (EBRT 45 Gy). Twenty-two patients (group 2) who had previously undergone biliary drainage underwent EBRT (57 Gy). All patients received injection Gemcitabine 300 mg/m2/weekly along with EBRT. Results Twenty-nine patients in group 1 and 22 patients in group 2 completed the treatment. Twenty-six (55%) patients achieved complete radiological response, 16 (64%) belonging to group 1 and 8 (44%) of group 2 (P=0.05). The median overall survival (MOS) was 17.5 and 16 months for group 1 and 2 respectively (P=0.07). The 1- and 2-year survival was 63%, and 18% for group I and 61% and 22% for group II respectively. The MOS was 5 months and 1 year survival was 14% for patients receiving EBBT only. MOS was significantly better after complete response (P=0.001). Conclusions Intensity modulated radiotherapy (IMRT) modulated high dose radiotherapy used either alone or with brachytherapy demonstrates potential to prolonged overall survival in unresectable hilar cholangiocarcinomas. PMID:28280622

Dose response explorer: an integrated open-source tool for exploring and modelling radiotherapy dose volume outcome relationships

NASA Astrophysics Data System (ADS)

El Naqa, I.; Suneja, G.; Lindsay, P. E.; Hope, A. J.; Alaly, J. R.; Vicic, M.; Bradley, J. D.; Apte, A.; Deasy, J. O.

2006-11-01

Radiotherapy treatment outcome models are a complicated function of treatment, clinical and biological factors. Our objective is to provide clinicians and scientists with an accurate, flexible and user-friendly software tool to explore radiotherapy outcomes data and build statistical tumour control or normal tissue complications models. The software tool, called the dose response explorer system (DREES), is based on Matlab, and uses a named-field structure array data type. DREES/Matlab in combination with another open-source tool (CERR) provides an environment for analysing treatment outcomes. DREES provides many radiotherapy outcome modelling features, including (1) fitting of analytical normal tissue complication probability (NTCP) and tumour control probability (TCP) models, (2) combined modelling of multiple dose-volume variables (e.g., mean dose, max dose, etc) and clinical factors (age, gender, stage, etc) using multi-term regression modelling, (3) manual or automated selection of logistic or actuarial model variables using bootstrap statistical resampling, (4) estimation of uncertainty in model parameters, (5) performance assessment of univariate and multivariate analyses using Spearman's rank correlation and chi-square statistics, boxplots, nomograms, Kaplan-Meier survival plots, and receiver operating characteristics curves, and (6) graphical capabilities to visualize NTCP or TCP prediction versus selected variable models using various plots. DREES provides clinical researchers with a tool customized for radiotherapy outcome modelling. DREES is freely distributed. We expect to continue developing DREES based on user feedback.

Dosimetric characteristics of a PIN diode for radiotherapy application.

PubMed

Kumar, R; Sharma, S D; Philomina, A; Topkar, A

2014-08-01

The PIN diode developed by Bhabha Atomic Research Centre (BARC) was modified for its use as a dosimeter in radiation therapy. For this purpose the diode was mounted on a printed circuit board (PCB) and provided with necessary connections so that its response against irradiation can be recorded by a standard radiotherapy electrometer. The dosimetric characteristics of the diode were studied in Co-60 gamma rays as well as high energy X-rays. The measured sensitivity of this PIN diode is 4 nC/cGy which is about ten times higher than some commercial diode dosimeters. The leakage current from the diode is 0.04 nA. The response of the PIN diode is linear in the range of 20-1000 cGy which covers the full range of radiation dose encountered in radiotherapy treatments. The non-linearity of the diode response is 3.5% at 20 cGy and it is less than 1.5% at higher dose values. Its repeatability is within 0.5%. The angular response variation is about 5.6% within 6608 with respect to normal beam incidence. The response of the PIN diode at 6 and 18 MV X-rays varies within 2% with respect to its response at Co-60 gamma rays. The source to surface distance (SSD) dependence of the PIN diode was studied for Co-60 beam. It was found that the response of the diode decreases almost linearly relative to given dose for beams with constant collimator setting but increasing SSD (decreasing dose-rate). Within this study the diode response varied by about 2.5% between the maximum and minimum SSD. The dose-rate dependence of the PIN diode for 6 and 15 MV-rays was studied. The variation in response of diode for both energies in the studied dose range is less than 1%. The field size dependence of the PIN diode response is within 1% with respect to the response of ionisation chamber. These studies indicate that the characteristics of the PIN diode are suitable for use in radiotherapy dosimetry.

Oedema-based model for diffuse low-grade gliomas: application to clinical cases under radiotherapy.

PubMed

Badoual, M; Gerin, C; Deroulers, C; Grammaticos, B; Llitjos, J-F; Oppenheim, C; Varlet, P; Pallud, J

2014-08-01

Diffuse low-grade gliomas are characterized by slow growth. Despite appropriate treatment, they change inexorably into more aggressive forms, jeopardizing the patient's life. Optimizing treatments, for example with the use of mathematical modelling, could help to prevent tumour regrowth and anaplastic transformation. Here, we present a model of the effect of radiotherapy on such tumours. Our objective is to explain observed delay of tumour regrowth following radiotherapy and to predict its duration. We have used a migration-proliferation model complemented by an equation describing appearance and draining of oedema. The model has been applied to clinical data of tumour radius over time, for a population of 28 patients. We were able to show that draining of oedema accounts for regrowth delay after radiotherapy and have been able to fit the clinical data in a robust way. The model predicts strong correlation between high proliferation coefficient and low progression-free gain of lifetime, due to radiotherapy among the patients, in agreement with clinical studies. We argue that, with reasonable assumptions, it is possible to predict (precision ~20%) regrowth delay after radiotherapy and the gain of lifetime due to radiotherapy. Our oedema-based model provides an early estimation of individual duration of tumour response to radiotherapy and thus, opens the door to the possibility of personalized medicine. © 2014 John Wiley & Sons Ltd.

The 1998 Australian external beam radiotherapy survey and IAEA/WHO TLD postal dose quality audit.

PubMed

Huntley, R; Izewska, J

2000-03-01

The results of an updated Australian survey of external beam radiotherapy centres are presented. Most of the centres provided most of the requested information. The relative caseloads of various linear accelerator photon and electron beams have not changed significantly since the previous survey in 1995. The mean age of Australian LINACs is 7.1 years and that of other radiotherapy machines is 14.7 years. Every Australian radiotherapy centre participated in a special run of the IAEA/WHO TLD postal dose quality audit program, which was provided for Australian centres by the IAEA and WHO in May 1998. The dose quoted by the centres was in nearly every case within 1.5% of the dose assessed by the IAEA. This is within the combined standard uncertainty of the IAEA TLD service (1.8%). The results confirm the accuracy and precision of radiotherapy dosimetry in Australia and the adequate dissemination of the Australian standards from ARL (now ARPANSA) to the centres. The Australian standards have recently been shown to agree with those of other countries to within 0.25% by comparison with the BIPM.

Targeted Alpha Therapy: The US DOE Tri-Lab (ORNL, BNL, LANL) Research Effort to Provide Accelerator-Produced 225Ac for Radiotherapy

NASA Astrophysics Data System (ADS)

John, Kevin

2017-01-01

Targeted radiotherapy is an emerging discipline of cancer therapy that exploits the biochemical differences between normal cells and cancer cells to selectively deliver a lethal dose of radiation to cancer cells, while leaving healthy cells relatively unperturbed. A broad overview of targeted alpha therapy including isotope production methods, and associated isotope production facility needs, will be provided. A more general overview of the US Department of Energy Isotope Program's Tri-Lab (ORNL, BNL, LANL) Research Effort to Provide Accelerator-Produced 225Ac for Radiotherapy will also be presented focusing on the accelerator-production of 225Ac and final product isolation methodologies for medical applications.

Functional imaging to monitor vascular and metabolic response in canine head and neck tumors during fractionated radiotherapy.

PubMed

Rødal, Jan; Rusten, Espen; Søvik, Åste; Skogmo, Hege Kippenes; Malinen, Eirik

2013-10-01

Radiotherapy causes alterations in tumor biology, and non-invasive early assessment of such alterations may become useful for identifying treatment resistant disease. The purpose of the current work is to assess changes in vascular and metabolic features derived from functional imaging of canine head and neck tumors during fractionated radiotherapy. Material and methods. Three dogs with spontaneous head and neck tumors received intensity-modulated radiotherapy (IMRT). Contrast-enhanced cone beam computed tomography (CE-CBCT) at the treatment unit was performed at five treatment fractions. Dynamic (18)FDG-PET (D-PET) was performed prior to the start of radiotherapy, at mid-treatment and at 3-12 weeks after the completion of treatment. Tumor contrast enhancement in the CE-CBCT images was used as a surrogate for tumor vasculature. Vascular and metabolic tumor parameters were further obtained from the D-PET images. Changes in these tumor parameters were assessed, with emphasis on intra-tumoral distributions. Results. For all three patients, metabolic imaging parameters obtained from D-PET decreased from the pre- to the inter-therapy session. Correspondingly, for two of three patients, vascular imaging parameters obtained from both CE-CBCT and D-PET increased. Only one of the tumors showed a clear metabolic response after therapy. No systematic changes in the intra-tumor heterogeneity in the imaging parameters were found. Conclusion. Changes in vascular and metabolic parameters could be detected by the current functional imaging methods. Vascular tumor features from CE-CBCT and D-PET corresponded well. CE-CBCT is a potential method for easy response assessment when the patient is at the treatment unit.

Phase I Trial Using Proteasome Inhibitor Bortezomib and Concurrent Temozolomide and Radiotherapy for Central Nervous System Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kubicek, Gregory J.; Werner-Wasik, Maria; Machtay, Mitchell

Purpose: To evaluate the toxicity and response rate of bortezomib with concurrent radiotherapy and temozolomide in the treatment of patients with central nervous system malignancies. Patients and Methods: This open-label, dose-escalation, Phase I clinical study evaluated the safety of three dose levels of intravenously administered bortezomib (0.7, 1.0, and 1.3 mg/m{sup 2}/dose) on Days 1, 4, 8, and 11 of a 21-day cycle, in addition to concurrent radiotherapy and temozolomide at a daily dose of 75 mg/m{sup 2} starting on Day 1. The primary endpoint was dose-limiting toxicity, defined as any Grade 4-5 toxicity or Grade 3 toxicity directly attributablemore » to protocol treatment, requiring hospitalization and/or radiotherapy interruption. The secondary endpoints included feasibility, non-dose-limiting toxicity, and treatment response. Results: A total of 27 patients were enrolled, 23 of whom had high-grade glioma (10 recurrent and 13 newly diagnosed). No dose-limiting toxicities were noted in any dose group, including the highest (1.3 mg/m{sup 2}/dose). The most frequent toxicities were Grade 1 and 2 stomatitis, erythema, and alopecia. All 27 patients were evaluable for response. At a median follow-up of 15.0 months, 9 patients were still alive, with a median survival of 17.4 months for all patients and 15.0 months for patients with high-grade glioma. Conclusion: Bortezomib administered at its typical 'systemic' dose (1.3 mg/m{sup 2}) is well tolerated and safe combined with temozolomide and radiotherapy when used in the treatment of central nervous system malignancies. A Phase II study to characterize efficacy is warranted.« less

Serum 8-Oxo-dG as a Predictor of Sensitivity and Outcome of Radiotherapy and Chemotherapy of Upper Gastrointestinal Tumours.

PubMed

Pour Khavari, Ali; Liu, Yongping; He, Ellen; Skog, Sven; Haghdoost, Siamak

2018-01-01

The level of oxidative stress is important in the initiation and progression of various age-related diseases, such as cancer. The level of oxidative stress may also play a significant role in cancer patients' response to treatment. We aimed to investigate whether serum 8-oxo-dG as a marker of oxidative stress is a predictor of tumour response. We used modified ELISA with a two-step filtration to analyse 8-oxo-dG in serum. The relationship between 8-oxo-dG levels, tumour response, and toxicity was studied in 19 oesophageal cancer patients who received radiotherapy and 16 gastric cancer patients who received chemotherapy. In the radiotherapy and the merged radio- and chemotherapy groups, the baseline levels of 8-oxo-dG were significantly lower in responder patients than in nonresponder patients and the increments after treatment were greater. In comparison with patients whose serum 8-oxo-dG levels decrease after treatment, patients with increasing levels had a longer median "progression-free survival." Our results, although preliminary, suggest that serum levels of 8-oxo-dG may potentially be used to predict the sensitivity and outcome of radiotherapy and chemotherapy of upper gastrointestinal tumours. Patients with 8-oxo-dG levels that are low prior to treatment and subsequently increase after treatment may be more likely to benefit from the therapy.

Radical chemo-irradiation using intensity-modulated radiotherapy for locally advanced head and neck cancer in elderly patients: Experience from a tertiary care center in South India.

PubMed

Chalissery, J R; Sudheeran, P C; Varghese, K M; Venkatesan, K

2016-01-01

To assess the feasibility, tolerance and response of radical chemo irradiation using Intensity modulated Radiotherapy [IMRT] in elderly patients [age >65] with locally advanced head and neck cancer. Patients aged 65 and above [range 65 to 84years] registered in oncology outpatient unit in our institution between December 2011 to 2014, with stage III and IV head and neck cancer were treated with radical dose of radiotherapy using IMRT and concurrent chemotherapy with cisplatin 40mg/sq.m weekly. Response evaluation and toxicity profile assessment was done 6 to 8 weeks after completion of treatment and 3 monthly thereafter with median follow up of 3 years. Total number of patients analysed were 47. 43(91.5%) patients tolerated 66-.70Gy of radiotherapy and 4 or more cycles of weekly chemotherapy with cisplatin. First follow up evaluation at 6 to 8 weeks showed 81% patients having complete loco regional response. Grade III skin reaction and mucositis was noticed in 24% and 47% respectively. No grade III neutropenia observed. Median follow up of 3 years showed a complete local control in 53% and overall survival of 60%. Radical chemo irradiation with IMRT in elderly patients is a feasible option. Long term local control and overall survival benefits needs to be followed up.

Phase II Trial of Full-Dose Gemcitabine and Bevacizumab in Combination With Attenuated Three-Dimensional Conformal Radiotherapy in Patients With Localized Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Small, William, E-mail: wsmall@nmff.or; Mulcahy, Mary F.; Rademaker, Alfred

Purpose: To evaluate response rate, survival, and toxicity in patients with nonmetastatic pancreatic cancer treated with gemcitabine, bevacizumab, and radiotherapy. Methods and Materials: Patients received three cycles of therapy over 10 weeks. In total, treatment consisted of intravenous (IV) gemcitabine, 1,000 mg/m{sup 2}, every 1 to 2 weeks (7 doses), IV bevacizumab, 10 mg/kg every 2 weeks (5 doses), and 36 Gy of radiotherapy (2.4-Gy fractions during cycle two). Response was assessed by cross-sectional imaging and carbohydrate antigen 19-9 (CA 19-9) levels. Patients with resectable tumors underwent surgery 6 to 8 weeks after the last dose of bevacizumab. Maintenance gemcitabinemore » and bevacizumab doses were delivered to patients who had unresected tumors and no progression. Results: Twenty-eight of the 32 enrolled patients completed all three cycles. The median follow-up was 11.07 months. Most grade 3 or 4 toxicities occurred in the initial treatment phase; the most frequent toxicities were leukopenia (21%), neutropenia (17%), and nausea (17%). At week 10, 1 patient (4%) had a complete response, 2 patients (7%) had partial responses, 21 patients (75%) had stable disease, and 4 patients (14%) had progressive disease. The median pretreatment and posttreatment CA 19-9 levels (25 patients) were 184.3 and 57.9 U/ml, respectively (p = 0.0006). One of 10 patients proceeding to surgery experienced a major complication. Two of 6 patients undergoing resection had complete pathologic responses. The median progression-free and overall survival durations were 9.9 months and 11.8 months, respectively. Conclusions: The combination of full-dose gemcitabine, bevacizumab, and radiotherapy was active and was not associated with a high rate of major surgical complications.« less

Predictive factors in the evaluation of treatment response to neoadjuvant chemoradiotherapy in patients with advanced esophageal squamous cell cancer

PubMed Central

Wong, Claudia

2017-01-01

Neoadjuvant therapy before esophagectomy is evidence-based, and is a standard-of-care for locally advanced and operable esophageal cancer. However response to such treatment varies in individual patients, from no clinical response to pathological complete response. It has been consistently shown that a good pathological responses is of prognostic value, but perhaps in the expense of those who do not. It is important to identify suitable predictive factors for response, so that patients are not exposed to potentially harmful chemotherapy and/or radiotherapy without benefits. Alternative management strategies can be devised. Various clinical, radiological, serological and potential molecular markers have been studied. None has been shown to be sufficiently reliable to be used in daily practice. Certainly more understanding of the molecular basis for response to chemotherapy/radiotherapy is needed, so that patient treatment can be tailored and individualized. PMID:28815073

Flavonoid silybin improves the response to radiotherapy in invasive bladder cancer.

PubMed

Prack Mc Cormick, Barbara; Langle, Yanina; Belgorosky, Denise; Vanzulli, Silvia; Balarino, Natalia; Sandes, Eduardo; Eiján, Ana M

2018-01-24

Conservative treatment for invasive bladder cancer (BC) involves a complete transurethral tumor resection combined with chemotherapy (CT) and radiotherapy (RT). The major obstacles of chemo-radiotherapy are the addition of the toxicities of RT and CT, and the recurrence due to RT and CT resistances. The flavonoid Silybin (Sb) inhibits pathways involved in cell survival and resistance mechanisms, therefore the purpose of this paper was to study in vitro and in vivo, the ability of Sb to improve the response to RT, in two murine BC cell lines, with different levels of invasiveness, placing emphasis on radio-sensitivity, and pathways involved in radio-resistance and survival. In vitro, Sb radio-sensitized murine invasive cells through the inhibition of RT-induced NF-κB and PI3K pathways, and the increase of oxidative stress, while non-invasive cells did not show to be sensitized. In vivo, Sb improved RT-response and overall survival in invasive murine tumors. As Sb is already being tested in clinical trials for other urological cancers and it improves RT-response in invasive BC, these results could have translational relevance, supporting further research. © 2018 Wiley Periodicals, Inc.

The information needs of new radiotherapy patients: how to measure? Do they want to know everything? And if not, why?

PubMed

Zeguers, Maaike; de Haes, Hanneke C J M; Zandbelt, Linda C; Ter Hoeven, Claartje L; Franssen, Sanne J; Geijsen, Debbie D; Koning, Caro C E; Smets, Ellen M A

2012-01-01

To establish 1) further psychometric properties of the information preference for radiotherapy patients scale (IPRP); 2) what information new radiotherapy patients want to receive; 3) which patients have a lower information need. Eligible patients (n = 159; response rate 54%) of 15 radiation oncologists completed the IPRP and provided background characteristics before their first radiotherapy consultation. Exclusion criteria were: age <18 years, having undergone radiotherapy before, unable to read and write Dutch, cognitive problems or a brain tumor. Reliability (Cronbach's alpha 0.84-0.97) and concurrent validity (r from .39 to .57, p < 0.001) of the subscales of the IPRP were good. New radiotherapy patients want extensive information about their disease, treatment, procedures, side effects, and prognosis (mean scores between 4.1 and 4.4 on a scale from 1 to 5) but less information about psychosocial issues (mean = 3.4). Patients who are older and male, have lung or rectal cancer, more difficulty understanding and a higher trait anxiety level, need less information. The IPRP can reliably and validly address information needs of patients undergoing radiation treatment. Most new radiotherapy patients want much information. Yet, information giving should be tailored according to their background, understanding and anxiety. Copyright © 2012 Elsevier Inc. All rights reserved.

The significance of size change of soft tissue sarcoma during preoperative radiotherapy.

PubMed

Miki, Y; Ngan, S; Clark, J C M; Akiyama, T; Choong, P F M

2010-07-01

To assess the significance of change in tumour size during preoperative radiotherapy in patients with soft tissue sarcoma (STS). A retrospective review of 91 cases with STS was performed. Inclusion criteria were localised extremity and truncal STS with measurable disease, older than 18 years, treated with preoperative radiotherapy and wide local excision, in the period between January 1966 and December 2005. Patients with head and neck STS, or who received neoadjuvant chemotherapy were excluded. A difference in excess of 10% of the greatest tumour diameter of the pre-radiotherapy and the post-radiotherapy MRI scans was considered as change in tumour size. Increase in tumour size was noted in 28 patients (31%) (Group 1). No change or decrease in size was observed in 63 patients (Group 2). There were no significance differences in local control or overall survival rates between the 2 groups. The estimated overall actuarial local recurrence free, event-free and overall survival rates were 90.5%, 64.4%, 62.9% in Group 1, and 85.7%, 60.8%, 68.9% in Group 2 respectively. Increase in tumour size during preoperative radiotherapy for soft tissue sarcoma does not seem to associate with inferior local tumour control or compromise survival. Lack of reduction in tumour size is not necessarily a sign of lack of response to preoperative radiotherapy.

The emerging potential of magnetic resonance imaging in personalizing radiotherapy for head and neck cancer: an oncologist's perspective.

PubMed

Wong, Kee H; Panek, Rafal; Bhide, Shreerang A; Nutting, Christopher M; Harrington, Kevin J; Newbold, Katie L

2017-03-01

Head and neck cancer (HNC) is a challenging tumour site for radiotherapy delivery owing to its complex anatomy and proximity to organs at risk (OARs) such as the spinal cord and optic apparatus. Despite significant advances in radiotherapy planning techniques, radiation-induced morbidities remain substantial. Further improvement would require high-quality imaging and tailored radiotherapy based on intratreatment response. For these reasons, the use of MRI in radiotherapy planning for HNC is rapidly gaining popularity. MRI provides superior soft-tissue contrast in comparison with CT, allowing better definition of the tumour and OARs. The lack of additional radiation exposure is another attractive feature for intratreatment monitoring. In addition, advanced MRI techniques such as diffusion-weighted, dynamic contrast-enhanced and intrinsic susceptibility-weighted MRI techniques are capable of characterizing tumour biology further by providing quantitative functional parameters such as tissue cellularity, vascular permeability/perfusion and hypoxia. These functional parameters are known to have radiobiological relevance, which potentially could guide treatment adaptation based on their changes prior to or during radiotherapy. In this article, we first present an overview of the applications of anatomical MRI sequences in head and neck radiotherapy, followed by the potentials and limitations of functional MRI sequences in personalizing therapy.

The emerging potential of magnetic resonance imaging in personalizing radiotherapy for head and neck cancer: an oncologist's perspective

PubMed Central

Panek, Rafal; Bhide, Shreerang A; Nutting, Christopher M; Harrington, Kevin J; Newbold, Katie L

2017-01-01

Head and neck cancer (HNC) is a challenging tumour site for radiotherapy delivery owing to its complex anatomy and proximity to organs at risk (OARs) such as the spinal cord and optic apparatus. Despite significant advances in radiotherapy planning techniques, radiation-induced morbidities remain substantial. Further improvement would require high-quality imaging and tailored radiotherapy based on intratreatment response. For these reasons, the use of MRI in radiotherapy planning for HNC is rapidly gaining popularity. MRI provides superior soft-tissue contrast in comparison with CT, allowing better definition of the tumour and OARs. The lack of additional radiation exposure is another attractive feature for intratreatment monitoring. In addition, advanced MRI techniques such as diffusion-weighted, dynamic contrast-enhanced and intrinsic susceptibility-weighted MRI techniques are capable of characterizing tumour biology further by providing quantitative functional parameters such as tissue cellularity, vascular permeability/perfusion and hypoxia. These functional parameters are known to have radiobiological relevance, which potentially could guide treatment adaptation based on their changes prior to or during radiotherapy. In this article, we first present an overview of the applications of anatomical MRI sequences in head and neck radiotherapy, followed by the potentials and limitations of functional MRI sequences in personalizing therapy. PMID:28256151

Sparing functional anatomical structures during intensity-modulated radiotherapy: an old problem, a new solution.

PubMed

Tan, Wenyong; Han, Guang; Wei, Shaozhong; Hu, Desheng

2014-08-01

During intensity-modulated radiotherapy, an organ is usually assumed to be functionally homogeneous and, generally, its anatomical and spatial heterogeneity with respect to radiation response are not taken into consideration. However, advances in imaging and radiation techniques as well as an improved understanding of the radiobiological response of organs have raised the possibility of sparing the critical functional structures within various organs at risk during intensity-modulated radiotherapy. Here, we discuss these structures, which include the critical brain structure, or neural nuclei, and the nerve fiber tracts in the CNS, head and neck structures related to radiation-induced salivary and swallowing dysfunction, and functional structures in the heart and lung. We suggest that these structures can be used as potential surrogate organs at risk in order to minimize their radiation dose and/or irradiated volume without compromising the dose coverage of the target volume during radiation treatment.

Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment

PubMed Central

Bonanno, Laura; Zago, Giulia; Marulli, Giuseppe; Del Bianco, Paola; Schiavon, Marco; Pasello, Giulia; Polo, Valentina; Canova, Fabio; Tonetto, Fabrizio; Loreggian, Lucio; Rea, Federico; Conte, PierFranco; Favaretto, Adolfo

2016-01-01

Objectives If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs). No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. Methods We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1), paclitaxel (200 mg/m2, d1), and gemcitabine (1,000 mg/m2 d1, 8) for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS) and overall survival (OS) were correlated to response, surgery, and clinical features. Results In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors–7th edition staging system). A total of 36 (62%) patients achieved partial response (PR), and six (10%) progressions were recorded. Grade 3–4 hematological toxicity was observed in 36 (62%) cases. After chemotherapy, 37 (64%) patients underwent surgery followed by adjuvant radiotherapy, and two patients received radical-intent radiotherapy. The median PFS and OS were 11 months and 23 months, respectively. Both PFS and OS were significantly correlated to objective response (P<0.0001) and surgery (P<0.0001 and P=0.002). Patients obtaining PR and receiving local treatment achieved a median PFS and OS of 35 and 48 months, respectively. Median PFS and OS of patients not achieving PR or not receiving local treatment were 5–7 and 11–15 months, respectively. The extension of surgery did not affect the outcome. Conclusion The multimodality treatment was feasible, and triple-agent induction was associated with a considerable rate of PR. Patients achieving PR and receiving radical surgery or radiotherapy (53%) achieved a median OS of 4 years. PMID:27382305

Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment.

PubMed

Bonanno, Laura; Zago, Giulia; Marulli, Giuseppe; Del Bianco, Paola; Schiavon, Marco; Pasello, Giulia; Polo, Valentina; Canova, Fabio; Tonetto, Fabrizio; Loreggian, Lucio; Rea, Federico; Conte, PierFranco; Favaretto, Adolfo

2016-01-01

If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs). No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1), paclitaxel (200 mg/m(2), d1), and gemcitabine (1,000 mg/m(2) d1, 8) for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS) and overall survival (OS) were correlated to response, surgery, and clinical features. In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors-7th edition staging system). A total of 36 (62%) patients achieved partial response (PR), and six (10%) progressions were recorded. Grade 3-4 hematological toxicity was observed in 36 (62%) cases. After chemotherapy, 37 (64%) patients underwent surgery followed by adjuvant radiotherapy, and two patients received radical-intent radiotherapy. The median PFS and OS were 11 months and 23 months, respectively. Both PFS and OS were significantly correlated to objective response (P<0.0001) and surgery (P<0.0001 and P=0.002). Patients obtaining PR and receiving local treatment achieved a median PFS and OS of 35 and 48 months, respectively. Median PFS and OS of patients not achieving PR or not receiving local treatment were 5-7 and 11-15 months, respectively. The extension of surgery did not affect the outcome. The multimodality treatment was feasible, and triple-agent induction was associated with a considerable rate of PR. Patients achieving PR and receiving radical surgery or radiotherapy (53%) achieved a median OS of 4 years.

Hyperthermia and radiotherapy in the management of head and neck cancers: A systematic review and meta-analysis.

PubMed

Datta, Niloy R; Rogers, Susanne; Ordóñez, Silvia Gómez; Puric, Emsad; Bodis, Stephan

2016-01-01

A systematic review and meta-analysis was conducted to evaluate the outcome of controlled clinical trials in head and neck cancers (HNCs) using hyperthermia and radiotherapy versus radiotherapy alone. A total of 498 abstracts were screened from four databases and hand searched as per the PRISMA guidelines. Only two-arm studies treating HNCs with either radiotherapy alone, or hyperthermia and radiotherapy without concurrent chemotherapy or surgery were considered. The evaluated end point was complete response (CR). Following a detailed screening of the titles, abstracts and full text papers, six articles fulfilling the above eligibility criteria were considered. In total 451 clinical cases from six studies were included in the meta-analysis. Five of six trials were randomised. The overall CR with radiotherapy alone was 39.6% (92/232) and varied between 31.3% and 46.9% across the six trials. With thermoradiotherapy, the overall CR reported was 62.5% (137/219), (range 33.9-83.3%). The odds ratio was 2.92 (95% CI: 1.58-5.42, p = 0.001); the risk ratio was 1.61 (95% CI: 1.32-1.97, p < 0.0001) and the risk difference was 0.25 (95% CI: 0.12-0.39, p < 0.0001), all in favour of combined treatment with hyperthermia and radiotherapy over radiotherapy alone. Acute and late grade III/IV toxicities were reported to be similar in both the groups. Hyperthermia along with radiotherapy enhances the likelihood of CR in HNCs by around 25% compared to radiotherapy alone with no significant additional acute and late morbidities. This level I evidence should justify the integration of hyperthermia into the multimodality therapy of HNCs.

Morphological and immunohistochemical criteria of tissue response to radiotherapy in rectal cancer.

PubMed

Ionescu, S; Brătucu, E; Zurac, S; Staniceanu, F; Pătraşcu, Tr; Burcoş, Tr; Herlea, V; Degeratu, D; Popa, I; Cristian, D

2013-01-01

Given the context that rectal tumours respond to a certain degree to radiotherapy, a necessity arises for estimating a tumour's capacity to react to radiation from the very moment of diagnostic biopsy. We have histologically and immunohistochemically analysed tissues coming from 52 patients with rectal adenocarcinomas. Of the studied parameters, the ones presenting significant variation under radiotherapy in terms of statistics(p 0.05) were: colloid type (p=0.001), EGFR in the tumour(p=0.00045), EGFR in the normal epithelium (p=0.0017),VEGF in the tumour (p=0.0132) and VEGF in the tumour stroma (p=0.030). Our study follows the same trends as the medical literature we have consulted regarding the variation of EGFR and VEGF with radiotherapy, and the distinct note of our study relies in the observation that normal stroma in case of rectal tumors also reacts to radiotherapy, sometimes more aggressively than the tumor itself, especially in which concerns the nerve and muscle fibers. Celsius.

Treatment of unicentric and multicentric Castleman disease and the role of radiotherapy.

PubMed

Chronowski, G M; Ha, C S; Wilder, R B; Cabanillas, F; Manning, J; Cox, J D

2001-08-01

Although surgery is considered standard therapy for unicentric Castleman disease, favorable responses to radiotherapy also have been documented. The authors undertook this study to analyze the clinical factors, treatment approaches, and outcomes of patients with unicentric or multicentric Castleman disease, and to report the outcomes of patients with unicentric Castleman disease treated with radiotherapy. The authors reviewed the medical records of 22 patients who had received a histologic diagnosis of Castleman disease at the University of Texas M. D. Anderson Cancer Center between 1988 and 1999. One patient with a concurrent histopathologic diagnosis of nonsecretory multiple myeloma was excluded from the study. In all patients, the diagnosis of Castleman disease was based on the results of lymph node biopsies. Disease was categorized as being either unicentric or multicentric and further subdivided into hyaline vascular, plasma cell, or mixed variant histologic types. Clinical variables and outcomes were analyzed according to treatment, which consisted of surgery, chemotherapy, or radiotherapy. Records from 21 patients were analyzed: 12 had unicentric disease, and 9 had multicentric disease. The mean follow-up time for the entire series was 51 months (median, 40 months). Four patients with unicentric disease were treated with radiotherapy alone: 2 remain alive and symptom free, 2 died of causes unrelated to Castleman disease and had no evidence of disease at last follow-up. Eight patients with unicentric disease were treated with complete or partial surgical resection, and all are alive and asymptomatic. All nine patients with multicentric disease were treated with combination chemotherapy: five are alive with no evidence of disease, and four are alive with progressive disease. Surgery results in excellent rates of cure in patients with unicentric Castleman disease; radiotherapy can also achieve clinical response and cure in selected patients. Multicentric Castleman disease is a more aggressive clinical entity and is most effectively treated with combination chemotherapy, whereas the role of radiotherapy in its treatment remains unclear. Copyright 2001 American Cancer Society.

Concomitant liposomal doxorubicin and daily palliative radiotherapy in advanced feline soft tissue sarcomas.

PubMed

Kleiter, Miriam; Tichy, Alexander; Willmann, Michael; Pagitz, Maximilian; Wolfesberger, Birgitt

2010-01-01

Local recurrence of feline soft tissue sarcomas is common despite aggressive treatment. Liposomal doxorubicin might serve as a depot radiosensitizer if administered concomitantly with daily radiotherapy and thus improve tumor control. In this pilot study, the feasibility of concomitant liposomal radiochemotherapy was evaluated in a palliative setting in 10 cats with advanced soft tissue sarcomas. Cats were treated with median number of 5 (range 5-7) daily fractions of radiotherapy and a median total dose of 20 Gy (range 20-31.5 Gy). One dose of liposomal doxorubicin was administered at the beginning of radiotherapy. Seven cats received further free or liposomal doxorubicin after completion of the liposomal doxorubicin/radiation protocol. Seven of the treated 10 cats (70%) achieved a partial (n=5) or complete (n=2) response with a median response duration of 237 days. The median progression free interval in all 10 cats was 117 days and the median overall survival time was 324 days. Concomitant liposomal radiochemotherapy was tolerated well in nine cats, one cat experienced temporary anorexia. Although the number of patients is too small to make definitive conclusions, results appear promising enough to investigate the role of liposomal doxorubicin as a radiosensitizer further.

Radiogenomics and radiotherapy response modeling

NASA Astrophysics Data System (ADS)

El Naqa, Issam; Kerns, Sarah L.; Coates, James; Luo, Yi; Speers, Corey; West, Catharine M. L.; Rosenstein, Barry S.; Ten Haken, Randall K.

2017-08-01

Advances in patient-specific information and biotechnology have contributed to a new era of computational medicine. Radiogenomics has emerged as a new field that investigates the role of genetics in treatment response to radiation therapy. Radiation oncology is currently attempting to embrace these recent advances and add to its rich history by maintaining its prominent role as a quantitative leader in oncologic response modeling. Here, we provide an overview of radiogenomics starting with genotyping, data aggregation, and application of different modeling approaches based on modifying traditional radiobiological methods or application of advanced machine learning techniques. We highlight the current status and potential for this new field to reshape the landscape of outcome modeling in radiotherapy and drive future advances in computational oncology.

Change in urinary markers of osteoclast activity following palliative radiotherapy for bone metastases.

PubMed

Chow, E; Hird, A; Zhang, Liying; Sinclair, E; Danjoux, C; Barnes, E; Tsao, M; Barbera, L; Wong, Shun; Vieth, R

2009-05-01

To examine the effect of radiotherapy for bone metastases on urinary markers of osteoclast activity. Patients with radiological evidence of bone metastases planned for palliative radiotherapy were eligible for the study. A urine specimen was collected before and 1 month after radiotherapy to assess levels of calcium, creatinine, magnesium, phosphate, N-telopeptide and pyridinoline. The Brief Pain Inventory was completed in person at baseline and by telephone follow-up at 1 month after radiotherapy. Patients were classified as responders (complete or partial pain response) or non-responders (stable or progressive pain) to radiotherapy based on the International Bone Metastases Consensus Criteria for end point measurements. Absolute values of urine markers were compared between responders and non-responders, or between responders and patients with progression. Our study population consisted of 74 men and 51 women. A single 8 Gy or 20 Gy in five daily fractions were commonly employed. At the 1 month follow-up, all Brief Pain Inventory functional interference scores showed a highly significant decrease from baseline (P<0.01). From our study population, 58 (64%) were classified as responders and 57 (46%) as non-responders to radiotherapy. We compared the urinary markers between the responders and the non-responders. There were no statistically significant differences between the two groups either in terms of baseline markers or in terms of month 1 follow-up markers. There was no significant change from baseline to the 1 month follow-up in responders or in non-responders to radiotherapy. Baseline levels of urinary markers could not predict which patient would benefit from palliative radiotherapy.

Comparing Relaxation Programs for Breast Cancer Patients Receiving Radiotherapy

Cancer.gov

In this study, women with breast cancer who have had surgery and are scheduled to undergo radiation therapy will be randomly assigned to one of two different stretching and relaxation programs or to a control group that will receive usual care.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeguers, Maaike; Haes, Hanneke C.J.M. de; Zandbelt, Linda C.

Purpose: To establish 1) further psychometric properties of the information preference for radiotherapy patients scale (IPRP); 2) what information new radiotherapy patients want to receive; 3) which patients have a lower information need. Methods and Materials: Eligible patients (n = 159; response rate 54%) of 15 radiation oncologists completed the IPRP and provided background characteristics before their first radiotherapy consultation. Exclusion criteria were: age <18 years, having undergone radiotherapy before, unable to read and write Dutch, cognitive problems or a brain tumor. Results: Reliability (Cronbach's alpha 0.84-0.97) and concurrent validity (r from .39 to .57, p < 0.001) of themore » subscales of the IPRP were good. New radiotherapy patients want extensive information about their disease, treatment, procedures, side effects, and prognosis (mean scores between 4.1 and 4.4 on a scale from 1 to 5) but less information about psychosocial issues (mean = 3.4). Patients who are older and male, have lung or rectal cancer, more difficulty understanding and a higher trait anxiety level, need less information. Conclusions: The IPRP can reliably and validly address information needs of patients undergoing radiation treatment. Most new radiotherapy patients want much information. Yet, information giving should be tailored according to their background, understanding and anxiety.« less

Definitive radiotherapy for extramedullary plasmacytomas of the head and neck.

PubMed

Michalaki, V J; Hall, J; Henk, J M; Nutting, C M; Harrington, K J

2003-10-01

Extramedullary plasmacytoma of the head and neck region (EMPHN) is an uncommon malignant plasma cell neoplasm. In this study we conducted a retrospective analysis of our experience of EMPHN with particular emphasis on the role of definitive radiotherapy. From 1982 to 2001, 10 patients (6 males, 4 females) with EMPHN were treated in our institution. Of nine patients treated at initial diagnosis, all received definitive radiotherapy. One patient treated at relapse underwent surgical resection followed by post-operative radiotherapy. The median age at diagnosis was 55 years (range 35-84 years). The disease was most frequently localized in the paranasal sinuses (50%). All nine patients who received definitive radiotherapy at a dose of 40-50 Gy achieved a complete response. The median follow up period was 29 months (range 7-67 months). Four patients (40%) relapsed, three have died of their disease. Two patients (20%) with paranasal sinus disease subsequently relapsed with multiple myeloma at 10 months and 24 months, respectively. Our results indicate that treatment of EMPHN with radiotherapy achieves excellent rates of local control. The relapse rate in neck nodes of 10% does not justify elective irradiation of the uninvolved neck.

Is it possible to improve radiotherapy team members' communication skills? A randomized study assessing the efficacy of a 38-h communication skills training program.

PubMed

Gibon, Anne-Sophie; Merckaert, Isabelle; Liénard, Aurore; Libert, Yves; Delvaux, Nicole; Marchal, Serge; Etienne, Anne-Marie; Reynaert, Christine; Slachmuylder, Jean-Louis; Scalliet, Pierre; Van Houtte, Paul; Coucke, Philippe; Salamon, Emile; Razavi, Darius

2013-10-01

Optimizing communication between radiotherapy team members and patients and between colleagues requires training. This study applies a randomized controlled design to assess the efficacy of a 38-h communication skills training program. Four radiotherapy teams were randomly assigned either to a training program or to a waiting list. Team members' communication skills and their self-efficacy to communicate in the context of an encounter with a simulated patient were the primary endpoints. These encounters were scheduled at the baseline and after training for the training group, and at the baseline and four months later for the waiting list group. Encounters were audiotaped and transcribed. Transcripts were analyzed with content analysis software (LaComm) and by an independent rater. Eighty team members were included in the study. Compared to untrained team members, trained team members used more turns of speech with content oriented toward available resources in the team (relative rate [RR]=1.38; p=0.023), more assessment utterances (RR=1.69; p<0.001), more empathy (RR=4.05; p=0.037), more negotiation (RR=2.34; p=0.021) and more emotional words (RR=1.32; p=0.030), and their self-efficacy to communicate increased (p=0.024 and p=0.008, respectively). The training program was effective in improving team members' communication skills and their self-efficacy to communicate in the context of an encounter with a simulated patient. Future study should assess the effect of this training program on communication with actual patients and their satisfaction. Moreover a cost-benefit analysis is needed, before implementing such an intensive training program on a broader scale. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Rationale for combining immunotherapy with chemotherapy.

PubMed

Dalgleish, Angus G

2015-01-01

Immunotherapy has usually been considered as an alternative to more traditional modalities. Moreover, it has previously been felt that chemotherapy is inherently immunosuppressive and not suitable for combining with immunotherapy. In this review, the concept of combining different modalities that result in cell death, such as radiotherapy and chemotherapy, with immunotherapy is explored. Tumors actively cause immune suppression which can be reversed by their removal but when this is not possible, enhancing the immune response with nonspecific immune stimulation can enhance the response to other modalities, such as radiotherapy and chemotherapy. Additionally, several chemotherapy agents at low doses selectively inhibit regulatory and suppressor cells.

Radiotherapy in the management of locally advanced breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zaharia, M.; Caceres, E.; Valdivia, S.

A retrospective study of 484 patients with locally advanced cancer of the breast treated with irradiation alone revealed a partial or complete response in 64% of the patients, with a mean duration of 13 months. The 5-year survival was 21.9% for the entire group of patients; 32% for patients responding, and 5% for non-responding patients. The data suggests that the size of the tumor and the age of the patients influence the quality of response. The results indicate that radiotherapy adequately controls local disease in a significant number of patients but systemic treatment is needed for better disease control.

Developing a mailed phantom to implement a local QA program in Egypt radiotherapy centers

NASA Astrophysics Data System (ADS)

Soliman, H. A.; Aletreby, M.

2016-07-01

In this work, a simple method that differs from the IAEA/WHO Thermoluminescent dosimeters (TLD) postal quality assurance (QA) program is developed. A small perspex; polymethyl methacrylate (PMMA), phantom measured 50 mm × 50 mm × 50 mm is constructed to be used for absorbed dose verification of high-energy photon beams in some major radiotherapy centers in Egypt. The phantom weighted only 140.7 g with two buildup covers weighted 14.8 and 43.19 g for the Cobalt-60 and the 6-MV X-ray beams, respectively. This phantom is aimed for use in the future's external audit/QA services in Egypt for the first time. TLD-700 chips are used for testing and investigating a convenient and national dosimetry QA program. Although the used methodology is comparable to previously introduced but new system; it has smaller size, less weight, and different more available material. Comparison with the previous similar designs is introduced. Theoretical calculations were done by the commercial Eclipse treatment planning system, implementing the pencil beam convolution algorithm to verify the accuracy of the experimental calculation of the dose conversion factor of water to the perspex phantom. The new constructed small phantom and methodology was applied in 10 participating radiotherapy centers. The absorbed dose was verified under the reference conditions for both 60Co and 6-MV high-energy photon beams. The checked beams were within the 5% limit except for four photon beams. There was an agreement of 0.2% between our experimental data and those previously published confirming the validity of the applied method in verifying radiotherapy absorbed dose.

Phase I clinical study of personalized peptide vaccination combined with radiotherapy for advanced hepatocellular carcinoma

PubMed Central

Shen, Jie; Wang, Li-Feng; Zou, Zheng-Yun; Kong, Wei-Wei; Yan, Jing; Meng, Fan-Yan; Chen, Fang-Jun; Du, Juan; Shao, Jie; Xu, Qiu-Ping; Ren, Hao-Zhen; Li, Ru-Tian; Wei, Jia; Qian, Xiao-Ping; Liu, Bao-Rui

2017-01-01

AIM To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination (PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma (HCC). METHODS A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases (the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL. RESULTS Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response (PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade II bone marrow suppression and the remaining patients had no significant hematological side effects. CONCLUSION Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective. PMID:28839440

High dose hypofractionated frameless volumetric modulated arc radiotherapy is a feasible method for treating canine trigeminal nerve sheath tumors.

PubMed

Dolera, Mario; Malfassi, Luca; Marcarini, Silvia; Mazza, Giovanni; Carrara, Nancy; Pavesi, Simone; Sala, Massimo; Finesso, Sara; Urso, Gaetano

2018-06-08

The aim of this prospective pilot study was to evaluate the feasibility and effectiveness of curative intent high dose hypofractionated frameless volumetric modulated arc radiotherapy for treatment of canine trigeminal peripheral nerve sheath tumors. Client-owned dogs with a presumptive imaging-based diagnosis of trigeminal peripheral nerve sheath tumor were recruited for the study during the period of February 2010 to December 2013. Seven dogs were enrolled and treated with high dose hypofractionated volumetric modulated arc radiotherapy delivered by a 6 MV linear accelerator equipped with a micro-multileaf beam collimator. The plans were computed using a Monte Carlo algorithm with a prescription dose of 37 Gy delivered in five fractions on alternate days. Overall survival was estimated using a Kaplan-Meier curve analysis. Magnetic resonance imaging (MRI) follow-up examinations revealed complete response in one dog, partial response in four dogs, and stable disease in two dogs. Median overall survival was 952 days with a 95% confidence interval of 543-1361 days. Volumetric modulated arc radiotherapy was demonstrated to be feasible and effective for trigeminal peripheral nerve sheath tumor treatment in this sample of dogs. The technique required few sedations and spared organs at risk. Even though larger studies are required, these preliminary results supported the use of high dose hypofractionated volumetric modulated arc radiotherapy as an alternative to other treatment modalities. © 2018 American College of Veterinary Radiology.

Molecular PET imaging for biology-guided adaptive radiotherapy of head and neck cancer.

PubMed

Hoeben, Bianca A W; Bussink, Johan; Troost, Esther G C; Oyen, Wim J G; Kaanders, Johannes H A M

2013-10-01

Integration of molecular imaging PET techniques into therapy selection strategies and radiation treatment planning for head and neck squamous cell carcinoma (HNSCC) can serve several purposes. First, pre-treatment assessments can steer decisions about radiotherapy modifications or combinations with other modalities. Second, biology-based objective functions can be introduced to the radiation treatment planning process by co-registration of molecular imaging with planning computed tomography (CT) scans. Thus, customized heterogeneous dose distributions can be generated with escalated doses to tumor areas where radiotherapy resistance mechanisms are most prevalent. Third, monitoring of temporal and spatial variations in these radiotherapy resistance mechanisms early during the course of treatment can discriminate responders from non-responders. With such information available shortly after the start of treatment, modifications can be implemented or the radiation treatment plan can be adapted tailing the biological response pattern. Currently, these strategies are in various phases of clinical testing, mostly in single-center studies. Further validation in multicenter set-up is needed. Ultimately, this should result in availability for routine clinical practice requiring stable production and accessibility of tracers, reproducibility and standardization of imaging and analysis methods, as well as general availability of knowledge and expertise. Small studies employing adaptive radiotherapy based on functional dynamics and early response mechanisms demonstrate promising results. In this context, we focus this review on the widely used PET tracer (18)F-FDG and PET tracers depicting hypoxia and proliferation; two well-known radiation resistance mechanisms.

Influence of P53 on the radiotherapy response of hepatocellular carcinoma

PubMed Central

Gomes, Ana R.; Abrantes, Ana M.; Brito, Ana F.; Laranjo, Mafalda; Casalta-Lopes, João E.; Gonçalves, Ana C.; Sarmento-Ribeiro, Ana B.; Tralhão, José G.

2015-01-01

Background/Aims Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it has a poor prognosis and few therapeutic options. Radiotherapy is one of the most effective forms of cancer treatment, and P53 protein is one of the key molecules determining how a cell responds to radiotherapy. The aim of this study was to determine the therapeutic efficacy of iodine-131 in three human HCC cell lines. Methods Western blotting was used to measure P53 expression. The effects of radiotherapy with iodine-131 were assessed by using the clonogenic assay to evaluate cell survival. Flow cytometry was carried out to examine the effects of iodine-131 on cell death, oxidative stress, reduced intracellular glutathione expression, the mitochondrial membrane potential, and the cell cycle. Results The P53 protein was not expressed in Hep3B2.1-7 cells, was expressed at normal levels in HepG2 cells, and was overexpressed in HuH7 cells. P53 expression in the HuH7 and HepG2 cell lines increased after internal and external irradiation with iodine-131. Irradiation induced a decrease in cell survival and led to a decrease in cell viability in all of the cell lines studied, accompanied by cell death via late apoptosis/necrosis and necrosis. Irradiation with 131-iodine induced mostly cell-cycle arrest in the G0/G1 phase. Conclusions These results suggest that P53 plays a key role in the radiotherapy response of HCC. PMID:26527121

COTS Silicon diodes as radiation detectors in proton and heavy charged particle radiotherapy 1.

PubMed

Kaiser, Franz-Joachim; Bassler, Niels; Jäkel, Oliver

2010-08-01

Modern radiotherapy facilities for cancer treatment such as the Heavy Ion Therapy Center (HIT) in Heidelberg, Germany, allow for sub-millimeter precision in dose deposition. For measurement of such dose distributions and characterization of the particle beams, detectors with high spatial resolution are necessary. Here, a detector based on the commercially available COTS photodiode (BPW-34) is presented. When applied in hadronic beams of protons and carbon ions, the detector reproduces dose distribution well, but its response decreases rapidly by radiation damage. However, for MeV photon beams, the detector exhibits a similar behavior as found in diode detectors usually applied in radiotherapy.

Radiotherapy of oral malignant melanomas in dogs.

PubMed

Blackwood, L; Dobson, J M

1996-07-01

To evaluate response to radiotherapy in dogs with oral malignant melanomas. Clinical trial. 36 dogs with histologically confirmed oral malignant melanomas. The prescribed radiation dose was 36 Gy given in 4 fractions of 9 Gy at 7-day intervals. The primary radiation source was a linear accelerator. In 25 of 36 dogs, complete remission was achieved, and in 9 dogs, partial remission was achieved. Recurrence of the primary tumor was the cause of euthanasia of 4 dogs. Twenty-one dogs were euthanatized because of metastasis. Radiotherapy was an effective palliative treatment for the primary tumor in dogs with oral malignant melanomas. However, rapid development of metastatic disease remained a major challenge.

Improvements in undergraduate oncology education introduced at Polish medical universities between 2004 and 2010 under Poland's "National Program for Combating Neoplastic Diseases".

PubMed

Matkowski, Rafał; Szelachowska, Jolanta; Szewczyk, Krzysztof; Staszek-Szewczyk, Urszula; Kornafel, Jan

2014-09-01

Cancer patient treatment in Poland remains unsatisfactory when compared to that in other countries. In 2005, this alarming situation prompted the Polish government to launch the "National Program for Combating Neoplastic Diseases" (NPCND). One part of this project was to improve the quality of oncology instruction at the undergraduate level over the years 2006 and 2007 (subsequently extended until 2010 thanks to promising results and the relatively small financial outlay). The program's main aims were to improve existing oncology therapy and to ameliorate the quality of undergraduate oncology education. To evaluate the changes in the quality of undergraduate education as a result of the NPCND program, medical universities were asked to fill out a questionnaire. Responses indicate that the program had a major positive impact on the quality of cancer education mainly as a result of the introduction of a uniform program of training and an increase in the number of classes devoted to oncology. The main unresolved problem is that university hospitals seldom have integrated units catering in-house for surgery, radiotherapy, chemotherapy, etc., and most such "hands-on" teaching still has to be done externally.

Hypofractionated Radiotherapy for Complicated Bone Metastases in Patients with Poor Performance Status: A Phase II International Trial.

PubMed

Silva, Mauricio F; Marta, Gustavo N; Lisboa, Felipe P C; Watte, Guilherme; Trippa, Fabio; Maranzano, Ernesto; da Motta, Neiro W; Popovic, Marko; Ha, Tuan; Burmeister, Bryan; Chow, Edward

2017-06-01

Purpose To evaluate the efficacy and safety of hypofractionated radiotherapy (16 Gy in 2 fractions, 1 week apart) in patients with complicated bone metastases and poor performance status. Methods A prospective single-arm phase II clinical trial was conducted from July 2014 to May 2016. The primary endpoint was pain response as defined in the International Consensus on Palliative Radiotherapy Endpoints. Secondary endpoints included quality of life as measured by quality of life questionnaire (QLQ) PAL-15 and QLQ-BM22 European Organisation for Research and Treatment of Cancer guidelines, pain flare, adverse events, re-irradiation, and skeletal complications. Results Fifty patients were enrolled. There were 23 men with a median age of 58 years (range 26-86). Of the 50 patients, 38 had an extraosseous soft tissue component, 18 needed postsurgical radiation, 3 had neuropathic pain, and 3 had an impending fracture in a weight-bearing bone. At 2 months, 33 patients were alive (66%). Four (12.5%) had a complete response and 12 (37.5%) had a partial response. A statistically significant improvement was seen in the functional interference (p = 0.01) and psychosocial aspects (p = 0.03) of the BM22. No patient had spinal cord compression. One patient required surgery for pathologic fracture, and another re-irradiation. Conclusions Hypofractionated radiotherapy (16 Gy in 2 fractions of 8 Gy 1 week apart) achieved satisfactory pain relief and safety results in patients with complicated bone metastases and poor performance status.

Monte Carlo role in radiobiological modelling of radiotherapy outcomes

NASA Astrophysics Data System (ADS)

El Naqa, Issam; Pater, Piotr; Seuntjens, Jan

2012-06-01

Radiobiological models are essential components of modern radiotherapy. They are increasingly applied to optimize and evaluate the quality of different treatment planning modalities. They are frequently used in designing new radiotherapy clinical trials by estimating the expected therapeutic ratio of new protocols. In radiobiology, the therapeutic ratio is estimated from the expected gain in tumour control probability (TCP) to the risk of normal tissue complication probability (NTCP). However, estimates of TCP/NTCP are currently based on the deterministic and simplistic linear-quadratic formalism with limited prediction power when applied prospectively. Given the complex and stochastic nature of the physical, chemical and biological interactions associated with spatial and temporal radiation induced effects in living tissues, it is conjectured that methods based on Monte Carlo (MC) analysis may provide better estimates of TCP/NTCP for radiotherapy treatment planning and trial design. Indeed, over the past few decades, methods based on MC have demonstrated superior performance for accurate simulation of radiation transport, tumour growth and particle track structures; however, successful application of modelling radiobiological response and outcomes in radiotherapy is still hampered with several challenges. In this review, we provide an overview of some of the main techniques used in radiobiological modelling for radiotherapy, with focus on the MC role as a promising computational vehicle. We highlight the current challenges, issues and future potentials of the MC approach towards a comprehensive systems-based framework in radiobiological modelling for radiotherapy.

Gut microbial dysbiosis may predict diarrhea and fatigue in patients undergoing pelvic cancer radiotherapy: a pilot study.

PubMed

Wang, Aiping; Ling, Zongxin; Yang, Zhixiang; Kiela, Pawel R; Wang, Tao; Wang, Cheng; Cao, Le; Geng, Fang; Shen, Mingqiang; Ran, Xinze; Su, Yongping; Cheng, Tianmin; Wang, Junping

2015-01-01

Fatigue and diarrhea are the most frequent adverse effects of pelvic radiotherapy, while their etiologies are largely unknown. The aim of this study is to investigate the correlations between fatigue, diarrhea, and alterations in gut microbiota induced by pelvic radiotherapy. During the 5-week treatment of pelvic radiotherapy in 11 cancer patients, the general fatigue score significantly increased and was more prominent in the patients with diarrhea. The fatigue score was closely correlated with the decrease of serum citrulline (an indicator of the functional enterocyte mass) and the increases of systemic inflammatory proteins, including haptoglobin, orosomuoid, α1-antitrypsin and TNF-α. Serum level of lipopolysaccharide (LPS) was also elevated, especially in the patients with diarrhea indicating epithelial barrier breach and endotoxemia. Pyrosequencing analysis of 16S rRNA gene revealed that microbial diversity, richness, and the Firmicutes/Bacteroidetes ratio were significantly altered prior to radiotherapy in patients who later developed diarrhea. Pelvic radiotherapy induced further changes in fecal microbial ecology, some of which were specific to the patients with or without diarrhea. Our results indicate that gut microbial dysbiosis prior to radiation therapy may be exploited to predict development of diarrhea and to guide preventive treatment options. Radiation-induced dysbiosis may contribute to pelvic radiation disease, including mucositis, diarrhea, systemic inflammatory response, and pelvic radiotherapy-associated fatigue in cancer patients.

Toxicity of aggressive multimodality therapy including cisplatinum, bleomycin and methotrexate with radiation and/or surgery for advanced head and neck cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weichselbaum, R.R.; Posner, M.R.; Ervin, T.J.

1982-05-01

A combined modality regimen employing induction chemotherapy with cisplatinum, bleomycin and methotrexate followed by surgery and/or radiation therapy was initiated in patients with advanced squamous cell carcinoma of the head and neck. In the first 23 patients treated with this program there was a 90% response rate to induction chemotherapy (9% CR and 81% PR). Toxicity associated with radiotherapy, but not surgery, was increased with 11 of 23 patients (48%) who experienced some toxicity during or immediately after radiotherapy. Mucositis was worse than expected and severe delayed mucositis was seen in 2 patients, one of whom required hospitalization. Late complications,more » possibly related to therapy included one myocardial infarction and one episode of hypoglycemia, both of which were fatal. One other patient voluntarily failed to take prescribed oral leucovorin, dying of unrescued methotrexate toxicity during adjuvant therapy, a questionable suicide. Further follow-up analysis of failure will be necessary to determine if the value of a combined modality regimen in producing an increased cure rate and long term survival will out weigh increased toxicity.« less

FAS Death Receptor: A Breast Cancer Subtype-Specific Radiation Response Biomarker and Potential Therapeutic Target

PubMed Central

Horton, Janet K.; Siamakpour-Reihani, Sharareh; Lee, Chen-Ting; Zhou, Ying; Chen, Wei; Geradts, Joseph; Fels, Diane R.; Hoang, Peter; Ashcraft, Kathleen A.; Groth, Jeff; Kung, Hsiu-Ni; Dewhirst, Mark W.; Chi, Jen-Tsan A.

2015-01-01

Although a standardized approach to radiotherapy has been used to treat breast cancer, regardless of subtype (e.g., luminal, basal), recent clinical data suggest that radiation response may vary significantly among subtypes. We hypothesized that this clinical variability may be due, in part, to differences in cellular radiation response. In this study, we utilized RNA samples for microarray analysis from two sources: 1. Paired pre- and postirradiation breast tumor tissue from 32 early-stage breast cancer patients treated in our unique preoperative radiation Phase I trial; and 2. Sixteen biologically diverse breast tumor cell lines exposed to 0 and 5 Gy irradiation. The transcriptome response to radiation exposure was derived by comparing gene expression in samples before and after irradiation. Genes with the highest coefficient of variation were selected for further evaluation and validated at the RNA and protein level. Gene editing and agonistic antibody treatment were performed to assess the impact of gene modulation on radiation response. Gene expression in our cohort of luminal breast cancer patients was distinctly different before and after irradiation. Further, two distinct patterns of gene expression were observed in our biologically diverse group of breast cancer cell lines pre- versus postirradiation. Cell lines that showed significant change after irradiation were largely luminal subtype, while gene expression in the basal and HER2+ cell lines was minimally impacted. The 100 genes with the most significant response to radiation in patients were identified and analyzed for differential patterns of expression in the radiation-responsive versus nonresponsive cell lines. Fourteen genes were identified as significant, including FAS, a member of the tumor necrosis factor receptor family known to play a critical role in programed cell death. Modulation of FAS in breast cancer cell lines altered radiation response phenotype and enhanced radiation sensitivity in radioresistant basal cell lines. Our findings suggest that cell-type-specific, radiation-induced FAS contributes to subtype-specific breast cancer radiation response and that activation of FAS pathways may be exploited for biologically tailored radiotherapy. PMID:26488758

Ultrasonic histogram assessment of early response to concurrent chemo-radiotherapy in patients with locally advanced cervical cancer: a feasibility study.

PubMed

Xu, Yan; Ru, Tong; Zhu, Lijing; Liu, Baorui; Wang, Huanhuan; Zhu, Li; He, Jian; Liu, Song; Zhou, Zhengyang; Yang, Xiaofeng

To monitor early response for locally advanced cervical cancers undergoing concurrent chemo-radiotherapy (CCRT) by ultrasonic histogram. B-mode ultrasound examinations were performed at 4 time points in thirty-four patients during CCRT. Six ultrasonic histogram parameters were used to assess the echogenicity, homogeneity and heterogeneity of tumors. I peak increased rapidly since the first week after therapy initiation, whereas W low , W high and A high changed significantly at the second week. The average ultrasonic histogram progressively moved toward the right and converted into more symmetrical shape. Ultrasonic histogram could be served as a potential marker to monitor early response during CCRT. Copyright © 2018 Elsevier Inc. All rights reserved.

Residual neck disease management in squamous-cell carcinoma of the head and neck treated with radiotherapy plus cetuximab.

PubMed

Montal, R; Oliva, M; Taberna, M; De Avila, L; Rovira, A; Cos, M; Mañós, M; Navarro, V; Nogués, J; Lozano, A; Rodríguez, L; Vilajosana, E; Vázquez, S; Mesia, R

2016-11-01

Management of residual neck disease (RND) is one of the unsolved points after bio-radiotherapy (BRT) in loco-regional advanced squamous-cell carcinoma of the head and neck (SCCHN). The aims of the study were to characterize the radiological pattern of response by computed tomography (CT) and to assess the role of positron-emission tomography (PET)/CT in this setting for a better decision-making in the indication of neck dissection (ND). We retrospectively reviewed 202 patients consecutively diagnosed with node-positive SCCHN (N1: 24; N2: 152; N3: 26) who had been treated with concomitant radiotherapy and cetuximab with or without previous induction chemotherapy between 2006 and 2013. Radiological evaluation after treatment was assessed by standard criteria using CT and in addition by PET/CT when RND was suspected in cases from 2010. There were 42 (21 %) patients who achieved complete response of the primary tumor persisting RND by CT. From this group, 24 patients were managed without PET/CT, leading to the performance of ND in 22 (92 %). On the other hand, 18 patients underwent PET/CT and ND was performed in only 6 (33 %). The overall survival was not different between both groups (p = 0.32). After histological examination and follow-up, PET/CT obtained a positive predictive value of 56 % and a negative predictive value of 89 %. Radiological response after BRT is similar to that after treatment with chemo-radiotherapy, thereby validating in this scenario the accepted CT criteria to define complete response of the neck. However, when RND is suspected by CT, PET/CT is useful to prevent unnecessary ND.

Anti-Ig autoantibody and complement-mediated destruction of neoplastic cells

NASA Technical Reports Server (NTRS)

Towmey, J. J.

1976-01-01

Some immune response are effected through immunoglobulins (Ig), of which five classes have been recognized, namely, IgA, IgD, IgE, IgG, and IgM. Auto-antibodies associated with rheumatoid arthritis, termed rheumatoid factors (RF) react with antigenic determinants on IgG heavy chains. RF has predominant but not complete IgM specificity. This auto-antibody response was not detected in treated patients with primary brain tumors (where tissue is sequestered from the immune system by an intact bloodbrain barrier) or with multiple myeloma where humoral immunity is usually impaired. In addition, the prevalence of RF is not increased with solid tumors prior to initiation of chemotherapy or radiotherapy. It is proposed that RF is related to prior chemotherapy or radiotherapy of tumors anatomically accessible to immunologic tissues capable of antibody responses. A primary IgG response occurs, antigen-antibody complexes form, complexed IgG becomes immunologic, and an RF response results.

Pretreatment Prediction of Brain Tumors' Response to Radiation Therapy Using High b-Value Diffusion-Weighted MRI1

PubMed Central

Mardor, Yael; Roth, Yiftach; Ocherashvilli, Aharon; Spiegelmann, Roberto; Tichler, Thomas; Daniels, Dianne; Maier, Stephan E; Nissim, Ouzi; Ram, Zvi; Baram, Jacob; Orenstein, Arie; Pfeffer, Raphael

2004-01-01

Abstract Diffusion-weighted magnetic resonance imaging (DWMRI) is sensitive to tissues' biophysical characteristics, including apparent diffusion coefficients (ADCs) and volume fractions of water in different populations. In this work, we evaluate the clinical efficacy of DWMRI and high diffusion-weighted magnetic resonance imaging (HDWMRI), acquired up to b = 4000 sec/mm2 to amplify sensitivity to water diffusion properties, in pretreatment prediction of brain tumors' response to radiotherapy. Twelve patients with 20 brain lesions were studied. Six ring-enhancing lesions were excluded due to their distinct diffusion characteristics. Conventional and DWMRI were acquired on a 0.5-T MRI. Response to therapy was determined from relative changes in tumor volumes calculated from contrast-enhanced T1-weighted MRI, acquired before and a mean of 46 days after beginning therapy. ADCs and a diffusion index, RD, reflecting tissue viability based on water diffusion were calculated from DWMRIs. Pretreatment values of ADC and RD were found to correlate significantly with later tumor response/nonresponse (r = 0.76, P < .002 and r = 0.77, P < .001). This correlation implies that tumors with low pretreatment diffusion values, indicating high viability, will respond better to radiotherapy than tumors with high diffusion values, indicating necrosis. These results demonstrate the feasibility of using DWMRI for pretreatment prediction of response to therapy in patients with brain tumors undergoing radiotherapy. PMID:15140402

Pretreatment prediction of brain tumors' response to radiation therapy using high b-value diffusion-weighted MRI.

PubMed

Mardor, Yael; Roth, Yiftach; Ochershvilli, Aharon; Spiegelmann, Roberto; Tichler, Thomas; Daniels, Dianne; Maier, Stephan E; Nissim, Ouzi; Ram, Zvi; Baram, Jacob; Orenstein, Arie; Pfeffer, Raphael

2004-01-01

Diffusion-weighted magnetic resonance imaging (DWMRI) is sensitive to tissues' biophysical characteristics, including apparent diffusion coefficients (ADCs) and volume fractions of water in different populations. In this work, we evaluate the clinical efficacy of DWMRI and high diffusion-weighted magnetic resonance imaging (HDWMRI), acquired up to b = 4000 sec/mm(2) to amplify sensitivity to water diffusion properties, in pretreatment prediction of brain tumors' response to radiotherapy. Twelve patients with 20 brain lesions were studied. Six ring-enhancing lesions were excluded due to their distinct diffusion characteristics. Conventional and DWMRI were acquired on a 0.5-T MRI. Response to therapy was determined from relative changes in tumor volumes calculated from contrast-enhanced T1-weighted MRI, acquired before and a mean of 46 days after beginning therapy. ADCs and a diffusion index, R(D), reflecting tissue viability based on water diffusion were calculated from DWMRIs. Pretreatment values of ADC and R(D) were found to correlate significantly with later tumor response/nonresponse (r = 0.76, P <.002 and r = 0.77, P <.001). This correlation implies that tumors with low pretreatment diffusion values, indicating high viability, will respond better to radiotherapy than tumors with high diffusion values, indicating necrosis. These results demonstrate the feasibility of using DWMRI for pretreatment prediction of response to therapy in patients with brain tumors undergoing radiotherapy.

An overview of the situation in radiotherapy with emphasis on the developing countries.

PubMed

Hanson, G P; Stjernswärd, J; Nofal, M; Durosinmi-Etti, F

1990-11-01

Radiotherapy services are closely linked to the level of medical care which, in turn, is an important component of the overall health care program, with its development related to social, economic, and educational factors. As a basis for understanding the situation regarding adequate coverage of the population by radiotherapy services, general information about the world population (currently 5 billion), age distribution, frequency of cancer occurrence, and causes of death is presented. For an appreciation of the obstacles that must be overcome, the situation with regard to Gross National Product (GNP), transfer of economic resources, and per capita expenditures for health services is shown. For example, in the developing world, most countries spend less than 5% of their GNP for health, and on a macro scale at least 20 billion U.S. dollars per year are being transferred from the poor nations of the southern hemisphere to the northern hemisphere. Information about the wide range of population coverage with radiotherapy resources and the trend regarding high-energy radiotherapy machines is presented. For example, in North America (USA) there are six high-energy machines for each one million persons, and each machine is used to treat about 230 new patients per year. In other parts of the world, such as large areas of Africa and South-East Asia, there may only be one high-energy radiotherapy machine for 20 to 40 million people, and one machine may be used to treat more than 600 new patients per year. Many cancer patients have no access to radiotherapy services. When estimates of the need for radiotherapy services in the developing world as a consequence of cancer incidence are compared with the current health expenditures, it is concluded that a combined effort of national authorities, donor and financial institutions, professional and scientific societies, and international organizations is required. The knowledge, skills, and technology are available in many excellent radiotherapy centers throughout the world. The key issues are priority and the commitment of sufficient resources.

Multiple comparisons permutation test for image based data mining in radiotherapy.

PubMed

Chen, Chun; Witte, Marnix; Heemsbergen, Wilma; van Herk, Marcel

2013-12-23

: Comparing incidental dose distributions (i.e. images) of patients with different outcomes is a straightforward way to explore dose-response hypotheses in radiotherapy. In this paper, we introduced a permutation test that compares images, such as dose distributions from radiotherapy, while tackling the multiple comparisons problem. A test statistic Tmax was proposed that summarizes the differences between the images into a single value and a permutation procedure was employed to compute the adjusted p-value. We demonstrated the method in two retrospective studies: a prostate study that relates 3D dose distributions to failure, and an esophagus study that relates 2D surface dose distributions of the esophagus to acute esophagus toxicity. As a result, we were able to identify suspicious regions that are significantly associated with failure (prostate study) or toxicity (esophagus study). Permutation testing allows direct comparison of images from different patient categories and is a useful tool for data mining in radiotherapy.

Preoperative radiotherapy and bevacizumab for angiosarcoma of the head and neck: two case studies.

PubMed

Koontz, Bridget F; Miles, Edward F; Rubio, Mary Ann D; Madden, John F; Fisher, Samuel R; Scher, Richard L; Brizel, David M

2008-02-01

Angiosarcoma of the face is a vascular tumor with poor local control and short median survival despite standard treatment. Bevacizumab is a humanized monoclonal antibody to vascular endothelial growth factor (VEGF), which can inhibit tumor growth. It is synergistic with radiotherapy in gastrointestinal malignancies. Given the vascular nature of angiosarcoma and the need for better treatment of this disease, we investigated the concurrent use of bevacizumab with preoperative radiotherapy for head and neck angiosarcoma. Two patients diagnosed with angiosarcoma of the nose were treated preoperatively with bevacizumab (5-10 mg/kg) and concurrent radiotherapy (50 Gy), followed by resection of the tumor bed. Both patients had a complete pathologic response with no residual disease. Neither has developed recurrence, with follow-up of 8.5 months and 2.1 years. The neoadjuvant combination of bevacizumab and radiation therapy is promising and should be further studied in the setting of vascular malignancies.

Concurrent chemoradiotherapy versus radiotherapy alone for locoregionally advanced nasopharyngeal carcinoma in the era of intensity-modulated radiotherapy: a meta-analysis.

PubMed

He, Yan; Guo, Tao; Guan, Hui; Wang, Jingjing; Sun, Yu; Peng, Xingchen

2018-01-01

In this study, we attempted to compare the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with radiotherapy alone (RT) for locoregionally advanced nasopharyngeal carcinoma (LANPC) in the era of intensity-modulated radiotherapy (IMRT) by meta-analysis. We searched databases, and all randomized controlled trials meeting the inclusion criteria were utilized for a meta-analysis with RevMan 5.3 based on the Cochrane methodology. Fifteen studies were found suitable based on the inclusion criteria. CCRT not only significantly improved the overall response rate (risk ratio [RR]=0.53, 95% CI 0.43-0.66) and the complete response rate (RR=0.60, 95% CI 0.51-0.71) but also contributed to longer overall survival. The incidence of grade 3-4 adverse events from CCRT group increased in hematologic toxicity (RR 2.25, 95% CI 1.54-3.29), radiation-induced oral mucositis (RR 1.64, 95% CI 1.14-2.35), and radiodermatitis (RR 1.80, 95% CI 1.13-2.88). Compared with IMRT alone, CCRT provided survival benefit with acceptable toxicity in patients with LANPC. However, we need multicenter randomized controlled trials and long-term follow-up to evaluate the eventual efficacy and toxicity of concurrent chemotherapy plus IMRT.

A prospective study: current problems in radiotherapy for nasopharyngeal carcinoma in yogyakarta, indonesia.

PubMed

Stoker, Sharon D; Wildeman, Maarten A; Fles, Renske; Indrasari, Sagung R; Herdini, Camelia; Wildeman, Pieter L; van Diessen, Judi N A; Tjokronagoro, Maesadji; Tan, I Bing

2014-01-01

Nasopharyngeal carcinoma (NPC) has a high incidence in Indonesia. Previous study in Yogyakarta revealed a complete response of 29% and a median overall survival of less than 2 years. These poor treatment outcome are influenced by the long diagnose-to-treatment interval to radiotherapy (DTI) and the extended overall treatment time of radiotherapy (OTT). This study reveals insight why the OTT and DTI are prolonged. All patients treated with curative intent radiotherapy for NPC between July 2011 until October 2012 were included. During radiotherapy a daily diary was kept, containing information on DTI, missed radiotherapy days, the reason for missing and length of OTT. Sixty-eight patients were included. The median DTI was 106 days (95% CI: 98-170). Fifty-nine patients (87%) finished the treatment. The median OTT for radiotherapy was 57 days (95% CI: 57-65). The main reason for missing days was an inoperative radiotherapy machine (36%). Other reasons were patient's poor condition (21%), public holidays (14%), adjustment of the radiation field (7%), power blackout (3%), inoperative treatment planning system (2%) and patient related reasons (9%). Patient's insurance type was correlated to DTI in disadvantage for poor people. Yogyakarta has a lack of sufficient radiotherapy units which causes a delay of 3-4 months, besides the OTT is extended by 10-12 days. This influences treatment outcome to a great extend. The best solution would be creating sufficient radiotherapy units and better management in health care for poor patients. The growing economy in Indonesia will expectantly in time enable these solutions, but in the meantime solutions are needed. Solutions can consist of radiation outside office hours, better maintenance of the facilities and more effort from patient, doctor and nurse to finish treatment in time. These results are valuable when improving cancer care in low and middle income countries.

Long-term survival in primary CNS lymphoma treated by high-dose methotrexate monochemotherapy: role of STAT6 activation as prognostic determinant.

PubMed

Yang, Seung-Ho; Lee, Kun Soo; Kim, Il Sup; Hong, Jae Taek; Sung, Jae Hoon; Son, Byung Chul; Lee, Sang Won; Hong, Yong-Kil

2009-03-01

We report a single-center experience of 16 immunocompetent patients diagnosed with primary central nervous system lymphoma and treated with monochemotherapy with high-dose methotrexate (MTX) and deferred radiotherapy. MTX was given at a dose of 8.0 g/m2 for induction and at a dose of 3.5-8.0 g/m2 for maintenance. There were eight complete responses (CR), one partial response, one stable disease, and six patients whose tumors progressed in spite of the chemotherapy. At final follow-up, five of five CRs were alive and well without radiotherapy, with median follow-up of 26 months. Overall survival in eight non-CRs treated with the subsequent radiotherapy was 36 months. In the immunohistochemical study, STAT6 was positively expressed in 8 out of 13 cases. They included all non-CRs and two CRs. This observation suggests that STAT6 expression can be used as a prognostic determinant for MTX chemotherapy.

Treatment results and prognostic factors of pediatric neuroblastoma: a retrospective study.

PubMed

El-Sayed, Mohamed I; Ali, Amany M; Sayed, Heba A; Zaky, Eman M

2010-12-24

We conducted a retrospective analysis to investigate treatment results and prognostic factors of pediatric neuroblastoma patients. This retrospective study was carried out analyzing the medical records of patients with the pathological diagnosis of neuroblastoma seen at South Egypt Cancer Institute, Assiut University during the period from January 2001 and January 2010. After induction chemotherapy, response according to international neuoblastoma response criteria was assessed. Radiotherapy to patients with residual primary tumor was applied. Overall and event free survival (OAS and EFS) rates were estimated using Graphed prism program. The Log-rank test was used to examine differences in OAS and EFS rates. Cox-regression multivariate analysis was done to determine the independent prognostic factors affecting survival rates. Fifty three cases were analyzed. The median follow-up duration was 32 months and ranged from 2 to 84 months. The 3-year OAS and EFS rates were 39.4% and 29.3% respectively. Poor prognostic factors included age >1 year of age, N-MYC amplification, and high risk group. The majority of patients (68%) presented in high risk group, where treatment outcome was poor, as only 21% of patients survived for 3 year. Multivariate analysis confirmed only the association between survival and risk group. However, in univariate analysis, local radiation therapy resulted in significant survival improvement. Therefore, radiotherapy should be given to patients with residual tumor evident after induction chemotherapy and surgery. Future attempts to improve OAS in high risk group patients with aggressive chemotherapy and bone marrow transplantation should be considered.

PyCMSXiO: an external interface to script treatment plans for the Elekta® CMS XiO treatment planning system

NASA Astrophysics Data System (ADS)

Xing, Aitang; Arumugam, Sankar; Holloway, Lois; Goozee, Gary

2014-03-01

Scripting in radiotherapy treatment planning systems not only simplifies routine planning tasks but can also be used for clinical research. Treatment planning scripting can only be utilized in a system that has a built-in scripting interface. Among the commercially available treatment planning systems, Pinnacle (Philips) and Raystation (Raysearch Lab.) have inherent scripting functionality. CMS XiO (Elekta) is a widely used treatment planning system in radiotherapy centres around the world, but it does not have an interface that allows the user to script radiotherapy plans. In this study an external scripting interface, PyCMSXiO, was developed for XiO using the Python programming language. The interface was implemented as a python package/library using a modern object-oriented programming methodology. The package was organized as a hierarchy of different classes (objects). Each class (object) corresponds to a plan object such as the beam of a clinical radiotherapy plan. The interface of classes was implemented as object functions. Scripting in XiO using PyCMSXiO is comparable with Pinnacle scripting. This scripting package has been used in several research projects including commissioning of a beam model, independent three-dimensional dose verification for IMRT plans and a setup-uncertainty study. Ease of use and high-level functions provided in the package achieve a useful research tool. It was released as an open-source tool that may benefit the medical physics community.

Development and evaluation of an instrument to measure health-related quality of life in Cuban breast cancer patients receiving radiotherapy.

PubMed

Lugo, Josefina; Nápoles, Misleidy; Pérez, Inés; Ordaz, Niurka; Luzardo, Mario; Fernández, Leticia

2014-01-01

INTRODUCTION Although modern technology has extended the survival of breast cancer patients, treatment's adverse effects impact their health-related quality of life. Currently, no instrument exists capable of identifying the range of problems affecting breast cancer patients receiving radiotherapy in Cuba's socioeconomic and cultural context. OBJECTIVES Construct and validate an instrument to measure the effects of breast cancer and radiotherapy on health-related quality of life in Cuban patients. METHODS The study was conducted at the Oncology and Radiobiology Institute, Havana, Cuba, from January 2010 through December 2011. Inclusion criteria were: adult female, histological diagnosis of breast cancer, treated with ambulatory radiotherapy, and written informed consent; patients unable to communicate orally or in writing, or who had neurologic or psychiatric conditions were excluded. Development phase: focus groups guided by a list of questions were carried out with 50 women. The patients reported 61 problems affecting their health-related quality-of-life. A nominal group (six oncologists and two nurses) identified the same problems. A syntactic analysis of the information was performed to create items for study and measurement scales. Content validity was determined by a nominal group of seven experts using professional judgment. Another 20 patients were selected to evaluate face validity. Validation phase: the instrument was applied to 230 patients at three different points: before radiotherapy, at the end of radiotherapy and four weeks after radiotherapy was concluded. Reliability, construct validity, discriminant validity, predictive validity, interpretability and response burden were evaluated. RESULTS The final instrument developed had 33 items distributed in 4 domains: physical functioning, psychological functioning, social and family relationships, and physical and emotional adverse effects of disease and treatment. There were two discrete items: perceived general health and perceived health-related quality of life. Content validity and face validity were assessed as acceptable, by experts and patients respectively. Homogeneity, construct validity, and discriminant validity were satisfactory. The best results were obtained with test-retest reliability, predictive validity, and interpretability; the low rate of unanswered questions indicated that the instrument did not produce excessive patient response burden. CONCLUSION The new instrument fulfilled the requirements for measuring impact of breast cancer and of radiotherapy on health-related quality of life in these Cuban patients, validating its usefulness for inclusion in clinical trial protocols.

Proton Radiotherapy for Solid Tumors of Childhood

PubMed Central

Cotter, Shane E.; McBride, Sean M.; Yock, Torunn I.

2012-01-01

The increasing efficacy of pediatric cancer therapy over the past four decades has produced many long-term survivors that now struggle with serious treatment related morbidities affecting their quality of life. Radiation therapy is responsible for a significant proportion of these late effects, but a relatively new and emerging modality, proton radiotherapy hold great promise to drastically reduce these treatment related late effects in long term survivors by sparing dose to normal tissues. Dosimetric studies of proton radiotherapy compared with best available photon based treatment show significant dose sparing to developing normal tissues. Furthermore, clinical data are now emerging that begin to quantify the benefit in decreased late treatment effects while maintaining excellent cancer control rates. PMID:22417062

Stereotactic ablative body radiotherapy combined with immunotherapy: present status and future perspectives.

PubMed

Rekers, N H; Troost, E G C; Zegers, C M L; Germeraad, W T V; Dubois, L J; Lambin, P

2014-10-01

Radiotherapy is along with surgery and chemotherapy one of the prime treatment modalities in cancer. It is applied in the primary, neoadjuvant as well as the adjuvant setting. Radiation techniques have rapidly evolved during the past decade enabling the delivery of high radiation doses, reducing side-effects in tumour-adjacent normal tissues. While increasing local tumour control, current and future efforts ought to deal with microscopic disease at a distance of the primary tumour, ultimately responsible for disease-progression. This review explores the possibility of bimodal treatment combining radiotherapy with immunotherapy. Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Second Malignant Neoplasms and Cardiovascular Disease Following Radiotherapy

PubMed Central

Ng, Andrea K.; Allan, James M.; Pui, Ching-Hon; Kennedy, Ann R.; Xu, X. George; Purdy, James A.; Applegate, Kimberly; Yahalom, Joachim; Constine, Louis S.; Gilbert, Ethel S.; Boice, John D.

2012-01-01

Second malignant neoplasms (SMNs) and cardiovascular disease (CVD) are among the most serious and life-threatening late adverse effects experienced by the growing number of cancer survivors worldwide and are due in part to radiotherapy. The National Council on Radiation Protection and Measurements (NCRP) convened an expert scientific committee to critically and comprehensively review associations between radiotherapy and SMNs and CVD, taking into account radiobiology; genomics; treatment (ie, radiotherapy with or without chemotherapy and other therapies); type of radiation; and quantitative considerations (ie, dose–response relationships). Major conclusions of the NCRP include: 1) the relevance of older technologies for current risk assessment when organ-specific absorbed dose and the appropriate relative biological effectiveness are taken into account and 2) the identification of critical research needs with regard to newer radiation modalities, dose–response relationships, and genetic susceptibility. Recommendation for research priorities and infrastructural requirements include 1) long-term large-scale follow-up of extant cancer survivors and prospectively treated patients to characterize risks of SMNs and CVD in terms of radiation dose and type; 2) biological sample collection to integrate epidemiological studies with molecular and genetic evaluations; 3) investigation of interactions between radiotherapy and other potential confounding factors, such as age, sex, race, tobacco and alcohol use, dietary intake, energy balance, and other cofactors, as well as genetic susceptibility; 4) focusing on adolescent and young adult cancer survivors, given the sparse research in this population; and 5) construction of comprehensive risk prediction models for SMNs and CVD to permit the development of follow-up guidelines and prevention and intervention strategies. PMID:22312134

In vivo potentiation of radiation response by topotecan in human rhabdomyosarcoma xenografted into nude mice.

PubMed

Chastagner, P; Merlin, J L; Marchal, C; Hoffstetter, S; Barberi-Heyob, M; Vassal, G; Duprez, A

2000-08-01

The lack of new highly efficacious drugs for cancer treatment promotes the search for innovative therapeutic modalities. The authors reported the results leading to the definition of parameters needed to demonstrate a possible radiopotentiation by topotecan (TPT) on two representative human rhabdomyosarcomas (RMSs) xenografted into nude mice. Experimental studies of radiopotentiation with different doses of topotecan showed that concomitant association of topotecan and RT for 5 consecutive days provided a synergistic therapeutic effect. Response rates were statistically higher with the radiochemotherapeutic combination (P < 0.001). Efficacy enhancement factors of this combination compared with the sum of the antitumoral activity of these treatments separately administrated were 1.54 and 1.60, respectively, on both rhabdomyosarcomas. Moreover, the efficiency of the combination of radiotherapy at the dose of 20 Gy with topotecan (12.5 mg/kg) was not statistically different from that of radiotherapy at the dose of 40 Gy. According to microscopy results, the analyses performed at different periods after topotecan treatment alone, radiotherapy alone, and their combination seemed to show that tumoral repopulation by malignant cells is as fast as the dose of radiotherapy and/or topotecan is low. Furthermore, lesions observed with the dose of 40 Gy were similar to those obtained with the association of topotecan at the dose of 12.5 mg/kg and radiotherapy at the dose of 20 Gy. In conclusion, all clinical and pathological results are consistent with a radiopotentiation effect of topotecan on the two xenografted human rhabdomyosarcomas and are currently leading to the design of clinical studies.

Immediate autologous breast reconstruction after neoadjuvant chemoradiotherapy for breast cancer: initial results of the first 29 patients.

PubMed

Grinsell, Damien; Pitcher, Meron; Wong, Shirley; Guerrieri, Mario; Nielsen, Hans H M

2018-03-01

Breast reconstruction after mastectomy in the treatment of locally advanced breast cancer is often done in stages and before radiotherapy. We have previously published an algorithm for immediate free autologous reconstruction after neoadjuvant chemotherapy and preoperative radiotherapy. This protocol was designed to provide a shorter and simpler reconstructive path whilst improving cosmesis and maintaining oncological efficiency. A total of 29 patients were included and underwent surgery for 30 cancers by the first author between 2010 and September 2015. Data were prospectively entered into a database and analysed for tumour size, chemotherapeutic response, lymph node involvement, surgical complications and tumour recurrence. The mean age was 55 ± 7 years. Eighty percent of patients had either a partial or complete chemotherapeutic response defined as >25% decrease in tumour size. Twenty-eight patients had free abdominal tissue transfer. One patient was excluded due to advanced disease. There were no take-backs due to microsurgical issues. One patient was reoperated on for a haematoma. Four patients had recurrent cancer during follow-up, three of whom are deceased. Many, but not all, breast reconstructive surgeons consider autologous reconstruction as the 'gold' standard in the presence of radiotherapy. Rearranging the order of radiotherapy and surgery means operating in a recently irradiated field. We believe the surgical challenges are outweighed by a shorter and simpler reconstructive journey that additionally results in a better cosmesis. It is possible to perform immediate free autologous reconstruction after neoadjuvant chemotherapy and preoperative radiotherapy with excellent results and at least equivalent oncological efficacy. © 2017 Royal Australasian College of Surgeons.

A Phase II feasibility study of oral etoposide given concurrently with radiotherapy followed by dose intensive adjuvant chemotherapy for children with newly diagnosed high-risk medulloblastoma (protocol POG 9631): A report from the Children's Oncology Group.

PubMed

Esbenshade, Adam J; Kocak, Mehmet; Hershon, Linda; Rousseau, Pierre; Decarie, Jean-Claude; Shaw, Susan; Burger, Peter; Friedman, Henry S; Gajjar, Amar; Moghrabi, Albert

2017-06-01

Children with high-risk medulloblastoma historically have had a poor prognosis. The Children's Oncology Group completed a Phase II study using oral etoposide given with radiotherapy followed by intensive chemotherapy. Patients enrolled in the study had high-risk disease defined as ≥1.5 cm 2 of residual disease postsurgery or definite evidence of central nervous metastasis. All patients underwent surgery followed by radiotherapy. During radiation, the patients received oral etoposide (21 days on, 7 off) at an initial dose of 50 mg/m 2 per day (treatment 1), which was reduced to 35 mg/m 2 per day (treatment 2) due to toxicity. After radiotherapy, the patients received chemotherapy with three cycles of cisplatin and oral etoposide, followed by eight courses of cyclophosphamide and vincristine. Between November 1998 and October 2002, 53 patients were accrued; 15 received treatment 1 and 38 treatment 2. Forty-seven patients (89%) were eligible. Response to radiation was excellent, with 19 (40.4%) showing complete response, 24 (51.1%) partial response, and four (8.5%) no recorded response. The overall 2- and 5-year progression-free survival (PFS) was 76.6 ± 6% and 70.2 ± 7%, respectively. The 2- and 5-year overall survival (OS) was 80.9 ± 6% and 76.6 ± 6%, respectively. Clinical response postradiation and PFS/OS were not significantly different between the treatment groups. There was a trend toward a difference in 5-year PFS between those without and with metastatic disease (P = 0.072). Oral etoposide was tolerable at 35 mg/m 2 (21 days on and 7 days off) when given during full-dose irradiation in patients with high-risk medulloblastoma with encouraging survival data. © 2016 Wiley Periodicals, Inc.

Nimotuzumab combined with radiotherapy for esophageal cancer: preliminary study of a Phase II clinical trial.

PubMed

Liang, Jun; E, Mingyan; Wu, Gang; Zhao, Lujun; Li, Xia; Xiu, Xia; Li, Ning; Chen, Bo; Hui, Zhouguang; Lv, Jima; Fang, Hui; Tang, Yu; Bi, Nan; Wang, Wenqing; Zhai, Yirui; Li, Tao; Chen, Dongfu; Zou, Shuangmei; Lu, Ning; Perez-Rodríguez, Rolando; Zheng, Junqi; Wang, Luhua

2013-01-01

To determine the safety and therapeutic effects of nimotuzumab (h-R3) combined with radiotherapy in esophageal cancer. This Phase II clinical trial involved 42 patients with stage II (inoperable or refused surgery) to stage IV (supraclavicular lymph node metastasis only) esophageal cancers treated between November 2008 and July 2010. All patients had squamous cell carcinomas, and all received three-dimensional conformal radiotherapy and 200 mg nimotuzumab per week during radiotherapy. There were 9, 25, and 8 patients with stage II, III and IV disease, respectively. All except two patients received 50-70 Gy radiation; 37 patients (88.1%) received more than five nimotuzumab doses. Grade III toxicities (21.4% of all adverse events) included esophagitis and gastrointestinal, dermatological and hematological toxicities. Complete response, partial response, stable disease, and progressive disease were observed in 0, 22 (52.4%), 17 (40.5%) and 3 (7.1%) patients at 1 month after the treatment. The epidermal growth factor receptor (EGFR) overexpression rate was 95.2%. After a median follow-up of 37 months, the median survival time (MST) was 14 months. The 2 year and 3 year overall survival (OS) rates were 33.3% and 26.2%, respectively. The median progression-free survival (PFS) time was 10 months. The 2 year and 3 year PFS rates were 24.5% and 22.1%, respectively. The MST in the 13 patients with (+++) EGFR expression (group A) and 7 patients with (++) EGFR expression (group B) was 15 and 11 months, respectively. The 2 year and 3 year OS rates were 46.2% and 38.5% in group A and 28.6% and 28.6% in group B, respectively (P = 0.405). Although concurrent chemoradiotherapy was the standard care for locally advanced esophageal cancer, radiotherapy was the choice for those who were refused or could not tolerate chemoradiotherapy. Our study shows that nimotuzumab combined with radiotherapy was well tolerated in patients with esophageal cancer. EGFR overexpression was more common than previously reported. OS was higher after combined therapy than after historical control radiotherapy alone. Further studies are required to confirm the therapeutic efficacy of nimotuzumab in esophageal cancer.

Audit of the job satisfaction levels of the UK radiography and physics workforce in UK radiotherapy centres 2012

PubMed Central

Beardmore, C; Patel, I; Massey, J; Wong, H; Probst, H

2014-01-01

Objective: Workforce planning reports identify a staff shortfall that jeopardizes the ability of UK radiotherapy centres to meet future demands. Obtaining an understanding of the work experiences of radiotherapy professionals will support the development of strategies to increase job satisfaction, productivity and effectiveness. Methods: A quantitative survey assessed job satisfaction, attitudes to incident reporting, stress and burnout, opportunities for professional development, workload, retention and turnover. Clinical oncologists were not included, as the Royal College of Radiologists, London, UK, had recently assessed their members' satisfaction. All questions were taken from validated instruments or adapted from the “UK National Health Service Staff Survey”. Results: The survey yielded 658 completed responses (approximately 16% response rate), from public and private sectors. Over a third (36%) of respondents were classified as satisfied for job satisfaction with 11% dissatisfied and the remaining 53% ambivalent. A significant proportion of clinical staff (37.5%) report high emotional exhaustion. Presenteeism was an issue with 42.4% attending work despite feeling unable to fulfil their role. Conclusion: Radiotherapy professionals are prone to the effects of compassion fatigue and burnout. Attention must be paid to workload and its impact on practitioners' job satisfaction. Professional development that is supported and informed by a performance development review is a simple and effective means of enhancing satisfaction. Individuals have a responsibility to themselves and their colleagues as their behaviours and attitudes influence job satisfaction. Advances in knowledge: This work identifies areas for future research to enhance the professional resilience of practitioners, in order to provide high-quality treatments. PMID:24786316

Audit of the job satisfaction levels of the UK radiography and physics workforce in UK radiotherapy centres 2012.

PubMed

Hutton, D; Beardmore, C; Patel, I; Massey, J; Wong, H; Probst, H

2014-07-01

Workforce planning reports identify a staff shortfall that jeopardizes the ability of UK radiotherapy centres to meet future demands. Obtaining an understanding of the work experiences of radiotherapy professionals will support the development of strategies to increase job satisfaction, productivity and effectiveness. A quantitative survey assessed job satisfaction, attitudes to incident reporting, stress and burnout, opportunities for professional development, workload, retention and turnover. Clinical oncologists were not included, as the Royal College of Radiologists, London, UK, had recently assessed their members' satisfaction. All questions were taken from validated instruments or adapted from the "UK National Health Service Staff Survey". The survey yielded 658 completed responses (approximately 16% response rate), from public and private sectors. Over a third (36%) of respondents were classified as satisfied for job satisfaction with 11% dissatisfied and the remaining 53% ambivalent. A significant proportion of clinical staff (37.5%) report high emotional exhaustion. Presenteeism was an issue with 42.4% attending work despite feeling unable to fulfil their role. Radiotherapy professionals are prone to the effects of compassion fatigue and burnout. Attention must be paid to workload and its impact on practitioners' job satisfaction. Professional development that is supported and informed by a performance development review is a simple and effective means of enhancing satisfaction. Individuals have a responsibility to themselves and their colleagues as their behaviours and attitudes influence job satisfaction. This work identifies areas for future research to enhance the professional resilience of practitioners, in order to provide high-quality treatments.

The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mehta, Minesh P.; Tsao, May N.; Whelan, Timothy J.

2005-09-01

Purpose: To systematically review the evidence for the use of stereotactic radiosurgery in adult patients with brain metastases. Methods: Key clinical questions to be addressed in this evidence-based review were identified. Outcomes considered were overall survival, quality of life or symptom control, brain tumor control or response and toxicity. MEDLINE (1990-2004 June Week 2), CANCERLIT (1990-2003), CINAHL (1990-2004 June Week 2), EMBASE (1990-2004 Week 25), and the Cochrane library (2004 issue 2) databases were searched using OVID. In addition, the Physician Data Query clinical trials database, the proceedings of the American Society of Clinical Oncology (ASCO) (1997-2004), ASTRO (1997-2004), andmore » the European Society of Therapeutic Radiology and Oncology (ESTRO) (1997-2003) were searched. Data from the literature search were reviewed and tabulated. This process included an assessment of the level of evidence. Results: For patients with newly diagnosed brain metastases, managed with whole-brain radiotherapy alone vs. whole-brain radiotherapy and radiosurgery boost, there were three randomized controlled trials, zero prospective studies, and seven retrospective series (which satisfied inclusion criteria). For patients with up to three (<4 cm) newly diagnosed brain metastases (and in one study up to four brain metastases), radiosurgery boost with whole-brain radiotherapy significantly improves local brain control rates as compared with whole-brain radiotherapy alone (Level I-III evidence). In one large randomized trial, survival benefit with whole-brain radiotherapy was observed in patients with single brain metastasis. In this trial, an overall increased ability to taper down on steroid dose and an improvement in Karnofsky performance status was seen in patients who were treated with radiosurgery boost as compared with patients treated with whole-brain radiotherapy alone. However, Level I evidence regarding overall quality of life outcomes using a validated instrument has not been reported. All randomized trials showed improved local control with the addition of radiosurgery to whole-brain radiotherapy. For patients with multiple brain metastases, there is no overall survival benefit with the use of radiosurgery boost to whole-brain radiotherapy (Level I-III evidence). Radiosurgery boost is associated with a small risk of early or late toxicity. In patients treated with radiosurgery alone (withholding whole-brain radiotherapy) as initial treatment, there were 2 randomized trials, 2 prospective cohort studies, and 16 retrospective series. There is Level I to Level III evidence that the use of radiosurgery alone does not alter survival as compared to the use of whole-brain radiotherapy. However, there is Level I to Level III evidence that omission of whole-brain radiotherapy results in poorer intracranial disease control, both local and distant (defined as remaining brain, outside the radiosurgery field). Quality of life outcomes have not been adequately reported. Radiosurgery is associated with a small risk of early or late toxicity. Radiosurgery as salvage for patients with brain metastases was reported in zero randomized trials, one prospective study, and seven retrospective series. Conclusions: Based on Level I-III evidence, for selected patients with small (up to 4 cm) brain metastases (up to three in number and four in one randomized trial), the addition of radiosurgery boost to whole-brain radiotherapy improves brain control as compared with whole-brain radiotherapy alone. In patients with a single brain metastasis, radiosurgery boost with whole-brain radiotherapy improves survival. There is a small risk of toxicity associated with radiosurgery boost as compared with whole-brain radiotherapy alone. In selected patients treated with radiosurgery alone for newly diagnosed brain metastases, overall survival is not altered. However, local and distant brain control is significantly poorer with omission of upfront whole-brain radiotherapy (Level I-III evidence). Whether neurocognition or quality of life outcomes are different between initial radiosurgery alone vs. whole-brain radiotherapy (with or without radiosurgery boost) is unknown, because this has not been adequately tested. There was no statistically significant difference in overall toxicity between those treated with radiosurgery alone vs. whole-brain radiotherapy and radiosurgery boost based on an interim report from one randomized study. There is insufficient evidence as to the clinical benefit/risks radiosurgery used in the setting of recurrent or progressive brain metastases, although radiographic responses are well-documented.« less

A reusable OSL-film for 2D radiotherapy dosimetry

NASA Astrophysics Data System (ADS)

Wouter, Crijns; Dirk, Vandenbroucke; Paul, Leblans; Tom, Depuydt

2017-11-01

Optical stimulated luminescence (OSL) combines reusability, sub-mm resolution, and a linear dose response in a single radiation detection technology. Such a combination is currently lacking in radiotherapy dosimetry. But OSL-films have a strong energy dependent response to keV photons due to a relative high effective atomic number (Z eff). The current work studied the applicability of a 2D OSL-film with a reduced Z eff as (IMRT/VMAT) dosimeter. Based on their commercial OSL-film experience, Agfa Healthcare N.V. produced a new experimental OSL-film for RT dosimetry. This film had a lower effective atomic number compared to the films used in radiology. Typical 2D dosimeter requirements such as uniformity, dose response, signal stability with time, and angular dependence were evaluated. Additionally, the impact of a possible residual energy dependence was assessed for the infield as well as the out-of-field region of both static beams and standard intensity modulated patterns (chair and pyramid). The OSL-film’s reusable nature allowed for a film specific absolute and linear calibration including a flood-field uniformity correction. The OSL-film was scanned with a CR-15X engine based reader using a strict timing (i.e. 4 min after ‘beam on’ or as soon as possible) to account for spontaneous recombination. The OSL-film had good basic response properties: non-uniformities  ⩽2.6%, a linear dose response (0-32 Gy), a linear signal decay (0.5% min-1) over the 20 min measured, and limited angular dependence  ⩽2.6%. Due to variations of the energy spectrum, larger dose differences were noted outside the central region of the homogenous phantom and outside both static and IMRT fields. However, the OSL-film’s measured dose differences of the IMRT patterns were lower than those of Gafchromic EBT measurements ([-1.6%, 2.1%] versus [-2.9%, 3.6%]). The current OSL-film could be used as a reusable high resolution dosimeter with read-out immediately after irradiation. Inside the (IMRT) treatment fields residual energy dependent effects were not observed. Novelty and significance: Implementing a reusable optical stimulated luminescence (OSL) film for radiotherapy dosimetry would enable user-friendly, sub(mm) resolution 2D dosimetry with instantaneous read-out. Radiology OSL-films have a strong energy dependent response which hampers accurate dosimetry. The current work reports measurements with a first 2D OSL-film tailored to the radiotherapy needs: including an improved water equivalent composition. The dosimeter adds the ability for sub-mm resolution repeated measurements to the portfolio of radiotherapy dosimetry.

A reusable OSL-film for 2D radiotherapy dosimetry.

PubMed

Wouter, Crijns; Dirk, Vandenbroucke; Paul, Leblans; Tom, Depuydt

2017-10-19

Optical stimulated luminescence (OSL) combines reusability, sub-mm resolution, and a linear dose response in a single radiation detection technology. Such a combination is currently lacking in radiotherapy dosimetry. But OSL-films have a strong energy dependent response to keV photons due to a relative high effective atomic number (Z eff ). The current work studied the applicability of a 2D OSL-film with a reduced Z eff as (IMRT/VMAT) dosimeter. Based on their commercial OSL-film experience, Agfa Healthcare N.V. produced a new experimental OSL-film for RT dosimetry. This film had a lower effective atomic number compared to the films used in radiology. Typical 2D dosimeter requirements such as uniformity, dose response, signal stability with time, and angular dependence were evaluated. Additionally, the impact of a possible residual energy dependence was assessed for the infield as well as the out-of-field region of both static beams and standard intensity modulated patterns (chair and pyramid). The OSL-film's reusable nature allowed for a film specific absolute and linear calibration including a flood-field uniformity correction. The OSL-film was scanned with a CR-15X engine based reader using a strict timing (i.e. 4 min after 'beam on' or as soon as possible) to account for spontaneous recombination. The OSL-film had good basic response properties: non-uniformities  ⩽2.6%, a linear dose response (0-32 Gy), a linear signal decay (0.5% min -1 ) over the 20 min measured, and limited angular dependence  ⩽2.6%. Due to variations of the energy spectrum, larger dose differences were noted outside the central region of the homogenous phantom and outside both static and IMRT fields. However, the OSL-film's measured dose differences of the IMRT patterns were lower than those of Gafchromic EBT measurements ([-1.6%, 2.1%] versus [-2.9%, 3.6%]). The current OSL-film could be used as a reusable high resolution dosimeter with read-out immediately after irradiation. Inside the (IMRT) treatment fields residual energy dependent effects were not observed. Novelty and significance: Implementing a reusable optical stimulated luminescence (OSL) film for radiotherapy dosimetry would enable user-friendly, sub(mm) resolution 2D dosimetry with instantaneous read-out. Radiology OSL-films have a strong energy dependent response which hampers accurate dosimetry. The current work reports measurements with a first 2D OSL-film tailored to the radiotherapy needs: including an improved water equivalent composition. The dosimeter adds the ability for sub-mm resolution repeated measurements to the portfolio of radiotherapy dosimetry.

A Matter of Timing: Identifying Significant Multi-Dose Radiotherapy Improvements by Numerical Simulation and Genetic Algorithm Search

PubMed Central

Angus, Simon D.; Piotrowska, Monika Joanna

2014-01-01

Multi-dose radiotherapy protocols (fraction dose and timing) currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA) techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5%) and 7.1% (13.3%) improvement (reduction) on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h), leading to the discovery that the performance of the GA search candidates could be replicated by 17–18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost-effecitive means of significantly improving clinical efficacy. PMID:25460164

A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search.

PubMed

Angus, Simon D; Piotrowska, Monika Joanna

2014-01-01

Multi-dose radiotherapy protocols (fraction dose and timing) currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA) techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5%) and 7.1% (13.3%) improvement (reduction) on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h), leading to the discovery that the performance of the GA search candidates could be replicated by 17-18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost-effecitive means of significantly improving clinical efficacy.

Persistent dysphagia after head and neck radiotherapy: a common and under-reported complication with significant effect on non-cancer-related mortality.

PubMed

Szczesniak, M M; Maclean, J; Zhang, T; Graham, P H; Cook, I J

2014-11-01

Dysphagia is a well-recognised acute complication after radiotherapy. However, knowledge about the long-term prevalence and effect remains limited. The aims of this study were to determine the prevalence, severity, morbidity, time course and reporting patterns of dysphagia symptoms after head and neck radiotherapy. An observational cross-sectional study was conducted in a large consecutive series of head and neck cancer patients. All patients in the St George Hospital Cancer Care database who had received head and neck radiotherapy with curative intent 0.5-8 years previously and recorded as being alive were surveyed using the Sydney Swallow Questionnaire (SSQ). Case notes were reviewed to determine the level of awareness of swallowing dysfunction in all patients, as well as the causes of mortality in the 83 deceased patients. The mean follow-up at the time of survey was 3 years after radiotherapy (range 0.5-8 years). Of the 116 patients surveyed by questionnaire, the response rate was 72% (83). Impaired swallowing (SSQ score > 234) was reported by 59% of patients. Dysphagia severity was not predicted by tumour site or stage, nor by the time since therapy, age, gender or adjuvant chemotherapy. Review of the hospital medical records and cancer database revealed that cancer accounted for 55% of deaths and aspiration pneumonia was responsible for 19% of non-cancer-related deaths. Of those with abnormal SSQ scores, only 47% reported dysphagia during follow-up clinic visits. Persistent dysphagia is a prevalent, under-recognised and under-reported long-term complication of head and neck radiotherapy which currently cannot be predicted on the basis of patient, tumour or treatment characteristics. Aspiration pneumonia is an important contributor to non-cancer-related mortality in these patients. These data highlight the need for closer monitoring of swallow dysfunction and its sequelae in this population. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Energy response of glass bead TLDs irradiated with radiation therapy beams

NASA Astrophysics Data System (ADS)

Jafari, S. M.; Jordan, T. J.; Hussein, M.; Bradley, D. A.; Clark, C. H.; Nisbet, A.; Spyrou, N. M.

2014-11-01

Glass beads are a novel TL dosimeter in radiotherapy. An important characteristic of TL dosimeters is their energy response, especially when intended for use in radiotherapy applications over a wide range of energies (typically from X-rays generated at 80 kVp up to 25 MV photon and MeV electron beams). In this paper, the energy response of glass beads (Mill Hill, Japan) is investigated for their TL response to kV X-rays from an orthovoltage radiotherapy unit and also for MV photon and MeV electron beams from a medical linear accelerator. The experimental findings show that for photon and electron beams, the TL response of this particular glass bead, normalised to unity for 6 MV X-rays (TPR20/10=0.670), decreases to 0.96±0.02 for 15 MV X-rays (TPR20/10=0.761) and to 0.95±0.01 for 20 MeV electron beams (R50,D=8.35 cm). This compares favourably with other TLD materials such as LiF and also alanine dosimeters that are readout with an EPR system. For kV X-rays, the response increases to 4.52±0.05 for 80 kV X-rays (HVL=2.4 mm Al) which approaches 3 times that of LiF TLDs and 5 times that of alanine. In conclusion, the particular glass beads, when used as a dosimeter material, show a relatively small energy dependence over the megavoltage range of clinically relevant radiation qualities, being clearly advantageous for accurate dosimetry. Conversely, the energy response is significant for photon beam energies covering the kV range. In both circumstances, in dosimetric evaluations the energy response needs to be taken into account.

Radiotherapy Dose Fractionation under Parameter Uncertainty

NASA Astrophysics Data System (ADS)

Davison, Matt; Kim, Daero; Keller, Harald

2011-11-01

In radiotherapy, radiation is directed to damage a tumor while avoiding surrounding healthy tissue. Tradeoffs ensue because dose cannot be exactly shaped to the tumor. It is particularly important to ensure that sensitive biological structures near the tumor are not damaged more than a certain amount. Biological tissue is known to have a nonlinear response to incident radiation. The linear quadratic dose response model, which requires the specification of two clinically and experimentally observed response coefficients, is commonly used to model this effect. This model yields an optimization problem giving two different types of optimal dose sequences (fractionation schedules). Which fractionation schedule is preferred depends on the response coefficients. These coefficients are uncertainly known and may differ from patient to patient. Because of this not only the expected outcomes but also the uncertainty around these outcomes are important, and it might not be prudent to select the strategy with the best expected outcome.

Multivalent Binding and Biomimetic Cell Rolling Improves the Sensitivity and Specificity of Circulating Tumor Cell Capture.

PubMed

Myung, Ja Hye; Eblan, Michael J; Caster, Joseph M; Park, Sin-Jung; Poellmann, Michael J; Wang, Kyle; Tam, Kevin A; Miller, Seth M; Shen, Colette; Chen, Ronald C; Zhang, Tian; Tepper, Joel E; Chera, Bhishamjit S; Wang, Andrew Z; Hong, Seungpyo

2018-06-01

Purpose: We aimed to examine the effects of multivalent binding and biomimetic cell rolling on the sensitivity and specificity of circulating tumor cell (CTC) capture. We also investigated the clinical significance of CTCs and their kinetic profiles in patients with cancer undergoing radiotherapy treatment. Experimental Design: Patients with histologically confirmed primary carcinoma undergoing radiotherapy, with or without chemotherapy, were eligible for enrollment. Peripheral blood was collected prospectively at up to five time points, including before radiotherapy, at the first week, mid-point and final week of treatment, as well as 4 to 12 weeks after completion of radiotherapy. CTC capture was accomplished using a nanotechnology-based assay (CapioCyte) functionalized with aEpCAM, aHER-2, and aEGFR. Results: CapioCyte was able to detect CTCs in all 24 cancer patients enrolled. Multivalent binding via poly(amidoamine) dendrimers further improved capture sensitivity. We also showed that cell rolling effect can improve CTC capture specificity (% of captured cells that are CK + /CD45 - /DAPI + ) up to 38%. Among the 18 patients with sequential CTC measurements, the median CTC decreased from 113 CTCs/mL before radiotherapy to 32 CTCs/mL at completion of radiotherapy ( P = 0.001). CTCs declined throughout radiotherapy in patients with complete clinical and/or radiographic response, in contrast with an elevation in CTCs at mid or post-radiotherapy in the two patients with known pathologic residual disease. Conclusions: Our study demonstrated that multivalent binding and cell rolling can improve the sensitivity and specificity of CTC capture compared with multivalent binding alone, allowing reliable monitoring of CTC changes during and after treatment. Clin Cancer Res; 24(11); 2539-47. ©2018 AACR . ©2018 American Association for Cancer Research.

Credentialing of radiotherapy centres in Australasia for TROG 09.02 (Chisel), a Phase III clinical trial on stereotactic ablative body radiotherapy of early stage lung cancer.

PubMed

Kron, Tomas; Chesson, Brent; Hardcastle, Nicholas; Crain, Melissa; Clements, Natalie; Burns, Mark; Ball, David

2018-05-01

A randomised clinical trial comparing stereotactic ablative body radiotherapy (SABR) with conventional radiotherapy for early stage lung cancer has been conducted in Australia and New Zealand under the auspices of the TransTasman Radiation Oncology Group (NCT01014130). We report on the technical credentialing program as prerequisite for centres joining the trial. Participating centres were asked to develop treatment plans for two test cases to assess their ability to create plans according to protocol. Dose delivery in the presence of inhomogeneity and motion was assessed during a site visit using a phantom with moving inserts. Site visits for the trial were conducted in 16 Australian and 3 New Zealand radiotherapy facilities. The tests with low density inhomogeneities confirmed shortcomings of the AAA algorithm for dose calculation. Dose was assessed for a typical treatment delivery including at least one non-coplanar beam in a stationary and moving phantom. This end-to-end test confirmed that all participating centres were able to deliver stereotactic ablative body radiotherapy with the required accuracy while the planning study demonstrated that they were able to produce acceptable plans for both test cases. The credentialing process documented that participating centres were able to deliver dose as required in the trial protocol. It also gave an opportunity to provide education about the trial and discuss technical issues such as four-dimensional CT, small field dosimetry and patient immobilisation with staff in participating centres. Advances in knowledge: Credentialing is an important quality assurance tool for radiotherapy trials using advanced technology. In addition to confirming technical competence, it provides an opportunity for education and discussion about the trial.

Local Control With Reduced-Dose Radiotherapy for Low-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group D9602 Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Breneman, John, E-mail: john.breneman@uchealth.com; Meza, Jane; Donaldson, Sarah S.

2012-06-01

Purpose: To analyze the effect of reduced-dose radiotherapy on local control in children with low-risk rhabdomyosarcoma (RMS) treated in the Children's Oncology Group D9602 study. Methods and Materials: Patients with low-risk RMS were nonrandomly assigned to receive radiotherapy doses dependent on the completeness of surgical resection of the primary tumor (clinical group) and the presence of involved regional lymph nodes. After resection, most patients with microscopic residual and uninvolved nodes received 36 Gy, those with involved nodes received 41.4 to 50.4 Gy, and those with orbital primary tumors received 45 Gy. All patients received vincristine and dactinomycin, with cyclophosphamide addedmore » for patient subsets with a higher risk of relapse in Intergroup Rhabdomyosarcoma Study Group III and IV studies. Results: Three hundred forty-two patients were eligible for analysis; 172 received radiotherapy as part of their treatment. The cumulative incidence of local/regional failure was 15% in patients with microscopic involved margins when cyclophosphamide was not part of the treatment regimen and 0% when cyclophosphamide was included. The cumulative incidence of local/regional failure was 14% in patients with orbital tumors. Protocol-specified omission of radiotherapy in girls with Group IIA vaginal tumors (n = 5) resulted in three failures for this group. Conclusions: In comparison with Intergroup Rhabdomyosarcoma Study Group III and IV results, reduced-dose radiotherapy does not compromise local control for patients with microscopic tumor after surgical resection or with orbital primary tumors when cyclophosphamide is added to the treatment program. Girls with unresected nonbladder genitourinary tumors require radiotherapy for postsurgical residual tumor for optimal local control to be achieved.« less

Low-dose radiotherapy as a chemo-potentiator of a chemotherapy regimen with pemetrexed for recurrent non-small-cell lung cancer: a prospective phase II study.

PubMed

Mantini, Giovanna; Valentini, Vincenzo; Meduri, Bruno; Margaritora, Stefano; Balducci, Mario; Micciché, Francesco; Nardone, Luigia; De Rose, Fiorenza; Cesario, Alfredo; Larici, Anna Rita; Maggi, Fabio; Calcagni, Maria Lucia; Granone, Pierluigi

2012-11-01

Low-dose radiotherapy (LDR) (<50 cGy) induces enhanced cell killing in vitro via the hyper-radiation sensitivity phenomenon. Aim of this study was to evaluate the safety and efficacy of a palliative regimen combining pemetrexed and LDR (as a chemopotentiator) on patients affected by recurrent non-small-cell lung cancer (NSCLC). Eligible patients had an ECOG performance status ≤2, one prior chemotherapy regimen for advanced NSCLC, adequate organ function, measurable lesions. Patients received pemetrexed (500 mg/m(2) IV) and concurrent LDR (40 cGy bid on days 1 and 2) delivered to target pulmonary or metastatic disease. This cycle was repeated fourfold every 21 days. The accrual was determined by the single proportion powered analysis (α=0.05, power=0.8) with H0 ("bad" response probability, 9% according to literature) and H1 ("good" response probability, 35% ongoing study); 19 is the number required. Nineteen patients with stage III and IV disease were enrolled. Only one patient experienced neutropenia grade 4. All patients are evaluable for clinical response of irradiated lesion: overall response rate was 42%. Low-dose radiotherapy combined with pemetrexed has a similar toxicity profile to chemotherapy alone. The response rate of this novel approach is encouraging, since it was higher than what was reported for pemetrexed alone (42% versus 9.1%). Additional scientific investigation of this new treatment paradigm is warranted. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Systemic effects of ionizing radiation at the proteome and metabolome levels in the blood of cancer patients treated with radiotherapy: the influence of inflammation and radiation toxicity.

PubMed

Jelonek, Karol; Pietrowska, Monika; Widlak, Piotr

2017-07-01

Blood is the most common replacement tissue used to study systemic responses of organisms to different types of pathological conditions and environmental insults. Local irradiation during cancer radiotherapy induces whole body responses that can be observed at the blood proteome and metabolome levels. Hence, comparative blood proteomics and metabolomics are emerging approaches used in the discovery of radiation biomarkers. These techniques enable the simultaneous measurement of hundreds of molecules and the identification of sets of components that can discriminate different physiological states of the human body. Radiation-induced changes are affected by the dose and volume of irradiated tissues; hence, the molecular composition of blood is a hypothetical source of biomarkers for dose assessment and the prediction and monitoring of systemic responses to radiation. This review aims to provide a comprehensive overview on the available evidence regarding molecular responses to ionizing radiation detected at the level of the human blood proteome and metabolome. It focuses on patients exposed to radiation during cancer radiotherapy and emphasizes effects related to radiation-induced toxicity and inflammation. Systemic responses to radiation detected at the blood proteome and metabolome levels are primarily related to the intensity of radiation-induced toxicity, including inflammatory responses. Thus, several inflammation-associated molecules can be used to monitor or even predict radiation-induced toxicity. However, these abundant molecular features have a rather limited applicability as universal biomarkers for dose assessment, reflecting the individual predisposition of the immune system and tissue-specific mechanisms involved in radiation-induced damage.

Comparison of genomics and functional imaging from canine sarcomas treated with thermoradiotherapy predicts therapeutic response and identifies combination therapeutics

PubMed Central

Chi, Jen-Tsan; Thrall, Donald E.; Jiang, Chen; Snyder, Stacey; Fels, Diane; Landon, Chelsea; McCall, Linda; Lan, Lan; Hauck, Marlene; MacFall, James R.; Viglianti, Benjamin L.; Dewhirst, Mark W.

2011-01-01

Purpose While hyperthermia is an effective adjuvant treatment to radiotherapy, we don’t completely understand the nature of the response heterogeneity. Experimental Design We performed gene expression analysis of 22 spontaneous canine sarcomas before and after the first hyperthermia treatment administered as an adjuvant to radiotherapy. In parallel, diffusion weighted MRI (DWI) was done prior to the treatment course and at the end of therapy. Results From the integrative analysis of gene expression and DWI, we identified significant correlation between tumor responses with genes involved in VEGF signaling, telomerase, DNA repair and inflammation. The treatment-induced changes in gene expression identified two distinct tumor subtypes with significant differences in their gene expression and treatment response, as defined by changes in DWI. The two tumor subtypes could also be readily identified by pre-treatment gene expression. The tumor subtypes, with stronger expression response and DWI increase, had higher levels of hsp70, POT1 and centrosomal proteins and lower levels of CD31, vWF and transferrin. Such differential gene expression between the two subtypes was used to interrogate connectivity map and identify linkages to an HSP90 inhibitor, geldanamycin. We further validated the ability of geldanamycin to enhance cell killing of human tumor cells with hyperthermia and radiotherapy in clonogenic assays. Conclusions To our knowledge, this is one of the first successful attempts to link changes in gene expression and functional imaging to understand the response heterogeneity and identify compounds enhancing thermoradiotherapy. This study also demonstrates the value of canine tumors to provide information generalizable to human tumors. PMID:21292819

Phase II Trial of Induction Chemotherapy Followed by Surgery for Squamous Cell Carcinoma of the Oral Tongue in Young Adults

PubMed Central

Kies, Merrill S.; Boatright, Dowin H.; Li, Guojun; Blumenschein, George; El-Naggar, Adel K.; Lewin, Jan S.; Steinhaus, Ganene; Sturgis, Erich M.

2013-01-01

Background We conducted a phase II clinical trial of induction chemotherapy followed by surgery ± radiotherapy for squamous cell carcinoma of the oral tongue (SCCOT) in young adults. Methods From September 2001 to October 2004, 23 patients aged 18–49 years with clinical T2-3N0-2M0 SCCOT and no prior radiotherapy, chemotherapy, or neck dissection underwent induction chemotherapy (paclitaxel, ifosfamide, and carboplatin) followed by glossectomy and neck dissection ± radiotherapy and chemotherapy. Results On final surgical pathology, 9 (39%) patients had a complete/major (2 complete) histologic response at the primary tumor site; 8 (35%) had no response or progression. Similarly, 9 (39%) patients had a complete response in the neck or remained node negative; 6 (26%) had an increase in nodal category. No treatment-associated deaths occurred, and toxicity was modest. At a median follow-up from the end of treatment of 52 months (minimum, 23 months), 10 (43%) patients developed recurrence, and all 10 died of cancer. Crude recurrence/cancer death rates were associated with ≤ a partial response at the tongue (P = .029), poor histologic differentiation (P = .012), and multiple adverse features on final surgical pathology (P = .040). Conclusions Response rates and overall survival with this induction chemotherapy regimen were limited, but complete/major response at the tongue was associated with excellent prognosis. Additionally, improved patient selection and predictive tumor biomarkers will be needed for induction chemotherapy to be routinely incorporated into the treatment of oral tongue cancer in young adults. PMID:22009800

Phase II trial of induction chemotherapy followed by surgery for squamous cell carcinoma of the oral tongue in young adults.

PubMed

Kies, Merrill S; Boatright, Dowin H; Li, Guojun; Blumenschein, George; El-Naggar, Adel K; Brandon Gunn, G; Lewin, Jan S; Steinhaus, Ganene D; Sturgis, Erich M

2012-09-01

We conducted a phase II clinical trial of induction chemotherapy followed by surgery ± radiotherapy for squamous cell carcinoma of the oral tongue (SCCOT) in young adults. From September 2001 to October 2004, 23 patients aged 18 to 49 years with clinical T2-3 N0-2 M0 SCCOT and no prior radiotherapy, chemotherapy, or neck dissection underwent induction chemotherapy (paclitaxel, ifosfamide, and carboplatin) followed by glossectomy and neck dissection ± radiotherapy and chemotherapy. On final surgical pathology, 9 patients (39%) had a complete/major (2 complete) histologic response at the primary tumor site; 8 patients (35%) had no response or progression. Similarly, 9 patients (39%) had a complete response in the neck or remained node negative; 6 patients (26%) had an increase in nodal category. No treatment-associated deaths occurred, and toxicity was modest. At a median follow-up from the end of treatment of 52 months (minimum, 23 months), 10 patients (43%) developed recurrence, and all 10 died of cancer. Crude recurrence/cancer death rates were associated with ≤ a partial response at the tongue (p = .029), poor histologic differentiation (p = .012), and multiple adverse features on final surgical pathology (p = .040). Response rates and overall survival with this induction chemotherapy regimen were limited, but complete/major response at the tongue was associated with excellent prognosis. Additionally, improved patient selection and predictive tumor biomarkers will be needed for induction chemotherapy to be routinely incorporated into the treatment of oral tongue cancer in young adults. Copyright © 2011 Wiley Periodicals, Inc.

[Survey of potential improvements during the course of the radiotherapy treatment--a patient questionnaire].

PubMed

Momm, Felix; Jooss, David; Xander, Carola J; Adebahr, Sonja; Duncker-Rohr, Viola; Heinemann, Felix; Kirste, Simon; Messmer, Marc-Benjamin; Grosu, Anca-Ligia; Becker, Gerhild

2011-11-01

In the context of quality assurance, increasing demands are placed on the whole radiotherapy treatment process. The patients directly concerned generally do not realize most aspects of the quality assurance program (e.g., additional safety checks) during their daily therapy. It was the aim of this study to systematically ask patients about potential improvements during the course of radiotherapy treatment from their own perspective. In the defined time span (1 month), 624 radiotherapy patients (600 questionnaires were returned, 96.2%) were interviewed using a questionnaire newly developed to inquire about several aspects of their treatment. Furthermore, they were asked for their specific needs and suggestions for improvements that could be made during the course of radiotherapy treatment. Overall, the patients were satisfied with the course of their radiotherapy treatment and with patient care. As an example, about 90% agreed with the statement: "My first contact with the radiation oncology unit proceeded with kindness and competence so that I was given the impression that I will be well cared for in this clinic." Considering the organization of the course of radiotherapy, a large majority of patients attached great value to set appointments for the therapy fractions. A main point of criticism was waiting times or delays caused by servicing or machine failures. Small, low cost improvements as music in the therapy room were considered as important as expensive measures (e.g., daylight in the therapy room). The patients emphasized the importance of staff friendliness. The situation of radiotherapy patients was, in general, satisfactory. Future improvements can be mainly expected from smooth organisation of both planning and treatment which can be achieved by electronic scheduling systems. Many results of the survey could be easily implemented in daily practice. In matters of organization radiation oncology with its complex procedures can be used as a model for other clinical departments.

In silico modelling of radiation effects towards personalised treatment in radiotherapy

NASA Astrophysics Data System (ADS)

Marcu, Loredana G.; Marcu, David

2017-12-01

In silico models applied in medical physics are valuable tools to assist in treatment optimization and personalization, which represent the ultimate goal of today's radiotherapy. Next to several biological and biophysical factors that influence tumour response to ionizing radiation, hypoxia and cancer stem cells are critical parameters that dictate the final outcome. The current work presents the results of an in silico model of tumour growth and response to radiation developed using Monte Carlo techniques. We are presenting the impact of partial oxygen tension and repopulation via cancer stem cells on tumour control after photon irradiation, highlighting some of the gaps that clinical research needs to fill for better customized treatment.

The Confluence of Stereotactic Ablative Radiotherapy and Tumor Immunology

PubMed Central

Finkelstein, Steven Eric; Timmerman, Robert; McBride, William H.; Schaue, Dörthe; Hoffe, Sarah E.; Mantz, Constantine A.; Wilson, George D.

2011-01-01

Stereotactic radiation approaches are gaining more popularity for the treatment of intracranial as well as extracranial tumors in organs such as the liver and lung. Technology, rather than biology, is driving the rapid adoption of stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), in the clinic due to advances in precise positioning and targeting. Dramatic improvements in tumor control have been demonstrated; however, our knowledge of normal tissue biology response mechanisms to large fraction sizes is lacking. Herein, we will discuss how SABR can induce cellular expression of MHC I, adhesion molecules, costimulatory molecules, heat shock proteins, inflammatory mediators, immunomodulatory cytokines, and death receptors to enhance antitumor immune responses. PMID:22162711

ATM Mutations and the Development of Severe Radiation-Induced Morbidity Following Radiotherapy for Breast Cancer

DTIC Science & Technology

2006-07-01

patients who are carriers of an alteration in this gene . This project is innovative as it represents the first study to use the powerful DHPLC mutation ...development of adverse responses to radiotherapy (5-6). The first gene to have received significant attention was the mutated in ataxia telangiectasia (AT...Group and Concannon PJ. 2003. Designing and implementing quality control for multi-center screening of mutations in the ATM gene among women with

Written information material and availability of sexual health care for men experiencing sexual dysfunction after prostate cancer treatment: An evaluation of Dutch urology and radiotherapy departments.

PubMed

Grondhuis Palacios, L A; Krouwel, E M; Duijn, M; den Oudsten, B L; den Ouden, M E M; Putter, H; Pelger, R C M; Elzevier, H W

2017-03-01

Objective was to investigate content of written information material and availability of sexual health care for men experiencing sexual dysfunction (SD) after prostate cancer treatment. A cross-sectional survey was conducted among Dutch urology and radiotherapy departments to evaluate information materials and availability of sexual health care. Out of 71 eligible departments, 34 urology and 15 radiotherapy departments participated in the survey (response rate 69.0%). Fifty-nine brochures corresponding to 31 urology and 11 radiotherapy departments were analysed. In 88.1% of collected information material, sexual health was mentioned. Regarding extensiveness, 20.4% of the brochures contained extensive information, 50.8% moderate amount of information and 28.8% contained little or no information. Urology departments provided pre-treatment nurse consultations more often than radiotherapy departments. Sexual counselling was more frequently provided by urology departments. Urology departments were more aware of adequate referral possibilities. Information material provided by Dutch urology and radiotherapy departments does not address treatment-related SD routinely. Sexual health care is not available everywhere for men experiencing SD. Applying a standard regarding content of sexual health in information material is recommended as well as improved awareness of referral possibilities and enhanced provision of pre-treatment nurse consultations for men experiencing SD after prostate cancer treatment. © 2016 John Wiley & Sons Ltd.

Radiogenetic therapy: strategies to overcome tumor resistance.

PubMed

Marples, B; Greco, O; Joiner, M C; Scott, S D

2003-01-01

The aim of cancer gene therapy is to selectively kill malignant cells at the tumor site, by exploiting traits specific to cancer cells and/or solid tumors. Strategies that take advantage of biological features common to different tumor types are particularly promising, since they have wide clinical applicability. Much attention has focused on genetic methods that complement radiotherapy, the principal treatment modality, or that exploit hypoxia, the most ubiquitous characteristic of most solid cancers. The goal of this review is to highlight two promising gene therapy methods developed specifically to target the tumor volume that can be readily used in combination with radiotherapy. The first approach uses radiation-responsive gene promoters to control the selective expression of a suicide gene (e.g., herpes simplex virus thymidine kinase) to irradiated tissue only, leading to targeted cell killing in the presence of a prodrug (e.g., ganciclovir). The second method utilizes oxygen-dependent promoters to produce selective therapeutic gene expression and prodrug activation in hypoxic cells, which are refractive to conventional radiotherapy. Further refining of tumor targeting can be achieved by combining radiation and hypoxia responsive elements in chimeric promoters activated by either and dual stimuli. The in vitro and in vivo studies described in this review suggest that the combination of gene therapy and radiotherapy protocols has potential for use in cancer care, particularly in cases currently refractory to treatment as a result of inherent or hypoxia-mediated radioresistance.

Elderly Patients With Painful Bone Metastases Should be Offered Palliative Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campos, Sarah; Presutti, Roseanna; Zhang Liying

2010-04-15

Purpose: To investigate the efficacy of palliative radiotherapy (RT) in relieving metastatic bone pain in elderly patients. Methods and Materials: The response to RT for palliation of metastatic bone pain was evaluated from a prospective database of 558 patients between 1999 and 2008. The pain scores and analgesic intake were used to calculate the response according to the International Bone Metastases Consensus Working Party palliative RT endpoints. Subgroup analyses for age and other demographic information were performed. Results: No significant difference was found in the response rate in patients aged >=65, >=70, and >=75 years compared with younger patients atmore » 1, 2, or 3 months after RT. The response was found to be significantly related to the performance status. Conclusion: Age alone did not affect the response to palliative RT for bone metastases. Elderly patients should be referred for palliative RT for their painful bone metastases, regardless of age, because they receive equal benefit from the treatment.« less

Multiple comparisons permutation test for image based data mining in radiotherapy

PubMed Central

2013-01-01

Comparing incidental dose distributions (i.e. images) of patients with different outcomes is a straightforward way to explore dose-response hypotheses in radiotherapy. In this paper, we introduced a permutation test that compares images, such as dose distributions from radiotherapy, while tackling the multiple comparisons problem. A test statistic Tmax was proposed that summarizes the differences between the images into a single value and a permutation procedure was employed to compute the adjusted p-value. We demonstrated the method in two retrospective studies: a prostate study that relates 3D dose distributions to failure, and an esophagus study that relates 2D surface dose distributions of the esophagus to acute esophagus toxicity. As a result, we were able to identify suspicious regions that are significantly associated with failure (prostate study) or toxicity (esophagus study). Permutation testing allows direct comparison of images from different patient categories and is a useful tool for data mining in radiotherapy. PMID:24365155

Three-dimensional power Doppler ultrasound in the early assessment of response to concurrent chemo-radiotherapy for advanced cervical cancer.

PubMed

Xu, Yan; Zhu, Lijing; Ru, Tong; Wang, Huanhuan; He, Jian; Zhou, Zhengyang; Yang, Xiaofeng

2017-09-01

Background Three-dimensional power Doppler ultrasound (3D-PDU) imaging has been widely applied to the differentiation of benign and malignant cervical lesions; however, its potential value for predicting response to chemo-radiotherapy has not been fully explored. Purpose To investigate the feasibility of 3D-PDU imaging in predicting treatment response in patients receiving concurrent chemo-radiotherapy (CCRT) for advanced cervical cancer. Material and Methods Fifty-two patients with advanced cervical cancer who received CCRT underwent 3D-PDU examinations at four timepoints: pre-therapy (baseline), 1 week and 2 weeks during, as well as immediately post CCRT. Final tumor response was determined by change in tumor size using magnetic resonance imaging (MRI). Cervical tumor volumes and vascular indices were calculated and compared with the clinical outcome. Results Of the 52 patients, 32 patients who completed all four examinations were included in the analyses: 21 were classified as complete response (CR) and 11 as partial response (PR). During the treatment, the CR group showed that 3D vascular indices (VI and VFI) significantly increased at 1 week ( P = 0.028, P = 0.017, respectively) then decreased at 2 weeks and obviously decreased at therapy completion (both P < 0.001), whereas tumors significantly decreased in volume at 2 weeks after therapy initiation ( P < 0.05). However, no significant differences in 3D vascular indices values were seen in the PR group during the treatment course (all P > 0.05). Conclusion Prospective longitudinal 3D-PDU imaging may have potentials in monitoring early therapeutic response to CCRT in patients with cervical cancer.

The frequency and cause of anxiety and depression amongst patients with malignant brain tumours between surgery and radiotherapy.

PubMed

Kilbride, Lynn; Smith, Graeme; Grant, Robin

2007-09-01

Between surgery and radiotherapy patients with a malignant glioma may encounter a number of psychosocial issues that could invoke an anxious or depressive response. This study explored the frequency, severity and cause of anxiety and depression in patients with presumed malignant brain tumours in the period between their surgery and radiotherapy. A prospective study of 51 patients used mixed methods to measure anxiety and depression at three time points; post surgery, three weeks post surgery and pre radiotherapy. Analysis was undertaken using statistical and content analysis of the Hospital Anxiety and Depression (HAD) scores and unstructured interviews respectively. Analysis of HAD scores indicated a heightened level of anxiety in patients pre radiotherapy. This anxiety is more prevalent in younger patients and is not related to the patients change in functional state. Five patients had a significant depression at one or more time points between surgery and radiotherapy. Four of the five patients who reported scores consistent with depression had past histories of depression. Content analysis of unstructured interviews indicated that the HAD scores underestimated the presence of anxiety and depression amongst this group of patients. Anxiety was more common in younger patients. Anxiety was slightly more frequent pre-radiotherapy. A past medical history of depression is a predictor of significant depression in the post-operative period. The HAD scale although useful is not an adequate measurement tool for detecting anxiety and depression amongst all patients and health care professionals should adopt other means to monitor for these signs and symptoms.

Misonidazole in patients receiving radical radiotherapy: pharmacokinetic effects of phenytoin tumor response and neurotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, J.L.; Biol, F.I.; Patterson, I.C.M.

1982-03-01

In 1978, a pilot study began of 29 patients with advanced tumors of the head and neck. The study showed an initial peripheral neuropathy rate of 55%, despite a dose limitation of 12 g/m/sup 2/ of misonidazole. Tumor response at 9 months was most encouraging. We are now able to examine tumor response and persistence of neuropathy in these patients 2 1/2 years after radical radiotherapy. The results are comparable with those obtained with hyperbaric oxygen in a clinical trial at this center during the 1970's. Neuropathy was a serious side effect but the drug phenytoin has been shown tomore » shorten the half-life of misonidazole. We have examined the effect of phenytoin on the pharmacokinetics of misonidazole in 13 patients who received radical radiotherapy for advanced head and neck tumors or oesophageal tumors. Misonidazole was given in multiple doses, i.e. daily or weekly as it would be used in conventional therapy. Phenytoin was given either daily throughout treatment, or it was withdrawn during treatment. There were dramatic changes in the half-life of misonidazole, but the concentration at the time of irradiation was little affected. The significant changes in the half-life of misonidazole and the increased concentration of the metabolite desmethylmisonidazole are discussed.« less

Icotinib and whole-brain radiotherapy for the treatment in patients with brain metastases from EGFR-mutant nonsmall cell lung cancer

PubMed Central

Jiang, Ai-Ying; Zhang, Jing; Luo, Hai-Long; Gao, Feng; Lv, Yu-Feng

2018-01-01

Abstract This study aimed to explore the effect and toxicity of icotinib and whole-brain radiotherapy (IWBRT) for the treatment of brain metastases from nonsmall cell lung cancer (BMNSCLC) with epidermal growth factor receptor (EGFR)-mutant among Chinese Han population. A total of 55 patients with EGFR-mutant BMNSCLC were included. They received orally icotinib (125 mg/tablet, 125 mg each time, 3 times daily) until disease progression. In addition, they also underwent whole-brain radiotherapy (3-Gy fractions once daily, 5 days weekly for a total dose of 30 Gy) in an attempt to extend their survival time. The outcomes consisted of complete response (CR), partial response (PR), stable disease (SD), progress disease (PD), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In addition, toxicity was also recorded in this study. The CR, PR, SD, PD, ORR, PFS, and OS were 38.2%, 52.8%, 5.4%, 3.6%, 90.1%, 12.5%, and 48.0% months, respectively. In addition, mild toxicity was observed in this study. This study demonstrated that IWBRT is efficacious with acceptable toxicity for patients with EGFR-mutant BMNSCLC among Chinese Han population. PMID:29642161

Icotinib and whole-brain radiotherapy for the treatment in patients with brain metastases from EGFR-mutant nonsmall cell lung cancer: A retrospective study.

PubMed

Jiang, Ai-Ying; Zhang, Jing; Luo, Hai-Long; Gao, Feng; Lv, Yu-Feng

2018-04-01

This study aimed to explore the effect and toxicity of icotinib and whole-brain radiotherapy (IWBRT) for the treatment of brain metastases from nonsmall cell lung cancer (BMNSCLC) with epidermal growth factor receptor (EGFR)-mutant among Chinese Han population.A total of 55 patients with EGFR-mutant BMNSCLC were included. They received orally icotinib (125 mg/tablet, 125 mg each time, 3 times daily) until disease progression. In addition, they also underwent whole-brain radiotherapy (3-Gy fractions once daily, 5 days weekly for a total dose of 30 Gy) in an attempt to extend their survival time. The outcomes consisted of complete response (CR), partial response (PR), stable disease (SD), progress disease (PD), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In addition, toxicity was also recorded in this study.The CR, PR, SD, PD, ORR, PFS, and OS were 38.2%, 52.8%, 5.4%, 3.6%, 90.1%, 12.5%, and 48.0% months, respectively. In addition, mild toxicity was observed in this study.This study demonstrated that IWBRT is efficacious with acceptable toxicity for patients with EGFR-mutant BMNSCLC among Chinese Han population.

Nonsmall Cell Lung Carcinoma with Giant Cell Features Expressing Programmed Death-Ligand 1: A Report of a Patient Successfully Treated with Pembrolizumab

PubMed Central

Nakayama, Shingo; Sasaki, Mamoru; Morinaga, Shojiroh

2018-01-01

Giant cell carcinoma, a rare variant of nonsmall cell lung carcinoma (NSCLC), is characterized by aggressive progression and poor response to conventional chemotherapy. This report is the first to describe a patient with NSCLC and giant cell features who was successfully treated with pembrolizumab, an antibody targeting programmed death-1 (PD-1). A 69-year-old woman was diagnosed with NSCLC with multiple brain metastases. Histological evaluation of lung biopsy specimens revealed proliferation of pleomorphic giant tumor cells with poor cohesiveness, findings consistent with giant cell carcinoma. Immunostaining showed that a high proportion of the tumor cells were positive for expression of programmed death-ligand 1 (PD-L1). The patient received stereotactic radiotherapy for the brain metastases, followed by administration of pembrolizumab. Treatment with pembrolizumab resulted in the rapid regression of the primary lung nodule, with the progression-free period maintained for at least four treatment cycles. Immunotherapy targeting PD-1/PD-L1 may be an option for patients with PD-L1-positive NSCLC with giant cell features. PMID:29736285

Nonsmall Cell Lung Carcinoma with Giant Cell Features Expressing Programmed Death-Ligand 1: A Report of a Patient Successfully Treated with Pembrolizumab.

PubMed

Nakayama, Shingo; Sasaki, Mamoru; Morinaga, Shojiroh; Minematsu, Naoto

2018-01-01

Giant cell carcinoma, a rare variant of nonsmall cell lung carcinoma (NSCLC), is characterized by aggressive progression and poor response to conventional chemotherapy. This report is the first to describe a patient with NSCLC and giant cell features who was successfully treated with pembrolizumab, an antibody targeting programmed death-1 (PD-1). A 69-year-old woman was diagnosed with NSCLC with multiple brain metastases. Histological evaluation of lung biopsy specimens revealed proliferation of pleomorphic giant tumor cells with poor cohesiveness, findings consistent with giant cell carcinoma. Immunostaining showed that a high proportion of the tumor cells were positive for expression of programmed death-ligand 1 (PD-L1). The patient received stereotactic radiotherapy for the brain metastases, followed by administration of pembrolizumab. Treatment with pembrolizumab resulted in the rapid regression of the primary lung nodule, with the progression-free period maintained for at least four treatment cycles. Immunotherapy targeting PD-1/PD-L1 may be an option for patients with PD-L1-positive NSCLC with giant cell features.

Blocking Indolamine-2,3-Dioxygenase Rebound Immune Suppression Boosts Antitumor Effects of Radio-Immunotherapy in Murine Models and Spontaneous Canine Malignancies.

PubMed

Monjazeb, Arta M; Kent, Michael S; Grossenbacher, Steven K; Mall, Christine; Zamora, Anthony E; Mirsoian, Annie; Chen, Mingyi; Kol, Amir; Shiao, Stephen L; Reddy, Abhinav; Perks, Julian R; T N Culp, William; Sparger, Ellen E; Canter, Robert J; Sckisel, Gail D; Murphy, William J

2016-09-01

Previous studies demonstrate that intratumoral CpG immunotherapy in combination with radiotherapy acts as an in-situ vaccine inducing antitumor immune responses capable of eradicating systemic disease. Unfortunately, most patients fail to respond. We hypothesized that immunotherapy can paradoxically upregulate immunosuppressive pathways, a phenomenon we term "rebound immune suppression," limiting clinical responses. We further hypothesized that the immunosuppressive enzyme indolamine-2,3-dioxygenase (IDO) is a mechanism of rebound immune suppression and that IDO blockade would improve immunotherapy efficacy. We examined the efficacy and immunologic effects of a novel triple therapy consisting of local radiotherapy, intratumoral CpG, and systemic IDO blockade in murine models and a pilot canine clinical trial. In murine models, we observed marked increase in intratumoral IDO expression after treatment with radiotherapy, CpG, or other immunotherapies. The addition of IDO blockade to radiotherapy + CpG decreased IDO activity, reduced tumor growth, and reduced immunosuppressive factors, such as regulatory T cells in the tumor microenvironment. This triple combination induced systemic antitumor effects, decreasing metastases, and improving survival in a CD8(+) T-cell-dependent manner. We evaluated this novel triple therapy in a canine clinical trial, because spontaneous canine malignancies closely reflect human cancer. Mirroring our mouse studies, the therapy was well tolerated, reduced intratumoral immunosuppression, and induced robust systemic antitumor effects. These results suggest that IDO maintains immune suppression in the tumor after therapy, and IDO blockade promotes a local antitumor immune response with systemic consequences. The efficacy and limited toxicity of this strategy are attractive for clinical translation. Clin Cancer Res; 22(17); 4328-40. ©2016 AACR. ©2016 American Association for Cancer Research.

Trial Watch: Anticancer radioimmunotherapy.

PubMed

Vacchelli, Erika; Vitale, Ilio; Tartour, Eric; Eggermont, Alexander; Sautès-Fridman, Catherine; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2013-09-01

Radiotherapy has extensively been employed as a curative or palliative intervention against cancer throughout the last century, with a varying degree of success. For a long time, the antineoplastic activity of X- and γ-rays was entirely ascribed to their capacity of damaging macromolecules, in particular DNA, and hence triggering the (apoptotic) demise of malignant cells. However, accumulating evidence indicates that (at least part of) the clinical potential of radiotherapy stems from cancer cell-extrinsic mechanisms, including the normalization of tumor vasculature as well as short- and long-range bystander effects. Local bystander effects involve either the direct transmission of lethal signals between cells connected by gap junctions or the production of diffusible cytotoxic mediators, including reactive oxygen species, nitric oxide and cytokines. Conversely, long-range bystander effects, also known as out-of-field or abscopal effects, presumably reflect the elicitation of tumor-specific adaptive immune responses. Ionizing rays have indeed been shown to promote the immunogenic demise of malignant cells, a process that relies on the spatiotemporally defined emanation of specific damage-associated molecular patterns (DAMPs). Thus, irradiation reportedly improves the clinical efficacy of other treatment modalities such as surgery (both in neo-adjuvant and adjuvant settings) or chemotherapy. Moreover, at least under some circumstances, radiotherapy may potentiate anticancer immune responses as elicited by various immunotherapeutic agents, including (but presumably not limited to) immunomodulatory monoclonal antibodies, cancer-specific vaccines, dendritic cell-based interventions and Toll-like receptor agonists. Here, we review the rationale of using radiotherapy, alone or combined with immunomodulatory agents, as a means to elicit or boost anticancer immune responses, and present recent clinical trials investigating the therapeutic potential of this approach in cancer patients.

Trial Watch

PubMed Central

Vacchelli, Erika; Vitale, Ilio; Tartour, Eric; Eggermont, Alexander; Sautès-Fridman, Catherine; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2013-01-01

Radiotherapy has extensively been employed as a curative or palliative intervention against cancer throughout the last century, with a varying degree of success. For a long time, the antineoplastic activity of X- and γ-rays was entirely ascribed to their capacity of damaging macromolecules, in particular DNA, and hence triggering the (apoptotic) demise of malignant cells. However, accumulating evidence indicates that (at least part of) the clinical potential of radiotherapy stems from cancer cell-extrinsic mechanisms, including the normalization of tumor vasculature as well as short- and long-range bystander effects. Local bystander effects involve either the direct transmission of lethal signals between cells connected by gap junctions or the production of diffusible cytotoxic mediators, including reactive oxygen species, nitric oxide and cytokines. Conversely, long-range bystander effects, also known as out-of-field or abscopal effects, presumably reflect the elicitation of tumor-specific adaptive immune responses. Ionizing rays have indeed been shown to promote the immunogenic demise of malignant cells, a process that relies on the spatiotemporally defined emanation of specific damage-associated molecular patterns (DAMPs). Thus, irradiation reportedly improves the clinical efficacy of other treatment modalities such as surgery (both in neo-adjuvant and adjuvant settings) or chemotherapy. Moreover, at least under some circumstances, radiotherapy may potentiate anticancer immune responses as elicited by various immunotherapeutic agents, including (but presumably not limited to) immunomodulatory monoclonal antibodies, cancer-specific vaccines, dendritic cell-based interventions and Toll-like receptor agonists. Here, we review the rationale of using radiotherapy, alone or combined with immunomodulatory agents, as a means to elicit or boost anticancer immune responses, and present recent clinical trials investigating the therapeutic potential of this approach in cancer patients. PMID:24319634

[Recommendations for inspections of the French nuclear safety authority].

PubMed

Rousse, C; Chauvet, B

2015-10-01

The French nuclear safety authority is responsible for the control of radiation protection in radiotherapy since 2002. Controls are based on the public health and the labour codes and on the procedures defined by the controlled health care facility for its quality and safety management system according to ASN decision No. 2008-DC-0103. Inspectors verify the adequacy of the quality and safety management procedures and their implementation, and select process steps on the basis of feedback from events notified to ASN. Topics of the inspection are communicated to the facility at the launch of a campaign, which enables them to anticipate the inspectors' expectations. In cases where they are not physicians, inspectors are not allowed to access information covered by medical confidentiality. The consulted documents must therefore be expunged of any patient-identifying information. Exchanges before the inspection are intended to facilitate the provision of documents that may be consulted. Finally, exchange slots between inspectors and the local professionals must be organized. Based on improvements achieved by the health care centres and on recommendations from a joint working group of radiotherapy professionals and the nuclear safety authority, changes will be made in the control procedure that will be implemented when developing the inspection program for 2016-2019. Copyright © 2015. Published by Elsevier SAS.

Erlotinib and radiation therapy for elderly patients with esophageal cancer - clinical and correlative results from a prospective multicenter phase 2 trial.

PubMed

Iyer, Renuka; Chhatrala, Ravi; Shefter, Tracey; Yang, Gary; Malhotra, Usha; Tan, Wei; Levea, Charles; Robins, Melissa; Khushalani, Nikhil

2013-01-01

Elderly patients with esophageal cancer who are not candidates for chemoradiation may benefit from targeted agents; hence erlotinib combined with radiotherapy was evaluated in this trial. Patients >65 years with carcinoma of the thoracic esophagus or gastroesophageal junction who were not eligible for platinum-based treatment received erlotinib daily for 1 year starting on day 1 of radiotherapy [50.4 Gy days 1-28 (Mon-Fri) at 1.8 Gy per fraction]. Response was assessed by endoscopy and computed tomography. The primary endpoint was overall survival (OS), and secondary endpoints were complete response, progression-free survival (PFS) and toxicity. The ECOG performance status in the 17 study patients was 0,1 and 2 in 2, 12 and 3 patients, respectively; 1, 5, 7 and 4 patients were in stage I, II, III and IV, respectively; adenocarcinoma was noted in 16 patients and squamous cell carcinoma in 1; there were 3 current, 12 past and 2 never smokers. Median OS was 7.3 months (95% confidence interval, CI: 3.8-22.3) with 14 deaths. There were 2 mucosal complete responses, 1 residual carcinoma in situ and 3 partial endoscopic responses in 9 patients who had endoscopy after radiotherapy. Estimated PFS was 4.5 months (95% CI: 2.4-7.3). Progression was distant (n = 3), locoregional (n = 6), unknown (n = 5) and too early (n = 3). Estimated 1-year survival was 29% (95% CI: 11-51%), 5 patients lived >12 months. Treatment-related toxicities of grade 3-4 occurred in 5 patients. Patients with epidermal growth factor receptor amplification and never smokers had the longest OS (22.3 and 16.6 months, respectively). Erlotinib with radiotherapy is tolerable and warrants further biomarker-driven evaluation in this population. Copyright © 2013 S. Karger AG, Basel.

Intricacies and strategies for the implementation of new technologies in radiotherapy: Reflections on the meaning and prevention of the error

NASA Astrophysics Data System (ADS)

Espejo-Villalobos, J. D.; Franco-Cabrera, M. C.; Estrada-Hernandez, C.; Quintero-Castelan, M. S.

2012-10-01

When facing the challenge of implementing new technologies in Radiotherapy, a reflection on philosophical and ethical principles is in order for the Medical Physicist to assume a reality of increased risks of harm to the patient. A series of ideas from philosophers and clinical professionals are reviewed to encourage an increased awareness of our ethical responsibility towards patients that entrust us with their hopes for alleviating their disease.

Treatment results and prognostic factors of pediatric neuroblastoma: a retrospective study

PubMed Central

2010-01-01

Background We conducted a retrospective analysis to investigate treatment results and prognostic factors of pediatric neuroblastoma patients. Methods This retrospective study was carried out analyzing the medical records of patients with the pathological diagnosis of neuroblastoma seen at South Egypt Cancer Institute, Assiut University during the period from January 2001 and January 2010. After induction chemotherapy, response according to international neuoblastoma response criteria was assessed. Radiotherapy to patients with residual primary tumor was applied. Overall and event free survival (OAS and EFS) rates were estimated using Graphed prism program. The Log-rank test was used to examine differences in OAS and EFS rates. Cox-regression multivariate analysis was done to determine the independent prognostic factors affecting survival rates. Results Fifty three cases were analyzed. The median follow-up duration was 32 months and ranged from 2 to 84 months. The 3-year OAS and EFS rates were 39.4% and 29.3% respectively. Poor prognostic factors included age >1 year of age, N-MYC amplification, and high risk group. The majority of patients (68%) presented in high risk group, where treatment outcome was poor, as only 21% of patients survived for 3 year. Conclusion Multivariate analysis confirmed only the association between survival and risk group. However, in univariate analysis, local radiation therapy resulted in significant survival improvement. Therefore, radiotherapy should be given to patients with residual tumor evident after induction chemotherapy and surgery. Future attempts to improve OAS in high risk group patients with aggressive chemotherapy and bone marrow transplantation should be considered. PMID:21182799

Distortion-free diffusion MRI using an MRI-guided Tri-Cobalt 60 radiotherapy system: Sequence verification and preliminary clinical experience.

PubMed

Gao, Yu; Han, Fei; Zhou, Ziwu; Cao, Minsong; Kaprealian, Tania; Kamrava, Mitchell; Wang, Chenyang; Neylon, John; Low, Daniel A; Yang, Yingli; Hu, Peng

2017-10-01

Monitoring tumor response during the course of treatment and adaptively modifying treatment plan based on tumor biological feedback may represent a new paradigm for radiotherapy. Diffusion MRI has shown great promises in assessing and predicting tumor response to radiotherapy. However, the conventional diffusion-weighted single-shot echo-planar-imaging (DW-ssEPI) technique suffers from limited resolution, severe distortion, and possibly inaccurate ADC at low field strength. The purpose of this work was to develop a reliable, accurate and distortion-free diffusion MRI technique that is practicable for longitudinal tumor response evaluation and adaptive radiotherapy on a 0.35 T MRI-guided radiotherapy system. A diffusion-prepared turbo spin echo readout (DP-TSE) sequence was developed and compared with the conventional diffusion-weighted single-shot echo-planar-imaging sequence on a 0.35 T MRI-guided radiotherapy system (ViewRay). A spatial integrity phantom was used to quantitate and compare the geometric accuracy of the two diffusion sequences for three orthogonal orientations. The apparent diffusion coefficient (ADC) accuracy was evaluated on a diffusion phantom under both 0 °C and room temperature to cover a diffusivity range between 0.40 × 10 -3 and 2.10 × 10 -3 mm 2 /s. Ten room temperature measurements repeated on five different days were conducted to assess the ADC reproducibility of DP-TSE. Two glioblastoma (GBM) and six sarcoma patients were included to examine the in vivo feasibility. The target registration error (TRE) was calculated to quantitate the geometric accuracy where structural CT or MR images were co-registered to the diffusion images as references. ADC maps from DP-TSE and DW-ssEPI were calculated and compared. A tube phantom was placed next to patients not treated on ViewRay, and ADCs of this reference tube were also compared. The proposed DP-TSE passed the spatial integrity test (< 1 mm within 100 mm radius and < 2 mm within 175 mm radius) under the three orthogonal orientations. The detected errors were 0.474 ± 0.355 mm, 0.475 ± 0.287 mm, and 0.546 ± 0.336 mm in the axial, coronal, and sagittal plane. DW-ssEPI, however, failed the tests due to severe distortion and low signal intensity. Noise correction must be performed for the DW-ssEPI to avoid ADC quantitation errors, whereas it is optional for DP-TSE. At 0 °C, the two sequences provided accurate quantitation with < 3% variation with the reference. In the room temperature study, discrepancies between ADCs from DP-TSE and the reference were within 4%, but could be as high as 8% for DW-ssEPI after the noise correction. Excellent ADC reproducibility with a coefficient of variation < 5% was observed among the 10 measurements of DP-TSE, indicating desirable robustness for ADC-based tumor response assessment. In vivo TRE in DP-TSE was less than 1.6 mm overall, whereas it could be greater than 12 mm in DW-ssEPI. For GBM patients, the CSF and brain tissue ADCs from DP-TSE were within the ranges found in literature. ADC differences between the two techniques were within 8% among the six sarcoma patients. For the reference tube that had a relatively low diffusivity, the two diffusion sequences provided matched measurements. A diffusion technique with excellent geometric fidelity, accurate, and reproducible ADC measurement was demonstrated for longitudinal tumor response assessment using a low-field MRI-guided radiotherapy system. © 2017 American Association of Physicists in Medicine.

A rapid communication from the AAPM Task Group 201: recommendations for the QA of external beam radiotherapy data transfer. AAPM TG 201: quality assurance of external beam radiotherapy data transfer.

PubMed

Siochi, R Alfredo; Balter, Peter; Bloch, Charles D; Santanam, Lakshmi; Blodgett, Kurt; Curran, Bruce H; Engelsman, Martijn; Feng, Wenzheng; Mechalakos, Jim; Pavord, Dan; Simon, Tom; Sutlieff, Steven; Zhu, X Ronald

2010-12-04

The transfer of radiation therapy data among the various subsystems required for external beam treatments is subject to error. Hence, the establishment and management of a data transfer quality assurance program is strongly recommended. It should cover the QA of data transfers of patient specific treatments, imaging data, manually handled data and historical treatment records. QA of the database state (logical consistency and information integrity) is also addressed to ensure that accurate data are transferred.

Prospective study of neoadjuvant chemoradiotherapy using intensity-modulated radiotherapy and 5 fluorouracil for locally advanced rectal cancer - toxicities and response assessment.

PubMed

Simson, David K; Mitra, Swarupa; Ahlawat, Parveen; Saxena, Upasna; Sharma, Manoj Kumar; Rawat, Sheh; Singh, Harpreet; Bansal, Babita; Sripathi, Lalitha Kameshwari; Tanwar, Aditi

2018-01-01

The past 2 decades witnessed the strengthening of evidence favoring the role of neoadjuvant chemoradiation (CHRT) in the treatment of locally advanced rectal cancer. The study aims to evaluate the response and acute toxicities to neoadjuvant CHRT using intensity-modulated radiotherapy (IMRT) in the treatment of rectal cancer. Predictive factors to achieve pathological complete response (pCR) were analyzed, as a secondary endpoint. All consecutive patients who underwent IMRT as part of neoadjuvant CHRT in the treatment of rectal cancer between August 2014 and December 2016 at a tertiary cancer care center were accrued for the study. The cohort underwent CHRT with IMRT technique at a dose of 50.4 Gy in 28 fractions concurrent with continuous infusion of 5 fluorouracil during the first and the last 4 days of CHRT. Surgery was performed 6 weeks later and the pathological response to CHRT was noted. Forty-three subjects were accrued for the study. Radiation dermatitis and diarrhea were the only observed grade ≥3 acute toxicities. Sphincter preservation rate (SPR) was 43.3%. pCR was observed in 32.6%. Univariate and multivariate logistic regression showed that carcinoembryonic antigen was the only independent predictive factor to achieve pCR. IMRT as part of neoadjuvant CHRT in the treatment of locally advanced rectal cancer is well tolerated and gives comparable results with respect to earlier studies in terms of pathological response and SPR. Further randomized controlled studies are needed to firmly state that IMRT is superior to 3-dimensional conformal radiotherapy.

A portable thermal imaging device as a feedback system for breast cancer treatment

NASA Astrophysics Data System (ADS)

Hoffer, Oshrit A.; Ben-David, Merav A.; Katz, Eyal; Sholomov, Meny; Kelson, Itzhak; Gannot, Israel

2018-02-01

Breast cancer is the most frequently diagnosed cancer among women in the Western world. Currently, no imaging technique assesses tumor heat generation and vasculature changes during radiotherapy in viable tumor and as adjuvant therapy. Thermography is a non-ionizing, non-invasive, portable and low-cost imaging modality. The purpose of this study was to investigate the use of thermography in cancer treatment monitoring for feedback purposes. Six stage-IV breast cancer patients with viable breast tumor and 8 patients (9 breasts) who underwent tumor resection were monitored by a thermal camera prior to radiotherapy sessions over several weeks of radiation treatment. The thermal changes over the treated breast were calculated and analyzed for comparison with healthy surrounded breast tissue or contralateral breast. A model of a breast with a tumor was created. The COMSOL FEM software was used to carry out the analysis. The effects of tumor metabolism and breast tissue perfusion on the temperature difference were analyzed. All patients with active tumors exhibited drops in maximal temperature of the tumor during radiation therapy. The patients who underwent radiotherapy as adjuvant treatment exhibited a rise in maximal temperature over the treated breast in correlation with skin erythema during radiation. This difference between the groups was statistically significant (P=0.001). The simulated human breast cancer models analysis showed that tumor aggressiveness reduction causes decrease in the tumor temperature. Inflammation causes vasodilatation and increases tissue perfusion, resulted in an increase in breast tissue temperature. A correlation was demonstrated between the clinical outcome and the simulation. We report a method for monitoring cancer response to radiation therapy, which measures the physiological response along with clinical response. These anticipatory efficacy evaluations of radiotherapy during treatment may further promote changes in treatment regimen, either radiation associated or combination as in chemo-radiation protocols. The probable treatment delivery changes may incorporate the total dose delivery, fraction dose and intensity as well as adding chemotherapy for non-responding tumors during radiotherapy. All the above possibilities will contribute to the advances of individualized, personalized cancer treatment for optimal treatment effectiveness.

Radiotherapy in the treatment of solitary plasmacytoma.

PubMed

Jyothirmayi, R; Gangadharan, V P; Nair, M K; Rajan, B

1997-05-01

Solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EMP) are rare. High local control rates are reported with radiotherapy, although the optimal dose and extent of radiotherapy portals remains controversial. Between 1983 and 1993, 30 patients with solitary plasmacytoma were seen at the Regional Cancer Centre, Trivandrum, India. 23 patients had SPB and seven EMP. The mean age was 52 years and the male to female ratio 3.2:1. Diagnosis of SPB was confirmed by biopsy in 16 patients and tumour excision in seven. 20 patients received megavoltage radiotherapy to the bone lesion with limited margins, and one received chemotherapy. Two patients who underwent complete tumour excision received no further treatment. All seven patients with EMP received megavoltage radiotherapy, four following biopsy and three after tumour excision. Local control was achieved in all patients with SPB. Nine progressed to multiple myeloma and one developed a solitary plasmacytoma in another bone. Six patients with EMP achieved local control. Three later progressed to multiple myeloma and one had local relapse. Median time to relapse was 28 months in SPB and 30 months in EMP. 5-year overall survival rates were 82% and 57% for patients with SPB and EMP, respectively. The corresponding progression free survival rates were 55% and 50%, respectively. Age, sex, site of tumour, serum M protein and haemoglobin levels did not significantly influence progression free survival. The extent of surgery, radiotherapy dose or time to relapse were not significant prognostic factors. Radiotherapy appears to be an effective modality of treatment of solitary plasmacytoma. No dose-response relationship is observed, and high local control rates are achieved with limited portals. Progression to multiple myeloma is the commonest pattern of failure, although no prognostic factors for progression are identified. The role of chemotherapy in preventing disease progression needs further evaluation.

S-1 versus S-1 plus cisplatin concurrent intensity modulated radiation therapy in the treatment of esophageal squamous cell carcinoma: Study protocol for a randomized controlled phase II trial.

PubMed

Wen, Yixue; Zhao, Zhenhuan; Miao, Jidong; Yang, Qilin; Gui, Yan; Sun, Mingqiang; Tian, Honggang; Jia, Qiang; Liao, Dongbiao; Yang, Chen; Du, Xiaobo

2017-12-01

Chemotherapy regimens are often a 2-drug regimen in concurrent chemotherapy and radiotherapy for esophageal cancer (EC). However, some retrospective studies have suggested that for patients with EC receiving radiotherapy combined with 2-drug chemotherapy have the severe toxicity. And S-1 alone with the combination of radiotherapy treatment effect is good, and achieved good clinical remission rate. The purpose of this trial is compare the efficacy and toxicity of combining S-1 or S-1 plus cisplatin with radiotherapy for esophageal squamous cell carcinoma. The study is a randomized, controlled, multicenter trial, comparing S-1 versus S-1 plus cisplatin concurrent radiotherapy for patients with esophageal squamous cell carcinoma. Eighty-eight patients with unresectable or medically unfit for surgery esophageal squamous cell carcinoma (clinical stage I to III), will randomly assigned to receive four cycles (2 concomitant and 2 postradiotherapy) S-1 or S-1 plus cisplatin along with radiotherapy 60-66 Gy/30 to 33 fractions. The primary outcome is complete response rate of primary tumor which will be measured by endoscopy and computer screen at 3 months after the completion of treatment. Secondary outcomes include survival and toxicity. To our knowledge, this study protocol is the first to test the effect between S-1 versus S-1 plus cisplatin concurrent intensity modulated radiation therapy in the treatment of esophageal squamous cell carcinoma. If the result will be the same effect and fewer side effects and less costly in S-1 plus radiotherapy. It will supply more treatment selection for esophageal squamous cell carcinoma.

Clinical translation of human microRNA 21 as a potential biomarker for exposure to ionizing radiation.

PubMed

Halimi, Mohammad; Parsian, Hadi; Asghari, S Mohsen; Sariri, Reyhaneh; Moslemi, Dariush; Yeganeh, Farshid; Zabihi, Ebrahim

2014-06-01

This study investigated to what extent the serum microRNA 21 (miR-21) level alters in response to ionizing radiation (IR). Initially, we evaluated the appropriateness of our RNA extraction efficiency and microRNA assay in serum, and then investigated the serum miR-21 level in 4 patients with breast cancer in 4 stages: pre- and postoperation, at the beginning radiotherapy, and after 25 sessions of radiotherapy with a total of 50 Gy irradiation, as well as in 20 healthy volunteers. The initial analysis showed the appropriateness of our RNA extraction efficiency and microRNA assay in serum for identifying people exposed to IR. We then analyzed the serum miR-21 level in another group of 40 patients with breast cancer before and after radiotherapy. During our large-scale analysis, the miR-21 level before radiotherapy was comparable with healthy volunteers (P = 0.10) and increased significantly after radiotherapy (P < 0.001)-an indication that this could discriminate irradiated patients from nonirradiated ones with high specificity (75%) and sensitivity (80%). According to this study, serum miR-21 has the potential to be used as a biomarker for the identification of people exposed to ionizing radiation. Copyright © 2014 Mosby, Inc. All rights reserved.

Low dose radiotherapy for plantar fasciitis. Treatment outcome of 171 patients.

PubMed

Badakhshi, Harun; Buadch, Volker

2014-12-01

Although the effectiveness of low-dose radiotherapy for chronic degenerative and inflammatory diseases has been documented in previous studies, patient-reported clinical outcomes are rarely available. This study aimed to determine the effect of low-dose radiotherapy on patients with painful plantar fasciitis. From 2002 to 2008, 200 patients older than 65 years of age with painful plantar fasciitis were treated in our hospital. Records from 171 of these patients were available for analysis. All patients were treated with an identical dose of 3Gy using identical equipment and techniques. Response was evaluated with patient-reported questionnaires and clinical visits. Minimum-term follow-up was 18 months, with mean follow-up at 54 months. Three months after receiving low-dose radiotherapy, 67.3% of patients had no or mild pain, and 57.9% had no or discrete mobility restriction. At a mean of 54 months, 61.4% of patients had no or mild pain and 64.9% of patients had no or discrete mobility restriction; 60.8% of patients reported improved quality of life. Low-dose radiotherapy is effective in most patients with painful plantar fasciitis. Due to minimal side effects and low costs, it represents an excellent treatment option compared to conventional therapies or surgery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dosimetry for audit and clinical trials: challenges and requirements

NASA Astrophysics Data System (ADS)

Kron, T.; Haworth, A.; Williams, I.

2013-06-01

Many important dosimetry audit networks for radiotherapy have their roots in clinical trial quality assurance (QA). In both scenarios it is essential to test two issues: does the treatment plan conform with the clinical requirements and is the plan a reasonable representation of what is actually delivered to a patient throughout their course of treatment. Part of a sound quality program would be an external audit of these issues with verification of the equivalence of plan and treatment typically referred to as a dosimetry audit. The increasing complexity of radiotherapy planning and delivery makes audits challenging. While verification of absolute dose delivered at a reference point was the standard of external dosimetry audits two decades ago this is often deemed inadequate for verification of treatment approaches such as Intensity Modulated Radiation Therapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT). As such, most dosimetry audit networks have successfully introduced more complex tests of dose delivery using anthropomorphic phantoms that can be imaged, planned and treated as a patient would. The new challenge is to adapt this approach to ever more diversified radiotherapy procedures with image guided/adaptive radiotherapy, motion management and brachytherapy being the focus of current research.

Radiation Planning Assistant - A Streamlined, Fully Automated Radiotherapy Treatment Planning System

PubMed Central

Court, Laurence E.; Kisling, Kelly; McCarroll, Rachel; Zhang, Lifei; Yang, Jinzhong; Simonds, Hannah; du Toit, Monique; Trauernicht, Chris; Burger, Hester; Parkes, Jeannette; Mejia, Mike; Bojador, Maureen; Balter, Peter; Branco, Daniela; Steinmann, Angela; Baltz, Garrett; Gay, Skylar; Anderson, Brian; Cardenas, Carlos; Jhingran, Anuja; Shaitelman, Simona; Bogler, Oliver; Schmeller, Kathleen; Followill, David; Howell, Rebecca; Nelson, Christopher; Peterson, Christine; Beadle, Beth

2018-01-01

The Radiation Planning Assistant (RPA) is a system developed for the fully automated creation of radiotherapy treatment plans, including volume-modulated arc therapy (VMAT) plans for patients with head/neck cancer and 4-field box plans for patients with cervical cancer. It is a combination of specially developed in-house software that uses an application programming interface to communicate with a commercial radiotherapy treatment planning system. It also interfaces with a commercial secondary dose verification software. The necessary inputs to the system are a Treatment Plan Order, approved by the radiation oncologist, and a simulation computed tomography (CT) image, approved by the radiographer. The RPA then generates a complete radiotherapy treatment plan. For the cervical cancer treatment plans, no additional user intervention is necessary until the plan is complete. For head/neck treatment plans, after the normal tissue and some of the target structures are automatically delineated on the CT image, the radiation oncologist must review the contours, making edits if necessary. They also delineate the gross tumor volume. The RPA then completes the treatment planning process, creating a VMAT plan. Finally, the completed plan must be reviewed by qualified clinical staff. PMID:29708544

University of Washington Clinical Neutron Facility: Report on 26 Years of Operation

NASA Astrophysics Data System (ADS)

Laramore, George E.; Emery, Robert; Reid, David; Banerian, Stefani; Kalet, Ira; Jacky, Jonathan; Risler, Ruedi

2011-12-01

Particle radiotherapy facilities are highly capital intensive and must operate over decades to recoup the original investment. We describe the successful, long-term operation of a neutron radiotherapy center at the University of Washington, which has been operating continuously since September 1984. To date, 2836 patients have received neutron radiotherapy. The mission of the facility has also evolved to include the production of unique radioisotopes that cannot be made with the low-energy cyclotrons more commonly found in nuclear medicine departments. The facility is also used for neutron damage testing for industrial devices. In this paper, we describe the challenges of operating such a facility over an extended time period, including a planned maintenance and upgrade program serving diverse user groups, and summarize the major clinical results in terms of tumor control and normal tissue toxicity. Over time, the mix of patients being treated has shifted from common tumors such as prostate cancer, lung cancer, and squamous cell tumors of the head and neck to the rarer tumors such as salivary gland tumors and sarcomas due to the results of clinical trials. Current indications for neutron radiotherapy are described and neutron tolerance doses for a range of normal tissues presented.

Comparative Analysis of Neural Network Training Methods in Real-time Radiotherapy.

PubMed

Nouri, S; Hosseini Pooya, S M; Soltani Nabipour, J

2017-03-01

The motions of body and tumor in some regions such as chest during radiotherapy treatments are one of the major concerns protecting normal tissues against high doses. By using real-time radiotherapy technique, it is possible to increase the accuracy of delivered dose to the tumor region by means of tracing markers on the body of patients. This study evaluates the accuracy of some artificial intelligence methods including neural network and those of combination with genetic algorithm as well as particle swarm optimization (PSO) estimating tumor positions in real-time radiotherapy. One hundred recorded signals of three external markers were used as input data. The signals from 3 markers thorough 10 breathing cycles of a patient treated via a cyber-knife for a lung tumor were used as data input. Then, neural network method and its combination with genetic or PSO algorithms were applied determining the tumor locations using MATLAB© software program. The accuracies were obtained 0.8%, 12% and 14% in neural network, genetic and particle swarm optimization algorithms, respectively. The internal target volume (ITV) should be determined based on the applied neural network algorithm on training steps.

A Platform to Monitor Tumor Cellular and Vascular Response to Radiation Therapy by Optical Coherence Tomography and Fluorescence Microscopy in vivo

NASA Astrophysics Data System (ADS)

Leung, Michael Ka Kit

Radiotherapy plays a significant role in cancer treatment, and is thought to be curative by mainly killing tumor cells through damage to their genetic material. However, recent findings indicate that the tumor's vascular blood supply is also a major determinant of radiation response. The goals of this thesis are to: (1) develop an experimental platform for small animals to deliver ionizing radiation and perform high-resolution optical imaging to treatment targets, and (2) use this toolkit to longitudinally monitor the response of tumors and the associated vasculature. The thesis has achieved: (1) customization of a novel micro-irradiator for mice, (2) technical development of an improved optical coherence tomography imaging system, (3) comprehensive experimental protocol and imaging optimization for optical microscopy in a specialized animal model, and (4) completion of a feasibility study to demonstrate the capabilities of the experimental platform in monitoring the response of tumor and vasculature to radiotherapy.

Non-surgical organ preservation strategies for locally advanced laryngeal tumors: what is the Italian attitude? Results of a national survey on behalf of AIRO and AIOM.

PubMed

Alterio, D; Franco, P; Numico, G; Licitra, L; Cossu Rocca, M; Ferrari, A; Pinto, C; Russi, E G; Ricardi, U; Jereczek Fossa, B A

2016-07-01

Chemoradiotherapy is the treatment mostly used as organ preservation (OP) strategy worldwide in advanced laryngo-hypopharyngeal cancer. Due to the not homogeneous results of the literature data regarding the pre-treatment assessment and treatment schedule in this setting of patients, the Italian societies of radiation oncology and medical oncology surveyed (by an online survey) their memberships regarding the Italian attitude on larynx preservation in clinical practice. The survey outline addressed different items such as: demographics (11 items), pre-treatment evaluation (12 items), treatment schedules (10 items) and outcomes (3 items). The survey was filled in by 116 clinical oncologists (64 % radiation and 36 % medical oncologists). Results highlighted that pretreatment evaluation was not homogeneous among the respondents. The treatment of choice for the OP program resulted the concurrent chemoradiotherapy (66 %). Induction chemotherapy was proposed mostly in case of aggressive tumors such as advanced stage (T4 or N3) and/or unfavorable primary sites (hypopharynx). Moreover, after induction chemotherapy, for responders patients most participants (46 %) proposed concurrent chemoradiotherapy, while 18 and 19 % proposed radiotherapy alone or radiotherapy and cetuximab, respectively. For patients with stable disease after induction chemotherapy, the respondents declared to suggest surgery, radiotherapy and cetuximab or radiotherapy alone in 38, 32 and 15 % of cases, respectively. Results of the present survey highlighted the variability of therapeutic approaches offered in clinical practice for patients candidate to a larynx OP program. Analysis of abovementioned results may give the chance to modify some clinical attitudes and create the background for future clinical investigation in this field.

Induction chemotherapy followed by alternating chemo-radiotherapy in non-endemic undifferentiated carcinoma of the nasopharynx: optimal compliance and promising 4-year results.

PubMed

Ponzanelli, Anna; Vigo, Viviana; Marcenaro, Michela; Bacigalupo, Almalina; Gatteschi, Beatrice; Ravetti, Jean-Luis; Corvò, Renzo; Benasso, Marco

2008-08-01

Concomitant chemo-radiotherapy is the standard treatment for advanced nasopharyngeal carcinoma (NPC). Induction chemotherapy may improve the results further by enhancing both loco-regional and distant control. Fifty patients with untreated, stage IV (UICC 1992) undifferentiated NPC were initially treated with three courses of epidoxorubicin, 90 mg/m(2), day 1 and cisplatin, 40 mg/m(2), days 1 and 2, every three weeks and then underwent three courses of cisplatin, 20 mg/m(2)/day, days 1-4 and fluorouracil, 200mg/m(2)/day, days 1-4 (weeks 1, 4, 7), alternated to three splits of radiation (week 2-3, 5-6, 8-9-10) up to 70 Gy. All patients but one received 3 cycles of induction chemotherapy. Toxicities from induction chemotherapy were grade III or IV mucositis (2%), grade III or IV nausea/vomiting (22%), grade III or IV hematological toxicity (6%). At the end of induction phase 12% of CRs, 84% of PRs were recorded. Toxicities from alternating chemo-radiotherapy were grade III or IV mucositis (30%), grade III or IV nausea/vomiting (8%), grade III or IV hematological toxicity (24%). Overall, 86% of CRs and 14% of PRs were observed. Four-year progression free survival and overall survival rates are 71% and 81%, respectively. In a small number of patients studied, no correlation between the level of EGFR overexpression and outcomes was detected. In locally advanced UNPC our combined program including induction chemotherapy followed by alternating chemo-radiotherapy is active and gives promising long-term outcomes with acceptable toxicity and optimal patients' compliance. This program merits to be tested in a phase III trial.

Quality control of involved field radiotherapy in the HD 13 and HD 14 trials : Report of the radiotherapy panel of the German Hodgkin Study Group (GHSG).

PubMed

Kriz, J; Baues, C; Engenhart-Cabillic, R; Haverkamp, U; Herfart, K; Lukas, P; Plütschow, A; Schmidberger, H; Staar, S; Fuchs, M; Engert, A; Eich, H T

2017-02-01

As part of the foundation of the German Hodgkin Study Group (GHSG) in 1978, a central radiotherapy (RT) reference centre was established to evaluate and to improve the quality of treatment. During the study generations, the quality assurance programs (QAP) were continued and adapted to the demands of each study. The purpose of this article is to demonstrate the results of the fifth study generation and to compare them to the previous findings. With the start of the fourth GHSG study generation (HD10-12), a central prospective review of all diagnostic images was established to create an individual treatment plan for each early stage study patient. The quality of involved field RT was retrospectively evaluated by an expert panel of radiation oncologists. In the fifth study generation (HD13-15), the retrospective review of radiotherapy performed was refined and the results were compared with the findings of the fourth generation. The expert panel analyzed the RT planning and application of 1037 (28 %) patients (HD13 n = 465, HD14 n = 572). Simulation films were available in 85 % of cases and verification films in 87 %. RT was assessed as major violation in 46 % (HD13 = 38 %, HD14 = 52 %), minor violation in 9 % (HD13 = 9 %, HD14 = 9 %) and according to the protocol in 45 % (HD13 = 52 %, HD14 = 38 %). The value for QAP of RT within the GHSG trials is well known. Still there were several protocol violations. In the future, the QAP program has to be adapted to the requirements of "modern RT" in malignant lymphoma.

Complete radiotherapy response in rectal cancer: A review of the evidence.

PubMed

Couch, Daniel G; Hemingway, David M

2016-01-14

Complete response to chemoradiotherapy for rectal cancer is becoming a common clinical entity. Techniques to diagnose complete response and how to survey these patients without operative intervention are still unclear. We review the most recent evidence. Barriers to firm conclusions regarding this are heterogeneity of diagnostic definitions, differing surveillance protocols, and a lack of randomised studies.

Spiritual Well-Being for Increasing Life Expectancy in Palliative Radiotherapy Patients: A Questionnaire-Based Study.

PubMed

Hematti, Simin; Baradaran-Ghahfarokhi, Milad; Khajooei-Fard, Rasha; Mohammadi-Bertiani, Zohreh

2015-10-01

Spiritual well-being in patients with an advanced cancer has been found to positively correlate with subjective well-being, lower pain levels, hope and positive mood states, high self-esteem, social competence, purpose in life, and overall quality of life. In this regard, Quran recitation is stated to be an efficient way to increase patient spirituality and also to handle life's everyday challenges. The aim of this study was to investigate the effects of listening, reading, and watching the text of the Holy Quran, called (in this study) Quran recitation, for increasing life expectancy (LE) in palliative radiotherapy patients admitted to Radiotherapy Department of Seyed alshohada Hospital, Isfahan, Iran. A questionnaire-based study was carried out on a total of 89 palliative radiotherapy patients between March 2012 and June 2012. Informed consent was obtained. The patients were requested to complete a standardized questionnaire which was designed based on the European Organization for Research and Treatment of Cancer C30 Scale Quality of Life Questionnaire (EORTC C30 Scale QLQ). A computer program (SPSS version 16.0, Chicago, IL, USA) was used, and data were analyzed by the Wilcoxon test and Spearman's rank correlation. All hypotheses were tested using a criterion level of P = 0.05. There was a significant difference for frequency and duration of Quran recitation among patients, before and after the diagnosis of their cancer (P = 0.03). Using the Spearman's rank correlation, it was found that there was a correlation between Quran recitation and subjective well-being (r = 0.352, P < 0.001). Moreover, there was a correlation between Quran recitation and increasing LE (r = 0.311, P < 0.003). More than 60% of the patients stated that more frequent recitation would lead to more LE and/or greater reassurance. On the basis of the present work, listening, reading, and watching the text of the Holy Quran are useful for increasing LE in palliative radiotherapy patients admitted to Radiotherapy Department. In other words, a benefit of Quran recitation on outcome of radiotherapy for palliative radiotherapy patients was found.

Adjoint sensitivity analysis of a tumor growth model and its application to spatiotemporal radiotherapy optimization.

PubMed

Fujarewicz, Krzysztof; Lakomiec, Krzysztof

2016-12-01

We investigate a spatial model of growth of a tumor and its sensitivity to radiotherapy. It is assumed that the radiation dose may vary in time and space, like in intensity modulated radiotherapy (IMRT). The change of the final state of the tumor depends on local differences in the radiation dose and varies with the time and the place of these local changes. This leads to the concept of a tumor's spatiotemporal sensitivity to radiation, which is a function of time and space. We show how adjoint sensitivity analysis may be applied to calculate the spatiotemporal sensitivity of the finite difference scheme resulting from the partial differential equation describing the tumor growth. We demonstrate results of this approach to the tumor proliferation, invasion and response to radiotherapy (PIRT) model and we compare the accuracy and the computational effort of the method to the simple forward finite difference sensitivity analysis. Furthermore, we use the spatiotemporal sensitivity during the gradient-based optimization of the spatiotemporal radiation protocol and present results for different parameters of the model.

Influence of secondary neutrons induced by proton radiotherapy for cancer patients with implantable cardioverter defibrillators

PubMed Central

2012-01-01

Background Although proton radiotherapy is a promising new approach for cancer patients, functional interference is a concern for patients with implantable cardioverter defibrillators (ICDs). The purpose of this study was to clarify the influence of secondary neutrons induced by proton radiotherapy on ICDs. Methods The experimental set-up simulated proton radiotherapy for a patient with an ICD. Four new ICDs were placed 0.3 cm laterally and 3 cm distally outside the radiation field in order to evaluate the influence of secondary neutrons. The cumulative in-field radiation dose was 107 Gy over 10 sessions of irradiation with a dose rate of 2 Gy/min and a field size of 10 × 10 cm2. After each radiation fraction, interference with the ICD by the therapy was analyzed by an ICD programmer. The dose distributions of secondary neutrons were estimated by Monte-Carlo simulation. Results The frequency of the power-on reset, the most serious soft error where the programmed pacing mode changes temporarily to a safety back-up mode, was 1 per approximately 50 Gy. The total number of soft errors logged in all devices was 29, which was a rate of 1 soft error per approximately 15 Gy. No permanent device malfunctions were detected. The calculated dose of secondary neutrons per 1 Gy proton dose in the phantom was approximately 1.3-8.9 mSv/Gy. Conclusions With the present experimental settings, the probability was approximately 1 power-on reset per 50 Gy, which was below the dose level (60-80 Gy) generally used in proton radiotherapy. Further quantitative analysis in various settings is needed to establish guidelines regarding proton radiotherapy for cancer patients with ICDs. PMID:22284700

The rapid access palliative radiotherapy program: blueprint for initiation of a one-stop multidisciplinary bone metastases clinic.

PubMed

Fairchild, A; Pituskin, E; Rose, B; Ghosh, S; Dutka, J; Driga, A; Tachynski, P; Borschneck, J; Gagnon, L; Macdonnell, S; Middleton, J; Thavone, K; Carstairs, S; Brent, D; Severin, D

2009-02-01

Radiotherapy (RT) for palliation of pain due to bone metastases (BM) is effective but underutilized likely due to the traditional practice of separate clinic visits for consultation, treatment planning, and RT delivery. However, recent evidence proves one RT treatment is as effective as multiple for analgesia, enabling investigation of an alternative model of RT delivery, the rapid access palliative radiotherapy program (RAPRP). Prior to the start of the program, needs assessment was performed to determine the composition of the optimal team. Screening tools were implemented to streamline holistic, multidisciplinary assessment. An advertising strategy, treatment and research protocols, and mechanisms for patient feedback were established. After RAPRP implementation, patient outcomes such as symptom relief were tracked. Eighty-six patients with painful BM were referred over the 25-week pilot. Median age was 69.9 years; 64% had prostate cancer, and median performance status was 70. Patient-rated pain was on average 6.1/10 at baseline, improving to 2.6/10 by week 4 post-RT. On average, 6.2 symptoms were reported (baseline) compared to 5.2 (week 4). Team members assessed 10-100% of patients and were successful in stabilizing or improving all symptoms in >75% contacted at week 4. One hundred percent of patients surveyed were satisfied with their experience. Early needs assessment was advantageous in determining the optimal team and methods of assessment for our 'one-stop' BM clinic. This approach was successful in improving pain and other symptoms, and the convenience of seeing multiple providers on 1 day was appreciated by the patients.

WE-FG-202-02: Exploration of High-Resolution Quantitative Ultrasonic Micro-Vascular Imaging for Early Assessment of Radiotherapy Tumor Response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kasoji, S; Rivera, J; Dayton, P

Purpose: Currently, we cannot predict an individual patient’s response to a given radiotherapy which normally is not detected for weeks to months post-treatment. As a result, precious time is wasted for patients with unresponsive tumors who could have switched to an alternative treatment much earlier. Presently, no early treatment response detection method exists that is effective, low-cost, non-invasive, and safe. We hypothesize that changes in tumor microvasculature predict tumor response to radiotherapy earlier than tumor volume changes. Recent radiobiology research suggests tumors undergo vascular remodeling in response to radiation well before manifesting changes in tumor volume. We propose monitoring tumormore » microvasculature post-radiation using Acoustic Angiography (AA), a novel ultrasound imaging modality developed and patented in-house. In this study, we investigate whether changes in tumor microvasculature, measured using AA, can be an early indicator of high-dose radiotherapy success, compared to changes in tumor volume. Methods: Fibrosarcoma xenograft tumor tissue was subcutaneously implanted into rodent flanks (N=10). Animal tumors (N=8) were irradiated with a single treatment of 15Gy using a clinical LINAC at 100SSD and 2×2cm field size. Two untreated rats were left as tumor controls. AA imaging was performed immediately posttreatment and every third day thereafter for 30 days, or until tumors disappeared. Tumor volumes and vascular densities were measured from anatomical b-mode ultrasound and AA images, respectively. Results: Statistical differences in vascular density between treatment responders and non-responders were observed on Day 10 (p=0.005), whereas statistical differences in tumor volume were not observed until Day 19 (p=0.02). Conclusions: Tumor vascularity differences may be observed substantially earlier than differences in tumor size. In addition, significant early increases in vascular density were observed in non-responding tumors. This data is consistent with a similar study we completed using the same tumor and animal models (N=10) at 20Gy. The project described was supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number UL1TR001111. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.« less

Accelerated hyperfractionated intensity-modulated radiotherapy for recurrent/unresectable rectal cancer in patients with previous pelvic irradiation: results of a phase II study.

PubMed

Cai, Gang; Zhu, Ji; Hu, Weigang; Zhang, Zhen

2014-12-11

This study was conducted to investigate the local effects and toxicity of accelerated hyperfractionated intensity-modulated radiotherapy for recurrent/unresectable rectal cancer in patients with previous pelvic irradiation. Twenty-two patients with recurrent/unresectable rectal cancer who previously received pelvic irradiation were enrolled in our single-center trial between January 2007 and August 2012. Reirradiation was scheduled for up to 39 Gy in 30 fractions using intensity-modulated radiotherapy plans. The dose was delivered via a hyperfractionation schedule of 1.3 Gy twice daily. Patient follow-up was performed by clinical examination, CT/MRI, or PET/CT every 3 months for the first 2 years and every 6 months thereafter. Tumor response was evaluated 1 month after reirradiation by CT/MRI based on the RECIST criteria. Adverse events were assessed using the National Cancer Institute (NCI) common toxicity criteria (version 3.0). The median time from the end of the initial radiation therapy to reirradiation was 30 months (range, 18-93 months). Overall local responses were observed in 9 patients (40.9%). None of the patients achieved a complete response (CR), and 9 patients (40.9%) had a partial response (PR). Thirteen patients failed to achieve a clinical response: 12 (54.5%) presented with stable disease (SD) and 1 (4.5%) with progressive disease (PD). Among all the patients who underwent reirradiation, partial or complete symptomatic relief was achieved in 6 patients (27.3%) and 13 patients (59.1%), respectively. Grade 4 acute toxicity and treatment-related deaths were not observed. The following grade 3 acute toxicities were observed: diarrhea (2 patients, 9.1%), cystitis (1 patient, 4.5%), dermatitis (1 patient, 4.5%), and intestinal obstruction (1 patient, 4.5%). Late toxicity was infrequent. Chronic severe diarrhea, small bowel obstruction, and dysuria were observed in 2 (9.1%), 1 (4.5%) and 2 (9.1%) of the patients, respectively. This study showed that accelerated hyperfractionated intensity-modulated radiotherapy significantly relieved local symptoms and led to a promising local response with an acceptable toxicity profile in patients with recurrent/unresectable rectal cancer and previous pelvic irradiation. Innovative treatment regimens should be evaluated in future studies to improve the clinical outcome while avoiding excessive toxicity in patients with recurrent rectal cancer and previous pelvic irradiation.

Quality assurance of the SCOPE 1 trial in oesophageal radiotherapy.

PubMed

Wills, Lucy; Maggs, Rhydian; Lewis, Geraint; Jones, Gareth; Nixon, Lisette; Staffurth, John; Crosby, Tom

2017-11-15

SCOPE 1 was the first UK based multi-centre trial involving radiotherapy of the oesophagus. A comprehensive radiotherapy trials quality assurance programme was launched with two main aims: 1. To assist centres, where needed, to adapt their radiotherapy techniques in order to achieve protocol compliance and thereby enable their participation in the trial. 2. To support the trial's clinical outcomes by ensuring the consistent planning and delivery of radiotherapy across all participating centres. A detailed information package was provided and centres were required to complete a benchmark case in which the delineated target volumes and organs at risk, dose distribution and completion of a plan assessment form were assessed prior to recruiting patients into the trial. Upon recruiting, the quality assurance (QA) programme continued to monitor the outlining and planning of radiotherapy treatments. Completion of a questionnaire was requested in order to gather information about each centre's equipment and techniques relating to their trial participation and to assess the impact of the trial nationally on standard practice for radiotherapy of the oesophagus. During the trial, advice was available for individual planning issues, and was circulated amongst the SCOPE 1 community in response to common areas of concern using bulletins. 36 centres were supported through QA processes to enable their participation in SCOPE1. We discuss the issues which have arisen throughout this process and present details of the benchmark case solutions, centre questionnaires and on-trial protocol compliance. The range of submitted benchmark case GTV volumes was 29.8-67.8cm 3 ; and PTV volumes 221.9-513.3 cm 3 . For the dose distributions associated with these volumes, the percentage volume of the lungs receiving 20Gy (V20Gy) ranged from 20.4 to 33.5%. Similarly, heart V40Gy ranged from 16.1 to 33.0%. Incidence of incorrect outlining of OAR volumes increased from 50% of centres at benchmark case, to 64% on trial. Sixty-five percent of centres, who returned the trial questionnaire, stated that their standard practice had changed as a result of their participation in the SCOPE1 trial. The SCOPE 1 QA programme outcomes lend support to the trial's clinical conclusions. The range of patient planning outcomes for the benchmark case indicated, at the outset of the trial, the significant degree of variation present in UK oesophageal radiotherapy planning outcomes, despite the presence of a protocol. This supports the case for increasingly detailed definition of practice by means of consensus protocols, training and peer review. The incidence of minor inconsistencies of technique highlights the potential for improved QA systems and the need for sufficient resource for this to be addressed within future trials. As indicated in questionnaire responses, the QA exercise as a whole has contributed to greater consistency of oesophageal radiotherapy in the UK via the adoption into standard practice of elements of the protocol. The SCOPE1 trial is an International Standard Randomized Controlled Trial, ISRCTN47718479 .

Enhancing radiotherapy for lung cancer using immunoadjuvants delivered in situ from new design radiotherapy biomaterials: a preclinical study

NASA Astrophysics Data System (ADS)

Hao, Yao; Yasmin-Karim, Sayeda; Moreau, Michele; Sinha, Neeharika; Sajo, Erno; Ngwa, Wilfred

2016-12-01

Studies show that radiotherapy of a primary tumor in combination with immunoadjuvants (IA) can result in increased survival or immune-mediated regression of metastasis outside the radiation field, a phenomenon known as abscopal effect. However, toxicities due to repeated systematic administration of IA have been shown to be a major obstacle in clinical trials. To minimize the toxicities and prime a more potent immune response, Ngwa et al have proposed that inert radiotherapy biomaterials such as fiducials could be upgraded to multifunctional ones loaded with IA for in situ delivery directly into the tumor sub-volume at no additional inconvenience to patients. In this preliminary study, the potential of such an approach is investigated for lung cancer using anti-CD40 antibody. First the benefit of using the anti-CD40 delivered in situ to enhance radiotherapy was tested in mice with subcutaneous tumors generated with the Lewis Lung cancer cell line LL/2 (LLC-1). The tumors were implanted on both flanks of the mice to simulate metastasis. Tumors on one flank were treated with and without anti-CD40 and the survival benefits compared. An experimentally determined in vivo diffusion coefficient for nanoparticles was then employed to estimate the time for achieving intratumoral distribution of the needed minimal concentrations of anti-CD40 nanoparticles if released from a multifuntional radiotherapy biomaterials. The studies show that the use of anti-CD40 significantly enhanced radiotherapy effect, slowing the growth of the treated and untreated tumors, and increasing survival. Meanwhile our calculations indicate that for a 2-4 cm tumor and 7 mg g-1 IA concentrations, it would take 4.4-17.4 d, respectively, following burst release, for the required concentration of IA nanoparticles to accumulate throughout the tumor during image-guided radiotherapy. The distribution of IA could be customized as a function of loading concentrations or nanoparticle size to fit current Stereotactic Body Radiotherapy schedules. Overall, the preliminary results support ongoing work in developing multifunctional radiotherapy biomaterials for in situ delivery of immunoadjuvants such as anti-CD40 to leverage the abscopal effect, while minimizing systemic toxicities. The potential of extending such an approach to other cancer types is discussed.

Enhancing radiotherapy for lung cancer using immunoadjuvants delivered in situ from new design radiotherapy biomaterials: a preclinical study.

PubMed

Hao, Yao; Yasmin-Karim, Sayeda; Moreau, Michele; Sinha, Neeharika; Sajo, Erno; Ngwa, Wilfred

2016-12-21

Studies show that radiotherapy of a primary tumor in combination with immunoadjuvants (IA) can result in increased survival or immune-mediated regression of metastasis outside the radiation field, a phenomenon known as abscopal effect. However, toxicities due to repeated systematic administration of IA have been shown to be a major obstacle in clinical trials. To minimize the toxicities and prime a more potent immune response, Ngwa et al have proposed that inert radiotherapy biomaterials such as fiducials could be upgraded to multifunctional ones loaded with IA for in situ delivery directly into the tumor sub-volume at no additional inconvenience to patients. In this preliminary study, the potential of such an approach is investigated for lung cancer using anti-CD40 antibody. First the benefit of using the anti-CD40 delivered in situ to enhance radiotherapy was tested in mice with subcutaneous tumors generated with the Lewis Lung cancer cell line LL/2 (LLC-1). The tumors were implanted on both flanks of the mice to simulate metastasis. Tumors on one flank were treated with and without anti-CD40 and the survival benefits compared. An experimentally determined in vivo diffusion coefficient for nanoparticles was then employed to estimate the time for achieving intratumoral distribution of the needed minimal concentrations of anti-CD40 nanoparticles if released from a multifuntional radiotherapy biomaterials. The studies show that the use of anti-CD40 significantly enhanced radiotherapy effect, slowing the growth of the treated and untreated tumors, and increasing survival. Meanwhile our calculations indicate that for a 2-4 cm tumor and 7 mg g -1 IA concentrations, it would take 4.4-17.4 d, respectively, following burst release, for the required concentration of IA nanoparticles to accumulate throughout the tumor during image-guided radiotherapy. The distribution of IA could be customized as a function of loading concentrations or nanoparticle size to fit current Stereotactic Body Radiotherapy schedules. Overall, the preliminary results support ongoing work in developing multifunctional radiotherapy biomaterials for in situ delivery of immunoadjuvants such as anti-CD40 to leverage the abscopal effect, while minimizing systemic toxicities. The potential of extending such an approach to other cancer types is discussed.

Effects of intensity-modulated radiotherapy and chemoradiotherapy on attention in patients with nasopharyngeal cancer

PubMed Central

Wei, Qing; Li, Ling; Zhu, Xiao-Dong; Qin, Ling; Mo, Yan-Lin; Liang, Zheng-You; Deng, Jia-Li; Tao, Su-Ping

2017-01-01

This study evaluated the short-term effects of intensity-modulated radiotherapy (IMRT) and cisplatin concurrent chemo-radiotherapy (CCRT) on attention in patients with nasopharyngeal cancer (NPC). Timely detection and early prevention of cognitive decline are important in cancer patients, because long-term cognitive effects may be permanent and irreversible. Thirty-eight NPC patients treated with IMRT (17/38) or CCRT (21/38) and 38 healthy controls were recruited for the study. Neuropsychological tests were administered to each patient before treatment initiation and within a week after treatment completion. Changes in attention performance over time were evaluated using difference values (D-values). Decreased attention was already observable in patients with NPC prior to treatment. Baseline quotient scores for auditory attention, auditory and visual vigilance, and auditory speed were lower in patients treated with CCRT than in healthy controls (P=0.037, P=0.001, P=0.007, P=0.032, respectively). Auditory stamina D-values were higher in patients treated with IMRT alone (P=0.042), while full-scale response control quotient D-values were lower in patients treated with CCRT (P=0.030) than in healthy controls. Gender, depression, education, and sleep quality were each related to decreased attention and response control. Our results showed that IMRT had no negative acute effects on attention in NPC patients, while CCRT decreased response control. PMID:28947979

IMRT for head and neck cancer: reducing xerostomia and dysphagia

PubMed Central

Wang, XiaoShen; Eisbruch, Avraham

2016-01-01

Dysphagia and xerostomia are the main sequellae of chemoradiotherapy for head and neck cancer, and the main factors in reducing long-term patient quality of life. IMRT uses advanced technology to focus the high radiation doses on the targets and avoid irradiation of non-involved tissues. The decisions about sparing organs and tissues whose damage causes xerostomia and dysphagia depends on the evidence for dose–response relationships for the organs causing these sequellae. This paper discusses the evidence for the contribution of radiotherapy to xerostomia via damage of the major salivary glands (parotid and submandibular) and minor salivary glands within the oral cavity, and the contribution of radiotherapy-related effect on important swallowing structures causing dysphagia. Recommendations for dose limits to these organs, based on measurements of xerostomia and dysphagia following radiotherapy, are provided here. PMID:27538846

Implementation of an intraoperative electron radiotherapy in vivo dosimetry program.

PubMed

López-Tarjuelo, Juan; Morillo-Macías, Virginia; Bouché-Babiloni, Ana; Boldó-Roda, Enrique; Lozoya-Albacar, Rafael; Ferrer-Albiach, Carlos

2016-03-15

Intraoperative electron radiotherapy (IOERT) is a highly selective radiotherapy technique which aims to treat restricted anatomic volumes during oncological surgery and is now the subject of intense re-evaluation. In vivo dosimetry has been recommended for IOERT and has been identified as a risk-reduction intervention in the context of an IOERT risk analysis. Despite reports of fruitful experiences, information about in vivo dosimetry in intraoperative radiotherapy is somewhat scarce. Therefore, the aim of this paper is to report our experience in developing a program of in vivo dosimetry for IOERT, from both multidisciplinary and practical approaches, in a consistent patient series. We also report several current weaknesses. Reinforced TN-502RDM-H mobile metal oxide semiconductor field effect transistors (MOSFETs) and Gafchromic MD-55-2 films were used as a redundant in vivo treatment verification system with an Elekta Precise fixed linear accelerator for calibrations and treatments. In vivo dosimetry was performed in 45 patients in cases involving primary tumors or relapses. The most frequent primary tumors were breast (37 %) and colorectal (29 %), and local recurrences among relapses was 83 %. We made 50 attempts to measure with MOSFETs and 48 attempts to measure with films in the treatment zones. The surgical team placed both detectors with supervision from the radiation oncologist and following their instructions. The program was considered an overall success by the different professionals involved. The absorbed doses measured with MOSFETs and films were 93.8 ± 6.7 % and 97.9 ± 9.0 % (mean ± SD) respectively using a scale in which 90 % is the prescribed dose and 100 % is the maximum absorbed dose delivered by the beam. However, in 10 % of cases we experienced dosimetric problems due to detector misalignment, a situation which might be avoided with additional checks. The useful MOSFET lifetime length and the film sterilization procedure should also be controlled. It is feasible to establish an in vivo dosimetry program for a wide set of locations treated with IOERT using a multidisciplinary approach according to the skills of the professionals present and the detectors used; oncological surgeons' commitment is key to success in this context. Films are more unstable and show higher uncertainty than MOSFETs but are cheaper and are useful and convenient if real-time treatment monitoring is not necessary.

Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy

NASA Astrophysics Data System (ADS)

Min, Yuanzeng; Roche, Kyle C.; Tian, Shaomin; Eblan, Michael J.; McKinnon, Karen P.; Caster, Joseph M.; Chai, Shengjie; Herring, Laura E.; Zhang, Longzhen; Zhang, Tian; Desimone, Joseph M.; Tepper, Joel E.; Vincent, Benjamin G.; Serody, Jonathan S.; Wang, Andrew Z.

2017-09-01

Immunotherapy holds tremendous promise for improving cancer treatment. To administer radiotherapy with immunotherapy has been shown to improve immune responses and can elicit the 'abscopal effect'. Unfortunately, response rates for this strategy remain low. Herein we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NP formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent on the NP surface properties. We showed that AC-NPs deliver tumour-specific proteins to antigen-presenting cells (APCs) and significantly improve the efficacy of αPD-1 (anti-programmed cell death 1) treatment using the B16F10 melanoma model, generating up to a 20% cure rate compared with 0% without AC-NPs. Mechanistic studies revealed that AC-NPs induced an expansion of CD8+ cytotoxic T cells and increased both CD4+T/Treg and CD8+T/Treg ratios (Treg, regulatory T cells). Our work presents a novel strategy to improve cancer immunotherapy with nanotechnology.

Development and validation of prognostic models in metastatic breast cancer: a GOCS study.

PubMed

Rabinovich, M; Vallejo, C; Bianco, A; Perez, J; Machiavelli, M; Leone, B; Romero, A; Rodriguez, R; Cuevas, M; Dansky, C

1992-01-01

The significance of several prognostic factors and the magnitude of their influence on response rate and survival were assessed by means of uni- and multivariate analyses in 362 patients with stage IV (UICC) breast carcinoma receiving combination chemotherapy as first systemic treatment over an 8-year period. Univariate analyses identified performance status and prior adjuvant radiotherapy as predictors of objective regression (OR), whereas the performance status, prior chemotherapy and radiotherapy (adjuvants), white blood cells count, SGOT and SGPT levels, and metastatic pattern were significantly correlated to survival. In multivariate analyses favorable characteristics associated to OR were prior adjuvant radiotherapy, no prior chemotherapy and postmenopausal status. Regarding survival, the performance status and visceral involvement were selected by the Cox model. The predictive accuracy of the logistic and the proportional hazards models was retrospectively tested in the training sample, and prospectively in a new population of 126 patients also receiving combined chemotherapy as first treatment for metastatic breast cancer. A certain overfitting to data in the training sample was observed with the regression model for response. However, the discriminative ability of the Cox model for survival was clearly confirmed.

Synthetic diamond devices for radio-oncology applications

NASA Astrophysics Data System (ADS)

Descamps, C.; Tromson, D.; Mer, C.; Nesládek, M.; Bergonzo, P.; Benabdesselam, M.

2006-09-01

Diamond exhibits a range of outstanding properties that make it a material of interest for radiation detection and particularly in the field of dosimetry applications. In fact, its crystallographic structure makes it chemically inert and radiation hard. Moreover, its atomic number (carbon Z = 6) close to the equivalent effective atomic number of human soft tissues (Z = 7.4) and of water (reference material in radiotherapy) enables a direct evaluation of the deposited dose without requiring corrections for material nature or energy. Finally, as a bio-compatible material, it can be sterilised, and it is non-toxic thus giving strong advantages for medical uses. Natural diamonds are expensive, rare and their use implies a severe gem selection to fabricate reproducible and reliable devices. The emergence of synthetic samples from the chemical vapour deposition (CVD) technique offers new possibilities in the fabrication of ionisation chamber for the particular field of radiotherapy. Previous studies have shown that defect levels present in material clearly influence the device response under irradiation. Therefore, in order to optimise dosimetric characteristics needed in radiotherapy applications, various low and precisely nitrogen concentrations were incorporated in the material during growth. Influence of these incorporations on ionisation chamber response under medical cobalt irradiator is presented in this paper.

Sequential cisplatin/cyclophosphamide chemotherapy and abdominopelvic radiotherapy in the management of advanced ovarian cancer.

PubMed Central

Green, J. A.; Warenius, H. M.; Errington, R. D.; Myint, S.; Spearing, G.; Slater, A. J.

1988-01-01

Forty-six previously untreated patients with advanced ovarian cancer were treated with combination chemotherapy comprising cisplatin 80 mg m-2 i.v. and cyclophosphamide 1 gm-2 i.v. every 28 days for 5 cycles. Eighty-five percent of patients received more than 75% of the calculated doses, and of 43 evaluable patients, a complete response was achieved in 31 (72%), a partial response in 4 (9.3%) and 8 patients had static or progressive disease. The actuarial survival of the whole group is 60% at a median follow-up of 2 years. Twenty-four patients in complete clinical or pathological remission were then treated with whole abdominal radiotherapy 2,500 cGy followed by a pelvic boost of 2,000 cGy. The pelvic boost was omitted in 3 patients, and the overall radiotherapy treatment time extended in a further 4 patients on account of myelosuppression. The actuarial survival of the 24 patients receiving both treatments at a median of 30 months follow-up is 75%. In the 10 patients with negative second-look procedures completing both treatments there have been no tumour related deaths at a median follow-up of 33 months. PMID:3219276

Sequential cisplatin/cyclophosphamide chemotherapy and abdominopelvic radiotherapy in the management of advanced ovarian cancer.

PubMed

Green, J A; Warenius, H M; Errington, R D; Myint, S; Spearing, G; Slater, A J

1988-11-01

Forty-six previously untreated patients with advanced ovarian cancer were treated with combination chemotherapy comprising cisplatin 80 mg m-2 i.v. and cyclophosphamide 1 gm-2 i.v. every 28 days for 5 cycles. Eighty-five percent of patients received more than 75% of the calculated doses, and of 43 evaluable patients, a complete response was achieved in 31 (72%), a partial response in 4 (9.3%) and 8 patients had static or progressive disease. The actuarial survival of the whole group is 60% at a median follow-up of 2 years. Twenty-four patients in complete clinical or pathological remission were then treated with whole abdominal radiotherapy 2,500 cGy followed by a pelvic boost of 2,000 cGy. The pelvic boost was omitted in 3 patients, and the overall radiotherapy treatment time extended in a further 4 patients on account of myelosuppression. The actuarial survival of the 24 patients receiving both treatments at a median of 30 months follow-up is 75%. In the 10 patients with negative second-look procedures completing both treatments there have been no tumour related deaths at a median follow-up of 33 months.

Cytopathologic evaluation of patients submitted to radiotherapy for uterine cervix cancer.

PubMed

Padilha, Cátia Martins Leite; Araújo, Mário Lúcio Cordeiro; Souza, Sergio Augusto Lopes de

2017-04-01

Cervical cancer is an important public health problem. Pap smear is the leading strategy of screening programs for cervical cancer worldwide. However, delayed diagnosis leads to more aggressive and less effective treatments. Patients with uterine cervix malignancies who are referred for radiotherapy have advanced-stage disease, which results in high rates of locoregional recurrence. The use of radiotherapy as a treatment for cervical cancer causes morphological changes in neoplastic and non-neoplastic epithelial cells, as well as in stromal cells, which make it difficult to diagnose the residual lesion, resulting in a dilemma in cytopathological routine. Based on the difficulties of cytopathologic evaluation for the follow-up of patients treated with radiotherapy for cervical cancer, our objective was to describe the actinic cytopathic effects. Our paper was based on a structured review including the period from June 2015 to April 2016, aiming at an exploratory-descriptive study. Bibliographic investigations were carried out through selection and analysis of articles, list of authors and keywords, selection of new articles focused on the analysis of bibliographic references to previously selected documents, as well as textbooks of recognized merit. The most incident actinic cytopathological alterations as described in the literature are: cellular gigantism, nuclear and cytoplasmic vacuolization, dyskeratosis, bi- and multinucleated (B/M) cells, macro and multiple nucleoli, anisokaryosis, anisonucleolosis and nuclear pyknosis. To date, a protocol has not been established that can precisely differentiate the morphological characteristics between benign cells with actinic effects from recurrent malignant cells on post-radiotherapy smears.

Quantitative multiparametric MRI assessment of glioma response to radiotherapy in a rat model.

PubMed

Hong, Xiaohua; Liu, Li; Wang, Meiyun; Ding, Kai; Fan, Ying; Ma, Bo; Lal, Bachchu; Tyler, Betty; Mangraviti, Antonella; Wang, Silun; Wong, John; Laterra, John; Zhou, Jinyuan

2014-06-01

The inability of structural MRI to accurately measure tumor response to therapy complicates care management for patients with gliomas. The purpose of this study was to assess the potential of several noninvasive functional and molecular MRI biomarkers for the assessment of glioma response to radiotherapy. Fourteen U87 tumor-bearing rats were irradiated using a small-animal radiation research platform (40 or 20 Gy), and 6 rats were used as controls. MRI was performed on a 4.7 T animal scanner, preradiation treatment, as well as at 3, 6, 9, and 14 days postradiation. Image features of the tumors, as well as tumor volumes and animal survival, were quantitatively compared. Structural MRI showed that all irradiated tumors still grew in size during the initial days postradiation. The apparent diffusion coefficient (ADC) values of tumors increased significantly postradiation (40 and 20 Gy), except at day 3 postradiation, compared with preradiation. The tumor blood flow decreased significantly postradiation (40 and 20 Gy), but the relative blood flow (tumor vs contralateral) did not show a significant change at most time points postradiation. The amide proton transfer weighted (APTw) signals of the tumor decreased significantly at all time points postradiation (40 Gy), and also at day 9 postradiation (20 Gy). The blood flow and APTw maps demonstrated tumor features that were similar to those seen on gadolinium-enhanced T1-weighted images. Tumor ADC, blood flow, and APTw were all useful imaging biomarkers by which to predict glioma response to radiotherapy. The APTw signal was most promising for early response assessment in this model. © The Author(s) 2013. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Prospective study of neoadjuvant chemoradiotherapy using intensity-modulated radiotherapy and 5 fluorouracil for locally advanced rectal cancer – toxicities and response assessment

PubMed Central

Simson, David K; Mitra, Swarupa; Ahlawat, Parveen; Saxena, Upasna; Sharma, Manoj Kumar; Rawat, Sheh; Singh, Harpreet; Bansal, Babita; Sripathi, Lalitha Kameshwari; Tanwar, Aditi

2018-01-01

Aims and objectives The past 2 decades witnessed the strengthening of evidence favoring the role of neoadjuvant chemoradiation (CHRT) in the treatment of locally advanced rectal cancer. The study aims to evaluate the response and acute toxicities to neoadjuvant CHRT using intensity-modulated radiotherapy (IMRT) in the treatment of rectal cancer. Predictive factors to achieve pathological complete response (pCR) were analyzed, as a secondary endpoint. Materials and methods All consecutive patients who underwent IMRT as part of neoadjuvant CHRT in the treatment of rectal cancer between August 2014 and December 2016 at a tertiary cancer care center were accrued for the study. The cohort underwent CHRT with IMRT technique at a dose of 50.4 Gy in 28 fractions concurrent with continuous infusion of 5 fluorouracil during the first and the last 4 days of CHRT. Surgery was performed 6 weeks later and the pathological response to CHRT was noted. Results Forty-three subjects were accrued for the study. Radiation dermatitis and diarrhea were the only observed grade ≥3 acute toxicities. Sphincter preservation rate (SPR) was 43.3%. pCR was observed in 32.6%. Univariate and multivariate logistic regression showed that carcinoembryonic antigen was the only independent predictive factor to achieve pCR. Conclusion IMRT as part of neoadjuvant CHRT in the treatment of locally advanced rectal cancer is well tolerated and gives comparable results with respect to earlier studies in terms of pathological response and SPR. Further randomized controlled studies are needed to firmly state that IMRT is superior to 3-dimensional conformal radiotherapy. PMID:29593430

Quantitative correlational study of microbubble-enhanced ultrasound imaging and magnetic resonance imaging of glioma and early response to radiotherapy in a rat model.

PubMed

Yang, Chen; Lee, Dong-Hoon; Mangraviti, Antonella; Su, Lin; Zhang, Kai; Zhang, Yin; Zhang, Bin; Li, Wenxiao; Tyler, Betty; Wong, John; Wang, Ken Kang-Hsin; Velarde, Esteban; Zhou, Jinyuan; Ding, Kai

2015-08-01

Radiotherapy remains a major treatment method for malignant tumors. Magnetic resonance imaging (MRI) is the standard modality for assessing glioma treatment response in the clinic. Compared to MRI, ultrasound imaging is low-cost and portable and can be used during intraoperative procedures. The purpose of this study was to quantitatively compare contrast-enhanced ultrasound (CEUS) imaging and MRI of irradiated gliomas in rats and to determine which quantitative ultrasound imaging parameters can be used for the assessment of early response to radiation in glioma. Thirteen nude rats with U87 glioma were used. A small thinned skull window preparation was performed to facilitate ultrasound imaging and mimic intraoperative procedures. Both CEUS and MRI with structural, functional, and molecular imaging parameters were performed at preradiation and at 1 day and 4 days postradiation. Statistical analysis was performed to determine the correlations between MRI and CEUS parameters and the changes between pre- and postradiation imaging. Area under the curve (AUC) in CEUS showed significant difference between preradiation and 4 days postradiation, along with four MRI parameters, T2, apparent diffusion coefficient, cerebral blood flow, and amide proton transfer-weighted (APTw) (all p < 0.05). The APTw signal was correlated with three CEUS parameters, rise time (r = - 0.527, p < 0.05), time to peak (r = - 0.501, p < 0.05), and perfusion index (r = 458, p < 0.05). Cerebral blood flow was correlated with rise time (r = - 0.589, p < 0.01) and time to peak (r = - 0.543, p < 0.05). MRI can be used for the assessment of radiotherapy treatment response and CEUS with AUC as a new technique and can also be one of the assessment methods for early response to radiation in glioma.

Phase II study of capecitabine (Xeloda (registered) ) and concomitant boost radiotherapy in patients with locally advanced rectal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krishnan, Sunil; Janjan, Nora A.; Skibber, John M.

2006-11-01

Purpose: The aim of this study was to determine the efficacy of capecitabine (Xeloda (registered) ), an oral fluoropyrimidine, as a radiosensitizer in the neoadjuvant treatment of locally advanced rectal cancer (LARC). Methods and Materials: We conducted a phase II study of capecitabine (825 mg/m{sup 2} orally, twice daily continuous) with radiotherapy (52.5 Gy/30 fractions to the primary tumor and perirectal nodes) in 54 patients with LARC (node-negative {>=}T3 or any node-positive tumor) staged by endoscopic ultrasound (EUS). The primary endpoint was pathologic response rate; secondary endpoints included toxicity profiles and survival parameters. Results: Of the 54 patients (median age,more » 56.7 years; range, 21.3-78.7 years; male:female ratio, 1.7; Eastern Cooperative Oncology Group performance status 0-1: 100%), 51 patients (94%) had T3N0 or T3N1 disease by EUS. Surgery was not performed in 3 patients; 2 of these patients had metastatic disease, and the third patient refused after a complete clinical response. Of the 51 patients evaluable for pathologic response, 9 patients (18%) achieved complete response, and 12 patients (24%) had microscopic residual disease (<10% viable cells). In addition, 26 patients of all 54 patients (51%) achieved T-downstaging, and 15 patients of 29 patients (52%) achieved N-downstaging. Grade 3/4 toxicities were radiation dermatitis (9%) and diarrhea (2%). Sphincter preservation rate for tumor {<=}5 cm from the anal verge was 67% (18/27). Conclusion: This regimen of radiotherapy plus capecitabine is well tolerated and is more convenient than protracted venous infusion of 5-FU. The pathologic response rate is comparable to our previous experience using protracted venous infusion 5-FU for LARC.« less

Evaluation of Radioresponse and Radiosensitizers in Glioblastoma Organotypic Cultures.

PubMed

Bayin, N Sumru; Ma, Lin; Placantonakis, Dimitris G; Barcellos-Hoff, Mary Helen

2018-01-01

Glioblastoma (GBM), a deadly primary brain malignancy, manifests pronounced radioresistance. Identifying agents that improve the sensitivity of tumor tissue to radiotherapy is critical for improving patient outcomes. The response to ionizing radiation is regulated by both cell-intrinsic and -extrinsic mechanisms. In particular, the tumor microenvironment is known to promote radioresistance in GBM. Therefore, model systems used to test radiosensitizing agents need to take into account the tumor microenvironment. We recently showed that GBM explant cultures represent an adaptable ex vivo platform for rapid and personalized testing of radiosensitizers. These explants preserve the cellular composition and tissue architecture of parental patient tumors and therefore capture the microenvironmental context that critically determines the response to radiotherapy. This chapter focuses on the detailed protocol for testing candidate radiosensitizing agents in GBM explants.

Sphere of equivalence--a novel target volume concept for intraoperative radiotherapy using low-energy X rays.

PubMed

Herskind, Carsten; Griebel, Jürgen; Kraus-Tiefenbacher, Uta; Wenz, Frederik

2008-12-01

Accelerated partial breast radiotherapy with low-energy photons from a miniature X-ray machine is undergoing a randomized clinical trial (Targeted Intra-operative Radiation Therapy [TARGIT]) in a selected subgroup of patients treated with breast-conserving surgery. The steep radial dose gradient implies reduced tumor cell control with increasing depth in the tumor bed. The purpose was to compare the expected risk of local recurrence in this nonuniform radiation field with that after conventional external beam radiotherapy. The relative biologic effectiveness of low-energy photons was modeled using the linear-quadratic formalism including repair of sublethal lesions during protracted irradiation. Doses of 50-kV X-rays (Intrabeam) were converted to equivalent fractionated doses, EQD2, as function of depth in the tumor bed. The probability of local control was estimated using a logistic dose-response relationship fitted to clinical data from fractionated radiotherapy. The model calculations show that, for a cohort of patients, the increase in local control in the high-dose region near the applicator partly compensates the reduction of local control at greater distances. Thus a "sphere of equivalence" exists within which the risk of recurrence is equal to that after external fractionated radiotherapy. The spatial distribution of recurrences inside this sphere will be different from that after conventional radiotherapy. A novel target volume concept is presented here. The incidence of recurrences arising in the tumor bed around the excised tumor will test the validity of this concept and the efficacy of the treatment. Recurrences elsewhere will have implications for the rationale of TARGIT.

SU-E-T-469: Implementation of VAs Web-Based Radiotherapy Incident Reporting and Analysis System (RIRAS)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kapoor, R; Palta, J; Hagan, M

Purpose: This Web-based Radiotherapy Incident Reporting and Analysis System (RIRAS) is a tool to improve quality of care for radiation therapy patients. This system is an important facet of continuing effort by our community to maintain and improve safety of radiotherapy.Material and Methods: VA’s National Radiation Oncology Program office has embarked on a program to electronically collect adverse events and good-catch data of radiation treatment of over 25,000 veterans treated with radiotherapy annually. This VA-Intranet based software design has made use of dataset taxonomies and data dictionaries defined in AAPM/ASTRO reports on error reporting. We used proven industrial and medicalmore » event reporting techniques to avoid several common problems faced in effective data collection such as incomplete data due to data entry fatigue by the reporters, missing data due to data difficult to obtain or not familiar to most reporters, missing reports due to fear of reprisal etc. This system encompasses the entire feedback loop of reporting an incident, analyzing it for salient details, and developing interventions to prevent it from happening again. The analysis reports with corrective, learning actions are shared with the reporter/facility and made public to the community (after deidentification) as part of the learning process. Results: Till date 50 incident/good catches have been reported in RIRAS and we have completed analysis on 100% of these reports. This is done due to the fact that each reported incidents is investigated and a complete analysis/patient-safety-work-product report is generated by radiation oncology domain-experts. Conclusions Because of the completeness of the data, the system has enabled us to analyze process steps and track trends of major errors which in the future will lead to implementing system wide process improvement steps and safe standard operating procedures for each radiotherapy treatment modality/technique and fulfills our goal of “Effecting Quality While Treating Safely”. RIRAS developed and copyrighted by TSG Innovations Inc.« less

Cell Death, Inflammation, Tumor Burden, and Proliferation Blood Biomarkers Predict Lung Cancer Radiotherapy Response and Correlate With Tumor Volume and Proliferation Imaging.

PubMed

Salem, Ahmed; Mistry, Hitesh; Backen, Alison; Hodgson, Clare; Koh, Pek; Dean, Emma; Priest, Lynsey; Haslett, Kate; Trigonis, Ioannis; Jackson, Alan; Asselin, Marie-Claude; Dive, Caroline; Renehan, Andrew; Faivre-Finn, Corinne; Blackhall, Fiona

2018-05-01

There is an unmet need to develop noninvasive biomarkers to stratify patients in drug-radiotherapy trials. In this pilot study we investigated lung cancer radiotherapy response and toxicity blood biomarkers and correlated findings with tumor volume and proliferation imaging. Blood samples were collected before and during (day 21) radiotherapy. Twenty-six cell-death, hypoxia, angiogenesis, inflammation, proliferation, invasion, and tumor-burden biomarkers were evaluated. Clinical and laboratory data were collected. Univariate analysis was performed on small-cell and non-small-cell lung cancer (NSCLC) whereas multivariate analysis focused on NSCLC. Blood samples from 78 patients were analyzed. Sixty-one (78.2%) harbored NSCLC, 48 (61.5%) received sequential chemoradiotherapy. Of tested baseline biomarkers, undetectable interleukin (IL)-1b (hazard ratio [HR], 4.02; 95% confidence interval [CI], 2.04-7.93; P < .001) was the only significant survival covariate. Of routinely collected laboratory tests, high baseline neutrophil count was a significant survival covariate (HR, 1.07; 95% CI, 1.02-1.11; P = .017). Baseline IL-1b and neutrophil count were prognostic for survival in a multivariate model. The addition of day-21 cytokeratin-19 antigen modestly improved this model's survival prediction (concordance probability, 0.75-0.78). Chemotherapy (P < .001) and baseline keratinocyte growth factor (P = .019) predicted acute esophagitis, but only chemotherapy remained significant after Bonferroni correction. Baseline angioprotein-1 and hepatocyte growth factor showed a direct correlation with tumor volume whereas changes in vascular cell adhesion molecule 1 showed significant correlations with 18F-fluorothymidine (FLT) positron emission tomography (PET). Select biomarkers are prognostic after radiotherapy in this lung cancer series. The correlation between circulating biomarkers and 18F-FLT PET is shown, to our knowledge for the first time, highlighting their potential role as imaging surrogates. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Non-Hodgkin's lymphomas of the tonsil: a retrospective analysis of twenty-eight patients with primary tonsillary lymphoma.

PubMed

Barişta, I; Tekuzman, G; Güllü, I; Baltali, E; Kars, A; Ozişik, Y; Güler, N; Celik, I; Atahan, I L; Firat, D

1995-01-01

To analyze the clinical and therapeutic aspects of patients with primary tonsillary non-Hodgkin's lymphoma. Twenty-eight patients with primary tonsillary non-Hodgkin's lymphoma who had been followed in the Hacettepe Oncology Institute between 1974 and 1992 were retrospectively analyzed. Fifteen patients were male, 13 were female. Median age was 55 years. Constitutional symptoms were present in 10 patients (35.7%). Stages according to the Ann Arbor classification were I and II in 12 and 16 patients, respectively. According to the Rappaport classification, poorly differentiated lymphocytic was the most common pathologic subgroup (42.9%). Grades according to the Working Formulation were low, intermediate and high in 3, 22 and 3 patients, respectively. Twenty-two patients had received chemotherapy. Cyclophosphamide, vincristine and prednisone (CVP), and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) were the regimens most commonly employed. Eighteen patients received radiotherapy to Waldeyer's ring and neck. Eight patients achieved remission with chemotherapy plus radio-therapy, 7 patients with chemotherapy alone, and 5 patients with radiotherapy alone. In addition to the 20 patients who achieved complete remission, 3 patients achieved partial remission; the overall response rate was 82.1%. The response rates and survival attained with the combined modality, chemotherapy, or radiotherapy alone were not statistically different (P > 0.05). The median follow-up was 14 months. Overall and disease-free survival at 5 years were 62.6% and 77.6%, respectively. Pathologic grade was the most important prognostic factor influencing overall survival in the Cox multivariate model. Poorly differentiated lymphocytic lymphomas were the most common pathologic subtype, and pathologic grade was the most important prognostic factor to influence survival in the present study. Although combined modality treatment did not appear to be superior to chemotherapy or radiotherapy alone, a larger number of patients is needed to draw definite conclusions.

Nasopharyngeal carcinoma in childhood and adolescence: analysis of a series of 32 patients treated with combined chemotherapy and radiotherapy.

PubMed

Daoud, J; Toumi, N; Bouaziz, M; Ghorbel, A; Jlidi, R; Drira, M M; Frikha, M

2003-11-01

Standard therapy for nasopharyngeal carcinoma (NPC) in children has generally followed the guidelines established for adults. We report here, the treatment outcomes in 32 children and adolescents with NPC and we discuss treatment approaches. Between 1993 and 1997, 32 NPC patients aged

Complete radiotherapy response in rectal cancer: A review of the evidence

PubMed Central

Couch, Daniel G; Hemingway, David M

2016-01-01

Complete response to chemoradiotherapy for rectal cancer is becoming a common clinical entity. Techniques to diagnose complete response and how to survey these patients without operative intervention are still unclear. We review the most recent evidence. Barriers to firm conclusions regarding this are heterogeneity of diagnostic definitions, differing surveillance protocols, and a lack of randomised studies. PMID:26811600

Clinical outcome and prognosis of carbon ion radiotherapy on thoracic malignant tumors

NASA Astrophysics Data System (ADS)

Li, Sha

Objective To evaluate the therapeutic efficacy and side-response of high-LET carbon ion radiotherapy on thoracic malignant tumors. Methods Ten patients with pathological confirmed thoracic malignant tumors received treatment using heavy ion accelerator, which included 6 cases with non-small lung cancer, one case with small lung cancer, 2 cases with metastatic sarcomas and one case with invasive thymoma. The applied regimen included fractioned dose (5.5-6.8GyE/Fraction), one faction/day, and 7 fractions/week. The total dose ranged from 55 to 70 GyE. Results The short-term results showed that the response rate (the complete response (CR) rate +the partial response (PR) rate) was 10% at the first month, 40% at the third month and 90% at the sixth month. The overall response rate was 90% and the rate of stable disease was 10%. There was no relation between the response rate and tumor pathology (P>0.05) while significance between the response rate and the tumor volume.At median follow-up of 27 months (range, 6 to 36 months), the local control rate and free-disease rate were respectively 100% an 90% at the first year, 90% and 80% at the secondary year, 80% and 70% at the third year. The death rate due to disease progression was 20% and the non-specific death rate was 10%. Side and toxicity effects: Grade I skin effect occurred in three cases and Grade I lung effect occurred in two cases. The blood counts didn’t reach significance among pre-radiation course, peri-radiation course and post-radiation course (P>0.05). The subgoups of T cells detected in humoral immunity and cytoimmunity didn’t change between pre-radiation and post radiation(P>0.05). Conclusions Carbon ion radiotherapy is effective and safe in the management of patients with thoracic malignant tumors. There were no obvious side effects. The long term of clinical outcome and the late effect need to be further observed.

MRI surveillance of cancer cell fate in a brain metastasis model after early radiotherapy.

PubMed

Murrell, Donna H; Zarghami, Niloufar; Jensen, Michael D; Dickson, Fiona; Chambers, Ann F; Wong, Eugene; Foster, Paula J

2017-10-01

Incidence of brain metastasis attributed to breast cancer is increasing and prognosis is poor. It is thought that disseminated dormant cancer cells persist in metastatic organs and may evade treatments, thereby facilitating a mechanism for recurrence. Radiotherapy is used to treat brain metastases clinically, but assessment has been limited to macroscopic tumor volumes detectable by clinical imaging. Here, we use cellular MRI to understand the concurrent responses of metastases and nonproliferative or slowly cycling cancer cells to radiotherapy. MRI cell tracking was used to investigate the impact of early cranial irradiation on the fate of individual iron-labeled cancer cells and outgrowth of breast cancer brain metastases in the human MDA-MB-231-BR-HER2 cell model. Early whole-brain radiotherapy significantly reduced the outgrowth of metastases from individual disseminated cancer cells in treated animals compared to controls. However, the numbers of nonproliferative iron-retaining cancer cells in the brain were not significantly different. Radiotherapy, when given early in cancer progression, is effective in preventing the outgrowth of solitary cancer cells to brain metastases. Future studies of the nonproliferative cancer cells' clonogenic potentials are warranted, given that their persistent presence suggests that they may have evaded treatment. Magn Reson Med 78:1506-1512, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Optimization of radiotherapy. Some notes on the principles and practice of optimization in cancer treatment and implications for clinical research.

PubMed

Andrews, J R

1981-01-01

Two methods dominate cancer treatment--one, the traditional best practice, individualized treatment method and two, the a priori determined decision method of the interinstitutional, cooperative, clinical trial. In the first, choices are infinite and can be made at the time of treatment; in the second, choices are finite and are made in advance of treatment on a random basis. Neither method systematically selects, identifies, or formalizes the optimum level of effect in the treatment chosen. Of the two, it can be argued that the first, other things being equal, is more likely to select the optimum treatment. The determination of level of effect for the optimization of cancer treatment requires the generation of dose-response relationships for both benefit and risk and the introduction of benefit and risk considerations and judgements. The clinical trial, as presently constituted, doses not yield this kind of information, it being, generally, of the binary yes or no, better or worse type. The best practice, individualized treatment method can yield, when adequately documented, both a range of dose-response relationships and a variety of benefit and risk considerations. The presentation will be limited to a consideration of a single modality of cancer treatment, radiation therapy, but an analogy with other modalities of cancer treatment will be inferred. Criteria for optimization will be developed and graphic means for its identification and formalization will be demonstrated with examples taken from the radiotherapy literature. The general problem of optimization theory and practice will be discussed; the necessity for its exploration in relation to the increasing complexity of cancer treatment will be developed; and recommendations for clinical research will be made including a proposal for the support of clinics as an alternative to the support of programs.

Expected Paradigm Shift in Brain Metastases Therapy-Immune Checkpoint Inhibitors.

PubMed

Jindal, Vishal; Gupta, Sorab

2018-01-30

Brain metastasis (BM) is one of the dreadful complications of malignancies. The prognosis after BM is extremely poor and life expectancy is meager. Currently, our treatment modalities are limited to radiotherapy and surgical resection, which also has poor outcomes and leads to various neurological deficits and affects the quality of life of patients. New treatment modality, i.e., immune checkpoint inhibitors, has brought revolution in management of melanoma, renal cancer, and non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors basically enhance the immune response of the body to fight against cancers. Immune response in the brain is highly regulated; therefore, it is challenging to use immune-modulator drugs in BM. The microenvironment of BM is rich in cytotoxic T lymphocytes and which is the target of immune checkpoint inhibitors. Few studies have shown some hope regarding use of immune checkpoint inhibitors in management of BM. It works through inhibiting immune check point gates, i.e., CTLA-4 (cytotoxic T-lymphocyte-associated protein) and PD-1/PD-L1 (programmed cell death protein-1/program death ligand-1). This article explains the basic mechanism of immune check point inhibitors, rationale behind their usage in BM, and some of the clinical studies which have shown the efficacy of immune check point inhibitors in BM.

Extraskeletal Ewing's sarcoma family of tumors in adults: prognostic factors and clinical outcome.

PubMed

Tural, Deniz; Molinas Mandel, Nil; Dervisoglu, Sergulen; Oner Dincbas, Fazilet; Koca, Sedat; Colpan Oksuz, Didem; Kantarci, Fatih; Turna, Hande; Selcukbiricik, Fatih; Hiz, Murat

2012-05-01

The aim of this study was to evaluate prognostic factors, survival rate and the efficacy of the treatment modalities used in patients with extraskeletal Ewing's sarcoma. Data of patients with extraskeletal Ewing's sarcoma followed up at our center between 1997 and 2010 were retrospectively analyzed. The median age of 27 patients was 24 years (range, 16-54 years). The median follow-up was 31.8 months (range, 6-144 months). Tumor size was between 1.5 and 14 cm (median: 8 cm). Eighty-five percent of patients had localized disease at presentation and 15% had metastatic disease. Local therapy was surgery alone in 16% of patients, surgery combined with radiotherapy in 42% and radiotherapy alone in 27%. All patients were treated with vincristine, doxorubicin, cyclophosphamide and actinomycin-D, alternating with ifosfamide and etoposide every 3 weeks. In patients with localized disease at presentation, the 5-year event-free survival and overall survival were 59.7 and 64.5%, respectively. At univariate analysis, patients with tumor size ≥ 8 cm, high serum lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy and positive surgical margin had significantly worse event-free survival. The significant predictors of worse overall survival at univariate analysis were tumor size 8 ≥ cm, high lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy, radiotherapy only as local treatment and positive surgical margin. Prognostic factors were similar to primary osseous Ewing's sarcomas. Adequate surgical resection, aggressive chemotherapy (vincristine, doxorubicin, cyclophosphamide and actinomycin-D alternating with ifosfamide and etoposide) and radiotherapy if indicated are the recommended therapy for patients with extraskeletal Ewing's sarcoma.

Continued EGFR-TKI with concurrent radiotherapy to improve time to progression (TTP) in patients with locally progressive non-small cell lung cancer (NSCLC) after front-line EGFR-TKI treatment.

PubMed

Wang, Y; Li, Y; Xia, L; Niu, K; Chen, X; Lu, D; Kong, R; Chen, Z; Sun, J

2018-03-01

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the optimal treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, most patients developed systemic or local progression due to acquired EGFR-TKI resistance. This retrospective study aimed to evaluate the feasibility of continued EGFR-TKI with concurrent radiotherapy (CTCRT) in patients with local progression after front-line EGFR-TKI treatment. Advanced NSCLC patients with active EGFR mutation who received EGFR-TKI were treated with CTCRT after local progression. Medical data were analyzed for time to progression (TTP), progression-free survival (PFS), tumor response rate, overall survival (OS) and adverse events. A total of 50 irradiated lesions from 44 patients were included. Median TTP and PFS of measurable lesions (n = 31) were both significantly prolonged after local radiotherapy (TTP1 + TTP2 vs. TTP1: 21.7 vs. 16.0 months, P = 0.010; PFS1 + PFS2 vs. PFS1: 21.3 vs. 16.0 months, P = 0.027). For all lesions (n = 50), objective response rate (ORR) and local tumor control rate (LCR) were 54.0 and 84.0%, respectively. Median OS was 26.6 months. There were no serious adverse events before or after radiotherapy. The treatment modality of CTCRT is considerable and effective for EGFR-mutant NSCLC patients even with local failure from front-line EGFR-TKI treatment.

SU-E-J-223: A BOLD Contrast Imaging Sequence to Evaluate Oxygenation Changes Due to Breath Holding for Breast Radiotherapy: A Pilot Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adamson, J; Chang, Z; Cai, J

Purpose: To develop a robust MRI sequence to measure BOLD breath hold induced contrast in context of breast radiotherapy. Methods: Two sequences were selected from prior studies as candidates to measure BOLD contrast attributable to breath holding within the breast: (1) T2* based Gradient Echo EPI (TR/TE = 500/41ms, flip angle = 60°), and (2) T2 based Single Shot Fast Spin Echo (SSFSE) (TR/TE = 3000/60ms). We enrolled ten women post-lumpectomy for breast cancer who were undergoing treatment planning for whole breast radiotherapy. Each session utilized a 1.5T GE MRI and 4 channel breast coil with the subject immobilized pronemore » on a custom board. For each sequence, 1–3 planes of the lumpectomy breast were imaged continuously during a background measurement (1min) and intermittent breath holds (20–40s per breath hold, 3–5 holds per sequence). BOLD contrast was quantified as correlation of changes in per-pixel intensity with the breath hold schedule convolved with a hemodynamic response function. Subtle motion was corrected using a deformable registration algorithm. Correlation with breath-holding was considered significant if p<0.001. Results: The percentage of the breast ROI with positive BOLD contrast measured by the two sequences were in agreement with a correlation coefficient of R=0.72 (p=0.02). While both sequences demonstrated areas with strong BOLD response, the response was more systematic throughout the breast for the SSFSE (T2) sequence (% breast with response in the same direction: 51.2%±0.7% for T2* vs. 68.1%±16% for T2). In addition, the T2 sequence was less prone to magnetic susceptibility artifacts, especially in presence of seroma, and provided a more robust image with little distortion or artifacts. Conclusion: A T2 SSFSE sequence shows promise for measuring BOLD contrast in the context of breast radiotherapy utilizing a breath hold technique. Further study in a larger patient cohort is warranted to better refine this novel technique.« less

Pooled Analysis of CNS Response to Alectinib in Two Studies of Pretreated Patients With ALK-Positive Non-Small-Cell Lung Cancer.

PubMed

Gadgeel, Shirish M; Shaw, Alice T; Govindan, Ramaswamy; Gandhi, Leena; Socinski, Mark A; Camidge, D Ross; De Petris, Luigi; Kim, Dong-Wan; Chiappori, Alberto; Moro-Sibilot, Denis L; Duruisseaux, Michael; Crino, Lucio; De Pas, Tommaso; Dansin, Eric; Tessmer, Antje; Yang, James Chih-Hsin; Han, Ji-Youn; Bordogna, Walter; Golding, Sophie; Zeaiter, Ali; Ou, Sai-Hong Ignatius

2016-12-01

Purpose Alectinib has shown activity in the CNS in phase I and II studies. To further evaluate this activity, we pooled efficacy and safety data from two single-arm phase II studies (NP28761 and NP28673; ClinicalTrials.gov identifiers: NCT01871805 and NCT01801111, respectively) in patients with ALK-positive non-small-cell lung cancer (NSCLC). Patients and Methods Both studies included patients with ALK-positive NSCLC who had previously received crizotinib; all patients received alectinib 600 mg twice per day. The primary end point in both studies was independent review committee (IRC)-assessed objective response rate (ORR; by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). Additional end points (all by IRC) included CNS ORR (CORR), CNS disease control rate (CDCR), and CNS duration of response (CDOR). Results One hundred thirty-six patients had baseline CNS metastases (60% of the overall study populations); 50 patients (37%) had measurable CNS disease at baseline. Ninety-five patients (70%) had prior CNS radiotherapy; 55 patients completed the CNS radiotherapy more than 6 months before starting alectinib. Median follow-up time was 12.4 months (range, 0.9 to 19.7 months). For patients with baseline measurable CNS disease, IRC CORR was 64.0% (95% CI, 49.2% to 77.1%), CDCR was 90.0% (95% CI, 78.2% to 96.7%), and median CDOR was 10.8 months (95% CI, 7.6 to 14.1 months). For patients with measurable and/or nonmeasurable baseline CNS disease, IRC CORR was 42.6% (95% CI, 34.2% to 51.4%), CDCR was 85.3% (95% CI, 78.2% to 90.8%), and median CDOR was 11.1 months (95% CI, 10.3 months to not evaluable). CORR was 35.8% (95% CI, 26.2% to 46.3%) for patients with prior radiotherapy (n = 95) and 58.5% (95% CI, 42.1% to 73.7%) for patients without prior radiotherapy (n = 41). As previously reported, alectinib was well tolerated, regardless of baseline CNS disease. Conclusion Alectinib showed good efficacy against CNS metastases, in addition to systemic activity, in crizotinib-refractory ALK-positive NSCLC.

Student Perspectives on the Impact of an Undergraduate Work-Integrated Learning Program on Admission and Transition to Medical School.

PubMed

McDonald, Rachel; Bobrowski, Adam; Drost, Leah; Rowbottom, Leigha; Pretti, Judene; Soliman, Hany; Chan, Stephanie; Chow, Edward

2018-05-05

Work-integrated learning (WIL) is a form of education that integrates academic and workplace study. Such programs provide students the opportunity to concurrently develop cognitive and non-cognitive competencies. The purpose of this study is to explore which experiences and skills learned in a WIL placement are useful in applying to medical school and transitioning into the first year of a Doctor of Medicine program. All individuals who worked in the Rapid Response Radiotherapy Program (RRRP; WIL placement) since 2004 and had completed at least 1 year of medical school were invited to participate. Semi-formal interviews were conducted and transcribed. A thematic analysis was completed to identify recurring concepts, and quotes were selected to represent them. Of 39 eligible individuals, 14 agreed to participate (36%). Students identified the volume of work, achieving a work-life balance, and time management as challenges in first-year medical school. Five themes emerged regarding the impact of the RRRP on applying and transitioning to medical school: time management skills, mentorship opportunities, research experience, clinical experience, and career choice. WIL placements present a unique opportunity for undergraduate students interested in pursuing medicine to acquire skills and experiences that will help them succeed in applying and transitioning to medical school.

Resistance of Nonmelanoma Skin Cancer to Nonsurgical Treatments. Part II: Photodynamic Therapy, Vismodegib, Cetuximab, Intralesional Methotrexate, and Radiotherapy.

PubMed

Gracia-Cazaña, T; Salazar, N; Zamarrón, A; Mascaraque, M; Lucena, S R; Juarranz, Á

2016-11-01

A wide range of treatments is now available for nonmelanoma skin cancer, including 5-fluorouracil, ingenol mebutate, imiquimod, diclofenac, photodynamic therapy, methotrexate, cetuximab, vismodegib, and radiotherapy. All are associated with high clinical and histologic response rates. However, some tumors do not respond due to resistance, which may be primary or acquired. Study of the resistance processes is a broad area of research that aims to increase our understanding of the nature of each tumor and the biologic features that make it resistant, as well as to facilitate the design of new therapies directed against these tumors. In this second article, having covered the topical treatments of nonmelanoma skin cancer, we review resistance to other nonsurgical treatments, such as monoclonal antibodies against basal and squamous cell carcinomas, intralesional chemotherapy, photodynamic therapy, and radiotherapy. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Postoperative radiation therapy of pT2-3N0M0 esophageal carcinoma-a review.

PubMed

Luo, Yijun; Wang, Xiaoli; Yu, Jinming; Zhang, Bin; Li, Minghuan

2016-11-01

Esophageal cancer is one of the most malignant gastrointestinal cancers worldwide. Despite advances in surgical technique, 5-year survival in pathologic stage T2-3N0M0 esophageal squamous cell carcinoma patients who are treated with surgery alone is still poor. The addition of adjuvant radiotherapy may confer a benefit for these patients. However, not all patients could get a benefit from radiotherapy and patients with esophageal squamous cell carcinoma receiving radiotherapy seem to have a disparity in treatment response. Thus, identifying effective prognostic indicator to complement current clinical staging approaches is extremely important. Those prognostic factors could give rise to a novel prognostic stratification system, which serve as criteria for selecting patients for adjuvant therapy. Consequently, it may help to define the subgroups who are more likely to benefit from postoperative radiation therapy.

A survey of current in vivo radiotherapy dosimetry practice.

PubMed

Edwards, C R; Grieveson, M H; Mountford, P J; Rolfe, P

1997-03-01

A questionnaire was sent out to 57 radiotherapy physics departments in the United Kingdom to determine the type of dosemeters used for in vivo measurements inside and outside X-ray treatment fields, and whether any correction is made for energy dependence when the dose to critical organs outside the main beam is estimated. 44 responses were received. 11 centres used a semi-conductor for central axis dosimetry compared with only two centres which used thermoluminescent dosimetry (TLD). 37 centres carried out dosimetry measurements outside the main beam; 25 centres used TLD and 12 centres used a semi-conductor detector. Of the 16 centres measuring the dose at both sites. 11 used a semi-conductor for the central axis measurement, but only four of those 11 changed to TLD for critical organ dosimetry despite the latter's lower variation in energy response. None of the centres stated that they made a correction for the variation in detector energy response when making measurements outside the main beam, indicating a need for a more detailed evaluation of the energy response of these detectors and the energy spectra outside the main beam.

Multi-modality imaging of tumor phenotype and response to therapy

NASA Astrophysics Data System (ADS)

Nyflot, Matthew J.

2011-12-01

Imaging and radiation oncology have historically been closely linked. However, the vast majority of techniques used in the clinic involve anatomical imaging. Biological imaging offers the potential for innovation in the areas of cancer diagnosis and staging, radiotherapy target definition, and treatment response assessment. Some relevant imaging techniques are FDG PET (for imaging cellular metabolism), FLT PET (proliferation), CuATSM PET (hypoxia), and contrast-enhanced CT (vasculature and perfusion). Here, a technique for quantitative spatial correlation of tumor phenotype is presented for FDG PET, FLT PET, and CuATSM PET images. Additionally, multimodality imaging of treatment response with FLT PET, CuATSM, and dynamic contrast-enhanced CT is presented, in a trial of patients receiving an antiangiogenic agent (Avastin) combined with cisplatin and radiotherapy. Results are also presented for translational applications in animal models, including quantitative assessment of proliferative response to cetuximab with FLT PET and quantification of vascular volume with a blood-pool contrast agent (Fenestra). These techniques have clear applications to radiobiological research and optimized treatment strategies, and may eventually be used for personalized therapy for patients.

NCI–RTOG Translational Program Strategic Guidelines for the Early-Stage Development of Radiosensitizers

PubMed Central

2013-01-01

The addition of chemotherapeutic agents to ionizing radiation has improved survival in many malignancies. Cure rates may be further improved by adding novel targeted agents to current radiotherapy or radiochemotherapy regimens. Despite promising laboratory data, progress in the clinical development of new drugs with radiation has been limited. To define and address the problems involved, a collaborative effort between individuals within the translational research program of the Radiation Oncology Therapy Group and the National Cancer Institute was established. We discerned challenges to drug development with radiation including: 1) the limited relevance of preclinical work, 2) the pharmaceutical industry’s diminished interest, and 3) the important individual skills and institutional commitments required to ensure a successful program. The differences between early-phase trial designs with and without radiation are noted as substantial. The traditional endpoints for early-phase clinical trials—acute toxicity and maximum-tolerated dose—are of limited value when combining targeted agents with radiation. Furthermore, response rate is not a useful surrogate marker of activity in radiation combination trials.Consequently, a risk-stratified model for drug-dose escalation with radiation is proposed, based upon the known and estimated adverse effects. The guidelines discuss new clinical trial designs, such as the time-to-event continual reassessment method design for phase I trials, randomized phase II “screening” trials, and the use of surrogate endpoints, such as pathological response. It is hoped that by providing a clear pathway, this article will accelerate the rate of drug development with radiation. PMID:23231975

Reduced risk of compressive optic neuropathy using orbital radiotherapy in patients with active thyroid eye disease.

PubMed

Shams, Pari N; Ma, Roy; Pickles, Tom; Rootman, Jack; Dolman, Peter J

2014-06-01

To compare the risk of developing compressive optic neuropathy in patients with active thyroid eye disease (TED) treated with corticosteroids with or without orbital radiotherapy. Retrospective single-center case-control study. The clinical charts of 351 patients with active TED who received corticosteroids with or without orbital radiotherapy between 1999 and 2010 were reviewed. Patients with compressive optic neuropathy at the time of presentation were excluded. Group 1 received corticosteroids only and Group 2 received corticosteroids as well as orbital radiotherapy. The primary outcome measure was the development of compressive optic neuropathy. Secondary outcome measures were changes in other parameters indicating the activity of TED, including soft tissue inflammation, diplopia, ocular motility restriction, and appearance. There were 144 cases in Group 1 and 105 in Group 2. Both groups were matched for age, sex, and stability of thyroid function. The 2 groups differed only in the modality of treatment for active TED. The main indication for treatment in both groups was soft tissue inflammation. Corticosteroids were initiated an average of 2.6 months following symptom onset in Group 1 and 2.5 months in Group 2. Group 2 received orbital radiotherapy on average 4.2 months following the initiation of corticosteroid therapy and 8% (9/105) were intolerant to corticosteroids. At an average of 3.2 years follow-up, compressive optic neuropathy had developed in 17% (25/144) of Group 1 and 0% of Group 2 (P < .0001), on average 5.5 months following the initiation of corticosteroid therapy. Although both groups experienced a significant reduction in periocular inflammation, the radiotherapy-treated group demonstrated a significantly greater improvement in ocular motility. The rate of compressive optic neuropathy was significantly lower and improvement in ocular motility greater in patients receiving orbital radiotherapy in addition to corticosteroids. Patients with active TED appear to have an effective and sustained response to orbital radiotherapy combined with corticosteroids that is protective against disease progression and the development of compressive optic neuropathy. Copyright © 2014 Elsevier Inc. All rights reserved.

HERO (Health Economics in Radiation Oncology): a pan-European project on radiotherapy resources and needs.

PubMed

Lievens, Y; Dunscombe, P; Defourny, N; Gasparotto, C; Borras, J M; Grau, C

2015-02-01

Radiotherapy continues to evolve at a rapid rate in technology and techniques, with both driving up costs in an era in which health care budgets are of increasing concern at every governmental level. Against this background, it is clear that the radiotherapy community needs to quantify the costs of state of the art practice and then to justify those costs through rigorous cost-effectiveness analyses. The European Society for Radiotherapy and Oncology-Health Economics in Radiation Oncology project is directed towards tackling this issue in the European context. The first step has been to provide a validated picture of the European radiotherapy landscape in terms of the availability of equipment, personnel and guidelines. An 84-item questionnaire was distributed to the 40 countries of the European Cancer Observatory, of which 34 provided partial or complete responses. There was a huge variation in the availability and sophistication of treatment equipment and staffing levels across Europe. The median number of MV units per million inhabitants was 5.3, but there was a seven-fold variation across the European countries. Likewise, although average staffing figures per million inhabitants were 12.8 for radiation oncologists, 7.6 for physicists, 3.5 for dosimetrists, 26.6 for radiation therapists and 14.8 for nurses, there was a 20-fold variation, even after grouping personnel with comparable duties in the radiotherapy process. Guidelines for capital and human resources were declared for most countries, but without explicitly providing metrics for developing capital and human resource inventories in many cases. Although courses delivered annually per resource item – be it equipment or staff – increase with decreasing gross national income (GNI) per capita, differences were observed in equipment and staff availability in countries with a higher GNI/n, indicating that health policy has a significant effect on the provision of services. Although more needs to be done to increase access to radiotherapy in Europe, the situation has improved considerably since the comparable RadioTherapy for Cancer: QUAnification of Infrastructure and Staffing Needs (QUARTS) study reported in 2005. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Radiotherapy of Painful Vertebral Hemangiomas: The Single Center Retrospective Analysis of 137 Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miszczyk, Leszek, E-mail: leszek@io.gliwice.pl; Tukiendorf, Andrzej

2012-02-01

Purpose: An evaluation of dose-response relationship and an attempt to define predictive factors. Methods and Materials: A total of 137 cases of painful vertebral hemangioma irradiations (101 patients). Fraction dose (fd) varied from 2 to 15 Gy (123 fractionated and 14 radiosurgical treatments), and total dose (TD) from 8 to 30 Gy (111 cases irradiated with fd of 2 GY to TD of 24 Gy). We evaluated pain relief, changes in analgesic requirements, and reossification. Results: Means of pain relief 1, 6, 12, and 18 months after radiotherapy (defined as a decrease of primary pain level expressed in percent) weremore » 60.5%, 65.4%, 68.3%, and 78.4%, respectively. Proportion of patients with no need for analgesics and patients using tramadol were 39%, 40%, 44%, 57%, and 20%, 17%, 22%, and 11% in these times. The proportion of patients experiencing complete/partial pain relief changed from 36/48% 1 month, to 64/22% 1.5 years after radiotherapy. No impact of radiotherapy on reossification was found. The positive impact of fd and TD increase for analgesics uptake reduction and pain relief was found. An increase of the fd by 1 Gy results in 27% chance of analgesics uptake reduction and 3.8% reduction of pain, whereas 14% analgesics uptake reduction and 2.2% of pain reduction in case of the TD. The predictive factors improving results were found: female gender, older age, better performance states (the chance of the lower analgesic treatment decreases over 2.5 times in comparison to the higher Zubrod degree), bigger Hb concentration, shorter symptoms duration and lower analgesics uptake before radiotherapy. Conclusions: The obtained data support the efficacy of radiotherapy in improving pain secondary to vertebral hemangioma, with the degree of pain amelioration being related to increasing fd and TD. The positive predictive factors were defined: female gender, older age, better performance status, increased Hb concentration, shorter symptoms duration, and lower analgesics uptake before radiotherapy.« less

Pathological complete response following neoadjuvant radiotherapy and intraperitoneal perfusion chemotherapy for recurrent colon carcinoma: A case report and literature review

PubMed Central

BIAN, XINYU; LIU, BAORUI; YANG, YANG

2016-01-01

The present study reports the case of a 28-year-old male who was diagnosed with sigmoid colon carcinoma and exhibited local recurrence following radical surgery and 6 cycles of adjuvant chemotherapy. The primary surgery consisted of a partial sigmoidectomy and bladder repair. At 8 months post-chemotherapy, the patient was referred to Nanjing Drum Tower Hospital (Nanjing, China) due to local recurrence at the anastomotic site, which was confirmed by colonoscopy and total abdominal computed tomography. Synchronous intensity modulation radiation therapy and intraperitoneal (IP) perfusion chemotherapy with irinotecan (100 mg/m2) was administered. Following treatment, the object efficacy evaluation revealed a complete response and a second resection of the remaining sigmoid colon was performed. The post-operative results showed a pathological complete response. This case indicated that a combination of therapies, including radiotherapy, IP perfusion chemotherapy and surgery, may be beneficial and effective in patients with recurrent colon cancer. PMID:27073546

Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials

PubMed Central

Chamberlain, Marc; Schiff, David; Reijneveld, Jaap C.; Armstrong, Terri S.; Ruda, Roberta; Wen, Patrick Y.; Weller, Michael; Koekkoek, Johan A. F.; Mittal, Sandeep; Arakawa, Yoshiki; Choucair, Ali; Gonzalez-Martinez, Jorge; MacDonald, David R.; Nishikawa, Ryo; Shah, Aashit; Vecht, Charles J.; Warren, Paula; van den Bent, Martin J.; DeAngelis, Lisa M.

2017-01-01

Patients with low-grade glioma frequently have brain tumor–related epilepsy, which is more common than in patients with high-grade glioma. Treatment for tumor-associated epilepsy usually comprises a combination of surgery, anti-epileptic drugs (AEDs), chemotherapy, and radiotherapy. Response to tumor-directed treatment is measured primarily by overall survival and progression-free survival. However, seizure frequency has been observed to respond to tumor-directed treatment with chemotherapy or radiotherapy. A review of the current literature regarding seizure assessment for low-grade glioma patients reveals a heterogeneous manner in which seizure response has been reported. There is a need for a systematic approach to seizure assessment and its influence on health-related quality-of-life outcomes in patients enrolled in low-grade glioma therapeutic trials. In view of the need to have an adjunctive metric of tumor response in these patients, a method of seizure assessment as a metric in brain tumor treatment trials is proposed. PMID:27651472

TH-E-202-02: The Use of Hypoxia PET Imaging for Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Humm, J.

2016-06-15

PET/CT is a very important imaging tool in the management of oncology patients. PET/CT has been applied for treatment planning and response evaluation in radiation therapy. This educational session will discuss: Pitfalls and remedies in PET/CT imaging for RT planning The use of hypoxia PET imaging for radiotherapy PET for tumor response evaluation The first presentation will address the issue of mis-registration between the CT and PET images in the thorax and the abdomen. We will discuss the challenges of respiratory gating and introduce an average CT technique to improve the registration for dose calculation and image-guidance in radiation therapy.more » The second presentation will discuss the use of hypoxia PET Imaging for radiation therapy. We will discuss various hypoxia radiotracers, the choice of clinical acquisition protocol (in particular a single late static acquisition versus a dynamic acquisition), and the compartmental modeling with different transfer rate constants explained. We will demonstrate applications of hypoxia imaging for dose escalation/de-escalation in clinical trials. The last presentation will discuss the use of PET/CT for tumor response evaluation. We will discuss anatomic response assessment vs. metabolic response assessment, visual evaluation and semi-quantitative evaluation, and limitations of current PET/CT assessment. We will summarize clinical trials using PET response in guiding adaptive radiotherapy. Finally, we will summarize recent advancements in PET/CT radiomics and non-FDG PET tracers for response assessment. Learning Objectives: Identify the causes of mis-registration of CT and PET images in PET/CT, and review the strategies to remedy the issue. Understand the basics of PET imaging of tumor hypoxia (radiotracers, how PET measures the hypoxia selective uptake, imaging protocols, applications in chemo-radiation therapy). Understand the basics of dynamic PET imaging, compartmental modeling and parametric images. Understand the basics of using FDG PET/CT for tumor response evaluation. Learn about recent advancement in PET/CT radiomics and non-FDG PET tracers for response assessment. This work was supported in part by the National Cancer Institute Grants R01CA172638.; W. Lu, This work was supported in part by the National Cancer Institute Grants R01CA172638.« less

Mathematical modelling of tumour volume dynamics in response to stereotactic ablative radiotherapy for non-small cell lung cancer

NASA Astrophysics Data System (ADS)

Tariq, Imran; Humbert-Vidan, Laia; Chen, Tao; South, Christopher P.; Ezhil, Veni; Kirkby, Norman F.; Jena, Rajesh; Nisbet, Andrew

2015-05-01

This paper reports a modelling study of tumour volume dynamics in response to stereotactic ablative radiotherapy (SABR). The main objective was to develop a model that is adequate to describe tumour volume change measured during SABR, and at the same time is not excessively complex as lacking support from clinical data. To this end, various modelling options were explored, and a rigorous statistical method, the Akaike information criterion, was used to help determine a trade-off between model accuracy and complexity. The models were calibrated to the data from 11 non-small cell lung cancer patients treated with SABR. The results showed that it is feasible to model the tumour volume dynamics during SABR, opening up the potential for using such models in a clinical environment in the future.

Non-standard radiotherapy fractionations delay the time to malignant transformation of low-grade gliomas.

PubMed

Henares-Molina, Araceli; Benzekry, Sebastien; Lara, Pedro C; García-Rojo, Marcial; Pérez-García, Víctor M; Martínez-González, Alicia

2017-01-01

Grade II gliomas are slowly growing primary brain tumors that affect mostly young patients. Cytotoxic therapies (radiotherapy and/or chemotherapy) are used initially only for patients having a bad prognosis. These therapies are planned following the "maximum dose in minimum time" principle, i. e. the same schedule used for high-grade brain tumors in spite of their very different behavior. These tumors transform after a variable time into high-grade gliomas, which significantly decreases the patient's life expectancy. In this paper we study mathematical models describing the growth of grade II gliomas in response to radiotherapy. We find that protracted metronomic fractionations, i.e. therapeutical schedules enlarging the time interval between low-dose radiotherapy fractions, may lead to a better tumor control without an increase in toxicity. Other non-standard fractionations such as protracted or hypoprotracted schemes may also be beneficial. The potential survival improvement depends on the tumor's proliferation rate and can be even of the order of years. A conservative metronomic scheme, still being a suboptimal treatment, delays the time to malignant progression by at least one year when compared to the standard scheme.

A Pilot Safety Study of Lenalidomide and Radiotherapy for Patients With Newly Diagnosed Glioblastoma Multiforme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Drappatz, Jan; Division of Cancer Neurology, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Wong, Eric T.

2009-01-01

Purpose: To define the maximum tolerated dose (MTD) of lenalidomide, an analogue of thalidomide with enhanced immunomodulatory and antiangiogenic properties and a more favorable toxicity profile, in patients with newly diagnosed glioblastoma multiforme (GBM) when given concurrently with radiotherapy. Patients and Methods: Patients with newly diagnosed GBM received radiotherapy concurrently with lenalidomide given for 3 weeks followed by a 1-week rest period and continued lenalidomide until tumor progression or unacceptable toxicity. Dose escalation occurred in groups of 6. Determination of the MTD was based on toxicities during the first 12 weeks of therapy. The primary endpoint was toxicity. Results: Twenty-threemore » patients were enrolled, of whom 20 were treated and evaluable for both toxicity and tumor response and 2 were evaluable for toxicity only. Common toxicities included venous thromboembolic disease, fatigue, and nausea. Dose-limiting toxicities were eosinophilic pneumonitis and transaminase elevations. The MTD for lenalidomide was determined to be 15 mg/m{sup 2}/d. Conclusion: The recommended dose for lenalidomide with radiotherapy is 15 mg/m{sup 2}/d for 3 weeks followed by a 1-week rest period. Venous thromboembolic complications occurred in 4 patients, and prophylactic anticoagulation should be considered.« less

An unusual case of diffuse Merkel cell carcinoma successfully treated with low dose radiotherapy.

PubMed

Chatzinasiou, Foteini; Papadavid, Euaggelia; Korkolopoulou, Penelope; Levidou, Georgia; Panayiotides, Ioannis; Theodoropoulos, Konstadinos; Pogka, Vasiliki; Asimakopoulos, Charalampos; Rigopoulos, Dimitrios

2015-01-01

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine carcinoma of the skin. MCC should be included in the diagnosis of a rapidly growing infiltrating mass and histology as well as laboratory investigations such as Merkel cell polyoma virus (MCPyV) detection are valuable in its diagnosis. We present an unusual case of giant MCC-positive MCPyV in a Greek woman located on the lower leg. Our patient is very unusual in terms of her extensive MCC and her rapid and complete response to radiotherapy. © 2015 Wiley Periodicals, Inc.

SU-D-207A-04: Use of Gradient Echo Plural Contrast Imaging (GEPCI) in MR-Guided Radiation Therapy: A Feasibility Study Targeting Brain Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai, B; Rao, Y; Tsien, C

Purpose: To implement the Gradient Echo Plural Contrast Imaging(GEPCI) technique in MRI-simulation for radiation therapy and assess the feasibility of using GEPCI images with advanced inhomogeneity correction in MRI-guided radiotherapy for brain treatment. Methods: An optimized multigradient-echo GRE sequence (TR=50ms;TE1=4ms;delta-TE=4ms;flip angle=300,11 Echoes) was developed to generate both structural (T1w and T2*w) and functional MRIs (field and susceptibility maps) from a single acquisition. One healthy subject (Subject1) and one post-surgical brain cancer patient (Subject2) were scanned on a Philips Ingenia 1.5T MRI used for radiation therapy simulation. Another healthy subject (Subject3) was scanned on a 0.35T MRI-guided radiotherapy (MR-IGRT) system (ViewRay).more » A voxel spread function (VSF) was used to correct the B0 inhomogeneities caused by surgical cavities and edema for Subject2. GEPCI images and standard radiotherapy planning MRIs for this patient were compared focusing the delineation of radiotherapy target region. Results: GEPCI brain images were successfully derived from all three subjects with scan times of <7 minutes. The images derived for Subjects1&2 demonstrated that GEPCI can be applied and combined into radiotherapy MRI simulation. Despite low field, T1-weighted and R2* images were successfully reconstructed for Subject3 and were satisfactory for contour and target delineation. The R2* distribution of grey matter (center=12,FWHM=4.5) and white matter (center=14.6, FWHM=2) demonstrated the feasibility for tissue segmentation and quantification. The voxel spread function(VSF) corrected surgical site related inhomogeneities for Subject2. R2* and quantitative susceptibility map(QSM) images for Subject2 can be used to quantitatively assess the brain structure response to radiation over the treatment course. Conclusion: We implemented the GEPCI technique in MRI-simulation and in MR-IGRT system for radiation therapy. The images demonstrated that it is feasible to adopt this technique in radiotherapy for structural delineation. The preliminary data also enable the opportunity for quantitative assessment of radiation response of the target region and normal tissue.« less

Influential factors in the response to salvage radiotherapy after radical prostatectomy.

PubMed

Algarra, R; Tienza, A; Hevia, M; Zudaire, J; Rosell, D; Robles, J E; Pascual, I

2014-12-01

To analyze the influential factors in the response in prostatectomized patients with subsequent biochemical relapse (BCR) and treated with salvage radiotherapy (RTP). We analyzed 313 patients with pT2/pT3 prostate cancer who were receiving salvage therapy due to biochemical relapse (from a series of 1,310 radical prostatectomies between 1989-2012). Of the 313 patients; 159 (50.8%) only received androgen deprivation (AD), 63 (20.1%) Radiotherapy (RTP) plus concomitant AD and 91 (29.1%) only RTP. Of these, 57 (62.6%) have maintained complete response and 34 (37.4%) had failure response with post-RTP BCR. Study of the group treated exclusively with salvage RTP. Ninety-one patients were treated with salvage RTP. Median follow-up was 6.4 years and median to recurrence 11 months. Post-RTP biochemical relapse-free survival (PRBRFS) was 68 ± 7% and 30 ± 10% in 5 to 10 years. Median PRBRFS was 7.3 years (6.3-8.3). Initial PSA (HR: 1.08; 95% CI: 1.01-1.1 P=.02) with best PSA cut-off point PSA>20 ng/ml (HR: 13.6; 95% CI: 2.1-86 P=.005) and PSA pre-RTP (HR: 1.9; 95% CI: 1.2-3.3; P=.009), best PSA cut-off point PSA preRTP 0.92 ng/ml (HR: 4.5; 95% CI: 1.3-15.6; P=.01) showed independent influence in the response in the multivariate study. PRBRFS at 5 years, 81 ± 9% versus 58 ± 9% with initial PSA <20 or >20 ng/ml (P=.03). PRBRFS at 5 years, 93 ± 5% versus 53 ± 10% according to PSA pre-RTP <0.9 or >0.9 ng/ml (P=.02). In patients treated with salvage RTP after radical prostatectomy, the preoperative PSA>20 ng/ml and PSA preRTP>0.92 ng/ml shows an independent influence on the response. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

CONCURRENT WHOLE BRAIN RADIOTHERAPY AND SHORT-COURSE CHLOROQUINE IN PATIENTS WITH BRAIN METASTASES: A PILOT TRIAL.

PubMed

Eldredge, Harriet Belding; Denittis, Albert; Duhadaway, James B; Chernick, Michael; Metz, Richard; Prendergast, George C

2013-09-01

The immune modulatory drug chloroquine (CQ) has been demonstrated to enhance survival following radiotherapy in patients with high-grade glioma in a clinical trial, but the efficacy in patients with brain metastases is unknown. We hypothesized that short-course CQ during whole brain radiotherapy (WBRT) would improve response to local therapy in patients with brain metastases. A prospective, single-cohort study was performed combining WBRT with concurrent CQ to assess both the feasibility of and intracranial response to combined therapy in patients with brain metastases. Safety, tolerability and overall survival of this combination was also examined, along with allelic status of IDO2 (indoleamine 2,3-dioxygenase 2), an immune modulatory enzyme inhibited by chloroquine that may affect survival outcomes. CQ therapy (250 mg by mouth daily) was initiated 1 week before WBRT (37.5 Gy in 2.5 Gy daily fractions) in patients with newly diagnosed brain metastases from biopsy-proven, primary lung, breast or ovarian solid tumors (n=20). The primary endpoint was radiologic response 3 months after combined CQ and WBRT therapy. Secondary endpoints included toxicity and overall survival. Patients were stratified by IDO2 allelic status. After a median clinical follow up of 5 months (range, 0.5-31), 16 patients were evaluable for radiologic response which was complete response in two patients, partial response in 13 patients and stable disease in one patient. There were no treatment-related grade≥3 toxicities or treatment interruption due to toxicity. Median and mean overall survival was 5.7 and 8.9 months, respectively (range, 0.8-31). A trend toward increased overall survival was observed in patients with wild-type IDO2 compared to patients with heterozygous or homozygous configurations that ablate IDO2 enzyme activity (10.4 mos vs. 4.1 mos.; p=0.07). WBRT with concurrent, short-course CQ is well tolerated in patients with brain metastases. The high intracranial disease control rate warrants additional study.

Value of radiotherapy for Peyronie's disease: presentation of 56 new case studies and review of the literature

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mira, J.G.; Chahbazian, C.M.; del Regato, J.A.

1980-02-01

Fifty-six patients with Peyronie's Disease who were treated with radiotherapy at Penrose Cancer Hospital were studied retrospectively. All were treated with orthovoltage, mainly with total dosages of 1000 to 1400 roentgens (from around 950 to 1330 rad), in 11 to 17 days. Penile induration was present in all patients; 87% had curvature of the penis during erection and 70% had pain during intercourse. After treatments, more than half the patients had complete resolution of pain. The overall response rate was 79%. The mean interval treatment-response was 2.8 months; 41% had already improved at the end of therapy or within onemore » month afterwards. Improvement of induration and penile deviation was less successful; there were almost no complete responders and about 40% had partial responses. Interval treatment-response was also longer (from 6 to 9 months). The size and location of the indurated placque did not influence response. The dosage, however, might influence the results; patients whose induration responded received a dose with a mean higher than non-responders. This difference was statistically significant. The duration of symptoms prior to treatment seems to be important. Eighty-one percent of responders had symptoms for less than five months; 76% of those with longer symptomatology did not benefit from irradiation. Failure by other methods of treatment did not preclude a response. Review of the literature shows that untreated patients have a benign course; a high percentage have eventual improvement or resolution of symptoms. However, spontaneous improvement occurs slowly and treatment seems to accelerate the process of recovery. Radiotherapy seems to be at least as successful as any other method of treatment. It should be recommended to patients who are troubled by their symptoms as a localized, painless, fast method of treatment, with no particular complications.« less

Assessment of the Changes in 9L and C6 Glioma pO2 by EPR Oximetry as a Prognostic Indicator of Differential Response to Radiotherapy

PubMed Central

Hou, Huagang; Mupparaju, Sriram P.; Lariviere, Jean P.; Hodge, Sassan; Gui, Jiang; Swartz, Harold M.; Khan, Nadeem

2013-01-01

Tumor hypoxia impedes the outcome of radiotherapy. As the extent of hypoxia in solid tumors varies during the course of radiotherapy, methods that can provide repeated assessment of tumor pO2 such as EPR oximetry may enhance the efficacy of radiotherapy by scheduling irradiations when the tumors are oxygenated. The repeated measurements of tumor pO2 may also identify responders, and thereby facilitate the design of better treatment plans for nonresponding tumors. We have investigated the temporal changes in the ectopic 9L and C6 glioma pO2 irradiated with single radiation doses less than 10 Gy by EPR oximetry. The 9L and C6 tumors were hypoxic with pO2 of approximately 5–9 mmHg. The pO2 of C6 tumors increased significantly with irradiation of 4.8–9.3 Gy. However, no change in the 9L tumor pO2 was observed. The irradiation of the oxygenated C6 tumors with a second dose of 4.8 Gy resulted in a significant delay in growth compared to hypoxic and 2 Gy × 5 treatment groups. The C6 tumors with an increase in pO2 of greater than 50% from the baseline of irradiation with 4.8 Gy (responders) had a significant tumor growth delay compared to nonresponders. These results indicate that the ectopic 9L and C6 tumors responded differently to radiotherapy. We propose that the repeated measurement of the oxygen levels in the tumors during radiotherapy can be used to identify responders and to design tumor oxygen guided treatment plans to improve the outcome. PMID:23391148

Phase I/II Study of Erlotinib Combined With Cisplatin and Radiotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herchenhorn, Daniel, E-mail: herchenhorn@hotmail.co; Dias, Fernando L.; Viegas, Celia M.P.

Purpose: Erlotinib, an oral tyrosine kinase inhibitor, is active against head-and-neck squamous cell carcinoma (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC. Methods and Materials: In this Phase I/II trial 100 mg/m{sup 2} of cisplatin was administered on Days 8, 29, and 50, and radiotherapy at 70 Gy was started on Day 8. During Phase I, the erlotinib dose was escalated (50 mg, 100 mg, and 150 mg) in consecutive cohorts of 3 patients, starting on Day 1 and continuingmore » during radiotherapy. Dose-limiting toxicity was defined as any Grade 4 event requiring radiotherapy interruptions. Phase II was initiated 8 weeks after the last Phase I enrollment. Results: The study accrued 9 patients in Phase I and 28 in Phase II; all were evaluable for efficacy and safety. No dose-limiting toxicity occurred in Phase I, and the recommended Phase II dose was 150 mg. The most frequent nonhematologic toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and in-field dermatitis, acneiform rash, and diarrhea. Of the 31 patients receiving a 150-mg daily dose of erlotinib, 23 (74%; 95% confidence interval, 56.8%-86.3%) had a complete response, 3 were disease free after salvage surgery, 4 had inoperable residual disease, and 1 died of sepsis during treatment. With a median 37 months' follow-up, the 3-year progression-free and overall survival rates were 61% and 72%, respectively. Conclusions: This combination appears safe, has encouraging activity, and deserves further studies in locally advanced HNSCC.« less

In vivo dosimetry in UK external beam radiotherapy: current and future usage.

PubMed

MacDougall, Niall D; Graveling, Michael; Hansen, Vibeke N; Brownsword, Kevin; Morgan, Andrew

2017-04-01

Towards Safer Radiotherapy recommended that radiotherapy (RT) centres should have protocols in place for in vivo dosimetry (IVD) monitoring at the beginning of patient treatment courses (Donaldson S. Towards safer radiotherapy. R Coll Radiol 2008). This report determines IVD implementation in the UK in 2014, the methods used and makes recommendations on future use. Evidence from peer-reviewed journals was used in conjunction with the first survey of UK RT centre IVD practice since the publication of Towards Safer Radiotherapy. In March 2014, profession-specific questionnaires were sent to radiographer, clinical oncologist and physics staff groups in each of the 66 UK RT centres. Response rates from each group were 74%, 45% and 74%, respectively. 73% of RT centres indicated that they performed IVD. Diodes are the most popular IVD device. Thermoluminescent dosimeter (TLD) is still in use in a number of centres but not as a sole modality, being used in conjunction with diodes and/or electronic portal imaging device (EPID). The use of EPID dosimetry is increasing and is considered of most potential value for both geometric and dosimetric verification. Owing to technological advances, such as electronic data transfer, independent monitor unit checking and daily image-guided radiotherapy, the overall risk of adverse treatment events in RT has been substantially reduced. However, the use of IVD may prevent a serious radiation incident. Point dose IVD is not considered suited to the requirements of verifying advanced RT techniques, leaving EPID dosimetry as the current modality likely to be developed as a future standard. Advances in knowledge: An updated perspective on UK IVD use and provision of professional guidelines for future implementation.

In vivo dosimetry in UK external beam radiotherapy: current and future usage

PubMed Central

Graveling, Michael; Hansen, Vibeke N; Brownsword, Kevin; Morgan, Andrew

2017-01-01

Objective: Towards Safer Radiotherapy recommended that radiotherapy (RT) centres should have protocols in place for in vivo dosimetry (IVD) monitoring at the beginning of patient treatment courses (Donaldson S. Towards safer radiotherapy. R Coll Radiol 2008). This report determines IVD implementation in the UK in 2014, the methods used and makes recommendations on future use. Methods: Evidence from peer-reviewed journals was used in conjunction with the first survey of UK RT centre IVD practice since the publication of Towards Safer Radiotherapy. In March 2014, profession-specific questionnaires were sent to radiographer, clinical oncologist and physics staff groups in each of the 66 UK RT centres. Results: Response rates from each group were 74%, 45% and 74%, respectively. 73% of RT centres indicated that they performed IVD. Diodes are the most popular IVD device. Thermoluminescent dosimeter (TLD) is still in use in a number of centres but not as a sole modality, being used in conjunction with diodes and/or electronic portal imaging device (EPID). The use of EPID dosimetry is increasing and is considered of most potential value for both geometric and dosimetric verification. Conclusion: Owing to technological advances, such as electronic data transfer, independent monitor unit checking and daily image-guided radiotherapy, the overall risk of adverse treatment events in RT has been substantially reduced. However, the use of IVD may prevent a serious radiation incident. Point dose IVD is not considered suited to the requirements of verifying advanced RT techniques, leaving EPID dosimetry as the current modality likely to be developed as a future standard. Advances in knowledge: An updated perspective on UK IVD use and provision of professional guidelines for future implementation. PMID:28205452

Gender, body weight, disease activity, and previous radiotherapy influence the response to pegvisomant.

PubMed

Parkinson, Craig; Burman, Pia; Messig, Michael; Trainer, Peter J

2007-01-01

To effectively normalize IGF-I in patients with acromegaly, various covariates may affect dosing and plasma concentrations of pegvisomant. We assessed whether sex, age, weight, and previous radiotherapy influence dosing of pegvisomant in patients with active disease. Data from 69 men and 49 women participating in multicenter, open-label trials of pegvisomant were retrospectively evaluated using multiple regression techniques. Sixty-nine subjects (39 men, 30 women) had undergone external beam pituitary radiotherapy. Serum IGF-I was at least 30% above age-related upper limit of normal in all patients at study entry. After a loading dose of pegvisomant (80 mg), patients were commenced on 10 mg/d. Pegvisomant dose was adjusted by 5 mg every eighth week until serum IGF-I was normalized. At baseline, men had significantly higher mean serum IGF-I levels than women despite similar GH levels. After treatment with pegvisomant, IGF-I levels were similar in men and women. A significant correlation between baseline GH, IGF-I, body weight, and the dose of pegvisomant required to normalize serum IGF-I was observed (all P < 0.001). Women required an average of 0.04 mg/kg more pegvisomant than men and a mean weight-corrected dose of 19.2 mg/d to normalize serum IGF-I [14.5 mg/d (men); P < 0.001]. Patients treated with radiotherapy required less pegvisomant to normalize serum IGF-I despite similar baseline GH/IGF-I levels (15.2 vs. 18.5 mg/d for no previous radiotherapy; P = 0.002). Sex, body weight, previous radiotherapy, and baseline GH/IGF-I influence the dose of pegvisomant required to normalize serum IGF-I in patients with active acromegaly.

Esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer: frequency and prediction.

PubMed

Atsumi, Kazushige; Shioyama, Yoshiyuki; Arimura, Hidetaka; Terashima, Kotaro; Matsuki, Takaomi; Ohga, Saiji; Yoshitake, Tadamasa; Nonoshita, Takeshi; Tsurumaru, Daisuke; Ohnishi, Kayoko; Asai, Kaori; Matsumoto, Keiji; Nakamura, Katsumasa; Honda, Hiroshi

2012-04-01

To determine clinical factors for predicting the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. The study group consisted of 109 patients with esophageal cancer of T1-4 and Stage I-III who were treated with definitive radiotherapy and achieved a complete response of their primary lesion at Kyushu University Hospital between January 1998 and December 2007. Esophageal stenosis was evaluated using esophagographic images within 3 months after completion of radiotherapy. We investigated the correlation between esophageal stenosis after radiotherapy and each of the clinical factors with regard to tumors and therapy. For validation of the correlative factors for esophageal stenosis, an artificial neural network was used to predict the esophageal stenotic ratio. Esophageal stenosis tended to be more severe and more frequent in T3-4 cases than in T1-2 cases. Esophageal stenosis in cases with full circumference involvement tended to be more severe and more frequent than that in cases without full circumference involvement. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. In the multivariate analysis, T stage, extent of involved circumference, and wall thickness of the tumor region were significantly correlated to esophageal stenosis (p = 0.031, p < 0.0001, and p = 0.0011, respectively). The esophageal stenotic ratio predicted by the artificial neural network, which learned these three factors, was significantly correlated to the actual observed stenotic ratio, with a correlation coefficient of 0.864 (p < 0.001). Our study suggested that T stage, extent of involved circumference, and esophageal wall thickness of the tumor region were useful to predict the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

Specific recommendations for accurate and direct use of PET-CT in PET guided radiotherapy for head and neck sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, C. M., E-mail: christopher.thomas@gstt.nhs.uk; Convery, D. J.; Greener, A. G.

2014-04-15

Purpose: To provide specific experience-based guidance and recommendations for centers wishing to develop, validate, and implement an accurate and efficient process for directly using positron emission tomography-computed tomography (PET-CT) for the radiotherapy planning of head and neck cancer patients. Methods: A PET-CT system was modified with hard-top couch, external lasers and radiotherapy immobilization and indexing devices and was subject to a commissioning and quality assurance program. PET-CT imaging protocols were developed specifically for radiotherapy planning and the image quality and pathway tested using phantoms and five patients recruited into an in-house study. Security and accuracy of data transfer was testedmore » throughout the whole data pathway. The patient pathway was fully established and tested ready for implementation in a PET-guided dose-escalation trial for head and neck cancer patients. Results: Couch deflection was greater than for departmental CT simulator machines. An area of high attenuation in the couch generated image artifacts and adjustments were made accordingly. Using newly developed protocols CT image quality was suitable to maintain delineation and treatment accuracy. Upon transfer of data to the treatment planning system a half pixel offset between PET and CT was observed and corrected. By taking this into account, PET to CT alignment accuracy was maintained below 1 mm in all systems in the data pathway. Transfer of structures delineated in the PET fusion software to the radiotherapy treatment planning system was validated. Conclusions: A method to perform direct PET-guided radiotherapy planning was successfully validated and specific recommendations were developed to assist other centers. Of major concern is ensuring that the quality of PET and CT data is appropriate for radiotherapy treatment planning and on-treatment verification. Couch movements can be compromised, bore-size can be a limitation for certain immobilization techniques, laser positioning may affect setup accuracy and couch deflection may be greater than scanners dedicated to radiotherapy. The full set of departmental commissioning and routine quality assurance tests applied to radiotherapy CT simulators must be carried out on the PET-CT scanner. CT image quality must be optimized for radiotherapy planning whilst understanding that the appearance will differ between scanners and may affect delineation. PET-CT quality assurance schedules will need to be added to and modified to incorporate radiotherapy quality assurance. Methods of working for radiotherapy and PET staff will change to take into account considerations of both parties. PET to CT alignment must be subject to quality control on a loaded and unloaded couch preferably using a suitable emission phantom, and tested throughout the whole data pathway. Data integrity must be tested throughout the whole pathway and a system included to verify that delineated structures are transferred correctly. Excellent multidisciplinary team communication and working is vital, and key staff members on both sides should be specifically dedicated to the project. Patient pathway should be clearly devised to optimize patient care and the resources of all departments. Recruitment of a cohort of patients into a methodology study is valuable to test the quality assurance methods and pathway.« less

Solid Tumors After Chemotherapy or Surgery for Testicular Nonseminoma: A Population-Based Study

PubMed Central

Fung, Chunkit; Fossa, Sophie D.; Milano, Michael T.; Oldenburg, Jan; Travis, Lois B.

2013-01-01

Purpose Increased risks of solid tumors after older radiotherapy strategies for testicular cancer (TC) are well established. Few population-based studies, however, focus on solid cancer risk among survivors of TC managed with nonradiotherapy approaches. We quantified the site-specific risk of solid cancers among testicular nonseminoma patients treated in the modern era of cisplatin-based chemotherapy, without radiotherapy. Patients and Methods Standardized incidence ratios (SIRs) for solid tumors were calculated for 12,691 patients with testicular nonseminoma reported to the population-based Surveillance, Epidemiology, and End Results program (1980 to 2008) and treated initially with either chemotherapy (n = 6,013) or surgery (n = 6,678) without radiotherapy. Patients accrued 116,073 person-years of follow-up. Results Two hundred ten second solid cancers were observed. No increased risk followed surgery alone (SIR, 0.93; 95% CI, 0.76 to 1.14; n = 99 solid cancers), whereas significantly increased 40% excesses (SIR, 1.43; 95% CI, 1.18 to 1.73; n = 111 solid cancers) occurred after chemotherapy. Increased risks of solid cancers after chemotherapy were observed in most follow-up periods (median latency, 12.5 years), including more than 20 years after treatment (SIR, 1.54; 95% CI, 0.96 to 2.33); significantly increased three- to seven-fold risks occurred for cancers of the kidney (SIR, 3.37; 95% CI, 1.79 to 5.77), thyroid (SIR, 4.40; 95% CI, 2.19 to 7.88), and soft tissue (SIR, 7.49; 95% CI, 3.59 to 13.78). Conclusion To our knowledge, this is the first large population-based series reporting significantly increased risks of solid cancers among patients with testicular nonseminoma treated in the modern era of cisplatin-based chemotherapy. Subsequent analytic studies should focus on the evaluation of dose-response relationships, types of solid cancers, latency patterns, and interactions with other possible factors, including genetic susceptibility. PMID:24043737

SU-E-T-128: Applying Failure Modes and Effects Analysis to a Risk-Based Quality Management for Stereotactic Radiosurgery in Brazil

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teixeira, F; Universidade do Estado do Rio de Janeiro, Rio De Janeiro, RJ; Almeida, C de

2015-06-15

Purpose: The goal of the present work was to evaluate the process maps for stereotactic radiosurgery (SRS) treatment at three radiotherapy centers in Brazil and apply the FMEA technique to evaluate similarities and differences, if any, of the hazards and risks associated with these processes. Methods: A team, consisting of professionals from different disciplines and involved in the SRS treatment, was formed at each center. Each team was responsible for the development of the process map, and performance of FMEA and FTA. A facilitator knowledgeable in these techniques led the work at each center. The TG100 recommended scales were usedmore » for the evaluation of hazard and severity for each step for the major process “treatment planning”. Results: Hazard index given by the Risk Priority Number (RPN) is found to range from 4–270 for various processes and the severity (S) index is found to range from 1–10. The RPN values > 100 and severity value ≥ 7 were chosen to flag safety improvement interventions. Number of steps with RPN ≥100 were found to be 6, 59 and 45 for the three centers. The corresponding values for S ≥ 7 are 24, 21 and 25 respectively. The range of RPN and S values for each center belong to different process steps and failure modes. Conclusion: These results show that interventions to improve safety is different for each center and it is associated with the skill level of the professional team as well as the technology used to provide radiosurgery treatment. The present study will very likely be a model for implementation of risk-based prospective quality management program for SRS treatment in Brazil where currently there are 28 radiotherapy centers performing SRS. A complete FMEA for SRS for these three radiotherapy centers is currently under development.« less

MO-D-BRF-01: Pediatric Treatment Planning II: The PENTEC Report On Normal Tissue Complications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Constine, L; Hodgson, D; Bentzen, S

With advances in multimodality therapy, childhood cancer cure rates approach 80%. However, both radiotherapy and chemotherapy may cause debilitating or even fatal ‘late effects’ that are critical to understand, mitigate, or prevent. QUANTEC identified the uncertainties relating to side-effects of adult treatments, but this is more complicated for children in whom a mosaic of tissues develops at different rates and temporal sequences. Childhood cancer survivors have long life expectancy and may develop treatmentinduced secondary cancers and severe organ/tissue injury decades after treatment. Collaborative long-term observational studies and clinical research programs for survivors of pediatric and adolescent cancer provide some dose-responsemore » data for follow-up periods exceeding 40 years. Data analysis is challenging due to the influence of both therapeutic and developmental variables. PENTEC is a group of radiation oncologists, pediatric oncologists, subsepcialty physicians, medical physicists, biomathematic modelers/statisticians, and epidemiologists charged with conducting a critical synthesis of existing literature aiming to: critically analyze radiation dose-volume effects on normal tissue tolerances as a function of age/development in pediatric cancer patients in order to inform treatment planning and improve outcomes for survivors; describe relevant physics issues specific to pediatric radiotherapy; propose dose-volumeoutcome reporting standards to improve the knowledge base to inform future treatment guidelines. PENTEC has developed guidelines for systematic literature reviews, data extraction tolls and data analysis. This education session will discuss:1. Special considerations for normal tissue radiation response of children/adolescents, e.g. the interplay between development and radiotherapy effects.2. Epidemiology of organ/tissue injuries and secondary cancers.3. Exploration of dose-response differences between children and adults4. Methodology for literature review, data mining of outcomes databases, and NTCP or longitudinal modeling of doseresponse. 5. PENTEC goals and timetable. Learning Objectives: Understand important differences between normal tissue effects of radiation therapy in pediatric and adult patients. Be able to identify situations where there is ‘interplay’ between organ development and radiation-induced complications. Identify methods to systematically extract quantitative dose-volumeresponse relationships from existing outcomes databases. Provide guidance for the medical physicist to properly understand, implement, guide and control contemporary technology and applications in pediatric radiation oncology.« less

Tumor spheroid model for the biologically targeted radiotherapy of neuroblastoma micrometastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walker, K.A.; Mairs, R.; Murray, T.

Neuroblastoma is a pediatric malignancy with a poor prognosis at least partly attributable to an early pattern of dissemination. New approaches to treatment of micrometastases include targeted radiotherapy using radiolabeled antibodies or molecules which are taken up preferentially by tumor cells. Multicellular tumor spheroids (MTS) resemble micrometastases during the avascular phase of their development. A human neuroblastoma cell line (NBl-G) was grown as MTS and incubated briefly with a radiolabeled monoclonal antibody ({sup 131}I-UJ13A) directed against neuroectodermal antigens. Spheroid response was evaluated in terms of regrowth delay or proportion sterilized. A dose-response relationship was demonstrated in terms of {sup 131}Imore » activity or duration of incubation. Control experiments using unlabeled UJ13A, radiolabeled nonspecific antibody (T2.10), radiolabeled human serum albumin, and radiolabeled sodium iodide showed these to be relatively ineffective compared to {sup 131}I-UJ13A. The cell line NBl-G grown as MTS has also been found to preferentially accumulate the radiolabeled catecholamine precursor molecule m-({sup 131}I)iodobenzylguanidine compared to cell lines derived from other tumor types. NBl-G cells grown as MTS provide a promising laboratory model for targeted radiotherapy of neuroblastoma micrometastases using radiolabeled antibodies or m-iodobenzylguanidine.« less

Oncology in Cambodia.

PubMed

Eav, S; Schraub, S; Dufour, P; Taisant, D; Ra, C; Bunda, P

2012-01-01

Cambodia, a country of 14 million inhabitants, was devastated during the Khmer Rouge period and thereafter. The resources of treatment are rare: only one radiotherapy department, renovated in 2003, with an old cobalt machine; few surgeons trained to operate on cancer patients; no hematology; no facilities to use intensive chemotherapy; no nuclear medicine department and no palliative care unit. Cervical cancer incidence is one of the highest in the world, while in men liver cancer ranks first (20% of all male cancers). Cancers are seen at stage 3 or 4 for 70% of patients. There is no prevention program - only a vaccination program against hepatitis B for newborns - and no screening program for cervical cancer or breast cancer. In 2010, oncology, recognized as a full specialty, was created to train the future oncologists on site at the University of Phnom Penh. A new National Cancer Center will be built in 2013 with modern facilities for radiotherapy, medical oncology, hematology and nuclear medicine. Cooperation with foreign countries, especially France, and international organizations has been established and is ongoing. Progress is occurring slowly due to the shortage of money for Cambodian institutions and the lay public. Copyright © 2012 S. Karger AG, Basel.

Application of biological effective dose (BED) to estimate the duration of symptomatic relief and repopulation dose equivalent in palliative radiotherapy and chemotherapy.

PubMed

Jones, Bleddyn; Cominos, Matilda; Dale, Roger G

2003-03-01

To investigate the potential for mathematic modeling in the assessment of symptom relief in palliative radiotherapy and cytotoxic chemotherapy. The linear quadratic model of radiation effect with the overall treatment time and the daily dose equivalent of repopulation is modified to include the regrowth time after completion of therapy. The predicted times to restore the original tumor volumes after treatment are dependent on the biological effective dose (BED) delivered and the repopulation parameter (K); it is also possible to estimate K values from analysis of palliative treatment response durations. Hypofractionated radiotherapy given at a low total dose may produce long symptom relief in slow-growing tumors because of their low alpha/beta ratios (which confer high fraction sensitivity) and their slow regrowth rates. Cancers that have high alpha/beta ratios (which confer low fraction sensitivity), and that are expected to repopulate rapidly during therapy, are predicted to have short durations of symptom control. The BED concept can be used to estimate the equivalent dose of radiotherapy that will achieve the same duration of symptom relief as palliative chemotherapy. Relatively simple radiobiologic modeling can be used to guide decision-making regarding the choice of the most appropriate palliative schedules and has important implications in the design of radiotherapy or chemotherapy clinical trials. The methods described provide a rationalization for treatment selection in a wide variety of tumors.

Phase I Study of Accelerated Conformal Radiotherapy for Stage I Non–Small-Cell Lung Cancer in Patients With Pulmonary Dysfunction: CALGB 39904

PubMed Central

Bogart, Jeffrey A.; Hodgson, Lydia; Seagren, Stephen L.; Blackstock, A. William; Wang, Xiaofei; Lenox, Robert; Turrisi, Andrew T.; Reilly, John; Gajra, Ajeet; Vokes, Everett E.; Green, Mark R.

2010-01-01

Purpose The optimal treatment for medically inoperable stage I non–small-cell lung cancer (NSCLC) has not been defined. Patients and Methods Cancer and Leukemia Group B trial 39904 prospectively assessed accelerated, once-daily, three-dimensional radiotherapy for early-stage NSCLC. The primary objectives were to define the maximally accelerated course of conformal radiotherapy and to describe the short-term and long-term toxicity of therapy. Entry was limited to patients with clinical stage T1N0 or T2N0 NSCLC (< 4 cm) and pulmonary dysfunction. The nominal total radiotherapy dose remained at 70 Gy, while the number of daily fractions in each successive cohort was reduced. Results Thirty-nine eligible patients were accrued (eight patients each on cohorts 1 to 4 and seven patients on cohort 5) between January 2001 and July 2005. One grade 3 nonhematologic toxicity was observed in both cohort 3 (dyspnea) and cohort 4 (pain). The major response rate was 77%. After a median follow-up time of 53 months, the actuarial median survival time of all eligible patients was 38.5 months. Local relapse was observed in three patients. Conclusion Accelerated conformal radiotherapy was well tolerated in a high-risk population with clinical stage I NSCLC. Outcomes are comparable to prospective reports of alternative therapies, including stereotactic body radiation therapy and limited resection, with less apparent severe toxicity. Further investigation of this approach is warranted. PMID:19933904

SU-F-T-243: Major Risks in Radiotherapy. A Review Based On Risk Analysis Literature

DOE Office of Scientific and Technical Information (OSTI.GOV)

López-Tarjuelo, J; Guasp-Tortajada, M; Iglesias-Montenegro, N

Purpose: We present a literature review of risk analyses in radiotherapy to highlight the most reported risks and facilitate the spread of this valuable information so that professionals can be aware of these major threats before performing their own studies. Methods: We considered studies with at least an estimation of the probability of occurrence of an adverse event (O) and its associated severity (S). They cover external beam radiotherapy, brachytherapy, intraoperative radiotherapy, and stereotactic techniques. We selected only the works containing a detailed ranked series of elements or failure modes and focused on the first fully reported quartile as much.more » Afterward, we sorted the risk elements according to a regular radiotherapy procedure so that the resulting groups were cited in several works and be ranked in this way. Results: 29 references published between 2007 and February 2016 were studied. Publication trend has been generally rising. The most employed analysis has been the Failure mode and effect analysis (FMEA). Among references, we selected 20 works listing 258 ranked risk elements. They were sorted into 31 groups appearing at least in two different works. 11 groups appeared in at least 5 references and 5 groups did it in 7 or more papers. These last sets of risks where choosing another set of images or plan for planning or treating, errors related with contours, errors in patient positioning for treatment, human mistakes when programming treatments, and planning errors. Conclusion: There is a sufficient amount and variety of references for identifying which failure modes or elements should be addressed in a radiotherapy department before attempting a specific analysis. FMEA prevailed, but other studies such as “risk matrix” or “occurrence × severity” analyses can also lead professionals’ efforts. Risk associated with human actions ranks very high; therefore, they should be automated or at least peer-reviewed.« less

Clinical radiotherapy audits in Belgium, 2011-2014.

PubMed

Scalliet, P G M

2015-10-01

Systematic clinical radiotherapy audits have been introduced in Belgium in 2011, as part of the Federal Cancer Plan. This is in compliance with article 11 of the 97/43 Council directive of Euratom states, translated into the Belgian legislation by royal decree in 2002. The principle of clinical audits has thus been part of the federal legal requirements for more than 10 years. However, its application had to wait for the development of a practical approach: what authority will audit, who will be the auditors, along which methodology, at what frequency, etc. Since 2002, the Federal College of Radiotherapy has the mission to monitor quality of radiotherapy at large. It was therefore decided after discussions with the relevant administration at the Ministry of Health and the Federal Agency for Nuclear Control that the College would practically organise the audits. Early in the 2000s, the IAEA developed a manual for comprehensive audits, as a tool for quality improvement. Auditors were professionals of the domain and the audit visit took the form of a peer review. Great care was taken to assemble an audit party able to cover all aspects of clinical radiotherapy with a radiation oncologist, a medical physicist, a radiation therapist and, on demand, a quality officer. The IAEA manual contains a series of questionnaires to be prepared by the audited centre in advance (pre-audit and self-assessment), indicating what specific areas the auditors would assess. It is also a template for the auditors, ensuring that no area is left aside or forgotten during the site visit. The report, at the end of the visit, is drafted according to a specific report template, also developed by IAEA. Several members of the Belgian radiotherapy community have developed their auditor's skills by participating to the IAEA audit program; they are the core of the auditor Belgian team. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Individualization of radiotherapy in breast cancer patients: possible usefulness of a DNA damage assay to measure normal cell radiosensitivity.

PubMed

Ruiz de Almodóvar, José Mariano; Guirado, Damian; Isabel Núñez, María; López, Escarlata; Guerrero, Rosario; Valenzuela, María Teresa; Villalobos, Mercedes; del Moral, Rosario

2002-03-01

The purpose of this study was to determine whether the distribution of sensitivities in breast cancer patients, measured using a DNA damage assay on lymphocytes, is likely to provide sufficient discrimination to enable the reliable identification of patients with abnormal sensitivities. Radiosensitivity (x) was assessed in 226 samples of lymphocytes from unselected women with breast cancer and was quantified as the initial number of DNA double-strand breaks (dsb) induced per Gy and per DNA unit (200 Mbp). The existence of an inter-individual variation in the parameter (x) is described through the range (0.40-4.72 dsb/Gy/DNA unit) of values found, which have been fitted to the mathematical model defined by the log-normal distribution (mu = 0.42+/-0.03; sigma = 0.52+/-0.03; R(2)=0.9475). A total of 189 patients received radiotherapy after surgical treatment. Among them, we have detected 15 patients who developed severe skin reactions and we have compared their radiosensitivity values with the rest of patients treated. Our results suggest that DNA initial damage measured on lymphocytes offers an approach to predict the acute response of human normal tissues prior to radiotherapy. Values of x higher than 3.20 dsb/Gy/DNA unit theoretically should correspond to the highly radio-sensitive patients. Using the experimental results, we have calculated the strength of the test by means of the area under the receiver operator characteristic curves (A(Z)) to determine whether the radiosensitivity assay can discriminate between patients according to their radiation response. The value found (A(Z)=0.675+/-0.072) is indicative of a fair-poor discriminating capacity of the test to identify the patients with higher risk of developing a severe acute reaction during the radiotherapy treatment.

Long-Term Follow-Up of Dose-Adapted and Reduced-Field Radiotherapy With or Without Chemotherapy for Central Nervous System Germinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jensen, Ashley W.; Issa Laack, Nadia N., E-mail: laack.nadia@mayo.ed; Buckner, Jan C.

Purpose: To update our institutional experience with neoadjuvant chemotherapy and minimized radiotherapy vs. radiation monotherapy for intracranial germinoma. Methods and Materials: We retrospectively reviewed records of 59 patients with diagnosis of primary intracranial germinoma between 1977 and 2007. Treatment was irradiation alone or neoadjuvant platinum-based chemotherapy and local irradiation (initial tumor plus margin) for patients with localized complete response and reduced-dose craniospinal irradiation for others. Results: For the chemoradiotherapy group (n = 28), median follow-up was 7 years. No patient died. The freedom from progression (FFP) rate was 88% at 5 years and 80% at 10 years. In 4 patients,more » disease recurred 1.1 to 6.8 years after diagnosis. All were young male patients who received 30.6 Gy to local fields after complete response to chemotherapy. The FFP rate was 88% for local irradiation vs. 100% for more extensive fields (p = .06). For the radiotherapy-alone group (n = 31), median follow-up was 15 years. Overall and disease-free survival rates were 93% and 93% at 5 years and 90% and 87% at 15 years. In 5 patients, disease recurred 1.1 to 4.9 years after diagnosis. Most patients in this group were young men 18 to 23 years of age with suprasellar primary disease treated with about 50 Gy to local fields. The FFP rate was 44% for local irradiation vs. 100% for more extensive fields (p < .01). Conclusions: The addition of neoadjuvant chemotherapy to local-field radiotherapy reduced central nervous system cancer recurrence when high-risk patients were excluded by thorough pretreatment staging. There was trend toward improved central nervous system tumor control when larger fields (whole brain, whole ventricle, or craniospinal axis) were used.« less

Phase II Study of Oral S-1 and Concurrent Radiotherapy in Patients With Unresectable Locally Advanced Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sudo, Kentaro, E-mail: kentarosudo9@yahoo.co.j; Yamaguchi, Taketo; Ishihara, Takeshi

2011-05-01

Purpose: S-1 is an oral fluoropyrimidine derivative that has demonstrated favorable antitumor activity in patients with metastatic pancreatic cancer. The aim of this study was to evaluate safety and efficacy of S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Methods and Materials: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day at a dose of 80 mg/m{sup 2}/day from day 1 to 14 and 22 to 35. Two weeksmore » after the completion of chemoradiotherapy, maintenance chemotherapy with S-1 was administered for 28 days every 6 weeks until progression. Results: Thirty-four patients were enrolled in this study. The most common Grade 3 toxicities during chemoradiotherapy were anorexia (24%) and nausea (12%). The overall response rate was 41% (95% confidence interval, 25%-58%) and overall disease control rate (partial response plus stable disease) was 97%. More than 50% decrease in serum CA 19-9 was seen in 27 of 29 evaluable patients (93%). The median progression-free survival was 8.7 months. The median overall survival and 1-year survival rate were 16.8 months and 70.6%, respectively. Conclusions: Oral S-1 and concurrent radiotherapy exerted a promising antitumor activity with acceptable toxicity in patients with locally advanced pancreatic cancer. This combination therapy seems to be an attractive alternative to conventional chemoradiotherapy using 5-fluorouracil infusion.« less

Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin’s lymphoma: a systematic review

PubMed Central

Herbst, Christine; Rehan, Fareed A.; Brillant, Corinne; Bohlius, Julia; Skoetz, Nicole; Schulz, Holger; Monsef, Ina; Specht, Lena; Engert, Andreas

2010-01-01

Combined modality treatment (CMT) of chemotherapy followed by localized radiotherapy is standard treatment for patients with early stage Hodgkin’s lymphoma. However, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication. We thus performed a systematic review with meta-analysis of randomized controlled trials comparing chemotherapy alone with CMT in patients with early stage Hodgkin’s lymphoma with respect to response rate, tumor control and overall survival (OS). We searched Medline, EMBASE and the Cochrane Library as well as conference proceedings from January 1980 to February 2009 for randomized controlled trials comparing chemotherapy alone versus the same chemotherapy regimen plus radiotherapy. Progression free survival and similar outcomes were analyzed together as tumor control. Effect measures used were hazard ratios for OS and tumor control as well as relative risks for complete response (CR). Meta-analyses were performed using RevMan5. Five randomized controlled trials involving 1,245 patients were included. The hazard ratio (HR) was 0.41 (95% confidence interval (CI) 0.25 to 0.66) for tumor control and 0.40 (95% CI 0.27 to 0.59) for OS for patients receiving CMT compared to chemotherapy alone. CR rates were similar between treatment groups. In sensitivity analyses another 6 trials were included that did not fulfill the inclusion criteria of our protocol but were considered relevant to the topic. These trials underlined the results of the main analysis. In conclusion, adding radiotherapy to chemotherapy improves tumor control and OS in patients with early stage Hodgkin’s lymphoma. PMID:19951972

Neoadjuvant radiotherapy with or without chemotherapy followed by extrafascial hysterectomy for locally advanced endometrial cancer clinically extending to the cervix or parametria.

PubMed

Vargo, John A; Boisen, Michelle M; Comerci, John T; Kim, Hayeon; Houser, Christopher J; Sukumvanich, Paniti; Olawaiye, Alexander B; Kelley, Joseph L; Edwards, Robert P; Huang, Marilyn; Courtney-Brooks, Madeleine; Beriwal, Sushil

2014-11-01

For locally-advanced uterine cancer clinically extending to the cervix, two treatment paradigms exist: surgical staging radical hysterectomy with tailored adjuvant therapy or neoadjuvant therapy followed by a less extensive simple hysterectomy. Currently, insufficient data exists to guide consensus guidelines and practical application of preoperative radiotherapy. Retrospective IRB approved cohort study from 1999 to 2014 of 36 endometrial cancer patients with clinical involvement of cervix±parametria treated with neoadjuvant external beam radiotherapy (45-50.4Gy in 25-28 fractions) and image-based HDR brachytherapy (5-5.5Gy times 3-4 fractions)±chemotherapy followed by extrafascial hysterectomy performed at a median of 6weeks after radiotherapy. All patients had clinical cervical extension, 50% also had parametria extension, and 31% had nodal involvement. At the time of surgery 91% had no clinical cervical involvement, 58% had no pathologic cervical involvement, and all had margin negative resection. The pathologic complete response rate was 24%. Median follow-up from the time of surgery was 20months (range: 0-153). The 3-year local control, regional control, distant control, disease free survival and overall survival rates were 96%, 89%, 84%, 73%, and 100%. The 3-year rate of grade 3 complications was 11%, with no grade 4+ toxicity. Neoadjuvant radiation therapy±chemotherapy followed by extrafascial hysterectomy appears to be a viable option for patients with endometrial cancer clinically extending to the cervix and parametria. The HDR brachytherapy schema of 5-5.5Gy times 3-4 fractions, for a cumulative EQD2 of 60-70Gy, is well tolerated with high rates of clinical and pathological response. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinical Study on Lobaplatin Combined with 5-Fu and Concurrent Radiotherapy in Treating Patients with Inoperable Esophageal Cancer.

PubMed

Jia, Xiao-Jing; Huang, Jing-Zi

2015-01-01

To investigate short- and long-term treatment effects and side reactions of lobaplatin plus 5-Fu combined and concurrent radiotherapy in treating patients with inoperable middle-advanced stage esophageal cancer. Sixty patients with middle-advanced stage esophageal squamous cell cancer were retrospectively analyzed. All patients were administered lobaplatin (50 mg intravenously) for 2 h on day 1, and 5-Fu (500 mg/m2) injected intravenously from day 1 to 5 for 1 cycle, in an interval of 21 days for totally 4 cycles. At the same time, late-course accelerated hyperfractionated three-dimensional conformal radiotherapy was performed. Patients were firstly treated with conventional fractionated irradiation (1.8 Gy/d, 5 times/week, a total of 23 treatments, and DT41.4 Gy), and then treated with accelerated hyperfractionated irradiation (1.5 Gy, 2 times/d, a total of 27 Gy in 9 days, an entire course of 6-7 weeks, and DT 68.4 Gy). All patients completed treatment, including 10 complete response (CR), 41 partial response (PR), 7 stable disease (SD), and 2 progressive disease (PD). The total effective rate was 85.0% (51/60). Thirty-nine patients had an increased KPS score. One-, 2-, and 3-year survival rates were 85.3%, 57.5%, and 41.7%, respectively. The median survival time was 27 months. The adverse reactions included myelosuppression, which was mainly degreeI and II. The occurrence rate of radiation esophagitis was 17.5%. No significant hepatic or renal toxicity was observed. Lobaplatin plus 5-Fu combined with concurrent radiotherapy is safe and effective in treating patients with middle-advanced stage esophageal cancer. However, this result warrants further evaluation by randomized clinical studies.

Phase II Trial of Preoperative Irinotecan-Cisplatin Followed by Concurrent Irinotecan-Cisplatin and Radiotherapy for Resectable Locally Advanced Gastric and Esophagogastric Junction Adenocarcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rivera, Fernando, E-mail: oncrhf@humv.e; Galan, Maica; Tabernero, Josep

Purpose: To determine in a Phase II trial whether preoperative irinotecan-cisplatin (IC) followed by concurrent IC therapy and radiotherapy (IC/RT) improved outcome in patients with resectable, locally advanced gastric adenocarcinoma (GC) or esophagogastric junction cancer (EGJC). Patients and Methods: Patients with resectable Stage II-IV, M0 GC or EGJC made up the study population. The primary endpoint was pathologic complete response (pCR). Two courses of IC (irinotecan, 65mg/m{sup 2}; cisplatin, 30mg/m{sup 2} on Days 1 and 8 every 21 days) were given. Patients without progression then received IC/RT, consisting of daily radiotherapy (45Gy) with concurrent IC (irinotecan, 65mg/m{sup 2}; cisplatin, 30mg/m{supmore » 2} on Days 1, 8, 15, and 22). Surgical resection was performed, if feasible, 5-8 weeks after the end of radiotherapy. Results: Twenty-three patients were included in the study: 10 with EGJC and 13 with GC. Two patients (9%) achieved pCR. The incidences of Grade 3-4 toxicities were as follows: IC: neutropenia 35% (febrile 13%), anemia 22%, diarrhea 22%, emesis 8%; IC/RT: neutropenia 52% (febrile 5%), asthenia 19%, anemia 9%, emesis 9%, diarrhea 5%, cardiotoxicity 5%. No patients died during IC or IC/RT. R0 resection was achieved in 15 patients (65%). Median survival was 14.5 months, and the actuarial 2-year survival rate was 35%. Conclusions: Preoperative IC followed by IC/RT resulted in moderate response and resection rates with mild toxicity in patients with GC and EGJC.« less

High spatial resolution dosimetric response maps for radiotherapy ionization chambers measured using kilovoltage synchrotron radiation

NASA Astrophysics Data System (ADS)

Butler, D. J.; Stevenson, A. W.; Wright, T. E.; Harty, P. D.; Lehmann, J.; Livingstone, J.; Crosbie, J. C.

2015-11-01

Small circular beams of synchrotron radiation (0.1 mm and 0.4 mm in diameter) were used to irradiate ionization chambers of the types commonly used in radiotherapy. By scanning the chamber through the beam and measuring the ionization current, a spatial map of the dosimetric response of the chamber was recorded. The technique is able to distinguish contributions to the large-field ionization current from the chamber walls, central electrode and chamber stem. Scans were recorded for the NE 2571 Farmer chamber, the PTW 30013, IBA FC65-G Farmer-type chambers, the NE 2611A and IBA CC13 thimble chambers, the PTW 31006 and 31014 pinpoint chambers, the PTW Roos and Advanced Markus plane-parallel chambers, and the PTW 23342 thin-window soft x-ray chamber. In all cases, large contributions to the response arise from areas where the incident beam grazes the cavity surfaces. Quantitative as well as qualitative information about the relative chamber response was extracted from the maps, including the relative contribution of the central electrode. Line scans using monochromatic beams show the effect of the photon energy on the chamber response. For Farmer-type chambers, a simple Monte Carlo model was in good agreement with the measured response.

SU-D-BRD-02: A Web-Based Image Processing and Plan Evaluation Platform (WIPPEP) for Future Cloud-Based Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chai, X; Liu, L; Xing, L

Purpose: Visualization and processing of medical images and radiation treatment plan evaluation have traditionally been constrained to local workstations with limited computation power and ability of data sharing and software update. We present a web-based image processing and planning evaluation platform (WIPPEP) for radiotherapy applications with high efficiency, ubiquitous web access, and real-time data sharing. Methods: This software platform consists of three parts: web server, image server and computation server. Each independent server communicates with each other through HTTP requests. The web server is the key component that provides visualizations and user interface through front-end web browsers and relay informationmore » to the backend to process user requests. The image server serves as a PACS system. The computation server performs the actual image processing and dose calculation. The web server backend is developed using Java Servlets and the frontend is developed using HTML5, Javascript, and jQuery. The image server is based on open source DCME4CHEE PACS system. The computation server can be written in any programming language as long as it can send/receive HTTP requests. Our computation server was implemented in Delphi, Python and PHP, which can process data directly or via a C++ program DLL. Results: This software platform is running on a 32-core CPU server virtually hosting the web server, image server, and computation servers separately. Users can visit our internal website with Chrome browser, select a specific patient, visualize image and RT structures belonging to this patient and perform image segmentation running Delphi computation server and Monte Carlo dose calculation on Python or PHP computation server. Conclusion: We have developed a webbased image processing and plan evaluation platform prototype for radiotherapy. This system has clearly demonstrated the feasibility of performing image processing and plan evaluation platform through a web browser and exhibited potential for future cloud based radiotherapy.« less

Toward semi-automated assessment of target volume delineation in radiotherapy trials: the SCOPE 1 pretrial test case.

PubMed

Gwynne, Sarah; Spezi, Emiliano; Wills, Lucy; Nixon, Lisette; Hurt, Chris; Joseph, George; Evans, Mererid; Griffiths, Gareth; Crosby, Tom; Staffurth, John

2012-11-15

To evaluate different conformity indices (CIs) for use in the analysis of outlining consistency within the pretrial quality assurance (Radiotherapy Trials Quality Assurance [RTTQA]) program of a multicenter chemoradiation trial of esophageal cancer and to make recommendations for their use in future trials. The National Cancer Research Institute SCOPE 1 trial is an ongoing Cancer Research UK-funded phase II/III randomized controlled trial of chemoradiation with capecitabine and cisplatin with or without cetuximab for esophageal cancer. The pretrial RTTQA program included a detailed radiotherapy protocol, an educational package, and a single mid-esophageal tumor test case that were sent to each investigator to outline. Investigator gross tumor volumes (GTVs) were received from 50 investigators in 34 UK centers, and CERR (Computational Environment for Radiotherapy Research) was used to perform an assessment of each investigator GTV against a predefined gold-standard GTV using different CIs. A new metric, the local conformity index (l-CI), that can localize areas of maximal discordance was developed. The median Jaccard conformity index (JCI) was 0.69 (interquartile range, 0.62-0.70), with 14 of 50 investigators (28%) achieving a JCI of 0.7 or greater. The median geographical miss index was 0.09 (interquartile range, 0.06-0.16), and the mean discordance index was 0.27 (95% confidence interval, 0.25-0.30). The l-CI was highest in the middle section of the volume, where the tumor was bulky and more easily definable, and identified 4 slices where fewer than 20% of investigators achieved an l-CI of 0.7 or greater. The available CIs analyze different aspects of a gold standard-observer variation, with JCI being the most useful as a single metric. Additional information is provided by the l-CI and can focus the efforts of the RTTQA team in these areas, possibly leading to semi-automated outlining assessment. Copyright © 2012 Elsevier Inc. All rights reserved.

Toward Semi-automated Assessment of Target Volume Delineation in Radiotherapy Trials: The SCOPE 1 Pretrial Test Case

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gwynne, Sarah, E-mail: Sarah.Gwynne2@wales.nhs.uk; Spezi, Emiliano; Wills, Lucy

2012-11-15

Purpose: To evaluate different conformity indices (CIs) for use in the analysis of outlining consistency within the pretrial quality assurance (Radiotherapy Trials Quality Assurance [RTTQA]) program of a multicenter chemoradiation trial of esophageal cancer and to make recommendations for their use in future trials. Methods and Materials: The National Cancer Research Institute SCOPE 1 trial is an ongoing Cancer Research UK-funded phase II/III randomized controlled trial of chemoradiation with capecitabine and cisplatin with or without cetuximab for esophageal cancer. The pretrial RTTQA program included a detailed radiotherapy protocol, an educational package, and a single mid-esophageal tumor test case that weremore » sent to each investigator to outline. Investigator gross tumor volumes (GTVs) were received from 50 investigators in 34 UK centers, and CERR (Computational Environment for Radiotherapy Research) was used to perform an assessment of each investigator GTV against a predefined gold-standard GTV using different CIs. A new metric, the local conformity index (l-CI), that can localize areas of maximal discordance was developed. Results: The median Jaccard conformity index (JCI) was 0.69 (interquartile range, 0.62-0.70), with 14 of 50 investigators (28%) achieving a JCI of 0.7 or greater. The median geographical miss index was 0.09 (interquartile range, 0.06-0.16), and the mean discordance index was 0.27 (95% confidence interval, 0.25-0.30). The l-CI was highest in the middle section of the volume, where the tumor was bulky and more easily definable, and identified 4 slices where fewer than 20% of investigators achieved an l-CI of 0.7 or greater. Conclusions: The available CIs analyze different aspects of a gold standard-observer variation, with JCI being the most useful as a single metric. Additional information is provided by the l-CI and can focus the efforts of the RTTQA team in these areas, possibly leading to semi-automated outlining assessment.« less

Redox-responsive manganese dioxide nanoparticles for enhanced MR imaging and radiotherapy of lung cancer

NASA Astrophysics Data System (ADS)

Cho, Mi Hyeon; Choi, Eun-Seok; Kim, Sehee; Goh, Sung-Ho; Choi, Yongdoo

2017-12-01

In this study, we synthesized manganese dioxide nanoparticles (MnO2 NPs) stabilized with biocompatible polymers (polyvinylpyrrolidone and polyacrylic acid) and analyzed their effect on non-small cell lung cancer (NSCLC) cells with or without gefitinib resistance in vitro. MnO2 NPs showed glutathione (GSH)-responsive dissolution and subsequent enhancement in magnetic resonance (MR) imaging. Of note, treatment with MnO2 NPs induced significant cytotoxic effects on NSCLC cells, and additional dose-dependent therapeutic effects were obtained upon X-ray irradiation. Normal cells treated with MnO2 NPs were viable at the tested concentrations. In addition, increased therapeutic efficacy could be achieved when the cells were treated with MnO2 NPs in hypoxic conditions. Therefore, we conclude that the use of MnO2 NPs in MR imaging and combination radiotherapy may be an efficient strategy for the imaging and therapy of NSCLC.

Current Status and Perspectives of Hyperthermia in Cancer Therapy

NASA Astrophysics Data System (ADS)

Hiraoka, Masahiro; Nagata, Yasushi; Mitsumori, Michihide; Sakamoto, Masashi; Masunaga, Shin-ichiro

2004-08-01

Clinical trials of hyperthermia in combination with radiation therapy or chemotherapy undertaken over the past decades in Japan have been reviewed. Originally developed heating devices were mostly used for these trials, which include RF (radiofrequency) capacitive heating devices, a microwave heating device with a lens applicator, an RF intracavitary heating device, an RF current interstitial heating device, and ferromagnetic implant heating device. Non-randomized trials for various cancers, demonstrated higher response rate in thermoradiotherapy than in radiotherapy alone. Randomized trials undertaken for esophageal cancers also demonstrated improved local response with the combined use of hyperthermia. Furthermore, the complications associated with treatment were not generally serious. These clinical results indicate the benefit of combined treatment of hyperthermia and radiotherapy for various malignancies. On the other hand, the presently available heating devices are not satisfactory from the clinical viewpoints. With the advancement of heating and thermometry technologies, hyperthermia will be more widely and safely used in the treatment of cancers.

Enhanced dynamic wedge and independent monitor unit verification.

PubMed

Howlett, S J

2005-03-01

Some serious radiation accidents have occurred around the world during the delivery of radiotherapy treatment. The regrettable incident in Panama clearly indicated the need for independent monitor unit (MU) verification. Indeed the International Atomic Energy Agency (IAEA), after investigating the incident, made specific recommendations for radiotherapy centres which included an independent monitor unit check for all treatments. Independent monitor unit verification is practiced in many radiotherapy centres in developed countries around the world. It is mandatory in USA but not yet in Australia. This paper describes development of an independent MU program, concentrating on the implementation of the Enhanced Dynamic Wedge (EDW) component. The difficult case of non centre of field (COF) calculation points under the EDW was studied in some detail. Results of a survey of Australasian centres regarding the use of independent MU check systems is also presented. The system was developed with reference to MU calculations made by Pinnacle 3D Radiotherapy Treatment Planning (RTP) system (ADAC - Philips) for 4MV, 6MV and 18MV X-ray beams used at the Newcastle Mater Misericordiae Hospital (NMMH) in the clinical environment. A small systematic error was detected in the equation used for the EDW calculations. Results indicate that COF equations may be used in the non COF situation with similar accuracy to that achieved with profile corrected methods. Further collaborative work with other centres is planned to extend these findings.

Agreement between gamma passing rates using computed tomography in radiotherapy and secondary cancer risk prediction from more advanced dose calculated models

PubMed Central

Balosso, Jacques

2017-01-01

Background During the past decades, in radiotherapy, the dose distributions were calculated using density correction methods with pencil beam as type ‘a’ algorithm. The objectives of this study are to assess and evaluate the impact of dose distribution shift on the predicted secondary cancer risk (SCR), using modern advanced dose calculation algorithms, point kernel, as type ‘b’, which consider change in lateral electrons transport. Methods Clinical examples of pediatric cranio-spinal irradiation patients were evaluated. For each case, two radiotherapy treatment plans with were generated using the same prescribed dose to the target resulting in different number of monitor units (MUs) per field. The dose distributions were calculated, respectively, using both algorithms types. A gamma index (γ) analysis was used to compare dose distribution in the lung. The organ equivalent dose (OED) has been calculated with three different models, the linear, the linear-exponential and the plateau dose response curves. The excess absolute risk ratio (EAR) was also evaluated as (EAR = OED type ‘b’ / OED type ‘a’). Results The γ analysis results indicated an acceptable dose distribution agreement of 95% with 3%/3 mm. Although, the γ-maps displayed dose displacement >1 mm around the healthy lungs. Compared to type ‘a’, the OED values from type ‘b’ dose distributions’ were about 8% to 16% higher, leading to an EAR ratio >1, ranged from 1.08 to 1.13 depending on SCR models. Conclusions The shift of dose calculation in radiotherapy, according to the algorithm, can significantly influence the SCR prediction and the plan optimization, since OEDs are calculated from DVH for a specific treatment. The agreement between dose distribution and SCR prediction depends on dose response models and epidemiological data. In addition, the γ passing rates of 3%/3 mm does not translate the difference, up to 15%, in the predictions of SCR resulting from alternative algorithms. Considering that modern algorithms are more accurate, showing more precisely the dose distributions, but that the prediction of absolute SCR is still very imprecise, only the EAR ratio could be used to rank radiotherapy plans. PMID:28811995

Radiotherapy-Induced Anti-Tumor Immunity Contributes to the Therapeutic Efficacy of Irradiation and Can Be Augmented by CTLA-4 Blockade in a Mouse Model

PubMed Central

Yoshimoto, Yuya; Suzuki, Yoshiyuki; Mimura, Kousaku; Ando, Ken; Oike, Takahiro; Sato, Hiro; Okonogi, Noriyuki; Maruyama, Takanori; Izawa, Shinichiro; Noda, Shin-ei; Fujii, Hideki; Kono, Koji; Nakano, Takashi

2014-01-01

Purpose There is growing evidence that tumor-specific immune responses play an important role in anti-cancer therapy, including radiotherapy. Using mouse tumor models we demonstrate that irradiation-induced anti-tumor immunity is essential for the therapeutic efficacy of irradiation and can be augmented by modulation of cytotoxic T lymphocyte (CTL) activity. Methods and Materials C57BL/6 mice, syngeneic EL4 lymphoma cells, and Lewis lung carcinoma (LL/C) cells were used. Cells were injected into the right femurs of mice. Ten days after inoculation, tumors were treated with 30 Gy of local X-ray irradiation and their growth was subsequently measured. The effect of irradiation on tumor growth delay (TGD) was defined as the time (in days) for tumors to grow to 500 mm3 in the treated group minus that of the untreated group. Cytokine production and serum antibodies were measured by ELISA and flow cytometry. Results In the EL4 tumor model, tumors were locally controlled by X-ray irradiation and re-introduced EL4 cells were completely rejected. Mouse EL4-specific systemic immunity was confirmed by splenocyte cytokine production and detection of tumor-specific IgG1 antibodies. In the LL/C tumor model, X-ray irradiation also significantly delayed tumor growth (TGD: 15.4 days) and prolonged median survival time (MST) to 59 days (versus 28 days in the non-irradiated group). CD8(+) cell depletion using an anti-CD8 antibody significantly decreased the therapeutic efficacy of irradiation (TGD, 8.7 days; MST, 49 days). Next, we examined whether T cell modulation affected the efficacy of radiotherapy. An anti-CTLA-4 antibody significantly increased the anti-tumor activity of radiotherapy (TGD was prolonged from 13.1 to 19.5 days), while anti-FR4 and anti-GITR antibodies did not affect efficacy. Conclusions Our results indicate that tumor-specific immune responses play an important role in the therapeutic efficacy of irradiation. Immunomodulation, including CTLA-4 blockade, may be a promising treatment in combination with radiotherapy. PMID:24686897

Radiotherapy-induced anti-tumor immunity contributes to the therapeutic efficacy of irradiation and can be augmented by CTLA-4 blockade in a mouse model.

PubMed

Yoshimoto, Yuya; Suzuki, Yoshiyuki; Mimura, Kousaku; Ando, Ken; Oike, Takahiro; Sato, Hiro; Okonogi, Noriyuki; Maruyama, Takanori; Izawa, Shinichiro; Noda, Shin-ei; Fujii, Hideki; Kono, Koji; Nakano, Takashi

2014-01-01

There is growing evidence that tumor-specific immune responses play an important role in anti-cancer therapy, including radiotherapy. Using mouse tumor models we demonstrate that irradiation-induced anti-tumor immunity is essential for the therapeutic efficacy of irradiation and can be augmented by modulation of cytotoxic T lymphocyte (CTL) activity. C57BL/6 mice, syngeneic EL4 lymphoma cells, and Lewis lung carcinoma (LL/C) cells were used. Cells were injected into the right femurs of mice. Ten days after inoculation, tumors were treated with 30 Gy of local X-ray irradiation and their growth was subsequently measured. The effect of irradiation on tumor growth delay (TGD) was defined as the time (in days) for tumors to grow to 500 mm3 in the treated group minus that of the untreated group. Cytokine production and serum antibodies were measured by ELISA and flow cytometry. In the EL4 tumor model, tumors were locally controlled by X-ray irradiation and re-introduced EL4 cells were completely rejected. Mouse EL4-specific systemic immunity was confirmed by splenocyte cytokine production and detection of tumor-specific IgG1 antibodies. In the LL/C tumor model, X-ray irradiation also significantly delayed tumor growth (TGD: 15.4 days) and prolonged median survival time (MST) to 59 days (versus 28 days in the non-irradiated group). CD8(+) cell depletion using an anti-CD8 antibody significantly decreased the therapeutic efficacy of irradiation (TGD, 8.7 days; MST, 49 days). Next, we examined whether T cell modulation affected the efficacy of radiotherapy. An anti-CTLA-4 antibody significantly increased the anti-tumor activity of radiotherapy (TGD was prolonged from 13.1 to 19.5 days), while anti-FR4 and anti-GITR antibodies did not affect efficacy. Our results indicate that tumor-specific immune responses play an important role in the therapeutic efficacy of irradiation. Immunomodulation, including CTLA-4 blockade, may be a promising treatment in combination with radiotherapy.

Influence of radiotherapy on the latest generation of implantable cardioverter-defibrillators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hurkmans, Coen W.; Scheepers, Egon; Springorum, Bob G.F.

2005-09-01

Purpose: Radiotherapy can influence the functioning of pacemakers and implantable cardioverter-defibrillators (ICDs). ICDs offer the same functionality as pacemakers, but are also able to deliver a high-voltage shock to the heart if needed. Guidelines for radiotherapy treatment of patients with an implanted rhythm device have been published in 1994 by The American Association of Physicists in Medicine, and are based only on experience with pacemakers. Data on the influence of radiotherapy on ICDs are limited. The objective of our study is to determine the influence of radiotherapy on the latest generation of ICDs. Methods and Materials: Eleven modern ICDs havemore » been irradiated in our department. The irradiation was performed with a 6-MV photon beam. The given dose was fractionated up to a cumulative dose of 120 Gy. Two to 5 days passed between consecutive irradiations. Frequency, output, sensing, telemetry, and shock energy were monitored. Results: Sensing interference by ionizing radiation on all ICDs has been demonstrated. For four ICDs, this would have caused the inappropriate delivery of a shock because of interference. At the end of the irradiation sessions, all devices had reached their point of failure. Complete loss of function was observed for four ICDs at dose levels between 0.5 Gy and 1.5 Gy. Conclusions: The effect of radiation therapy on the newest generation of ICDs varies widely. If tachycardia monitoring and therapy are functional (programmed on) during irradiation, the ICD might inappropriately give antitachycardia therapy, often resulting in a shock. Although most ICDs did not fail below 80 Gy, some devices had already failed at doses below 1.5 Gy. Guidelines are formulated for the treatment of patients with an ICD.« less

Quantitative correlational study of microbubble-enhanced ultrasound imaging and magnetic resonance imaging of glioma and early response to radiotherapy in a rat model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Chen; Lee, Dong-Hoon; Zhang, Kai

Purpose: Radiotherapy remains a major treatment method for malignant tumors. Magnetic resonance imaging (MRI) is the standard modality for assessing glioma treatment response in the clinic. Compared to MRI, ultrasound imaging is low-cost and portable and can be used during intraoperative procedures. The purpose of this study was to quantitatively compare contrast-enhanced ultrasound (CEUS) imaging and MRI of irradiated gliomas in rats and to determine which quantitative ultrasound imaging parameters can be used for the assessment of early response to radiation in glioma. Methods: Thirteen nude rats with U87 glioma were used. A small thinned skull window preparation was performedmore » to facilitate ultrasound imaging and mimic intraoperative procedures. Both CEUS and MRI with structural, functional, and molecular imaging parameters were performed at preradiation and at 1 day and 4 days postradiation. Statistical analysis was performed to determine the correlations between MRI and CEUS parameters and the changes between pre- and postradiation imaging. Results: Area under the curve (AUC) in CEUS showed significant difference between preradiation and 4 days postradiation, along with four MRI parameters, T{sub 2}, apparent diffusion coefficient, cerebral blood flow, and amide proton transfer-weighted (APTw) (all p < 0.05). The APTw signal was correlated with three CEUS parameters, rise time (r = − 0.527, p < 0.05), time to peak (r = − 0.501, p < 0.05), and perfusion index (r = 458, p < 0.05). Cerebral blood flow was correlated with rise time (r = − 0.589, p < 0.01) and time to peak (r = − 0.543, p < 0.05). Conclusions: MRI can be used for the assessment of radiotherapy treatment response and CEUS with AUC as a new technique and can also be one of the assessment methods for early response to radiation in glioma.« less

Radiotherapy equipment and departments in the European countries: final results from the ESTRO-HERO survey.

PubMed

Grau, Cai; Defourny, Noémie; Malicki, Julian; Dunscombe, Peter; Borras, Josep M; Coffey, Mary; Slotman, Ben; Bogusz, Marta; Gasparotto, Chiara; Lievens, Yolande; Kokobobo, Arianit; Sedlmayer, Felix; Slobina, Elena; Feyen, Karen; Hadjieva, Tatiana; Odrazka, Karel; Grau Eriksen, Jesper; Jaal, Jana; Bly, Ritva; Chauvet, Bruno; Willich, Normann; Polgar, Csaba; Johannsson, Jakob; Cunningham, Moya; Magrini, Stefano; Atkocius, Vydmantas; Untereiner, Michel; Pirotta, Martin; Karadjinovic, Vanja; Levernes, Sverre; Sladowski, Krystol; Lurdes Trigo, Maria; Šegedin, Barbara; Rodriguez, Aurora; Lagerlund, Magnus; Pastoors, Bert; Hoskin, Peter; Vaarkamp, Jaap; Cleries Soler, Ramon

2014-08-01

Documenting the distribution of radiotherapy departments and the availability of radiotherapy equipment in the European countries is an important part of HERO - the ESTRO Health Economics in Radiation Oncology project. HERO has the overall aim to develop a knowledge base of the provision of radiotherapy in Europe and build a model for health economic evaluation of radiation treatments at the European level. The aim of the current report is to describe the distribution of radiotherapy equipment in European countries. An 84-item questionnaire was sent out to European countries, principally through their national societies. The current report includes a detailed analysis of radiotherapy departments and equipment (questionnaire items 26-29), analyzed in relation to the annual number of treatment courses and the socio-economic status of the countries. The analysis is based on validated responses from 28 of the 40 European countries defined by the European Cancer Observatory (ECO). A large variation between countries was found for most parameters studied. There were 2192 linear accelerators, 96 dedicated stereotactic machines, and 77 cobalt machines reported in the 27 countries where this information was available. A total of 12 countries had at least one cobalt machine in use. There was a median of 0.5 simulator per MV unit (range 0.3-1.5) and 1.4 (range 0.4-4.4) simulators per department. Of the 874 simulators, a total of 654 (75%) were capable of 3D imaging (CT-scanner or CBCT-option). The number of MV machines (cobalt, linear accelerators, and dedicated stereotactic machines) per million inhabitants ranged from 1.4 to 9.5 (median 5.3) and the average number of MV machines per department from 0.9 to 8.2 (median 2.6). The average number of treatment courses per year per MV machine varied from 262 to 1061 (median 419). While 69% of MV units were capable of IMRT only 49% were equipped for image guidance (IGRT). There was a clear relation between socio-economic status, as measured by GNI per capita, and availability of radiotherapy equipment in the countries. In many low income countries in Southern and Central-Eastern Europe there was very limited access to radiotherapy and especially to equipment for IMRT or IGRT. The European average number of MV machines per million inhabitants and per department is now better in line with QUARTS recommendations from 2005, but the survey also showed a significant heterogeneity in the access to modern radiotherapy equipment in Europe. High income countries especially in Northern-Western Europe are well-served with radiotherapy resources, other countries are facing important shortages of both equipment in general and especially machines capable of delivering high precision conformal treatments (IMRT, IGRT). Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Espinoza, I; Peschke, P; Karger, C

Purpose: In radiotherapy, it is important to predict the response of tumour to irradiation prior to the treatment. Mathematical modelling of tumour control probability (TCP) based on the dose distribution, medical imaging and other biological information may help to improve this prediction and to optimize the treatment plan. The aim of this work is to develop an image based 3D multiscale radiobiological model, which describes the growth and the response to radiotherapy of hypoxic tumors. Methods: The computer model is based on voxels, containing tumour, normal (including capillary) and dead cells. Killing of tumour cells due to irradiation is calculatedmore » by the Linear Quadratic Model (extended for hypoxia), and the proliferation and resorption of cells are modelled by exponential laws. The initial shape of the tumours is taken from CT images and the initial vascular and cell density information from PET and/or MR images. Including the fractionation regime and the physical dose distribution of the radiation treatment, the model simulates the spatial-temporal evolution of the tumor. Additionally, the dose distribution may be biologically optimized. Results: The model describes the appearance of hypoxia during tumour growth and the reoxygenation processes during radiotherapy. Among other parameters, the TCP is calculated for different dose distributions. The results are in accordance with published results. Conclusion: The simulation model may contribute to the understanding of the influence of biological parameters on tumor response during treatment, and specifically on TCP. It may be used to implement dose-painting approaches. Experimental and clinical validation is needed. This study is supported by a grant from the Ministry of Education of Chile, Programa Mece Educacion Superior (2)« less

Volumetric response of intracranial meningioma after photon or particle irradiation.

PubMed

Mozes, Petra; Dittmar, Jan Oliver; Habermehl, Daniel; Tonndorf-Martini, Eric; Hideghety, Katalin; Dittmar, Anne; Debus, Jürgen; Combs, Stephanie E

2017-03-01

Meningiomas are usually slow growing, well circumscribed intracranial tumors. In symptom-free cases observation with close follow-up imaging could be performed. Symptomatic meningiomas could be surgically removed and/or treated with radiotherapy. The study aimed to evaluate the volumetric response of intracranial meningiomas at different time points after photon, proton, and a mixed photon and carbon ion boost irradiation. In Group A 38 patients received proton therapy (median dose: 56 GyE in 1.8-2 GyE daily fractions) or a mixed photon/carbon ion therapy (50 Gy in 2 Gy daily fractions with intensity modulated radiotherapy (IMRT) and 18 GyE in 3 GyE daily dose carbon ion boost). Thirty-nine patients (Group B) were treated by photon therapy with IMRT or fractionated stereotactic radiotherapy technique (median dose: 56 Gy in 1.8-2 Gy daily fractions). The delineation of the tumor volume was based on the initial, one- and two-year follow-up magnetic resonance imaging and these volumes were compared to evaluate the volumetric tumor response. Significant tumor volume shrinkage was detected at one- and at two-year follow-up both after irradiation by particles and by photons. No significant difference in tumor volume change was observed between photon, proton or combined photon plus carbon ion boost treated patients. WHO grade and gender appear to be determining factors for tumor volume shrinkage. Significant volumetric shrinkage of meningiomas could be observed independently of the applied radiation modality. Long-term follow-up is recommended to evaluate further dynamic of size reduction and its correlation with outcome data.

Feasibility study of a lead(II) iodide-based dosimeter for quality assurance in therapeutic radiology

NASA Astrophysics Data System (ADS)

Heo, Y. J.; Kim, K. T.; Oh, K. M.; Lee, Y. K.; Ahn, K. J.; Cho, H. L.; Kim, J. Y.; Min, B. I.; Mun, C. W.; Park, S. K.

2017-09-01

The most widely used form of radiotherapy to treat tumors uses a linear accelerator, and the apparatus requires regular quality assurance (QA). QA for a linear accelerator demands accuracy throughout, from mock treatment and treatment planning, up to treatment itself. Therefore, verifying a radiation dose is essential to ensure that the radiation is being applied as planned. In current clinical practice, ionization chambers and diodes are used for QA. However, using conventional gaseous ionization chambers presents drawbacks such as complex analytical procedures, difficult measurement procedures, and slow response time. In this study, we discuss the potential of a lead(II) iodide (PbI2)-based radiation dosimeter for radiotherapy QA. PbI2 is a semiconductor material suited to measurements of X-rays and gamma rays, because of its excellent response properties to radiation signals. Our results show that the PbI2-based dosimeter offers outstanding linearity and reproducibility, as well as dose-independent characteristics. In addition, percentage depth dose (PDD) measurements indicate that the error at a fixed reference depth Dmax was 0.3%, very similar to the measurement results obtained using ionization chambers. Based on these results, we confirm that the PbI2-based dosimeter has all the properties required for radiotherapy: stable dose detection, dose linearity, and rapid response time. Based on the evidence of this experimental verification, we believe that the PbI2-based dosimeter could be used commercially in various fields for precise measurements of radiation doses in the human body and for measuring the dose required for stereotactic radiosurgery or localized radiosurgery.

Meta-analysis of whole-brain radiotherapy plus temozolomide compared with whole-brain radiotherapy for the treatment of brain metastases from non-small-cell lung cancer.

PubMed

Xin, Yong; Guo, WenWen; Yang, Chun Sheng; Huang, Qian; Zhang, Pei; Zhang, Long Zhen; Jiang, Guan

2018-04-01

The aim of this meta-analysis was to compare the efficiency of whole-brain radiotherapy (WBRT) plus temozolomide (TMZ) with WBRT for the treatment of brain metastases from non-small-cell lung cancer (NSCLC). For dichotomous variables, outcomes were reported as relative risk ratio (RR) and 95% confidence interval (CI) was used to investigate the following outcome measures: overall response rate, headache, gastrointestinal adverse reactions, and hematological adverse reactions. Twelve randomized controlled trials involving 925 participants (480 received WBRT plus TMZ; 445 received WBRT) were included in the meta-analysis. There was a significant difference between the overall response rate (RR = 1.40, 95% CI 1.24-1.57; Z = 5.51; P < 0.00001), gastrointestinal adverse reactions (RR = 1.46, 95% CI 1.05-2.04; Z = 2.27; P = 0.02), and hematological adverse reactions (RR = 1.45, 95% CI 1.04-2.02; Z = 2.21; P = 0.03) of patients treated with WBRT plus TMZ compared with patients treated with WBRT alone. There was no significant difference between headaches (RR = 1.11, 95% CI 0.93-1.02; Z = 1.13; P = 0.26) in patients treated with WBRT plus TMZ compared with patients treated with WBRT alone. In conclusion, the currently available evidence shows that WBRT plus TMZ increases the overall response rate in patients with brain metastases of NSCLC compared with WBRT alone. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Dynamic skin changes of acute radiation dermatitis revealed by in vivo reflectance confocal microscopy.

PubMed

Vano-Galvan, S; Fernandez-Lizarbe, E; Truchuelo, M; Diaz-Ley, B; Grillo, E; Sanchez, V; Ríos-Buceta, L; Paoli, J; Sancho, S; Montero, A; Hernanz, R; Ramos, A; Jaen, P; Gonzalez, S

2013-09-01

A better knowledge of the dynamic biological changes that the skin undergoes in response to ionizing radiation is advisable to improve the management of radiation dermatitis, allowing selection of patients needing treatment or close monitoring. To describe the evolution of the skin in response to ionizing radiation through the reflectance confocal microscopy (RCM) features of acute radiation dermatitis. In this prospective descriptive study, six women (median age, 55 years; range, 45-80 years) diagnosed with breast cancer in stages IA-IB undergoing adjuvant radiotherapy were included in the study through consecutive sampling. Clinical, dermoscopic and RCM evaluation of the skin were performed prior to treatment and on days 1, 15, 30 and 45 after radiotherapy. While clinical features of radiation dermatitis emerged after 30 days on average, histopathological changes were detectable by RCM after a mean time of 15 days. The main RCM features included initial appearance of spongiosis, exocytosis and inflammatory cells followed by the presence of dendritic-shaped cells, 'streaming-like figures', 'broken geographic papillae', epidermal architectural disarray, effacement of rete ridges, melanophages and, finally, hyperpigmentation of the basal layer. RCM may safely detect the dynamic biological changes that the skin undergoes in response to ionizing radiation, even before than clinical onset of acute radiation dermatitis. Therefore, RCM may be useful to make an early and non-invasive diagnosis of radiation dermatitis during radiotherapy, allowing an early selection of patients needing treatment or close monitoring and avoiding skin biopsies. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

Nanoparticles generated by laser in liquids as contrast medium and radiotherapy intensifiers

NASA Astrophysics Data System (ADS)

Restuccia, Nancy; Torrisi, Lorenzo

2018-01-01

The synthesis of Au and Ag nanoparticles (NP) though laser ablation in liquids as a function the laser parameters is presented. Spherical NPs with diameter distribution within 1 and 100 nm were prepared by laser ablation in water. The nanoparticles characterization was performed using optical spectroscopy and electronic microscopy (SEM and TEM) measurements. Studies of the possible use of metallic nanoparticles as intensifier of diagnostics imaging contrast medium and absorbing dose from ionizing radiations in traditional radiotherapy and protontherapy are presented. Examples of in vitro (in tissue equivalent materials) and in vivo (in mice), were conducted thank to simulation programs permitting to evaluate the enhancement of efficiency in imaging and therapy as a function of the NPs concentrations and irradiation conditions.

Optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes.

PubMed

Paul-Gilloteaux, Perrine; Potiron, Vincent; Delpon, Grégory; Supiot, Stéphane; Chiavassa, Sophie; Paris, François; Costes, Sylvain V

2017-05-23

The concept of hypofractionation is gaining momentum in radiation oncology centres, enabled by recent advances in radiotherapy apparatus. The gain of efficacy of this innovative treatment must be defined. We present a computer model based on translational murine data for in silico testing and optimization of various radiotherapy protocols with respect to tumour resistance and the microenvironment heterogeneity. This model combines automata approaches with image processing algorithms to simulate the cellular response of tumours exposed to ionizing radiation, modelling the alteration of oxygen permeabilization in blood vessels against repeated doses, and introducing mitotic catastrophe (as opposed to arbitrary delayed cell-death) as a means of modelling radiation-induced cell death. Published data describing cell death in vitro as well as tumour oxygenation in vivo are used to inform parameters. Our model is validated by comparing simulations to in vivo data obtained from the radiation treatment of mice transplanted with human prostate tumours. We then predict the efficacy of untested hypofractionation protocols, hypothesizing that tumour control can be optimized by adjusting daily radiation dosage as a function of the degree of hypoxia in the tumour environment. Further biological refinement of this tool will permit the rapid development of more sophisticated strategies for radiotherapy.

Epithelioid hemangioendothelioma of the spine treated with RapidArc volumetric-modulated radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guy, Jean-Baptiste; Trone, Jane-Chloé; Chargari, Cyrus

2014-10-01

Radiotherapy for epithelioid hemangioendothelioma (EHE) using volumetric intensity-modulated arc radiotherapy (VMAT). A 48-year-old woman was referred for curative irradiation of a vertebral EHE after failure of surgery. A comparison between VMAT and conventional conformal tridimensional (3D) dosimetry was performed and potential advantage of VMAT for sparing critical organs from irradiation's side effects was discussed. The total delivered dose on the planning target volume was 54 Gy in 27 fractions. The patient was finally treated with VMAT. The tolerance was excellent. There was no acute toxicity, including no increase in pain. With a follow-up of 18 months, no delayed toxicity wasmore » reported. The clinical response consisted of a decrease in the dorsal pain. The D{sub max} for the spinal cord was reduced from 55 Gy (3D-radiotherapy [RT]) (which would be an unacceptable dose to the spine because of the risk of myelopathy) to 42.8 Gy (VMAT), which remains below the recommended dose threshold (45 Gy). The dose delivered to 20% of organ volume (D{sub 20}) was reduced from 47 Gy (3D-RT) to 3 Gy (VMAT) for the spinal cord. The study shows that VMAT allows the delivery of curative treatment for vertebral EHEs because of critical organ sparing.« less

Efficient Active Oxygen Free Radical Generated in Tumor Cell by Loading-(HCONH2)·H2O2 Delivery Nanosystem with Soft-X-ray Radiotherapy

PubMed Central

Xu, Lei; Shao, Yiran; Chang, Chengkang; Zhu, Yingchun

2018-01-01

Tumor hypoxia is known to result in radiotherapy resistance and traditional radiotherapy using super-hard X-ray irradiation can cause considerable damage to normal tissue. Therefore, formamide peroxide (FPO) with high reactive oxygen content was employed to enhance the oxygen concentration in tumor cells and increase the radio-sensitivity of low-energy soft-X-ray. To improve stability of FPO, FPO is encapsulated into polyacrylic acid (PAA)-coated hollow mesoporous silica nanoparticles (FPO@HMSNs-PAA). On account of the pH-responsiveness of PAA, FPO@HMSNs-PAA will release more FPO in simulated acidic tumor microenvironment (pH 6.50) and subcellular endosomes (pH 5.0) than in simulated normal tissue media (pH 7.40). When exposed to soft-X-ray irradiation, the released FPO decomposes into oxygen and the generated oxygen further formed many reactive oxygen species (ROS), leading to significant tumor cell death. The ROS-mediated cytotoxicity of FPO@HMSNs-PAA was confirmed by ROS-induced green fluorescence in tumor cells. The presented FPO delivery system with soft-X-ray irradiation paves a way for developing the next opportunities of radiotherapy toward efficient tumor prognosis. PMID:29649155

Radiation-induced autophagy promotes esophageal squamous cell carcinoma cell survival via the LKB1 pathway.

PubMed

Lu, Chi; Xie, Conghua

2016-06-01

Radiotherapy is an important treatment modality for esophageal cancer; however, the clinical efficacy of radiotherapy is limited by tumor radioresistance. In the present study, we explored the hypothesis that radiation induces tumor cell autophagy as a cytoprotective adaptive response, which depends on liver kinase B1 (LKB1) also known as serine/threonine kinase 11 (STK11). Radiation-induced Eca-109 cell autophagy was found to be dependent on signaling through the LKB1 pathway, and autophagy inhibitors that disrupted radiation-induced Eca-109 cell autophagy increased cell cycle arrest and cell death in vitro. Inhibition of autophagy also reduced the clonogenic survival of the Eca-109 cells. When treated with radiation alone, human esophageal carcinoma xenografts showed increased LC3B and p-LKB1 expression, which was decreased by the autophagy inhibitor chloroquine. In vivo inhibition of autophagy disrupted tumor growth and increased tumor apoptosis when combined with 6 Gy of ionizing radiation. In summary, our findings elucidate a novel mechanism of resistance to radiotherapy in which radiation-induced autophagy, via the LKB1 pathway, promotes tumor cell survival. This indicates that inhibition of autophagy can serve as an adjuvant treatment to improve the curative effect of radiotherapy.

miR-139-5p Modulates Radiotherapy Resistance in Breast Cancer by Repressing Multiple Gene Networks of DNA Repair and ROS Defense.

PubMed

Pajic, Marina; Froio, Danielle; Daly, Sheridan; Doculara, Louise; Millar, Ewan; Graham, Peter H; Drury, Alison; Steinmann, Angela; de Bock, Charles E; Boulghourjian, Alice; Zaratzian, Anaiis; Carroll, Susan; Toohey, Joanne; O'Toole, Sandra A; Harris, Adrian L; Buffa, Francesca M; Gee, Harriet E; Hollway, Georgina E; Molloy, Timothy J

2018-01-15

Radiotherapy is essential to the treatment of most solid tumors and acquired or innate resistance to this therapeutic modality is a major clinical problem. Here we show that miR-139-5p is a potent modulator of radiotherapy response in breast cancer via its regulation of genes involved in multiple DNA repair and reactive oxygen species defense pathways. Treatment of breast cancer cells with a miR-139-5p mimic strongly synergized with radiation both in vitro and in vivo , resulting in significantly increased oxidative stress, accumulation of unrepaired DNA damage, and induction of apoptosis. Several miR-139-5p target genes were also strongly predictive of outcome in radiotherapy-treated patients across multiple independent breast cancer cohorts. These prognostically relevant miR-139-5p target genes were used as companion biomarkers to identify radioresistant breast cancer xenografts highly amenable to sensitization by cotreatment with a miR-139-5p mimetic. Significance: The microRNA described in this study offers a potentially useful predictive biomarker of radiosensitivity in solid tumors and a generally applicable druggable target for tumor radiosensitization. Cancer Res; 78(2); 501-15. ©2017 AACR . ©2017 American Association for Cancer Research.

Dosimetry in nuclear medicine therapy: radiobiology application and results.

PubMed

Strigari, L; Benassi, M; Chiesa, C; Cremonesi, M; Bodei, L; D'Andrea, M

2011-04-01

The linear quadratic model (LQM) has largely been used to assess the radiobiological damage to tissue by external beam fractionated radiotherapy and more recently has been extended to encompass a general continuous time varying dose rate protocol such as targeted radionuclide therapy (TRT). In this review, we provide the basic aspects of radiobiology, from a theoretical point of view, starting from the "four Rs" of radiobiology and introducing the biologically effective doses, which may be used to quantify the impact of a treatment on both tumors and normal tissues. We also present the main parameters required in the LQM, and illustrate the main models of tumor control probability and normal tissue complication probability and summarize the main dose-effect responses, reported in literature, which demonstrate the tentative link between targeted radiotherapy doses and those used in conventional radiotherapy. A better understanding of the radiobiology and mechanisms of action of TRT could contribute to describe the clinical data and guide the development of future compounds and the designing of prospective clinical trials.

The synergistic effects of traditional Chinese herbs and radiotherapy for cancer treatment

PubMed Central

JIA, LILI; MA, SHUMEI; HOU, XUE; WANG, XIN; QASED, ABU BAKER LAYTH; SUN, XUEFEI; LIANG, NAN; LI, HUICHENG; YI, HEQING; KONG, DEJUAN; LIU, XIAODONG; FAN, FEIYUE

2013-01-01

Traditional Chinese medicine (TCM) has been demonstrated to have potent cytotoxic activity against certain malignant tumors. Ionizing radiation (IR) is one of the most effective methods used in the clinical treatment of cancer. The drawback of a single formula is that it limits the treatment efficacy for cancer, while comprehensive strategies require additional theoretical support. However, a combination of different antitumor treatment modalities is advantageous in restricting the non-specific toxicity often observed with an extremely high dose of a single regimen. The induction of apoptotic cell death is a significant process in tumor cells following radiotherapy or chemotherapy, and resistance to these treatments has been linked to a low propensity for apoptosis. Autophagy is a response of cancer cells to IR or chemotherapy, and involves the prominent formation of autophagic vacuoles in the cytoplasm. In this review, the synergistic effects of TCM and radiotherapy are summarized and the underlying mechanisms are illustrated, providing new therapeutic strategies for cancer. PMID:23760551

Improving the neutron-to-photon discrimination capability of detectors used for neutron dosimetry in high energy photon beam radiotherapy.

PubMed

Irazola, L; Terrón, J A; Bedogni, R; Pola, A; Lorenzoli, M; Sánchez-Nieto, B; Gómez, F; Sánchez-Doblado, F

2016-09-01

The increasing interest of the medical community to radioinduced second malignancies due to photoneutrons in patients undergoing high-energy radiotherapy, has stimulated in recent years the study of peripheral doses, including the development of some dedicated active detectors. Although these devices are designed to respond to neutrons only, their parasitic photon response is usually not identically zero and anisotropic. The impact of these facts on measurement accuracy can be important, especially in points close to the photon field-edge. A simple method to estimate the photon contribution to detector readings is to cover it with a thermal neutron absorber with reduced secondary photon emission, such as a borated rubber. This technique was applied to the TNRD (Thermal Neutron Rate Detector), recently validated for thermal neutron measurements in high-energy photon radiotherapy. The positive results, together with the accessibility of the method, encourage its application to other detectors and different clinical scenarios. Copyright © 2016 Elsevier Ltd. All rights reserved.

Medical marijuana use in head and neck squamous cell carcinoma patients treated with radiotherapy.

PubMed

Elliott, David A; Nabavizadeh, Nima; Romer, Jeanna L; Chen, Yiyi; Holland, John M

2016-08-01

The purpose of the study was to better understand why patients with history of head and neck cancer (HNC) treated with radiotherapy are using medical marijuana (MM). Established HNC quality of life questionnaires and our own MM quality of life questionnaire were sent to 15 HNC patients treated at our institution who reported using MM. Patients are clinically disease free and currently using MM to manage long-term side effects after curative HNC treatment. There was a 100 % response rate. Median time from treatment was 45 months (21-136 months). Most patients smoked marijuana (12 patients), while others reported ingestion (4 patients), vaporizing (3 patients), and use of homemade concentrated oil (1 patient). Six patients reported prior recreational marijuana use before diagnosis. MM provided benefit in altered sense, weight maintenance, depression, pain, appetite, dysphagia, xerostomia, muscle spasm, and sticky saliva. HNC patients report MM use to help with long-term side effects of radiotherapy.

Functional Imaging Biomarkers: Potential to Guide an Individualised Approach to Radiotherapy.

PubMed

Prestwich, R J D; Vaidyanathan, S; Scarsbrook, A F

2015-10-01

The identification of robust prognostic and predictive biomarkers would transform the ability to implement an individualised approach to radiotherapy. In this regard, there has been a surge of interest in the use of functional imaging to assess key underlying biological processes within tumours and their response to therapy. Importantly, functional imaging biomarkers hold the potential to evaluate tumour heterogeneity/biology both spatially and temporally. An ever-increasing range of functional imaging techniques is now available primarily involving positron emission tomography and magnetic resonance imaging. Small-scale studies across multiple tumour types have consistently been able to correlate changes in functional imaging parameters during radiotherapy with disease outcomes. Considerable challenges remain before the implementation of functional imaging biomarkers into routine clinical practice, including the inherent temporal variability of biological processes within tumours, reproducibility of imaging, determination of optimal imaging technique/combinations, timing during treatment and design of appropriate validation studies. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

IMRT for head and neck cancer: reducing xerostomia and dysphagia.

PubMed

Wang, XiaoShen; Eisbruch, Avraham

2016-08-01

Dysphagia and xerostomia are the main sequellae of chemoradiotherapy for head and neck cancer, and the main factors in reducing long-term patient quality of life. IMRT uses advanced technology to focus the high radiation doses on the targets and avoid irradiation of non-involved tissues. The decisions about sparing organs and tissues whose damage causes xerostomia and dysphagia depends on the evidence for dose-response relationships for the organs causing these sequellae. This paper discusses the evidence for the contribution of radiotherapy to xerostomia via damage of the major salivary glands (parotid and submandibular) and minor salivary glands within the oral cavity, and the contribution of radiotherapy-related effect on important swallowing structures causing dysphagia. Recommendations for dose limits to these organs, based on measurements of xerostomia and dysphagia following radiotherapy, are provided here. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Evaluation of the response of concurrent high dose rate intracavitary brachytherapy with external beam radiotherapy in management of early stage carcinoma cervix.

PubMed

Patidar, Arvind Kumar; Kumar, H S; Walke, Rahul V; Hirapara, Pushpendra H; Jakhar, Shankar Lal; Bardia, M R

2012-10-01

To evaluate local disease control and early complications of concomitant brachytherapy with external beam-radiotherapy in early stage carcinoma cervix. Fifty patients of early stage carcinoma cervix (FIGO-IB/IIA) were randomly divided into study group concomitant external beam irradiation (EBRT) and HDR-ICBT (intra-cavitary brachytherapy, xrt = 50 Gy/25 Fr, HDR 5.2 Gy*5 Fr) and the control group EBRT followed by HDR-ICBT (xrt = 50 Gy/25 Fr, HDR 7.5 Gy*3 Fr). Acute reactions and local disease response were compared between treatment and at 6-month follow up. Median overall treatment times were 38 and 61 days in the study and the control groups, respectively. Acute skin reactions and diarrhea were more in the study but manageable. At the completion of the study, there were 80 and 68 % complete responses, 16 and 20 % partial responses, 0 and 8 % stable diseases in the study group and the control group, respectively. Response was better in the study group but statistically insignificant. Larger number of patients and longer follow up are required to arrive at concrete conclusion.

Accelerated superfractionated radiotherapy for inflammatory breast carcinoma: complete response predicts outcome and allows for breast conservation.

PubMed

Arthur, D W; Schmidt-Ullrich, R K; Friedman, R B; Wazer, D E; Kachnic, L A; Amir, C; Bear, H D; Hackney, M H; Smith, T J; Lawrence, W

1999-05-01

Chemotherapy and accelerated superfractionated radiotherapy were prospectively applied for inflammatory breast carcinoma with the intent of breast conservation. The efficacy, failure patterns, and patient tolerance utilizing this approach were analyzed. Between 1983 and 1996, 52 patients with inflammatory breast carcinoma presented to the Medical College of Virginia Hospitals of VCU and the New England Medical Center. Thirty-eight of these patients were jointly evaluated in multidisciplinary breast clinics and managed according to a defined prospectively applied treatment policy. Patients received induction chemotherapy, accelerated superfractionated radiotherapy, selected use of mastectomy, and concluded with additional chemotherapy. The majority were treated with 1.5 Gy twice daily to field arrangements covering the entire breast and regional lymphatics. An additional 18-21 Gy was then delivered to the breast and clinically involved nodal regions. Total dose to clinically involved areas was 63-66 Gy. Following chemoradiotherapy, patients were evaluated with physical examination, mammogram, and fine needle aspiration x 3. Mastectomy was reserved for those patients with evidence of persistent or progressive disease in the involved breast. All patients received additional chemotherapy. Median age was 51 years. Median follow-up was 23.9 months (6-86) months. The breast preservation rate at the time of last follow-up was 74%. The treated breast or chest wall as the first site of failure occurred in only 13%, and the ultimate local control rate with the selected use of mastectomy was 74%. Ten patients underwent mastectomy, 2 of which had pathologically negative specimens despite a clinically palpable residual mass. Response to chemotherapy was predictive of treatment outcome. Of the 15 patients achieving a complete response, 87% remain locoregionally controlled without the use of mastectomy. Five-year overall survival for complete responders was 68%. This is in contrast to the 14% 5-year overall survival observed with incomplete responders. The 5-year actuarial disease-free survival and overall survival for the entire patient cohort was 11% and 33%, respectively. All patients tolerated irradiation with limited acute effects, of which all were managed conservatively. Our experience demonstrates that induction chemotherapy, accelerated superfractionated radiotherapy, and the selected use of mastectomy results in excellent locoregional control rates, is well tolerated, and optimizes breast preservation. Based on our present results, we recommend that a patient's response to induction chemotherapy guide the treatment approach used for locoregional disease, such that mastectomy be reserved for incomplete responders and avoided in those achieving a complete response.

Management of Adolescent Low-Risk Classical Hodgkin Lymphoma: Which Chemotherapy Backbone Gives the Best Chance of Omitting Radiotherapy Safely.

PubMed

Algiraigri, Ali H; Essa, Mohammed F

2016-03-01

Even though more than 90% of adolescents with low-risk classical Hodgkin lymphoma (LRcHL) will be cured with first-line therapy, many will suffer serious late toxic effects from radiotherapy (RT). The goals for care have shifted toward minimizing late toxic effects without compromising the outstanding cure rates by adapting a risk and response-based therapy. Recent published and ongoing randomized clinical trials, using functional imaging, may allow for better identification of those patients for whom RT may be safely omitted while maintaining excellent cure rates. To evaluate the best chemotherapy regimens with a reasonable toxicity profile and that are expected to have a high chance of omitting RT based on a response-directed therapy while maintaining high cure rates, a mini review was conducted of the recent clinical trials in pediatric and adult LRcHL. The UK RAPID trial chemotherapy backbone (3 × ABVD) followed by a response-based positron emission tomography scan offers up to a 75% chance of safely omitting RT without compromising the cure rate, which remained well above 90%.

Localization of sclerotic-type chronic graft-vs-host disease to sites of skin injury: potential insight into the mechanism of isomorphic and isotopic responses.

PubMed

Martires, Kathryn J; Baird, Kristin; Citrin, Deborah E; Hakim, Fran T; Pavletic, Steven Z; Cowen, Edward W

2011-09-01

The mechanisms responsible for the variable manifestations of chronic cutaneous graft-vs-host disease (cGVHD) are poorly understood. Localization of sclerotic-type chronic graft-vs-host disease to sites of skin injury (isomorphic and isotopic responses), a recognized phenomenon in morphea, suggests a potential common pathway between cGVHD and other sclerotic skin conditions. Four cases of sclerotic-type cGVHD developed at the site of disparate skin injuries (ionizing radiotherapy, repeated needle sticks, central catheter site, and varicella-zoster virus infection). We review the spectrum of previously reported cases of sclerotic and nonsclerotic cGVHD relating to external forces on the skin. Localization of sclerotic-type cGVHD may occur after many types of skin injury, including UV and ionizing radiotherapy, needle sticks, viral infection, and pressure or friction. Recognition of this phenomenon may be helpful for the early diagnosis of sclerotic disease. Recent insights into the immunological consequences of minor skin injury may provide important clues to the underlying pathogenesis of cGVHD-mediated skin disease.

Hypofractionated Palliative Radiotherapy with Concurrent Radiosensitizing Chemotherapy for Advanced Head and Neck Cancer Using the "QUAD-SHOT Regimen".

PubMed

Gamez, Mauricio E; Agarwal, Manuj; Hu, Kenneth S; Lukens, John N; Harrison, Louis B

2017-02-01

To analyze the outcomes using the hypofractionated palliative radiotherapy regimen "QUAD-Shot" with concurrent radiosensitizing chemotherapy for advanced head and neck cancer. We analyzed twenty-one patients with newly-diagnosed or recurrent head and neck cancer treated with palliative hypofractionated concurrent chemoradiation using the QUAD-Shot regimen. All patients received at least one cycle of RT, with sixteen patients (76%) completing all three cycles. 85.7 % of patients had objective response to therapy with five patients (23.8%) demonstrating complete response (CR) and thirteen patients (61.9%) demonstrating partial response (PR). Palliation of symptoms was achieved in all (100%) of the sixteen patients that completed the three cycles. Median overall survival and median progression-free survival were 7 and 4 months, respectively. QUAD-Shot palliative radiation therapy coupled with radiosensitizing chemotherapy is efficacious and well-tolerated in patients with newly-diagnosed or recurrent head and neck cancer not amenable to curative therapy. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Breast interest group faculty of radiation oncology: Australian and New Zealand patterns of practice survey on breast radiotherapy.

PubMed

Nguyen, Kimberley; Mackenzie, Penny; Allen, Angela; Dreosti, Marcus; Morgia, Marita; Zissiadis, Yvonne; Lamoury, Gilian; Windsor, Apsara

2017-08-01

This patterns of practice study was conducted on behalf of the RANZCR Breast Interest Group in order to document current radiotherapy practices for breast cancer in Australia and New Zealand. The survey identifies variations and highlights potential contentious aspects of radiotherapy management of breast cancer. A fifty-eight question survey was disseminated via the Survey Monkey digital platform to 388 Radiation Oncologists in Australia and New Zealand. In total, 156 responses were received and collated. Areas of notable consensus among respondents included hypofractionation (77.3% of respondents would 'always' or 'sometimes' consider hypofractionation in the management of ductal carcinoma in-situ and 99.3% in early invasive breast cancer); margin status in early breast cancer (73.8% believe a clear inked margin is sufficient and does not require further surgery) and use of bolus in post-mastectomy radiotherapy (PMRT) (91.1% of participants use bolus in PMRT). Areas with a wider degree of variability amongst respondents included regional nodal irradiation and components of radiotherapy planning and delivery (examples include the technique used for delivery of boost and frequency of bolus application for PMRT). The results of these patterns of practice survey informs radiation oncologists in Australia and New Zealand of the current clinical practices being implemented by their peers. The survey identifies areas of consensus and contention, the latter of which may lead to a development of research trials and/or educational activities to address these areas of uncertainty. © 2016 The Royal Australian and New Zealand College of Radiologists.

The Efficacy of Radiotherapy in the Treatment of Orbital Pseudotumor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matthiesen, Chance, E-mail: chance-matthiesen@ouhsc.ed; Bogardus, Carl; Thompson, J. Spencer

Purpose: To review institutional outcomes for patients treated with external-beam radiotherapy (EBRT) for orbital pseudotumor. Methods and Materials: This is a single-institution retrospective review of 20 orbits in 16 patients diagnosed with orbital pseudotumor that received EBRT at the University of Oklahoma, Department of Radiation Oncology. Treated patients had a median follow-up of 16.5 months. Results: Fifteen patients (93.7%) were initially treated with corticosteroids. Eight had recurrence after steroid cessation, six were unable to taper corticosteroids completely or partially, and one experienced progression of symptoms despite corticosteroid therapy. Fourteen patients (87.5%) initially responded to radiotherapy indicated by clinical improvement ofmore » preradiation symptoms and/or tapering of corticosteroid dose. Mean EBRT dose was 20 Gy (range, 14-30 Gy). Thirteen patients (81.2%) continued to improve after radiation therapy. Patient outcomes were complete cessation of corticosteroid therapy in nine patients (56.3%) and reduced corticosteroid dose in four patients (25%). Radiotherapy did not achieve long-term control for three patients (18.7%), who still required preradiation corticosteroid dosages. Three patients received retreatment(s) of four orbits, of which two patients achieved long-term symptom control without corticosteroid dependence. One patient received retreatment to an orbit three times, achieving long-term control without corticosteroid dependence. No significant late effects have been observed in retreated patients. Conclusions: Radiotherapy is an effective treatment for acute symptomatic improvement and long-term control of orbital pseudotumor. Orbital retreatment can be of clinical benefit, without apparent increase in morbidity, when initial irradiation fails to achieve complete response.« less

Lapatinib in Combination With Radiation Diminishes Tumor Regrowth in HER2+ and Basal-Like/EGFR+ Breast Tumor Xenografts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sambade, Maria J.; Kimple, Randall J.; Camp, J. Terese

2010-06-01

Purpose: To determine whether lapatinib, a dual epidermal growth factor receptor (EGFR)/HER2 kinase inhibitor, can radiosensitize EGFR+ or HER2+ breast cancer xenografts. Methods and Materials: Mice bearing xenografts of basal-like/EGFR+ SUM149 and HER2+ SUM225 breast cancer cells were treated with lapatinib and fractionated radiotherapy and tumor growth inhibition correlated with alterations in ERK1 and AKT activation by immunohistochemistry. Results: Basal-like/EGFR+ SUM149 breast cancer tumors were completely resistant to treatment with lapatinib alone but highly growth impaired with lapatinib plus radiotherapy, exhibiting an enhancement ratio average of 2.75 and a fractional tumor product ratio average of 2.20 during the study period.more » In contrast, HER2+ SUM225 breast cancer tumors were highly responsive to treatment with lapatinib alone and yielded a relatively lower enhancement ratio average of 1.25 during the study period with lapatinib plus radiotherapy. Durable tumor control in the HER2+ SUM225 model was more effective with the combination treatment than either lapatinib or radiotherapy alone. Immunohistochemical analyses demonstrated that radiosensitization by lapatinib correlated with ERK1/2 inhibition in the EGFR+ SUM149 model and with AKT inhibition in the HER2+ SUM225 model. Conclusion: Our data suggest that lapatinib combined with fractionated radiotherapy may be useful against EGFR+ and HER2+ breast cancers and that inhibition of downstream signaling to ERK1/2 and AKT correlates with sensitization in EGFR+ and HER2+ cells, respectively.« less

Radiotherapy With or Without Surgery for Patients With Idiopathic Sclerosing Orbital Inflammation Refractory or Intolerant to Steroid Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Jong Hoon; Kim, Yeon-Sil, E-mail: yeonkim7@catholic.ac.kr; Yang, Suk Woo

Purpose: To evaluate the outcomes of patients with idiopathic sclerosing orbital inflammation (ISOI) treated with radiotherapy with or without surgery. Methods and Materials: We retrospectively reviewed 22 patients with histopathologically confirmed ISOI who had been refractory or intolerant to steroid therapy and treated with radiation with or without surgery. The radiation dose ranged from 20 to 40 Gy (median, 20 Gy) at 2 Gy per fraction. Presenting signs and treatment outcomes were assessed. Results: Proptosis was the most common sign at presentation, seen in 19 (86.3%) patients, followed by restriction of extraocular movements in 10 (45.4%) patients. Response to radiotherapymore » was complete in 15 (68.1%) patients, partial in 3 (13.6%) patients, and none in 4 (18.2%) patients. At the median follow-up of 34 months, 14 (63.6%) patients had progression-free state of symptoms and signs, with the progression-free duration ranging from 3 to 75 months (median, 41.5 months), whereas 8 (36.4%) patients had recurrent or persistent disease although they had received radiotherapy. Of the 14 progression-free patients, 6 underwent a bimodality treatment of debulking surgery of ocular disease and radiotherapy. They had had no recurrent disease. Cataract was the most common late complications, and 2 patients experienced a Grade 3 cataract. Conclusion: Our study suggests that for patients with ISOI who are refractory or intolerant to steroid therapy, 20 Gy of radiotherapy appears to be effective for the control of disease with acceptable complications, especially when it is combined with surgery.« less

Age at exposure and attained age variations of cancer risk in the Japanese A-bomb and radiotherapy cohorts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schneider, Uwe, E-mail: uwe.schneider@uzh.ch; Walsh, Linda

Purpose: Phenomenological risk models for radiation-induced cancer are frequently applied to estimate the risk of radiation-induced cancers at radiotherapy doses. Such models often include the effect modification, of the main risk to radiation dose response, by age at exposure and attained age. The aim of this paper is to compare the patterns in risk effect modification by age, between models obtained from the Japanese atomic-bomb (A-bomb) survivor data and models for cancer risks previously reported for radiotherapy patients. Patterns in risk effect modification by age from the epidemiological studies of radiotherapy patients were also used to refine and extend themore » risk effect modification by age obtained from the A-bomb survivor data, so that more universal models can be presented here. Methods: Simple log-linear and power functions of age for the risk effect modification applied in models of the A-bomb survivor data are compared to risks from epidemiological studies of second cancers after radiotherapy. These functions of age were also refined and fitted to radiotherapy risks. The resulting age models provide a refined and extended functional dependence of risk with age at exposure and attained age especially beyond 40 and 65 yr, respectively, and provide a better representation than the currently available simple age functions. Results: It was found that the A-bomb models predict risk similarly to the outcomes of testicular cancer survivors. The survivors of Hodgkin’s disease show steeper variations of risk with both age at exposure and attained age. The extended models predict solid cancer risk increase as a function of age at exposure beyond 40 yr and the risk decrease as a function of attained age beyond 65 yr better than the simple models. Conclusions: The standard functions for risk effect modification by age, based on the A-bomb survivor data, predict second cancer risk in radiotherapy patients for ages at exposure prior to 40 yr and attained ages before 55 yr reasonably well. However, for larger ages, the refined and extended models can be applied to predict the risk as a function of age.« less

Age at exposure and attained age variations of cancer risk in the Japanese A-bomb and radiotherapy cohorts.

PubMed

Schneider, Uwe; Walsh, Linda

2015-08-01

Phenomenological risk models for radiation-induced cancer are frequently applied to estimate the risk of radiation-induced cancers at radiotherapy doses. Such models often include the effect modification, of the main risk to radiation dose response, by age at exposure and attained age. The aim of this paper is to compare the patterns in risk effect modification by age, between models obtained from the Japanese atomic-bomb (A-bomb) survivor data and models for cancer risks previously reported for radiotherapy patients. Patterns in risk effect modification by age from the epidemiological studies of radiotherapy patients were also used to refine and extend the risk effect modification by age obtained from the A-bomb survivor data, so that more universal models can be presented here. Simple log-linear and power functions of age for the risk effect modification applied in models of the A-bomb survivor data are compared to risks from epidemiological studies of second cancers after radiotherapy. These functions of age were also refined and fitted to radiotherapy risks. The resulting age models provide a refined and extended functional dependence of risk with age at exposure and attained age especially beyond 40 and 65 yr, respectively, and provide a better representation than the currently available simple age functions. It was found that the A-bomb models predict risk similarly to the outcomes of testicular cancer survivors. The survivors of Hodgkin's disease show steeper variations of risk with both age at exposure and attained age. The extended models predict solid cancer risk increase as a function of age at exposure beyond 40 yr and the risk decrease as a function of attained age beyond 65 yr better than the simple models. The standard functions for risk effect modification by age, based on the A-bomb survivor data, predict second cancer risk in radiotherapy patients for ages at exposure prior to 40 yr and attained ages before 55 yr reasonably well. However, for larger ages, the refined and extended models can be applied to predict the risk as a function of age.

Genetic Analysis of T Cell Lymphomas in Carbon Ion-Irradiated Mice Reveals Frequent Interstitial Chromosome Deletions: Implications for Second Cancer Induction in Normal Tissues during Carbon Ion Radiotherapy.

PubMed

Blyth, Benjamin J; Kakinuma, Shizuko; Sunaoshi, Masaaki; Amasaki, Yoshiko; Hirano-Sakairi, Shinobu; Ogawa, Kanae; Shirakami, Ayana; Shang, Yi; Tsuruoka, Chizuru; Nishimura, Mayumi; Shimada, Yoshiya

2015-01-01

Monitoring mice exposed to carbon ion radiotherapy provides an indirect method to evaluate the potential for second cancer induction in normal tissues outside the radiotherapy target volume, since such estimates are not yet possible from historical patient data. Here, male and female B6C3F1 mice were given single or fractionated whole-body exposure(s) to a monoenergetic carbon ion radiotherapy beam at the Heavy Ion Medical Accelerator in Chiba, Japan, matching the radiation quality delivered to the normal tissue ahead of the tumour volume (average linear energy transfer = 13 keV x μm(-1)) during patient radiotherapy protocols. The mice were monitored for the remainder of their lifespan, and a large number of T cell lymphomas that arose in these mice were analysed alongside those arising following an equivalent dose of 137Cs gamma ray-irradiation. Using genome-wide DNA copy number analysis to identify genomic loci involved in radiation-induced lymphomagenesis and subsequent detailed analysis of Notch1, Ikzf1, Pten, Trp53 and Bcl11b genes, we compared the genetic profile of the carbon ion- and gamma ray-induced tumours. The canonical set of genes previously associated with radiation-induced T cell lymphoma was identified in both radiation groups. While the pattern of disruption of the various pathways was somewhat different between the radiation types, most notably Pten mutation frequency and loss of heterozygosity flanking Bcl11b, the most striking finding was the observation of large interstitial deletions at various sites across the genome in carbon ion-induced tumours, which were only seen infrequently in the gamma ray-induced tumours analysed. If such large interstitial chromosomal deletions are a characteristic lesion of carbon ion irradiation, even when using the low linear energy transfer radiation to which normal tissues are exposed in radiotherapy patients, understanding the dose-response and tissue specificity of such DNA damage could prove key to assessing second cancer risk in carbon ion radiotherapy patients.

Long-term decision regret after post-prostatectomy image-guided intensity-modulated radiotherapy.

PubMed

Shakespeare, Thomas P; Chin, Stephen; Manuel, Lucy; Wen, Shelly; Hoffman, Matthew; Wilcox, Shea W; Aherne, Noel J

2017-02-01

Decision regret (DR) may occur when a patient believes their outcome would have been better if they had decided differently about their management. Although some studies investigate DR after treatment for localised prostate cancer, none report DR in patients undergoing surgery and post-prostatectomy radiotherapy. We evaluated DR in this group of patients overall, and for specific components of therapy. We surveyed 83 patients, with minimum 5 years follow-up, treated with radical prostatectomy (RP) and post-prostatectomy image-guided intensity-modulated radiotherapy (IG-IMRT) to 64-66 Gy following www.EviQ.org.au protocols. A validated questionnaire identified DR if men either indicated that they would have been better off had they chosen another treatment, or they wished they could change their mind about treatment. There was an 85.5% response rate, with median follow-up post-IMRT 78 months. Adjuvant IG-IMRT was used in 28% of patients, salvage in 72% and ADT in 48%. A total of 70% of patients remained disease-free. Overall, 16.9% of patients expressed DR for treatment, with fourfold more regret for the RP component of treatment compared to radiotherapy (16.9% vs 4.2%, P = 0.01). DR for androgen deprivation was 14.3%. Patients were regretful of surgery due to toxicity, not being adequately informed about radiotherapy as an alternative, positive margins and surgery costs (83%, 33%, 25% and 8% of regretful patients respectively). Toxicity caused DR in the three radiotherapy-regretful and four ADT-regretful patients. Patients were twice as regretful overall, and of surgery, for salvage vs adjuvant approaches (both 19.6% vs 10.0%). Decision regret after RP and post-prostatectomy IG-IMRT is uncommon, although patients regret RP more than post-operative IG-IMRT. This should reassure urologists referring patients for post-prostatectomy IG-IMRT, particularly in the immediate adjuvant setting. Other implications include appropriate patient selection for RP (and obtaining clear margins), and ensuring adequately discussing definitive radiotherapy as an alternative to surgery. © 2016 The Royal Australian and New Zealand College of Radiologists.

p53 sequence analysis predicts treatment response and outcome of patients with esophageal carcinoma.

PubMed

Ribeiro, U; Finkelstein, S D; Safatle-Ribeiro, A V; Landreneau, R J; Clarke, M R; Bakker, A; Swalsky, P A; Gooding, W E; Posner, M C

1998-07-01

The ability to predict biologic behavior and treatment responsiveness would be a valuable asset in the multimodality approach to esophageal carcinoma. The authors examined whether alterations of the p53 gene correlate with clinicopathologic parameters, response to preoperative chemotherapy/radiotherapy, and outcome in patients with esophageal carcinoma. METHODS. Histopathologic/genetic analysis of p53 was performed on formalin fixed, paraffin embedded tissues. Tissue sections were stained immunohistochemically for p53 protein followed by topographic genotyping comprised of polymerase chain reaction amplification and direct sequencing of p53 exons 5-8. All patients received induction chemotherapy (5-fluorouracil, cisplatin, and alpha-interferon) and concurrent external beam radiotherapy (4500 centigrays) followed by resection. p53 analysis performed on 42 tumors from patients with potentially resectable esophageal carcinoma revealed 25 of the 42 tumors (59.5%) to be p53 immunopositive; however, only 17 of the 42 tumors (40.5%) were proven to contain p53 point mutational damage in exons 8 (n=5), 5 (n=5), 7 (n=4), and 6 (n=3). Eight cases were weakly immunopositive and had no genotype mutation suggesting hyperexpression of normal wild-type p53. Genotyping also identified two immunonegative cases with deletion-type mutations (exons 5 and 6). Tissue samples collected before and after chemotherapy/radiotherapy exhibited fidelity in p53 mutational genotype in all cases. The presence of a p53 point mutation positively correlated with pTNM stage (P=0.003) and residual disease in the resected specimen (P=0.01). Moreover, survival of patients with p53 mutations was significantly lower than that of patients without mutations (overall survival of 21.6 months vs. 40 months; P=0.0038; and disease free survival of 14.1 months vs. 38 months; P=0.0004). Histopathologic/genetic analysis is a better determinant of p53 mutational damage than immunohistochemistry alone and can be used as a prognostic marker for esophageal carcinoma. p53 genotyping may define a subset of patients who respond to chemotherapy/radiotherapy and may predict who potentially benefits from multimodality therapy.

Overall survival and the response to radiotherapy among molecular subtypes of breast cancer brain metastases treated with targeted therapies.

PubMed

Miller, Jacob A; Kotecha, Rupesh; Ahluwalia, Manmeet S; Mohammadi, Alireza M; Chao, Samuel T; Barnett, Gene H; Murphy, Erin S; Vogelbaum, Michael A; Angelov, Lilyana; Peereboom, David M; Suh, John H

2017-06-15

The current study was conducted to investigate survival and the response to radiotherapy among patients with molecular subtypes of breast cancer brain metastases treated with or without targeted therapies. Patients diagnosed with breast cancer brain metastases at a single tertiary care institution were included. The primary outcome was overall survival, whereas secondary outcomes included the cumulative incidences of distant intracranial failure, local failure, and radiation necrosis. Competing risks regression was used to model secondary outcomes. Within the study period, 547 patients presented with 3224 brain metastases and met inclusion criteria. Among patients with human epidermal growth factor receptor 2 (HER2)-amplified disease, 80% received HER2 antibodies and 38% received HER2/epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The median survival was significantly shorter in the basal cohort (8.4 months), and progressively increased in the luminal A (12.3 months), HER2-positive (15.4 months), and luminal B (18.8 months) cohorts (P<.001). Among patients with HER2-amplified disease, the median survival was extended with the use of both HER2 antibodies (17.9 months vs 15.1 months; P = .04) and TKIs (21.1 months vs 15.4 months; P = .03). The 12-month cumulative incidences of local failure among molecular subtypes were 6.0% in the luminal A cohort, 10.3% in the luminal B cohort, 15.4% in the HER2-positive cohort, and 9.9% in the basal cohort (P = .01). Concurrent HER2/epidermal growth factor receptor TKIs with stereotactic radiosurgery significantly decreased the 12-month cumulative incidence of local failure from 15.1% to 5.7% (P<.001). Molecular subtypes appear to be prognostic for survival and predictive of the response to radiotherapy. TKIs were found to improve survival and local control, and may decrease the rate of distant failure. To preserve neurocognition, these results support a paradigm of upfront radiosurgery and HER2-directed therapy in the HER2-amplified population, reserving whole-brain radiotherapy for salvage. Cancer 2017;123:2283-2293. © 2017 American Cancer Society. © 2017 American Cancer Society.

Proton and carbon ion radiotherapy for primary brain tumors delivered with active raster scanning at the Heidelberg Ion Therapy Center (HIT): early treatment results and study concepts

PubMed Central

2012-01-01

Background Particle irradiation was established at the University of Heidelberg 2 years ago. To date, more than 400 patients have been treated including patients with primary brain tumors. In malignant glioma (WHO IV) patients, two clinical trials have been set up-one investigating the benefit of a carbon ion (18 GyE) vs. a proton boost (10 GyE) in addition to photon radiotherapy (50 Gy), the other one investigating reirradiation with escalating total dose schedules starting at 30 GyE. In atypical meningioma patients (WHO °II), a carbon ion boost of 18 GyE is applied to macroscopic tumor residues following previous photon irradiation with 50 Gy. This study was set up in order to investigate toxicity and response after proton and carbon ion therapy for gliomas and meningiomas. Methods 33 patients with gliomas (n = 26) and meningiomas (n = 7) were treated with carbon ion (n = 26) and proton (n = 7) radiotherapy. In 22 patients, particle irradiation was combined with photon therapy. Temozolomide-based chemotherapy was combined with particle therapy in 17 patients with gliomas. Particle therapy as reirradiation was conducted in 7 patients. Target volume definition was based upon CT, MRI and PET imaging. Response was assessed by MRI examinations, and progression was diagnosed according to the Macdonald criteria. Toxicity was classified according to CTCAE v4.0. Results Treatment was completed and tolerated well in all patients. Toxicity was moderate and included fatigue (24.2%), intermittent cranial nerve symptoms (6%) and single episodes of seizures (6%). At first and second follow-up examinations, mean maximum tumor diameters had slightly decreased from 29.7 mm to 27.1 mm and 24.9 mm respectively. Nine glioma patients suffered from tumor relapse, among these 5 with infield relapses, causing death in 8 patients. There was no progression in any meningioma patient. Conclusions Particle radiotherapy is safe and feasible in patients with primary brain tumors. It is associated with little toxicity. A positive response of both gliomas and meningiomas, which is suggested in these preliminary data, must be evaluated in further clinical trials. PMID:22436135

Merkel Cell Carcinoma Therapeutic Update.

PubMed

Cassler, Nicole M; Merrill, Dean; Bichakjian, Christopher K; Brownell, Isaac

2016-07-01

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Early-stage disease can be cured with surgical resection and radiotherapy (RT). Sentinel lymph node biopsy (SLNB) is an important staging tool, as a microscopic MCC is frequently identified. Adjuvant RT to the primary excision site and regional lymph node bed may improve locoregional control. However, newer studies confirm that patients with biopsy-negative sentinel lymph nodes may not benefit from regional RT. Advanced MCC currently lacks a highly effective treatment as responses to chemotherapy are not durable. Recent work suggests that immunotherapy targeting the programmed cell death receptor 1/programmed cell death ligand 1 (PD-1/PD-L1) checkpoint holds great promise in treating advanced MCC and may provide durable responses in a portion of patients. At the same time, high-throughput sequencing studies have demonstrated significant differences in the mutational profiles of tumors with and without the Merkel cell polyomavirus (MCV). An important secondary endpoint in the ongoing immunotherapy trials for MCC will be determining if there is a response difference between the virus-positive MCC tumors that typically lack a large mutational burden and the virus-negative tumors that have a large number of somatic mutations and predicted tumor neoantigens. Interestingly, sequencing studies have failed to identify a highly recurrent activated driver pathway in the majority of MCC tumors. This may explain why targeted therapies can demonstrate exceptional responses in case reports but fail when treating all comers with MCC. Ultimately, a precision medicine approach may be more appropriate for treating MCC, where identified driver mutations are used to direct targeted therapies. At a minimum, stratifying patients in future clinical trials based on tumor viral status should be considered as virus-negative tumors are more likely to harbor activating driver mutations.

The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation.

PubMed

Mendes, Fernando; Domingues, Cátia; Rodrigues-Santos, Paulo; Abrantes, Ana Margarida; Gonçalves, Ana Cristina; Estrela, Jéssica; Encarnação, João; Pires, Ana Salomé; Laranjo, Mafalda; Alves, Vera; Teixo, Ricardo; Sarmento, Ana Bela; Botelho, Maria Filomena; Rosa, Manuel Santos

2016-04-01

Immune surveillance seems to represent an effective tumor suppressor mechanism. However, some cancer cells survive and become variants, being poorly immunogenic and able to enter a steady-state phase. These cells become functionally dormant or remain hidden clinically throughout. Neoplastic cells seem to be able to instruct immune cells to undergo changes promoting malignancy. Radiotherapy may act as a trigger of the immune response. After radiotherapy a sequence of reactions occurs, starting in the damage of oncogenic cells by multiple mechanisms, leading to the immune system positive feedback against the tumor. The link between radiotherapy and the immune system is evident. T cells, macrophages, Natural Killer cells and other immune cells seem to have a key role in controlling the tumor. T cells may be dysfunctional and remain in a state of T cell exhaustion, nonetheless, they often retain a high potential for successful defense against cancer, being able to be mobilized to become highly functional. The lack of clinical trials on a large scale makes data a little robust, in spite of promising information, there are still many variables in the studies relating to radiation and immune system. The clarification of the mechanisms underlying immune response to radiation exposure may contribute to treatment improvement, gain of life quality and span of patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Radiotherapy timing in the treatment of limited-stage small cell lung cancer: the impact of thoracic and brain irradiation on survival.

PubMed

Scotti, Vieri; Meattini, Icro; Franzese, Ciro; Saieva, Calogero; Bertocci, Silvia; Meacci, Fiammetta; Furfaro, Ilaria; Scartoni, Daniele; Cecchini, Sara; Desideri, Isacco; Ferrari, Katia; Bruni, Alessio; De Luca Cardillo, Carla; Bastiani, Paolo; Agresti, Benedetta; Mangoni, Monica; Livi, Lorenzo; Biti, Giampaolo

2014-01-01

Small cell lung cancer is an aggressive histologic subtype of lung cancer in which the role of chemotherapy and radiotherapy has been well established in limited-stage disease. We retrospectively reviewed a series of limited-stage small cell lung cancers treated with chemotherapy and thoracic and brain radiotherapy. A total of 124 patients affected by limited-stage small cell lung cancer has been treated over 10 years in our Institute. Fifty-three patients (42.8%) had concomitant radio-chemotherapy treatment and 71 patients (57.2%) a sequential treatment. Eighty-eight patients (70.9%) underwent an association of a platinum-derived drug (cisplatinum or carboplatinum) and etoposide. Prophylactic cranial irradiation was planned in all patients with histologically proven complete response to primary radio-chemotherapy. With a mean follow-up of 2.2 years, complete response was obtained in 50.8% of cases. We found a significant difference between different radio-chemotherapy association approaches (P = 0.007): percentages of overall survival were respectively 10.0%, 12.9% and 5.6% in early, late concomitant and sequential radio-chemotherapy timing. Cranial prophylaxis did not seem to influence overall survival (P = 0.21) or disease-free survival for local relapse (P = 0.34). Concomitant radio-chemotherapy is the best approach according to our experience. Our results show a benefit of prophylactic cranial irradiation in distant metastasis-free survival.

[A case of lung metastasis from esophageal cancer resistant to fluorouracil and cisplatin combination therapy but responsive to radiation therapy].

PubMed

Ami, Katsunori; Seki, Ryouta; Takasaki, Jun; Amagasa, Hidetoshi; Kamikozuru, Hirotaka; Ganno, Hideaki; Kurokawa, Toshiaki; Fukuda, Akira; Nagahama, Takeshi; Ando, Masayuki; Yamada, Yosuke; Kodaka, Fumi; Arai, Kuniyoshi

2012-11-01

At present, fluorouracil and cisplatin combination therapy is the standard chemotherapy against esophageal cancer, but the choice of second-line chemotherapy is controversial. Furthermore, the effect of radiation therapy against lung metastasis from esophageal cancer is unclear. We report a case of lung metastasis from esophageal cancer resistant to fluorouracil and cisplatin combination therapy but responsive to radiation therapy. The patient was a 55-year-old woman who had undergone an operation for esophageal cancer at another hospital. A single right lung metastasis appeared 1 year after the operation. Combined fluorouracil and cisplatin therapy was administrated for 5 courses, but the lung metastasis increased in size. Afterwards, she was admitted to our hospital. We treated her with 14 courses of S-1 and docetaxel combination therapy administered over 13 months. The lung metastasis was decreased for a period. Furthermore, radiofrequency ablation under computed tomography was performed against the lung metastasis re-growth at another hospital. Although the lung metastasis increased in size, no further metastases were detected during the clinical course. The patient was treated with radiotherapy for the lung metastasis re-growth. The tumor had almost disappeared by 10 months after the completion of radiotherapy. Currently, she is receiving palliative care as an outpatient and the lung metastasis has not been evident for 2 years since the completion of radiotherapy.

Texture analysis of medical images for radiotherapy applications

PubMed Central

Rizzo, Giovanna

2017-01-01

The high-throughput extraction of quantitative information from medical images, known as radiomics, has grown in interest due to the current necessity to quantitatively characterize tumour heterogeneity. In this context, texture analysis, consisting of a variety of mathematical techniques that can describe the grey-level patterns of an image, plays an important role in assessing the spatial organization of different tissues and organs. For these reasons, the potentiality of texture analysis in the context of radiotherapy has been widely investigated in several studies, especially for the prediction of the treatment response of tumour and normal tissues. Nonetheless, many different factors can affect the robustness, reproducibility and reliability of textural features, thus limiting the impact of this technique. In this review, an overview of the most recent works that have applied texture analysis in the context of radiotherapy is presented, with particular focus on the assessment of tumour and tissue response to radiations. Preliminary, the main factors that have an influence on features estimation are discussed, highlighting the need of more standardized image acquisition and reconstruction protocols and more accurate methods for region of interest identification. Despite all these limitations, texture analysis is increasingly demonstrating its ability to improve the characterization of intratumour heterogeneity and the prediction of clinical outcome, although prospective studies and clinical trials are required to draw a more complete picture of the full potential of this technique. PMID:27885836

Dosimetry quality audit of high energy photon beams in greek radiotherapy centers.

PubMed

Hourdakis, Constantine J; Boziari, A

2008-04-01

Dosimetry quality audits and intercomparisons in radiotherapy centers is a useful tool in order to enhance the confidence for an accurate therapy and to explore and dissolve discrepancies in dose delivery. This is the first national comprehensive study that has been carried out in Greece. During 2002--2006 the Greek Atomic Energy Commission performed a dosimetry quality audit of high energy external photon beams in all (23) Greek radiotherapy centers, where 31 linacs and 13 Co-60 teletherapy units were assessed in terms of their mechanical performance characteristics and relative and absolute dosimetry. The quality audit in dosimetry of external photon beams took place by means of on-site visits, where certain parameters of the photon beams were measured, calculated and assessed according to a specific protocol and the IAEA TRS 398 dosimetry code of practice. In each radiotherapy unit (Linac or Co-60), certain functional parameters were measured and the results were compared to tolerance values and limits. Doses in water under reference and non reference conditions were measured and compared to the stated values. Also, the treatment planning systems (TPS) were evaluated with respect to irradiation time calculations. The results of the mechanical tests, dosimetry measurements and TPS evaluation have been presented in this work and discussed in detail. This study showed that Co-60 units had worse performance mechanical characteristics than linacs. 28% of all irradiation units (23% of linacs and 42% of Co-60 units) exceeded the acceptance limit at least in one mechanical parameter. Dosimetry accuracy was much worse in Co60 units than in linacs. 61% of the Co60 units exhibited deviations outside +/-3% and 31% outside +/-5%. The relevant percentages for the linacs were 24% and 7% respectively. The results were grouped for each hospital and the sources of errors (functional and human) have been investigated and discussed in details. This quality audit proved to be a useful tool for the improvement of quality in radiotherapy. It succeeded to disseminate the IAEA TRS-398 protocol in nearly all radiotherapy centers achieving homogenization and consistency of dosimetry within the country. Also, it detected discrepancies in dosimetry and provided guidance and recommendations to eliminate sources of errors. Finally, it proved that quality assurance programs, periodic quality control tests, maintenance and service play an important role for achieving accuracy and safe operation in radiotherapy.

Stanford V program for locally extensive and advanced Hodgkin lymphoma: the Memorial Sloan-Kettering Cancer Center experience.

PubMed

Edwards-Bennett, S M; Jacks, L M; Moskowitz, C H; Wu, E J; Zhang, Z; Noy, A; Portlock, C S; Straus, D J; Zelenetz, A D; Yahalom, J

2010-03-01

The Stanford group has reported excellent results with the Stanford V regimen for patients with bulky and/or advanced Hodgkin lymphoma (HL). However, Gobbi reported markedly inferior failure-free survival (FFS) comparing Stanford V to other regimens but included major deviations from the original program. We retrospectively examined whether treatment at our institution carefully following Stanford V guidelines would confirm the original Stanford outcome data. From June 1995 to May 2002, 126 patients with either locally extensive or advanced HL were treated with the 12-week Stanford V chemotherapy program followed by 36-Gy involved-field radiotherapy to sites initially > or =5 cm and/or to macroscopic splenic disease. Overall, 26% had stage IV disease and 20% had international prognostic score (IPS) > or =4. Overall survival (OS), disease-specific survival, progression-free survival (PFS), FFS, and freedom from second relapse (FF2R) were determined. The 5- and 7-year OS were 90% and 88%, respectively. The 5-year FFS was 78%. IPS > or =4 was a significant independent predictor of worse OS and PFS. The FF2R was 64% at 3 years. Stanford V with appropriate radiotherapy is a highly effective regimen for locally extensive and advanced HL.

New quality assurance program integrating "modern radiotherapy" within the German Hodgkin Study Group.

PubMed

Kriz, J; Baues, C; Engenhart-Cabillic, R; Haverkamp, U; Herfarth, K; Lukas, P; Schmidberger, H; Marnitz-Schulze, S; Fuchs, M; Engert, A; Eich, H T

2017-02-01

Field design changed substantially from extended-field RT (EF-RT) to involved-field RT (IF-RT) and now to involved-node RT (IN-RT) and involved-site RT (IS-RT) as well as treatment techniques in radiotherapy (RT) of Hodgkin's lymphoma (HL). The purpose of this article is to demonstrate the establishment of a quality assurance program (QAP) including modern RT techniques and field designs within the German Hodgkin Study Group (GHSG). In the era of modern conformal RT, this QAP had to be fundamentally adapted and a new evaluation process has been intensively discussed by the radiotherapeutic expert panel of the GHSG. The expert panel developed guidelines and criteria to analyse "modern" field designs and treatment techniques. This work is based on a dataset of 11 patients treated within the sixth study generation (HD16-17). To develop a QAP of "modern RT", the expert panel defined criteria for analysing current RT procedures. The consensus of a modified QAP in ongoing and future trials is presented. With this schedule, the QAP of the GHSG could serve as a model for other study groups.

Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes.

PubMed

López, Escarlata; Guerrero, Rosario; Núñez, Maria Isabel; del Moral, Rosario; Villalobos, Mercedes; Martínez-Galán, Joaquina; Valenzuela, Maria Teresa; Muñoz-Gámez, José Antonio; Oliver, Francisco Javier; Martín-Oliva, David; Ruiz de Almodóvar, José Mariano

2005-01-01

Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects. Intrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments. Radiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects. After radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity. Further research is warranted to identify the major determinants of normal tissue radiation response to make it possible to individualize treatments and improve the outcome of radiotherapy in cancer patients.

SU-E-J-211: Design and Study of In-House Software Based Respiratory Motion Monitoring, Controlling and Breath-Hold Device for Gated Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shanmugam, Senthilkumar

Purpose: The purpose of this present work was to fabricate an in-house software based respiratory monitoring, controlling and breath-hold device using computer software programme which guides the patient to have uniform breath hold in response to request during the gated radiotherapy. Methods: The respiratory controlling device consists of a computer, inhouse software, video goggles, a highly sensitive sensor for measurement of distance, mounting systems, a camera, a respiratory signal device, a speaker and a visual indicator. The computer is used to display the respiratory movements of the patient with digital as well as analogue respiration indicators during the respiration cycle,more » to control, breath-hold and analyze the respiratory movement using indigenously developed software. Results: Studies were conducted with anthropomophic phantoms by simulating the respiratory motion on phantoms and recording the respective movements using the respiratory monitoring device. The results show good agreement between the simulated and measured movements. Further studies were conducted for 60 cancer patients with several types of cancers in the thoracic region. The respiratory movement cycles for each fraction of radiotherapy treatment were recorded and compared. Alarm indications are provided in the system to indicate when the patient breathing movement exceeds the threshold level. This will help the patient to maintain uniform breath hold during the radiotherapy treatment. Our preliminary clinical test results indicate that our device is highly reliable and able to maintain the uniform respiratory motion and breathe hold during the entire course of gated radiotherapy treatment. Conclusion: An indigenous respiratory monitoring device to guide the patient to have uniform breath hold device was fabricated. The alarm feature and the visual waveform indicator in the system guide the patient to have normal respiration. The signal from the device can be connected to the radiation unit in near future to carry out the gated radiotherapy treatment.« less

Effects of yoga on symptom management in breast cancer patients: A randomized controlled trial.

PubMed

Vadiraja, S Hosakote; Rao, M Raghavendra; Nagendra, R Hongasandra; Nagarathna, Raghuram; Rekha, Mohan; Vanitha, Nanjundiah; Gopinath, S Kodaganuru; Srinath, Bs; Vishweshwara, Ms; Madhavi, Ys; S Ajaikumar, Basavalingaiah; Ramesh, S Bilimagga; Rao, Nalini

2009-07-01

This study compares the effects of an integrated yoga program with brief supportive therapy on distressful symptoms in breast cancer outpatients undergoing adjuvant radiotherapy. Eighty-eight stage II and III breast cancer outpatients were randomly assigned to receive yoga (n = 44) or brief supportive therapy (n = 44) prior to their radiotherapy treatment. Intervention consisted of yoga sessions lasting 60 min daily while the control group was imparted supportive therapy once in 10 days during the course of their adjuvant radiotherapy. Assessments included Rotterdam Symptom Check List and European Organization for Research in the Treatment of Cancer-Quality of Life (EORTC QoL C30) symptom scale. Assessments were done at baseline and after 6 weeks of radiotherapy treatment. A GLM repeated-measures ANOVA showed a significant decrease in psychological distress (P = 0.01), fatigue (P = 0.007), insomnia (P = 0.001), and appetite loss (P = 0.002) over time in the yoga group as compared to controls. There was significant improvement in the activity level (P = 0.02) in the yoga group as compared to controls. There was a significant positive correlation between physical and psychological distress and fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, and constipation. There was a significant negative correlation between the activity level and fatigue, nausea and vomiting, pain, dyspnea, insomnia, and appetite loss. The results suggest beneficial effects with yoga intervention in managing cancer-and treatment-related symptoms in breast cancer patients.

Effects of yoga on symptom management in breast cancer patients: A randomized controlled trial

PubMed Central

Vadiraja, S Hosakote; Rao, M Raghavendra; Nagendra, R Hongasandra; Nagarathna, Raghuram; Rekha, Mohan; Vanitha, Nanjundiah; Gopinath, S Kodaganuru; Srinath, BS; Vishweshwara, MS; Madhavi, YS; S Ajaikumar, Basavalingaiah; Ramesh, S Bilimagga; Rao, Nalini

2009-01-01

Objectives: This study compares the effects of an integrated yoga program with brief supportive therapy on distressful symptoms in breast cancer outpatients undergoing adjuvant radiotherapy. Materials and Methods: Eighty-eight stage II and III breast cancer outpatients were randomly assigned to receive yoga (n = 44) or brief supportive therapy (n = 44) prior to their radiotherapy treatment. Intervention consisted of yoga sessions lasting 60 min daily while the control group was imparted supportive therapy once in 10 days during the course of their adjuvant radiotherapy. Assessments included Rotterdam Symptom Check List and European Organization for Research in the Treatment of Cancer—Quality of Life (EORTC QoL C30) symptom scale. Assessments were done at baseline and after 6 weeks of radiotherapy treatment. Results: A GLM repeated-measures ANOVA showed a significant decrease in psychological distress (P = 0.01), fatigue (P = 0.007), insomnia (P = 0.001), and appetite loss (P = 0.002) over time in the yoga group as compared to controls. There was significant improvement in the activity level (P = 0.02) in the yoga group as compared to controls. There was a significant positive correlation between physical and psychological distress and fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, and constipation. There was a significant negative correlation between the activity level and fatigue, nausea and vomiting, pain, dyspnea, insomnia, and appetite loss. Conclusion: The results suggest beneficial effects with yoga intervention in managing cancer-and treatment-related symptoms in breast cancer patients. PMID:20842268

Neurocognitive Effects of Radiotherapy

DTIC Science & Technology

2015-10-01

performance of the two groups on the Audiovisual Attentional Shift Test did not differ. These tests have not been used previously within the proton...Timing Functions, Serial Response, and Audiovisual Attentional Shift) Table 2. Organs at Risk. #The percent of patients with radiation doses exceeding the

TU-G-BRD-06: The Imaging and Radiation Oncology Core Houston (IROC Houston) QA Center International Activities Outside North America

DOE Office of Scientific and Technical Information (OSTI.GOV)

Followill, D; Kry, S; Molineu, A

Purpose: To describe the extent of IROC Houston’s (formerly the RPC) QA activities and audit results for radiotherapy institutions outside of North America (NA). Methods: The IROC Houston’s QA program components were designed to audit the radiation dose calculation chain from the NIST traceable reference beam calibration, to inclusion of dosimetry parameters used to calculate tumor doses, to the delivery of the radiation dose. The QA program provided to international institutions includes: 1) remote TLD/OSLD audit of machine output, 2) credentialing for advanced technologies, and 3) review of patient treatment records. IROC Houston uses the same standards and acceptance criteriamore » for all of its audits whether for North American or international sites. Results: IROC Houston’s QA program has reached out to radiotherapy sites in 43 different countries since 2013 through their participation in clinical trials. In the past two years, 2,778 international megavoltage beam outputs were audited with OSLD/TLD. While the average IROC/Inst ratio is near unity for all sites monitored, there are international regions whose results are significantly different from the NA region. In the past 2 years, 477 and 87 IMRT H&N phantoms were irradiated at NA and international sites, respectively. Regardless of the OSLD beam audit results, the overall pass rate (87 percent) for all international sites (no region separation) is equal to the NA sites. Of the 182 international patient charts reviewed, 10.7 percent of the dose calculation points did not meet our acceptance criterion as compared to 13.6 percent for NA sites. The lower pass rate for NA sites results from a much larger brachytherapy component which has been shown to be more error prone. Conclusion: IROC Houston has expanded its QA services worldwide and continues a long history of improving radiotherapy dose delivery in many countries. Funding received for QA audit services from the Korean GOG, DAHANCA, EORTC, ICON and CMIC Group.« less

TU-AB-BRD-04: Development of Quality Management Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomadsen, B.

2015-06-15

Current quality assurance and quality management guidelines provided by various professional organizations are prescriptive in nature, focusing principally on performance characteristics of planning and delivery devices. However, published analyses of events in radiation therapy show that most events are often caused by flaws in clinical processes rather than by device failures. This suggests the need for the development of a quality management program that is based on integrated approaches to process and equipment quality assurance. Industrial engineers have developed various risk assessment tools that are used to identify and eliminate potential failures from a system or a process before amore » failure impacts a customer. These tools include, but are not limited to, process mapping, failure modes and effects analysis, fault tree analysis. Task Group 100 of the American Association of Physicists in Medicine has developed these tools and used them to formulate an example risk-based quality management program for intensity-modulated radiotherapy. This is a prospective risk assessment approach that analyzes potential error pathways inherent in a clinical process and then ranks them according to relative risk, typically before implementation, followed by the design of a new process or modification of the existing process. Appropriate controls are then put in place to ensure that failures are less likely to occur and, if they do, they will more likely be detected before they propagate through the process, compromising treatment outcome and causing harm to the patient. Such a prospective approach forms the basis of the work of Task Group 100 that has recently been approved by the AAPM. This session will be devoted to a discussion of these tools and practical examples of how these tools can be used in a given radiotherapy clinic to develop a risk based quality management program. Learning Objectives: Learn how to design a process map for a radiotherapy process Learn how to perform failure modes and effects analysis analysis for a given process Learn what fault trees are all about Learn how to design a quality management program based upon the information obtained from process mapping, failure modes and effects analysis and fault tree analysis. Dunscombe: Director, TreatSafely, LLC and Center for the Assessment of Radiological Sciences; Consultant to IAEA and Varian Thomadsen: President, Center for the Assessment of Radiological Sciences Palta: Vice President of the Center for the Assessment of Radiological Sciences.« less

External beam radiotherapy for palliation of painful bone metastases: pooled data bioeffect dose response analysis of dose fractionation

NASA Astrophysics Data System (ADS)

Naveen, T.; Supe, Sanjay S.; Ganesh, K. M.; Samuel, Jacob

2009-01-01

Bone metastases develop in up to 70% of newly diagnosed cancer patients and result in immobility, anxiety, and depression, severely diminishing the patients quality of life. Radiotherapy is a frequently used modality for bone metastasis and has been shown to be effective in reducing metastatic bone pain and in some instances, causing tumor shrinkage or growth inhibition. There is controversy surrounding the optimal fractionation schedule and total dose of external beam radiotherapy, despite many randomized trials and overviews addressing the issue. This study was undertaken to apply BED to clinical fractionation data of radiotherapeutic management of bone metastases in order to arrive at optimum BED values for acceptable level of response rate. A computerised literature search was conducted to identify all prospective clinical studies that addressed the issue of fractionation for the treatment of bone metastasis. The results of these studies were pooled together to form the database for the analysis. A total of 4111 number of patients received radiation dose ranging from 4 to 40.5 Gy in 1 to 15 fractions with dose per fraction ranging from 2 to 10 Gy. Single fraction treatments were delivered in 2013 patients and the dose varied from 4 to 10 Gy. Multifraction treatments were delivered in 2098 patients and the dose varied from 15 to 40.5 Gy. The biological effective dose (BED) was evaluated for each fractionation schedule using the linear quadratic model and an α/β value of 10 Gy. Response rate increased significantly beyond a BED value of 14.4 Gy (p < 0.01). Based on our analysis and indications from the literature about higher retreatment and fracture rate of single fraction treatments, minimum BED value of 14.4 Gy is recommended.

High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma.

PubMed

Chamberlain, Marc C; Johnston, Sandra K

2010-07-01

We conducted a prospective Phase II study of high-dose methotrexate (HD-MTX) and rituximab with deferred whole brain radiotherapy in patients with newly diagnosed B-cell primary central nervous system lymphoma with a primary objective of evaluating progression-free survival (PFS). Forty patients (25 men; 15 women), ages 18-93 years (median 61.5), were treated. All patients received biweekly HD-MTX/rituximab (8 g/m(2)/dose; 375 mg/m(2)/dose) for 4-6 cycles (induction) and following best radiographic response, with every 4 weeks HD-MTX (8 g/m(2)/dose) for 4 cycles (maintenance). Neurological and neuroradiographic evaluation were performed every 4 weeks during induction therapy and every 8 weeks during maintenance therapy. All patients were evaluable. A total of 303 cycles of HD-MTX (median 8 cycles; range 4-10) was administered. HD-MTX/rituximab-related toxicity included 16 grade 3 adverse events in 13 patients (32.5%). Following induction, 8 patients (20%) demonstrated progressive disease and discontinued therapy; 32 patients (80%) demonstrated a partial (8/40; 20%) or complete (24/40; 60%) radiographic response. At the conclusion of maintenance therapy (6-10 months of total therapy), 28 patients (70%) demonstrated either a partial (1/28) or complete (27/28) response. Overall, survival of these 28 patients ranged from 11 to 80 months (median 33.5). Survival in the entire cohort ranged from 6 to 80 months with an estimated median of 29 months. Overall, PFS ranged from 2 to 80 months (median 21.0). HD-MTX/rituximab and deferred radiotherapy demonstrated similar or better efficacy similar to other HD-MTX-only regimens and reduced time on therapy on average to 6 months.

High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma

PubMed Central

Chamberlain, Marc C.; Johnston, Sandra K.

2010-01-01

We conducted a prospective Phase II study of high-dose methotrexate (HD-MTX) and rituximab with deferred whole brain radiotherapy in patients with newly diagnosed B-cell primary central nervous system lymphoma with a primary objective of evaluating progression-free survival (PFS). Forty patients (25 men; 15 women), ages 18–93 years (median 61.5), were treated. All patients received biweekly HD-MTX/rituximab (8 g/m2/dose; 375 mg/m2/dose) for 4–6 cycles (induction) and following best radiographic response, with every 4 weeks HD-MTX (8 g/m2/dose) for 4 cycles (maintenance). Neurological and neuroradiographic evaluation were performed every 4 weeks during induction therapy and every 8 weeks during maintenance therapy. All patients were evaluable. A total of 303 cycles of HD-MTX (median 8 cycles; range 4–10) was administered. HD-MTX/rituximab-related toxicity included 16 grade 3 adverse events in 13 patients (32.5%). Following induction, 8 patients (20%) demonstrated progressive disease and discontinued therapy; 32 patients (80%) demonstrated a partial (8/40; 20%) or complete (24/40; 60%) radiographic response. At the conclusion of maintenance therapy (6–10 months of total therapy), 28 patients (70%) demonstrated either a partial (1/28) or complete (27/28) response. Overall, survival of these 28 patients ranged from 11 to 80 months (median 33.5). Survival in the entire cohort ranged from 6 to 80 months with an estimated median of 29 months. Overall, PFS ranged from 2 to 80 months (median 21.0). HD-MTX/rituximab and deferred radiotherapy demonstrated similar or better efficacy similar to other HD-MTX-only regimens and reduced time on therapy on average to 6 months. PMID:20511181

TGFbeta1 (Leu10Pro), p53 (Arg72Pro) can predict for increased risk for breast cancer in south Indian women and TGFbeta1 Pro (Leu10Pro) allele predicts response to neo-adjuvant chemo-radiotherapy.

PubMed

Rajkumar, Thangarajan; Samson, Mani; Rama, Ranganathan; Sridevi, Veluswami; Mahji, Urmila; Swaminathan, Rajaraman; Nancy, Nirmala K

2008-11-01

The breast cancer incidence has been increasing in the south Indian women. A case (n=250)-control (n=500) study was undertaken to investigate the role of Single Nucleotide Polymorphisms (SNP's) in GSTM1 (Present/Null); GSTP1 (Ile105Val), p53 (Arg72Pro), TGFbeta1 (Leu10Pro), c-erbB2 (Ile655Val), and GSTT1 (Null/Present) in breast cancer. In addition, the value of the SNP's in predicting primary tumor's pathologic response following neo-adjuvant chemo-radiotherapy was assessed. Genotyping was done using PCR (GSTM1, GSTT1), Taqman Allelic discrimination assay (GSTP1, c-erbB2) and PCR-CTPP (p53 and TGFbeta1). None of the gene SNP's studied were associated with a statistically significant increased risk for the breast cancer. However, combined analysis of the SNP's showed that p53 (Arg/Arg and Arg/Pro) with TGFbeta1 (Pro/Pro and Leu/Pro) were associated with greater than 2 fold increased risk for breast cancer in Univariate (P=0.01) and Multivariate (P=0.003) analysis. There was no statistically significant association for the GST family members with the breast cancer risk. TGFbeta1 (Pro/Pro) allele was found to predict complete pathologic response in the primary tumour following neo-adjuvant chemo-radiotherapy (OR=6.53 and 10.53 in Univariate and Multivariate analysis respectively) (P=0.004) and was independent of stage. This study suggests that SNP's can help predict breast cancer risk in south Indian women and that TGFbeta1 (Pro/Pro) allele is associated with a better pCR in the primary tumour.

SMAD4 gene mutation renders pancreatic cancer resistance to radiotherapy through promotion of autophagy.

PubMed

Wang, Feng; Xia, Xiaojun; Yang, Chunying; Shen, Jianliang; Mai, Junhua; Kim, Han-Cheon; Kirui, Dickson; Kang, Ya'an; Fleming, Jason B; Koay, Eugene J; Mitra, Sankar; Ferrari, Mauro; Shen, Haifa

2018-03-30

Understanding the mechanism of radioresistance could help develop strategies to improve therapeutic response of patients with PDAC. The SMAD4 gene is frequently mutated in pancreatic cancer. In this study, we investigated the role of SMAD4 deficiency in pancreatic cancer cells' response to radiotherapy. We downregulated SMAD4 expression with SMAD4 siRNA or SMAD4 shRNA and overexpressed SMAD4 in SMAD4 mutant pancreatic cancer cells followed by clonogenic survival assay to evaluate their effects on cell radioresistance. To study the mechanism of radioresistance, the effects of SMAD4 loss on reactive oxygen species (ROS) and autophagy were determined by Flow Cytometry and immunoblot analysis, respectively. Furthermore, we measured radioresistance by clonogenic survival assay after treatment with autophagy inhibitor (Chloroquine) and ROS inhibitor (N-acetyl-L-cysteine) in SMAD4 -depleted pancreatic cancer cells. Finally, the effects of SMAD4 on radioresistance were also confirmed in an orthotopic tumor model derived from SMAD4 -depleted Panc-1 cells. SMAD4 -depleted pancreatic cancer cells were more resistant to radiotherapy based on clonogenic survival assay. Overexpression of wild type SMAD4 in SMAD4 -mutant cells rescued their radiosensitivity. Radioresistance mediated by SMAD4 depletion was associated with persistently higher levels of ROS and radiation-induced autophagy. Finally, SMAD4 depletion induced in vivo radioresistance in Panc-1-derived orthotopic tumor model ( P = 0.038). More interestingly, we observed that the protein level of SMAD4 is inversely correlated with autophagy in orthotopic tumor tissue samples. Our results demonstrate that defective SMAD4 is responsible for radioresistance in pancreatic cancer through induction of ROS and increased level of radiation-induced autophagy. Copyright ©2018, American Association for Cancer Research.

[Feasibility and short-term efficacy of simplified intensity-modulated radiotherapy and concurrent chemotherapy for neck and upper thoracic esophageal carcinoma].

PubMed

Zhu, Wei-Guo; Yu, Chang-Hua; Han, Ji-Hua; Li, Tao; Zhou, Xi-Lei; Tao, Guang-Zhou

2009-12-01

For neck and upper thoracic esophageal carcinoma, three dimensional conformal radiation therapy (3D-CRT) does not necessarily meet all clinical requirements while intensity modulated radiation therapy (IMRT) may take up a lot of labour power and material resources. This study was to explore the feasibility of simplified IMPT(sIMRT) and concurrent chemotherapy for neck and upper thoracic esophageal carcinoma, and to investigate the acute toxicities and short-term efficacy of this treatment modality. sIMRT plans were designed for 30 patients with neck and upper thoracic esophageal carcinoma. Two target volumes were defined: PTV1, which was designed to irradiate to 64 Gy (2.13 Gy x 30 fractions); PTV2, which was given to 54 Gy (1.8 Gy x 30). The sIMRT plan included five equiangular coplanar beams. All patients concurrently received DDP+5-FU regimen with radiotherapy on d1-5 and d29-33. Chemotherapy was repeated for two cycles 28 days after radiotherapy. The treatment was completed for all patients within 6 weeks, and only one patient had Grade 3 acute bronchitis. The complete response (CR) rate was 90.0% (27/30) and the partial response (PR) rate 10.0% (3/30). Overall response was 100% for esophageal lesions and the CR rate 76.5% (13/17). The PR rate was 23.5% (4/17) in lymph node lesions. The major toxicities observed were Grades I-II leukocytopenia. sIMRT can generate desirable dose distribution for neck and upper thoracic esophageal carcinoma, which is similar to sophisticated IMRT but obviously better than 3D-CRT. The short-term efficacy of sIMRT is satisfactory and its acute toxicities are tolerable.

Preoperative Chemoradiation With Cetuximab, Irinotecan, and Capecitabine in Patients With Locally Advanced Resectable Rectal Cancer: A Multicenter Phase II Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Sun Young; Hong, Yong Sang; Kim, Dae Yong

Purpose: To evaluate the efficacy and safety of preoperative chemoradiation with cetuximab, irinotecan, and capecitabine in patients with rectal cancer. Methods and Materials: Forty patients with locally advanced, nonmetastatic, and mid- to lower rectal cancer were enrolled. Radiotherapy was delivered at a dose of 50.4 Gy/28 fractions. Concurrent chemotherapy consisted of an initial dose of cetuximab of 400 mg/m{sup 2} 1 week before radiotherapy, and then cetuximab 250 mg/m{sup 2}/week, irinotecan 40 mg/m{sup 2}/week for 5 consecutive weeks and capecitabine 1,650 mg/m{sup 2}/day for 5 days a week (weekdays only) from the first day during radiotherapy. Total mesorectal excision wasmore » performed within 6 {+-} 2 weeks. The pathologic responses and survival outcomes were evaluated as study endpoints, and an additional KRAS mutation analysis was performed. Results: In total, 39 patients completed their planned preoperative chemoradiation and underwent R0 resection. The pathologic complete response rate was 23.1% (9/39), and 3 patients (7.7%) showed near total regression of tumor. The 3-year disease-free and overall survival rates were 80.0% and 94.7%, respectively. Grade 3/4 toxicities included leukopenia (4, 10.3%), neutropenia (2, 5.1%), anemia (1, 2.6%), diarrhea (2, 5.1%), fatigue (1, 2.6%), skin rash (1, 2.6%), and ileus (1, 2.6%). KRAS mutations were found in 5 (13.2%) of 38 patients who had available tissue for testing. Clinical outcomes were not significantly correlated with KRAS mutation status. Conclusions: Preoperative chemoradiation with cetuximab, irinotecan, and capecitabine was active and well tolerated. KRAS mutation status was not a predictive factor for pathologic response in this study.« less

Two-week course of preoperative chemoradiotherapy followed by delayed surgery for rectal cancer: a phase II multi-institutional clinical trial (KROG 11-02).

PubMed

Lee, Jong Hoon; Kim, Jun-Gi; Oh, Seong Taek; Lee, Myung Ah; Chun, Hoo Geun; Kim, Dae Yong; Kim, Tae Hyun; Kim, Sun Young; Baek, Ji Yeon; Park, Ji Won; Oh, Jae Hwan; Park, Hee Chul; Choi, Doo Ho; Park, Young Suk; Kim, Hee Cheol; Chie, Eui Kyu; Jang, Hong Seok

2014-01-01

The aim of this study was to evaluate the efficacy and safety of a two-week schedule of radiotherapy with oral capecitabine in locally advanced rectal cancer. Eighty patients with rectal cancer located in the mid to low rectum, staged cT3-4N0-2M0, were prospectively enrolled. They underwent preoperative chemoradiotherapy and delayed surgery 6-8 weeks after the completion of radiation therapy. A radiation dose of 33 Gy in 10 fractions was delivered to the pelvis for 2 weeks. One cycle of oral capecitabine was administered at a dose of 1650 mg/m(2)/day during radiotherapy. Tumor response and toxicity were the study endpoints. This study was registered at ClinicalTrials.gov (number, NCT01431599). All included patients underwent total mesorectal excisions including 12 cases of robot assisted surgery and 50 cases of laparoscopic surgery. Of the 80 patients, 27 (33.8%) achieved downstaging (ypT0-2N0) of a rectal tumor and 11 (13.8%) had a pathologically complete response (ypCR). Downstaging rates were 45% for T classification and 65% for N classification. Sphincter saving was achieved in 73 (91.3%) of the 80 patients. Of the 80 patients, 3 (3.8%) experienced grade 3 hematologic toxicity, and 2 (2.5%) had grade 3 postoperative complications such as ileus and wound dehiscence. There was no grade 4 toxicity. A two-week schedule of radiotherapy with oral capecitabine in locally advanced rectal cancer patients showed low toxicity profiles and promising results in terms of tumor response. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The dose-response of salvage radiotherapy following radical prostatectomy: A systematic review and meta-analysis.

PubMed

King, Christopher R

2016-11-01

To date neither the optimal radiotherapy dose nor the existence of a dose-response has been established for salvage RT (SRT). A systematic review from 1996 to 2015 and meta-analysis was performed to identify the pathologic, clinical and treatment factors associated with relapse-free survival (RFS) after SRT (uniformly defined as a PSA>0.2ng/mL or rising above post-SRT nadir). A sigmoidal dose-response curve was objectively fitted and a non-parametric statistical test used to determine significance. 71 studies (10,034 patients) satisfied the meta-analysis criteria. SRT dose (p=0.0001), PSA prior to SRT (p=0.0009), ECE+ (p=0.039) and SV+ (p=0.046) had significant associations with RFS. Statistical analyses confirmed the independence of SRT dose-response. Omission of series with ADT did not alter results. Dose-response is well fit by a sigmoidal curve (p=0.0001) with a TCD 50 of 65.8Gy, with a dose of 70Gy achieving 58.4% RFS vs. 38.5% for 60Gy. A 2.0% [95% CI 1.1-3.2] improvement in RFS is achieved for each Gy. The SRT dose-response remarkably parallels that for definitive RT of localized disease. This study provides level 2a evidence for dose-escalated SRT>70Gy. The presence of an SRT dose-response for microscopic disease supports the hypothesis that prostate cancer is inherently radio-resistant. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Definitive radiotherapy for locally advanced squamous cell carcinoma of the vulva and technical issues: a case report

NASA Astrophysics Data System (ADS)

Kumar, Gokula; Norhafizah, I.; Shazril, I.; Nursyatina, AR; Aziz, MZ Abdul; Zin, Hafiz M.; Zakir, MK; Norjayadi; Norliza, AS; Ismail, A.; Khairun, N.

2017-05-01

This case report describes a complex radical 3D-Conformal Radiotherapy treatment planning, dosimetric issues and outcome of definitive treatment of un-resectable carcinoma of the vulvar in a 42-year old lady. The patient presented with large fungating mass of the vulva which was biopsy confirmed as Keratinizing Squamous Cell Carcinoma. Further staging investigation revealed locally advanced disease (T4), with bilateral inguinal lymph nodes involvement. There is no systemic metastasis or intra-pelvic nodes. The patient was seen by Gynae-Oncology team and the disease was deemed un-resectable without significant morbidity. She was treated to a total dose of 64.8Gy in 36 fractions over 7 weeks with concurrent weekly Cisplatinum in 2 phases. 3D-Conformal radiotherapy technique using the modified segmental boost technique (MSBT, large PA and small AP photon fields with inguinal electron matching) was used. TLD chips were used for in-vivo dose verification in phase 1 and 2 of the treatment. At completion of planned radiotherapy, patient had a complete clinical response, grade 2-3 skin toxicity, grade 2 rectal toxicity, and grade 2 dysuria Vulval Squamous Cell Carcinomas are very radiosensitive tumours and the skills of the treating Radiation Oncologist, Dosimetrists, Physicist, Radiation Therapist and also nurses is of foremost importance is ensuring good clinical outcomes.

Increased pancreatic cancer risk following radiotherapy for testicular cancer.

PubMed

Hauptmann, Michael; Børge Johannesen, Tom; Gilbert, Ethel S; Stovall, Marilyn; van Leeuwen, Flora E; Rajaraman, Preetha; Smith, Susan A; Weathers, Rita E; Aleman, Berthe M P; Andersson, Michael; Curtis, Rochelle E; Dores, Graça M; Fraumeni, Joseph F; Hall, Per; Holowaty, Eric J; Joensuu, Heikki; Kaijser, Magnus; Kleinerman, Ruth A; Langmark, Frøydis; Lynch, Charles F; Pukkala, Eero; Storm, Hans H; Vaalavirta, Leila; van den Belt-Dusebout, Alexandra W; Morton, Lindsay M; Fossa, Sophie D; Travis, Lois B

2016-09-27

Pancreatic cancer risk is elevated among testicular cancer (TC) survivors. However, the roles of specific treatments are unclear. Among 23 982 5-year TC survivors diagnosed during 1947-1991, doses from radiotherapy to the pancreas were estimated for 80 pancreatic cancer patients and 145 matched controls. Chemotherapy details were recorded. Logistic regression was used to estimate odds ratios (ORs). Cumulative incidence of second primary pancreatic cancer was 1.1% at 30 years after TC diagnosis. Radiotherapy (72 (90%) cases and 115 (80%) controls) was associated with a 2.9-fold (95% confidence interval (CI) 1.0-7.8) increased risk. The OR increased linearly by 0.12 per Gy to the pancreas (P-trend<0.001), with an OR of 4.6 (95% CI 1.9-11.0) for ⩾25 Gy vs <25 Gy. Radiation-related risks remained elevated ⩾20 years after TC diagnosis (P=0.020). The risk increased with the number of cycles of chemotherapy with alkylating or platinum agents (P=0.057), although only one case was exposed to platinum. A dose-response relationship exists between radiation to the pancreas and subsequent cancer risk, and persists for over 20 years. These excesses, although small, should be considered when radiotherapy with exposure to the pancreas is considered for newly diagnosed patients. Additional data are needed on the role of chemotherapy.

Bladder radiotherapy treatment: A retrospective comparison of 3-dimensional conformal radiotherapy, intensity-modulated radiation therapy, and volumetric-modulated arc therapy plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pasciuti, Katia, E-mail: k.pasciuti@virgilio.it; Kuthpady, Shrinivas; Anderson, Anne

To examine tumor's and organ's response when different radiotherapy plan techniques are used. Ten patients with confirmed bladder tumors were first treated using 3-dimensional conformal radiotherapy (3DCRT) and subsequently the original plans were re-optimized using the intensity-modulated radiation treatment (IMRT) and volumetric-modulated arc therapy (VMAT)-techniques. Targets coverage in terms of conformity and homogeneity index, TCP, and organs' dose limits, including integral dose analysis were evaluated. In addition, MUs and treatment delivery times were compared. Better minimum target coverage (1.3%) was observed in VMAT plans when compared to 3DCRT and IMRT ones confirmed by a statistically significant conformity index (CI) results.more » Large differences were observed among techniques in integral dose results of the femoral heads. Even if no statistically significant differences were reported in rectum and tissue, a large amount of energy deposition was observed in 3DCRT plans. In any case, VMAT plans provided better organs and tissue sparing confirmed also by the normal tissue complication probability (NTCP) analysis as well as a better tumor control probability (TCP) result. Our analysis showed better overall results in planning using VMAT techniques. Furthermore, a total time reduction in treatment observed among techniques including gantry and collimator rotation could encourage using the more recent one, reducing target movements and patient discomfort.« less

Combining Chk1/2 Inhibition with Cetuximab and Radiation Enhances In Vitro and In Vivo Cytotoxicity in Head and Neck Squamous Cell Carcinoma

PubMed Central

Zeng, Ling; Beggs, Reena R.; Cooper, Tiffiny S.; N.Weaver, Alice; S.Yang, Eddy

2017-01-01

EGFR inhibition and radiotherapy are potent inducers of DNA damage. Checkpoint kinases 1 and 2 (Chk1/2) are critical regulators of the DNA-damage response, controlling cell-cycle checkpoints that may permit recovery from therapy-associated genomic stress. We hypothesized that Chk1/2 inhibition (CHKi) with prexasertib may enhance cytotoxicity from EGFR inhibition plus radiotherapy in head and neck squamous cell carcinoma (HNSCC). In this study, we found that the addition of CHKi to the EGFR inhibitor cetuximab with and without radiotherapy significantly decreased cell proliferation and survival fraction in human papillomavirus virus (HPV)-positive and HPV-negative HNSCC cell lines. Reduced proliferation was accompanied by decreased checkpoint activation, induced S-phase accumulation, persistent DNA damage, and increased caspase cleavage and apoptosis. Importantly, a significant tumor growth delay was observed in vivo in both HPV-positive and HPV-negative cell line xenografts receiving triple combination therapy with CHKi, cetuximab, and radiotherapy without a concomitant increase in toxicity as assessed by mouse body weight. Taken together, the combination of CHKi with cetuximab plus irradiation displayed significant antitumor effects in HNSCCs both in vitro and in vivo, suggesting that this combination therapy may increase clinical benefit. A clinical trial to test this treatment for patients with head and neck cancer is currently ongoing (NCT02555644). PMID:28138028

Supratentorial primitive neuroectodermal tumors (S-PNET) in children: A prospective experience with adjuvant intensive chemotherapy and hyperfractionated accelerated radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Massimino, Maura; Gandola, Lorenza; Spreafico, Filippo

Purpose: Supratentorial primitive neuroectodermal tumors (S-PNET) are rare and have a grim prognosis, frequently taking an aggressive course with local relapse and metastatic spread. We report the results of a mono-institutional therapeutic trial. Methods and Materials: We enrolled 15 consecutive patients to preradiation chemotherapy (CT) consisting of high-dose methotrexate, high-dose etoposide, high-dose cyclophosphamide, and high-dose carboplatin, craniospinal irradiation (CSI) with hyperfractionated accelerated radiotherapy (HART) plus focal boost, maintenance with vincristine/lomustine or consolidation with high-dose thiotepa followed by autologous stem-cell rescue. Results: Median age was 9 years; 7 were male, 8 female. Site of disease was pineal in 3, elsewhere inmore » 12. Six patients were had no evidence of disease after surgery (NED). Of those with evidence of disease after surgery (ED), 2 had central nervous system spread. Of the 9 ED patients, 2 had complete response (CR) and 2 partial response (PR) after CT, 4 stable disease, and 1 progressive disease. Of the 7 ED patients before radiotherapy, 1 had CR, 4 PR, and 2 minor response, thus obtaining a 44% CR + PR after CT and 71% after HART. Because of rapid progression in 2 of the first 5 patients, high-dose thiotepa was systematically adopted after HART in the subsequent 10 patients. Six of 15 patients relapsed (4 locally, 1 locally with dissemination, 1 with dissemination) a mean of 6 months after starting CT, 2 developed second tumors; 5 of 6 relapsers died at a median of 13 months. Three-year progression-free survival, event-free survival, and overall survival were 54%, 34%, and 61%, respectively. Conclusion: Hyperfractionated accelerated RT was the main tool in obtaining responses in S-PNET; introducing the myeloablative phase improved the prognosis (3/10 vs. 3/5 relapses), though the outcome remained unsatisfactory despite the adoption of this intensive treatment.« less

A retrospective pooled analysis of response patterns and risk factors in recurrent malignant glioma patients receiving a nitrosourea-based chemotherapy.

PubMed

Paccapelo, Alessandro; Lolli, Ivan; Fabrini, Maria Grazia; Silvano, Giovanni; Detti, Beatrice; Perrone, Franco; Savio, Giuseppina; Santoni, Matteo; Bonizzoni, Erminio; Perrone, Tania; Scoccianti, Silvia

2012-05-14

At recurrence the use of nitrosoureas is widely-used as a therapeutic option for glioblastoma (GBM) patients. The efficacy of fotemustine (FTM) has been demonstrated in phase II clinical trials; however, these papers report a wide range of progression-free-survival (PFS-6 m) rates, ranging from 21% to 52%. We investigated whether FTM could have a different response pattern in respect to time to adjuvant temozolomide failure, or whether specific independent risk factors could be responsible for the wide range of response rates observed. Recurrent GBM patients have been treated with fotemustine 75-100 mg/sqm at day 1, 8, 15 and after 4/5 weeks of rest with 100 mg/sqm every 21 days. Patients were stratified in 4 groups according to time to temozolomide failure: before starting (B0), during the first 6 months (B1), after more than 6 months of therapy (B2), and after a treatment-free interval (B3). Primary endpoint was PFS-6 m. A multivariable analysis was performed to identify whether gender, time after radiotherapy, second surgery and number of TMZ cycles could be independent predictors of the clinical benefit to FTM treatment. 163 recurrent GBM patients were included in the analysis. PFS-6 m rates for the B0, B1, B2 and B3 groups were 25%, 28%, 31.1% and 43.8%, respectively. The probability of disease control was higher in patients with a longer time after radiotherapy (p = 0.0161) and in those who had undergone a second surgery (p = 0.0306). FTM is confirmed as a valuable therapeutic option for patients with recurrent GBM and was active in all study patient groups. Time after the completion of radiotherapy and second surgery are independent treatment-related risk factors that were predictive of clinical benefit.

A retrospective pooled analysis of response patterns and risk factors in recurrent malignant glioma patients receiving a nitrosourea-based chemotherapy

PubMed Central

2012-01-01

Background At recurrence the use of nitrosoureas is widely-used as a therapeutic option for glioblastoma (GBM) patients. The efficacy of fotemustine (FTM) has been demonstrated in phase II clinical trials; however, these papers report a wide range of progression-free-survival (PFS-6 m) rates, ranging from 21% to 52%. We investigated whether FTM could have a different response pattern in respect to time to adjuvant temozolomide failure, or whether specific independent risk factors could be responsible for the wide range of response rates observed. Methods Recurrent GBM patients have been treated with fotemustine 75-100 mg/sqm at day 1, 8, 15 and after 4/5 weeks of rest with 100 mg/sqm every 21 days. Patients were stratified in 4 groups according to time to temozolomide failure: before starting (B0), during the first 6 months (B1), after more than 6 months of therapy (B2), and after a treatment-free interval (B3). Primary endpoint was PFS-6 m. A multivariable analysis was performed to identify whether gender, time after radiotherapy, second surgery and number of TMZ cycles could be independent predictors of the clinical benefit to FTM treatment. Results 163 recurrent GBM patients were included in the analysis. PFS-6 m rates for the B0, B1, B2 and B3 groups were 25%, 28%, 31.1% and 43.8%, respectively. The probability of disease control was higher in patients with a longer time after radiotherapy (p = 0.0161) and in those who had undergone a second surgery (p = 0.0306). Conclusions FTM is confirmed as a valuable therapeutic option for patients with recurrent GBM and was active in all study patient groups. Time after the completion of radiotherapy and second surgery are independent treatment-related risk factors that were predictive of clinical benefit. PMID:22583678

DOE Office of Scientific and Technical Information (OSTI.GOV)

Atsumi, Kazushige; Shioyama, Yoshiyuki, E-mail: shioyama@radiol.med.kyushu-u.ac.jp; Arimura, Hidetaka

Purpose: To determine clinical factors for predicting the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. Methods and Materials: The study group consisted of 109 patients with esophageal cancer of T1-4 and Stage I-III who were treated with definitive radiotherapy and achieved a complete response of their primary lesion at Kyushu University Hospital between January 1998 and December 2007. Esophageal stenosis was evaluated using esophagographic images within 3 months after completion of radiotherapy. We investigated the correlation between esophageal stenosis after radiotherapy and each of the clinical factors with regard to tumors andmore » therapy. For validation of the correlative factors for esophageal stenosis, an artificial neural network was used to predict the esophageal stenotic ratio. Results: Esophageal stenosis tended to be more severe and more frequent in T3-4 cases than in T1-2 cases. Esophageal stenosis in cases with full circumference involvement tended to be more severe and more frequent than that in cases without full circumference involvement. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. In the multivariate analysis, T stage, extent of involved circumference, and wall thickness of the tumor region were significantly correlated to esophageal stenosis (p = 0.031, p < 0.0001, and p = 0.0011, respectively). The esophageal stenotic ratio predicted by the artificial neural network, which learned these three factors, was significantly correlated to the actual observed stenotic ratio, with a correlation coefficient of 0.864 (p < 0.001). Conclusion: Our study suggested that T stage, extent of involved circumference, and esophageal wall thickness of the tumor region were useful to predict the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer.« less

Predicting Late Effects of Pelvic Radiotherapy: Is There a Better Approach?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wedlake, Linda J.; Thomas, Karen B.Sc.; Lalji, Amyn

2010-11-15

Purpose: Significant chronic symptoms following pelvic radiotherapy occur more frequently than commonly realized. Predictive factors for the development of late symptoms are poorly defined. Moderate sustained acute (cumulative) toxicity might predict severe late effects better than peak reaction. Methods and Materials: To determine prospectively whether peak or cumulative gastrointestinal (GI) acute symptoms better predict late symptoms in patients receiving pelvic radiotherapy. Symptom scores were measured weekly from the start of radiotherapy, and at 1 year using the Modified Inflammatory Bowel Disease Questionnaire-Bowel subset. The possible prognostic impact of patient-related factors was explored. Results: Three hundred and eight patients were recruited.more » 100 were excluded due to lack of follow-up data at one year resulting from death, too ill, stoma, relapsed, non-response or withdrawal. A further 15 were excluded for incomplete data, leaving 193 patients with evaluable data. Of these, 28 had GI, 101 urological, and 64 gynecological cancers. Patients' median age was 65 years (range, 23-82), and they were treated with median 60 Gy dose for a median of 6 weeks. Univariate analysis revealed a significant association between cumulative acute symptom scores and scores at 1 year (p < 0.001), which was dose-independent (p < 0.001). Acute peak and 1-year scores were not associated (p = 0.431). The correlation coefficient between cumulative acute symptoms and symptoms at 1 year was 0.367 and for peak acute symptoms was weaker at 0.057. Patients with an abnormal body mass index and current smokers were more likely to experience worse symptoms at 1 year. Conclusion: Cumulative acute symptoms are more predictive of late symptoms than peak acute changes in score. This association is independent of the radiotherapy dose delivered and is suggestive of a consequential late effect.« less

Durable brain response with pulse-dose crizotinib and ceritinib in ALK-positive non-small cell lung cancer compared with brain radiotherapy.

PubMed

Dudnik, Elizabeth; Siegal, Tali; Zach, Leor; Allen, Aaron M; Flex, Dov; Yust-Katz, Shlomit; Limon, Dror; Hirsch, Fred R; Peled, Nir

2016-04-01

Crizotinib achieves excellent systemic control in anaplastic lymphoma kinase-rearranged (ALK+) non-small cell lung cancer (NSCLC); however, central nervous system (CNS) metastases frequently occur as an early event. Whole brain irradiation, the standard treatment, results in neurocognitive impairment. We present a case series of three ALK+ NSCLC patients with progressing CNS metastases who were treated with pulse-dose crizotinib followed by ceritinib. Three ALK+ NSCLC patients treated between 2011 and 2014 (two males, two never smokers, age range 20-54years, all echinoderm microtubule-associated protein-like 4/ALK rearrangement), were diagnosed with progressing cerebral disease while receiving crizotinib. Clinico-pathological characteristics, treatments, and outcomes were analyzed. In two patients the progression was limited to the CNS, and radiological evidence of leptomeningeal spread was present in one patient. Sequential use of crizotinib 500mg administered once daily (pulse-dose) followed by ceritinib on progression achieved control of the disease in the CNS for over 18 months and over 7 months in Patient 1 and Patient 2, respectively. This strategy provided durable CNS control after whole-brain radiotherapy failure in Patient 1, and allowed the whole-brain radiotherapy to be deferred in Patient 2. Limited CNS progression was documented in Patient 3 while he was on standard-dose/pulse-dose crizotinib for 15months; durable (over 7 months) complete remission was achieved with stereotactic radiotherapy and ceritinib. Manipulating the crizotinib schedule in ALK+ NSCLC patients with CNS metastases and using a novel ALK-inhibitor at the time of further progression may provide durable CNS control and allow brain radiotherapy to be deferred. Copyright © 2015 Elsevier Ltd. All rights reserved.

Radiotherapy quality assurance report from children's oncology group AHOD0031

PubMed Central

Dharmarajan, Kavita V.; Friedman, Debra L.; FitzGerald, T.J.; McCarten, Kathleen M.; Constine, Louis S.; Chen, Lu; Kessel, Sandy K.; Iandoli, Matt; Laurie, Fran; Schwartz, Cindy L.; Wolden, Suzanne L.

2016-01-01

Purpose A phase III trial assessing response-based therapy in intermediate-risk Hodgkin lymphoma, mandated real-time central review of involved field radiotherapy and imaging records by a centralized review center to maximize protocol compliance. We report the impact of centralized radiotherapy review upon protocol compliance. Methods Review of simulation films, port films, and dosimetry records was required pre-treatment and after treatment completion. Records were reviewed by study-affiliated or review center-affiliated radiation oncologists. A 6–10% deviation from protocol-specified dose was scored as “minor”; >10% was “major”. A volume deviation was scored as “minor” if margins were less than specified, or “major” if fields transected disease-bearing areas. Interventional review and final compliance review scores were assigned to each radiotherapy case and compared. Results Of 1712 patients enrolled, 1173 underwent IFRT at 256 institutions in 7 countries. An interventional review was performed in 88% and a final review in 98%. Overall, minor and major deviations were found in 12% and 6%, respectively. Among the cases for which ≥ 1 pre-IFRT modification was requested by QARC and subsequently made by the treating institution, 100% were made compliant on final review. In contrast, among the cases for which ≥ 1 modification was requested but not made by the treating institution, 10% were deemed compliant on final review. Conclusion In a large trial with complex treatment pathways and heterogeneous radiotherapy fields, central review was performed in a large percentage of cases pre-IFRT and identified frequent potential deviations in a timely manner. When suggested modifications were performed by the institutions, deviations were almost eliminated. PMID:25670539

Patient specific quality control for Stereotactic Ablative Body Radiotherapy (SABR): it takes more than one phantom

NASA Astrophysics Data System (ADS)

Kron, T.; Ungureanu, E.; Antony, R.; Hardcastle, N.; Clements, N.; Ukath, J.; Fox, C.; Lonski, P.; Wanigaratne, D.; Haworth, A.

2017-01-01

Stereotactic Ablative Body Radiotherapy (SABR) is an extension of the concepts of Stereotactic Radiosurgery from intracranial procedures to extracranial targets. This brings with it new technological challenges for set-up of a SABR program and continuing quality assurance. Compared with intracranial procedures SABR requires consideration of motion and inhomogeneities and has to deal with a much larger variety of targets ranging from lung to liver, kidney and bone. To meet many of the challenges virtually all advances in modern radiotherapy, such as Intensity Modulated and Image Guided Radiation Therapy (IMRT and IGRT) are used. Considering the few fractions and high doses per fraction delivered to complex targets it is not surprising that patient specific quality control is considered essential for safe delivery. Given the variety of targets and clinical scenarios we employ different strategies for different patients to ensure that the most important aspects of the treatment are appropriately tested, be it steep dose gradients, inhomogeneities or the delivery of dose in the presence of motion. The current paper reviews the different approaches and phantoms utilised at Peter MacCallum Cancer Centre for SABR QA.

Movie making as a cognitive distraction for paediatric patients receiving radiotherapy treatment: qualitative interview study.

PubMed

Shrimpton, Bradley J M; Willis, David J; Tongs, Cáthal D; Rolfo, Aldo G

2013-01-16

To establish the outcomes achieved by using an innovative movie-making programme designed to reduce fear of radiotherapy among paediatric patients. Qualitative descriptive evaluation based on semistructured, qualitative interviews with purposeful sampling and thematic analysis. Tertiary Cancer Centre. 20 parents of paediatric patients who had produced a movie of their radiation therapy experience and were in a follow-up phase of cancer management. Participants attributed a broad range of outcomes to the movie-making program. These included that the programme had helped reduce anxiety and distress exhibited by paediatric patients and contributed to a willingness to receive treatment. Other outcomes were that the completed movies had been used in school reintegration and for maintaining social connections. Allowing children to create a video of their experience of radiotherapy provided a range of benefits to paediatric patients that varied according to their needs. For some patients, movie-making offered a valuable medium for overcoming fear of the unknown as well as increasing understanding of treatment processes. For others, the development of a personalised video offered an important cognitive/attentional distraction through engaging with an age-appropriate activity. Together these outcomes helped children maintain self-control and a positive outlook.

Pathophysiological Responses in Rat and Mouse Models of Radiation-Induced Brain Injury.

PubMed

Yang, Lianhong; Yang, Jianhua; Li, Guoqian; Li, Yi; Wu, Rong; Cheng, Jinping; Tang, Yamei

2017-03-01

The brain is the major dose-limiting organ in patients undergoing radiotherapy for assorted conditions. Radiation-induced brain injury is common and mainly occurs in patients receiving radiotherapy for malignant head and neck tumors, arteriovenous malformations, or lung cancer-derived brain metastases. Nevertheless, the underlying mechanisms of radiation-induced brain injury are largely unknown. Although many treatment strategies are employed for affected individuals, the effects remain suboptimal. Accordingly, animal models are extremely important for elucidating pathogenic radiation-associated mechanisms and for developing more efficacious therapies. So far, models employing various animal species with different radiation dosages and fractions have been introduced to investigate the prevention, mechanisms, early detection, and management of radiation-induced brain injury. However, these models all have limitations, and none are widely accepted. This review summarizes the animal models currently set forth for studies of radiation-induced brain injury, especially rat and mouse, as well as radiation dosages, dose fractionation, and secondary pathophysiological responses.

Long term results after fractionated stereotactic radiotherapy (FSRT) in patients with craniopharyngioma: maximal tumor control with minimal side effects.

PubMed

Harrabi, Semi B; Adeberg, Sebastian; Welzel, Thomas; Rieken, Stefan; Habermehl, Daniel; Debus, Jürgen; Combs, Stephanie E

2014-09-16

There are already numerous reports about high local control rates in patients with craniopharyngioma but there are only few studies with follow up times of more than 10 years. This study is an analysis of long term control, tumor response and side effects after fractionated stereotactic radiotherapy (FSRT) for patients with craniopharyngioma. 55 patients who were treated with FSRT for craniopharyngioma were analyzed. Median age was 37 years (range 6-70 years), among them eight children < 18 years. Radiotherapy (RT) was indicated for progressive disease after neurosurgical resection or postoperatively after repeated resection or partial resection. A median dose of 52.2 Gy (50 - 57.6 Gy) was applied with typical dose per fraction of 1.8 Gy five times per week. The regular follow up examinations comprised in addition to contrast enhanced MRI scans thorough physical examinations and clinical evaluation. During median follow up of 128 months (2 - 276 months) local control rate was 95.3% after 5 years, 92.1% after 10 years and 88.1% after 20 years. Overall survival after 10 years was 83.3% and after 20 years 67.8% whereby none of the deaths were directly attributed to craniopharyngioma. Overall treatment was tolerated well with almost no severe acute or chronic side effects. One patient developed complete anosmia, another one's initially impaired vision deteriorated further. In 83.6% of the cases with radiological follow up a regression of irradiated tumor residues was monitored, in 7 cases complete response was achieved. 44 patients presented themselves initially with endocrinologic dysfunction none of them showed signs of further deterioration during follow up. No secondary malignancies were observed. Long term results for patients with craniopharyngioma after stereotactic radiotherapy are with respect to low treatment related side effects as well as to local control and overall survival excellent.

SU-G-TeP3-13: The Role of Nanoscale Energy Deposition in the Development of Gold Nanoparticle-Enhanced Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kirkby, C; The University of Calgary, Calgary, AB; Koger, B

2016-06-15

Purpose: Gold nanoparticles (GNPs) can enhance radiotherapy effects. The high photoelectric cross section of gold relative to tissue, particularly at lower energies, leads to localized dose enhancement. However in a clinical context, photon energies must also be sufficient to reach a target volume at a given depth. These properties must be balanced to optimize such a therapy. Given that nanoscale energy deposition patterns around GNPs play a role in determining biological outcomes, in this work we seek to establish their role in this optimization process. Methods: The PENELOPE Monte Carlo code was used to generate spherical dose deposition kernels inmore » 1000 nm diameter spheres around 50 nm diameter GNPs in response to monoenergetic photons incident on the GNP. Induced “lesions” were estimated by either a local effect model (LEM) or a mean dose model (MDM). The ratio of these estimates was examined for a range of photon energies (10 keV to 2 MeV), for three sets of linear-quadratic parameters. Results: The models produce distinct differences in expected lesion values, the lower the alpha-beta ratio, the greater the difference. The ratio of expected lesion values remained constant within 5% for energies of 40 keV and above across all parameter sets and rose to a difference of 35% for lower energies only for the lowest alpha-beta ratio. Conclusion: Consistent with other work, these calculations suggest nanoscale energy deposition patterns matter in predicting biological response to GNP-enhanced radiotherapy. However the ratio of expected lesions between the different models is largely independent of energy, indicating that GNP-enhanced radiotherapy scenarios can be optimized in photon energy without consideration of the nanoscale patterns. Special attention may be warranted for energies of 20 keV or below and low alpha-beta ratios.« less

Phase I Trial of Simultaneous In-Field Boost With Helical Tomotherapy for Patients With One to Three Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodrigues, George, E-mail: george.rodrigues@lhsc.on.ca; Yartsev, Slav; Yaremko, Brian

2011-07-15

Purpose: Stereotactic radiosurgery is an alternative to surgical resection for selected intracranial lesions. Integrated image-guided intensity-modulated-capable radiotherapy platforms such as helical tomotherapy (HT) could potentially replace traditional radiosurgery apparatus. The present study's objective was to determine the maximally tolerated dose of a simultaneous in-field boost integrated with whole brain radiotherapy for palliative treatment of patients with one to three brain metastases using HT. Methods and Materials: The inclusion/exclusion criteria and endpoints were consistent with the Radiation Therapy Oncology Group 9508 radiosurgery trial. The cohorts were constructed with a 3 + 3 design; however, additional patients were enrolled in the lowermore » dose tolerable cohorts during the toxicity assessment periods. Whole brain radiotherapy (30 Gy in 10 fractions) was delivered with a 5-30-Gy (total lesion dose of 35-60 Gy in 10 fractions) simultaneous in-field boost delivered to the brain metastases. The maximally tolerated dose was determined by the frequency of neurologic Grade 3-5 National Cancer Institute Common Toxicity Criteria, version 3.0, dose-limiting toxicity events within each Phase I cohort. Results: A total of 48 patients received treatment in the 35-Gy (n = 3), 40-Gy (n = 16), 50-Gy (n = 15), 55-Gy (n = 8), and 60-Gy (n = 6) cohorts. No patients experienced dose-limiting toxicity events in any of the trial cohorts. The 3-month RECIST assessments available for 32 of the 48 patients demonstrated a complete response in 2, a partial response in 16, stable disease in 6, and progressive disease in 8 patients. Conclusion: The delivery of 60 Gy in 10 fractions to one to three brain metastases synchronously with 30 Gy whole brain radiotherapy was achieved without dose-limiting central nervous system toxicity as assessed 3 months after treatment. This approach is being tested in a Phase II efficacy trial.« less

A feasibility study of dynamic adaptive radiotherapy for nonsmall cell lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Minsun, E-mail: mk688@uw.edu; Phillips, Mark H.

2016-05-15

Purpose: The final state of the tumor at the end of a radiotherapy course is dependent on the doses given in each fraction during the treatment course. This study investigates the feasibility of using dynamic adaptive radiotherapy (DART) in treating lung cancers assuming CBCT is available to observe midtreatment tumor states. DART adapts treatment plans using a dynamic programming technique to consider the expected changes of the tumor in the optimization process. Methods: DART is constructed using a stochastic control formalism framework. It minimizes the total expected number of tumor cells at the end of a treatment course, which ismore » equivalent to maximizing tumor control probability, subject to the uncertainty inherent in the tumor response. This formulation allows for nonstationary dose distributions as well as nonstationary fractional doses as needed to achieve a series of optimal plans that are conformal to the tumor over time, i.e., spatiotemporally optimal plans. Sixteen phantom cases with various sizes and locations of tumors and organs-at-risk (OAR) were generated using in-house software. Each case was planned with DART and conventional IMRT prescribing 60 Gy in 30 fractions. The observations of the change in the tumor volume over a treatment course were simulated using a two-level cell population model. Monte Carlo simulations of the treatment course for each case were run to account for uncertainty in the tumor response. The same OAR dose constraints were applied for both methods. The frequency of replanning was varied between 1, 2, 5 (weekly), and 29 times (daily). The final average tumor dose and OAR doses have been compared to quantify the potential dosimetric benefits of DART. Results: The average tumor max, min, mean, and D95 doses using DART relative to these using conventional IMRT were 124.0%–125.2%, 102.1%–114.7%, 113.7%–123.4%, and 102.0%–115.9% (range dependent on the frequency of replanning). The average relative maximum doses for the cord and esophagus, mean doses for the heart and lungs, and D05 for the unspecified tissue resulting 84%–102.4%, 99.8%–106.9%, 66.9%–85.6%, 58.2%–78.8%, and 85.2%–94.0%, respectively. Conclusions: It is feasible to apply DART to the treatment of NSCLC using CBCT to observe the midtreatment tumor state. Potential increases in the tumor dose and reductions in the OAR dose, particularly for parallel OARs with mean or dose–volume constraints, could be achieved using DART compared to nonadaptive IMRT.« less

Declining Use of Radiotherapy for Adverse Features After Radical Prostatectomy: Results From the National Cancer Data Base.

PubMed

Sineshaw, Helmneh M; Gray, Phillip J; Efstathiou, Jason A; Jemal, Ahmedin

2015-11-01

Patterns of postoperative radiotherapy (RT) use in prostate cancer (PCa) after the publication of major randomized trials have not been well characterized. To describe patterns of postoperative RT use after radical prostatectomy (RP) in patients with adverse pathologic features in the United States. Retrospective analysis of 97 270 patients with PCa diagnosed between 2005 and 2011 whose presentation and outcomes were recorded in the National Cancer Data Base. Temporal changes in receipt of postoperative RT and factors associated with receipt of this treatment using the Cochran-Armitage trend test and multiple logistic regression, respectively. Between 2005 and 2011, receipt of postoperative RT decreased steadily from 9.1% to 7.3% (ptrend<0.001). Use of RT with or without androgen deprivation therapy monotonically decreased with advancing age from 8.5% in patients aged 18-59 yr to 6.8% in patients aged 70-79 yr (ptrend<0.001). Receipt of RT was higher at community cancer programs compared with teaching/research centers (14% vs 7.3%; odds ratio [OR]: 2.16; p<0.001), in those with pT3-4 disease and positive margins compared with those with pT3-4 and negative margins (17% vs 5.9%; OR: 2.89; p<0.001), and in patients with a Gleason score of 8-10 compared with those with a Gleason score of 2-6 (17% vs 4.2%; OR: 3.50; p<0.001). Limitations include lack of postprostatectomy prostate-specific antigen level. Postoperative RT use for localized PCa in patients with adverse pathologic features is declining in the United States. In this report, we show that use of postoperative radiotherapy in patients with prostate cancer with adverse pathologic features is declining. Patients treated at community cancer programs, those with locally advanced disease and positive margins, and those with a high Gleason score were more likely to receive postoperative radiotherapy. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Carbon-ion radiotherapy for marginal lymph node recurrences of cervical cancer after definitive radiotherapy: a case report.

PubMed

Tamaki, Tomoaki; Ohno, Tatsuya; Kiyohara, Hiroki; Noda, Shin-ei; Ohkubo, Yu; Ando, Ken; Wakatsuki, Masaru; Kato, Shingo; Kamada, Tadashi; Nakano, Takashi

2013-04-05

Recurrences of cervical cancer after definitive radiotherapy often occur at common iliac or para-aortic lymph nodes as marginal lymph node recurrences. Patients with these recurrences have a chance of long-term survival by optimal re-treatment with radiotherapy. However, the re-irradiation often overlaps the initial and the secondary radiotherapy fields and can result in increased normal tissue toxicities in the bowels or the stomach. Carbon-ion radiotherapy, a form of particle beam radiotherapy using accelerated carbon ions, offers more conformal and sharp dose distribution than X-ray radiotherapy. Therefore, this approach enables the delivery of high radiation doses to the target while sparing its surrounding normal tissues. Marginal lymph node recurrences in common iliac lymph nodes after radiotherapy were treated successfully by carbon-ion radiotherapy in two patients. These two patients were initially treated with a combination of external beam radiotherapy and intracavitary and interstitial brachytherapy. However, the diseases recurred in the lymph nodes near the border of the initial radiotherapy fields after 22 months and 23 months. Because re-irradiation with X-ray radiotherapy may deliver high doses to a section of the bowels, carbon-ion radiotherapy was selected to treat the lymph node recurrences. A total dose of 48 Gy (RBE) in 12 fractions over 3 weeks was given to the lymph node recurrences, and the tumors disappeared completely with no severe acute toxicities. The two patients showed no evidence of disease for 75 months and 63 months after the initial radiotherapy and for 50 months and 37 months after the carbon-ion radiotherapy, respectively. No severe late adverse effects are observed in these patients. The two presented cases suggest that the highly conformal dose distribution of carbon-ion radiotherapy may be beneficial in the treatment of marginal lymph node recurrences after radiotherapy. In addition, the higher biological effect of carbon-ion radiotherapy and its superior dose distribution may provide more effective tumor control in treatment for re-irradiation of the marginal recurrences in radiation resistant tumors other than cervical cancer.

Radiation-Induced Chromosomal Aberrations and Immunotherapy: Micronuclei, Cytosolic DNA, and Interferon-Production Pathway.

PubMed

Durante, Marco; Formenti, Silvia C

2018-01-01

Radiation-induced chromosomal aberrations represent an early marker of late effects, including cell killing and transformation. The measurement of cytogenetic damage in tissues, generally in blood lymphocytes, from patients treated with radiotherapy has been studied for many years to predict individual sensitivity and late morbidity. Acentric fragments are lost during mitosis and create micronuclei (MN), which are well correlated to cell killing. Immunotherapy is rapidly becoming a most promising new strategy for metastatic tumors, and combination with radiotherapy is explored in several pre-clinical studies and clinical trials. Recent evidence has shown that the presence of cytosolic DNA activates immune response via the cyclic GMP-AMP synthase/stimulator of interferon genes pathway, which induces type I interferon transcription. Cytosolic DNA can be found after exposure to ionizing radiation either as MN or as small fragments leaking through nuclear envelope ruptures. The study of the dependence of cytosolic DNA and MN on dose and radiation quality can guide the optimal combination of radiotherapy and immunotherapy. The role of densely ionizing charged particles is under active investigation to define their impact on the activation of the interferon pathway.

Actual change and inaccurate recall contribute to posttraumatic growth following radiotherapy.

PubMed

Ransom, Sean; Sheldon, Kennon M; Jacobsen, Paul B

2008-10-01

People with cancer often report that they experience personal growth as a result of the disease, but such reports have unclear validity. Some suggest such growth results from Rogers's (1951) hypothesized organismic valuing process (OVP), an innate tendency for people to gravitate toward well-being; others suggest this growth may be a positive illusion resulting from temporal self-comparisons. To test these conceptualizations, the authors examined 83 individuals with Stages 0-III breast or prostate cancer. Patients completed measures of positive attributes and personal life goals before radiotherapy (Time 1) and after radiotherapy (Time 2). At Time 2, participants also attempted to recreate their Time 1 responses and completed a posttraumatic growth (PTG) measure. PTG was significantly related with actual increases (but not perceived increases) in the relative importance of intrinsic goals versus extrinsic goals and with perceived increases (but not actual increases) in positive attributes. These measures were unrelated to one another and thus explained unique variance in PTG. Data suggest that both actual change processes related to the OVP and biases in autobiographic recall may independently contribute to PTG reports. (c) 2008 APA, all rights reserved.

Complete response in a patient with gynecological hidradenocarcinoma treated with exclusive external beam radiotherapy and brachytherapy: a case report.

PubMed

Giannelli, Flavio; Chiola, Ilaria; Belgioia, Liliana; Garelli, Stefania; Pastorino, Alice; Marcenaro, Michela; Mammoliti, Serafina; Costantini, Sergio; Bizzarri, Nicolò; Vellone, Valerio; Barra, Salvina; Corvò, Renzo

2017-12-01

Hidradenocarcinoma (HC) is a very rare disease. This case report illustrates a successful treatment of a 60-year-old woman with vulvo-vaginal localization of hidradenocarcinoma treated with external beam radiotherapy delivered by helical tomotherapy with a simultaneous integrated boost (SIB), followed by brachytherapy. External beam radiotherapy dose prescription was 50.4 Gy in 28 fractions, five fractions per week to whole pelvis (planning target volume 1 - PTV1), 60.2 Gy in 28 fractions to SIB1 (fundus of uterus and right inguinal node), and 58.8 Gy in 28 fractions to SIB2 (lower/middle third of vagina, paraurethral region and right inguinal lymph nodes). Brachytherapy dose prescription was 28 Gy in 4 fractions for cervix, fundus of uterus and upper third of vagina (HR-CTV1), and 22 Gy in 4 fractions to middle third of vagina and paraurethral region (HR-CTV2). D 90 for whole treatment was 91.9 Gy and 86.0 Gy for HR-CTV1 and HR-CTV2, respectively. Patient remained 12-months disease-free without treatment related side effects.

Implementation of a software for REmote COMparison of PARticlE and photon treatment plans: ReCompare.

PubMed

Löck, Steffen; Roth, Klaus; Skripcak, Tomas; Worbs, Mario; Helmbrecht, Stephan; Jakobi, Annika; Just, Uwe; Krause, Mechthild; Baumann, Michael; Enghardt, Wolfgang; Lühr, Armin

2015-09-01

To guarantee equal access to optimal radiotherapy, a concept of patient assignment to photon or particle radiotherapy using remote treatment plan exchange and comparison - ReCompare - was proposed. We demonstrate the implementation of this concept and present its clinical applicability. The ReCompare concept was implemented using a client-server based software solution. A clinical workflow for the remote treatment plan exchange and comparison was defined. The steps required by the user and performed by the software for a complete plan transfer were described and an additional module for dose-response modeling was added. The ReCompare software was successfully tested in cooperation with three external partner clinics and worked meeting all required specifications. It was compatible with several standard treatment planning systems, ensured patient data protection, and integrated in the clinical workflow. The ReCompare software can be applied to support non-particle radiotherapy institutions with the patient-specific treatment decision on the optimal irradiation modality by remote treatment plan exchange and comparison. Copyright © 2015. Published by Elsevier GmbH.

Histogram analysis of apparent diffusion coefficient for monitoring early response in patients with advanced cervical cancers undergoing concurrent chemo-radiotherapy.

PubMed

Meng, Jie; Zhu, Lijing; Zhu, Li; Ge, Yun; He, Jian; Zhou, Zhengyang; Yang, Xiaofeng

2017-11-01

Background Apparent diffusion coefficient (ADC) histogram analysis has been widely used in determining tumor prognosis. Purpose To investigate the dynamic changes of ADC histogram parameters during concurrent chemo-radiotherapy (CCRT) in patients with advanced cervical cancers. Material and Methods This prospective study enrolled 32 patients with advanced cervical cancers undergoing CCRT who received diffusion-weighted (DW) magnetic resonance imaging (MRI) before CCRT, at the end of the second and fourth week during CCRT and one month after CCRT completion. The ADC histogram for the entire tumor volume was generated, and a series of histogram parameters was obtained. Dynamic changes of those parameters in cervical cancers were investigated as early biomarkers for treatment response. Results All histogram parameters except AUC low showed significant changes during CCRT (all P < 0.05). There were three variable trends involving different parameters. The mode, 5th, 10th, and 25th percentiles showed similar early increase rates (33.33%, 33.99%, 34.12%, and 30.49%, respectively) at the end of the second week of CCRT. The pre-CCRT 5th and 25th percentiles of the complete response (CR) group were significantly lower than those of the partial response (PR) group. Conclusion A series of ADC histogram parameters of cervical cancers changed significantly at the early stage of CCRT, indicating their potential in monitoring early tumor response to therapy.

Hypofractionated Radiotherapy Is Superior to Conventional Fractionation in an Orthotopic Model of Anaplastic Thyroid Cancer.

PubMed

Oweida, Ayman; Phan, Andy; Vancourt, Benjamin; Robin, Tyler; Hararah, Mohammad K; Bhatia, Shilpa; Milner, Dallin; Lennon, Shelby; Pike, Laura; Raben, David; Haugen, Bryan; Pozdeyev, Nikita; Schweppe, Rebecca; Karam, Sana D

2018-06-01

Anaplastic thyroid cancer (ATC) is an aggressive and highly lethal disease with poor outcomes and resistance to therapy. Despite multimodality treatment, including radiation therapy and chemotherapy, response rates remain <15%, with a median time to progression of less than three months. Recent advances in radiotherapy (RT) delivery and gene-expression profiling may help guide patient selection for personalized therapy. The purpose of this study was to characterize the response to radiation in a panel of ATC cell lines and to test alternative RT fractionation schedules for overcoming radioresistance. The cellular response to radiation was characterized based on clonogenic assays. Radiation response was correlated with microarray gene-expression data. Hypofractionated and conventional RT was tested in an orthotopic ATC tumor model, and tumor growth was assayed locally and distantly with in vivo and ex vivo bioluminescence imaging. A spectrum of radiosensitivities was observed in ATC cell lines. Radioresistant cell lines had higher levels of CXCR4 compared to radiosensitive cell lines. Compared to conventionally fractionated RT, hypofractionated RT resulted in significantly improved tumor growth delay, decreased regional and distant metastases, and improved overall survival. The findings demonstrate the heterogeneity of response to radiation in ATC tumors and the superiority of hypofractionated RT in improving local control, metastatic spread, and survival in preclinical models. These data support the design of clinical trials targeting radioresistant pathways in combination with hypofractionated RT.

Gamma rays induce a p53-independent mitochondrial biogenesis that is counter-regulated by HIF1α

PubMed Central

Bartoletti-Stella, A; Mariani, E; Kurelac, I; Maresca, A; Caratozzolo, M F; Iommarini, L; Carelli, V; Eusebi, L H; Guido, A; Cenacchi, G; Fuccio, L; Rugolo, M; Tullo, A; Porcelli, A M; Gasparre, G

2013-01-01

Mitochondrial biogenesis is an orchestrated process that presides to the regulation of the organelles homeostasis within a cell. We show that γ-rays, at doses commonly used in the radiation therapy for cancer treatment, induce an increase in mitochondrial mass and function, in response to a genotoxic stress that pushes cells into senescence, in the presence of a functional p53. Although the main effector of the response to γ-rays is the p53-p21 axis, we demonstrated that mitochondrial biogenesis is only indirectly regulated by p53, whose activation triggers a murine double minute 2 (MDM2)-mediated hypoxia-inducible factor 1α (HIF1α) degradation, leading to the release of peroxisome-proliferator activated receptor gamma co-activator 1β inhibition by HIF1α, thus promoting mitochondrial biogenesis. Mimicking hypoxia by HIF1α stabilization, in fact, blunts the mitochondrial response to γ-rays as well as the induction of p21-mediated cell senescence, indicating prevalence of the hypoxic over the genotoxic response. Finally, we also show in vivo that post-radiotherapy mitochondrial DNA copy number increase well correlates with lack of HIF1α increase in the tissue, concluding this may be a useful molecular tool to infer the trigger of a hypoxic response during radiotherapy, which may lead to failure of activation of cell senescence. PMID:23764844

The alfa and beta of tumours: a review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies.

PubMed

van Leeuwen, C M; Oei, A L; Crezee, J; Bel, A; Franken, N A P; Stalpers, L J A; Kok, H P

2018-05-16

Prediction of radiobiological response is a major challenge in radiotherapy. Of several radiobiological models, the linear-quadratic (LQ) model has been best validated by experimental and clinical data. Clinically, the LQ model is mainly used to estimate equivalent radiotherapy schedules (e.g. calculate the equivalent dose in 2 Gy fractions, EQD 2 ), but increasingly also to predict tumour control probability (TCP) and normal tissue complication probability (NTCP) using logistic models. The selection of accurate LQ parameters α, β and α/β is pivotal for a reliable estimate of radiation response. The aim of this review is to provide an overview of published values for the LQ parameters of human tumours as a guideline for radiation oncologists and radiation researchers to select appropriate radiobiological parameter values for LQ modelling in clinical radiotherapy. We performed a systematic literature search and found sixty-four clinical studies reporting α, β and α/β for tumours. Tumour site, histology, stage, number of patients, type of LQ model, radiation type, TCP model, clinical endpoint and radiobiological parameter estimates were extracted. Next, we stratified by tumour site and by tumour histology. Study heterogeneity was expressed by the I 2 statistic, i.e. the percentage of variance in reported values not explained by chance. A large heterogeneity in LQ parameters was found within and between studies (I 2  > 75%). For the same tumour site, differences in histology partially explain differences in the LQ parameters: epithelial tumours have higher α/β values than adenocarcinomas. For tumour sites with different histologies, such as in oesophageal cancer, the α/β estimates correlate well with histology. However, many other factors contribute to the study heterogeneity of LQ parameters, e.g. tumour stage, type of LQ model, TCP model and clinical endpoint (i.e. survival, tumour control and biochemical control). The value of LQ parameters for tumours as published in clinical radiotherapy studies depends on many clinical and methodological factors. Therefore, for clinical use of the LQ model, LQ parameters for tumour should be selected carefully, based on tumour site, histology and the applied LQ model. To account for uncertainties in LQ parameter estimates, exploring a range of values is recommended.

Drug priming enhances radiosensitivity of adamantinomatous craniopharyngioma via downregulation of survivin.

PubMed

Stache, Christina; Bils, Christiane; Fahlbusch, Rudolf; Flitsch, Jörg; Buchfelder, Michael; Stefanits, Harald; Czech, Thomas; Gaipl, Udo; Frey, Benjamin; Buslei, Rolf; Hölsken, Annett

2016-12-01

OBJECTIVE In this study, the authors investigated the underlying mechanisms responsible for high tumor recurrence rates of adamantinomatous craniopharyngioma (ACP) after radiotherapy and developed new targeted treatment protocols to minimize recurrence. ACPs are characterized by the activation of the receptor tyrosine kinase epidermal growth factor receptor (EGFR), known to mediate radioresistance in various tumor entities. The impact of tyrosine kinase inhibitors (TKIs) gefitinib or CUDC-101 on radiation-induced cell death and associated regulation of survivin gene expression was evaluated. METHODS The hypothesis that activated EGFR promotes radioresistance in ACP was investigated in vitro using human primary cell cultures of ACP (n = 10). The effects of radiation (12 Gy) and combined radiochemotherapy on radiosensitivity were assessed via cell death analysis using flow cytometry. Changes in target gene expression were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Survivin, identified in qRT-PCR to be involved in radioresistance of ACP, was manipulated by small interfering RNA (siRNA), followed by proliferation and vitality assays to further clarify its role in ACP biology. Immunohistochemically, survivin expression was assessed in patient tumors used for primary cell cultures. RESULTS In primary human ACP cultures, activation of EGFR resulted in significantly reduced cell death levels after radiotherapy. Treatment with TKIs alone and in combination with radiotherapy increased cell death response remarkably, assessed by flow cytometry. CUDC-101 was significantly more effective than gefitinib. The authors identified regulation of survivin expression after therapeutic intervention as the underlying molecular mechanism of radioresistance in ACP. EGFR activation promoting ACP cell survival and proliferation in vitro is consistent with enhanced survivin gene expression shown by qRT-PCR. TKI treatment, as well as the combination with radiotherapy, reduced survivin levels in vitro. Accordingly, ACP showed reduced cell viability and proliferation after survivin downregulation by siRNA. CONCLUSIONS These results indicate an impact of EGFR signaling on radioresistance in ACP. Inhibition of EGFR activity by means of TKI treatment acts as a radiosensitizer on ACP tumor cells, leading to increased cell death. Additionally, the results emphasize the antiapoptotic and pro-proliferative role of survivin in ACP biology and its regulation by EGFR signaling. The suppression of survivin by treatment with TKI and combined radiotherapy represents a new promising treatment strategy that will be further assessed in in vivo models of ACP.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laskar, Siddhartha, E-mail: laskars2000@yahoo.co; Nair, Chandrika; Mallik, Suman

Purpose: To evaluate the prognostic factors and treatment outcome of patients with Askin-Rosai tumor of the chest wall treated at a single institution. Methods and Materials: Treatment comprised multiagent chemotherapy and local therapy, which was either in the form of surgery alone, radical external-beam radiotherapy (EBRT) alone, or a combination of surgery and EBRT. Thirty-two patients (40%) were treated with all three modalities, 21 (27%) received chemotherapy and radical EBRT, and 19 (24%) underwent chemotherapy followed by surgery only. Results: One hundred four consecutive patients aged 3-60 years were treated at the Tata Memorial Hospital from January 1995 to Octobermore » 2003. Most (70%) were male (male/female ratio, 2.3:1). Asymptomatic swelling (43%) was the most common presenting symptom, and 25% of patients presented with distant metastasis. After a median follow-up of 28 months, local control, disease-free survival, and overall survival rates were 67%, 36%, and 45%, respectively. Median time to relapse was 25 months, and the median survival was 76 months. Multivariate analysis revealed age {>=}18 years, poor response to induction chemotherapy, and presence of pleural effusion as indicators of inferior survival. Fifty-six percent of patients with metastatic disease at presentation died within 1 month of diagnosis, with 6-month and 5-year actuarial survival of 14% and 4%, respectively. Conclusion: Primary tumor size, pleural effusion, response to chemotherapy, and optimal radiotherapy were important prognostic factors influencing outcome. The combination of neoadjuvant chemotherapy, surgery, and radiotherapy resulted in optimal outcome.« less

The combination of radiotherapy and immunotherapy using glycated chitosan as an immunological stimulant

NASA Astrophysics Data System (ADS)

Chang, Chun-Yuan; Leu, Jyh-Der; Wang, Chung-Yi; Chen, Wei R.; Lee, Yi-Jang

2015-03-01

Immunotherapy has been reported to effectively treat various cancers. In addition, scientists are dedicated in finding whether the combination of radiotherapy and immunotherapy can efficiently suppress cancer progression and recurrence. Although radiotherapy has been widely used for breast cancer, better strategies to overcome the latestage breast cancer remains explored. The glycated chitosan (GC), a novel immunological stimulant, was demonstrated to trigger local immune response facilitating the enhancement of radiosensitivity. Our previous study also revealed that the cell mortality and invasive ability were decreased under GC treatment, but the underlying mechanism remains unclear. In this study, we used 4T1-3R-L, a derived murine breast cancer cell line from the spontaneous metastasized liver lesion. We combined ionizing radiation with GC to treat 4T1-3R-L and found the expression of DNA damage-related genes such as gamma-H2AX was more than radiation alone In addition, the cell cycle distribution and colony forming assay showed an increased sub-G1 population and decreased cell survival rate after IR combined GC treatment. Taken together, we sought to elucidate the underlying mechanism by the investigation of DNA damage repair process when IR combined with GC, and to explore another advantage of GC to aid other cancer treatments. Based on our most updated results, the GC treatment is able to effectively increase the radiosensitivity through an immune-responsive signaling transduction, indicating that GC could be a valuable therapeutic strategy for treating against advanced breast cancers.

Performance characteristics of mobile MOSFET dosimeter for kilovoltage X-rays used in image guided radiotherapy.

PubMed

Kumar, A Sathish; Singh, I Rabi Raja; Sharma, S D; Ravindran, B Paul

2015-01-01

The main objective of this study was to investigate the characteristics of metal oxide semiconductor field effect transistor (MOSFET) dosimeter for kilovoltage (kV) X-ray beams in order to perform the in vivo dosimetry during image guidance in radiotherapy. The performance characteristics of high sensitivity MOSFET dosimeters were investigated for 80, 90, 100, 110, 120, and 125 kV X-ray beams used for imaging in radiotherapy. This study was performed using Clinac 2100 C/D medical electron linear accelerator with on-board imaging and kV cone beam computed tomography system. The characteristics studied in this work include energy dependence, angular dependence, and linearity. The X-ray beam outputs were measured as per American Association of Physicists in Medicine (AAPM) TG 61 recommendations using PTW parallel plate (PP) ionization chamber, which was calibrated in terms of air kerma (Nk) by the National Standard Laboratory. The MOSFET dosimeters were calibrated against the PP ionization chamber for all the kV X-ray beams and the calibration coefficient was found to be 0.11 cGy/mV with a standard deviation of about ±1%. The response of MOSFET was found to be energy independent for the kV X-ray energies used in this study. The response of the MOSFET dosimeter was also found independent of angle of incidence for the gantry angles in the range of 0° to 360° in-air as well as at 3 cm depth in tissue equivalent phantom.

MO-AB-201-01: Regulatory Compliance and Safety with New Radiotherapies: Spheres and Ra-223

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phillips, L.

2015-06-15

The role of the Radiation Safety Officer at a medical facility can be complicated. The complexity of the position is based on the breadth of services provided at the institution and the nature of the radioactive materials license. Medical practices are constantly changing and the use of ionizing radiation continues to rise in this area. Some of the newer medical applications involving radiation have unique regulatory and safety issues that must be addressed. Oversight of the uses of radiation start at the local level (radiation safety officer, radiation safety committee) and are heavily impacted by outside agencies (i.e. Nuclear Regulatorymore » Commission, State Radiologic Health, The Joint Commission (TJC), etc). This session will provide both an overview of regulatory oversight and essential compliance practices as well as practical ways to assess and introduce some of the new applications utilizing radioactive materials into your medical facility. Learning Objectives: Regulatory Compliance and Safety with New Radiotherapies: Spheres and Ra-223 (Lance Phillips) Understand the radioactive materials license amendment process to add new radiotherapies (i.e., SIR-Spheres, Therasphere, Xofigo). Understand the AU approval process for microspheres and Xofigo. Examine the training and handling requirements for new procedures. Understand the process involved with protocol development, SOP in order to define roles and responsibilities. The RSO and The RSC: Challenges and Opportunities (Colin Dimock) Understand how to form an effective Committee. Examine what the Committee does for the Program and the RSO. Understand the importance of Committee engagement. Discuss the balance of the complimentary roles of the RSO and the Committee. The Alphabet Soup of Regulatory Compliance: Being Prepared for Inspections (Linda Kroger) Recognize the various regulatory bodies and organizations with oversight or impact in Nuclear Medicine, Radiology and Radiation Oncology. Examine 10CFR35 requirements as they relate to the everyday practice of Nuclear Medicine and Radiation Oncology. Understand the nature of available guidance documents (e.g., NUREG 1556). Examine the commonalities between TJC and CMS preparedness.« less

Telomerase inhibition improves tumor response to radiotherapy in a murine orthotopic model of human glioblastoma.

PubMed

Ferrandon, Sylvain; Malleval, Céline; El Hamdani, Badia; Battiston-Montagne, Priscillia; Bolbos, Radu; Langlois, Jean-Baptiste; Manas, Patrick; Gryaznov, Sergei M; Alphonse, Gersende; Honnorat, Jérôme; Rodriguez-Lafrasse, Claire; Poncet, Delphine

2015-07-17

Glioblastoma (GBM) is the most frequent and aggressive type of adult brain tumor. Most GBMs express telomerase; a high level of intra-tumoral telomerase activity (TA) is predictive of poor prognosis. Thus, telomerase inhibitors are promising options to treat GBM. These inhibitors increase the response to radiotherapy (RT), in vitro as well as in vivo. Since typical treatments for GBM include RT, our objective was to evaluate the efficiency of Imetelstat (TA inhibitor) combined with RT. We used a murine orthotopic model of human GBM (N = 8 to11 mice per group) and μMRI imaging to evaluate the efficacy of Imetelstat (delivered by intra-peritoneal injection) alone and combined with RT. Using a clinically established protocol, we demonstrated that Imetelstat significantly: (i) inhibited the TA in the very center of the tumor, (ii) reduced tumor volume as a proportion of TA inhibition, and (iii) increased the response to RT, in terms of tumor volume regression and survival increase. Imetelstat is currently evaluated in refractory brain tumors in young patients (without RT). Our results support its clinical evaluation combined with RT to treat GBM.

MET inhibition overcomes radiation resistance of glioblastoma stem-like cells.

PubMed

De Bacco, Francesca; D'Ambrosio, Antonio; Casanova, Elena; Orzan, Francesca; Neggia, Roberta; Albano, Raffaella; Verginelli, Federica; Cominelli, Manuela; Poliani, Pietro L; Luraghi, Paolo; Reato, Gigliola; Pellegatta, Serena; Finocchiaro, Gaetano; Perera, Timothy; Garibaldi, Elisabetta; Gabriele, Pietro; Comoglio, Paolo M; Boccaccio, Carla

2016-05-01

Glioblastoma (GBM) contains stem-like cells (GSCs) known to be resistant to ionizing radiation and thus responsible for therapeutic failure and rapidly lethal tumor recurrence. It is known that GSC radioresistance relies on efficient activation of the DNA damage response, but the mechanisms linking this response with the stem status are still unclear. Here, we show that the MET receptor kinase, a functional marker of GSCs, is specifically expressed in a subset of radioresistant GSCs and overexpressed in human GBM recurring after radiotherapy. We elucidate that MET promotes GSC radioresistance through a novel mechanism, relying on AKT activity and leading to (i) sustained activation of Aurora kinase A, ATM kinase, and the downstream effectors of DNA repair, and (ii) phosphorylation and cytoplasmic retention of p21, which is associated with anti-apoptotic functions. We show that MET pharmacological inhibition causes DNA damage accumulation in irradiated GSCs and their depletion in vitro and in GBMs generated by GSC xenotransplantation. Preclinical evidence is thus provided that MET inhibitors can radiosensitize tumors and convert GSC-positive selection, induced by radiotherapy, into GSC eradication. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Nitrosourea-based chemotherapy for low grade gliomas failing initial treatment with temozolomide.

PubMed

Kaloshi, Gentian; Sierra del Rio, Monica; Ducray, François; Psimaras, Dimitri; Idbaih, Ahmed; Laigle-Donadey, Florence; Taillibert, Sophie; Houillier, Caroline; Dehais, Caroline; Omuro, Antonio; Sanson, Marc; Delattre, Jean-Yves; Hoang-Xuan, Khe

2010-12-01

There is a growing evidence of using Temozolomide as upfront therapy for progressive low grade gliomas. No data exist on the efficacy of nitrosoureas as an alternative to radiotherapy in those patients who progress after Temozolomide. We retrospectively reviewed 30 patients with median age of 46 years. Twenty-one patients had pure oligodendrogliomas. Thirteen patients had a non-enhancing tumor at progression after Temozolomide. The chromosomes 1p/19q were co-deleted in 5 cases and retained in 10 cases. Response rate was 10% (3 minor responses achieved in non-enhancing tumors). Tolerance was acceptable (17% grade III and IV myelosupression). Median PFS was 6.5 months. Median OS from start of salvage treatment was 23.4 months. Tumors without contrast enhancement demonstrated a better prognosis than those with contrast enhancement both in term of PFS (P = 0.0003) and OS (P = 0.0006). Chromosomes 1p/19q codeletion was not predictive for objective response to salvage treatment but correlated with a better PFS (P = 0.02). In conclusion, salvage NU chemotherapy provide disappointing results in TMZ-pretreated low grade gliomas (LGG), which should be treated in priority by conventional radiotherapy especially in LGG that display contrast enhancement at progression.

The efficacy and safety of simultaneous integrated boost intensity-modulated radiation therapy for esophageal squamous cell carcinoma in Chinese population: A single institution experience.

PubMed

Xu, Yujin; Wang, Zhun; Liu, Guan; Zheng, Xiao; Wang, Yuezhen; Feng, Wei; Lai, Xiaojing; Zhou, Xia; Li, Pu; Ma, Honglian; Wang, Jin; Hu, Xiao; Chen, Ming

2016-10-01

To evaluate the clinical efficacy and toxicity of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) in patients with esophageal squamous cell carcinoma (ESCC) in Chinese population. Patients with ESCC, who received SIB-IMRT from September 2011 to January 2013 were retrospectively analyzed. The SIB-IMRT plans were designed to deliver primary gross tumor volume at 60-64.4 Gy in 28-30 fractions, and planning target volume at 50.4-56 Gy in 28-30 fractions. Treatment-related toxicities were estimated based on Common Terminology Criteria for Adverse Events version 4.0, and tumor response after the treatment was estimated according to Response Evaluation Criteria in Solid Tumors version 1.0. Overall survival (OS), locoregional progression-free survival (LPFS), and progression-free survival (PFS) were estimated with Kaplan-Meier. All patients completed definitive radiotherapy, 54 (78.3%) received combined chemotherapy, of which 31 (44.9%) were concurrent chemoradiotherapy and 23 (33.3%) were sequential chemotherapy. The objective response rate is 82.6% (56/69), with complete response 11 (15.9%), partial response 45 (65.2%), stable disease 8 (11.6%), and progressive disease 5 (7.2%). The 1-, 2- and 3-year LPFS was 74.4%, 57.8%, and 55.6%, respectively. The 1-, 2- and 3-year PFS was 62.3%, 41.0%, and 34.2%, respectively, and the 1-, 2-, and 3-year OS was 73.8%, 57.4%, and 41.0%, respectively, with a median OS of 27.1 months (4.5-54.9 m). For those who received concurrent chemotherapy, the 1-, 2-, and 3-year OS was 75.9%, 69.0%, and 55.2%, respectively, better than those who had sequential chemotherapy or radiotherapy alone (χ2 = 3.115, P = 0.078). Radiation esophagitis occurred in 63.8% and 14.5% with Grade 2 and 3, respectively. No patients occurred ≥ Grade 3 radiation pneumonia. It is safe and effective using SIB-IMRT technology to treat patients with ESCC. More prospective clinical studies should be needed.

Simultaneous PET/MRI in assessing the response to chemo/radiotherapy in head and neck carcinoma: initial experience.

PubMed

Romeo, Valeria; Iorio, Brigida; Mesolella, Massimo; Ugga, Lorenzo; Verde, Francesco; Nicolai, Emanuele; Covello, Mario

2018-06-19

The purpose of the study was to assess by simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) the response to chemotherapy (CHT) and/or radiotherapy (RT) in patients with head and neck squamous cell carcinoma (HNSCC). Five patients with HNSCC underwent simultaneous PET/MRI examination before and after CHT and/or RT. Standard uptake volume (SUV), apparent diffusion coefficient (ADC), Ktrans, Kep, Ve, and iAUC pre- and post-treatment values were extracted and compared. The response to treatment was assessed according to RECIST criteria and classified as complete response (CR), partial response (PR), stable disease (SD), and progression disease (PD). In patient 1, PR was observed with increased ADC, Ktrans, and Ve values and reduction of SUV, iAUC, and Kep values; during clinical and instrumental follow-up, the patient experienced disease progression. Patient 2, classified as PR, showed increased ADC values and reduction of SUV and all perfusion parameters; follow-up demonstrated disease stability. Patient 3, considered as SD, showed increase of ADC and all perfusion values with a mild decrease of SUV; PD was observed during clinical and instrumental follow-up. Patients 4 and 5 showed a CR with no detectable tumor lesions at post-treatment PET/MRI examination, confirmed by 1-year follow-up. Multiparametric evaluation with simultaneous PET/MRI could be a useful tool to assess and predict the response to CHT and/or RT in patients with HNSCC.

PD-1 Modulates Radiation-Induced Cardiac Toxicity through Cytotoxic T Lymphocytes.

PubMed

Du, Shisuo; Zhou, Lin; Alexander, Gregory S; Park, Kyewon; Yang, Lifeng; Wang, Nadan; Zaorsky, Nicholas G; Ma, Xinliang; Wang, Yajing; Dicker, Adam P; Lu, Bo

2018-04-01

Combined immune checkpoint blockade has led to rare autoimmune complications, such as fatal myocarditis. Recent approvals of several anti-programmed death 1 (anti-PD-1) drugs for lung cancer treatment prompted ongoing clinical trials that directly combine PD-1 inhibitors with thoracic radiotherapy for locally advanced lung cancer. Overlapping toxicities from either modality have the potential to increase the risk for radiation-induced cardiotoxicity (RICT), which is well documented among patients with Hodgkin's disease and breast cancer. To investigate cardiotoxicity without the compounding pulmonary toxicity from thoracic radiotherapy, we developed a technique to deliver cardiac irradiation (CIR) in a mouse model concurrently with PD-1 blockade to determine the presence of cardiac toxicity by using physiological testing and mortality as end points along with histological analysis. We observed an acute mortality of 30% within 2 weeks after CIR plus anti-PD-1 antibody compared with 0% from CIR plus immunoglobulin G (p = 0.023). Physiological testing demonstrated a reduced left ventricular ejection fraction (p < 0.01) by echocardiogram. Tissue analyses revealed increased immune cell infiltrates within cardiac tissue. Depletion of CD8-positive lymphocytes with anti-CD8 antibody reversed the acute mortality, suggesting that the toxicity is CD8-positive cell-mediated. To validate these findings using a clinically relevant fractionated radiotherapy regimen, we repeated the study by delivering five daily fractions of 6 Gy. Similar mortality, cardiac dysfunction, and histological changes were observed in mice receiving fractionated radiotherapy with concurrent anti-PD-1 therapy. This study provides strong preclinical evidence that radiation-induced cardiotoxicity is modulated by the PD-1 axis and that PD-1 blockade should be administered with careful radiotherapy planning with an effort of reducing cardiac dose. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Xerostomia, salivary characteristics and gland volumes following intensity-modulated radiotherapy for nasopharyngeal carcinoma: a two-year follow up.

PubMed

Sim, Cpc; Soong, Y L; Pang, Epp; Lim, C; Walker, G D; Manton, D J; Reynolds, E C; Wee, Jts

2018-06-01

To evaluate changes in xerostomia status, salivary characteristics and gland volumes 2 years following radiotherapy in nasopharyngeal carcinoma patients. Xerostomia scores, salivary flow rates, pH and buffering capacity were measured at pre-radiotherapy, mid-radiotherapy, 2 weeks, 3 months and 2 years post-radiotherapy. Salivary gland volumes and their correlation with radiation dose were also assessed. Mean radiation dose to oral cavity, parotid and submandibular glands (SMG) was 44.5, 65.0 and 38.6 Gy respectively. Parotid and SMG volumes decreased 33% at 3 months post-radiotherapy; volumes at 2 years post-radiotherapy were 84% and 51% of pre-radiotherapy levels, respectively. Correlations were observed between parotid gland volume per cent reduction and its radiation dose and between resting salivary flow rate reduction and post-radiotherapy/pre-radiotherapy SMG volume ratio. Salivary flow rates and resting saliva pH remained significantly low at 2 years post-radiotherapy (both flow rates, P = 0.001; resting saliva pH, P = 0.005). Similarly, xerostomia scores remained significantly higher compared with pre-radiotherapy levels. Submandibular gland volumetric shrinkage persisted 2 years after radiotherapy. Xerostomia scores remained significantly higher, and salivary flow rates and resting saliva pH remained significantly lower, suggesting that study participants were still at risk for hyposalivation-related oral diseases. © 2018 Australian Dental Association.

Radiotherapy staffing in the European countries: final results from the ESTRO-HERO survey.

PubMed

Lievens, Yolande; Defourny, Noémie; Coffey, Mary; Borras, Josep M; Dunscombe, Peter; Slotman, Ben; Malicki, Julian; Bogusz, Marta; Gasparotto, Chiara; Grau, Cai; Kokobobo, Arianit; Sedlmayer, Felix; Slobina, Elena; Coucke, Philippe; Gabrovski, Roumen; Vosmik, Milan; Eriksen, Jesper Grau; Jaal, Jana; Dejean, Catherine; Polgar, Csaba; Johannsson, Jakob; Cunningham, Moya; Atkocius, Vydmantas; Back, Carlo; Pirotta, Martin; Karadjinovic, Vanja; Levernes, Sverre; Maciejewski, Boguslaw; Trigo, Maria Lurdes; Šegedin, Barbara; Palacios, Amalia; Pastoors, Bert; Beardmore, Charlotte; Erridge, Sara; Smyth, Gaile; Cleries Soler, Ramon

2014-08-01

The ESTRO Health Economics in Radiation Oncology (HERO) project has the overall aim to develop a knowledge base of the provision of radiotherapy in Europe and build a model for health economic evaluation of radiation treatments at the European level. The first milestone was to assess the availability of radiotherapy resources within Europe. This paper presents the personnel data collected in the ESTRO HERO database. An 84-item questionnaire was sent out to European countries, through their national scientific and professional radiotherapy societies. The current report includes a detailed analysis of radiotherapy staffing (questionnaire items 47-60), analysed in relation to the annual number of treatment courses and the socio-economic status of the countries. The analysis was conducted between February and July 2014, and is based on validated responses from 24 of the 40 European countries defined by the European Cancer Observatory (ECO). A large variation between countries was found for most parameters studied. Averages and ranges for personnel numbers per million inhabitants are 12.8 (2.5-30.9) for radiation oncologists, 7.6 (0-19.7) for medical physicists, 3.5 (0-12.6) for dosimetrists, 26.6 (1.9-78) for RTTs and 14.8 (0.4-61.0) for radiotherapy nurses. The combined average for physicists and dosimetrists is 9.8 per million inhabitants and 36.9 for RTT and nurses. Radiation oncologists on average treat 208.9 courses per year (range: 99.9-348.8), physicists and dosimetrists conjointly treat 303.3 courses (range: 85-757.7) and RTT and nurses 76.8 (range: 25.7-156.8). In countries with higher GNI per capita, all personnel categories treat fewer courses per annum than in less affluent countries. This relationship is most evident for RTTs and nurses. Different clusters of countries can be distinguished on the basis of available personnel resources and socio-economic status. The average personnel figures in Europe are now consistent with, or even more favourable than the QUARTS recommendations, probably reflecting a combination of better availability as such, in parallel with the current use of more complex treatments than a decade ago. A considerable variation in available personnel and delivered courses per year however persists among the highest and lowest staffing levels. This not only reflects the variation in cancer incidence and socio-economic determinants, but also the stage in technology adoption along with treatment complexity and the different professional roles and responsibilities within each country. Our data underpin the need for accurate prediction models and long-term education and training programmes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Review of cetuximab in the treatment of squamous cell carcinoma of the head and neck

PubMed Central

Merlano, Marco; Occelli, Marcella

2007-01-01

Cetuximab is a monoclonal antibody able to inhibit and to degrade the transmembrane receptor Her-1, also known as epidermal growth factor receptor (EGFR). The inhibition of EGFR is of major importance since the receptor influences many important tumor cell activities including tumor growth, neo-angiogenesis, inhibition of the apoptotic response to chemotherapy and radiotherapy. Available experimental data suggest that cetuximab may enhance chemotherapy and radiotherapy activity, reverse resistance to some anticancer drugs and has itself anticancer activity Early clinical data support experimental results. This paper reviews the published experiences on cetuximab in the treatment of advanced head and neck cancer and points out the future objectives of the clinical research on this drug. PMID:18473010

[Big data, generalities and integration in radiotherapy].

PubMed

Le Fèvre, C; Poty, L; Noël, G

2018-02-01

The many advances in data collection computing systems (data collection, database, storage), diagnostic and therapeutic possibilities are responsible for an increase and a diversification of available data. Big data offers the capacities, in the field of health, to accelerate the discoveries and to optimize the management of patients by combining a large volume of data and the creation of therapeutic models. In radiotherapy, the development of big data is attractive because data are very numerous et heterogeneous (demographics, radiomics, genomics, radiogenomics, etc.). The expectation would be to predict the effectiveness and tolerance of radiation therapy. With these new concepts, still at the preliminary stage, it is possible to create a personalized medicine which is always more secure and reliable. Copyright © 2017. Published by Elsevier SAS.

Spot-scanning beam delivery with laterally- and longitudinally-mixed spot size pencil beams in heavy ion radiotherapy

NASA Astrophysics Data System (ADS)

Yan, Yuan-Lin; Liu, Xin-Guo; Dai, Zhong-Ying; Ma, Yuan-Yuan; He, Peng-Bo; Shen, Guo-Sheng; Ji, Teng-Fei; Zhang, Hui; Li, Qiang

2017-09-01

The three-dimensional (3D) spot-scanning method is one of the most commonly used irradiation methods in charged particle beam radiotherapy. Generally, spot-scanning beam delivery utilizes the same size pencil beam to irradiate the tumor targets. Here we propose a spot-scanning beam delivery method with laterally- and longitudinally-mixed size pencil beams for heavy ion radiotherapy. This uses pencil beams with a bigger spot size in the lateral direction and wider mini spread-out Bragg peak (mini-SOBP) to irradiate the inner part of a target volume, and pencil beams with a smaller spot size in the lateral direction and narrower mini-SOBP to irradiate the peripheral part of the target volume. Instead of being controlled by the accelerator, the lateral size of the pencil beam was adjusted by inserting Ta scatterers in the beam delivery line. The longitudinal size of the pencil beam (i.e. the width of the mini-SOBP) was adjusted by tilting mini ridge filters along the beam direction. The new spot-scanning beam delivery using carbon ions was investigated theoretically and compared with traditional spot-scanning beam delivery. Our results show that the new spot-scanning beam delivery has smaller lateral penumbra, steeper distal dose fall-off and the dose homogeneity (1-standard deviation/mean) in the target volume is better than 95%. Supported by Key Project of National Natural Science Foundation of China (U1232207), National Key Technology Support Program of the Ministry of Science and Technology of China (2015BAI01B11), National Key Research and Development Program of the Ministry of Science and Technology of China (2016YFC0904602) and National Natural Science Foundation of China (11075191, 11205217, 11475231, 11505249)

Dosimetric comparison of carbon ion and X-ray radiotherapy for Stage IIIA non-small cell lung cancer.

PubMed

Kubo, Nobuteru; Saitoh, Jun-Ichi; Shimada, Hirofumi; Shirai, Katsuyuki; Kawamura, Hidemasa; Ohno, Tatsuya; Nakano, Takashi

2016-09-01

The present study compared the dose-volume histograms of patients with Stage IIIA non-small cell lung cancer (NSCLC) treated with carbon ion radiotherapy with those of patients treated with X-ray radiotherapy. Patients with Stage IIIA NSCLC (n = 10 patients for each approach) were enrolled. Both radiotherapy plans were calculated with the same targets and organs at risk on the same CT. The treatment plan for the prophylactic lymph node and primary tumor (PTV1) delivered 40 Gy for X-ray radiotherapy and 40 Gy (relative biological effectiveness; RBE) for carbon ion radiotherapy. The total doses for the primary tumor and clinically positive lymph nodes (PTV2) were 60 Gy for X-ray radiotherapy and 60 Gy (RBE) for carbon ion radiotherapy. The homogeneity indexes for PTV1 and PTV2 were superior for carbon ion radiotherapy in comparison with X-ray radiotherapy (PTV1, 0.57 vs 0.65, P = 0.009; PTV2, 0.07 vs 0.16, P = 0.005). The normal lung mean dose, V5, V10 and V20 for carbon ion radiotherapy were 7.7 Gy (RBE), 21.4%, 19.7% and 17.0%, respectively, whereas the corresponding doses for X-ray radiotherapy were 11.9 Gy, 34.9%, 26.6% and 20.8%, respectively. Maximum spinal cord dose, esophageal maximum dose and V50, and bone V10, V30 and V50 were lower with carbon ion radiotherapy than with X-ray radiotherapy. The present study indicates that carbon ion radiotherapy provides a more homogeneous target dose and a lower dose to organs at risk than X-ray radiotherapy for Stage IIIA non-small cell lung cancer. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Prior irradiation results in elevated programmed cell death protein 1 (PD-1) in T cells.

PubMed

Li, Deguan; Chen, Renxiang; Wang, Yi-Wen; Fornace, Albert J; Li, Heng-Hong

2018-05-01

In this study we addressed the question whether radiation-induced adverse effects on T cell activation are associated with alterations of T cell checkpoint receptors. Expression levels of checkpoint receptors on T cell subpopulations were analyzed at multiple post-radiation time points ranging from one to four weeks in mice receiving a single fraction of 1 or 4 Gy of γ-ray. T cell activation associated metabolic changes were assessed. Our results showed that prior irradiation resulted in significant elevated expression of programmed cell death protein 1 (PD-1) in both CD4+ and CD8+ populations, at all three post-radiation time points. T cells with elevated PD-1 mostly were either central memory or naïve cells. In addition, the feedback induction of PD-1 expression in activated T cells declined after radiation. Taken together, the elevated PD-1 level observed at weeks after radiation exposure is connected to T cell dysfunction. Recent preclinical and clinical studies have showed that a combination of radiotherapy and T cell checkpoint blockade immunotherapy including targeting the programmed death-ligand 1 (PD-L1)/PD-1 axis may potentiate the antitumor response. Understanding the dynamic changes in PD-1 levels in T cells after radiation should help in the development of a more effective therapeutic strategy.

Stereotactic body radiotherapy for lung cancer: how much does it really cost?

PubMed

Lievens, Yolande; Obyn, Caroline; Mertens, Anne-Sophie; Van Halewyck, Dries; Hulstaert, Frank

2015-03-01

Despite the lack of randomized evidence, stereotactic body radiotherapy (SBRT) is being accepted as superior to conventional radiotherapy for patients with T1-2N0 non-small-cell lung cancer in the periphery of the lung and unfit or unwilling to undergo surgery. To introduce SBRT in a system of coverage with evidence development, a correct financing had to be determined. A time-driven activity-based costing model for radiotherapy was developed. Resource cost calculation of all radiotherapy treatments, standard and innovative, was conducted in 10 Belgian radiotherapy centers in the second half of 2012. The average cost of lung SBRT across the 10 centers (6221&OV0556;) is in the range of the average costs of standard fractionated 3D-conformal radiotherapy (5919&OV0556;) and intensity-modulated radiotherapy (7379&OV0556;) for lung cancer. Hypofractionated 3D-conformal radiotherapy and intensity-modulated radiotherapy schemes are less costly (3993&OV0556; respectively 4730&OV0556;). The SBRT cost increases with the number of fractions and is highly dependent of personnel and equipment use. SBRT cost varies more by centre than conventional radiotherapy cost, reflecting different technologies, stages in the learning curve and a lack of clear guidance in this field. Time-driven activity-based costing of radiotherapy is feasible in a multicentre setup, resulting in real-life resource costs that can form the basis for correct reimbursement schemes, supporting an early yet controlled introduction of innovative radiotherapy techniques in clinical practice.

Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes

PubMed Central

López, Escarlata; Guerrero, Rosario; Núñez, Maria Isabel; del Moral, Rosario; Villalobos, Mercedes; Martínez-Galán, Joaquina; Valenzuela, Maria Teresa; Muñoz-Gámez, José Antonio; Oliver, Francisco Javier; Martín-Oliva, David; de Almodóvar, José Mariano Ruiz

2005-01-01

Introduction Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects. Methods Intrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments. Results Radiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects. Conclusion After radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity. Further research is warranted to identify the major determinants of normal tissue radiation response to make it possible to individualize treatments and improve the outcome of radiotherapy in cancer patients. PMID:16168114

Examining Determinants of Radiotherapy Access: Do Cost and Radiotherapy Inconvenience Affect Uptake of Breast-conserving Treatment for Early Breast Cancer?

PubMed

Lam, J; Cook, T; Foster, S; Poon, R; Milross, C; Sundaresan, P

2015-08-01

Radiotherapy utilisation is likely affected by multiple factors pertaining to radiotherapy access. Radiotherapy is an integral component of breast-conserving treatment (BCT) for early breast cancer. We aimed to determine if stepwise improvements in radiotherapy access in regional Australia affected the uptake of BCT and thus radiotherapy. Breast cancer operations in the Central Coast of New South Wales between January 2010 and March 2014 for T1-2N0-1M0 invasive or in situ (≤5 cm) disease in female patients eligible for BCT were examined. BCT uptake was calculated for three 1 year periods: period 1 (local radiotherapy available at cost to user or out of area radiotherapy with travel cost and inconvenience); period 2 (as per period 1 + publicly funded transport and radiotherapy at out of area facilities at no cost to user); period 3 (as per period 1 + publicly funded local radiotherapy at no cost to user). In total, 574 cases met eligibility criteria. BCT declined with increasing distance to publicly funded radiotherapy (P = 0.035). BCT rates for periods 1, 2 and 3 were 63% (113/180), 61% (105/173) and 71% (156/221). There were no statistically significant differences in BCT between periods 1 and 2 in the whole cohort or within age, histology or tumour size subgroups. Overall, there was a 9% increase in BCT in the whole cohort in period 3 compared with periods 1 and 2 (P = 0.031). This increase was statistically significant for women over 70 years (19% increase, P = 0.034), for women with ductal carcinoma in situ (25% increase, P = 0.013) and for women with primary tumours that were ≤10 mm (21% increase, P = 0.016). Improving the affordability of radiotherapy through publicly funded transport and radiotherapy at out of area facilities did not improve BCT uptake in a region where radiotherapy was locally available, albeit at cost to the user. Improving both affordability and convenience through the provision of local publicly funded radiotherapy increased BCT uptake. Service availability and affordability have long been recognised as important determinants of radiotherapy access. Our findings suggest that inconvenience may also influence radiotherapy utilisation. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Very Early Salvage Radiotherapy Improves Distant Metastasis-Free Survival.

PubMed

Abugharib, Ahmed; Jackson, William C; Tumati, Vasu; Dess, Robert T; Lee, Jae Y; Zhao, Shuang G; Soliman, Moaaz; Zumsteg, Zachary S; Mehra, Rohit; Feng, Felix Y; Morgan, Todd M; Desai, Neil; Spratt, Daniel E

2017-03-01

Early salvage radiotherapy following radical prostatectomy for prostate cancer is commonly advocated in place of adjuvant radiotherapy. We aimed to determine the optimal definition of early salvage radiotherapy. We performed a multi-institutional retrospective study of 657 men who underwent salvage radiotherapy between 1986 and 2013. Two comparisons were made to determine the optimal definition of early salvage radiotherapy, including 1) the time from radical prostatectomy to salvage radiotherapy (less than 9, 9 to 21, 22 to 47 or greater than 48 months) and 2) the level of detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 or greater than 0.5 ng/ml). Outcomes included freedom from salvage androgen deprivation therapy, and biochemical relapse-free, distant metastases-free and prostate cancer specific survival. Median followup was 9.8 years. Time from radical prostatectomy to salvage radiotherapy did not correlate with 10-year biochemical relapse-free survival rates (R 2 = 0.18). Increasing pre-salvage radiotherapy prostate specific antigen strongly correlated with biochemical relapse-free survival (R 2 = 0.91). Increasing detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 and greater than 0.5 ng/ml) predicted worse 10-year biochemical relapse-free survival (62%, 44% and 27%), freedom from salvage androgen deprivation therapy (77%, 66% and 49%), distant metastases-free survival (86%, 79% and 66%, each p <0.001) and prostate cancer specific survival (93%, 89% and 80%, respectively, p = 0.001). On multivariable analysis early salvage radiotherapy (prostate specific antigen greater than 0.2 to 0.5 ng/ml) was associated with a twofold increase in biochemical failure, use of salvage androgen deprivation therapy and distant metastases compared to very early salvage radiotherapy (prostate specific antigen 0.01 to 0.2 ng/ml). The duration from radical prostatectomy to salvage radiotherapy is not independently prognostic for outcomes after salvage radiotherapy and it should not be used to define early salvage radiotherapy. Grouping all patients with pre-salvage radiotherapy prostate specific antigen 0.5 ng/ml or less may be inadequate to define early salvage radiotherapy and it has a relevant impact on ongoing and future clinical trials. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Distinct transcriptome profiles identified in normal human bronchial epithelial cells after exposure to γ-rays and different elemental particles of high Z and energy.

PubMed

Ding, Liang-Hao; Park, Seongmi; Peyton, Michael; Girard, Luc; Xie, Yang; Minna, John D; Story, Michael D

2013-06-01

Ionizing radiation composed of accelerated ions of high atomic number (Z) and energy (HZE) deposits energy and creates damage in cells in a discrete manner as compared to the random deposition of energy and damage seen with low energy radiations such as γ- or x-rays. Such radiations can be highly effective at cell killing, transformation, and oncogenesis, all of which are concerns for the manned space program and for the burgeoning field of HZE particle radiotherapy for cancer. Furthermore, there are differences in the extent to which cells or tissues respond to such exposures that may be unrelated to absorbed dose. Therefore, we asked whether the energy deposition patterns produced by different radiation types would cause different molecular responses. We performed transcriptome profiling using human bronchial epithelial cells (HBECs) after exposure to γ-rays and to two different HZE particles (28Si and 56Fe) with different energy transfer properties to characterize the molecular response to HZE particles and γ-rays as a function of dose, energy deposition pattern, and time post-irradiation. Clonogenic assay indicated that the relative biological effectiveness (RBE) for 56Fe was 3.91 and for 28Si was 1.38 at 34% cell survival. Unsupervised clustering analysis of gene expression segregated samples according to the radiation species followed by the time after irradiation, whereas dose was not a significant parameter for segregation of radiation response. While a subset of genes associated with p53-signaling, such as CDKN1A, TRIM22 and BTG2 showed very similar responses to all radiation qualities, distinct expression changes were associated with the different radiation species. Gene enrichment analysis categorized the differentially expressed genes into functional groups related to cell death and cell cycle regulation for all radiation types, while gene pathway analysis revealed that the pro-inflammatory Acute Phase Response Signaling was specifically induced after HZE particle irradiation. A 73 gene signature capable of predicting with 96% accuracy the radiation species to which cells were exposed, was developed. These data suggest that the molecular response to the radiation species used here is a function of the energy deposition characteristics of the radiation species. This novel molecular response to HZE particles may have implications for radiotherapy including particle selection for therapy and risk for second cancers, risk for cancers from diagnostic radiation exposures, as well as NASA's efforts to develop more accurate lung cancer risk estimates for astronaut safety. Lastly, irrespective of the source of radiation, the gene expression changes observed set the stage for functional studies of initiation or progression of radiation-induced lung carcinogenesis.

Distinct transcriptome profiles identified in normal human bronchial epithelial cells after exposure to γ-rays and different elemental particles of high Z and energy

PubMed Central

2013-01-01

Background Ionizing radiation composed of accelerated ions of high atomic number (Z) and energy (HZE) deposits energy and creates damage in cells in a discrete manner as compared to the random deposition of energy and damage seen with low energy radiations such as γ- or x-rays. Such radiations can be highly effective at cell killing, transformation, and oncogenesis, all of which are concerns for the manned space program and for the burgeoning field of HZE particle radiotherapy for cancer. Furthermore, there are differences in the extent to which cells or tissues respond to such exposures that may be unrelated to absorbed dose. Therefore, we asked whether the energy deposition patterns produced by different radiation types would cause different molecular responses. We performed transcriptome profiling using human bronchial epithelial cells (HBECs) after exposure to γ-rays and to two different HZE particles (28Si and 56Fe) with different energy transfer properties to characterize the molecular response to HZE particles and γ-rays as a function of dose, energy deposition pattern, and time post-irradiation. Results Clonogenic assay indicated that the relative biological effectiveness (RBE) for 56Fe was 3.91 and for 28Si was 1.38 at 34% cell survival. Unsupervised clustering analysis of gene expression segregated samples according to the radiation species followed by the time after irradiation, whereas dose was not a significant parameter for segregation of radiation response. While a subset of genes associated with p53-signaling, such as CDKN1A, TRIM22 and BTG2 showed very similar responses to all radiation qualities, distinct expression changes were associated with the different radiation species. Gene enrichment analysis categorized the differentially expressed genes into functional groups related to cell death and cell cycle regulation for all radiation types, while gene pathway analysis revealed that the pro-inflammatory Acute Phase Response Signaling was specifically induced after HZE particle irradiation. A 73 gene signature capable of predicting with 96% accuracy the radiation species to which cells were exposed, was developed. Conclusions These data suggest that the molecular response to the radiation species used here is a function of the energy deposition characteristics of the radiation species. This novel molecular response to HZE particles may have implications for radiotherapy including particle selection for therapy and risk for second cancers, risk for cancers from diagnostic radiation exposures, as well as NASA’s efforts to develop more accurate lung cancer risk estimates for astronaut safety. Lastly, irrespective of the source of radiation, the gene expression changes observed set the stage for functional studies of initiation or progression of radiation-induced lung carcinogenesis. PMID:23724988

Clinical outcome for patients of solitary bone only metastasis.

PubMed

Hosaka, Seiichi; Katagiri, Hirohisa; Honda, Yosuke; Wasa, Junji; Murata, Hideki; Takahashi, Mitsuru

2016-03-01

Solitary bone only metastasis (SBOM) is a rare condition in which metastasis is limited to a single skeletal lesion originating from a previously treated or controllable primary lesion. The study objective was to evaluate the clinical features and survival regarding this rare condition and to clarify its treatment strategy. A total of 1453 patients with bone metastasis registered in our hospital database were enrolled. To assess the primary and/or metastatic lesion we used plain X-ray images, CT, MRI and FDG-PET scans as well as bone scans. Among the patients, only 27 (1.8%) had SBOM. The primary cancers responsible for SBOM were lung in seven patients, breast in five, kidney in four, prostate in two, uterus in two and other types in seven. Treatment of SBOM involved resection in four patients, radiotherapy only in 17, radiotherapy in combination with zoledronate in six and chemotherapy with zoledronate in one. Local recurrence did not develop in the four cases treated with resection. However, in-field recurrence was found in 4 of 22 (18%) patients who underwent radiotherapy. All three patients who received >40 Gy did not develop in-field recurrence. The overall and event free survival rates at 5 years were 63% and 41%, respectively. Solitary bone only metastasis should be treated with wide resection or long-course radiotherapy at doses 40-50 Gy to achieve long lasting local tumor control. Copyright © 2015 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harwood, A.R.; Krajbich, J.I.; Fornasier, V.L.

A retrospective analysis of 31 cases of chondrosarcoma of bone treated by radiotherapy is presented. In comparison with other large series, our group of patients were found to have been unfavourably selected with respect to the known prognostic factors: histology site, adequacy of operative treatment, and presenting symptoms. Twelve patients with primary chondrosarcoma were radically irradiated; 6 of these 12 have been alive and well without tumor for periods ranging from three and a half to 16 years and 3 of these are alive and well for 15 years or more following radiotherapy. The other 6 patients responded or deseasemore » stabilized following radiotherapy for periods ranging from 16 months to eight years. One poorly differentiated tumor was radically irradiated and did not respond. Eleven patients were irradiated palliatively, generally with low doses of irradiation, and only 4 responded transiently for periods ranging from three to 12 months. Seven patients with mesenchymal and dedifferentiated tumors were radically irradiated. Four responded or disease stabilized, and 1 of these patients was alive and well at 3 years; 3 did not respond. Six died with distant metastasis. It is concluded that chondrosarcoma of bone is a radioresponsive tumor and the place of radiotherapy in the treatment of this disease and the reason for its being labelled a radioresistant tumor are discussed. The problems of assessing response of chondrosarcoma to therapy are also discussed. It is suggested that chemotherapy may have a role in the management of mesenchymal and dedifferentiated chondrosarcoma.« less

A pilot study using dynamic contrast enhanced-MRI as a response biomarker of the radioprotective effect of memantine in patients receiving whole brain radiotherapy

PubMed Central

Wong, Philip; Leppert, Ilana R.; Roberge, David; Boudam, Karim; Brown, Paul D.; Muanza, Thierry; Pike, G. Bruce; Chankowsky, Jeffrey; Mihalcioiu, Catalin

2016-01-01

Purpose This pilot prospective study sought to determine whether dynamic contrast enhanced MRI (DCE-MRI) could be used as a clinical imaging biomarker of tissue toxicity from whole brain radiotherapy (WBRT). Method 14 patients who received WBRT were imaged using dynamic contrast enhanced DCE-MRI prior to and at 8-weeks, 16-weeks and 24-weeks after the initiation of WBRT. Twelve of the patients were also enrolled in the RTOG 0614 trial, which randomized patients to the use of placebo or memantine. After the unblinding of the treatments received by RTOG 0614 patients, DCE-MRI measures of tumor tissue and normal appearing white matter (NAWM) vascular permeability (Initial Area Under the Curve (AUC) Blood Adjusted) was analyzed. Cognitive, quality-of-life (QOL) assessment and blood samples were collected according to the patient's ability to tolerate the exams. Circulating endothelial cells (CEC) were measured using flow cytometry. Results Following WBRT, there was an increasing trend in the vascular permeability of tumors (p=0.09) and NAWM (p=0.06) with time. Memantine significantly (p=0.01) reduced NAWM AUC changes following radiotherapy. Patients on memantine retained (COWA p= 0.03) better cognitive functions than those on placebo. No association was observed between the level of CEC and DCE-MRI changes, time from radiotherapy or memantine use. Conclusions DCE-MRI can detect vascular damage secondary to WBRT. Our data suggests that memantine reduces WBRT-induced brain vasculature damages. PMID:27248467

Multimodality therapy for medulloblastoma. [Efficacy and complications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, P.R.M.; Duffner, P.K.; Cohen, M.E.

1980-02-15

Eight patients with recurrent medulloblastoma were treated with a chemotherapy regimen consisting of vincristine, BCNU, dexamethasone and intrathecal and intermediate dose intravenous methotrexate (500 mg/m/sup 2/). Five also received local low dose radiotherapy (RT). All 8 patients responded to treatment; 6 completely and 2 partially. These latter 2 were in their second and third recurrences. Three remain in remission. The median duration of response was 18.8 months, and median time from start of chemotherapy to death was 32 months using the Kaplan-Meier technique. In addition, 9 other patients with newly diagnosed medulloblastoma were treated with craniospinal radiation and the samemore » adjuvant chemotherapy as above. The first 5 patients also received intraventricular methotrexate and/or intravenous BCNU during radiotherapy. The toxicity in the 5 patients was very severe. There were three toxic deaths, one death from cancer; one patient survives disease-free, but he is demented. With the discontinuance of intraventricular methotrexate and the postponement of myelosuppressive chemotherapy until after the completion of radiotherapy, the regimen has been well tolerated. All 4 patients treated this way remain alive, well, and disease-free at intervals up to 36 months. We conclude that recurrent medulloblastomas are sensitive to multiagent chemotherapy and that prolonged remissions may occur. With primary adjuvant chemotherapy, extreme caution with myelosuppressive drugs must be exercised during the period of craniospinal radiotherapy. We also do not recommend the use of intraventricular methotrexate. When these two criteria were followed, the preliminary results with adjuvant chemotherapy appear encouraging.« less

Clinicopathologic Comparison of High-Dose-Rate Endorectal Brachytherapy versus Conventional Chemoradiotherapy in the Neoadjuvant Setting for Resectable Stages II and III Low Rectal Cancer

PubMed Central

Smith, Jessica A.; Wild, Aaron T.; Singhi, Aatur; Raman, Siva P.; Qiu, Haoming; Kumar, Rachit; Hacker-Prietz, Amy; Hruban, Ralph H.; Kamel, Ihab R.; Efron, Jonathan; Wick, Elizabeth C.; Azad, Nilofer S.; Diaz, Luis A.; Le, Yi; Armour, Elwood P.; Gearhart, Susan L.; Herman, Joseph M.

2012-01-01

Purpose. To assess for differences in clinical, radiologic, and pathologic outcomes between patients with stage II-III rectal adenocarcinoma treated neoadjuvantly with conventional external beam radiotherapy (3D conformal radiotherapy (3DRT) or intensity-modulated radiotherapy (IMRT)) versus high-dose-rate endorectal brachytherapy (EBT). Methods. Patients undergoing neoadjuvant EBT received 4 consecutive daily 6.5 Gy fractions without chemotherapy, while those undergoing 3DRT or IMRT received 28 daily 1.8 Gy fractions with concurrent 5-fluorouracil. Data was collected prospectively for 7 EBT patients and retrospectively for 25 historical 3DRT/IMRT controls. Results. Time to surgery was less for EBT compared to 3DRT and IMRT (P < 0.001). There was a trend towards higher rate of pathologic CR for EBT (P = 0.06). Rates of margin and lymph node positivity at resection were similar for all groups. Acute toxicity was less for EBT compared to 3DRT and IMRT (P = 0.025). Overall and progression-free survival were noninferior for EBT. On MRI, EBT achieved similar complete response rate and reduction in tumor volume as 3DRT and IMRT. Histopathologic comparison showed that EBT resulted in more localized treatment effects and fewer serosal adhesions. Conclusions. EBT offers several practical benefits over conventional radiotherapy techniques and appears to be at least as effective against low rectal cancer as measured by short-term outcomes. PMID:22830003

Clinical results of conformal versus intensity-modulated radiotherapy using a focal simultaneous boost for muscle-invasive bladder cancer in elderly or medically unfit patients.

PubMed

Lutkenhaus, Lotte J; van Os, Rob M; Bel, Arjan; Hulshof, Maarten C C M

2016-03-18

For elderly or medically unfit patients with muscle-invasive bladder cancer, cystectomy or chemotherapy are contraindicated. This leaves radical radiotherapy as the only treatment option. It was the aim of this study to retrospectively analyze the treatment outcome and associated toxicity of conformal versus intensity-modulated radiotherapy (IMRT) using a focal simultaneous tumor boost for muscle-invasive bladder cancer in patients not suitable for cystectomy. One hundred eighteen patients with T2-4 N0-1 M0 bladder cancer were analyzed retrospectively. Median age was 80 years. Treatment consisted of either a conformal box technique or IMRT and included a simultaneous boost to the tumor. To enable an accurate boost delivery, fiducial markers were placed around the tumor. Patients were treated with 40 Gy in 20 fractions to the elective treatment volumes, and a daily tumor boost up to 55-60 Gy. Clinical complete response was seen in 87 % of patients. Three-year overall survival was 44 %, with a locoregional control rate of 73 % at 3 years. Toxicity was low, with late urinary and intestinal toxicity rates grade ≥ 2 of 14 and 5 %, respectively. The use of IMRT reduced late intestinal toxicity, whereas fiducial markers reduced acute urinary toxicity. Radical radiotherapy using a focal boost is feasible and effective for elderly or unfit patients, with a 3-year locoregional control of 73 %. Toxicity rates were low, and were reduced by the use of IMRT and fiducial markers.

Local irradiation does not enhance the effect of immunostimulatory AdCD40L gene therapy combined with low dose cyclophosphamide in melanoma patients

PubMed Central

Irenaeus, Sandra; Schiza, Aglaia; Mangsbo, Sara M.; Wenthe, Jessica; Eriksson, Emma; Krause, Johan; Sundin, Anders; Ahlström, Håkan; Tötterman, Thomas H.; Loskog, Angelica; Ullenhag, Gustav J.

2017-01-01

Background AdCD40L is an immunostimulatory gene therapy under evaluation for advanced melanoma, including ocular melanoma. Herein, we present the final data of a Phase I/IIa trial using AdCD40L alone or in combination with low dose cyclophosphamide +/- radiation therapy. Methods AdCD40L is a replication-deficient adenovirus carrying the gene for CD40 ligand (CD40L). Twenty-four patients with advanced melanoma were enrolled and treated with AdCD40L monotherapy, or combined with cyclophosphamide +/- single fraction radiotherapy. The patients were monitored for 10 weeks using immunological and radiological evaluations and thereafter for survival. Results AdCD40L treatment was safe and well tolerated both alone and in combination with cyclophosphamide as well as local radiotherapy. Four out of twenty-four patients had >1 year survival. Addition of cyclophosphamide was beneficial but adding radiotherapy did not further extend survival. High initial plasma levels of IL12 and MIP3b correlated to overall survival, whereas IL8 responses post-treatment correlated negatively with survival. Interestingly, antibody reactions to the virus correlated negatively with post IL6 and pre IL1b levels in blood. Conclusions AdCD40L was safely administered to patients and effect was improved by cyclophosphamide but not by radiotherapy. Immune activation profile at baseline may predict responders better than shortly after treatment. PMID:29108250

Outcomes of Preoperative Chemoradiotherapy and Combined Chemotherapy with Radiotherapy Without Surgery for Locally Advanced Rectal Cancer.

PubMed

Supaadirek, Chunsri; Pesee, Montien; Thamronganantasakul, Komsan; Thalangsri, Pimsiree; Krusun, Srichai; Supakalin, Narudom

2016-01-01

To evaluate the treatment outcomes of patients with locally advanced rectal cancer treated with preoperative concurrent chemoradiotherapy (CCRT) or combined chemotherapy together with radiotherapy (CMTRT) without surgery. A total of 84 patients with locally advanced rectal adenocarcinoma (stage II or III) between January 1st, 2003 and December 31st, 2013 were enrolled, 48 treated with preoperative CCRT (Gr.I) and 36 with combined chemotherapy and radiotherapy (CMTRT) without surgery (Gr.II). The chemotherapeutic agents used concurrent with radiotherapy were either 5fluorouracil short infusion plus leucovorin and/or capecitabine or 5fluorouracil infusion alone. All patients received pelvic irradiation. There were 5 patients (10.4%) with a complete pathological response. The 3 yearoverall survival rates were 83.2% in Gr.I and 24.8 % in Gr.II (p<0.01). The respective 5 yearoverall survival rates were 70.3% and 0% (p<0.01). The 5 yearoverall survival rates in Gr.I for patients who received surgery within 56 days after complete CCRT as compared to more than 56 days were 69.5% and 65.1% (p=0.91). Preoperative CCRT used for 12 of 30 patients in Gr.I (40%) with lower rectal cancer demonstrated that in preoperative CCRT a sphincter sparing procedure can be performed. The results of treatment with preoperative CCRT for locally advanced rectal cancer showed comparable rates of overall survival and sphincter sparing procedures as compared to previous studies.

Combining Chk1/2 Inhibition with Cetuximab and Radiation Enhances In Vitro and In Vivo Cytotoxicity in Head and Neck Squamous Cell Carcinoma.

PubMed

Zeng, Ling; Beggs, Reena R; Cooper, Tiffiny S; Weaver, Alice N; Yang, Eddy S

2017-04-01

EGFR inhibition and radiotherapy are potent inducers of DNA damage. Checkpoint kinases 1 and 2 (Chk1/2) are critical regulators of the DNA-damage response, controlling cell-cycle checkpoints that may permit recovery from therapy-associated genomic stress. We hypothesized that Chk1/2 inhibition (CHKi) with prexasertib may enhance cytotoxicity from EGFR inhibition plus radiotherapy in head and neck squamous cell carcinoma (HNSCC). In this study, we found that the addition of CHKi to the EGFR inhibitor cetuximab with and without radiotherapy significantly decreased cell proliferation and survival fraction in human papillomavirus virus (HPV)-positive and HPV-negative HNSCC cell lines. Reduced proliferation was accompanied by decreased checkpoint activation, induced S-phase accumulation, persistent DNA damage, and increased caspase cleavage and apoptosis. Importantly, a significant tumor growth delay was observed in vivo in both HPV-positive and HPV-negative cell line xenografts receiving triple combination therapy with CHKi, cetuximab, and radiotherapy without a concomitant increase in toxicity as assessed by mouse body weight. Taken together, the combination of CHKi with cetuximab plus irradiation displayed significant antitumor effects in HNSCCs both in vitro and in vivo , suggesting that this combination therapy may increase clinical benefit. A clinical trial to test this treatment for patients with head and neck cancer is currently ongoing (NCT02555644). Mol Cancer Ther; 16(4); 591-600. ©2017 AACR . ©2017 American Association for Cancer Research.

A pilot study using dynamic contrast enhanced-MRI as a response biomarker of the radioprotective effect of memantine in patients receiving whole brain radiotherapy.

PubMed

Wong, Philip; Leppert, Ilana R; Roberge, David; Boudam, Karim; Brown, Paul D; Muanza, Thierry; Pike, G Bruce; Chankowsky, Jeffrey; Mihalcioiu, Catalin

2016-08-09

This pilot prospective study sought to determine whether dynamic contrast enhanced MRI (DCE-MRI) could be used as a clinical imaging biomarker of tissue toxicity from whole brain radiotherapy (WBRT). 14 patients who received WBRT were imaged using dynamic contrast enhanced DCE-MRI prior to and at 8-weeks, 16-weeks and 24-weeks after the initiation of WBRT. Twelve of the patients were also enrolled in the RTOG 0614 trial, which randomized patients to the use of placebo or memantine. After the unblinding of the treatments received by RTOG 0614 patients, DCE-MRI measures of tumor tissue and normal appearing white matter (NAWM) vascular permeability (Initial Area Under the Curve (AUC) Blood Adjusted) was analyzed. Cognitive, quality-of-life (QOL) assessment and blood samples were collected according to the patient's ability to tolerate the exams. Circulating endothelial cells (CEC) were measured using flow cytometry. Following WBRT, there was an increasing trend in the vascular permeability of tumors (p=0.09) and NAWM (p=0.06) with time. Memantine significantly (p=0.01) reduced NAWM AUC changes following radiotherapy. Patients on memantine retained (COWA p= 0.03) better cognitive functions than those on placebo. No association was observed between the level of CEC and DCE-MRI changes, time from radiotherapy or memantine use. DCE-MRI can detect vascular damage secondary to WBRT. Our data suggests that memantine reduces WBRT-induced brain vasculature damages.

Outcome of accelerated radiotherapy alone or accelerated radiotherapy followed by exenteration of the nasal cavity in dogs with intranasal neoplasia: 53 cases (1990-2002).

PubMed

Adams, William M; Bjorling, Dale E; McAnulty, Jonathan E; Green, Eric M; Forrest, Lisa J; Vail, David M

2005-09-15

To compare long-term results of radiotherapy alone versus radiotherapy followed by exenteration of the nasal cavity in dogs with malignant intranasal neoplasia. Retrospective study. 53 dogs with malignant intranasal neoplasia. All dogs underwent radiotherapy consisting of administration of 10 fractions of 4.2 Gy each on consecutive weekdays. For dogs in the surgery group (n=13), follow-up computed tomography was performed, and dogs were scheduled for surgery if persistent or recurrent tumor was seen. Perioperative complications for dogs that underwent surgery included hemorrhage requiring transfusion (2 dogs) and subcutaneous emphysema (8). Rhinitis and osteomyelitis-osteonecrosis occurred significantly more frequently in dogs in the radiotherapy and surgery group (9 and 4 dogs, respectively) than in dogs in the radiotherapy-only group (4 and 3 dogs, respectively). Two- and 3-year survival rates were 44% and 24%, respectively, for dogs in the radiotherapy group and 69% and 58%, respectively, for dogs in the surgery group. Overall median survival time for dogs in the radiotherapy and surgery group (477 months) was significantly longer than time for dogs in the radiotherapy-only group (19.7 months). Results suggest that exenteration of the nasal cavity significantly prolongs survival time in dogs with intranasal neoplasia that have undergone radiotherapy. Exenteration after radiotherapy may increase the risk of chronic complications.

Therapy of primary CNS lymphoma with methotrexate-based chemotherapy and deferred radiotherapy: preliminary results.

PubMed

Cher, L; Glass, J; Harsh, G R; Hochberg, F H

1996-06-01

Disease-free survival in primary CNS lymphoma has improved with the advent of methotrexate-based pre-irradiation chemotherapy. Prolonged response durations have been noted in six of eight patients refusing radiation therapy in two of our prior series. We have treated an additional 11 patients with methotrexate-based chemotherapy without subsequent planned irradiation. Some received maintenance chemotherapy. Most have had durable responses with little or no toxicity. Prolonged responses can be maintained without radiation therapy, thus avoiding potential long-term radiation toxicity.

Postoperative Radiotherapy Patterns of Care and Survival Implications for Medulloblastoma in Young Children.

PubMed

Kann, Benjamin H; Park, Henry S; Lester-Coll, Nataniel H; Yeboa, Debra N; Benitez, Viviana; Khan, Atif J; Bindra, Ranjit S; Marks, Asher M; Roberts, Kenneth B

2016-12-01

Postoperative radiotherapy to the craniospinal axis is standard-of-care for pediatric medulloblastoma but is associated with long-term morbidity, particularly in young children. With the advent of modern adjuvant chemotherapy strategies, postoperative radiotherapy deferral has gained acceptance in children younger than 3 years, although it remains controversial in older children. To analyze recent postoperative radiotherapy national treatment patterns and implications for overall survival in patients with medulloblastoma ages 3 to 8 years. Using the National Cancer Data Base, patients ages 3 to 8 years diagnosed as having histologically confirmed medulloblastoma in 2004 to 2012, without distant metastases, who underwent surgery and adjuvant chemotherapy with or without postoperative radiotherapy at facilities nationwide accredited by the Commission on Cancer were identified. Patients were designated as having "postoperative radiotherapy upfront" if they received radiotherapy within 90 days of surgery or "postoperative radiotherapy deferred" otherwise. Factors associated with postoperative radiotherapy deferral were identified using multivariable logistic regression. Overall survival (OS) was compared using Kaplan-Meier analysis with log-rank tests and multivariable Cox regression. Statistical tests were 2-sided. Postoperative radiotherapy utilization and overall survival. Among 816 patients, 123 (15.1%) had postoperative radiotherapy deferred, and 693 (84.9%) had postoperative radiotherapy upfront; 36.8% of 3-year-olds and 4.1% of 8-year-olds had postoperative radiotherapy deferred (P < .001). On multivariable logistic regression, variables associated with postoperative radiotherapy deferral were age (odds ratio [OR], 0.57 per year; 95% CI, 0.49-0.67 per year) and year of diagnosis (OR, 1.18 per year; 95% CI, 1.08-1.29 per year). On survival analysis, with median follow-up of 4.8 years, OS was improved for those receiving postoperative radiotherapy upfront vs postoperative radiotherapy deferred (5-year OS: 82.0% vs 63.4%; P < .001). On multivariable analysis, variables associated with poorer OS were postoperative radiotherapy deferral (hazards ratio [HR], 1.95; 95% CI, 1.15-3.31); stage M1-3 disease (HR, 1.86; 95% CI, 1.10-3.16), and low facility volume (HR, 1.75; 95% CI, 1.04-2.94). Our national database analysis reveals a higher-than-expected and increasing rate of postoperative radiotherapy deferral in children with medulloblastoma ages 3 to 8 years. The analysis suggests that postoperative radiotherapy deferral is associated with worse survival in this age group, even in the modern era of chemotherapy.

MO-DE-BRA-03: The Ottawa Medical Physics Institute (OMPI): A Practical Model for Academic Program Collaboration in a Multi-Centre City

DOE Office of Scientific and Technical Information (OSTI.GOV)

McEwen, M; Rogers, D; Johns, P

Purpose: To build a world-class medical physics educational program that capitalizes on expertise distributed over several clinical, government, and academic centres. Few if any of these centres would have the critical mass to solely resource a program. Methods: In order to enable an academic program, stakeholders from five institutions made a proposal to Carleton University for a) a research network with defined membership requirements and a process for accepting new members, and b) a graduate specialization (MSc and PhD) in medical physics. Both proposals were accepted and the program has grown steadily. Our courses are taught by medical physicists frommore » across the collaboration. Our students have access to physicists in: clinical radiotherapy (the Ottawa Cancer Centre treats 4500 new patients/y), radiology, cardiology and nuclear medicine, Canada’s primary standards dosimetry laboratory, radiobiology, and university-based medical physics research. Our graduate courses emphasize the foundational physics plus applied aspects of imaging, radiotherapy, and radiobiology. Active researchers in the city-wide volunteer-run network are appointed as adjunct professors by Physics, giving them access to national funding competitions and partial student funding through teaching assistantships while opening up facilities in their institutions for student thesis research. Results: The medical physics network has grown to ∼40 members from eight institutions and includes five full-time faculty in Physics and 17 adjunct research professors. The graduate student population is ∼20. Our graduates have proceeded to a spectrum of careers. Our alumni list includes a CCPM Past-President, the current COMP President, many clinical physicists, and the heads of at least three major clinical medical physics departments. Our PhD was Ontario’s first CAMPEP-accredited program. Conclusion: A self-governing volunteer network is the foundational element that enables an MSc/PhD medical physics program in a city with multiple physicist employers. It enriches graduate education with an unusually broad range of expertise.« less

Patterns of radiotherapy infrastructure in Japan and in other countries with well-developed radiotherapy infrastructures.

PubMed

Nakamura, Katsumasa; Konishi, Kenta; Komatsu, Tetsuya; Sasaki, Tomonari; Shikama, Naoto

2018-05-01

In high-income countries, the number of radiotherapy machine per population reaches a sufficient level. However, the patterns of infrastructure of radiotherapy in high-income countries are not well known. Among 29 high-income countries with gross national income of $25,000 or more per capita, we selected 23 countries whose total number of newly diagnosed cancer patients in 2012 was reported in the Organisation for Economic Co-operation and Development Health Statistics 2017. The numbers of radiotherapy centers and teletherapy machines in each of these 23 countries were collected using the Dictionary of Radiotherapy Centers database. The number of cancer patients per teletherapy machine was 452.35-1398.22 (median 711.66) with a three-fold variation, whereas the number of cancer patients per radiotherapy center varied even more widely, from 826.16 to 5159.86 (median 2259.83) with a six-fold variation. The average number of teletherapy machines per radiotherapy center also ranged widely, from 1.24 to 8.29 (median 3.11) with a seven-fold variation. The number of teletherapy machines in each country was almost proportional to that of cancer patients, and the number of teletherapy machines per radiotherapy center was inversely related to the number of radiotherapy centers per cancer patients. The number of teletherapy machines per radiotherapy center in Japan was 1.24, the most fragmented among the high-income countries. The percentage of large radiotherapy centers having three or more teletherapy machines in Japan was the smallest among 23 high-income countries. Optimization of the radiotherapy infrastructure in Japan should be carefully considered.

Effect of radiotherapy after breast-conserving surgery in older patients with early breast cancer and breast ductal carcinoma in situ: a meta-analysis

PubMed Central

Chen, Wen-jun; Zhang, Xi; Wu, Cong-cong; Zhang, Chao-ying; Sun, Shuang-shuang; Wu, Jian

2017-01-01

Background There are no consistent agreements on whether radiotherapy after breast-conserving surgery (BCS) could provide local control and survival benefit for older patients with early breast cancer or breast ductal carcinoma in situ (DCIS). The present study aimed to evaluate the efficacy of radiotherapy after BCS in older patients with early breast cancer or DCIS. Results Radiotherapy could reduce the risk of local relapse in older patients with early breast cancer. The 5-year AR of local relapse was 2.2% and 6.2% for radiotherapy and non-radiotherapy group, respectively, with low 5-year ARD of 4.0% and high NNT of 25. The 10-year AR of local relapse was 5.3% and 10.5% for radiotherapy and non-radiotherapy group, respectively, with the 10-year ARD of 5.2% and NNT of 20. However, radiotherapy could not improve survival benefits, including overall survival, cancer-specific survival, breast-cancer-specific survival, and distant relapse. Moreover, radiotherapy could reduce the risk of ipsilateral breast events in older patients with DCIS. Materials and Methods PubMed and Embase database were searched for relevant studies. Hazard ratios (HRs), risk ratios (RRs), absolute risk (AR), absolute risk difference (ARD), and number needed to treat (NNT) were used as effect measures to evaluate the efficacy of radiotherapy in older patients. Conclusions Our study indicates that radiotherapy could slightly reduce the risk of local relapse in older patients with favorable early breast cancer. However, radiotherapy cannot translate into significant survival benefits. PMID:28415667

Barriers to radiotherapy access at the University College Hospital in Ibadan, Nigeria.

PubMed

Anakwenze, Chidinma P; Ntekim, Atara; Trock, Bruce; Uwadiae, Iyobosa B; Page, Brandi R

2017-08-01

Nigeria has the biggest gap between radiotherapy availability and need, with one machine per 19.4 million people, compared to one machine per 250,000 people in high-income countries. This study aims to identify its patient-level barriers to radiotherapy access. This was a cross sectional study consisting of patient questionnaires ( n  = 50) conducted in January 2016 to assess patient demographics, types of cancers seen, barriers to receiving radiotherapy, health beliefs and practices, and factors leading to treatment delay. Eighty percent of patients could not afford radiotherapy without financial assistance and only 6% of the patients had federal insurance, which did not cover radiotherapy services. Of the patients who had completed radiotherapy treatment, 91.3% had experienced treatment delay or often cancellation due to healthcare worker strike, power failure, machine breakdown, or prolonged wait time. The timeliness of a patient's radiotherapy care correlated with their employment status and distance from radiotherapy center ( p  < 0.05). Barriers to care at a radiotherapy center in a low- and middle-income country (LMIC) have previously not been well characterized. These findings can be used to inform efforts to expand the availability of radiotherapy and improve current treatment capacity in Nigeria and in other LMICs.

TU-AB-BRD-00: Task Group 100

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2015-06-15

Current quality assurance and quality management guidelines provided by various professional organizations are prescriptive in nature, focusing principally on performance characteristics of planning and delivery devices. However, published analyses of events in radiation therapy show that most events are often caused by flaws in clinical processes rather than by device failures. This suggests the need for the development of a quality management program that is based on integrated approaches to process and equipment quality assurance. Industrial engineers have developed various risk assessment tools that are used to identify and eliminate potential failures from a system or a process before amore » failure impacts a customer. These tools include, but are not limited to, process mapping, failure modes and effects analysis, fault tree analysis. Task Group 100 of the American Association of Physicists in Medicine has developed these tools and used them to formulate an example risk-based quality management program for intensity-modulated radiotherapy. This is a prospective risk assessment approach that analyzes potential error pathways inherent in a clinical process and then ranks them according to relative risk, typically before implementation, followed by the design of a new process or modification of the existing process. Appropriate controls are then put in place to ensure that failures are less likely to occur and, if they do, they will more likely be detected before they propagate through the process, compromising treatment outcome and causing harm to the patient. Such a prospective approach forms the basis of the work of Task Group 100 that has recently been approved by the AAPM. This session will be devoted to a discussion of these tools and practical examples of how these tools can be used in a given radiotherapy clinic to develop a risk based quality management program. Learning Objectives: Learn how to design a process map for a radiotherapy process Learn how to perform failure modes and effects analysis analysis for a given process Learn what fault trees are all about Learn how to design a quality management program based upon the information obtained from process mapping, failure modes and effects analysis and fault tree analysis. Dunscombe: Director, TreatSafely, LLC and Center for the Assessment of Radiological Sciences; Consultant to IAEA and Varian Thomadsen: President, Center for the Assessment of Radiological Sciences Palta: Vice President of the Center for the Assessment of Radiological Sciences.« less

TU-AB-BRD-03: Fault Tree Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dunscombe, P.

2015-06-15

Current quality assurance and quality management guidelines provided by various professional organizations are prescriptive in nature, focusing principally on performance characteristics of planning and delivery devices. However, published analyses of events in radiation therapy show that most events are often caused by flaws in clinical processes rather than by device failures. This suggests the need for the development of a quality management program that is based on integrated approaches to process and equipment quality assurance. Industrial engineers have developed various risk assessment tools that are used to identify and eliminate potential failures from a system or a process before amore » failure impacts a customer. These tools include, but are not limited to, process mapping, failure modes and effects analysis, fault tree analysis. Task Group 100 of the American Association of Physicists in Medicine has developed these tools and used them to formulate an example risk-based quality management program for intensity-modulated radiotherapy. This is a prospective risk assessment approach that analyzes potential error pathways inherent in a clinical process and then ranks them according to relative risk, typically before implementation, followed by the design of a new process or modification of the existing process. Appropriate controls are then put in place to ensure that failures are less likely to occur and, if they do, they will more likely be detected before they propagate through the process, compromising treatment outcome and causing harm to the patient. Such a prospective approach forms the basis of the work of Task Group 100 that has recently been approved by the AAPM. This session will be devoted to a discussion of these tools and practical examples of how these tools can be used in a given radiotherapy clinic to develop a risk based quality management program. Learning Objectives: Learn how to design a process map for a radiotherapy process Learn how to perform failure modes and effects analysis analysis for a given process Learn what fault trees are all about Learn how to design a quality management program based upon the information obtained from process mapping, failure modes and effects analysis and fault tree analysis. Dunscombe: Director, TreatSafely, LLC and Center for the Assessment of Radiological Sciences; Consultant to IAEA and Varian Thomadsen: President, Center for the Assessment of Radiological Sciences Palta: Vice President of the Center for the Assessment of Radiological Sciences.« less

TU-AB-BRD-01: Process Mapping

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palta, J.

2015-06-15

Current quality assurance and quality management guidelines provided by various professional organizations are prescriptive in nature, focusing principally on performance characteristics of planning and delivery devices. However, published analyses of events in radiation therapy show that most events are often caused by flaws in clinical processes rather than by device failures. This suggests the need for the development of a quality management program that is based on integrated approaches to process and equipment quality assurance. Industrial engineers have developed various risk assessment tools that are used to identify and eliminate potential failures from a system or a process before amore » failure impacts a customer. These tools include, but are not limited to, process mapping, failure modes and effects analysis, fault tree analysis. Task Group 100 of the American Association of Physicists in Medicine has developed these tools and used them to formulate an example risk-based quality management program for intensity-modulated radiotherapy. This is a prospective risk assessment approach that analyzes potential error pathways inherent in a clinical process and then ranks them according to relative risk, typically before implementation, followed by the design of a new process or modification of the existing process. Appropriate controls are then put in place to ensure that failures are less likely to occur and, if they do, they will more likely be detected before they propagate through the process, compromising treatment outcome and causing harm to the patient. Such a prospective approach forms the basis of the work of Task Group 100 that has recently been approved by the AAPM. This session will be devoted to a discussion of these tools and practical examples of how these tools can be used in a given radiotherapy clinic to develop a risk based quality management program. Learning Objectives: Learn how to design a process map for a radiotherapy process Learn how to perform failure modes and effects analysis analysis for a given process Learn what fault trees are all about Learn how to design a quality management program based upon the information obtained from process mapping, failure modes and effects analysis and fault tree analysis. Dunscombe: Director, TreatSafely, LLC and Center for the Assessment of Radiological Sciences; Consultant to IAEA and Varian Thomadsen: President, Center for the Assessment of Radiological Sciences Palta: Vice President of the Center for the Assessment of Radiological Sciences.« less

TU-AB-BRD-02: Failure Modes and Effects Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huq, M.

2015-06-15

Current quality assurance and quality management guidelines provided by various professional organizations are prescriptive in nature, focusing principally on performance characteristics of planning and delivery devices. However, published analyses of events in radiation therapy show that most events are often caused by flaws in clinical processes rather than by device failures. This suggests the need for the development of a quality management program that is based on integrated approaches to process and equipment quality assurance. Industrial engineers have developed various risk assessment tools that are used to identify and eliminate potential failures from a system or a process before amore » failure impacts a customer. These tools include, but are not limited to, process mapping, failure modes and effects analysis, fault tree analysis. Task Group 100 of the American Association of Physicists in Medicine has developed these tools and used them to formulate an example risk-based quality management program for intensity-modulated radiotherapy. This is a prospective risk assessment approach that analyzes potential error pathways inherent in a clinical process and then ranks them according to relative risk, typically before implementation, followed by the design of a new process or modification of the existing process. Appropriate controls are then put in place to ensure that failures are less likely to occur and, if they do, they will more likely be detected before they propagate through the process, compromising treatment outcome and causing harm to the patient. Such a prospective approach forms the basis of the work of Task Group 100 that has recently been approved by the AAPM. This session will be devoted to a discussion of these tools and practical examples of how these tools can be used in a given radiotherapy clinic to develop a risk based quality management program. Learning Objectives: Learn how to design a process map for a radiotherapy process Learn how to perform failure modes and effects analysis analysis for a given process Learn what fault trees are all about Learn how to design a quality management program based upon the information obtained from process mapping, failure modes and effects analysis and fault tree analysis. Dunscombe: Director, TreatSafely, LLC and Center for the Assessment of Radiological Sciences; Consultant to IAEA and Varian Thomadsen: President, Center for the Assessment of Radiological Sciences Palta: Vice President of the Center for the Assessment of Radiological Sciences.« less

A singular value decomposition linear programming (SVDLP) optimization technique for circular cone based robotic radiotherapy.

PubMed

Liang, Bin; Li, Yongbao; Wei, Ran; Guo, Bin; Xu, Xuang; Liu, Bo; Li, Jiafeng; Wu, Qiuwen; Zhou, Fugen

2018-01-05

With robot-controlled linac positioning, robotic radiotherapy systems such as CyberKnife significantly increase freedom of radiation beam placement, but also impose more challenges on treatment plan optimization. The resampling mechanism in the vendor-supplied treatment planning system (MultiPlan) cannot fully explore the increased beam direction search space. Besides, a sparse treatment plan (using fewer beams) is desired to improve treatment efficiency. This study proposes a singular value decomposition linear programming (SVDLP) optimization technique for circular collimator based robotic radiotherapy. The SVDLP approach initializes the input beams by simulating the process of covering the entire target volume with equivalent beam tapers. The requirements on dosimetry distribution are modeled as hard and soft constraints, and the sparsity of the treatment plan is achieved by compressive sensing. The proposed linear programming (LP) model optimizes beam weights by minimizing the deviation of soft constraints subject to hard constraints, with a constraint on the l 1 norm of the beam weight. A singular value decomposition (SVD) based acceleration technique was developed for the LP model. Based on the degeneracy of the influence matrix, the model is first compressed into lower dimension for optimization, and then back-projected to reconstruct the beam weight. After beam weight optimization, the number of beams is reduced by removing the beams with low weight, and optimizing the weights of the remaining beams using the same model. This beam reduction technique is further validated by a mixed integer programming (MIP) model. The SVDLP approach was tested on a lung case. The results demonstrate that the SVD acceleration technique speeds up the optimization by a factor of 4.8. Furthermore, the beam reduction achieves a similar plan quality to the globally optimal plan obtained by the MIP model, but is one to two orders of magnitude faster. Furthermore, the SVDLP approach is tested and compared with MultiPlan on three clinical cases of varying complexities. In general, the plans generated by the SVDLP achieve steeper dose gradient, better conformity and less damage to normal tissues. In conclusion, the SVDLP approach effectively improves the quality of treatment plan due to the use of the complete beam search space. This challenging optimization problem with the complete beam search space is effectively handled by the proposed SVD acceleration.

A singular value decomposition linear programming (SVDLP) optimization technique for circular cone based robotic radiotherapy

NASA Astrophysics Data System (ADS)

Liang, Bin; Li, Yongbao; Wei, Ran; Guo, Bin; Xu, Xuang; Liu, Bo; Li, Jiafeng; Wu, Qiuwen; Zhou, Fugen

2018-01-01

With robot-controlled linac positioning, robotic radiotherapy systems such as CyberKnife significantly increase freedom of radiation beam placement, but also impose more challenges on treatment plan optimization. The resampling mechanism in the vendor-supplied treatment planning system (MultiPlan) cannot fully explore the increased beam direction search space. Besides, a sparse treatment plan (using fewer beams) is desired to improve treatment efficiency. This study proposes a singular value decomposition linear programming (SVDLP) optimization technique for circular collimator based robotic radiotherapy. The SVDLP approach initializes the input beams by simulating the process of covering the entire target volume with equivalent beam tapers. The requirements on dosimetry distribution are modeled as hard and soft constraints, and the sparsity of the treatment plan is achieved by compressive sensing. The proposed linear programming (LP) model optimizes beam weights by minimizing the deviation of soft constraints subject to hard constraints, with a constraint on the l 1 norm of the beam weight. A singular value decomposition (SVD) based acceleration technique was developed for the LP model. Based on the degeneracy of the influence matrix, the model is first compressed into lower dimension for optimization, and then back-projected to reconstruct the beam weight. After beam weight optimization, the number of beams is reduced by removing the beams with low weight, and optimizing the weights of the remaining beams using the same model. This beam reduction technique is further validated by a mixed integer programming (MIP) model. The SVDLP approach was tested on a lung case. The results demonstrate that the SVD acceleration technique speeds up the optimization by a factor of 4.8. Furthermore, the beam reduction achieves a similar plan quality to the globally optimal plan obtained by the MIP model, but is one to two orders of magnitude faster. Furthermore, the SVDLP approach is tested and compared with MultiPlan on three clinical cases of varying complexities. In general, the plans generated by the SVDLP achieve steeper dose gradient, better conformity and less damage to normal tissues. In conclusion, the SVDLP approach effectively improves the quality of treatment plan due to the use of the complete beam search space. This challenging optimization problem with the complete beam search space is effectively handled by the proposed SVD acceleration.

Radical radiotherapy incorporating a brachytherapy boost for the treatment of carcinoma of the thoracic oesophagus: results from a cohort of patients and review of the literature.

PubMed

Churn, M; Jones, B; Myint, A Sun

2002-04-01

The optimal treatment for potentially curable carcinoma of the oesophagus unsuitable for surgical resection is unresolved. An intraluminal brachytherapy boost (ILBT) can be used following external beam radiotherapy (EBRT) with or without concurrent chemotherapy (CRT). ILBT increases the dose to the tumour volume substantially while reducing the lung dose but the corresponding high dose to the oesophageal wall may cause increased complications. We report the outcomes of 32 consecutive patients treated with radical radiotherapy. A dose of 45-55 Gy in 20-25 fractions with external beam radiotherapy (EBRT) followed by an ILBT boost. Earlier in the series a low dose rate (LDR) brachytherapy technique using 125Iodine seeds delivering a dose of 20-22 Gy at 25-40 cGy/h was used. This was later superseded by high dose rate (HDR) treatments delivering 8.5-10 Gy in one fraction at 1 cm from the catheter. Patients of age below 76 years, of good performance status and with no other medical contraindication were considered for concurrent chemotherapy (CRT) using a planned regime of cisplatin (80 mg/m2 day 1) and 5-flurouracil (1 g/m2 days 1 to 4) in the first and last weeks of radiotherapy (13 patients). The EBRT and ILBT were well tolerated but 8/13 (62%) patients had dose modifications of chemotherapy in one or both cycles due to advanced age, co-morbidity or toxicity. The median follow-up period of surviving patients was 37 months (range 35-39) and the median overall survival for the whole group was 9 months. The overall survival at 1 year was 34.4% (17.6-51.2%), 15.6% (2.8-28.4%) at 2 and 3 years. Local recurrence-free survival at 1 year was 35.3% (15.9-54.7%) and 24.5% (8.3-44.6%) at 2 and 3 years (Fig. 2). Though symptom relief was good there were six cases of ulceration, six of stricture and two fistulae. Biological equivalent for tumour response (BED Gy,10) and late radiation effects (BED Gy3) were calculated for the different radiotherapy regimens using equations derived from the linear quadratic model. In this series no advantage was found in terms of local control or survival for patients receiving radiotherapy doses resulting in a BED Gy10 greater than 75% of the maximum. Similarly, no significant increase in complications was noted in those patients receiving doses resulting in a BED Gy3 > 75% of the maximum. The merits and hazards of the ILBT boost used in radical radiotherapy are discussed and the relevant literature reviewed.

Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.

PubMed

Donovan, J L; Hamdy, F C; Lane, J A; Mason, M; Metcalfe, C; Walsh, E; Blazeby, J M; Peters, T J; Holding, P; Bonnington, S; Lennon, T; Bradshaw, L; Cooper, D; Herbert, P; Howson, J; Jones, A; Lyons, N; Salter, E; Thompson, P; Tidball, S; Blaikie, J; Gray, C; Bollina, P; Catto, J; Doble, A; Doherty, A; Gillatt, D; Kockelbergh, R; Kynaston, H; Paul, A; Powell, P; Prescott, S; Rosario, D J; Rowe, E; Davis, M; Turner, E L; Martin, R M; Neal, D E

2016-10-13

Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. The negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group. Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat, except for the increasing frequency of bloody stools; bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life. In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups. (Funded by the U.K. National Institute for Health Research Health Technology Assessment Program; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

Analysis of outcomes in radiation oncology: An integrated computational platform

PubMed Central

Liu, Dezhi; Ajlouni, Munther; Jin, Jian-Yue; Ryu, Samuel; Siddiqui, Farzan; Patel, Anushka; Movsas, Benjamin; Chetty, Indrin J.

2009-01-01

Radiotherapy research and outcome analyses are essential for evaluating new methods of radiation delivery and for assessing the benefits of a given technology on locoregional control and overall survival. In this article, a computational platform is presented to facilitate radiotherapy research and outcome studies in radiation oncology. This computational platform consists of (1) an infrastructural database that stores patient diagnosis, IMRT treatment details, and follow-up information, (2) an interface tool that is used to import and export IMRT plans in DICOM RT and AAPM/RTOG formats from a wide range of planning systems to facilitate reproducible research, (3) a graphical data analysis and programming tool that visualizes all aspects of an IMRT plan including dose, contour, and image data to aid the analysis of treatment plans, and (4) a software package that calculates radiobiological models to evaluate IMRT treatment plans. Given the limited number of general-purpose computational environments for radiotherapy research and outcome studies, this computational platform represents a powerful and convenient tool that is well suited for analyzing dose distributions biologically and correlating them with the delivered radiation dose distributions and other patient-related clinical factors. In addition the database is web-based and accessible by multiple users, facilitating its convenient application and use. PMID:19544785

Patient safety in external beam radiotherapy, results of the ACCIRAD project: Current status of proactive risk assessment, reactive analysis of events, and reporting and learning systems in Europe.

PubMed

Malicki, Julian; Bly, Ritva; Bulot, Mireille; Godet, Jean-Luc; Jahnen, Andreas; Krengli, Marco; Maingon, Philippe; Prieto Martin, Carlos; Przybylska, Kamila; Skrobała, Agnieszka; Valero, Marc; Jarvinen, Hannu

2017-04-01

To describe the current status of implementation of European directives for risk management in radiotherapy and to assess variability in risk management in the following areas: 1) in-country regulatory framework; 2) proactive risk assessment; (3) reactive analysis of events; and (4) reporting and learning systems. The original data were collected as part of the ACCIRAD project through two online surveys. Risk assessment criteria are closely associated with quality assurance programs. Only 9/32 responding countries (28%) with national regulations reported clear "requirements" for proactive risk assessment and/or reactive risk analysis, with wide variability in assessment methods. Reporting of adverse error events is mandatory in most (70%) but not all surveyed countries. Most European countries have taken steps to implement European directives designed to reduce the probability and magnitude of accidents in radiotherapy. Variability between countries is substantial in terms of legal frameworks, tools used to conduct proactive risk assessment and reactive analysis of events, and in the reporting and learning systems utilized. These findings underscore the need for greater harmonisation in common terminology, classification and reporting practices across Europe to improve patient safety and to enable more reliable inter-country comparisons. Copyright © 2017 Elsevier B.V. All rights reserved.

Cancer Deaths due to Lack of Universal Access to Radiotherapy in the Brazilian Public Health System.

PubMed

Mendez, L C; Moraes, F Y; Fernandes, G Dos S; Weltman, E

2018-01-01

Radiotherapy plays a fundamental role in the treatment of cancer. Currently, the Brazilian public health system cannot match the national radiotherapy demand and many patients requiring radiotherapy are never exposed to this treatment. This study estimated the number of preventable deaths in the public health system if access to radiotherapy was universal. Incidence rates for the year 2016 provided by Instituto Nacional de Cancer were used in this analysis. The number of untreated patients requiring radiotherapy was obtained through the difference between the total number of patients requiring radiotherapy and the total amount of delivered radiotherapy treatments in the public health system. The number of deaths for the three most common cancers in each gender due to radiotherapy shortage was calculated. Initially, the total number of patients per cancer type was divided in stages using Brazilian epidemiological data. Subsequently, previously published tree arm diagrams were used to define the rate of patients requiring radiotherapy in each specific clinical setting. Finally, the clinical benefit of radiotherapy in overall survival was extracted from studies with level 1 evidence. Over 596 000 cancer cases were expected in Brazil in 2016. The public health system covers more than 75% of the Brazilian population and an estimated 111 432 patients who required radiotherapy in 2016 did not receive this treatment. Breast, colorectal and cervix cancers are the most frequent malignant tumours in women and prostate, lung and colorectal in men. The number of deaths due to a radiotherapy shortage in the year 2016 for these types of cancer were: (i) breast: 1011 deaths in 10 years; (ii) cervix: 2006 deaths in 2 years; (iii) lung: 1206 deaths in 2 years; (iv) prostate, intermediate risk: 562 deaths in 13 years; high risk: 298 deaths in 10 years; (v) colorectal: 0 deaths, as radiotherapy has no proven benefit in overall survival. Thousands of cancer patients requiring radiotherapy do not have access to this treatment in the Brazilian public health system. The shortage of radiotherapy has a significant detrimental effect on cancer survival; over 5000 deaths would probably be prevented in the most common cancer types if radiotherapy access was universal. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Local tumor control probability modeling of primary and secondary lung tumors in stereotactic body radiotherapy.

PubMed

Guckenberger, Matthias; Klement, Rainer J; Allgäuer, Michael; Andratschke, Nicolaus; Blanck, Oliver; Boda-Heggemann, Judit; Dieckmann, Karin; Duma, Marciana; Ernst, Iris; Ganswindt, Ute; Hass, Peter; Henkenberens, Christoph; Holy, Richard; Imhoff, Detlef; Kahl, Henning K; Krempien, Robert; Lohaus, Fabian; Nestle, Ursula; Nevinny-Stickel, Meinhard; Petersen, Cordula; Semrau, Sabine; Streblow, Jan; Wendt, Thomas G; Wittig, Andrea; Flentje, Michael; Sterzing, Florian

2016-03-01

To evaluate whether local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) varies between lung metastases of different primary cancer sites and between primary non-small cell lung cancer (NSCLC) and secondary lung tumors. A retrospective multi-institutional (n=22) database of 399 patients with stage I NSCLC and 397 patients with 525 lung metastases was analyzed. Irradiation doses were converted to biologically effective doses (BED). Logistic regression was used for local tumor control probability (TCP) modeling and the second-order bias corrected Akaike Information Criterion was used for model comparison. After median follow-up of 19 months and 16 months (n.s.), local tumor control was observed in 87.7% and 86.7% of the primary and secondary lung tumors (n.s.), respectively. A strong dose-response relationship was observed in the primary NSCLC and metastatic cohort but dose-response relationships were not significantly different: the TCD90 (dose to achieve 90% TCP; BED of maximum planning target volume dose) estimates were 176 Gy (151-223) and 160 Gy (123-237) (n.s.), respectively. The dose-response relationship was not influenced by the primary cancer site within the metastatic cohort. Dose-response relationships for local tumor control in SBRT were not different between lung metastases of various primary cancer sites and between primary NSCLC and lung metastases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Protracted Hypofractionated Radiotherapy for Graves' Ophthalmopathy: A Pilot Study of Clinical and Radiologic Response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Casimiro de Deus Cardoso, Cejana; Giordani, Adelmo Jose; Borri Wolosker, Angela Maria

Purpose: To evaluate the clinical and radiologic response of patients with Graves' ophthalmopathy given low-dose orbital radiotherapy (RT) with a protracted fractionation. Methods and Materials: Eighteen patients (36 orbits) received orbital RT with a total dose of 10 Gy, fractionated in 1 Gy once a week over 10 weeks. Of these, 9 patients received steroid therapy as well. Patients were evaluated clinically and radiologically at 6 months after treatment. Clinical response assessment was carried out using three criteria: by physical examination, by a modified clinical activity score, and by a verbal questionnaire considering the 10 most common signs and symptomsmore » of the disease. Radiologic response was assessed by magnetic resonance imaging. Results: Improvement in ocular pain, palpebral edema, visual acuity, and ocular motility was observed in all patients. Significant decrease in symptoms such as tearing (p < 0.001) diplopia (p = 0.008), conjunctival hyperemia (p = 0.002), and ocular grittiness (p = 0.031) also occurred. Magnetic resonance imaging showed decrease in ocular muscle thickness and in the intensity of the T2 sequence signal in the majority of patients. Treatments were well tolerated, and to date no complications from treatment have been observed. There was no statistical difference in clinical and radiologic response between patients receiving RT alone and those receiving RT plus steroid therapy. Conclusion: RT delivered in at a low dose and in a protracted scheme should be considered as a useful therapeutic option for patients with Graves' ophthalmopathy.« less

Post-radiotherapy hypothyroidism in dogs treated for thyroid carcinomas.

PubMed

Amores-Fuster, I; Cripps, P; Blackwood, L

2017-03-01

Hypothyroidism is a common adverse event after head and neck radiotherapy in human medicine, but uncommonly reported in canine patients. Records of 21 dogs with histologically or cytologically confirmed thyroid carcinoma receiving definitive or hypofractionated radiotherapy were reviewed. Nine cases received 48 Gy in 12 fractions, 10 received 36 Gy in 4 fractions and 2 received 32 Gy in 4 fractions. Seventeen cases had radiotherapy in a post-operative setting. Ten cases developed hypothyroidism (47.6%) after radiotherapy. The development of hypothyroidism was not associated with the radiotherapy protocol used. Median time to diagnosis of hypothyroidism was 6 months (range, 1-13 months). Hypothyroidism is a common side effect following radiotherapy for thyroid carcinomas. Monitoring of thyroid function following radiotherapy is recommended. No specific risk factors have been identified. © 2015 John Wiley & Sons Ltd.

High performance computing for deformable image registration: towards a new paradigm in adaptive radiotherapy.

PubMed

Samant, Sanjiv S; Xia, Junyi; Muyan-Ozcelik, Pinar; Owens, John D

2008-08-01

The advent of readily available temporal imaging or time series volumetric (4D) imaging has become an indispensable component of treatment planning and adaptive radiotherapy (ART) at many radiotherapy centers. Deformable image registration (DIR) is also used in other areas of medical imaging, including motion corrected image reconstruction. Due to long computation time, clinical applications of DIR in radiation therapy and elsewhere have been limited and consequently relegated to offline analysis. With the recent advances in hardware and software, graphics processing unit (GPU) based computing is an emerging technology for general purpose computation, including DIR, and is suitable for highly parallelized computing. However, traditional general purpose computation on the GPU is limited because the constraints of the available programming platforms. As well, compared to CPU programming, the GPU currently has reduced dedicated processor memory, which can limit the useful working data set for parallelized processing. We present an implementation of the demons algorithm using the NVIDIA 8800 GTX GPU and the new CUDA programming language. The GPU performance will be compared with single threading and multithreading CPU implementations on an Intel dual core 2.4 GHz CPU using the C programming language. CUDA provides a C-like language programming interface, and allows for direct access to the highly parallel compute units in the GPU. Comparisons for volumetric clinical lung images acquired using 4DCT were carried out. Computation time for 100 iterations in the range of 1.8-13.5 s was observed for the GPU with image size ranging from 2.0 x 10(6) to 14.2 x 10(6) pixels. The GPU registration was 55-61 times faster than the CPU for the single threading implementation, and 34-39 times faster for the multithreading implementation. For CPU based computing, the computational time generally has a linear dependence on image size for medical imaging data. Computational efficiency is characterized in terms of time per megapixels per iteration (TPMI) with units of seconds per megapixels per iteration (or spmi). For the demons algorithm, our CPU implementation yielded largely invariant values of TPMI. The mean TPMIs were 0.527 spmi and 0.335 spmi for the single threading and multithreading cases, respectively, with <2% variation over the considered image data range. For GPU computing, we achieved TPMI =0.00916 spmi with 3.7% variation, indicating optimized memory handling under CUDA. The paradigm of GPU based real-time DIR opens up a host of clinical applications for medical imaging.

Orbital Radiotherapy Combined With Corticosteroid Treatment for Thyroid Eye Disease-Compressive Optic Neuropathy.

PubMed

Gold, Katherine G; Scofield, Stacy; Isaacson, Steven R; Stewart, Michael W; Kazim, Michael

To evaluate the effectiveness of orbital radiotherapy (ORT) in the treatment of thyroid eye disease (TED)-compressive optic neuropathy. A retrospective review of patients with corticosteroid-responsive compressive optic neuropathy due to TED treated with ORT. Study was conducted in compliance with Health Insurance Portability and Accountability Act. One hundred four patients (163 orbits) with a mean age of 61.7 years met inclusion criteria. Seventy-four percent (77/104) were female, and 32.7% (34/104) were current or previous smokers. A total absorbed dose of 2000 cGy fractionated in 10 treatment doses over the course of 2 weeks was administered to the retroocular tissues according to a standard protocol. The primary end point was failure of ORT, defined as persistent optic neuropathy following completion of radiotherapy that mandated urgent orbital decompression surgery. Ninety-eight of 104 (94%) patients or 152 of 163 (93.3%) orbits did not require orbital decompression surgery during the acute phase. Patients who responded successfully to ORT had similar improvements in visual acuity, color vision, Humphrey threshold visual field testing, and afferent pupillary defects compared with patients who failed ORT and underwent urgent decompression surgery. Only 36.7% of successfully treated patients ultimately underwent elective surgery, including orbital decompression, strabismus, or eyelid surgery, during the inactive phase of TED. The data from this study, the largest retrospective review reported to date, supports the use of ORT in eyes with corticosteroid-responsive TED-compressive optic neuropathy. ORT may favorably alter the natural history of active-phase TED by preventing recurrent compressive optic neuropathy after withdrawal of corticosteroids.

Characterization of the distribution, retention, and efficacy of internal radiation of 188Re-lipid nanocapsules in an immunocompromised human glioblastoma model.

PubMed

Cikankowitz, Annabelle; Clavreul, Anne; Tétaud, Clément; Lemaire, Laurent; Rousseau, Audrey; Lepareur, Nicolas; Dabli, Djamel; Bouchet, Francis; Garcion, Emmanuel; Menei, Philippe; Couturier, Olivier; Hindré, François

2017-01-01

Internal radiation strategies hold great promise for glioblastoma (GB) therapy. We previously developed a nanovectorized radiotherapy that consists of lipid nanocapsules loaded with a lipophilic complex of Rhenium-188 (LNC 188 Re-SSS). This approach resulted in an 83 % cure rate in the 9L rat glioma model, showing great promise. The efficacy of LNC 188 Re-SSS treatment was optimized through the induction of a T-cell immune response in this model, as it is highly immunogenic. However, this is not representative of the human situation where T-cell suppression is usually encountered in GB patients. Thus, in this study, we investigated the efficacy of LNC 188 Re-SSS in a human GB model implanted in T-cell deficient nude mice. We also analyzed the distribution and tissue retention of LNC 188 Re-SSS. We observed that intratumoral infusion of LNCs by CED led to their complete distribution throughout the tumor and peritumoral space without leakage into the contralateral hemisphere except when large volumes were used. Seventy percent of the 188 Re-SSS activity was present in the tumor region 24 h after LNC 188 Re-SSS injection and no toxicity was observed in the healthy brain. Double fractionated internal radiotherapy with LNC 188 Re-SSS triggered survival responses in the immunocompromised human GB model with a cure rate of 50 %, which was not observed with external radiotherapy. In conclusion, LNC 188 Re-SSS can induce long-term survival in an immunosuppressive environment, highlighting its potential for GB therapy.

Modern Radiotherapy Concepts and the Impact of Radiation on Immune Activation

PubMed Central

Deloch, Lisa; Derer, Anja; Hartmann, Josefin; Frey, Benjamin; Fietkau, Rainer; Gaipl, Udo S.

2016-01-01

Even though there is extensive research carried out in radiation oncology, most of the clinical studies focus on the effects of radiation on the local tumor tissue and deal with normal tissue side effects. The influence of dose fractionation and timing particularly with regard to immune activation is not satisfactorily investigated so far. This review, therefore, summarizes current knowledge on concepts of modern radiotherapy (RT) and evaluates the potential of RT for immune activation. Focus is set on radiation-induced forms of tumor cell death and consecutively the immunogenicity of the tumor cells. The so-called non-targeted, abscopal effects can contribute to anti-tumor responses in a specific and systemic manner and possess the ability to target relapsing tumor cells as well as metastases. The impact of distinct RT concepts on immune activation is outlined and pre-clinical evidence and clinical observations on RT-induced immunity will be discussed. Knowledge on the radiosensitivity of immune cells as well as clinical evidence for enhanced immunity after RT will be considered. While stereotactic ablative body radiotherapy seem to have a beneficial outcome over classical RT fractionation in pre-clinical animal models, in vitro model systems suggest an advantage for classical fractionated RT for immune activation. Furthermore, the optimal approach may differ based on the tumor site and/or genetic signature. These facts highlight that clinical trials are urgently needed to identify whether high-dose RT is superior to induce anti-tumor immune responses compared to classical fractionated RT and in particular how the outcome is when RT is combined with immunotherapy in selected tumor entities. PMID:27379203

Concurrent chemo-radiotherapy with S-1 as an alternative therapy for elderly Chinese patients with non-metastatic esophageal squamous cancer: evidence based on a systematic review and meta-analysis.

PubMed

Song, Guo-Min; Tian, Xu; Liu, Xiao-Ling; Chen, Hui; Zhou, Jian-Guo; Bian, Wei; Chen, Wei-Qing

2017-06-06

This systematic review and meta-analysis aims to systematically assess the effects of concurrent chemo-radiotherapy (CRT) compared with radiotherapy (RT) alone for elderly Chinese patients with non-metastatic esophageal squamous cancer. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), China Biomedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI) databases. We retrieved randomized controlled trials on concurrent CRT with Gimeraciland Oteracil Porassium (S-1) compared with RT alone for aged Chinese patients with non-metastatic esophageal squamous cancer performed until August 2016. Eight eligible studies involving 536 patients were subjected to meta-analysis. As a response rate measure, a relative risk (RR) of 1.37 [95% confidence intervals (CIs): 1.24, 1.53; P = 0.00], which reached statistical significance, was estimated when concurrent CRT with S-1 was performed compared with RT alone. Sensitivity analysis on response rate confirmed the robustness of the pooled result. The RR values of 1.44 (95% CIs: 1.22, 1.70; P = 0.00) and 1.77 (95% CIs: 1.26, 2.48; P = 0.00) estimated for 1- and 2-year survival rate indices, respectively, were also statistically significant. The incidence of adverse events was similar in both groups. This review concluded that concurrent CRT with S-1 can improve the efficacy and prolong the survival period of elderly Chinese patients with non-metastatic esophageal squamous cancer and does not significantly increase the acute adverse effects of RT alone.

Is neoadjuvant chemotherapy prior to radio-chemotherapy beneficial in T4 anal carcinoma?

PubMed

Moureau-Zabotto, L; Viret, F; Giovaninni, M; Lelong, B; Bories, E; Delpero, J R; Pesenti, C; Caillol, F; de Chaisemartin, C; Minsat, M; Monges, G; Sarran, A; Resbeut, M

2011-07-01

This study retrospectively describes the outcome of a series of 38 patients (pts) with T4 anal carcinoma exclusively treated by radio and chemotherapy. From 1992 to 2007, 38 pts with UST4-N0-2-M0 anal carcinoma were treated with exclusive radiotherapy and chemotherapy. All patients received external beam radiotherapy (EBRT) (median dose 45 Gy) with a concomitant chemotherapy (5-fluorouracil-cisplatin). Eleven patients received neo-adjuvant chemotherapy (5-fluorouracil-cisplatin). After 2-8 weeks, a 15-20 Gy boost was delivered either with EBRT (20 pts) or interstitial (192)Ir brachytherapy (18 pts). Mean follow-up was 66 months. After chemoradiation therapy (CRT), 13 pts (34%) had a complete response, 23 pts (60%) a response >50% (2 pts were not evaluated). The 5-year-disease-free survival was 79.2 ± 6.5%, and the 5-year overall survival was 83.9 ± 6%. Eight patients developed tumor progression (mean delay 8.8 months), six of them requiring a salvage surgery with definitive colostomy for local relapse. Late severe complication requiring colostomy was observed in 2 pts. The 5-year-colostomy-free survival was 78 ± 6.9%. Patients who received primary chemotherapy had a statistically significant better 5-year colostomy-free survival (100% vs. 38 ± 16.4%, P = 0.0006). T4 anal carcinoma can be treated with a curative intent using a sphincter-sparing approach of CRT, and neo-adjuvant chemotherapy should be considered prior to radiotherapy. Copyright © 2011 Wiley-Liss, Inc.

Performance characteristics of mobile MOSFET dosimeter for kilovoltage X-rays used in image guided radiotherapy

PubMed Central

Kumar, A. Sathish; Singh, I. Rabi Raja; Sharma, S. D.; Ravindran, B. Paul

2015-01-01

The main objective of this study was to investigate the characteristics of metal oxide semiconductor field effect transistor (MOSFET) dosimeter for kilovoltage (kV) X-ray beams in order to perform the in vivo dosimetry during image guidance in radiotherapy. The performance characteristics of high sensitivity MOSFET dosimeters were investigated for 80, 90, 100, 110, 120, and 125 kV X-ray beams used for imaging in radiotherapy. This study was performed using Clinac 2100 C/D medical electron linear accelerator with on-board imaging and kV cone beam computed tomography system. The characteristics studied in this work include energy dependence, angular dependence, and linearity. The X-ray beam outputs were measured as per American Association of Physicists in Medicine (AAPM) TG 61 recommendations using PTW parallel plate (PP) ionization chamber, which was calibrated in terms of air kerma (Nk) by the National Standard Laboratory. The MOSFET dosimeters were calibrated against the PP ionization chamber for all the kV X-ray beams and the calibration coefficient was found to be 0.11 cGy/mV with a standard deviation of about ±1%. The response of MOSFET was found to be energy independent for the kV X-ray energies used in this study. The response of the MOSFET dosimeter was also found independent of angle of incidence for the gantry angles in the range of 0° to 360° in-air as well as at 3 cm depth in tissue equivalent phantom. PMID:26500397

Capecitabine Initially Concomitant to Radiotherapy Then Perioperatively Administered in Locally Advanced Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zampino, Maria Giulia; Magni, Elena; Leonardi, Maria Cristina

2009-10-01

Purpose: To evaluate the impact of neoadjuvant capecitabine, concomitant to radiotherapy, followed by capecitabine monotherapy, in operable locally advanced rectal cancer (LARC) by measuring pathologic response and conservative surgery rate, toxicity profile, and disease-free survival (DFS). Methods and Materials: From October 2002 to July 2006, a total of 51 patients affected by LARC (T3-T4 or any node positive tumor), received capecitabine (825 mg/m{sup 2}, orally, twice daily continuously) concomitant to radiotherapy on the pelvis (50.4 Gy/ 28 fractions), followed by two cycles of capecitabine (1,250 mg/m{sup 2}, orally, twice daily, 14 days on 7 days off) up until 2 weeksmore » before surgery. Tailored adjuvant systemic treatment was discussed according to pathologic stage. Results: Of 51 patients, (median age 61 years, range 38-82 years; 19 women and 32 men; ECOG performance status 0/1/2: 46/4/1), 50 were evaluable for response: 18% complete pathologic remission; 12% T-downstaging, and 30% N-downstaging. One patient died before surgery from mesenteric stroke. Grade 3 acute toxicities were 2% diarrhea, 8% dermatitis, 2% liver function test elevation, and 2% hand-foot syndrome. Sphincter preservation rates for tumors {<=}6 cm from the anal verge were 62% and 80% for the whole population. Median follow up was 43.0 months (range 0.8-68.6 months). Five-years DFS was 85.4% (95% CI = 75.3-95.4%). Conclusions: Based on our study results, we conclude that this regimen is well tolerated and active and compares favorably with existing capecitabine-based approaches.« less

Complete Resolution of a Recurrent Canine Anal Sac Squamous Cell Carcinoma with Palliative Radiotherapy and Carboplatin Chemotherapy

PubMed Central

Giuliano, Antonio; Dobson, Jane; Mason, Sarah

2017-01-01

Anal sac squamous cell carcinoma (SCC) is a rare tumor in dogs. Only eight cases have been described in the literature, and previous reports of treatment only describe surgery or palliative treatment with non-steroidal anti-inflammatory drugs. We report a case of a 12-year-old female neutered Labrador with locally advanced anal sac SCC. The dog was treated with four cycles of carboplatin 300 mg/m2 and four weekly fractions of 8.5 Gy radiation. The dog achieved a complete response, and one year later the dog is still alive and well with no evidence of tumor recurrence. Radiotherapy in combination with carboplatin chemotherapy was effective in the long-term control of this rare disease. PMID:29056703

Kill and spread the word: stimulation of antitumor immune responses in the context of radiotherapy.

PubMed

Gaipl, Udo S; Multhoff, Gabriele; Scheithauer, Heike; Lauber, Kirsten; Hehlgans, Stefanie; Frey, Benjamin; Rödel, Franz

2014-01-01

Besides the direct, targeted effects of ionizing irradiation (x-ray) on cancer cells, namely DNA damage and cell death induction, indirect, nontargeted ones exist, which are mediated in large part by the immune system. Immunogenic forms of tumor cell death induced by x-ray, including immune modulating danger signals like the heat shock protein 70, adenosine triphosphate, and high-mobility group box 1 protein are presented. Further, antitumor effects exerted by cells of the innate (natural killer cells) as well as adaptive immune system (T cells activated by dendritic cells) are outlined. Tumor cell death inhibiting molecules such as survivin are introduced as suitable target for molecularly tailored therapies in combination with x-ray. Finally, reasonable combinations of immune therapies with radiotherapy are discussed.

[Application of elastic registration based on Demons algorithm in cone beam CT].

PubMed

Pang, Haowen; Sun, Xiaoyang

2014-02-01

We applied Demons and accelerated Demons elastic registration algorithm in radiotherapy cone beam CT (CBCT) images, We provided software support for real-time understanding of organ changes during radiotherapy. We wrote a 3D CBCT image elastic registration program using Matlab software, and we tested and verified the images of two patients with cervical cancer 3D CBCT images for elastic registration, based on the classic Demons algorithm, minimum mean square error (MSE) decreased 59.7%, correlation coefficient (CC) increased 11.0%. While for the accelerated Demons algorithm, MSE decreased 40.1%, CC increased 7.2%. The experimental verification with two methods of Demons algorithm obtained the desired results, but the small difference appeared to be lack of precision, and the total registration time was a little long. All these problems need to be further improved for accuracy and reducing of time.

[Timing of Brain Radiation Therapy Impacts Outcomes in Patients with 
Non-small Cell Lung Cancer Who Develop Brain Metastases].

PubMed

Wang, Yang; Fang, Jian; Nie, Jun; Dai, Ling; Hu, Weiheng; Zhang, Jie; Ma, Xiangjuan; Han, Jindi; Chen, Xiaoling; Tian, Guangming; Wu, Di; Han, Sen; Long, Jieran

2016-08-20

Radiotherapy combined with chemotherapy or molecular targeted therapy remains the standard of treatment for brain metastases from non-small cell lung cancer (NSCLC). The aim of this study is to determine if the deferral of brain radiotherapy impacts patient outcomes. Between May 2003 and December 2015, a total of 198 patients with brain metastases from NSCLC who received both brain radiotherapy and systemic therapy (chemotherapy or targeted therapy) were identified. The rate of grade 3-4 adverse reactions related to chemotherapy and radiotherapy had no significant difference between two groups. 127 patients received concurrent brain radiotherapy and systemic therapy, and 71 patients received deferred brain radiotherapy after at least two cycles of chemotherapy or targeted therapy. Disease specific-graded prognostic assessment was similar in early radiotherapy group and deferred radiotherapy group. Median overall survival (OS) was longer in early radiotherapy group compared to deferred radiotherapy group (17.9 months vs 12.6 months; P=0.038). Progression free survival (PFS) was also improved in patients receiving early radiotherapy compared to those receiving deferred radiotherapy (4.0 months vs 3.0 months; P<0.01). Receiving tyrosine kinase inhibitor (TKI) therapy after the diagnosis of brain metastases as any line therapy improved the OS (20.0 months vs 10.7 months; P<0.01), whereas receiving TKI as first line therapy did not (17.9 months vs 15.2 months; P=0.289). Our study suggests that the use of deferred brain radiotherapy may resulted in inferior OS in patients with NSCLC who develop brain metastases. A prospective multi-central randomized study is imminently needed.

Radiotherapy access in Belgium: How far are we from evidence-based utilisation?

PubMed

Lievens, Y; De Schutter, H; Stellamans, K; Rosskamp, M; Van Eycken, L

2017-10-01

Underutilisation of radiotherapy has been observed worldwide. To evaluate the current situation in Belgium, optimal utilisation proportions (OUPs) adopted from the European SocieTy for Radiotherapy and Oncology - Health Economics in Radiation Oncology (ESTRO-HERO) project were compared to actual utilisation proportions (AUPs) and with radiotherapy advised during the multidisciplinary cancer team (MDT) meetings. In addition, the impact of independent variables was analysed. AUPs and advised radiotherapy were calculated overall and by cancer type for 110,810 unique cancer diagnoses in 2009-2010. Radiotherapy utilisation was derived from reimbursement data and distinguished between palliative and curative intent external beam radiotherapy (EBRT) and/or brachytherapy (BT). Sensitivity analyses regarding the influence of the follow-up period, the survival length and patient's age were performed. Advised radiotherapy was calculated based on broad treatment categories as reported at MDT meetings. The overall AUP of 37% (39% including BT) was lower than the OUP of 53%, but in line with advised radiotherapy (35%). Large variations by tumour type were observed: in some tumours (e.g. lung and prostate cancer) AUP was considerably lower than OUP, whereas in others there was reasonable concordance (e.g. breast and rectal cancer). Overall, 84% of treatments started within 9 months following diagnosis. Survival time influenced AUP in a cancer type-dependent way. Elderly patients received less radiotherapy. Although the actually delivered radiotherapy in Belgium aligns well to MDT advices, it is lower than the evidence-based optimum. Further analysis of potential barriers is needed for radiotherapy forecasting and planning, and in order to promote adequate access to radiotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.