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Sample records for intraoperative radiotherapy combined

  1. Intraoperative radiotherapy for breast cancer.

    PubMed

    Vaidya, Jayant S; Tobias, Jeffrey S; Baum, Michael; Keshtgar, Mohammed; Joseph, David; Wenz, Frederik; Houghton, Joan; Saunders, Christobel; Corica, Tammy; D'Souza, Derek; Sainsbury, Richard; Massarut, Samuele; Taylor, Irving; Hilaris, Basil

    2004-03-01

    Postoperative radiotherapy, which forms part of breast-conserving therapy, may not need to encompass the whole breast. Apart from the consumption of huge resources and patients' time, postoperative radiotherapy deters many women from receiving the benefits of breast-conserving surgery, forcing them to choose a mastectomy instead. If radiotherapy could be given in the operating theatre immediately after surgery, many of these disadvantages could be overcome. One striking fact about local recurrence after breast-conserving surgery is that most occurs in the area of breast immediately next to the primary tumour; this is despite the finding that two-thirds of mastectomy samples have microscopic tumours distributed throughout the breast, even when radiotherapy is omitted. Thus, only the area adjacent to the tumour may need treatment with radiotherapy. On the basis of this premise, clinical scientists have used new technology to administer radiotherapy to the area at greatest risk of local recurrence, with the aim of completing the whole local treatment in one sitting. In this review, we have elaborated on the rationale and different methods of delivery of intraoperative radiotherapy. If this approach is validated by the results of current randomised trials, it could save time, money, and breasts.

  2. Intraoperative Radiotherapy Combined With Adjuvant Chemoradiotherapy for Locally Advanced Gastric Adenocarcinoma

    SciTech Connect

    Fu Shen; Lu Jiade; Zhang Qing Yang Zhe; Peng Lihua; Xiong, Fei

    2008-12-01

    Purpose: To evaluate the efficacy of intraoperative radiotherapy (IORT) followed by concurrent chemotherapy and external beam RT (EBRT) in the treatment of locally advanced gastric adenocarcinoma. Methods and Materials: A total of 97 consecutive and nonselected patients with newly diagnosed Stage T3, T4, or N+ adenocarcinoma of the stomach underwent gastrectomy with D2 lymph node dissection between March 2003 and October 2005. Of the 97 patients, 51 received adjuvant concurrent chemotherapy (5-fluorouracil, leucovorin, docetaxel, and cisplatin) and EBRT (EBRT group) and 46 received IORT (dose range, 12-15 Gy) immediately after gastrectomy and lymph node dissection before concurrent chemoradiotherapy (EBRT+IORT group). Results: After a median follow-up of 24 months, the 3-year locoregional control rate was 77% and 63% in the two groups with or without IORT, respectively (p = 0.05). The 3-year overall survival and disease-free survival rate was 47% and 36% in the EBRT group and 56% and 44% in the EBRT+IORT group, respectively (p > 0.05). Multivariate analyses revealed that the use of IORT, presence of residual disease after surgery, and pN category were independent prognostic factors for locoregional control and that IORT, pN, and pT categories were independent prognostic factors for overall survival (p < 0.05). Four patients experienced Grade 3 or 4 late complications, but no significant difference was observed between the two groups. Conclusions: Radical gastrectomy with D2 lymph node dissection and IORT followed by adjuvant chemoradiotherapy appeared to be feasible and well-tolerated in the treatment of locally advanced gastric cancer. The addition of IORT to the trimodality treatment significantly improved the 3-year locoregional control rate.

  3. Intraoperative radiotherapy for breast cancer

    PubMed Central

    Williams, Norman R.; Pigott, Katharine H.; Brew-Graves, Chris

    2014-01-01

    Intra-operative radiotherapy (IORT) as a treatment for breast cancer is a relatively new technique that is designed to be a replacement for whole breast external beam radiotherapy (EBRT) in selected women suitable for breast-conserving therapy. This article reviews twelve reasons for the use of the technique, with a particular emphasis on targeted intra-operative radiotherapy (TARGIT) which uses X-rays generated from a portable device within the operating theatre immediately after the breast tumour (and surrounding margin of healthy tissue) has been removed. The delivery of a single fraction of radiotherapy directly to the tumour bed at the time of surgery, with the capability of adding EBRT at a later date if required (risk-adaptive technique) is discussed in light of recent results from a large multinational randomised controlled trial comparing TARGIT with EBRT. The technique avoids irradiation of normal tissues such as skin, heart, lungs, ribs and spine, and has been shown to improve cosmetic outcome when compared with EBRT. Beneficial aspects to both institutional and societal economics are discussed, together with evidence demonstrating excellent patient satisfaction and quality of life. There is a discussion of the published evidence regarding the use of IORT twice in the same breast (for new primary cancers) and in patients who would never be considered for EBRT because of their special circumstances (such as the frail, the elderly, or those with collagen vascular disease). Finally, there is a discussion of the role of the TARGIT Academy in developing and sustaining high standards in the use of the technique. PMID:25083504

  4. Intraoperative radiotherapy (IORT) combined with external beam radiotherapy (EBRT) for soft-tissue sarcomas – a retrospective evaluation of the Homburg experience in the years 1995–2007

    PubMed Central

    Niewald, Marcus; Fleckenstein, Jochen; Licht, Norbert; Bleuzen, Caroline; Ruebe, Christian

    2009-01-01

    Purpose To retrospectively evaluate the results after a regimen of surgery, IORT (intraoperative radiotherapy), and EBRT (external beam radiotherapy) for soft-tissue sarcomas Methods 38 consecutive patients underwent IORT for soft-tissue sarcoma; 29 were treated for primary tumours, 9 for recurrences. There were 14 cases with liposarcomas, 8 with leiomyosarcomas, 7 with malignant fibrous histiocytomas. 27/38 tumours were located in the extremities, the remaining ones in the retroperitoneum or the chest. Radical resection was attempted in all patients; a R0-resection was achieved in 15/38 patients, R1 in 12/38 pats and R2 in 4/38 pats. IORT was performed using a J-125 source and a HDR (high dose rate) afterloading machine after suturing silicone flaps to the tumour bed. The total dose applied ranged from 8–15 Gy/0.5 cm tissue depth measured from the flap surface. After wound healing external beam radiotherapy (EBRT) was applied in 31/38 patients with total doses of 23–56 Gy dependent on resection status and wound situation. The mean duration of follow-up was 2.3 years. Results A local recurrence was found in 10/36 patients, lymph node metastases in 2/35, and distant metastases in 6/35 patients. The actuarial local control rate was 63%/5 years. The overall survival rate was 57%/5 years. There was no statistically significant difference between the results after treatment for primaries or for recurrences. Late toxicity to the skin was found in 13/31 patients, wound healing problems in 5/31 patients. A neuropathy was never seen. Conclusion The combination of surgery, IORT, and EBRT yields favourable local control and survival data which are well within the range of the results reported in the literature. The complication rates, however, are considerable although the complications are not severe, they should be taken into account when therapy decisions are made. PMID:19709420

  5. Intraoperative Radiotherapy in Childhood Malignant Astrocytoma

    PubMed Central

    Rana, Sohail R.; Haddy, Theresa B.; Ashayeri, Ebrahim; Goldson, Alfred L.

    1984-01-01

    A 12-year-old black male patient with glioblastoma multiforme was treated with intraoperative radiotherapy followed by conventional external beam radiation and chemotherapy. The authors' clinical experience with these therapeutic measures is discussed. PMID:6330375

  6. Combination of external-beam radiotherapy with intraoperative electron-beam therapy is effective in incompletely resected pediatric malignancies

    SciTech Connect

    Oertel, Susanne; Niethammer, Andreas G.; Krempien, Robert . E-mail: robert_krempien@med.uni-heidelberg.de; Roeder, Falk; Eble, Michael J.; Baer, Claudia; Huber, Peter E.; Kulozik, Andreas; Waag, Karl-Ludwig; Treiber, Martina; Debus, Juergen

    2006-01-01

    Purpose: Intraoperative electron-beam radiotherapy (IOERT) has been applied for local dose escalation in over 1,400 patients in Heidelberg since 1991. Among these were 30 children, in 18 of whom IOERT was employed in radiation treatment with external-beam radiotherapy (EBRT) on account of incomplete resection. We address the question whether IOERT is able to compensate for microscopic or macroscopic tumor residue if employed in the overall radiation regimen. Methods and Materials: The data of the aforementioned 18 children were analyzed with regard to local recurrence, overall survival, and complication rates. All children suffered from either sarcomas or neuroblastomas. In all children, IOERT was employed for local dose escalation after or before EBRT. Results: After a median follow-up of 60.5 months, 15 of the treated children are alive. One local failure has been observed. Six children show clinically significant late morbidity, including the loss of a treated limb (Radiation Therapy Oncology Group Grade 4 [RTOG 4]), a severe nerve lesion (RTOG 3), an orthopedic complication (RTOG 2), a ureteral stenosis (not clinically significant), and a kidney hypotrophy (not clinically significant). In 1 child a fracture due to radionecrosis (RTOG 4) was diagnosed; however, in the follow-up, local tumor relapse was diagnosed as another possible reason for the fracture. Conclusions: Regarding the low incidence of local failure, IOERT seems to be able to compensate incomplete tumor resection in childhood sarcoma and neuroblastoma patients. The incidence of late morbidity is low enough to justify the employment of IOERT as part of the radiation treatment regimen for pediatric patients.

  7. [Intraoperative radiotherapy in abdominal-pelvic cancer surgery].

    PubMed

    Signor, M; Fongione, S

    1997-12-01

    Intraoperative radiotherapy consists in the irradiation of the affected area, exposed using anesthesiological and laparotomic procedures, following the removal of a neoplasia using palliative or macroscopically radical surgical. This increases local tumour control and augments the selectivity of treatment between healthy and neoplastic tissues, thus obtaining a marked improvement in survival or palliation. The authors analyse the data reported in international literature regarding the possible use of intraoperative radiotherapy in patients undergoing abdomino-pelvic oncological surgery. The aim of the study was to evaluate this method for use in selected and combined treatment in which surgery represents an obligatory step. Studies were carried out in a few highly specialised centres given that special technical, logistic and professional skills were required. The populations studied were often very small with a marked prevalence of feasibility studies compared to random studies. In spite of this intraoperative radiotherapy is undoubtedly indicated in locally advanced gastric, rectal and vesical neoplasia, it represents a valid palliative solution in pancreatic neoplasia and in pelvic recidivation, and an effective alternative solution to mutilating surgery in the initial stages of vesical cancer. Positive results are obtained in prostate and uterine cancer, but they are reported by non-conclusive studies. Toxicity is acceptable and non-limiting within a given range of doses and irradiated volume. The "repercussion" in terms of knowledge, experience, scientific integration between oncological surgeons and radiotherapists is basic, with a marked improved in the management of cancer treatment.

  8. Our intraoperative boost radiotherapy experience and applications

    PubMed Central

    Günay, Semra; Alan, Ömür; Yalçın, Orhan; Türkmen, Aygen; Dizdar, Nihal

    2016-01-01

    Objective: To present our experience since November 2013, and case selection criteria for intraoperative boost radiotherapy (IObRT) that significantly reduces the local recurrence rate after breast conserving surgery in patients with breast cancer. Material and Methods: Patients who were suitable for IObRT were identified within the group of patients who were selected for breast conserving surgery at our breast council. A MOBETRON (mobile linear accelerator for IObRT) was used for IObRt during surgery. Results: Patients younger than 60 years old with <3 cm invasive ductal cancer in one focus (or two foci within 2 cm), with a histologic grade of 2–3, and a high possibility of local recurrence were admitted for IObRT application. Informed consent was obtained from all participants. Lumpectomy and sentinel lymph node biopsy was performed and advancement flaps were prepared according to the size and inclination of the conus following evaluation of tumor size and surgical margins by pathology. Distance to the thoracic wall was measured, and a radiation oncologist and radiation physicist calculated the required dose. Anesthesia was regulated with slower ventilation frequency, without causing hypoxia. The skin and incision edges were protected, the field was radiated (with 6 MeV electron beam of 10 Gy) and the incision was closed. In our cases, there were no major postoperative surgical or early radiotherapy related complications. Conclusion: The completion of another stage of local therapy with IObRT during surgery positively effects sequencing of other treatments like chemotherapy, hormonotherapy and radiotherapy, if required. IObRT increases disease free and overall survival, as well as quality of life in breast cancer patients. PMID:26985156

  9. Role of intraoperative radiotherapy in the treatment of sacral chordoma.

    PubMed

    Jullien-Petrelli, A C; Asencio, J M; Orue-Echebarria, M I; Lozano, P; Álvarez, A; Serrano, J; Calvo, F M; Calvo-Haro, J A; Lasso, J M; García-Sabrido, J L

    2017-09-04

    Sacral chordoma is a rare entity with high local recurrence rates when complete resection is not achieved. Till date, there are not any series available in literature combining surgery and intraoperative radiotherapy (IORT). To report the experience of our Centre in the management of sacral chordoma combining radical resection with both external radiotherapy and intraoperative radiotherapy (IORT). Retrospective case series. 15 patients with sacral chordoma resected in our centre from 1998 to 2015. Overall survival (OS), Disease free survival and rates of local and distant recurrence. We retrospectively revised the records of all the patients with sacral chordoma resected in our centre from 1998 to December 2015. Overall survival (OS), Disease free survival and rates of local and distant recurrence were calculated. Results between patients treated with or without IORT were compared. A total of 15 patients were identified: 8 males and 7 females. Median age was 59 years (range 28-77). IORT was applied in 9 patients and 6 were treated with surgical resection without IORT. In 13 patients we performed the treatment of the primary tumor and in 2 patients we performed the treatment of recurrence disease. A posterior approach was used in 4 patients. Wide surgical margins (R0) were achieved in 6 patients, marginal margins (R1) in 7 patients and there were not any patient with intralesional (R2) margins. At a median follow up of 38 months (range 11-209 months), the 5 years OS in the IORT group was 100% versus 53% in the group of non-IORT (p=0.05). The median DFS in the IORT group was 85 months versus 41 months in the non-IORT group. In the group without IORT, two patients died and nobody died during the follow up in the group treated with IORT. High sacrectomy treated patients had a median survival of 41 months versus 90 months in low sacrectomy treated patients. DFS in patients without gluteal involvement was 100% at 5 years, and 40% in patients with gluteal involvement (fig

  10. Long-Term Results of Targeted Intraoperative Radiotherapy (Targit) Boost During Breast-Conserving Surgery

    SciTech Connect

    Vaidya, Jayant S.; Baum, Michael; Tobias, Jeffrey S.; Wenz, Frederik; Massarut, Samuele; Keshtgar, Mohammed; Hilaris, Basil; Saunders, Christobel; Williams, Norman R.; Brew-Graves, Chris; Corica, Tammy; Roncadin, Mario; Kraus-Tiefenbacher, Uta; Suetterlin, Marc; Bulsara, Max; Joseph, David

    2011-11-15

    Purpose: We have previously shown that delivering targeted radiotherapy to the tumour bed intraoperatively is feasible and desirable. In this study, we report on the feasibility, safety, and long-term efficacy of TARGeted Intraoperative radioTherapy (Targit), using the Intrabeam system. Methods and Materials: A total of 300 cancers in 299 unselected patients underwent breast-conserving surgery and Targit as a boost to the tumor bed. After lumpectomy, a single dose of 20 Gy was delivered intraoperatively. Postoperative external beam whole-breast radiotherapy excluded the usual boost. We also performed a novel individualized case control (ICC) analysis that computed the expected recurrences for the cohort by estimating the risk of recurrence for each patient using their characteristics and follow-up period. Results: The treatment was well tolerated. The median follow up was 60.5 months (range, 10-122 months). Eight patients have had ipsilateral recurrence: 5-year Kaplan Meier estimate for ipsilateral recurrence is 1.73% (SE 0.77), which compares well with that seen in the boosted patients in the European Organization for Research and Treatment of Cancer study (4.3%) and the UK STAndardisation of breast RadioTherapy study (2.8%). In a novel ICC analysis of 242 of the patients, we estimated that there should be 11.4 recurrences; in this group, only 6 recurrences were observed. Conclusions: Lumpectomy and Targit boost combined with external beam radiotherapy results in a low local recurrence rate in a standard risk patient population. Accurate localization and the immediacy of the treatment that has a favorable effect on tumour microenvironment may contribute to this effect. These long-term data establish the long-term safety and efficacy of the Targit technique and generate the hypothesis that Targit boost might be superior to an external beam boost in its efficacy and justifies a randomized trial.

  11. Targeted intraoperative radiotherapy (TARGIT) yields very low recurrence rates when given as a boost

    SciTech Connect

    Vaidya, Jayant S. . E-mail: j.s.vaidya@dundee.ac.uk; Baum, Michael; Tobias, Jeffrey S.; Massarut, Samuele; Wenz, Frederik; Murphy, Olive; Hilaris, Basil; Houghton, Joan B.Sc.; Saunders, Christobel; Corica, Tammy; Roncadin, Mario; Kraus-Tiefenbacher, Uta; Melchaert, Frank; Keshtgar, Mohammed; Sainsbury, Richard; Douek, Michael; Harrison, Elly; Thompson, Alastair; Joseph, David

    2006-12-01

    Purpose: Patients undergoing breast-conserving surgery were offered boost radiotherapy with targeted intraoperative radiotherapy (TARGIT) using the Intrabeam system to test the feasibility, safety, and efficacy of the new approach. Methods and Materials: We treated 302 cancers in 301 unselected patients. This was not a low-risk group. One-third of patients (98/301) were younger than 51 years of age. More than half of the tumors (172, 57%) were between 1 cm and 2 cm, and one-fifth (62, 21%) were >2 cm; 29% (86) had a Grade 3 tumor and, in 29% (87), axillary lymph nodes contained metastasis. After primary surgery, 20 Gy was delivered intraoperatively to the surface of the tumor bed, followed by external-beam radiotherapy (EBRT), but excluding the usual boost. Results: The treatment was well tolerated. The follow-up ranged from 3 to 80 months (164 and 90 patients completed 2 and 3 years follow-up, respectively). Four patients (1.3%) had local recurrence. The Kaplan-Meier estimate of local recurrence is 2.6% (SE = 1.7) at 5 years. This compares favorably with the 4.3% recurrence rate in boosted patients from the EORTC boost study, in which only 8.1% patients were node-positive, as opposed to 29% in our series. Conclusion: Targeted intraoperative radiotherapy combined with EBRT results in a low local recurrence rate. This could be attributed to both accurate targeting and timeliness of the treatment. These data support the need for a randomized trial to test whether the TARGIT boost is superior to conventional external boost, especially in high-risk women.

  12. Intraoperative Radiotherapy for Parotid Cancer: A Single-Institution Experience

    SciTech Connect

    Zeidan, Youssef H.; Shiue, Kevin; Weed, Daniel; Johnstone, Peter A.; Terry, Colin; Freeman, Stephen; Krowiak, Edward; Borrowdale, Robert; Huntley, Tod; Yeh, Alex

    2012-04-01

    Purpose: Our practice policy has been to provide intraoperative radiotherapy (IORT) at resection to patients with head-and-neck malignancies considered to be at high risk of recurrence. The purpose of the present study was to review our experience with the use of IORT for primary or recurrent cancer of the parotid gland. Methods and Materials: Between 1982 and 2007, 96 patients were treated with gross total resection and IORT for primary or recurrent cancer of the parotid gland. The median age was 62.9 years (range, 14.3-88.1). Of the 96 patients, 33 had previously undergone external beam radiotherapy as a component of definitive therapy. Also, 34 patients had positive margins after surgery, and 40 had perineural invasion. IORT was administered as a single fraction of 15 or 20 Gy with 4-6-MeV electrons. The median follow-up period was 5.6 years. Results: Only 1 patient experienced local recurrence, 19 developed regional recurrence, and 12 distant recurrence. The recurrence-free survival rate at 1, 3, and 5 years was 82.0%, 68.5%, and 65.2%, respectively. The 1-, 3-, and 5-year overall survival rate after surgery and IORT was 88.4%, 66.1%, and 56.2%, respectively. No perioperative fatalities occurred. Complications developed in 26 patients and included vascular complications in 7, trismus in 6, fistulas in 4, radiation osteonecrosis in 4, flap necrosis in 2, wound dehiscence in 2, and neuropathy in 1. Of these 26 patients, 12 had recurrent disease, and 8 had undergone external beam radiotherapy before IORT. Conclusions: IORT results in effective local disease control at acceptable levels of toxicity and should be considered for patients with primary or recurrent cancer of the parotid gland.

  13. 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

  14. Intraoperative Electron Radiotherapy for the Management of Aggressive Fibromatosis

    SciTech Connect

    Roeder, Falk; Timke, Carmen; Oertel, Susanne; Hensley, Frank W.; Bischof, Marc; Muenter, Marc W.; Weitz, Juergen; Buchler, Markus W.; Lehner, Burkhard; Debus, Juergen; Krempien, Robert

    2010-03-15

    Purpose: We analyzed our experience with intraoperative electron radiotherapy (IOERT) followed by moderate doses of external beam radiotherapy (EBRT) after organ-sparing surgery in patients with primary or recurrent aggressive fibromatosis. Methods and Materials: Indication for IOERT and postoperative EBRT as an individual treatment approach to avoid mutilating surgical procedures was seen when complete surgical removal seemed to be unlikely or impossible. A total of 31 lesions in 30 patients were treated by surgery and IOERT with a median dose of 12 Gy. Median age was 31 years (range, 13-59 years). Resection status was close margin in six lesions, microscopically positive in 13, and macroscopically positive in 12. Median tumor size was 9 cm. In all, 25 patients received additional EBRT, with a median dose of 45 Gy (range, 36-54 Gy). Results: After a median follow-up of 32 months (range, 3-139 months), no disease-related deaths occurred. A total of five local recurrences were seen, resulting in actuarial 3-year local control rates of 82% overall and 91% inside the IOERT areas. Trends to improved local control were seen for older age (>31 years) and negative margins, but none of these factors reached significance. Perioperative complications were found in six patients, in particular as wound healing disturbances in five patients and venous thrombosis in one patient. Late toxicity was seen in five patients. Conclusion: Introduction of IOERT into a multimodal treatment approach in patients with aggressive fibromatosis is feasible with low toxicity and yielded good local control rates even in patients with microscopical or gross residual disease.

  15. The First Simultaneous Intraoperative Hyperthermia and Radiotherapy Procedure: Dog Experiment and Technique

    PubMed Central

    Ashayeri, Ebrahim; Halyard, Michele; Goldson, Alfred L.; Cruz, Leon; Nibhanupudy, J. Rao; DeWitty, Robert; Galal, Fathy; Marquis, Bernard; Slaughter, Lynnard; Landes, Fred

    1987-01-01

    The Department of Radiation Therapy of Howard University Hospital was the first to revive (1976) the use of intraoperative radiotherapy, or direct view irradiation, using electron beam (IORTe−) in the United States. Since that time, this pioneering effort has gained both national and international acceptance. Now, many leading centers employ this investigational treatment modality. Recently, a new mode of cancer therapy has been gaining acceptance, namely hyperthermia (the treatment of cancer by heat). Hyperthermia has been shown, both experimentally and clinically, to improve the rate of local control (thermal enchancement ratio [TER]) when combined with radiation therapy in the treatment of cancer. Maximal TER has been observed with simultaneous or immediate application of radiation and hyperthermia for both tumor and normal tissues. Therefore, to achieve maximum therapeutic gain, selective, intraoperative, simultaneous heating and irradiation of the tumor with mechanical retraction of the normal and sensitive structures from the treatment field seems a promising alternative. There have been no published reports, to the authors' knowledge, on the combination of simultaneous IORTe− with intraoperative hyperthermia (IOHT). To employ this combination in human subjects, several questions must be answered first using animal models, including the technical and practical feasibility, the toxicity and morbidity, as well as the pathologic changes that may arise. The technical aspects of the first animal case, using a mongrel dog, applying simultaneous IORTe− and IOHT are presented. PMID:3112416

  16. Response of canine esophagus to intraoperative electron beam radiotherapy

    SciTech Connect

    Sindelar, W.F.; Hoekstra, H.J.; Kinsella, T.J.; Barnes, M.; DeLuca, A.M.; Tochner, Z.; Pass, H.I.; Kranda, K.C.; Terrill, R.E.

    1988-09-01

    Tolerance of esophagus to intraoperative radiotherapy (IORT) was investigated in dogs. Thirteen adult foxhounds were subjected to right thoractomy, mobilization of the intrathoracic esophagus, and IORT to a 6 cm full-thickness esophageal segment using 9 MeV electrons at doses of 0, 2,000, or 3,000 cGy. Dogs were followed clinically and were evaluated at regular intervals after treatment with fiberoptic esophagoscopy, barium swallows, and postmortem histologic evaluations. One sham-irradiated control dog showed no abnormalities during follow-up of 24 months. Seven dogs receiving 2,000 cGy IORT showed transient mild dysphagia and mild esophagitis, but no clinically or pathologically significant complications. Five dogs receiving 3,000 cGy demonstrated severe ulcerative esophagitis within 6 weeks of treatment which progressed to chronic ulcerative esophagitis with stricture formation by 9 months following IORT. One 3,000 cGy dog died at 13 months from an esophageal perforation. On the basis of a pilot experience using 13 experimental animals, it was concluded that intact canine esophagus tolerates IORT well to doses of 2,000 cGy, but doses of 3,000 cGy pose serious and potentially lethal risks. The clinical application of IORT to the treatment of human intrathoracic neoplasms requiring esophageal irradiation should be approached with caution, particularly at doses exceeding 2,000 cGy.

  17. [What is the role of intraoperative radiotherapy in breast cancer treatment?].

    PubMed

    Aumont, M

    2016-10-01

    Breast-conserving surgery followed by whole breast postoperative irradiation is considered to be the current standard treatment for patients with early stage breast cancer. It allows an excellent local tumour control with 6% of local recurrence. Over the last years, partial breast radiotherapy has been developed to reduce treatment volume and duration. Intraoperative radiotherapy is one of the techniques. It offers an excellent delineation of the tumour bed and high normal tissue sparing. This purpose of this review is to describe the different intraoperative radiotherapy techniques available, to assess their potential clinical efficiency and tolerance, the recommendations for new practice with a selected population of patients and for future research.

  18. Threshold dose for peripheral neuropathy following intraoperative radiotherapy (IORT) in a large animal model

    SciTech Connect

    Kinsella, T.J.; DeLuca, A.M.; Barnes, M.; Anderson, W.; Terrill, R.; Sindelar, W.F. )

    1991-04-01

    Radiation injury to peripheral nerve is a dose-limiting toxicity in the clinical application of intraoperative radiotherapy, particularly for pelvic and retroperitoneal tumors. Intraoperative radiotherapy-related peripheral neuropathy in humans receiving doses of 20-25 Gy is manifested as a mixed motor-sensory deficit beginning 6-9 months following treatment. In a previous experimental study of intraoperative radiotherapy-related neuropathy of the lumbro-sacral plexus, an approximate inverse linear relationship was reported between the intraoperative dose (20-75 Gy range) and the time to onset of hind limb paresis (1-12 mos following intraoperative radiotherapy). The principal histological lesion in irradiated nerve was loss of large nerve fibers and perineural fibrosis without significant vascular injury. Similar histological changes in irradiated nerves were found in humans. To assess peripheral nerve injury to lower doses of intraoperative radiotherapy in this same large animal model, groups of four adult American Foxhounds received doses of 10, 15, or 20 Gy to the right lumbro-sacral plexus and sciatic nerve using 9 MeV electrons. The left lumbro-sacral plexus and sciatic nerve were excluded from the intraoperative field to allow each animal to serve as its own control. Following treatment, a complete neurological exam, electromyogram, and nerve conduction studies were performed monthly for 1 year. Monthly neurological exams were performed in years 2 and 3 whereas electromyogram and nerve conduction studies were performed every 3 months during this follow-up period. With follow-up of greater than or equal to 42 months, no dog receiving 10 or 15 Gy IORT shows any clinical or laboratory evidence of peripheral nerve injury. However, all four dogs receiving 20 Gy developed right hind limb paresis at 8, 9, 9, and 12 mos following intraoperative radiotherapy.

  19. Intraoperative radiotherapy with electrons: fundamentals, results, and innovation.

    PubMed

    Calvo, Fa; Sole, Cv; Herranz, R; Lopez-Bote, M; Pascau, J; Santos, A; Muñoz-Calero, A; Ferrer, C; Garcia-Sabrido, Jl

    2013-01-01

    To analyse the programme activity and clinical innovation and/or technology developed over a period of 17 years with regard to the introduction and the use of intraoperative radiotherapy (IORT) as a therapeutic component in a medical-surgical multidisciplinary cancer hospital. To standardise and record this procedure, the Radiation Oncology service has an institutional programme and protocols that must be completed by the different specialists involved. For 17 years, IORT procedures were recorded on a specific database that includes 23 variables with information recorded on institutional protocols. As part of the development and innovation activity, two technological tools were implemented (RADIANCE and MEDTING) in line with the standardisation of this modality in clinical practice. During the 17 years studied, 1,004 patients were treated through 1,036 IORT procedures. The state of the disease at the time of IORT was 77% primary and 23% recurrent. The origin and distribution of cancers were 62% gastrointestinal, 18% sarcomas, 5% pancreatic, 2% paediatric, 3% breast, 7% less common locations, and 2% others. The research and development projects have generated a patent on virtual planning (RADIANCE) and proof of concept to explore as a professional social network (MEDTING). During 2012, there were 69 IORT procedures. There was defined treatment volume (target or target region) in all of them, and 43 were conducted by the virtual planning RADIANCE system. Eighteen have been registered on the platform MEDTING as clinical cases. The IORT programme, developed in a university hospital with an academic tradition, and interdisciplinary surgical oncology, is a feasible care initiative, able to generate the necessary intense clinical activity for tending to the cancer patient. Moreover, it is a competitive source for research, development, and scientific innovation.

  20. Intraoperative radiotherapy in early stage breast cancer: potential indications and evidence to date

    PubMed Central

    Kirby, A M

    2015-01-01

    Following early results of recent studies of intraoperative radiotherapy (IORT) in the adjuvant treatment of patients with early breast cancer, the clinical utility of IORT is a subject of much recent debate within the breast oncology community. This review describes the intraoperative techniques available, the potential indications and the evidence to date pertaining to local control and toxicity. We also discuss any implications for current practice and future research. PMID:25734489

  1. Development of a Novel Method for Intraoperative Radiotherapy During Kyphoplasty for Spinal Metastases (Kypho-IORT)

    SciTech Connect

    Schneider, Frank; Greineck, Fabian; Clausen, Sven; Mai, Sabine; Obertacke, Udo; Reis, Tina; Wenz, Frederik

    2011-11-15

    Purpose: Approximately 30% of patients with cancer receive bone metastases, of which 50% are in the spine. Approximately 20% present with unstable lesions requiring surgical intervention, followed by fractionated radiotherapy over 2-4 weeks to prevent early regrowth. Because of the limited survival time of patients with metastatic cancer, novel treatment concepts shortening the overall treatment time or hospitalization are desirable. In this study, we established a novel approach for intraoperative radiotherapy during kyphoplasty (Kypho-IORT), a method that combines stabilizing surgery and radiotherapy within one visit, after estimating the percentage of eligible patients for this treatment. Methods and Materials: To estimate the percentage of eligible patients, 53 planning CTs (897 vertebrae) of patients with spinal metastases were evaluated. The number of infiltrated vertebrae were counted and classified in groups eligible or not eligible for Kypho-IORT. The Kypho-IORT was performed in a donated body during a standard balloon kyphoplasty using the INTRABEAM system and specially designed applicators. A single dose of 10 Gy (in 10 mm) was delivered over 4 min to the vertebra. This was verified using two ionization chambers and a Monte Carlo simulation. Results: The estimation of eligible patients resulted in 34% of the evaluated patients, and thus 34% of patients with instable spinal metastases are suitable for Kypho-IORT. This study shows also that, using the approach presented here, it is possible to perform an IORT during kyphoplasty with an additional 15 min operation time. The measurement in the donated body resulted in a maximum dose of 3.8 Gy in the spinal cord. However, the Monte Carlo depth dose simulation in bone tissue showed 68% less dose to the prescription depth. Conclusion: We present for the first time a system using an x-ray source that can be used for single-dose IORT during kyphoplasty. The described Kypho-IORT can decrease the overall treatment

  2. Comparing the dosimetric characteristics of the electron beam from dedicated intraoperative and conventional radiotherapy accelerators.

    PubMed

    Baghani, Hamid Reza; Aghamiri, Seyed Mahmoud Reza; Mahdavi, Seyed Rabi; Akbari, Mohammad Esmail; Mirzaei, Hamid Reza

    2015-03-08

    The specific design of the mobile dedicated intraoperative radiotherapy (IORT) accelerators and different electron beam collimation system can change the dosimetric characteristics of electron beam with respect to the conventional accelerators. The aim of this study is to measure and compare the dosimetric characteristics of electron beam produced by intraoperative and conventional radiotherapy accelerators. To this end, percentage depth dose along clinical axis (PDD), transverse dose profile (TDP), and output factor of LIAC IORT and Varian 2100C/D conventional radiotherapy accelerators were measured and compared. TDPs were recorded at depth of maximum dose. The results of this work showed that depths of maximum dose, R90, R50, and RP for LIAC beam are lower than those of Varian beam. Furthermore, for all energies, surface doses related to the LIAC beam are substantially higher than those of Varian beam. The symmetry and flatness of LIAC beam profiles are more desirable compared to the Varian ones. Contrary to Varian accelerator, output factor of LIAC beam substantially increases with a decrease in the size of the applicator. Dosimetric characteristics of beveled IORT applicators along clinical axis were different from those of the flat ones. From these results, it can be concluded that dosimetric characteristics of intraoperative electron beam are substantially different from those of conventional clinical electron beam. The dosimetric characteristics of the LIAC electron beam make it a useful tool for intraoperative radiotherapy purposes.

  3. Intraoperative Radiotherapy Versus Whole-Breast External Beam Radiotherapy in Early-Stage Breast Cancer

    PubMed Central

    Zhang, Li; Zhou, Zhirui; Mei, Xin; Yang, Zhaozhi; Ma, Jinli; Chen, Xingxing; Wang, Junqi; Liu, Guangyu; Yu, Xiaoli; Guo, Xiaomao

    2015-01-01

    Abstract There has not been a clear answer about the efficacy of intraoperative radiotherapy (IORT) for women with early-stage breast cancer. The aim of this meta-analysis was to summarize the available evidence comparing the efficacy and safety of IORT with those of whole-breast external beam radiotherapy (EBRT) for women with early-stage breast cancer. MEDLINE, EMBASE, the Web of Science, and the Cochrane Library were searched up to October 2014. Two authors independently conducted the literature selection and data extraction. Studies that compared IORT with whole-breast EBRT were included in the systematic review. IORT was defined as a single dose of irradiation to the tumor bed during breast-conserving surgery rather than whole-breast irradiation. Qualities of RCTs were evaluated according to the PEDro scale. Qualities of non-RCTs were evaluated according to the Methodological Index for Non-Randomized Studies (MINORS). The risk ratios (RRs) of ipsilateral breast tumor recurrence, overall mortality, breast cancer mortality, non-breast cancer mortality, and distant metastasis were pooled using a random-effects model. Four studies with 5415 patients were included in this meta-analysis, including 2 randomized controlled trials (RCTs) and 2 non-RCTs. Ipsilateral breast tumor recurrence was significantly higher in patients with IORT compared to those with whole-breast EBRT (RR 2.83, 95% CI 1.23–6.51), but with significant heterogeneity (I2 = 58.5%, P = 0.065). Comparing IORT with whole-breast EBRT, the pooled RRs for overall mortality, breast cancer mortality, non-breast cancer mortality, and distant metastasis were 0.88 (95% CI: 0.66–1.17), 1.20 (95% CI: 0.77–1.86), 0.76 (95% CI: 0.44–1.31), and 0.95 (95% CI: 0.61–1.49), respectively. IORT had a significantly higher risk of ipsilateral breast tumor recurrence than whole-breast EBRT. Overall mortality did not differ significantly. IORT should be used in conjunction with the prudent selection of

  4. Clinical toxicity of peripheral nerve to intraoperative radiotherapy in a canine model

    SciTech Connect

    Johnstone, P.A.S.; DeLuca, A.M.; Terrill, R.E.

    1995-07-15

    The clinical late effects of intraoperative radiotherapy (IORT) on peripheral nerve were investigated in a foxhound model. Between 1982 and 1987, 40 animals underwent laparotomy with intraoperative radiotherapy of doses from 0-75 Gy administered to the right lumbosacral plexus. Subsequently, all animals were monitored closely and sacrificed to assess clinical effects to peripheral nerve. This analysis reports final clinical results of all animals, with follow-up to 5 years. All animals treated with {>=} 25 Gy developed ipsilateral neuropathy. An inverse relationship was noted between intraoperative radiotherapy dose and time to neuropathy, with an effective dose for 50% paralysis (ED{sub 50}) of 17.2 Gy. One of the animals treated with 15 Gy IORT developed paralysis, after a much longer latency than the other animals. Doses of 15 Gy delivered intraoperatively may be accompanied by peripheral neuropathy with long-term follow-up. This threshold is less than that reported with shorter follow-up. The value of ED{sub 50} determined here is in keeping with data from other animal trials, and from clinical trials in humans. 11 refs., 2 figs.

  5. Histopathological effects of intraoperative radiotherapy on pancreas and adjacent tissues: a postmortem analysis

    SciTech Connect

    Hoekstra, H.J.; Restrepo, C.; Kinsella, T.J.; Sindelar, W.F.

    1988-02-01

    Intraoperative radiotherapy (IORT) has been utilized in the treatment of resectable and unresectable pancreatic carcinoma at the National Cancer Institute. Detailed autopsy analyses of the radiation effects on the pancreas and adjacent tissues were performed on 13 patients dying at various times following therapy. IORT can induce a progressive retroperitoneal fibrosis and fibrosis of the porta hepatis in patients with resectable pancreatic carcinoma. In unresectable pancreatic carcinoma, the major expression of intraoperative irradiation with external beam irradiation is a progressive fibrosis of the pancreas with vascular sclerosis, nerve degeneration, atrophy of acinar cells, and atypical changes in the ducts of the pancreas, as well as degenerative changes of the pancreatic tumor.

  6. Intraoperative Radiotherapy for Resected Pancreatic Cancer: A Multi-Institutional Retrospective Analysis of 210 Patients

    SciTech Connect

    Ogawa, Kazuhiko; Karasawa, Katsuyuki; Ito, Yoshinori; Ogawa, Yoshihiro; Jingu, Keiichi

    2010-07-01

    Purpose: To retrospectively analyze the results of intraoperative radiotherapy (IORT) with or without external beam radiotherapy (EBRT) for resected pancreatic cancer. Methods and Materials: The records of 210 patients treated with gross complete resection (R0: 147 patients; R1: 63 patients) and IORT with or without EBRT were reviewed. One hundred forty-seven patients (70.0%) were treated without EBRT and 114 patients (54.3%) were treated in conjunction with chemotherapy. The median doses of IORT and EBRT were 25 Gy (range, 20-30 Gy) and 45 Gy (range, 20-60Gy), respectively. The median follow-up of the surviving 62 patients was 26.3 months (range, 2.7-90.5 months). Results: At the time of this analysis, 150 of 210 patients (71.4%) had disease recurrences. Local failure was observed in 31 patients (14.8%), and the 2-year local control rate in all patients was 83.7%. The median survival time and the 2-year actuarial overall survival (OS) in all 210 patients were 19.1 months and 42.1%, respectively. Patients treated with IORT and chemotherapy had a significantly more favorable OS than those treated with IORT alone (p = 0.0011). On univariate analysis, chemotherapy use, degree of resection, carbohydrate antigen 19-9, and pathological N stage had a significant impact on OS and on multivariate analysis; these four factors were significant prognostic factors. Late gastrointestinal morbidity of NCI-CTC Grade 4 was observed in 7 patients (3.3%). Conclusion: IORT yields an excellent local control rate for resected pancreatic cancer with few frequencies of severe late toxicity, and IORT combined with chemotherapy confers a survival benefit compared with that of IORT alone.

  7. Intraoperative Radiotherapy for Unresectable Pancreatic Cancer: A Multi-Institutional Retrospective Analysis of 144 Patients

    SciTech Connect

    Ogawa, Kazuhiko; Karasawa, Katsuyuki; Ito, Yoshinori; Ogawa, Yoshihiro; Jingu, Keiichi; Onishi, Hiroshi; Aoki, Shinichi; Wada, Hitoshi; Kokubo, Masaki; Ogo, Etsuyo; Etoh, Hidehiro; Kazumoto, Tomoko; Takayama, Makoto; Nemoto, Kenji; Nishimura, Yasumasa

    2011-05-01

    Purpose: To retrospectively analyze the results of intraoperative radiotherapy (IORT) + external beam radiotherapy (EBRT) for unresectable pancreatic cancer. Methods and Materials: The records of 144 patients treated with IORT, with or without, EBRT were reviewed. One hundred and thirteen patients (78.5%) were treated with IORT + EBRT and 114 patients (79.2%) were treated in conjunction with chemotherapy. The median doses of IORT and EBRT were 25 Gy and 45 Gy, respectively. The median follow-up of all 144 patients was 9.6 months (range, 0.5-69.7 months). Results: At the time of this analysis, 131 of 144 patients (91.0%) had disease recurrences. Local progression was observed in 60 patients (41.7%), and the 2-year local control (LC) rate in all patients was 44.6%. Patients treated with IORT, with or without, EBRT had significantly more favorable LC (2-year LC, 50.9%) than those treated with IORT without EBRT (p = 0.0004). The 2-year overall survival (OS) rate and the median survival time in all 144 patients were 14.7% and 10.5 months, respectively. Patients treated with chemotherapy had a significantly favorable OS than those treated without chemotherapy (p < 0.0001). On univariate analysis, chemotherapy use alone had a significant impact on OS and on multivariate analysis; chemotherapy use was a significant prognostic factor. Late gastrointestinal morbidity of National Cancer Institute-Common Terminology Criteria Grade 3 was observed in 2 patients (1.4%). Conclusion: IORT + EBRT yields a relatively favorable LC rate for unresectable pancreatic cancer with low frequency of severe late toxicity, and IORT combined with chemotherapy conferred a survival benefit compared with IORT without chemotherapy.

  8. Long-Term Outcome and Toxicities of Intraoperative Radiotherapy for High-Risk Neuroblastoma

    SciTech Connect

    Gillis, Amy M.; Sutton, Elizabeth; DeWitt, Kelly D.; Matthay, Katherine K.; Weinberg, Vivian; Fisch, Benjamin M.; Chan, Albert; Gooding, Charles; Daldrup-Link, Heike; Wara, William M.; Farmer, Diana L.; Harrison, Michael R.; Haas-Kogan, Daphne

    2007-11-01

    Purpose: To review a historical cohort of consecutively accrued patients with high-risk neuroblastoma treated with intraoperative radiotherapy (IORT) to determine the therapeutic effect and late complications of this treatment. Methods and Materials: Between 1986 and 2002, 31 patients with newly diagnosed high-risk neuroblastoma were treated with IORT as part of multimodality therapy. Their medical records were reviewed to determine the outcome and complications. Kaplan-Meier probability estimates of local control, progression-free survival, and overall survival at 36 months after diagnosis were recorded. Results: Intraoperative radiotherapy to the primary site and associated lymph nodes achieved excellent local control at a median follow-up of 44 months. The 3-year estimate of the local recurrence rate was 15%, less than that of most previously published series. Only 1 of 22 patients who had undergone gross total resection developed recurrence at the primary tumor site. The 3-year estimate of local control, progression-free survival, and overall survival was 85%, 47%, and 60%, respectively. Side effects attributable to either the disease process or multimodality treatment were observed in 7 patients who developed either hypertension or vascular stenosis. These late complications resulted in the death of 2 patients. Conclusions: Intraoperative radiotherapy at the time of primary resection offers effective local control in patients with high-risk neuroblastoma. Compared with historical controls, IORT achieved comparable control and survival rates while avoiding many side effects associated with external beam radiotherapy in young children. Although complications were observed, additional analysis is needed to determine the relative contributions of the disease process and specific components of the multimodality treatment to these adverse events.

  9. Full-dose intraoperative radiotherapy with electrons during breast-conserving surgery: experience with 590 cases.

    PubMed

    Veronesi, Umberto; Orecchia, Roberto; Luini, Alberto; Galimberti, Viviana; Gatti, Giovanna; Intra, Mattia; Veronesi, Paolo; Leonardi, Maria Cristina; Ciocca, Mario; Lazzari, Roberta; Caldarella, Pietro; Simsek, Serife; Silva, Luzemira Santos; Sances, Daniele

    2005-07-01

    Previous studies show that local recurrences after breast-conserving treatment occur in the site of the primary tumor. The need for postoperative radiotherapy on the whole breast is challenged in favor of radiotherapy limited to the area of the breast at high risk of recurrence. The new mobile linear accelerators easily moved close to the operating table to allow the full-dose irradiation during surgery. From July 1999 to December 2003, 590 patients affected by unifocal breast carcinoma up to a diameter of 2.5 cm received wide resection of the breast followed by intraoperative radiotherapy with electrons (ELIOT). Most patients received 21 Gy intraoperatively, biologically equivalent to 58 to 60 Gy in standard fractionation. Patients were evaluated 1, 3, 6, and 12 months after surgery, and thereafter every 6 months, to look for early, intermediate, late complications, and other events. After a follow-up from 4 to 57 months (mean, 24 months; median, 20 months), 19 patients (3.2%) developed breast fibrosis, mild in 18, severe in 1, which resolved within 24 months. Three patients (0.5%) developed local recurrences, 3 patients ipsilateral carcinomas in other quadrants and other 5 patients contralateral breast carcinoma. One patient (0.2%) died of distant metastases. ELIOT is a safe method for treating conservatively operated breasts, avoids the long period of postoperative radiotherapy, and reduces drastically the cost of radiotherapy. ELIOT reduces radiation to normal tissues and organs. Results on short-term and middle-term toxicity up to 5 years of follow-up are good. Data on local control are encouraging.

  10. Full-Dose Intraoperative Radiotherapy With Electrons During Breast-Conserving Surgery

    PubMed Central

    Veronesi, Umberto; Orecchia, Roberto; Luini, Alberto; Galimberti, Viviana; Gatti, Giovanna; Intra, Mattia; Veronesi, Paolo; Leonardi, Maria Cristina; Ciocca, Mario; Lazzari, Roberta; Caldarella, Pietro; Simsek, Serife; Silva, Luzemira Santos; Sances, Daniele

    2005-01-01

    Background: Previous studies show that local recurrences after breast-conserving treatment occur in the site of the primary tumor. The need for postoperative radiotherapy on the whole breast is challenged in favor of radiotherapy limited to the area of the breast at high risk of recurrence. The new mobile linear accelerators easily moved close to the operating table to allow the full-dose irradiation during surgery. Patients and Methods: From July 1999 to December 2003, 590 patients affected by unifocal breast carcinoma up to a diameter of 2.5 cm received wide resection of the breast followed by intraoperative radiotherapy with electrons (ELIOT). Most patients received 21 Gy intraoperatively, biologically equivalent to 58 to 60 Gy in standard fractionation. Patients were evaluated 1, 3, 6, and 12 months after surgery, and thereafter every 6 months, to look for early, intermediate, late complications, and other events. Results: After a follow-up from 4 to 57 months (mean, 24 months; median, 20 months), 19 patients (3.2%) developed breast fibrosis, mild in 18, severe in 1, which resolved within 24 months. Three patients (0.5%) developed local recurrences, 3 patients ipsilateral carcinomas in other quadrants and other 5 patients contralateral breast carcinoma. One patient (0.2%) died of distant metastases. Conclusions: ELIOT is a safe method for treating conservatively operated breasts, avoids the long period of postoperative radiotherapy, and reduces drastically the cost of radiotherapy. ELIOT reduces radiation to normal tissues and organs. Results on short-term and middle-term toxicity up to 5 years of follow-up are good. Data on local control are encouraging. PMID:15973107

  11. Intraoperative Radiotherapy for Breast Cancer: The Lasting Effects of a Fleeting Treatment

    PubMed Central

    Rosenberg, Anne L.

    2014-01-01

    In well-selected patients who choose to pursue breast conservation therapy (BCT) for early-stage breast cancer, partial breast irradiation (PBI) delivered externally or intraoperatively, may be a viable alternative to conventional whole breast irradiation. Two large, contemporary randomized trials have demonstrated breast intraoperative radiotherapy (IORT) to be noninferior to whole breast external beam radiotherapy (EBRT) when assessing for ipsilateral breast tumor recurrence in select patients. Additionally, IORT and other PBI techniques are likely to be more widely adopted in the future because they improve patient convenience by offering an accelerated course of treatment. Coupled with these novel techniques for breast radiotherapy (RT) are distinct toxicity profiles and unique cosmetic alterations that differ from conventional breast EBRT and have the potential to impact disease surveillance and patient satisfaction. This paper will review the level-one evidence for treatment efficacy as well as important secondary endpoints like RT toxicity, breast cosmesis, quality of life, patient satisfaction, and surveillance mammography following BCT with IORT. PMID:25180098

  12. In Vivo Dosimetry for Single-Fraction Targeted Intraoperative Radiotherapy (TARGIT) for Breast Cancer

    SciTech Connect

    Eaton, David J.; Best, Bronagh; Brew-Graves, Chris; Duck, Stephen; Ghaus, Tabasom; Gonzalez, Regina; Pigott, Katharine; Reynolds, Claire; Williams, Norman R.; Keshtgar, Mohammed R.S.

    2012-04-01

    Purpose: In vivo dosimetry provides an independent check of delivered dose and gives confidence in the introduction or consistency of radiotherapy techniques. Single-fraction intraoperative radiotherapy of the breast can be performed with the Intrabeam compact, mobile 50 kV x-ray source (Carl Zeiss Surgical, Oberkochen, Germany). Thermoluminescent dosimeters (TLDs) can be used to estimate skin doses during these treatments. Methods and Materials: Measurements of skin doses were taken using TLDs for 72 patients over 3 years of clinical treatments. Phantom studies were also undertaken to assess the uncertainties resulting from changes in beam quality and backscatter conditions in vivo. Results: The mean measured skin dose was 2.9 {+-} 1.6 Gy, with 11% of readings higher than the prescription dose of 6 Gy, but none of these patients showed increased complications. Uncertainties due to beam hardening and backscatter reduction were small compared with overall accuracy. Conclusions: TLDs are a useful and effective method to measure in vivo skin doses in intraoperative radiotherapy and are recommended for the initial validation or any modification to the delivery of this technique. They are also an effective tool to show consistent and safe delivery on a more frequent basis or to determine doses to other critical structures as required.

  13. Single-Fraction Intraoperative Radiotherapy for Breast Cancer: Early Cosmetic Results

    SciTech Connect

    Beal, Kathryn McCormick, Beryl; Zelefsky, Michael J.; Borgen, Patrick; Fey, Jane; Goldberg, Jessica; Sacchini, Virgilio

    2007-09-01

    Purpose: To evaluate the cosmetic outcome of patients treated with wide local excision and intraoperative radiotherapy for early-stage breast cancer. Methods and Materials: A total of 50 women were treated on a pilot study to evaluate the feasibility of intraoperative radiotherapy at wide local excision. The eligibility criteria included age >60, tumor size {<=}2.0 cm, clinically negative lymph nodes, and biopsy-established diagnosis. After wide local excision, a custom breast applicator was placed in the excision cavity, and a dose of 20 Gy was prescribed to a depth of 1 cm. After 18 patients were treated, the dose was constrained laterally to 18 Gy. The cosmetic outcome was evaluated by photographs at baseline and at 6 and 12 months postoperatively. Four examiners graded the photographs for symmetry, edema, discoloration, contour, and scarring. The grades were evaluated in relationship to the volume of irradiated tissue, tumor location, and dose at the lateral aspects of the cavity. Results: The median volume of tissue receiving 100% of the prescription dose was 47 cm{sup 3} (range, 20-97 cm{sup 3}). Patients with {<=}47 cm{sup 3} of treated tissue had better cosmetic outcomes than did the women who had >47 cm{sup 3} of treated tissue. Women who had received 18 Gy at the lateral aspects of their cavities had better cosmetic outcomes than did women who had received 20 Gy at the lateral aspects. When comparing the 6- and 12-month results, the scores remained stable for 63%, improved for 17%, and worsened for 20%. Conclusion: Intraoperative radiotherapy appears feasible for selected patients. A favorable cosmetic outcome appears to be related to a smaller treatment volume. The cosmetic outcome is acceptable, although additional follow-up is necessary.

  14. [Practical dosimetry and constancy check at introduction of intraoperative radiotherapy with Intrabeam (Zeiss)].

    PubMed

    Härtl, Petra Maria; Dobler, Barbara; Kölbl, Oliver; Treutwein, Marius

    2009-01-01

    The check of dosimetry of the intraoperative radiotherapy system Intrabeam is predefined by the manufacture (Zeiss). The purpose of the study was to develop and implement a method to verify the internal dosimetry of Intrabeam (Zeiss). Additionally the long-term stability of Intrabeam was checked for dose and isotropy. For dose to water measurements an Unidos was combined with a soft jet chamber (TM 23342) which was calibrated in water absorbed dose and as a phantom the type 2962 (PTW Freiburg) was used. RW1 plates were inserted as build up material. The applicators were placed in a bag filled with water to consider the side-scattering. At the surface of the applicator there was a mean difference of 3 percent between the dose to water measurement and the internal dosimetry. The constancy of the dose rate showed a mean deviation of 0.3% at the reference point. The analysis of the dose distribution perpendicular to the applicator axis z (reference z-axis) resulted in a mean deviation of -2.7% (x-direction) and -7,1% (-x-direction) for the x-axis and, respectively -4.1% (y-direction) and -5.3% (-y-direction) for the y-axis. The proposed method is suitable to verify the absolute dose of Intrabeam. The dose values measured by this method were congruent to the dosimetry of the manufacture (Zeiss). From our point of view it is sufficient to verify the absolute dosimetry only at time of commissioning of the system or in the case of changing the applicator. For the daily routine the check of constancy specified by the manufacture is adequate, because the dose rate is checked on a daily basis. Additionally the test of constancy showed a high long-term stability in terms of dose rate and symmetry.

  15. Intraoperative Radiotherapy During Radical Prostatectomy for Locally Advanced Prostate Cancer: Technical and Dosimetric Aspects

    SciTech Connect

    Krengli, Marco; Terrone, Carlo; Ballare, Andrea; Loi, Gianfranco; Tarabuzzi, Roberto; Marchioro, Giansilvio; Beldi, Debora; Mones, Eleonora; Bolchini, Cesare R.T.; Volpe, Alessandro; Frea, Bruno

    2010-03-15

    Purpose: To analyze the feasibility of intraoperative radiotherapy (IORT) in patients with high-risk prostate cancer and candidates for radical prostatectomy. Methods and Materials: A total of 38 patients with locally advanced prostate cancer were enrolled. No patients had evidence of lymph node or distant metastases, probability of organ-confined disease >25%, or risk of lymph node involvement >15% according to the Memorial Sloan-Kettering Cancer Center Nomogram. The IORT was delivered after exposure of the prostate by a dedicated linear accelerator with beveled collimators using electrons of 9 to 12 MeV to a total dose of 10-12 Gy. Rectal dose was measured in vivo by radiochromic films placed on a rectal probe. Administration of IORT was followed by completion of radical prostatectomy and regional lymph node dissection. All cases with extracapsular extension and/or positive margins were scheduled for postoperative radiotherapy. Patients with pT3 to pT4 disease or positive nodes received adjuvant hormonal therapy. Results: Mean dose detected by radiochromic films was 3.9 Gy (range, 0.4-8.9 Gy) to the anterior rectal wall. The IORT procedure lasted 31 min on average (range, 15-45 min). No major intra- or postoperative complications occurred. Minor complications were observed in 10/33 (30%) of cases. Of the 27/31 patients who completed the postoperative external beam radiotherapy, 3/27 experienced Grade 2 rectal toxicity and 1/27 experienced Grade 2 urinary toxicity. Conclusions: Use of IORT during radical prostatectomy is feasible and allows safe delivery of postoperative external beam radiotherapy to the tumor bed without relevant acute rectal toxicity.

  16. Monte Carlo skin dose simulation in intraoperative radiotherapy of breast cancer using spherical applicators

    NASA Astrophysics Data System (ADS)

    Moradi, F.; Ung, N. M.; Khandaker, M. U.; Mahdiraji, G. A.; Saad, M.; Malik, R. Abdul; Bustam, A. Z.; Zaili, Z.; Bradley, D. A.

    2017-08-01

    The relatively new treatment modality electronic intraoperative radiotherapy (IORT) is gaining popularity, irradiation being obtained within a surgically produced cavity being delivered via a low-energy x-ray source and spherical applicators, primarily for early stage breast cancer. Due to the spatially dramatic dose-rate fall off with radial distance from the source and effects related to changes in the beam quality of the low keV photon spectra, dosimetric account of the Intrabeam system is rather complex. Skin dose monitoring in IORT is important due to the high dose prescription per treatment fraction. In this study, modeling of the x-ray source and related applicators were performed using the Monte Carlo N-Particle transport code. The dosimetric characteristics of the model were validated against measured data obtained using an ionization chamber and EBT3 film as dosimeters. By using a simulated breast phantom, absorbed doses to the skin for different combinations of applicator size (1.5-5 cm) and treatment depth (0.5-3 cm) were calculated. Simulation results showed overdosing of the skin (>30% of prescribed dose) at a treatment depth of 0.5 cm using applicator sizes larger than 1.5 cm. Skin doses were significantly increased with applicator size, insofar as delivering 12 Gy (60% of the prescribed dose) to skin for the largest sized applicator (5 cm diameter) and treatment depth of 0.5 cm. It is concluded that the recommended 0.5-1 cm distance between the skin and applicator surface does not guarantee skin safety and skin dose is generally more significant in cases with the larger applicators. Highlights: • Intrabeam x-ray source and spherical applicators were simulated and skin dose was calculated. • Skin dose for constant skin to applicator distance strongly depends on applicator size. • Use of larger applicators generally results in higher skin dose. • The recommended 0.5-1 cm skin to applicator distance does not guarantee skin

  17. Virtual 3D tumor marking-exact intraoperative coordinate mapping improve post-operative radiotherapy

    PubMed Central

    2011-01-01

    The quality of the interdisciplinary interface in oncological treatment between surgery, pathology and radiotherapy is mainly dependent on reliable anatomical three-dimensional (3D) allocation of specimen and their context sensitive interpretation which defines further treatment protocols. Computer-assisted preoperative planning (CAPP) allows for outlining macroscopical tumor size and margins. A new technique facilitates the 3D virtual marking and mapping of frozen sections and resection margins or important surgical intraoperative information. These data could be stored in DICOM format (Digital Imaging and Communication in Medicine) in terms of augmented reality and transferred to communicate patient's specific tumor information (invasion to vessels and nerves, non-resectable tumor) to oncologists, radiotherapists and pathologists. PMID:22087558

  18. Shielding considerations for an operating room based intraoperative electron radiotherapy unit.

    PubMed

    Mills, M D; Almond, P R; Boyer, A L; Ochran, T G; Madigan, W; Rich, T A; Dally, E B

    1990-05-01

    The leakage radiation characteristics of a dedicated intraoperative radiotherapy linear accelerator have been measured on a machine designed to minimize the shielding required to allow it to be placed in an operating room suite. The scattering foil design was optimized to produce a flat beam for the field sizes employed while generating minimal bremsstrahlung contamination over the available energy range. More lead shielding was used in the treatment head than is used in conventional accelerators. A small amount of borated polyethylene shielding was also employed since neutron production was present at measurable levels. The room shielding installed in the operating room was demonstrated to be adequate to treat at least 20 patients each month to an average dose of 20 Gy. The worst case exposure was found to be 73% maximum permissible exposure. Administrative control was required for adjoining areas when calibrations and maintenance were performed.

  19. Long-term outcomes with intraoperative radiotherapy as a component of treatment for locally advanced or recurrent uterine sarcoma.

    PubMed

    Barney, Brandon M; Petersen, Ivy A; Dowdy, Sean C; Bakkum-Gamez, Jamie N; Haddock, Michael G

    2012-05-01

    To report our institutional experience with intraoperative radiotherapy (IORT) as a component of treatment for women with locally advanced or recurrent uterine sarcoma. From 1990 to 2010, 16 women with primary (n = 3) or locoregionally recurrent (n = 13) uterine sarcoma received IORT as a component of combined modality treatment. Tumor histology studies found leiomyosarcoma (n = 9), endometrial stromal sarcoma (n = 4), and carcinosarcoma (n = 3). Surgery consisted of gross total resection in 2 patients, subtotal resection in 6 patients, and resection with close surgical margins in 8 patients. The median IORT dose was 12.5 Gy (range, 10-20 Gy). All patients received perioperative external beam radiotherapy (EBRT; median dose, 50.4 Gy; range, 20-62.5 Gy), and 6 patients also received perioperative systemic therapy. Seven of the 16 patients are alive at a median follow-up of 44 months (range, 11-203 months). The 3-year Kaplan-Meier estimate of local relapse (within the EBRT field) was 7%, and central control (within the IORT field) was 100%. No local failures occurred in any of the 6 patients who underwent subtotal resection. The 3-year freedom from distant relapse was 48%, with failures occurring most frequently in the lungs or mediastinum. Median survival was 18 months, and 3-year Kaplan-Meier estimates of cause-specific and overall survival were 58% and 53%, respectively. Three patients (19%) experienced late Grade 3 toxicity. A combined modality approach with perioperative EBRT, surgery, and IORT for locally advanced or recurrent uterine sarcoma resulted in excellent local disease control with acceptable toxicity, even in patients with positive resection margins. With this approach, some patients were able to experience long-term freedom from recurrence. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Long-Term Outcomes With Intraoperative Radiotherapy as a Component of Treatment for Locally Advanced or Recurrent Uterine Sarcoma

    SciTech Connect

    Barney, Brandon M.; Petersen, Ivy A.; Dowdy, Sean C.; Bakkum-Gamez, Jamie N.; Haddock, Michael G.

    2012-05-01

    Purpose: To report our institutional experience with intraoperative radiotherapy (IORT) as a component of treatment for women with locally advanced or recurrent uterine sarcoma. Methods and Materials: From 1990 to 2010, 16 women with primary (n = 3) or locoregionally recurrent (n = 13) uterine sarcoma received IORT as a component of combined modality treatment. Tumor histology studies found leiomyosarcoma (n = 9), endometrial stromal sarcoma (n = 4), and carcinosarcoma (n = 3). Surgery consisted of gross total resection in 2 patients, subtotal resection in 6 patients, and resection with close surgical margins in 8 patients. The median IORT dose was 12.5 Gy (range, 10-20 Gy). All patients received perioperative external beam radiotherapy (EBRT; median dose, 50.4 Gy; range, 20-62.5 Gy), and 6 patients also received perioperative systemic therapy. Results: Seven of the 16 patients are alive at a median follow-up of 44 months (range, 11-203 months). The 3-year Kaplan-Meier estimate of local relapse (within the EBRT field) was 7%, and central control (within the IORT field) was 100%. No local failures occurred in any of the 6 patients who underwent subtotal resection. The 3-year freedom from distant relapse was 48%, with failures occurring most frequently in the lungs or mediastinum. Median survival was 18 months, and 3-year Kaplan-Meier estimates of cause-specific and overall survival were 58% and 53%, respectively. Three patients (19%) experienced late Grade 3 toxicity. Conclusions: A combined modality approach with perioperative EBRT, surgery, and IORT for locally advanced or recurrent uterine sarcoma resulted in excellent local disease control with acceptable toxicity, even in patients with positive resection margins. With this approach, some patients were able to experience long-term freedom from recurrence.

  1. Intraoperative radiotherapy in gynaecological and genito-urinary malignancies: focus on endometrial, cervical, renal, bladder and prostate cancers.

    PubMed

    Krengli, Marco; Pisani, Carla; Deantonio, Letizia; Surico, Daniela; Volpe, Alessandro; Surico, Nicola; Terrone, Carlo

    2017-01-19

    Intraoperative radiotherapy (IORT) refers to the delivery of a single radiation dose to a limited volume of tissue during a surgical procedure. A literature review was performed to analyze the role of IORT in gynaecological and genito-urinary cancer including endometrial, cervical, renal, bladder and prostate cancers.Literature search was performed by Pubmed and Scopus, using the words "intraoperative radiotherapy/IORT", "gynaecological cancer", "uterine/endometrial cancer", "cervical/cervix cancer", "renal/kidney cancer", "bladder cancer" and "prostate cancer". Forty-seven articles were selected from the search databases, analyzed and briefly described.Literature data show that IORT has been used to optimize local control rate in genito-urinary tumours mainly in retrospective studies. The results suggest that IORT could be advantageous in the setting of locally advanced and recurrent disease although further prospective trials are needed to confirm this findings.

  2. Targeted Intraoperative Radiotherapy for Breast Cancer in Patients in Whom External Beam Radiation Is Not Possible

    SciTech Connect

    Keshtgar, Mohammed R.S.; Joseph, David; Stacey, Chris; Metaxas, Marinos G.; Corica, Tammy; Williams, Norman R.; Baum, Michael

    2011-05-01

    Purpose: External beam radiation therapy (EBRT) following wide local excision of the primary tumor is the standard treatment in early breast cancer. In some circumstances this procedure is not possible or is contraindicated or difficult. The purpose of this study was to determine the safety and efficacy of targeted intraoperative radiotherapy (TARGIT) when EBRT is not feasible. Methods and Materials: We report our experience with TARGIT in three centers (Australia, Germany, and the United Kingdom) between 1999 and 2008. Patients at these centers received a single radiation dose of 20 Gy to the breast tissue in contact with the applicator (or 6 Gy at 1-cm distance), as they could not be given EBRT and were keen to avoid mastectomy. Results: Eighty patients were treated with TARGIT. Reasons for using TARGIT were 21 patients had previously received EBRT, and 31 patients had clinical reasons such as systemic lupus erythematosus, motor neuron disease, Parkinson's disease, ankylosing spondylitis, morbid obesity, and cardiovascular or severe respiratory disease. Three of these patients received percutaneous radiotherapy without surgery; 28 patients were included for compelling personal reasons, usually on compassionate grounds. After a median follow-up of 38 months, only two local recurrences were observed, an annual local recurrence rate of 0.75% (95% confidence interval, 0.09%-2.70%). Conclusions: While we await the results of the randomized trial (over 2,000 patients have already been recruited), TARGIT is an acceptable option but only in highly selected cases that cannot be recruited in the trial and in whom EBRT is not feasible/possible.

  3. Intraoperative Radiotherapy for Pancreatic Cancer: 30-Year Experience in a Single Institution in Japan

    SciTech Connect

    Jingu, Keiichi; Tanabe, Takaya; Nemoto, Kenji; Ariga, Hisanori; Umezawa, Rei; Ogawa, Yoshihiro; Takeda, Ken; Koto, Masashi; Sugawara, Toshiyuki; Kubozono, Masaki; Shimizu, Eiji; Abe, Keiko; Yamada, Shogo

    2012-07-15

    Purpose: To analyze retrospectively the results of intraoperative radiotherapy (IORT) with or without external beam radiotherapy ({+-} EBRT) for localized pancreatic cancer in the past three decades and to analyze prognostic factors by multivariate analysis. Methods and Materials: Records for 322 patients with pancreatic cancer treated by IORT {+-} EBRT in Tohoku University Hospital between 1980 and 2009 were reviewed. One hundred ninety-two patients who had no distant organ metastases or dissemination at the time of laparotomy were enrolled in the present study. Results: Eighty-three patients underwent gross total resection (R0: 48 patients, R1: 35 patients), and 109 patients underwent only biopsy or palliative resection. Fifty-five patients underwent adjuvant EBRT, and 124 underwent adjuvant chemotherapy. The median doses of IORT and EBRT were 25 and 40 Gy, respectively. The median follow-up period was 37.5 months. At the time of the analysis, 166 patients had disease recurrence, and 35 patients had local failure. The 2-year local control (LC) and overall survival (OS) rates were 71.0% and 16.9%, respectively. Comparison of the results for each decade showed that OS was significantly improved decade by decade (2-year: 25.0% vs. 18.8% vs. 4.2%, p < 0.001). Multivariate analysis showed that degree of resection (R0-1 vs. R2, hazard ratio = 1.97, p = 0.001) and adjuvant chemotherapy (yes vs. no, hazard ratio = 1.54, p = 0.028) had significant impacts on OS. Late gastrointestinal morbidity of Common Terminology Criteria for Adverse Events version 3.0 grade 4 or 5 was observed in four patients. Conclusion: Excellent local control for pancreatic cancer with few cases of severe late toxicity was achieved by using IORT. OS of patients with pancreatic cancer treated by IORT {+-} EBRT improved significantly decade by decade. Multivariate analysis showed that degree of resection and adjuvant chemotherapy had significant impacts on OS.

  4. Long-term toxicity of an intraoperative radiotherapy boost using low energy X-rays during breast-conserving surgery

    SciTech Connect

    Kraus-Tiefenbacher, Uta . E-mail: uta.kraus-tiefenbacher@radonk.ma.uni-heidelberg.de; Bauer, Lelia; Scheda, Antonella; Fleckenstein, Katharina; Keller, Anke; Herskind, Carsten; Steil, Volker; Melchert, Frank; Wenz, Frederik

    2006-10-01

    Purpose: Intraoperative radiotherapy (IORT) as a boost for breast cancer delivers a high single dose of radiation to a late-reacting tissue; therefore late toxicity is of particular interest, and long-term follow-up is warranted. To date there are only limited data available on breast cancer patients treated with IORT using low energy X-rays. We analyzed toxicity and cosmesis after IORT as a boost with a minimum follow-up of 18 months. Methods and Materials: A total of 73 patients treated with IORT (20 Gy/50 kV X-rays; INTRABEAM [Carl Zeiss Surgical, Oberkochen, Germany]) to the tumor bed during breast-conserving surgery as a boost followed by whole-breast radiotherapy (WBRT, 46 Gy) underwent a prospective, predefined follow-up (median, 25 months; range 18-44 months), including clinical examination and breast ultrasound at 6-months and mammographies at 1-year intervals. Toxicities were documented using the common toxicity criteria (CTC)/European Organization for Research and Treatment of Cancer and the LENT-SOMA score. Cosmesis was evaluated with a score from 1 to 4. Results: The IORT in combination with WBRT was well tolerated, with no Grade 3 or 4 skin toxicities and no telangiectasias. Fibrosis of the entire breast was observed in 5% of the patients. A circumscribed fibrosis around the tumor bed was palpable in up to 27% with a peak around 18 months after therapy and a decline thereafter. The observed toxicitiy rates were not influenced by age, tumor stage, or systemic therapy. The cosmetic outcome was good to excellent in {>=}90% of cases. Conclusions: After IORT of the breast using low-energy X-rays, no unexpected toxicity rates were observed during long-term-follow-up.

  5. Intraoperative radiotherapy during breast conserving surgery: a study on 1,822 cases treated with electrons.

    PubMed

    Veronesi, Umberto; Orecchia, Roberto; Luini, Alberto; Galimberti, Viviana; Zurrida, Stefano; Intra, Mattia; Veronesi, Paolo; Arnone, Paolo; Leonardi, Maria Cristina; Ciocca, Mario; Lazzari, Roberta; Caldarella, Pietro; Rotmensz, Nicole; Sangalli, Claudia; Sances, Daniele; Maisonneuve, Patrick

    2010-11-01

    Intraoperative radiotherapy with electrons (ELIOT) after conservative surgery for breast carcinoma was introduced at the IEO in 1999 as a research programme. The results on 1,822 patients treated from January 2000 to December 2008 are reported. Women with unicentric primary breast carcinoma of less than 2.5 cm in the largest diameter were assessed by imaging. All patients were treated with breast-conserving surgery (quadrantectomy). ELIOT was delivered by two mobile linear accelerators immediately after breast resection with a single dose of 21 Gy. Local side effects of ELIOT were mainly liponecrosis (4.2%) and fibrosis (1.8%). After a mean follow-up of 36.1 months, 42 women (2.3%) developed a local recurrence, 24 (1.3%) a new primary ipsilateral carcinomas and 26 (1.4%) distant metastases as first event. Forty-six women died (2.5%), 28 for breast carcinoma and 18 for other causes. Five- and ten-year survivals were, respectively, 97.4 and 89.7%. ELIOT appears a promising feature in early breast cancer treated with breast conserving surgery, reducing the exposure of normal tissues to radiations and shortening the radiation course from 6 weeks to one single session.

  6. Exclusive electron intraoperative radiotherapy in early-stage breast cancer: a monoinstitutional experience.

    PubMed

    Osti, Mattia Falchetto; Carnevale, Alessia; Bracci, Stefano; Amanti, Claudio; Lombardi, Augusto; Maggi, Stefano; DE Sanctis, Vitaliana; Valeriani, Maurizio; Enrici, Riccardo Maurizi

    2013-03-01

    To evaluate the effectiveness of intra-operative radiotherapy (IORT) in breast cancer in terms of local control, esthetic results and disease-free survival. From June 2007 to October 2011, 110 patients with early-stage breast cancer were submitted to quadrantectomy and IORT. A total dose of 21 Gy prescribed at 90-100% isodose was delivered in all cases. Patients were evaluated after surgery for early and late complications. Median follow-up was 27 (range: 2-54) months. In 10 patients (9.1%), breast ultrasound showed liponecrosis. Six patients (5.5%) developed grade 2 fibrosis. Disease-free survival rates at 2 and 3 years were 96.8% and 92.9 %. Three patients (2.7%) developed local recurrence, two patients (1.8%) distant metastasis. Two patients died. The 2- and 3-year overall survival rates were 100% and 97.3%, respectively. IORT could be an appropriate therapeutic alternative in selected patients although it remains investigational; longer follow-up to confirm these results is required.

  7. Full-dose intra-operative radiotherapy with electrons (ELIOT) during breast-conserving surgery: experience with 1246 cases.

    PubMed

    Veronesi, U; Orecchia, R; Luini, A; Galimberti, V; Gatti, G; Intra, M; Veronesi, P; Leonardi, M C; Ciocca, M; Lazzari, R; Caldarella, P; Rotmensz, N; Sangalli, C; Silva, L S; Sances, D

    2008-01-01

    Previous studies showed that after breast-conserving surgery for breast cancer, radiotherapy may be applied to the portion of the breast where the primary tumour was removed (partial breast irradiation (PBI), avoiding the irradiation of the whole breast. We developed a procedure of PBI consisting of a single high dose of radiotherapy of 21 Gy with electrons equivalent to 58-60 Gy in fractionated doses, delivered during the surgical session by a mobile linear accelerator, positioned close to the operating table. From July 1999 to December 2006, 1246 patients with primary carcinoma of less than 2.5-cm maximum diameter, mostly over 48 years, were treated with electron intra-operative radiotherapy (ELIOT) at a single dose of 21 Gy. After a follow-up from 0.3 to 94.7 months (median 26), 24 (1.9%) patients showed a local recurrence and 22 developed distant metastases. Sixteen patients died, seven from breast carcinoma and nine from others causes. The five-year crude survival was 96.5%. Six (0.5%) developed severe breast fibrosis, which resolved in 2-3 years. An additional 40 patients suffered for mild fibrosis. Cosmetic results were good. Electron intra-operative radiotherapy is a safe method for treating conservatively operated breasts and avoids the long period of post-operative radiotherapy, greatly improving the quality of life and reduces the cost of radiotherapy. ELIOT markedly reduces the radiation to normal surrounding tissues and deep organs. Results on short- and medium-term toxicity are good. Data on local control are encouraging.

  8. In vivo dosimetry with radiochromic films in low-voltage intraoperative radiotherapy of the breast

    SciTech Connect

    Avanzo, M.; Rink, A.; Dassie, A.; Massarut, S.; Roncadin, M.; Borsatti, E.; Capra, E.

    2012-05-15

    Purpose: EBT2 radiochromic films were studied and used for in vivo dosimetry in targeted intraoperative radiotherapy (TARGIT), a technique in which the Intrabeam system (Carl Zeiss, Oberkochen, Germany) is used to perform intraoperative partial breast irradiation with x-rays of 50 kV{sub p}. Methods: The energy of the radiation emitted by the Intrabeam with the different spherical applicators, under 1 and 2 cm of solid water, and under the tungsten impregnated rubber used for shielding of the heart in TARGIT of the breast, was characterized with measurements of half-value layer (HVL). The stability of response of EBT2 was verified inside this range of energies. EBT2 films were calibrated using the red and green channels of the absorption spectrum in the 0-20 Gy dose range delivered by the Intrabeam x-rays. The dependence of film response on temperature during irradiation was measured. For in vivo dosimetry, pieces of radiochromic films wrapped in sterile envelopes were inserted after breast conserving surgery and before TARGIT into the excision cavity, on the skin and on the shielded pectoralis fascia for treatments of the left breast. Results: HVLs of the Intrabeam in TARGIT of the breast correspond to effective energies of 20.7-36.3 keV. The response of EBT2 was constant inside this range of energies. We measured the dose to the target tissue and to organs at risk in 23 patients and obtained an average dose of 13.52 {+-} 1.21 Gy to the target tissue. Dose to the skin in close proximity to the applicator was 2.22 {+-} 0.97 Gy, 0.29 {+-} 0.17 Gy at 5-10 cm from the applicator, and 0.08 {+-} 0.07 Gy at more than 10 cm from the applicator. Dose to the pectoral muscle for left breast treatment was 0.57 {+-} 0.23 Gy. Conclusions: Our results show that EBT2 films are accurate at the beam energies, dose range, and irradiation temperature found in TARGIT and that in vivo dosimetry in TARGIT with EBT2 films wrapped in sterile envelopes is a feasible procedure. Measured

  9. Intraoperative Radiotherapy in Early-Stage Breast Cancer: Results of the Montpellier Phase II Trial

    SciTech Connect

    Lemanski, Claire; Azria, David; Gourgon-Bourgade, Sophie; Gutowski, Marian; Rouanet, Phillippe; Saint-Aubert, Bernard; Ailleres, Norbert; Fenoglietto, Pascal; Dubois, Jean-Bernard

    2010-03-01

    Purpose: We recently presented the intraoperative radiotherapy (IORT) technique given as a reliable alternative to conventional boost radiation after breast-conserving surgery. The low crude numbers of recurrence in elderly patients led us to investigate the feasibility and the efficacy of this procedure as a sole treatment. Methods and Materials: We included 94 patients older than 65 years in this phase II trial. Among them, 42 patients presented with all the inclusion criteria, i.e., stages pT0 to pT1 and pN0, ductal invasive unifocal carcinoma, and tumor-free margin of >2 mm. IORT was delivered using a dedicated linear accelerator. One 21-Gy fraction was prescribed and specified at the 90% isodose, using electrons. In vivo dosimetry was performed for all patients. The primary endpoint was the quality index. Secondary endpoints were quality of life, local recurrences, cosmetic results, and specific and overall rates of survival. Results: The median follow-up was 30 months (range, 12-49 months), and median age was 72 years (range, 66-80 years). The median tumor diameter was 10 mm. All patients received the total prescribed dose. No acute grade 3 toxicities were observed. Endpoints for all but one patient corresponded to acceptable quality index criteria. Pretreatment quality-of-life scores were maximal, and no significant decrease was observed during follow-up. Cosmesis was good to excellent at 6 months. Two patients experienced recurrence but underwent salvage mastectomy. Conclusion: Our results confirm that exclusive partial-breast IORT is feasible for treating early-stage breast cancer in the elderly. IORT may be considered an alternative treatment for a selected population and offers a safe one-step treatment.

  10. SU-E-T-756: Tissue Inhomogeneity Corrections in Intra-Operative Radiotherapy

    SciTech Connect

    Sethi, A; Chinsky, B; Gros, S; Diak, A; Roeske, J; Emami, B; Small, W

    2015-06-15

    Purpose: Investigate the impact of tissue inhomogeneities on dose distributions produced by low-energy X-rays in intra-operative radiotherapy (IORT). Methods: A 50-kV INTRABEAM X-ray device with superficial (Flat and Surface) applicators was commissioned at our institution. For each applicator, percent depth-dose (PDD), dose-profiles (DP) and output factors (OF) were obtained. Calibrated GaFchromic (EBT3) films were used to measure dose distributions in solid water phantom at various depths (2, 5, 10, and 15 mm). All recommended precautions for film-handling, film-exposure and scanning were observed. The effects of tissue inhomogeneities on dose distributions were examined by placing air-cavities and bone and tissue equivalent materials of different density (ρ), atomic number (Z), and thickness (t = 0–4mm) between applicator and film detector. All inhomogeneities were modeled as a cylindrical cavity (diameter 25 mm). Treatment times were calculated to deliver 1Gy dose at 5mm depth. Film results were verified by repeat measurements with a thin-window parallel plate ion-chamber (PTW 34013A) in a water tank. Results: For a Flat-4cm applicator, the measured dose rate at 5mm depth in solid water was 0.35 Gy/min. Introduction of a cylindrical air-cavity resulted in an increased dose past the inhomogeneity. Compared to tissue equivalent medium, dose enhancement due to 1mm, 2mm, 3mm and 4mm air cavities was 10%, 16%, 24%, and 35% respectively. X-ray attenuation by 2mm thick cortical bone resulted in a significantly large (58%) dose decrease. Conclusion: IORT dose calculations assume homogeneous tissue equivalent medium. However, soft X-rays are easily affected by non-tissue equivalent materials. The results of this study may be used to estimate and correct IORT dose delivered in the presence of tissue inhomogeneities.

  11. Intraoperative radiotherapy during lung cancer surgery: Technical description and early clinical results

    SciTech Connect

    Calvo, F.A.; Ortiz de Urbina, D.; Abuchaibe, O.; Azinovic, I.; Aristu, J.; Santos, M.; Escude, L.; Herreros, J.; Llorens, R. )

    1990-07-01

    A phase I-II study of intraoperative radiotherapy (IORT) for Stage III lung cancer was performed in 34 patients during a period of 58 months. Loco-regional treatment included tumor resection if technically feasible, IORT boost of electron beams using moderate single doses (10-15 Gy) to tumor bearing areas and external photon beam irradiation (46-50 Gy in 5 weeks) using conventional fields. Indications for this study were unresectable hiliar tumors (14, 41%), and mediastinal, hiliar and/or chest wall residual disease following resection (20, 59%). Thirty-four procedures, with 40 IORT fields, have been analyzed to describe the relevant technical aspects and the toxicity. IORT was delivered using acrylic transparent cones of different diameters. Surgical approach consisted in a lateral thoracotomy in all patients (21 right side and 13 left side). Tissues included within the IORT field were: tumor or residual tumor tissues (34, 100%), collapsed lung parenchyma and main bronchus not surgically manipulated (14, 41%), bronchial stump and vascular suture following resection (19, 55%), mediastinal structures (20, 58%), and brachial plexus (1, 3%). The bronchial suture was covered with pleural or pericardial flap after IORT in 10 cases (29%). Life threatening toxicity related to IORT consisted in broncho-pleural fistula (1, 3%) and massive hemoptysis (1, 3%). Other reversible toxic events were acute pneumonitis (12, 85%) and esophagitis (10, 50%). Long term asymptomatic lung fibrosis was detected in 11 cases (32%). Median survival time for the entire group has been 12 months. With a median follow-up time of 12 months the freedom from thoracic recurrence rate is 30% (65% in cases with tumor resection). Projected actuarial survival rates at 4 years were 28% for resected group and 7% for unresected cases.

  12. Tumor induction following intraoperative radiotherapy: Late results of the National Cancer Institute canine trials

    SciTech Connect

    Barnes, M.; Duray, P.; DeLuca, A.; Anderson, W.; Sindelar, W.; Kinsella, T. )

    1990-09-01

    Intraoperative radiotherapy has been employed in human cancer research for over a decade. Since 1979, trials to assess the acute and late toxicity of IORT have been carried out at the National Cancer Institute in an adult dog model in an attempt to establish dose tolerance guidelines for a variety of organs. Of the 170 animals entered on 12 studies with a minimum follow-up of 2 years, 148 dogs received IORT; 22 control animals received only surgery. Animals were sacrificed at designated intervals following IORT, usually at 1, 6, 12, 24, and 60 month intervals. 102 of 148 irradiated dogs were sacrificed less than 24 months; 46 dogs were followed greater than or equal to 24 months after IORT. To date, 34 of the 46 animals have been sacrificed; the 12 remaining animals are to be followed to 5 years. These 12 animals have minimum follow-up of 30 months. In the irradiated group followed for greater than or equal to 24 months, 10 tumors have arisen in 9 animals. One animal developed an incidental spontaneous breast carcinoma outside the IORT port, discovered only at scheduled post-mortem exam. The remaining nine tumors arose within IORT ports. Two tumors were benign neural tumors--a neuroma and a neurofibroma. One animal had a collision tumor comprised of grade I chondrosarcoma adjacent to grade III osteosarcoma arising in lumbar vertebrae. Two other grade III osteosarcomas, one grade III fibrosarcoma, and one grade III malignant fibrous histiocytoma arose in retroperitoneal/paravertebral sites. An embryonal rhabdomyosarcoma (sarcoma botryoides) arose within the irradiated urinary bladder of one animal. No sham irradiated controls nor IORT animals sacrificed less than 24 months have developed any spontaneous or radiation-induced tumors. The time range of diagnoses of tumors was 24-58 months. The IORT dose range associated with tumor development was 20-35 Gy.

  13. Long-Term Survivors Using Intraoperative Radiotherapy for Recurrent Gynecologic Malignancies

    SciTech Connect

    Tran, Phuoc T.; Su Zheng; Hara, Wendy; Husain, Amreen; Teng, Nelson; Kapp, Daniel S.

    2007-10-01

    Purpose: To analyze the outcomes of therapy and identify prognostic factors for patients treated with surgery followed by intraoperative radiotherapy (IORT) for gynecologic malignancies at a single institution. Methods and Materials: We performed a retrospective review of 36 consecutive patients treated with IORT to 44 sites with mean follow-up of 50 months. The primary site was the cervix in 47%, endometrium in 31%, vulva in 14%, vagina in 6%, and fallopian tubes in 3%. Previous RT had failed in 72% of patients, and 89% had recurrent disease. Of 38 IORT sessions, 84% included maximal cytoreductive surgery, including 18% exenterations. The mean age was 52 years (range, 30-74), mean tumor size was 5 cm (range, 0.5-12), previous disease-free interval was 32 months (range, 0-177), and mean IORT dose was 1,152 cGy (range, 600-1,750). RT and systemic therapy after IORT were given to 53% and 24% of the cohort, respectively. The outcomes measured were locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and treatment-related complications. Results: The Kaplan-Meier 5-year LRC, DMFS, and DSS probability for the whole group was 44%, 51%, and 47%, respectively. For cervical cancer patients, the Kaplan-Meier 5-year LRC, DMFS, and DSS estimate was 45%, 60%, and 46%, respectively. The prognostic factors found on multivariate analysis (p {<=} 0.05) were the disease-free interval for LRC, tumor size for DMFS, and cervical primary, previous surgery, and locoregional relapse for DSS. Our cohort had 10 Grade 3-4 complications associated with treatment (surgery and IORT) and a Kaplan-Meier 5-year Grade 3-4 complication-free survival rate of 72%. Conclusions: Survival for pelvic recurrence of gynecologic cancer is poor (range, 0-25%). IORT after surgery seems to confer long-term local control in carefully selected patients.

  14. Intra-Operative Vertebroplasty Combined with Posterior Cord Decompression

    PubMed Central

    Allegretti, Luca; Mavilio, Nicola; Fiaschi, Pietro; Bragazzi, Roberto; Pacetti, Mattia; Castelletti, Lara; Saitta, Laura; Castellan, Lucio

    2014-01-01

    Summary Percutaneous vertebroplasty (VP) is a minimally invasive technique for the treatment of vertebral pathology providing early vertebral stabilization and pain relief. In cases of vertebral pathology complicated by spinal cord compression with associated neurological deficits, VP alone cannot be performed free of risks. We describe a combined approach in which decompressive laminectomy and intra-operative vertebroplasty (IVP) are performed during a single session. Among the 252 VP performed in our centre in the past three years, 12 patients (12 vertebral levels) with different pathologies (six symptomatic haemangiomas, two metastatic fractures, four osteoporotic fractures) were treated with an open procedure combined with surgery. All cases were treated with decompressive laminectomy and IVP (mono/bipeduncular or median-posterior trans-somatic access). Five patients with symptomatic haemangiomas were treated with endovascular embolization prior to the combined approach. A visual analogue scale (VAS) was applied to assess pain intensity before and after surgery. The neurological deficits were evaluated with an ASIA impairment scale. In all cases benefit from pain and neurological deficits was observed. The mean VAS score decreased from 7.8 to 2.5 after surgery. The ASIA score improved in all cases (five cases from D to E and five cases from C to D). No clinical complications were observed. In one case a CT scan performed after the procedure showed a foraminal accumulation of PMMA, but the patient referred no symptoms. IVP can be successfully applied in different pathologies affecting the vertebrae. In our limited series this approach proved safe and efficient to provide decompression of spinal cord and dural sac and vertebral body stabilization in a single session. PMID:25363261

  15. Intraoperative electron boost radiation followed by moderate doses of external beam radiotherapy in limb-sparing treatment of patients with extremity soft-tissue sarcoma

    SciTech Connect

    Oertel, Susanne; Treiber, Martina; Zahlten-Hinguranage, Angelika; Eichin, Steffen; Roeder, Falk; Funk, Angela; Hensley, Frank W.; Timke, Carmen; Niethammer, Andreas G.; Huber, Peter E.; Weitz, Juergen; Eble, Micheal J.; Buchler, Markus W.; Bernd, Ludger; Debus, Juergen; Krempien, Robert C. . E-mail: robert_krempien@med.uni-heidelberg.de

    2006-04-01

    Purpose: To analyze long-term prognosis and morbidity after limb-sparing treatment of patients with extremity soft-tissue sarcoma, with intraoperative electron boost radiotherapy (IOERT) followed by a moderate dose of external beam radiotherapy (EBRT). Methods and Materials: A total of 153 patients who were treated in a single center from 1991 to 2004 were evaluated. Median IOERT dose was 15 Gy, mean EBRT dose 43 Gy (range, 40-50.4 Gy) in conventional fractionation (1.8-2 Gy). Median duration of follow-up was 33 months. Acute toxicity was assessed with Common Toxicity Criteria; late toxic effects were scored according to European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. Results: Five-year overall survival and 5-year local control rates were 77% and 78%, respectively. Whereas tumor size, patient age, and EBRT dose did not significantly affect outcome, resection status and grading were significant for survival; resection status and IOERT dose were significant for local control. Extremity salvage until death or time of follow-up was achieved in 90% of our patients, 86% of whom showed excellent limb function without impairment in activities of daily life. Acute toxicity Grade 2-4 was observed in 23% and late toxicity Grade 2-4 in 17% of patients. Conclusions: Treatment with IOERT combined with moderate doses of external beam irradiation yields high local control and extremity preservation rates in resected extremity soft-tissue sarcoma.

  16. Combining Radiotherapy and Immunotherapy to Target Survivin in Prostate Cancer

    DTIC Science & Technology

    2009-01-01

    1-0114 TITLE: Combining radiotherapy and immunotherapy to target survivin in prostate cancer PRINCIPAL INVESTIGATOR: Dorthe Schaue...radiotherapy and immunotherapy to target survivin in prostate cancer . 5b. GRANT NUMBER PC060403 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER DORTHE...cells to examine the vaccination responses to human survivin epitopes and to other clinically relevant human prostate cancer associated antigens

  17. An experimental attenuation plate to improve the dose distribution in intraoperative electron beam radiotherapy for breast cancer

    NASA Astrophysics Data System (ADS)

    Oshima, T.; Aoyama, Y.; Shimozato, T.; Sawaki, M.; Imai, T.; Ito, Y.; Obata, Y.; Tabushi, K.

    2009-06-01

    Intraoperative electron beam radiotherapy (IOERT) is a technique in which a single-fraction high dose is intraoperatively delivered to subclinical tumour cells using an electron beam after breast-conserving surgery. In IOERT, an attenuation plate consisting of a pair of metal disks is commonly used to protect the normal tissues posterior to the breast. However, the dose in front of the plate is affected by backscatter, resulting in an unpredictable delivered dose to the tumour cells. In this study, an experimental attenuation plate, termed a shielding plate, was designed using Monte Carlo simulation, which significantly diminished the electron beam without introducing any backscatter radiation. The plate's performance was verified by measurements. It was made of two layers, a first layer (source side) of polymethyl methacrylate (PMMA) and a second layer of copper, which was selected from among other metals (aluminium, copper and lead) after testing for shielding capability and the range and magnitude of backscatter. The optimal thicknesses of the PMMA (0.71 cm) and copper (0.3 cm) layers were determined by changing their thicknesses during simulations. On the basis of these results, a shielding plate was prototyped and depth doses with and without the plate were measured by radiophotoluminescence glass dosimeters using a conventional stationary linear accelerator and a mobile linear accelerator dedicated for IOERT. The trial shielding plate functioned as intended, indicating its applicability in clinical practice.

  18. Intraoperative radiotherapy given as a boost for early breast cancer: Long-term clinical and cosmetic results

    SciTech Connect

    Lemanski, Claire; Azria, David . E-mail: azria@valdorel.fnclcc.fr; Thezenas, Simon; Gutowski, Marian; Saint-Aubert, Bernard; Rouanet, Philippe; Fenoglietto, Pascal; Ailleres, Norbert; Dubois, Jean-Bernard

    2006-04-01

    Purpose: The standard radiotherapy (RT) of breast cancer consists of 50 Gy external beam RT (EBRT) to the whole breast followed by an electron boost of 10-16 Gy to the tumor bed, but this has several cosmetic disadvantages. Intraoperative radiotherapy (IORT) could be an alternative to overcome these. Methods and Materials: We evaluated 50 women with early breast cancer operated on in a dedicated IORT facility. Median dose of 10 Gy was delivered using 9-MeV electron beams. All patients received postoperative EBRT (50 Gy in 2 Gy fractions). Late toxicity and cosmetic results were assessed independently by two physicians according to the Common Terminology Criteria for Adverse Event v3.0 grading system and the European Organization for Research and Treatment of Cancer questionnaires. Results: After a median follow-up of 9.1 years (range, 5-15 years), two local recurrences were observed within the primary tumor bed. At the time of analysis, 45 patients are alive with (n = 1) or without disease. Among the 42 disease-free remaining patients, 6 experienced Grade 2 late subcutaneous fibrosis within the boost area. Overall, the scores indicated a very good quality of life and cosmesis was good to excellent in the evaluated patients. Conclusion: Our results confirm that IORT given as a boost after breast-conserving surgery is a reliable alternative to conventional postoperative fractionated boost radiation.

  19. In vivo dosimetry with optically stimulated dosimeters and RTQA2 radiochromic film for intraoperative radiotherapy of the breast

    SciTech Connect

    Price, Caleb; Pederson, Aaron; Frazier, Chanté; Duttenhaver, John

    2013-09-15

    Purpose: Measurements were taken with optically stimulated luminescence dosimeters (OSLDs) and with RTQA2 radiochromic film to evaluate the use of each for in vivo dosimetry with intraoperative radiotherapy of the breast.Methods: Nonlinear calibration curves were established for OSLDs and RTQA2 radiochromic film using the Intrabeam 50 kV{sub p} source. Measurements were taken in a water phantom and compared to absolute dose measurements taken with an ionization chamber to investigate the characteristics of both types of dosimeters, including energy response and radiative absorption. In vivo readings were taken on the skin and in the tumor cavity using OSLDs and RTQA2 radiochromic film for 10 patients and 20 patients respectively. A prescription of 20 Gy to the surface of the applicator was used for all in vivo measurements in this study.Results: OSLDs were found to have an approximate uncertainty of ±7% for readings near the surface of the applicator and ±17% for readings at distances typical to the skin. The radiative absorption by OSLD was negative, indicating that this type of dosimeter absorbs less radiation than water in the targeted intraoperative radiotherapy energy range. RTQA2 film exhibited no energy dependence and all film readings were within ±8% of the delivered dose. The maximum radiative absorption in film was 8.5%. Radiochromic film measurements were found to be on average 18.2 ± 3.3 Gy for the tumor cavity and 2.1 ± 0.8 Gy for positions on the skin superior and inferior to the Intrabeam applicator. Average cavity measurements taken with OSLDs were 15.9 ± 3.9 Gy and average skin doses were 1.4 ± 0.8 Gy.Conclusions: OSLDs produce results with an uncertainty comparable to other dosimeters near the surface of the applicator but the uncertainty increases to an unacceptably high level with distance from the applicator. RTQA2 radiochromic film is shown to be accurate both at the surface of the applicator and at distances of 1–2 cm.

  20. Long-Term Outcomes After Maximal Surgical Resection and Intraoperative Electron Radiotherapy for Locoregionally Recurrent or Locoregionally Advanced Primary Renal Cell Carcinoma

    SciTech Connect

    Hallemeier, Christopher L.; Choo, Richard; Davis, Brian J.; Pisansky, Thomas M.; Gunderson, Leonard L.; Leibovich, Bradley C.; Haddock, Michael G.

    2012-04-01

    Purpose: To report outcomes of a multimodality therapy combining maximal surgical resection and intraoperative electron radiotherapy (IOERT) for patients with locoregionally (LR) recurrent renal cell carcinoma (RCC) after radical nephrectomy or LR advanced primary RCC. Methods and Materials: From 1989 through 2005, a total of 22 patients with LR recurrent (n = 19) or LR advanced primary (n = 3) RCC were treated with this multimodality approach. The median patient age was 63 years (range 46-78). Twenty-one patients (95%) received perioperative external beam radiotherapy (EBRT) with a median dose of 4,500 cGy (range, 4,140-5,500). Surgical resection was R0 (negative margins) in 5 patients (23%) and R1 (residual microscopic disease) in 17 patients (77%). The median IOERT dose delivered was 1,250 cGy (range, 1,000-2,000). Overall survival (OS) and disease-free survival (DFS) and relapse patterns were estimated using the Kaplan-Meier method. Results: The median follow-up for surviving patients was 9.9 years (range, 3.6-20 years). The OS and DFS at 1, 5, and 10 years were 91%, 40%, and 35% and 64%, 31%, and 31%, respectively. Central recurrence (within the IOERT field), LR relapse (tumor bed or regional lymph nodes), and distant metastases at 5 years were 9%, 27%, and 64%, respectively. Mortality within 30 days of surgery and IOERT was 0%. Five patients (23%) experienced acute or late National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) Version 4 Grade 3 to 5 toxicities. Conclusions: In patients with LR recurrent or LR advanced primary RCC, a multimodality approach of perioperative EBRT, maximal surgical resection, and IOERT yielded encouraging results. This regimen warrants further investigation.

  1. Combination chemotherapy and radiotherapy in non-Hodgkin's lymphomata.

    PubMed Central

    Bonadonna, G.; De Lena, M.; Lattuada, A.; Milani, F.; Monfardini, S.; Beretta, G.

    1975-01-01

    The results obtained with intensive chemotherapy and intensive chemotherapy plus radiotherapy in non-Hodgkin's lymphomata are reported. A quintuple drug regimen (mechloretamine, adriamycin, bleomycin, vincristine and prednisone) in histiocytic lymphomata (Stage III and IV) yielded complete remissions in 53% and complete plus partial remissions in 77%. These figures were 44% and 64% respectively in lymphocytic lymphoma. In Stage III complete responders after combination chemotherapy were subsequently irradiated (involved field irradiation). The median duration of complete remission after completion of radiotherapy was 9-5 months in histiocytic and 12-0 months in lymphocytic lymphomata. At 2 years actuarial survival in Stage III and IV was better in patients with the lymphocytic type and with nodular pattern than with histiocytic and diffuse patterns. A more recent trial compares, in Stage IV patients, cyclophosphamide, vincristine and prednisone (CVP) versus adriamycin, bleomycin and prednisone (ABP). Although the number of evaluable patients is still limited, there appears to be no difference in the response rate between CVP and ABP. In Stages I and II, 6 cycles of CVP were given as adjuvant treatment after radiotherapy. At the present moment, there is no statistical difference in the relapse rate between the group of patients treated with radiotherapy alone and that with radiotherapy plus CVP. PMID:52367

  2. Histopathological and biochemical effects of intraoperative interstitial radiofrequency-induced hyperthermia and intraoperative electron radiation, alone and in combination, on normal canine liver tissue

    SciTech Connect

    Williford, K.J.

    1988-01-01

    Acute and chronic histopathologic and biochemical effects on normal canine liver tissue from a single intraoperative application of heat and radiation, heat alone, and radiation alone have been evaluated in 54 adult mongrel dogs. The tolerance of normal canine liver tissue to single doses of intraoperative radiation therapy (IORT) was evaluated at doses of 5, 10, 20, 30, and 40 Gy. In addition, intraoperative interstitial hyperthermia (43{degree}C, 60 minutes, 500 kHz) was applied alone and in combination with a single intraoperative dose of 30 Gy from an 18 MeV electron beam. Blood flow at the center of the implantation site before, during and after hyperthermia treatments was also evaluated.

  3. Microdosimetric characteristics of 50 kV X rays at different depths for breast intraoperative radiotherapy.

    PubMed

    Wuu, Cheng-Shie; Sheu, Ren-Dih; Chen, Jing

    2015-09-01

    An intraoperative radiation therapy (IORT) device with 50 kV X rays was designed to deliver a single dose to the tumour bed after local excision of breast cancer. The quality of a radiation can be determined by the microscopic distribution of energy transfers along and across the charged particle tracks. The lineal energy, y, serves as an accurate measure of local energy concentration. The dose mean lineal energy, yD, is an indicator of radiation quality. For low linear energy transfer radiation, the ratio of its dose mean lineal energy to that of (60)Co gamma rays can serve as a good indicator of the relative biological effectiveness (RBE) at low doses. In this study, microdosimetric simulations are performed for soft tissue irradiated by 50 kV X rays generated from the IORT device, with a 4-cm breast applicator attached. All energy transfers are recorded with the location coordinates in the tissue. Microdosimetric single events in a sphere of 1 µm in diameter are scored as a function of radial distances from the applicator surface. Single-event spectra are then constructed. From those single-event spectra, dose mean lineal energy is calculated. Compared with dose mean lineal energy of (60)Co gamma rays, the estimated RBEs at low doses are given for the X rays at different depths in the tissue. The RBEs at clinically relevant doses, as a function of depth, are also presented.

  4. Multimodality therapy including salvage surgical resection and intraoperative radiotherapy for patients with squamous-cell carcinoma of the anus with residual or recurrent disease after primary chemoradiotherapy.

    PubMed

    Hallemeier, Christopher L; You, Y Nancy; Larson, David W; Dozois, Eric J; Nelson, Heidi; Klein, Kristi A; Miller, Robert C; Haddock, Michael G

    2014-04-01

    For patients with residual or recurrent squamous-cell carcinoma of the anus after primary chemoradiotherapy, the standard treatment is surgical salvage. Patients with unresectable or borderline unresectable disease have poor outcomes, thus adjunctive treatments should be explored. The aim of this study is to report outcomes for patients with residual/recurrent anal cancer treated with multimodality therapy including salvage surgical resection and intraoperative radiotherapy. This is an observational study. This study was conducted at a tertiary referral center. Thirty-two patients were treated between 1993 and 2012. Median age was 53 years (range, 34-87). Salvage treatment was performed for residual disease (n = 9), first recurrence (n = 17), or second recurrence (n = 6) after primary chemoradiotherapy. Patients with recurrent disease received preoperative external beam reirradiation with concurrent chemotherapy. All patients underwent salvage surgical resection and intraoperative radiotherapy. Extent of surgical resection was R0 (negative margins, n = 16), R1 (microscopic residual, n = 13), or R2 (macroscopic residual, n = 3). The median intraoperative radiotherapy dose was 12.5 Gy. Treatment-related adverse events were classified according to the National Cancer Institute - Common Toxicity Criteria. Overall and disease-free survival were estimated by using the Kaplan-Meier technique. Central, local-regional, and distant failure were estimated by the use of the cumulative incidence method. Median length of hospital stay was 9 days. Mortality at 30 days after surgery and intraoperative radiotherapy was 0%. Fifteen patients (47%) experienced a total of 16 grade 3 treatment-related adverse events (wound complication (n = 6), bowel obstruction (n = 5), and ureteral obstruction (n = 3)). The 5-year estimates of overall and disease-free survival were 23% and 17%. The 5-year estimates of central, local-regional, and distant failure were 21%, 51%, and 40%. This was a

  5. Combining radiotherapy and immunotherapy: A revived partnership

    SciTech Connect

    Demaria, Sandra; Bhardwaj, Nina; McBride, William H.; Formenti, Silvia C. . E-mail: silvia.formenti@med.nyu.edu

    2005-11-01

    Ionizing radiation therapy (RT) is an important local modality for the treatment of cancer. The current rationale for its use is based largely on the ability of RT to kill the cancer cells by a direct cytotoxic effect. Nevertheless, considerable evidence indicates that RT effects extend beyond the mere elimination of the more radiosensitive fraction of cancer cells present within a tumor at the time of radiation exposure. For instance, a large body of evidence is accumulating on the ability of RT to modify the tumor microenvironment and generate inflammation. This might have far-reaching consequences regarding the response of a patient to treatment, especially if radiation-induced tumor cell kill were to translate into the generation of effective antitumor immunity. Although much remains to be learned about how radiation can impact tumor immunogenicity, data from preclinical studies provide the proof of principle that different immunotherapeutic strategies can be combined with RT to enhance antitumor effects. Conversely, RT could be a useful tool to combine with immunotherapy. This article will briefly summarize what is known about the impact of RT on tumor immunity, including tumor-associated antigens, antigen-presenting cells, and effector mechanisms. In addition, the experimental evidence supporting the contention that RT can be used as a tool to induce antitumor immunity is discussed, and a new approach to radioimmunotherapy of cancer is proposed.

  6. Improving external beam radiotherapy by combination with internal irradiation.

    PubMed

    Dietrich, A; Koi, L; Zöphel, K; Sihver, W; Kotzerke, J; Baumann, M; Krause, M

    2015-07-01

    The efficacy of external beam radiotherapy (EBRT) is dose dependent, but the dose that can be applied to solid tumour lesions is limited by the sensitivity of the surrounding tissue. The combination of EBRT with systemically applied radioimmunotherapy (RIT) is a promising approach to increase efficacy of radiotherapy. Toxicities of both treatment modalities of this combination of internal and external radiotherapy (CIERT) are not additive, as different organs at risk are in target. However, advantages of both single treatments are combined, for example, precise high dose delivery to the bulk tumour via standard EBRT, which can be increased by addition of RIT, and potential targeting of micrometastases by RIT. Eventually, theragnostic radionuclide pairs can be used to predict uptake of the radiotherapeutic drug prior to and during therapy and find individual patients who may benefit from this treatment. This review aims to highlight the outcome of pre-clinical studies on CIERT and resultant questions for translation into the clinic. Few clinical data are available until now and reasons as well as challenges for clinical implementation are discussed.

  7. Improving external beam radiotherapy by combination with internal irradiation

    PubMed Central

    Koi, L; Zöphel, K; Sihver, W; Kotzerke, J; Baumann, M; Krause, M

    2015-01-01

    The efficacy of external beam radiotherapy (EBRT) is dose dependent, but the dose that can be applied to solid tumour lesions is limited by the sensitivity of the surrounding tissue. The combination of EBRT with systemically applied radioimmunotherapy (RIT) is a promising approach to increase efficacy of radiotherapy. Toxicities of both treatment modalities of this combination of internal and external radiotherapy (CIERT) are not additive, as different organs at risk are in target. However, advantages of both single treatments are combined, for example, precise high dose delivery to the bulk tumour via standard EBRT, which can be increased by addition of RIT, and potential targeting of micrometastases by RIT. Eventually, theragnostic radionuclide pairs can be used to predict uptake of the radiotherapeutic drug prior to and during therapy and find individual patients who may benefit from this treatment. This review aims to highlight the outcome of pre-clinical studies on CIERT and resultant questions for translation into the clinic. Few clinical data are available until now and reasons as well as challenges for clinical implementation are discussed. PMID:25782328

  8. Results of intraoperative electron beam radiotherapy containing multimodality treatment for locally unresectable T4 rectal cancer: a pooled analysis of the Mayo Clinic Rochester and Catharina Hospital Eindhoven.

    PubMed

    Holman, Fabian A; Haddock, Michael G; Gunderson, Leonard L; Kusters, Miranda; Nieuwenhuijzen, Grard A P; van den Berg, Hetty A; Nelson, Heidi; Rutten, Harm J T

    2016-12-01

    The aim of this study is to analyse the pooled results of intraoperative electron beam radiotherapy (IOERT) containing multimodality treatment of locally advanced T4 rectal cancer, initially unresectable for cure, from the Mayo Clinic, Rochester, USA (MCR) and Catharina Hospital, Eindhoven, The Netherlands (CHE), both major referral centers for locally advanced rectal cancer. A rectal tumor is called locally unresectable for cure if after full clinical work-up infiltration into the surrounding structures or organs has been demonstrated, which would result in positive surgical margins if resection was the initial component of treatment. This was the reason to refer these patients to the IOERT program of one of the centers. In the period from 1981 to 2010, 417 patients with locally unresectable T4 rectal carcinomas at initial presentation were treated with multimodality treatment including IOERT at either one of the two centres. The preferred treatment approach was preoperative (chemo) radiation and intended radical surgery combined with IOERT. Risk factors for local recurrence (LR), cancer specific survival, disease free survival and distant metastases (DM) were assessed. A total of 306 patients (73%) underwent a R0 resection. LRs and metastases occurred more frequently after an R1-2 resection (P<0.001 and P<0.001 respectively). Preoperative chemoradiation (preop CRT) was associated with a higher probability of having a R0 resection. Waiting time after preoperative treatment was inversely related with the chance of developing a LR, especially after R+ resection. In 16% of all cases a LR developed. Five-year disease free survival and overall survival (OS) were 55% and 56% respectively. An acceptable survival can be achieved in treatment of patients with initially unresectable T4 rectal cancer with combined modality therapy that includes preop CRT and IOERT. Completeness of the resection is the most important predictive and prognostic factor in the treatment of T4

  9. Nimotuzumab in combination with radiotherapy in high grade glioma patients

    PubMed Central

    Solomon, Maria Teresa; Miranda, Nederlay; Jorrín, Eugenia; Chon, Ivonne; Marinello, Jorge Juan; Alert, José; Lorenzo-Luaces, Patricia; Crombet, Tania

    2014-01-01

    Nimotuzumab, a humanized antibody targeting epidermal growth factor receptor, has potent anti-proliferative, anti-angiogenic, and pro-apoptotic effects in vitro and in vivo. It also reduces the number of radio-resistant CD133+ glioma stem cells. The antibody has been extensively evaluated in patients with advanced head and neck, glioma, lung, esophageal, pancreatic, and gastric cancer. In this single institution experience, 35 patients with anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) were treated with irradiation and 200 mg doses of nimotuzumab. The first 6 doses were administered weekly, together with radiotherapy, and then treatment continued every 21 days until 1 year. The median number of doses was 12, and the median cumulative dose was thus 2400 mg of nimotuzumab. The most frequent treatment-related toxicities were increase in liver function tests, fever, nausea, anorexia, asthenia, dizziness, and tremors. These adverse reactions were classified as mild and moderate. The median survival time was 12.4 mo or 27.0 mo for patients with GBM or AA patients, respectively, who received curative-intent radiotherapy in combination with the antibody. The survival time of a matched population treated at the same hospital with irradiation alone was decreased (median 8.0 and 12.2 mo for GBM and AA patients, respectively) compared with that of the patients who received nimotuzumab and curative-intent radiotherapy. We have thus confirmed that nimotuzumab is a very well-tolerated drug, lacking cumulative toxicity after maintenance doses. This study, in a poor prognosis population, validates the previous data of survival gain after combining nimotuzumab and radiotherapy, in newly diagnosed high-grade glioma patients. PMID:24521695

  10. [The effect of radiotherapy on the antitumor immune response. Possibilities to combine radiotherapy with immunotherapy].

    PubMed

    Lumniczky, Katalin; Sáfrány, Géza

    2016-03-02

    The past three decades of immunology research led to a drastic increase in the knowledge of antitumor immune response mechanisms and in parallel to a rapid development in various antitumor immune therapy strategies. This will most probably result in the implementation of immunotherapeutic protocols within the standard anticancer regimens in a very near future. Though, it is obvious that combination of immunotherapy with traditional anticancer treatment modalities will only be legitimate if the combination has at least an additive, or perhaps a synergistic effect. The similarly dynamic progress in the radiobiological knowledge proved that ionizing radiation does not have a general immune suppressing effect, as it has been thought for decades, but might possess certain immune stimulatory effects, as well. It is also known by now that local irradiation due to its out-of-field effects has systemic immune modulatory capacity, too. In the light of all these novel findings the optimal combination between antitumor immunotherapy and radiotherapy has become an increasing option. The first part of the present review summarizes the main antitumor mechanisms that can be influenced by ionizing radiation, and the second part attempts to provide a comprehensive overview of those antitumor immunotherapeutic modalities that are currently being used in combination with radiotherapy in preclinical and/or clinical trials for the treatment of various tumors.

  11. Breast-conserving surgery with intra-operative radiotherapy: the right approach for the 21st century?

    PubMed

    Tobias, J S; Vaidya, J S; Keshtgar, M; Douek, M; Metaxas, M; Stacey, C; Sainsbury, R; D'Souza, D; Baum, M

    2006-04-01

    Wide local excision followed by external beam radiation therapy (EBRT) to the whole breast has become the standard of care for most patients with localised 'early' breast cancer in the UK, Europe, and the USA. Local relapse rates are low, and overall survival figures have improved during the past decade, with the advent of more effective systemic endocrine- and chemo-therapy. A policy of EBRT for every patient undergoing breast conserving surgery (BCS) is however associated with a number of practical difficulties, acute radiation side effects and longer term toxicity, all of which detract from the obvious benefits of EBRT. In addition, with a disease as common as early breast cancer and a treatment programme typically requiring sophisticated radiation planning and many fractions of treatment, the policy of BCS plus EBRT has enormous resource implications within departments of oncology, greatly contributing to lengthy pre-treatment delays. For all these reasons, we and others have developed an increasing interest in techniques of partial breast irradiation, with an emphasis in our own Department on the emerging technique of intra-operative radiotherapy (IORT), which we initially employed as a boost to the tumour bed for use in conjunction with EBRT to the whole breast. To test the possibility of replacing the whole of the EBRT 3-6 week programme by a single application of IORT at the time of surgery, we and others have commenced a large scale prospectively randomised clinical trail in selected patients. Nine international centres are currently participating, and 350 patients have now been randomised to receive either IORT as part of the initial surgical excision or conventional EBRT with a pragmatic dose policy according to the preference of the contributing centre. The majority of patients undergoing IORT receive this at the time of initial surgery but it is also permissible within the trial programme to randomise suitable patients after the excised specimen has

  12. In vivo dosimetry in intraoperative electron radiotherapy: microMOSFETs, radiochromic films and a general-purpose linac.

    PubMed

    López-Tarjuelo, Juan; Bouché-Babiloni, Ana; Morillo-Macías, Virginia; de Marco-Blancas, Noelia; Santos-Serra, Agustín; Quirós-Higueras, Juan David; Ferrer-Albiach, Carlos

    2014-10-01

    In vivo dosimetry is desirable for the verification, recording, and eventual correction of treatment in intraoperative electron radiotherapy (IOERT). Our aim is to share our experience of metal oxide semiconductor field-effect transistors (MOSFETs) and radiochromic films with patients undergoing IOERT using a general-purpose linac. We used MOSFETs inserted into sterile bronchus catheters and radiochromic films that were cut, digitized, and sterilized by means of gas plasma. In all, 59 measurements were taken from 27 patients involving 15 primary tumors (seven breast and eight non-breast tumors) and 12 relapses. Data were subjected to an outliers' analysis and classified according to their compatibility with the relevant doses. Associations were sought regarding the type of detector, breast and non-breast irradiation, and the radiation oncologist's assessment of the difficulty of detector placement. At the same time, 19 measurements were carried out at the tumor bed with both detectors. MOSFET measurements ([Formula: see text]  = 93.5 %, sD  =  6.5 %) were not significantly shifted from film measurements ([Formula: see text]  =  96.0 %, sD  =  5.5 %; p  =  0.109), and no associations were found (p = 0.526, p = 0.295,  and p = 0.501, respectively). As regards measurements performed at the tumor bed with both detectors, MOSFET measurements ([Formula: see text]  =  95.0 %, sD  =  5.4 % were not significantly shifted from film measurements ([Formula: see text]  =  96.4 %, sD  =  5.0 %; p  =  0.363). In vivo dosimetry can produce satisfactory results at every studied location with a general-purpose linac. Detector choice should depend on user factors, not on the detector performance itself. Surgical team collaboration is crucial to success.

  13. Combining radiotherapy and angiogenesis inhibitors: Clinical trial design

    SciTech Connect

    Citrin, Deborah . E-mail: citrind@mail.nih.gov; Menard, Cynthia; Camphausen, Kevin

    2006-01-01

    Radiotherapy (RT) plays a vital role in the multimodality treatment of cancer. Recent advances in RT have primarily involved improvements in dose delivery. Future improvements in tumor control and disease outcomes will likely involve the combination of RT with targeted therapies. Preclinical evaluations of angiogenesis inhibitors in combination with RT have yielded promising results with increased tumor 'cure.' It remains to be seen whether these improvements in tumor control in the laboratory will translate into improved outcomes in the clinic. Multiple differences between these agents and cytotoxic chemotherapy must be taken into account when designing clinical trials evaluating their effectiveness in combination with RT. We discuss important considerations for designing clinical trials of angiogenesis inhibitors with RT.

  14. Surgical Management of Combined Intramedullary Arteriovenous Malformation and Perimedullary Arteriovenous Fistula within the Hybrid Operating Room after Five Years of Performing Focus Fractionated Radiotherapy: Case Report

    PubMed Central

    GEKKA, Masayuki; SEKI, Toshitaka; HIDA, Kazutoshi; OSANAI, Toshiya; HOUKIN, Kiyohiro

    2014-01-01

    Perimedullary arteriovenous fistula (AVF) shunts occur on the spinal cord surface and can be treated surgically or by endovascular embolization. In contrast, the nidus of an intramedullary arteriovenous malformation (AVM) is located in the spinal cord and is difficult to treat surgically or by endovascular techniques. The benefits of radiotherapy for treating intramedullary AVM have been published, but are anecdotal and consist largely of case reports. We present a case of combined cervical intramedullary AVM and perimedullary AVF which received surgical treatment within a hybrid operating room (OR) after 5 years of focus fractionated radiotherapy. A 37-year-old male presented with stepwise worsening myelopathy. Magnetic resonance imaging and spinal angiography revealed intramedullary AVM and perimedullary AVF at the C3 to C5 levels. In order to reduce nidus size and blood flow, we first performed focal fractionated radiotherapy. Five years later, the lesion volume was reduced. Following this, direct surgery was performed by an anterior approach using corpectomy in the hybrid OR. The spinal cord was monitored by motor-evoked potential throughout the surgery. Complete obliteration of the fistulous connection was confirmed by intraoperative indocyanine green video-angiography and intraoperative angiography, preserving the anterior spinal artery. We conclude that surgical treatment following focal fractionated radiotherapy may become one strategy for patients who are initially deemed ineligible for endovascular embolization and surgical treatment. Furthermore, the hybrid OR enables safe and precise treatment for spinal vascular disorders in the fields of endovascular treatment and neurosurgery. PMID:25367581

  15. Single high dose intraoperative electrons for advanced stage pancreatic cancer: Phase I pilot study

    SciTech Connect

    Goldson, A.L.; Ashaveri, E.; Espinoza, M.C.

    1981-07-01

    Phase I toxicity studies with intraoperative radiotherapy proved to be a feasible adjunct to surgery for unresectable malignancies of the pancreas at Howard University Hospital. There have been minimal side effects or complications related to the combination of limited surgical decompression and intraoperative radiotherapy alone. The toxic effects of intraoperative radiotherapy on normal tissues is being assessed on a dose volume basis. Doses of 2000 to 2500 rad in a single exposure to include the pancreas, regional nodes and duodenum are acceptable if the total treatment volume is less than or equal to 100 cm. The tumoricidal effects on the cancer are demonstratable when one reviews the pathological specimens that illustrate massive tumor necrosis and fibros replacement, but in all cases reviewed, viable cancer was noted. Intraoperative radiotherapy, therefore, represents a significant boost dose for resectable, partially resectable or non-resectable tumors when added to conventional external beam irradiation and/or chemotherapy. Preliminary clinical data and minimal toxicity justifies further investigation.

  16. Results of intraoperative electron beam radiotherapy containing multimodality treatment for locally unresectable T4 rectal cancer: a pooled analysis of the Mayo Clinic Rochester and Catharina Hospital Eindhoven

    PubMed Central

    Holman, Fabian A.; Haddock, Michael G.; Gunderson, Leonard L.; Kusters, Miranda; Nieuwenhuijzen, Grard A. P.; van den Berg, Hetty A.; Nelson, Heidi

    2016-01-01

    Background The aim of this study is to analyse the pooled results of intraoperative electron beam radiotherapy (IOERT) containing multimodality treatment of locally advanced T4 rectal cancer, initially unresectable for cure, from the Mayo Clinic, Rochester, USA (MCR) and Catharina Hospital, Eindhoven, The Netherlands (CHE), both major referral centers for locally advanced rectal cancer. A rectal tumor is called locally unresectable for cure if after full clinical work-up infiltration into the surrounding structures or organs has been demonstrated, which would result in positive surgical margins if resection was the initial component of treatment. This was the reason to refer these patients to the IOERT program of one of the centers. Methods In the period from 1981 to 2010, 417 patients with locally unresectable T4 rectal carcinomas at initial presentation were treated with multimodality treatment including IOERT at either one of the two centres. The preferred treatment approach was preoperative (chemo) radiation and intended radical surgery combined with IOERT. Risk factors for local recurrence (LR), cancer specific survival, disease free survival and distant metastases (DM) were assessed. Results A total of 306 patients (73%) underwent a R0 resection. LRs and metastases occurred more frequently after an R1-2 resection (P<0.001 and P<0.001 respectively). Preoperative chemoradiation (preop CRT) was associated with a higher probability of having a R0 resection. Waiting time after preoperative treatment was inversely related with the chance of developing a LR, especially after R+ resection. In 16% of all cases a LR developed. Five-year disease free survival and overall survival (OS) were 55% and 56% respectively. Conclusions An acceptable survival can be achieved in treatment of patients with initially unresectable T4 rectal cancer with combined modality therapy that includes preop CRT and IOERT. Completeness of the resection is the most important predictive and

  17. Environmental and social benefits of the targeted intraoperative radiotherapy for breast cancer: data from UK TARGIT-A trial centres and two UK NHS hospitals offering TARGIT IORT

    PubMed Central

    Coombs, Nathan J; Coombs, Joel M; Vaidya, Uma J; Singer, Julian; Bulsara, Max; Tobias, Jeffrey S; Wenz, Frederik; Joseph, David J; Brown, Douglas A; Rainsbury, Richard; Davidson, Tim; Adamson, Douglas J A; Massarut, Samuele; Morgan, David; Potyka, Ingrid; Corica, Tammy; Falzon, Mary; Williams, Norman; Baum, Michael; Vaidya, Jayant S

    2016-01-01

    Objective To quantify the journeys and CO2 emissions if women with breast cancer are treated with risk-adapted single-dose targeted intraoperative radiotherapy (TARGIT) rather than several weeks' course of external beam whole breast radiotherapy (EBRT) treatment. Setting (1) TARGIT-A randomised clinical trial (ISRCTN34086741) which compared TARGIT with traditional EBRT and found similar breast cancer control, particularly when TARGIT was given simultaneously with lumpectomy, (2) 2 additional UK centres offering TARGIT. Participants 485 UK patients (249 TARGIT, 236 EBRT) in the prepathology stratum of TARGIT-A trial (where randomisation occurred before lumpectomy and TARGIT was delivered simultaneously with lumpectomy) for whom geographical data were available and 22 patients treated with TARGIT after completion of the TARGIT-A trial in 2 additional UK breast centres. Outcome measures The shortest total journey distance, time and CO2 emissions from home to hospital to receive all the fractions of radiotherapy. Methods Distances, time and CO2 emissions were calculated using Google Maps and assuming a fuel efficiency of 40 mpg. The groups were compared using the Student t test with unequal variance and the non-parametric Wilcoxon rank-sum (Mann-Whitney) test. Results TARGIT patients travelled significantly fewer miles: TARGIT 21 681, mean 87.1 (SE 19.1) versus EBRT 92 591, mean 392.3 (SE 30.2); had lower CO2 emissions 24.7 kg (SE 5.4) vs 111 kg (SE 8.6) and spent less time travelling: 3 h (SE 0.53) vs 14 h (SE 0.76), all p<0.0001. Patients treated with TARGIT in 2 hospitals in semirural locations were spared much longer journeys (753 miles, 30 h, 215 kg CO2 per patient). Conclusions The use of TARGIT intraoperative radiotherapy for eligible patients with breast cancer significantly reduces their journeys for treatment and has environmental benefits. If widely available, 5 million miles (8 000 000 km) of travel, 170 000 woman-hours and 1200

  18. Combining Targeted Agents With Modern Radiotherapy in Soft Tissue Sarcomas

    PubMed Central

    Wong, Philip; Houghton, Peter; Kirsch, David G.; Finkelstein, Steven E.; Monjazeb, Arta M.; Xu-Welliver, Meng; Dicker, Adam P.; Ahmed, Mansoor; Vikram, Bhadrasain; Teicher, Beverly A.; Coleman, C. Norman; Machtay, Mitchell; Curran, Walter J.

    2014-01-01

    Improved understanding of soft-tissue sarcoma (STS) biology has led to better distinction and subtyping of these diseases with the hope of exploiting the molecular characteristics of each subtype to develop appropriately targeted treatment regimens. In the care of patients with extremity STS, adjunctive radiation therapy (RT) is used to facilitate limb and function, preserving surgeries while maintaining five-year local control above 85%. In contrast, for STS originating from nonextremity anatomical sites, the rate of local recurrence is much higher (five-year local control is approximately 50%) and a major cause of death and morbidity in these patients. Incorporating novel technological advancements to administer accurate RT in combination with novel radiosensitizing agents could potentially improve local control and overall survival. RT efficacy in STS can be increased by modulating biological pathways such as angiogenesis, cell cycle regulation, cell survival signaling, and cancer-host immune interactions. Previous experiences, advancements, ongoing research, and current clinical trials combining RT with agents modulating one or more of the above pathways are reviewed. The standard clinical management of patients with STS with pretreatment biopsy, neoadjuvant treatment, and primary surgery provides an opportune disease model for interrogating translational hypotheses. The purpose of this review is to outline a strategic vision for clinical translation of preclinical findings and to identify appropriate targeted agents to combine with radiotherapy in the treatment of STS from different sites and/or different histology subtypes. PMID:25326640

  19. Combined liver-kidney transplantation complicated by intraoperative discovery of a bronchobiliary fistula.

    PubMed

    Stock, E; Vannucci, A; Doyle, M; Patterson, G A; Chapman, W; Kangrga, I

    2010-09-01

    Herein, we report the case of an intraoperative diagnosis of bronchobiliary fistula during combined liver-kidney transplantation because of polycystic disease. The diagnosis necessitated changes in surgical and anesthesiologic management and in the overall medical decision-making process. Emergent isolation of the affected lung was instituted to mitigate a large air leak and ensure adequate respiratory exchange, and to enable surgical repair. The kidney transplantation procedure was delayed for a few hours, enabling hemodynamic and respiratory stabilization in the intensive care unit before conditions were deemed adequate to proceed. The posttransplantation course was complicated but eventually successful, and the patient recovered both liver and kidney function. At a later evaluation, we realized that diagnosis of bronchobiliary fistula could have been made preoperatively had the chest radiograph been interpreted correctly and had the clinicians involved had a higher degree of suspicion for this complication of polycystic liver disease. 2010 Elsevier Inc. All rights reserved.

  20. Cosmetic Outcomes for Accelerated Partial Breast Irradiation Before Surgical Excision of Early-Stage Breast Cancer Using Single-Dose Intraoperative Radiotherapy

    SciTech Connect

    Kimple, Randall J.; Klauber-DeMore, Nancy; Kuzmiak, Cherie M.; Pavic, Dag; Lian, Jun; Livasy, Chad A.; Esler, Laura; Moore, Dominic T.; Sartor, Carolyn I.; Ollila, David W.

    2011-02-01

    Purpose: Determine cosmetic outcome and toxicity profile of intraoperative radiation delivered before tumor excision for patients with early-stage breast cancer. Methods and Materials: Patients age 48 or older with ultrasound-visible invasive ductal cancers <3 cm and clinically negative lymph nodes were eligible for treatment on this institutional review board-approved Phase II clinical trial. Treatment planning ultrasound was used to select an electron energy and cone size sufficient to cover the tumor plus a 1.5- to 2.0-cm circumferential margin laterally and a 1-cm-deep margin with the 90% isodose line. The dose was prescribed to a nominal 15 Gy and delivered using a Mobetron electron irradiator before tumor excision by segmental mastectomy. Physician- and patient-assessed cosmetic outcome and patient satisfaction were determined by questionnaire. Results: From March 2003 to July 2007, 71 patients were treated with intraoperative radiation therapy. Of those, 56 patients were evaluable, with a median follow-up of 3.1 years (minimum 1 year). Physician and patient assessment of cosmesis was 'good or excellent' (Radiation Therapy Oncology Group cosmesis scale) in 45/56 (80%) and 32/42 (76%) of all patients, respectively. Eleven patients who received additional whole breast radiation had similar rates of good or excellent cosmesis: 40/48 (83%) and 29/36 (81%), respectively). Grade 1 or 2 acute toxicities were seen in 4/71 (6%) patients. No Grade 3 or 4 toxicities or serious adverse events have been seen. Conclusion: Intraoperative radiotherapy delivered to an in situ tumor is feasible with acceptable acute tolerance. Patient and physician assessment of the cosmetic outcome is good to excellent.

  1. Combined radiotherapy and chemotherapy for high-grade brain tumours

    NASA Astrophysics Data System (ADS)

    Barazzuol, Lara

    Glioblastoma (GBM) is the most common primary brain tumour in adults and among the most aggressive of all tumours. For several decades, the standard care of GBM was surgical resection followed by radiotherapy alone. In 2005, a landmark phase III clinical trial coordinated by the European Organization for Research and Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC) demonstrated the benefit of radiotherapy with concomitant and adjuvant temozolomide (TMZ) chemotherapy. With TMZ, the median life expectancy in optimally managed patients is still only 12-14 months, with only 25% surviving 24 months. There is an urgent need for new therapies in particular in those patients whose tumour has an unmethylated methylguanine methyltransferase gene (MGMT) promoter, which is a predictive factor of benefit from TMZ. In this dissertation, the nature of the interaction between TMZ and radiation is investigated using both a mathematical model, based on in vivo population statistics of survival, and in vitro experimentation on a panel of human GBM cell lines. The results show that TMZ has an additive effect in vitro and that the population-based model may be insufficient in predicting TMZ response. The combination of TMZ with particle therapy is also investigated. Very little preclinical data exists on the effects of charged particles on GBM cell lines as well as on the concomitant application of chemotherapy. In this study, human GBM cells are exposed to 3 MeV protons and 6 MeV alpha particles in concomitance with TMZ. The results suggest that the radiation quality does not affect the nature of the interaction between TMZ and radiation, showing reproducible additive cytotoxicity. Since TMZ and radiation cause DNA damage in cancer cells, there has been increased attention to the use of poly(ADP-ribose) polymerase (PARP) inhibitors. PARP is a family of enzymes that play a key role in the repair of DNA breaks. In this study, a novel PARP inhibitor, ABT-888

  2. Combinations of Radiotherapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

    PubMed Central

    Barker, Christopher A.; Postow, Michael A.

    2015-01-01

    Radiotherapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiotherapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiotherapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiotherapy. The cytokines interferon-alpha and interleukin-2 have been combined with radiotherapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiotherapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested radiotherapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiotherapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study. PMID:24661650

  3. Exclusive intraoperative radiotherapy for invasive breast cancer in elderly patients (>70 years): proportion of eligible patients and local recurrence-free survival.

    PubMed

    Lambaudie, Eric; Houvenaeghel, Gilles; Ziouèche, Amira; Knight, Sophie; Dravet, François; Garbay, Jean Remy; Giard, Sylvie; Charitansky, Hélène; Cohen, Monique; Faure, Christelle; Hudry, Delphine; Azuar, Paul; Villet, Richard; Gimbergues, Pierre; de Lara, Christine Tunon; Tallet, Agnès; Bannier, Marie; Minsat, Mathieu; Resbeut, Michel

    2016-11-15

    To estimate the proportion of elderly patients (>70 years) with breast cancer eligible for an Exclusive IntraOperative RadioTherapy (E-IORT) and to evaluate their local recurrence-free survival rate. This retrospective study examining two cohorts focuses on patients over 70 years old: a multi-centric cohort of 1411 elderly patients and a mono-centric cohort of 592 elderly patients. All patients underwent conservative surgery followed by external radiotherapy for T0-T3 N0-N1 invasive breast cancer, between 1980 and 2008. Within each cohort two groups were identified according to the inclusion criteria of the RIOP trial (R group) and TARGIT E study (T group). Each group was divided into two sub-groups, patients eligible (E) or non-eligible (nE) for IORT. The population of patients that were eligible in the TARGIT E study but not in the RIOP trial were also studied in both cohorts. The proportion of patients eligible for IORT was calculated, according to the eligibility criteria of each study. A comparison of the 5-year local or locoregional recurrence-free survival rate between eligible vs non-eligible patients was made. In both cohorts, the proportion of patients eligible according to the RIOP trial's eligibility criteria was 35.4 and 19.3%, and according to the TARGIT E study criteria was 60.9 and 45.3%. The 5-year locoregional recurrence-free survival rate was not significantly different between RE and RnE groups, TE and TnE groups. In both cohorts RE and (TE-RE) groups were not significantly different. Our results encourage further necessary studies to define and to extend the eligibility criteria for per operative exclusive radiotherapy.

  4. Intra-operative vertebroplasty combined with posterior cord decompression. A report of twelve cases.

    PubMed

    Allegretti, Luca; Mavilio, Nicola; Fiaschi, Pietro; Bragazzi, Roberto; Pacetti, Mattia; Castelletti, Lara; Saitta, Laura; Castellan, Lucio

    2014-10-31

    Percutaneous vertebroplasty (VP) is a minimally invasive technique for the treatment of vertebral pathology providing early vertebral stabilization and pain relief. In cases of vertebral pathology complicated by spinal cord compression with associated neurological deficits, VP alone cannot be performed free of risks. We describe a combined approach in which decompressive laminectomy and intra-operative vertebroplasty (IVP) are performed during a single session. Among the 252 VP performed in our centre in the past three years, 12 patients (12 vertebral levels) with different pathologies (six symptomatic haemangiomas, two metastatic fractures, four osteoporotic fractures) were treated with an open procedure combined with surgery. All cases were treated with decompressive laminectomy and IVP (mono/bipeduncular or median-posterior trans-somatic access). Five patients with symptomatic haemangiomas were treated with endovascular embolization prior to the combined approach. A visual analogue scale (VAS) was applied to assess pain intensity before and after surgery. The neurological deficits were evaluated with an ASIA impairment scale. In all cases benefit from pain and neurological deficits was observed. The mean VAS score decreased from 7.8 to 2.5 after surgery. The ASIA score improved in all cases (five cases from D to E and five cases from C to D). No clinical complications were observed. In one case a CT scan performed after the procedure showed a foraminal accumulation of PMMA, but the patient referred no symptoms. IVP can be successfully applied in different pathologies affecting the vertebrae. In our limited series this approach proved safe and efficient to provide decompression of spinal cord and dural sac and vertebral body stabilization in a single session.

  5. Effect of surgical wound fluids after intraoperative electron radiotherapy on the cancer stem cell phenotype in a panel of human breast cancer cell lines.

    PubMed

    Zaleska, Karolina; Suchorska, Wiktoria Maria; Przybyła, Anna; Murawa, Dawid

    2016-11-01

    The wound healing process after surgery alters the area surrounding the original tumor and around the scar, and the modified microenvironment is more favorable for tumor recurrence. Intraoperative radiotherapy (IORT) is one of the more novel strategies in breast cancer (BC) treatment. Irradiation during surgery has effects on the tumor microenvironment, abrogating the proliferative cascade induced by surgical wound healing. The aim of the present study was to determine the effect of surgical wound fluids from IOERT treatment (RT-WF) compared with wound fluids from conservative-breast surgery only (WF) on the cancer stem cell phenotype in a panel of BC cell lines. Post-operative wound fluids were derived from patients with BC who underwent a tumor resection (quadrantectomy) plus intraoperative electron radiotherapy using a single dose of ≤10 Gy on the tumor bed and surrounding tissues, or from those who underwent a tumor resection without IOERT. Cell lines were incubated with 10% wound fluids, and after 4 days, the cluster of differentiation (CD)44(+)/CD24(-/low) phenotype and aldehyde dehydrogenase 1 (ALDH1) activity were determined by flow cytometry. The two types of fluid each affected the CD44(+)/CD24(-/low) phenotype. The results varied markedly between each cell line, even for the same histological subtypes. RT-WF decreased the CD44(+)/CD24(-/low) populations in the basal-like BT-549 and MDA-MB-468 cell lines, whereas in the luminal type MCF7 cell line, the two fluids inhibited these populations. The HER-OE subtypes harbored a minimal CD44(+)/CD24(-/low) population, but the growth of SK-BR-3 was stimulated by the two post-operative fluids. WF exhibited a stronger effect on ALDH1 activity compared with RT-WF. The stimulatory effect was dependent on the histological subtype of the cell line and the strongest dependence was observed in luminal subtypes characterized by low dehydrogenase activity in the control group. The present results enable a better

  6. Effect of surgical wound fluids after intraoperative electron radiotherapy on the cancer stem cell phenotype in a panel of human breast cancer cell lines

    PubMed Central

    Zaleska, Karolina; Suchorska, Wiktoria Maria; Przybyła, Anna; Murawa, Dawid

    2016-01-01

    The wound healing process after surgery alters the area surrounding the original tumor and around the scar, and the modified microenvironment is more favorable for tumor recurrence. Intraoperative radiotherapy (IORT) is one of the more novel strategies in breast cancer (BC) treatment. Irradiation during surgery has effects on the tumor microenvironment, abrogating the proliferative cascade induced by surgical wound healing. The aim of the present study was to determine the effect of surgical wound fluids from IOERT treatment (RT-WF) compared with wound fluids from conservative-breast surgery only (WF) on the cancer stem cell phenotype in a panel of BC cell lines. Post-operative wound fluids were derived from patients with BC who underwent a tumor resection (quadrantectomy) plus intraoperative electron radiotherapy using a single dose of ≤10 Gy on the tumor bed and surrounding tissues, or from those who underwent a tumor resection without IOERT. Cell lines were incubated with 10% wound fluids, and after 4 days, the cluster of differentiation (CD)44+/CD24−/low phenotype and aldehyde dehydrogenase 1 (ALDH1) activity were determined by flow cytometry. The two types of fluid each affected the CD44+/CD24−/low phenotype. The results varied markedly between each cell line, even for the same histological subtypes. RT-WF decreased the CD44+/CD24−/low populations in the basal-like BT-549 and MDA-MB-468 cell lines, whereas in the luminal type MCF7 cell line, the two fluids inhibited these populations. The HER-OE subtypes harbored a minimal CD44+/CD24−/low population, but the growth of SK-BR-3 was stimulated by the two post-operative fluids. WF exhibited a stronger effect on ALDH1 activity compared with RT-WF. The stimulatory effect was dependent on the histological subtype of the cell line and the strongest dependence was observed in luminal subtypes characterized by low dehydrogenase activity in the control group. The present results enable a better understanding of

  7. Multimodality therapy including surgical resection and intraoperative electron radiotherapy for recurrent or advanced primary carcinoma of the urinary bladder or ureter.

    PubMed

    Hallemeier, Christopher L; Karnes, Robert J; Pisansky, Thomas M; Davis, Brian J; Gunderson, Leonard L; Leibovich, Bradley C; Haddock, Michael G; Choo, Richard

    2013-12-01

    To report outcomes of multimodality therapy incorporating surgical resection and intraoperative electron radiotherapy (IOERT) for patients with locoregionally (LR) recurrent or advanced primary urothelial carcinoma. From 1983 to 2009, 17 patients, consisting of 11 with LR recurrence after cystectomy for bladder carcinoma, 4 with LR recurrence after nephroureterectomy for ureteral carcinoma, and 2 with advanced primary bladder carcinoma were treated with multimodality therapy. In 8 patients with LR recurrence, the multimodality treatment was a second salvage attempt. Sixteen patients received perioperative external beam radiotherapy (median dose, 50.4 Gy; range, 21.6 to 60 Gy). Extent of resection was R0 (n=7), R1 (n=1), and R2 (n=9). The median IOERT dose was 12.5 Gy (range, 10 to 20 Gy). Overall survival (OS) and relapse patterns were determined from the date of resection and IOERT using the Kaplan-Meier method. The median follow-up for surviving patients was 3.6 years (range, 1.1 to 10 y). OS at 1, 2, and 5 years was 53%, 31%, and 16%, respectively. Central (within the IOERT field), LR (tumor bed or regional lymph nodes), and distant relapses at 2 years were 15%, 49%, and 67%, respectively. On univariate analysis, resection of all gross disease (R0-1) was associated with improved OS (P=0.03). Mortality within 30 days was 0%. Two patients (12%) experienced NCI-CTCAE grades 4 and 5 late adverse events. In patients with recurrent or advanced urothelial carcinoma, this multimodality approach yielded a low rate of recurrence within the IOERT field with acceptable toxicity. However, LR and distant relapse were common, indicating a need for better patient selection, LR therapy, and systemic therapy.

  8. [Efficacy of whole body gamma-knife radiotherapy combined with thermochemotherapy on locally advanced pancreatic cancer].

    PubMed

    Zhang, Li-Ping; Nie, Qing; Kang, Jing-Bo; Wang, Bin; Cai, Chang-Lan; Li, Jian-Guo; Qi, Wen-Jie

    2008-11-01

    Radiotherapy and chemotherapy are major therapies for locally advanced pancreatic cancer. This study was to evaluate the efficacy of three-dimensional conformal gamma-knife radiotherapy combined with thermochemotherapy on locally advanced pancreatic cancer. From December 2001 to January 2006, 75 patients with locally advanced pancreatic cancer were divided into radiotherapy group (37 patients) and combination group (38 patients). All patients received gamma-knife radiotherapy using Stereotactic Radiotherapy Gamma Rays System, with iso-dose curves of 50%-60%, tumor encircling dose of 3.0-4.5 Gy per fraction, 8-11 fractions. The patients in combination group received simultaneous thermotherapy at 41.5-43.5 celsius (1 h/fraction, twice a week for 6 times), and chemotherapy with venous administration of tegafur (0.5-1.0 g) and calcium folinate (CF, 0.2 g) for 4-6 times, or venous administration of gemcitabine (0.6-1.0 g/m2) on Days 1 and 8 and cisplatin (DDP) (20-30 mg/m2) on Days 1-3, repeated every 28 days for 3-6 cycles. At 3 months after treatment, the total response (complete remission and partial remission) rate was 70.7% (53/75); the response rate was 73.7% in combination group and 67.5% in radiotherapy group. The 1-year survival rate was 48.3%, and the 2-year survival rate was 22.1%. The 1-and 2-year survival rates were 51.2% and 26.5% in combination group, and 45.2% and 17.6% in radiotherapy group. No serious complications, such as perforation, bleeding and high fever, were seen during treatment and follow-up. 3-D conformal gamma-knife radiotherapy combined with thermochemotherapy is well tolerated and is relatively effective for most patients with locally advanced pancreatic cancer.

  9. Can the risk of secondary cancer induction after breast conserving therapy be reduced using intraoperative radiotherapy (IORT) with low-energy x-rays?

    PubMed Central

    2011-01-01

    Background Radiation induced secondary cancers are a rare but severe late effect after breast conserving therapy. Intraoperative radiotherapy (IORT) is increasingly used during breast conserving surgery. The purpose of this analysis was to estimate secondary cancer risks after IORT compared to other modalities of breast radiotherapy (APBI - accelerated partial breast irradiation, EBRT - external beam radiotherapy). Methods Computer-tomography scans of an anthropomorphic phantom were acquired with an INTRABEAM IORT applicator (diameter 4 cm) in the outer quadrant of the breast and transferred via DICOM to the treatment planning system. Ipsilateral breast, contralateral breast, ipsilateral lung, contralateral lung, spine and heart were contoured. An INTRABEAM source (50 kV) was defined with the tip of the drift tube at the center of the spherical applicator. A dose of 20 Gy at 0 mm depth from the applicator surface was prescribed for IORT and 34 Gy (5 days × 2 × 3.4 Gy) at 10 mm depth for APBI. For EBRT a total dose of 50 Gy in 2 Gy fractions was planned using two tangential fields with wedges. The mean and maximal doses, DVHs and volumes receiving more than 0.1 Gy and 4 Gy of organs at risk (OAR) were calculated and compared. The life time risk for secondary cancers was estimated according to NCRP report 116. Results IORT delivered the lowest maximal doses to contralateral breast (< 0.3 Gy), ipsilateral (1.8 Gy) and contralateral lung (< 0.3 Gy), heart (1 Gy) and spine (< 0.3 Gy). In comparison, maximal doses for APBI were 2-5 times higher. EBRT delivered a maximal dose of 10.4 Gy to the contralateral breast and 53 Gy to the ipsilateral lung. OAR volumes receiving more than 4 Gy were 0% for IORT, < 2% for APBI and up to 10% for EBRT (ipsilateral lung). The estimated risk for secondary cancer in the respective OAR is considerably lower after IORT and/or APBI as compared to EBRT. Conclusions The calculations for maximal doses and volumes of OAR suggest that the risk

  10. Phase I study of intraoperative radiotherapy with photon radiosurgery system in children with recurrent brain tumors: Preliminary report of first dose level (10 Gy)

    SciTech Connect

    Kalapurakal, John A. . E-mail: j-kalapurakal@northwestern.edu; Goldman, Stewart; Stellpflug, Wendy; Curran, John; Sathiaseelan, Vythialingam; Marymont, Maryanne H.; Tomita, Tadanori

    2006-07-01

    Purpose: To describe the preliminary results after intraoperative radiotherapy (IORT) with the photon radiosurgery system in children with recurrent brain tumors treated at the first dose level (10 Gy) of a Phase I protocol. Methods and Materials: A Phase I IORT dose escalation protocol was initiated at Children's Memorial Hospital to determine the maximal tolerated IORT dose in children with recurrent brain tumors. Results: Fourteen children have received IORT thus far. Eight had been previously irradiated. Thirteen children had ependymoma. The median follow-up was 16 months. Three patients (21%) developed radiation necrosis on follow-up MRI scans 6 to 12 months after IORT. They had not been previously irradiated and had received 10 Gy to a depth of 5 mm. One required surgery and the other two had resolution of their lesions without treatment. All 3 patients were asymptomatic at the last follow-up. No other late toxicity was observed at the last follow-up visit. Eight patients (57%) had tumor control within the surgical bed after IORT. Conclusion: Our findings have demonstrated the safety and feasibility of IORT to a dose of 10 Gy to 2 mm in children with previously irradiated brain tumors. IORT to a dose of 10 Gy at 5 mm was associated with a greater complication rate.

  11. Intraoperative irradiation: precision medicine for quality cancer control promotion.

    PubMed

    Calvo, Felipe A

    2017-02-02

    Intraoperative irradiation was implemented 4 decades ago, pioneering the efforts to improve precision in local cancer therapy by combining real-time surgical exploration/resection with high single dose radiotherapy (Gunderson et al., Intraoperative irradiation: techniques and results, 2011). Clinical and technical developments have led to very precise radiation dose deposit. The ability to deliver a very precise dose of radiation is an essential element of contemporary multidisciplinary individualized oncology.This issue of Radiation Oncology contains a collection of expert review articles and updates with relevant data regarding intraoperative radiotherapy. Technology, physics, biology of single dose and clinical results in a variety of cancer sites and histologies are described and analyzed. The state of the art for advanced cancer care through medical innovation opens a significant opportunity for individualize cancer management across a broad spectrum of clinical practice. The advantage for tailoring diagnostic and treatment decisions in an individualized fashion will translate into precise medical treatment.

  12. An Innovative Tool for Intraoperative Electron Beam Radiotherapy Simulation and Planning: Description and Initial Evaluation by Radiation Oncologists

    SciTech Connect

    Pascau, Javier; Santos Miranda, Juan Antonio; Calvo, Felipe A.; Bouche, Ana; Morillo, Virgina; Gonzalez-San Segundo, Carmen; Ferrer, Carlos; Lopez Tarjuelo, Juan; and others

    2012-06-01

    Purpose: Intraoperative electron beam radiation therapy (IOERT) involves a modified strategy of conventional radiation therapy and surgery. The lack of specific planning tools limits the spread of this technique. The purpose of the present study is to describe a new simulation and planning tool and its initial evaluation by clinical users. Methods and Materials: The tool works on a preoperative computed tomography scan. A physician contours regions to be treated and protected and simulates applicator positioning, calculating isodoses and the corresponding dose-volume histograms depending on the selected electron energy. Three radiation oncologists evaluated data from 15 IOERT patients, including different tumor locations. Segmentation masks, applicator positions, and treatment parameters were compared. Results: High parameter agreement was found in the following cases: three breast and three rectal cancer, retroperitoneal sarcoma, and rectal and ovary monotopic recurrences. All radiation oncologists performed similar segmentations of tumors and high-risk areas. The average applicator position difference was 1.2 {+-} 0.95 cm. The remaining cancer sites showed higher deviations because of differences in the criteria for segmenting high-risk areas (one rectal, one pancreas) and different surgical access simulated (two rectal, one Ewing sarcoma). Conclusions: The results show that this new tool can be used to simulate IOERT cases involving different anatomic locations, and that preplanning has to be carried out with specialized surgical input.

  13. Design, construction and performance evaluation of the target tissue thickness measurement system in intraoperative radiotherapy for breast cancer

    NASA Astrophysics Data System (ADS)

    Yazdani, Mohammad Reza; Setayeshi, Saeed; Arabalibeik, Hossein; Akbari, Mohammad Esmaeil

    2017-05-01

    Intraoperative electron radiation therapy (IOERT), which uses electron beams for irradiating the target directly during the surgery, has the advantage of delivering a homogeneous dose to a controlled layer of tissue. Since the dose falls off quickly below the target thickness, the underlying normal tissues are spared. In selecting the appropriate electron energy, the accuracy of the target tissue thickness measurement is critical. In contrast to other procedures applied in IOERT, the routine measurement method is considered to be completely traditional and approximate. In this work, a novel mechanism is proposed for measuring the target tissue thickness with an acceptable level of accuracy. An electronic system has been designed and manufactured with the capability of measuring the tissue thickness based on the recorded electron density under the target. The results indicated the possibility of thickness measurement with a maximum error of 2 mm for 91.35% of data. Aside from system limitation in estimating the thickness of 5 mm phantom, for 88.94% of data, maximum error is 1 mm.

  14. Combined Modality Therapy Including Intraoperative Electron Irradiation for Locally Recurrent Colorectal Cancer

    SciTech Connect

    Haddock, Michael G.; Miller, Robert C.; Nelson, Heidi; Pemberton, John H.; Dozois, Eric J.; Alberts, Steven R.; Gunderson, Leonard L.

    2011-01-01

    Purpose: To evaluate survival, relapse patterns, and prognostic factors in patients with colorectal cancer relapse treated with curative-intent therapy, including intraoperative electron radiation therapy (IOERT). Methods and Materials: From April 1981 through January 2008, 607 patients with recurrent colorectal cancer received IOERT as a component of treatment. IOERT was preceded or followed by external radiation (median dose, 45.5 Gy) in 583 patients (96%). Resection was classified as R0 in 227 (37%), R1 in 224 (37%), and R2 in 156 (26%). The median IOERT dose was 15 Gy (range, 7.5-30 Gy). Results: Median overall survival was 36 months. Five- and 10-year survival rates were 30% and 16%, respectively. Survival estimates at 5 years were 46%, 27%, and 16% for R0, R1, and R2 resection, respectively. Multivariate analysis revealed that R0 resection, no prior chemotherapy, and more recent treatment (in the second half of the series) were associated with improved survival. The 3-year cumulative incidence of central, local, and distant relapse was 12%, 23%, and 49%, respectively. Central and local relapse were more common in previously irradiated patients and in those with subtotal resection. Toxicity Grade 3 or higher partially attributable to IOERT was observed in 66 patients (11%). Neuropathy was observed in 94 patients (15%) and was more common with IOERT doses exceeding 12.5 Gy. Conclusions: Long-term survival and disease control was achievable in patients with locally recurrent colorectal cancer. Continued evaluation of curative-intent, combined-modality therapy that includes IOERT is warranted in this high-risk population.

  15. Radiotherapy combined with surgery as treatment for advanced cervical cancer.

    PubMed

    Perches, R D; Lobaton, A T; Garcia, M C

    1983-12-01

    Experience obtained in a group of 44 patients with advanced cervical cancer is reported here. In this study, patients with residual cancer underwent laparotomy eight weeks after one or two different radiotherapy protocols. Sixty-eight percent of patients underwent radical surgery, 85% of patients pelvic exenterations, and 15% radical hysterectomies. In 27% of patients, no evidence of residual cancer was found in surgical specimens. Radical surgery was well tolerated, and one-third of patients were free of disease for one year or more. Control of disease was obtained in 50% of pelvic exenterations and in 60% of radical hysterectomies, regardless of prognosis, clinical stage or radiotherapy scheme. Although results show an improvement of up to 22% when comparing this to other more conventional treatments, we have concluded that we must obtain a wider experience in order to support our findings.

  16. Intraoperative Combined Use of Somatosensory Evoked Potential, Microvascular Doppler Sonography, and Indocyanine Green Angiography in Clipping of Intracranial Aneurysm.

    PubMed

    Li, Zhili; Zhang, Guanni; Huang, Guangfu; Wang, Zhengyu; Tan, Haibin; Liu, Jinping; Li, Aiguo

    2016-02-04

    BACKGROUND The aim of this study was to evaluate the effect of combining application of somatosensory evoked potential (SEP), microvascular Doppler sonography (MDS), and indocyanine green angiography (ICGA) in intracranial aneurysm clipping surgery. MATERIAL AND METHODS A total of 158 patients undergoing an intracranial aneurysm clipping operation were recruited. All patients were evaluated with intraoperative SEP and MDS monitoring, and 28 of them were evaluated with intraoperative combined monitoring of SEP, MDS, and ICGA. RESULTS The SEP waves dropped during temporary occlusion of arteries in 19 cases (12.0%), and returned to normal after the clips were repositioned. After aneurysms were clipped, the vortex flow signals were detected by MDS in 6 cases. The aneurysm neck remnants were detected by ICGA in 2 cases of olfactory artery (OA) and in 1 case of middle cerebral artery (MCA), which disappeared after the clips were repositioned. Postoperative CTA or DSA showed that aneurysms were clipped completely and parent arteries and perforating vessels were patent. GOS at 1 month after the surgery was good in 111 cases (70.3%), mild disability in 22 cases (13.9%), severe disability in 14 cases (8.9%), vegetative state in 5 cases (3.2%), and death in 6 cases (3.8%). CONCLUSIONS Intraoperative combining application of SEP, MDS, and ICGA can reduce brain tissue ischemia and damage and disability and mortality rate after effective clipping of intracranial aneurysms, thereby improving surgical outcomes.

  17. Intraoperative Combined Use of Somatosensory Evoked Potential, Microvascular Doppler Sonography, and Indocyanine Green Angiography in Clipping of Intracranial Aneurysm

    PubMed Central

    Li, Zhili; Zhang, Guanni; Huang, Guangfu; Wang, Zhengyu; Tan, Haibin; Liu, Jinping; Li, Aiguo

    2016-01-01

    Background The aim of this study was to evaluate the effect of combining application of somatosensory evoked potential (SEP), microvascular Doppler sonography (MDS), and indocyanine green angiography (ICGA) in intracranial aneurysm clipping surgery. Material/Methods A total of 158 patients undergoing an intracranial aneurysm clipping operation were recruited. All patients were evaluated with intraoperative SEP and MDS monitoring, and 28 of them were evaluated with intraoperative combined monitoring of SEP, MDS, and ICGA. Results The SEP waves dropped during temporary occlusion of arteries in 19 cases (12.0%), and returned to normal after the clips were repositioned. After aneurysms were clipped, the vortex flow signals were detected by MDS in 6 cases. The aneurysm neck remnants were detected by ICGA in 2 cases of olfactory artery (OA) and in 1 case of middle cerebral artery (MCA), which disappeared after the clips were repositioned. Postoperative CTA or DSA showed that aneurysms were clipped completely and parent arteries and perforating vessels were patent. GOS at 1 month after the surgery was good in 111 cases (70.3%), mild disability in 22 cases (13.9%), severe disability in 14 cases (8.9%), vegetative state in 5 cases (3.2%), and death in 6 cases (3.8%). Conclusions Intraoperative combining application of SEP, MDS, and ICGA can reduce brain tissue ischemia and damage and disability and mortality rate after effective clipping of intracranial aneurysms, thereby improving surgical outcomes. PMID:26845425

  18. Clinical trial of thalidomide combined with radiotherapy in patients with esophageal cancer

    PubMed Central

    Yu, Jing-Ping; Sun, Su-Ping; Sun, Zhi-Qiang; Ni, Xin-Chu; Wang, Jian; Li, Yi; Hu, Li-Jun; Li, Dong-Qing

    2014-01-01

    AIM: To investigate the short-term efficacy and tolerability of radiotherapy plus thalidomide in patients with esophageal cancer (EC). METHODS: Serum samples from 86 EC patients were collected before, during, and after radiotherapy, and the vascular endothelial growth factor (VEGF) level was examined by ELISA. According to the change in serum VEGF level during radiotherapy, the patients were divided into two groups: in the drug group, VEGF level was increased or remained unchanged, and thalidomide was administered up to the end of radiotherapy; in the non-drug group, VEGF level was decreased and radiotherapy was given alone. Thirty healthy volunteers served as controls. The efficacy and safety of radiotherapy plus thalidomide therapy were investigated. RESULTS: The 86 EC patients had a significantly higher level of VEGF compared with the 30 healthy controls before radiotherapy (P < 0.01), and the VEGF level was significantly correlated with primary tumor size, lymph node metastasis, histopathologic type, and clinical stage (P < 0.01). Of 83 evaluable cases, VEGF level was significantly decreased after radiotherapy in 32 patients in the drug group (P < 0.05), with an effective rate of 71.88%. The incidence of dizziness and/or burnout in the drug group and non-drug group was 62.50% and 15.69%, respectively (P = 0.000), and the incidence of somnolence was 12.50% and 0%, respectively (P = 0.019). No significant differences were observed. CONCLUSION: Thalidomide can down-regulate serum VEGF level in EC patients, and combined with radiotherapy may improve treatment outcome. Thalidomide was well tolerated by EC patients. PMID:24803825

  19. An international randomised controlled trial to compare TARGeted Intraoperative radioTherapy (TARGIT) with conventional postoperative radiotherapy after breast-conserving surgery for women with early-stage breast cancer (the TARGIT-A trial).

    PubMed

    Vaidya, Jayant S; Wenz, Frederik; Bulsara, Max; Tobias, Jeffrey S; Joseph, David J; Saunders, Christobel; Brew-Graves, Chris; Potyka, Ingrid; Morris, Stephen; Vaidya, Hrisheekesh J; Williams, Norman R; Baum, Michael

    2016-09-01

    Based on our laboratory work and clinical trials we hypothesised that radiotherapy after lumpectomy for breast cancer could be restricted to the tumour bed. In collaboration with the industry we developed a new radiotherapy device and a new surgical operation for delivering single-dose radiation to the tumour bed - the tissues at highest risk of local recurrence. We named it TARGeted Intraoperative radioTherapy (TARGIT). From 1998 we confirmed its feasibility and safety in pilot studies. To compare TARGIT within a risk-adapted approach with whole-breast external beam radiotherapy (EBRT) over several weeks. The TARGeted Intraoperative radioTherapy Alone (TARGIT-A) trial was a pragmatic, prospective, international, multicentre, non-inferiority, non-blinded, randomised (1 : 1 ratio) clinical trial. Originally, randomisation occurred before initial lumpectomy (prepathology) and, if allocated TARGIT, the patient received it during the lumpectomy. Subsequently, the postpathology stratum was added in which randomisation occurred after initial lumpectomy, allowing potentially easier logistics and a more stringent case selection, but which needed a reoperation to reopen the wound to give TARGIT as a delayed procedure. The risk-adapted approach meant that, in the experimental arm, if pre-specified unsuspected adverse factors were found postoperatively after receiving TARGIT, EBRT was recommended. Pragmatically, this reflected how TARGIT would be practised in the real world. Thirty-three centres in 11 countries. Women who were aged ≥ 45 years with unifocal invasive ductal carcinoma preferably ≤ 3.5 cm in size. TARGIT within a risk-adapted approach and whole-breast EBRT. The primary outcome measure was absolute difference in local recurrence, with a non-inferiority margin of 2.5%. Secondary outcome measures included toxicity and breast cancer-specific and non-breast-cancer mortality. In total, 3451 patients were recruited between March 2000 and June 2012. The

  20. Challenges of Using High-Dose Fractionation Radiotherapy in Combination Therapy.

    PubMed

    Yang, Ying-Chieh; Chiang, Chi-Shiun

    2016-01-01

    Radiotherapy is crucial and substantially contributes to multimodal cancer treatment. The combination of conventional fractionation radiotherapy (CFRT) and systemic therapy has been established as the standard treatment for many cancer types. With advances in linear accelerators and image-guided techniques, high-dose fractionation radiotherapy (HFRT) is increasingly introduced in cancer centers. Clinicians are currently integrating HFRT into multimodality treatment. The shift from CFRT to HFRT reveals different effects on the tumor microenvironment and responses, particularly the immune response. Furthermore, the combination of HFRT and drugs yields different results in different types of tumors or using different treatment schemes. We have reviewed clinical trials and preclinical evidence on the combination of HFRT with drugs, such as chemotherapy, targeted therapy, and immune therapy. Notably, HFRT apparently enhances tumor cell killing and antigen presentation, thus providing opportunities and challenges in treating cancer.

  1. Challenges of Using High-Dose Fractionation Radiotherapy in Combination Therapy

    PubMed Central

    Yang, Ying-Chieh; Chiang, Chi-Shiun

    2016-01-01

    Radiotherapy is crucial and substantially contributes to multimodal cancer treatment. The combination of conventional fractionation radiotherapy (CFRT) and systemic therapy has been established as the standard treatment for many cancer types. With advances in linear accelerators and image-guided techniques, high-dose fractionation radiotherapy (HFRT) is increasingly introduced in cancer centers. Clinicians are currently integrating HFRT into multimodality treatment. The shift from CFRT to HFRT reveals different effects on the tumor microenvironment and responses, particularly the immune response. Furthermore, the combination of HFRT and drugs yields different results in different types of tumors or using different treatment schemes. We have reviewed clinical trials and preclinical evidence on the combination of HFRT with drugs, such as chemotherapy, targeted therapy, and immune therapy. Notably, HFRT apparently enhances tumor cell killing and antigen presentation, thus providing opportunities and challenges in treating cancer. PMID:27446811

  2. Combined treatment with interstitial hyperthermia and interstitial radiotherapy in an animal tumor model.

    PubMed

    Ruifrok, A C; Levendag, P C; Lakeman, R F; Deurloo, I K; Visser, A G

    1991-06-01

    An interstitial hyperthermia system operating at 27 MHz has been developed at the Dr. Daniel den Hoed Cancer Center. To test this system in combination with interstitial radiotherapy and to study the interactions of interstitial radiotherapy and interstitial hyperthermia, animal experiments were performed using rhabdomyosarcoma type R1 transplanted in the flanks of female Wag/Rij rats. Using the 27 MHz system, it appeared feasible to obtain hyperthermic temperatures. In this experiment a thermal dose of 44 degrees C for 30 minutes was delivered by controlling the temperature at the periphery of the tumor to 44 degrees C. The interstitial heating applicators were inserted in four standard afterloading catheters implanted with a fixed spacing of 7 mm; the same catheters were used for the radioactive sources for interstitial radiotherapy treatment following the interstitial hyperthermia sessions. Interstitial radiotherapy was given by means of four Ir192 wires with an average activity of 4.5.10(7) Bq/cm. Minimum tumor doses of 20 to 115 Gy with a mean dose rate of 47 cGy/hour were applied. Interstitial hyperthermia alone resulted in a growth delay (GD1) of 6 +/- 2 days without significant reduction of tumor volume. The 50% tumor cure dose after interstitial radiotherapy alone was 95 +/- 9 Gy. Combination of interstitial hyperthermia and interstitial radiotherapy resulted in reduction of the 50% tumor cure dose to 48 +/- 13 Gy. The dose-effect data for cure for these modalities are compared to existing data for external irradiation and external hyperthermia in the same tumor model. It was found that the addition of hyperthermia to different modes of irradiation, that is, either to single dose or protracted radiotherapy, results in a common level of radiosensitivity through impaired repair of sublethal damage. This study demonstrates the feasibility of the 27 MHz heating system in achieving hyperthermic temperatures; in the combined modality experiments a thermal

  3. Updated Long-Term Outcomes and Prognostic Factors for Patients With Unresectable Locally Advanced Pancreatic Cancer Treated With Intraoperative Radiotherapy at the Massachusetts General Hospital, 1978 to 2010

    PubMed Central

    Cai, Sophie; Hong, Theodore S.; Goldberg, Saveli I.; Castillo, Carlos Fernandez-del; Thayer, Sarah P.; Ferrone, Cristina R.; Ryan, David P.; Blaszkowsky, Lawrence S.; Kwak, Eunice L.; Willett, Christopher G.; Lillemoe, Keith D.; Warshaw, Andrew L.; Wo, Jennifer Y.

    2014-01-01

    BACKGROUND In the current study, the authors evaluated long-term outcomes, intraoperative radiotherapy (IORT)-related toxicity, and prognostic factors for overall survival (OS) among patients with unresectable locally advanced pancreatic cancer (LAPC) who received IORT as part of their treatment at the Massachusetts General Hospital (MGH). METHODS Medical records were reviewed for 194 consecutive patients with unresectable LAPC who were treated with IORT at MGH between 1978 and 2010. OS was calculated using the Kaplan-Meier method. Prognostic factors were evaluated at the univariate level by the log-rank test and at the multivariate level by the Cox proportional hazards model. Rates of disease progression and treatment toxicity were calculated. RESULTS The 1-year, 2-year, and 3-year survival rates were 49%, 16%, and 6%, respectively. Six patients (3%) survived for > 5 years. The median OS was 12.0 months. Among 183 patients with known post-IORT disease status, the 2-year local progression-free survival and distant metastasis-free survival rates were 41% and 28%, respectively. On multivariate analysis, an IORT applicator diameter ≤ 8 cm (hazards ratio [HR], 0.51; 95% confidence interval [95% CI], 0.30–0.84 [P = .009]), a Charlson age-comorbidity index ≤3 (HR, 0.47; 95% CI, 0.31–0.73 [P = .001]), and receipt of chemotherapy (HR, 0.46; 95% CI, 0.33–0.66 [P < .001]) predicted improved OS. The median OS for patients with all 3 positive prognostic factors was 21.2 months. CONCLUSIONS Well-selected patients with LAPC with small tumors and low Charlson age-comorbidity indices can achieve good long-term survival outcomes with a treatment regimen that incorporates chemotherapy and IORT. PMID:24006012

  4. An international randomised controlled trial to compare TARGeted Intraoperative radioTherapy (TARGIT) with conventional postoperative radiotherapy after breast-conserving surgery for women with early-stage breast cancer (the TARGIT-A trial).

    PubMed Central

    Vaidya, Jayant S; Wenz, Frederik; Bulsara, Max; Tobias, Jeffrey S; Joseph, David J; Saunders, Christobel; Brew-Graves, Chris; Potyka, Ingrid; Morris, Stephen; Vaidya, Hrisheekesh J; Williams, Norman R; Baum, Michael

    2016-01-01

    BACKGROUND Based on our laboratory work and clinical trials we hypothesised that radiotherapy after lumpectomy for breast cancer could be restricted to the tumour bed. In collaboration with the industry we developed a new radiotherapy device and a new surgical operation for delivering single-dose radiation to the tumour bed - the tissues at highest risk of local recurrence. We named it TARGeted Intraoperative radioTherapy (TARGIT). From 1998 we confirmed its feasibility and safety in pilot studies. OBJECTIVE To compare TARGIT within a risk-adapted approach with whole-breast external beam radiotherapy (EBRT) over several weeks. DESIGN The TARGeted Intraoperative radioTherapy Alone (TARGIT-A) trial was a pragmatic, prospective, international, multicentre, non-inferiority, non-blinded, randomised (1 : 1 ratio) clinical trial. Originally, randomisation occurred before initial lumpectomy (prepathology) and, if allocated TARGIT, the patient received it during the lumpectomy. Subsequently, the postpathology stratum was added in which randomisation occurred after initial lumpectomy, allowing potentially easier logistics and a more stringent case selection, but which needed a reoperation to reopen the wound to give TARGIT as a delayed procedure. The risk-adapted approach meant that, in the experimental arm, if pre-specified unsuspected adverse factors were found postoperatively after receiving TARGIT, EBRT was recommended. Pragmatically, this reflected how TARGIT would be practised in the real world. SETTING Thirty-three centres in 11 countries. PARTICIPANTS Women who were aged ≥ 45 years with unifocal invasive ductal carcinoma preferably ≤ 3.5 cm in size. INTERVENTIONS TARGIT within a risk-adapted approach and whole-breast EBRT. MAIN OUTCOME MEASURES The primary outcome measure was absolute difference in local recurrence, with a non-inferiority margin of 2.5%. Secondary outcome measures included toxicity and breast cancer-specific and non

  5. Hypofractionated stereotactic radiotherapy combined with topotecan in recurrent malignant glioma

    SciTech Connect

    Wurm, Reinhard E. . E-mail: Reinhard.Wurm@charite.de; Kuczer, David A.; Schlenger, Lorenz; Matnjani, Gesa; Scheffler, Dirk; Cosgrove, Vivian P.; Ahlswede, Julia; Woiciechowsky, Christian; Budach, Volker

    2006-11-15

    Purpose: To assess hypofractionated stereotactic radiotherapy (H-SRT) with concurrent topotecan in patients with recurrent malignant glioma. Methods and Materials: Between February 1998 and December 2001, 25 patients with recurrent malignant glioma were treated in a phase I-II study (8 females and 17 males; median age, 45 years; range, 11-66 years; median Karnofsky performance status, 80%, range, 50-100%; median Mini Mental Standard Examination score, 25 points; range, 10-30 points). Of the 25 patients, 20% had World Health Organization Grade III and 80% World Health Organization Grade IV glioma. All patients had been treated previously by external beam radiotherapy with 54.4 Gy in 34 fractions twice daily, at least 6 h apart, within 3.5 weeks or 60 Gy in 30 fractions within 6 weeks. In addition, 84% had already received at least one chemotherapy regimen for recurrence. The median H-SRT dose at the 80% isodose was 25 Gy, and the maximal dose was 30 Gy delivered in five to six fractions on consecutive days. Topotecan (1.1 mg/m{sup 2}/d) was given as a continuous i.v. infusion during H-SRT. Depending on the toxicity and compliance, patients received an additional 48 topotecan courses. Results: For all patients, the actuarial median progression-free survival was 10.5 months (range, 1.4-47.8 months), the median functional survival was 12.6 months (range, 1.6-49.5 months), and the median overall survival was 14.5 months (range, 3-56.4 months). Twelve percent of patients developed presumed adverse radiation effects (Radiation Therapy Oncology Group Grade 2). According to the Common Toxicity Criteria, version 2.0, no topotecan-related Grade 4 toxicity was noted. Grade 3 neutropenia was documented after 14 and Grade 3 thrombopenia after 12 courses. Conclusion: H-SRT with topotecan is feasible and well-tolerated in patients with recurrent high-grade glioma and results in similar survival compared with other repeat treatment modalities.

  6. Mixed beam radiotherapy and combination chemotherapy in localized pancreatic adenocarcinoma - preliminary results

    SciTech Connect

    Bukowski, R.M.; Gahbauer, R.; Rodriquez-Antunez, A.; Hermann, R.

    1982-07-01

    A pilot study of mixed beam radiotherapy (fast neutrons alternating with photons) followed by combination chemotherapy with SMF (streptozotocin, 5-flouoruracil, mitomycin C) in localized pancreatic cancer was performed. Thirteen patients were treated and a median survival of 10.0 months was noted (range 5-30+). Toxicity was mild to moderate. Further studies of radiation and chemotherapy are indicated.

  7. Combined preoperative neoadjuvant radiotherapy and chemotherapy for anal and rectal cancer

    SciTech Connect

    Smith, D.E.; Muff, N.S.; Shetabi, H.

    1986-05-01

    Neoadjuvant therapy combining 5-fluorouracil, mitomycin C, and moderate-dose radiotherapy was given preoperatively to 29 patients with adenocarcinoma of the rectum, 3 patients with squamous cell cancer, and 1 patient with basaloid carcinoma of the anus. Significant downstaging, and even eradication, of these lesions was realized in a high percentage of cases. Population-based data for the period of 1979 to 1984 which encompasses the time of our study indicate the survival of those treated by the neoadjuvant therapy was superior to that of patients treated by surgery alone or by surgery followed by radiotherapy. In general, patients with the poorest clinical presentation had been referred for this therapy.

  8. Combining targeted agents and hypo- and hyper-fractionated radiotherapy in NSCLC

    PubMed Central

    Popat, Sanjay

    2014-01-01

    Radical radiotherapy remains the cornerstone of treatment for patients with unresectable locally advanced non small cell lung cancer (NSCLC) either as single modality treatment for poor performance status patients or with sequential or concomitant chemotherapy for good performance status patients. Advances in understanding of tumour molecular biology, targeted drug development and experiences of novel agents in the advanced disease setting have brought targeted agents into the NSCLC clinic. In parallel experience using modified accelerated fractionation schedules in locally advanced disease have demonstrated improved outcomes compared to conventional fractionation in the single modality and sequential chemo-radiotherapy settings. Early studies of targeted agents combined with (chemo-) radiotherapy in locally advanced disease in different clinical settings are discussed below and important areas for future studies are high-lighted. PMID:24688780

  9. SU-E-T-412: Evaluation of Tungsten-Based Functional Paper for Attenuation Device in Intraoperative Radiotherapy for Breast Cancer

    SciTech Connect

    Kamomae, T; Monzen, H; Okudaira, K; Miyake, Y; Oguchi, H; Komori, M; Kawamura, M; Itoh, Y; Kikumori, T; Naganawa, S

    2015-06-15

    Purpose: Intraoperative radiotherapy (IORT) with an electron beam is one of the accelerated partial breast irradiation methods that have recently been used in early-stage breast cancer. A protective acrylic resin-copper disk is inserted between the breast tissue and the pectoralis muscle to minimize the dose received by the posterior structures. However, a problem with this protective disk is that the surgical incision must be larger than the field size because the disk is manufactured from stiff and unyielding materials. The purpose of this study was to assess the applicability of a new tungsten-based functional paper (TFP) as an alternative to the existing protective disk in IORT. Methods: The newly introduced TFP (Toppan Printing Co., Ltd., Tokyo, JP) is anticipated to become a useful device that is lead-free, light, flexible, and easily processed. The radiation shielding performance of TFP was verified by experimental measurements and Monte Carlo (MC) simulations using PHITS code. The doses transmitted through the protective disk or TFP were measured on a Mobetron mobile accelerator. The same geometries were then reproduced, and the dose distributions were simulated by the MC method. Results: The percentages of transmitted dose relative to the absence of the existing protective disk were lower than 2% in both the measurements and MC simulations. In the experimental measurements, the percentages of transmitted dose for a 9 MeV electron beam were 48.1, 2.3, and 0.6% with TFP thicknesses of 1.9, 3.7, and 7.4 mm, respectively. The percentages for a 12 MeV were 76.0, 49.3, 20.0, and 5.5% with TFP thicknesses of 1.9, 3.7, 7.4, and 14.8 mm, respectively. The results of the MC simulation showed a slight dose increase at the incident surface of the TFP caused by backscattered radiation. Conclusion: The results indicate that a small-incision procedure may be possible by the use of TFP.

  10. The benefit of adjuvant chemotherapy combined with postoperative radiotherapy for endometrial cancer: a meta-analysis.

    PubMed

    Park, Hyun Jong; Nam, Eun Ji; Kim, Sunghoon; Kim, Yong Bae; Kim, Young Tae

    2013-09-01

    The objective of our study was to determine whether adjuvant chemotherapy combined with postoperative radiotherapy would have benefits for the disease-free survival and overall survival in patients with high-risk endometrial cancer. Electronic searches for studies of adjuvant chemotherapy combined with postoperative radiotherapy in endometrial cancer patients between March 1971 and March 2012 were made on MEDLINE, SCOPUS, and the Cochrane library. Articles with more than 4 stars on the Newcastle-Ottawa scale or a score of more than 4 on the modified Jadad scale were included. A meta-analysis was performed, and pooled hazard ratios (HR) of progression-free survival (PFS) and overall survival (OS) between patients whose adjuvant chemotherapy was combined with radiotherapy (the CTx+RTx group) and patients with adjuvant radiotherapy only (the RTx group) were derived from the fixed effect model or random effect model. Three observational studies and 3 randomized clinical trials (RCTs) were included in the final analysis. Subgroup analysis for FIGO stage showed that the CTx+RTx group had a more significant survival benefit compared to that of the RTx group in advanced stage endometrial cancer (OS HR 0.53, 95% CI 0.36-0.80; PFS HR 0.54, 95% CI 0.37-0.77), but no significant benefit in early stage endometrial cancer (OS HR 0.96, 95% CI 0.70-1.32; PFS HR 1.00, 95% CI 0.39-2.58). This meta-analysis suggests that adjuvant chemotherapy combined with postoperative radiotherapy could probably reduce disease progression and overall death in patients with advanced-stage disease. In order to examine whether the multimodal treatment has benefit in high-risk endometrial cancer, we need further large-scale RCTs. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Surgical subinguinal approach to varicocele combined with antegrade intraoperative sclerosis of venous vessels.

    PubMed

    Colpi, Giovanni Maria; Carmignani, Luca; Bozzini, Giorgio; Picozzi, Stefano

    2012-09-01

    Varicocele is treated by different surgical techniques, none of which is yet acknowledged as the "gold standard." Some of these techniques, especially microsurgical techniques, are very time consuming and thus expensive, and the treatment of varicocele still causes some complications and recurrences. Marmar and Kim's technique presents some indisputable advantages: it allows the preservation of the arteries and seems to offer the highest percentage of success and lowest number of complications. The authors modified and simplified the microsurgical technique of Marmar and Kim, using a subinguinal approach with intraoperative antegrade sclerotherapy of dilated veins. After the cord has been clamped, 1.5 to 3 mL of 3% aetoxisclerol mixed with 0.5 mL of air is injected. Commonly, minor complications can occur. The most common complication is transient penile lymphangitis, the cause of which is unclear. As the procedure allows selective sparing of the lymphatic vessels, it avoids hydrocele due to the performed procedure.

  12. Phase I/II Clinical Trial of Carbon Ion Radiotherapy for Malignant Gliomas: Combined X-Ray Radiotherapy, Chemotherapy, and Carbon Ion Radiotherapy

    SciTech Connect

    Mizoe, Jun-Etsu Tsujii, Hirohiko; Hasegawa, Azusa D.D.S.; Yanagi, Tsuyoshi; Takagi, Ryo D.D.S.; Kamada, Tadashi; Tsuji, Hiroshi; Takakura, Kintomo

    2007-10-01

    Purpose: To report the results of a Phase I/II clinical trial for patients with malignant gliomas, treated with combined X-ray radiotherapy (XRT), chemotherapy, and carbon ion radiotherapy (CRT). Methods and Materials: Between October 1994 and February 2002, 48 patients with histologically confirmed malignant gliomas (16 anaplastic astrocytoma (AA) and 32 glioblastoma multiforme (GBM) were enrolled in a Phase I/II clinical study. The treatment involved the application of 50 Gy/25 fractions/5 weeks of XRT, followed by CRT at 8 fractions/2 weeks. Nimustine hydrochloride (ACNU) were administered at a dose of 100 mg/m{sup 2} concurrently in weeks 1, 4, or 5 of XRT. The carbon ion dose was increased from 16.8 to 24.8 Gray equivalent (GyE) in 10% incremental steps (16.8, 18.4, 20.0, 22.4, and 24.8 GyE, respectively). Results: There was no Grade 3 or higher acute reaction in the brain. The late reactions included four cases of Grade 2 brain morbidity and four cases of Grade 2 brain reaction among 48 cases. The median survival time (MST) of AA patients was 35 months and that of GBM patients 17 months (p = 0.0035). The median progression-free survival and MST of GBM showed 4 and 7 months for the low-dose group, 7 and 19 months for the middle-dose group, and 14 and 26 months for the high-dose group. Conclusion: The results of combined therapy using XRT, ACNU chemotherapy, and CRT showed the potential efficacy of CRT for malignant gliomas in terms of the improved survival rate in those patients who received higher carbon doses.

  13. BRAF inhibitors and radiotherapy for melanoma brain metastases: potential advantages and disadvantages of combination therapy

    PubMed Central

    Chowdhary, Mudit; Patel, Kirtesh R; Danish, Hasan H; Lawson, David H; Khan, Mohammad K

    2016-01-01

    Melanoma is an aggressive malignancy that frequently spreads to the brain, resulting in rapid deterioration in both quality and quantity of life. Historically, treatment options for melanoma brain metastases (MBM) have predominantly consisted of surgery and radiotherapy. While these options can help provide local control, the majority of patients still develop intracranial progression. Indeed, novel therapeutic options, including molecularly targeted agents and immunotherapy, have improved outcomes and are now changing the role of radiotherapy. Up to 50% of melanomas contain an activating BRAF mutation, resulting in hyperactive cellular proliferation and survival. Drugs that target BRAF have been introduced for the treatment of metastatic melanoma and offer hope in improving disease outcomes; however, many of these trials either excluded or had a limited amount of patients with MBM. Recent studies have revealed that melanoma cell lines become more radiosensitive following BRAF inhibition, thus providing a potential synergistic mechanism when combining BRAF inhibitor (BRAFi) and radiotherapy. However, neurotoxicity concerns also exist with this combination. This article reviews the efficacy and limitations of BRAFi therapy for MBM, describes current evidence for combining BRAFis with radiation, discusses the rationale and evidence for combination modalities, and highlights emerging clinical trials specifically investigating this combination in MBM. PMID:28003758

  14. Combination ibandronate and radiotherapy for the treatment of bone metastases: Clinical evaluation and radiologic assessment

    SciTech Connect

    Vassiliou, Vassilios; Kalogeropoulou, Christine; Christopoulos, Christos; Solomou, Ekaterini; Leotsinides, Michael; Kardamakis, Dimitrios . E-mail: kardim@med.upatras.gr

    2007-01-01

    Purpose: Ibandronate is a single-nitrogen, noncyclic bisphosphonate with proven efficacy for reducing metastatic bone pain. In this study, we assessed the palliative effects of combined ibandronate and radiotherapy. Methods and Materials: Forty-five patients with bone metastases from various solid tumors received external-beam radiotherapy, 30-40 Gy over 3-4.5, weeks combined with 10 cycles of monthly intravenous ibandronate, 6 mg. Results: After combined therapy, mean bone pain scores (graded from 0 to 10) were reduced from 6.3 at baseline to 0.8 after 3 months, with further reductions at later time points (all p < 0.001). Opioid use decreased from 84% of patients at baseline (38/45) to 24% (11/45) at 3 months, with further subsequent reductions (all p < 0.001). Mean performance status and functioning scores also significantly improved. Bone density (assessed by computed tomography scan) increased by 20% vs. baseline at 3 months, 46% at 6 months, and 73% at 10 months (all p < 0.001). Lesion improvement was also demonstrated by magnetic resonance imaging. Treatment was well tolerated with no renal toxicity. Conclusions: In this pilot study, combined radiotherapy and ibandronate provided substantial bone pain relief and increased bone density. Computed tomography-based or magnetic resonance imaging-based evaluations offer objective methods for assessing therapeutic outcomes.

  15. The rationale of combined radiotherapy and chemotherapy - Joint action of Castor and Pollux.

    PubMed

    Brunner, Thomas B

    2016-08-01

    This article aims to review the rationale behind the combination of radiotherapy and chemotherapy. Theoretical concepts describing the principles of the joint effects of chemoradiotherapy are reviewed. Preclinical and clinical evidence are collected and summarised demonstrating the co-operation between the two modalities which form the mainstay of the treatment of most solid tumours. Initially, the evolution of chemoradiotherapy was mostly empirically driven which is true for both, the early studies and the experimental investigations, rather than relying on scientific rationale. To date, the revised Steel's model proposes five mechanisms, spatial cooperation, cytotoxic enhancement, biological co-operation, temporary modulation and normal tissue protection to describe the interaction between radiotherapy and chemotherapy. Chemoradiotherapy has become the standard modality for most patients with locally advanced solid tumours due to better control of loco-regional disease and prolonged survival. Gradually, molecular prediction of efficacy is integrated such as MGMT status for combining temozolomide with radiotherapy in glioblastoma. As molecular targeted drugs are ready to be taken into triple combinations with chemoradiotherapy it is crucial to have a good understanding of the mechanisms of chemoradiotherapy for the rational development of future combinations.

  16. [Combined therapy and radiotherapy in stage-II Hodgkin disease].

    PubMed

    Il'in, N V; Vinogradova, Iu N; Nikolaeva, E N; Ivanova, E I; Shenderova, I A; Smirnova, E V; Izomov, B M; Trishkina, E V; Kritskaia, A V; Leenman, E E

    2010-01-01

    The aim of the study was to raise efficacy of combined treatment of stage II Hodgkin's disease by optimization of fractionation and volume of irradiation. It included 179 patients with involvement of supradiaphragmatic lymph nodes treated in 1986-2006. It was found that multi-fractionation was followed by lower frequency of relapse as compared with standard regimens as well as rates of early ones. The most efficient dosage was 30-36 Gy as far as frequency, term of relapse occurrence and recurrence-free survival were concerned.

  17. Surgical benefits of combined awake craniotomy and intraoperative magnetic resonance imaging for gliomas associated with eloquent areas.

    PubMed

    Motomura, Kazuya; Natsume, Atsushi; Iijima, Kentaro; Kuramitsu, Shunichiro; Fujii, Masazumi; Yamamoto, Takashi; Maesawa, Satoshi; Sugiura, Junko; Wakabayashi, Toshihiko

    2017-01-06

    OBJECTIVE Maximum extent of resection (EOR) for lower-grade and high-grade gliomas can increase survival rates of patients. However, these infiltrative gliomas are often observed near or within eloquent regions of the brain. Awake surgery is of known benefit for the treatment of gliomas associated with eloquent regions in that brain function can be preserved. On the other hand, intraoperative MRI (iMRI) has been successfully used to maximize the resection of tumors, which can detect small amounts of residual tumors. Therefore, the authors assessed the value of combining awake craniotomy and iMRI for the resection of brain tumors in eloquent areas of the brain. METHODS The authors retrospectively reviewed the records of 33 consecutive patients with glial tumors in the eloquent brain areas who underwent awake surgery using iMRI. Volumetric analysis of MRI studies was performed. The pre-, intra-, and postoperative tumor volumes were measured in all cases using MRI studies obtained before, during, and after tumor resection. RESULTS Intraoperative MRI was performed to check for the presence of residual tumor during awake surgery in a total of 25 patients. Initial iMRI confirmed no further tumor resection in 9 patients (36%) because all observable tumors had already been removed. In contrast, intraoperative confirmation of residual tumor during awake surgery led to further tumor resection in 16 cases (64%) and eventually an EOR of more than 90% in 8 of 16 cases (50%). Furthermore, EOR benefiting from iMRI by more than 15% was found in 7 of 16 cases (43.8%). Interestingly, the increase in EOR as a result of iMRI for tumors associated mainly with the insular lobe was significantly greater, at 15.1%, than it was for the other tumors, which was 8.0% (p = 0.001). CONCLUSIONS This study revealed that combining awake surgery with iMRI was associated with a favorable surgical outcome for intrinsic brain tumors associated with eloquent areas. In particular, these benefits were

  18. Usefulness of HIF-1 Imaging for Determining Optimal Timing of Combining Bevacizumab and Radiotherapy

    SciTech Connect

    Ou Guangfei; Itasaka, Satoshi Zeng Lihua; Shibuya, Keiko; Yi Junlin; Harada, Hiroshi; Hiraoka, Masahiro

    2009-10-01

    Purpose: To study the relationship between the hypoxia-inducible factor-1 (HIF-1) activity level after bevacizumab treatment and the antitumor effects of radiation to determine the optimal combination schedule of bevacizumab with radiotherapy. Methods and Materials: The tumor hypoxia changes induced after bevacizumab treatment were evaluated using optical imaging with a HIF-1-dependent reporter gene using the NCI-H441 human lung adenocarcinoma xenograft model. The combined effects of bevacizumab with radiation were evaluated according to the timing of combination. Results: In vivo imaging experiments revealed that bevacizumab treatment had little effect on intratumoral HIF-1 activity 1 day after bevacizumab treatment, but it dramatically upregulated it thereafter through increases in the hypoxic fractions of the tumors. When bevacizumab treatment was combined with 14 Gy of radiation at 24 h or 72 h after bevacizumab treatment, the former combination delayed, but the latter combination accelerated, tumor growth compared with irradiation alone. Conclusion: These data suggest that an optimal window exists for combining bevacizumab with radiotherapy that determines whether the combination will be beneficial and that the imaging of HIF-1 activity would be useful in determining this window.

  19. 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

  20. Inhibitory effect of endostar in combination with radiotherapy in a mouse model of human CNE2 nasopharyngeal carcinoma.

    PubMed

    Zhou, Ning; Hu, Guangyuan; Mei, Qi; Qiu, Hong; Long, Guoxian; Chen, Chunli; Guoqing, Hu

    2011-02-01

    The inhibitory effects of Endostar in combination with radiotherapy in BALB/c nude mice model of human CNE2 nasopharyngeal carcinoma and the mechanism were investigated. In nude mice model of CNE2 nasopharyngeal carcinoma, the inhibitory rate and the sensitizing enhancement ratio (E/O) were calculated according to the tumor volumes in different groups. The expression of microvascular density (MVD) in tumor tissues was examined by using immunohistochemistry staining. The transcription of VEGF gene was detected by using RT-PCR. The inhibitory rate in Endostar+ radiotherapy group was higher than in other groups. In Endostar+radiotherapy group, the tumor volume was significantly decreased and the E/O ratio was 2.335, suggesting that Endostar could be a radiosensitizer. The expression of MVD of tumor tissues in Endostar+radiotherapy group was reduced significantly. The expression of the MVD in treatment groups was significantly different from that in control group (P<0.05). Compared to other groups, VEGF mRNA expression in Endostar+radiotherapy group was decreased remarkably. Endostar in combination with radiotherapy significantly inhibited the growth of CNE2 tumor. The combination therapy decreased the expression of VEGF, and inhibited tumor angiogenesis and proliferation. When combined with radiotherapy, Endostar acted as a radiosensitizer.

  1. Combination of immune checkpoint inhibitors and radiotherapy: Review of the literature.

    PubMed

    Sindoni, Alessandro; Minutoli, Fabio; Ascenti, Giorgio; Pergolizzi, Stefano

    2017-05-01

    Literature experiences in cancer treatment usually deal with either targeting the tumour cell or the immune system, which often fail to reach the curative purposes in many solid tumours. On the other hand, one mechanism of radiation-induced tumour control is the activation of the adaptive immune system by tumour antigen release following radiotherapy. So, combining radiation therapy with immune checkpoint blockade treatment at the same time may represent a way to stimulate the adaptive immune system, with further amplification of immune responses reached through systemic immune checkpoint blockade. Until now, only few studies deal with the association of immune checkpoint blockade treatment and radiotherapy. In this review, we evaluate this association, highlighting this possibility as a new strategy to improve outcome in cancer patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Pilot studies of superfractionated radiotherapy and combination chemotherapy in limited oat cell carcinoma of the bronchus

    SciTech Connect

    Hodson, D.I.; Malaker, K.; Meikle, A.L.; Levitt, M.

    1984-10-01

    There are sound radiobiologic and suggestive clinical rationale for superfractionating the radiotherapeutic regimens employed for the therapy of rapidly growing malignancies. Oat cell carcinoma of the bronchus is such a tumor. The authors report their experience combining aggressive systemic combination chemotherapy with supperfractionated radiotherapy for the treatment of limited oat cell carcinoma of the bronchus. Overall, patient tolerance was satisfactory and a complete remission rate of 74% was achieved. It remains to be proven, in a prospective randomized fashion, whether this approach is superior to current conventional management.

  3. Referee: hyperthermia alone or combined with cisplatin in addition to radiotherapy for advanced uterine cervical cancer.

    PubMed

    Dahl, O; Mella, O

    2002-01-01

    There are two evidence based therapeutic options for locally advanced cervical cancer: Radiotherapy and concurrent chemotherapy (cisplatin alone or combined with other drugs) or radiation and hyperthermia, documented in randomised trials. The weight of evidence is less for the most advanced stages. Combination of all three options are currently tested in several centres with good clinical response and acceptable toxicity. Based on a pragmatic approach we propose to proceed with a trial selecting cisplatin concurrent with radiation therapy as the standard arm to be compared with the same regimen with the addition of hyperthermia once a week.

  4. Nimotuzumab in combination with radiotherapy in high grade glioma patients: a single institution experience.

    PubMed

    Solomon, Maria Teresa; Miranda, Nederlay; Jorrín, Eugenia; Chon, Ivonne; Marinello, Jorge Juan; Alert, José; Lorenzo-Luaces, Patricia; Crombet, Tania

    2014-05-01

    Nimotuzumab, a humanized antibody targeting epidermal growth factor receptor, has potent anti-proliferative, anti-angiogenic, and pro-apoptotic effects in vitro and in vivo. It also reduces the number of radio-resistant CD133(+) glioma stem cells. The antibody has been extensively evaluated in patients with advanced head and neck, glioma, lung, esophageal, pancreatic, and gastric cancer. In this single institution experience, 35 patients with anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) were treated with irradiation and 200 mg doses of nimotuzumab. The first 6 doses were administered weekly, together with radiotherapy, and then treatment continued every 21 days until 1 year. The median number of doses was 12, and the median cumulative dose was thus 2400 mg of nimotuzumab. The most frequent treatment-related toxicities were increase in liver function tests, fever, nausea, anorexia, asthenia, dizziness, and tremors. These adverse reactions were classified as mild and moderate. The median survival time was 12.4 mo or 27.0 mo for patients with GBM or AA patients, respectively, who received curative-intent radiotherapy in combination with the antibody. The survival time of a matched population treated at the same hospital with irradiation alone was decreased (median 8.0 and 12.2 mo for GBM and AA patients, respectively) compared with that of the patients who received nimotuzumab and curative-intent radiotherapy. We have thus confirmed that nimotuzumab is a very well-tolerated drug, lacking cumulative toxicity after maintenance doses. This study, in a poor prognosis population, validates the previous data of survival gain after combining nimotuzumab and radiotherapy, in newly diagnosed high-grade glioma patients.

  5. Cytotoxic Effect of Erythroxylum suberosum Combined with Radiotherapy in Head and Neck Cancer Cell Lines.

    PubMed

    Macedo, Taysa B C; Elias, Silvia T; Torres, Hianne M; Yamamoto-Silva, Fernanda Paula; Silveira, Dâmaris; Magalhães, Pérola O; Lofrano-Porto, Adriana; Guerra, Eliete N S; Silva, Maria Alves G

    2016-01-01

    The mouth and oropharynx cancer is the 6th most common type of cancer in the world. The treatment may involve surgery, chemotherapy and radiotherapy. More than 50% of drugs against cancer were isolated from natural sources, such as Catharanthus roseus and epipodophyllotoxin, isolated from Podophyllum. The biggest challenge is to maximize the control of the disease, while minimizing morbidity and toxicity to the surrounding normal tissues. The Erythroxylum suberosum is a common plant in the Brazilian Cerrado biome and is popularly known as "cabelo-de-negro". The objective of this study was to evaluate the cytotoxic activity of Erythroxylum suberosum plant extracts of the Brazilian Cerrado biome associated with radiotherapy in human cell lines of oral and hypopharynx carcinomas. Cells were treated with aqueous, ethanolic and hexanic extracts of Erythroxylum suberosum and irradiated at 4 Gy, 6 Gy and 8 Gy. Cytotoxicity was evaluated by MTT assay and the absorbance was measured at 570 nm in a Beckman Counter reader. Cisplatin, standard chemotherapy, was used as positive control. The use of Erythroxylum suberosum extracts showed a possible radiosensitizing effect in vitro for head and neck cancer. The cytotoxicity effect in the cell lines was not selective and it is very similar to the effect of standard chemotherapy. The aqueous extract of Erythroxylum suberosum, combined with radiotherapy was the most cytotoxic extract to oral and hypopharynx carcinomas.

  6. Combination epidermal growth factor receptor inhibition and radical radiotherapy for NSCLC.

    PubMed

    Rogers, Susanne J; Harrington, Kevin J; Eccles, Suzanne A; Nutting, Christopher M

    2004-08-01

    Non-small cell lung cancer (NSCLC) remains the most common cause of cancer-related death in the developed world. Despite advances in therapy with conventional modalities, over 85% of patients will die from their disease within 5 years of diagnosis. For patients with inoperable lung cancer, the addition of chemotherapy to radical radiotherapy yields a small but significant 10% survival benefit at 3 years. However, the systemic toxicity of chemotherapy is common and may be severe. Over the past 20 years, dramatic improvements in our understanding of the molecular etiology of cancer have enabled the development of novel targeted therapies. Overexpression of the epidermal growth factor receptor (EGFR) in lung cancer correlates with an aggressive disease course and poor tumor response to radiotherapy. Strategies to inhibit this molecular switch have become a focus for drug development. Preclinical efficacy has been repeatedly demonstrated with anti-EGFR monoclonal antibodies and small molecule tyrosine kinase inhibitors, and responses have been documented in the clinic with acceptable toxicity. Phase III trials combining EGFR tyrosine kinase inhibitors with radical chemoradiation are recruiting at present. This review addresses the current challenges of discovering how best to use these new anticancer therapies, with particular emphasis on the enhancement of existing therapeutic strategies such as radical radiotherapy, factors relating to patient selection and prediction of clinical response.

  7. Radiotherapy combined with TLR7/8 activation induces strong immune responses against gastrointestinal tumors

    PubMed Central

    Tietz, Alexandra; Rahbari, Nuh N.; Bork, Ulrich; Schmidt, Thomas; Kahlert, Christoph; Haberkorn, Uwe; Tomai, Mark A.; Lipson, Kenneth E.; Carretero, Rafael; Weitz, Jürgen; Koch, Moritz; Huber, Peter E.

    2015-01-01

    In addition to local cytotoxic activity, radiotherapy may also elicit local and systemic antitumor immunity, which may be augmented by immunotherapeutic agents including Toll-like receptor (TLR) 7/8 agonists. Here, we investigated the ability of 3M-011 (854A), a TLR7/8 agonist, to boost the antigen-presenting activity of dendritic cells (DC) as an adjuvant to radiotherapy. The combined treatment induced marked local and systemic responses in subcutaneous and orthotopic mouse models of colorectal and pancreatic cancer. In vitro cytotoxicity assays as well as in vivo depletion experiments with monoclonal antibodies identified NK and CD8 T cells as the cell populations mediating the cytotoxic effects of the treatment, while in vivo depletion of CD11c+ dendritic cells (DC) in CD11c-DTR transgenic mice revealed DC as the pivotal immune hub in this setting. The specificity of the immune reaction was confirmed by ELISPOT assays. TLR7/8 agonists therefore seem to be potent adjuvants to radiotherapy, inducing strong local and profound systemic immune responses to tumor antigens released by conventional therapy. PMID:25609199

  8. [Laryngeal conservative surgery in patients candidates for combined treatment with chemo-radiotherapy].

    PubMed

    Gallegos-Hernández, José Francisco; Cruz-Esquivel, Iván; Ortiz-Maldonado, Alma Lilia; Minauro-Muñoz, Gerardo Gabriel; Arias-Ceballos, Héctor; Pichardo-Romero, Pablo

    2016-01-01

    The standard of care for advanced-stage laryngeal cancer is combined treatment (chemo-radiotherapy). However, the complications with this treatment are not few, mainly in swallowing. Conservative laryngeal surgery remains an effective alternative for cancer control without the complications of chemo-radiotherapy. Retrospective study was conducted on patients with laryngeal cancer cT3, cN0 with paraglottic infiltration, fixation of the vocal cord, minimal invasion of the hyo-thyroepiglottic space, but with normal arytenoid mobility and no sub-glottic extension, were treated with subtotal supracricoid laryngectomy. Complications, sequels of treatment, and local recurrence were evaluated. Bronchial aspiration was studied with radioactive swallow. There were 25 patients, 22 with negative surgical margins, one had tumour contact with the surgical margins, and 2 were positive. Two patients received postoperative radiotherapy. The mean decannulation was 15 days and removal of nasogastric tube 25 days. During the mean follow-up of 26 months, none of the patients had tumour recurrence or required conversion to total laryngectomy. In all patients swallowing has been normal and none required permanent or temporary tracheotomy or definitive gastrostomy. The voice is considered intelligible in all patients. Radioactive swallow showed aspiration in 15/25 patients, with none being clinically relevant. There were postoperative complications in 5 patients, and 4 patients required re-intervention but no conversion to total laryngectomy. Conservative surgery is an effective surgical-alternative to chemo-radiotherapy in patients with locally advanced laryngeal cancer, providing oncological control, acceptable complications and minimal sequels. Although most patients have aspiration, this does not affect functional status. Copyright © 2015. Published by Masson Doyma México S.A.

  9. 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.

  10. Therapeutic and scintigraphic applications of polymeric micelles: combination of chemotherapy and radiotherapy in hepatocellular carcinoma

    PubMed Central

    Shih, Ying-Hsia; Peng, Cheng-Liang; Chiang, Ping-Fang; Lin, Wuu-Jyh; Luo, Tsai-Yueh; Shieh, Ming-Jium

    2015-01-01

    This study evaluated a multifunctional micelle simultaneously loaded with doxorubicin (Dox) and labeled with radionuclide rhenium-188 (188Re) as a combined radiotherapy and chemotherapy treatment for hepatocellular carcinoma. We investigated the single photon emission computed tomography, biodistribution, antitumor efficacy, and pathology of 188Re-Dox micelles in a murine orthotopic luciferase-transfected BNL tumor cells hepatocellular carcinoma model. The single photon emission computed tomography and computed tomography images showed high radioactivity in the liver and tumor, which was in agreement with the biodistribution measured by γ-counting. In vivo bioluminescence images showed the smallest size tumor (P<0.05) in mice treated with the combined micelles throughout the experimental period. In addition, the combined 188Re-Dox micelles group had significantly longer survival compared with the control, 188ReO4 alone (P<0.005), and Dox micelles alone (P<0.01) groups. Pathohistological analysis revealed that tumors treated with 188Re-Dox micelles had more necrotic features and decreased cell proliferation. Therefore, 188Re-Dox micelles may enable combined radiotherapy and chemotherapy to maximize the effectiveness of treatment for hepatocellular carcinoma. PMID:26719687

  11. Optimization of combination therapy of arsenic trioxide and fractionated radiotherapy for malignant glioma

    SciTech Connect

    Ning Shoucheng; Knox, Susan J. . E-mail: sknox@stanford.edu

    2006-06-01

    Purpose: The primary objective was to optimize the combined treatment regimen using arsenic trioxide (ATO) and fractionated radiotherapy for the treatment of malignant glioma. Methods and Materials: Nude mice with human glioma xenograft tumors were treated with fractionated local tumor radiation of 250 cGy/fraction/day and 5 mg/kg ATO for 5-10 days. Results: Time course experiments demonstrated that maximal tumor growth delay occurred when ATO was administered between 0 and 4 h after radiation. The combination treatment of ATO and radiation synergistically inhibited tumor growth and produced a tumor growth delay time of 13.2 days, compared with 1.4 days and 6.5 days for ATO and radiation alone (p < 0.01), respectively. The use of concurrent therapy of radiation and ATO initially, followed by ATO as maintenance therapy, was superior to the use of preloading with ATO before combined therapy and produced a tumor growth delay time of 22.7 days as compared with 11.7 days for the ATO preloading regimen (p < 0.01). The maintenance dose of ATO after concurrent therapy was effective and important for continued inhibition of tumor growth. Conclusions: The combined use of fractionated radiation and ATO is effective for the treatment of glioma xenograft tumors. ATO was most effective when administered 0-4 h after radiation without pretreatment with ATO. These results have important implications for the optimization of treatment regimen using ATO and fractionated radiotherapy for the treatment of brain tumors.

  12. Cisplatin combined with hyperthermia kills HepG2 cells in intraoperative blood salvage but preserves the function of erythrocytes.

    PubMed

    Yang, Jin-ting; Tang, Li-hui; Liu, Yun-qing; Wang, Yin; Wang, Lie-ju; Zhang, Feng-jiang; Yan, Min

    2015-05-01

    The safe use of intraoperative blood salvage (IBS) in cancer surgery remains controversial. Here, we investigated the killing effect of cisplatin combined with hyperthermia on human hepatocarcinoma (HepG2) cells and erythrocytes from IBS in vitro. HepG2 cells were mixed with concentrated erythrocytes and pretreated with cisplatin (50, 100, and 200 μg/ml) alone at 37 °C for 60 min and cisplatin (25, 50, 100, and 200 μg/ml) combined with hyperthermia at 42 °C for 60 min. After pretreatment, the cell viability, colony formation and DNA metabolism in HepG2 and the Na(+)-K(+)-ATPase activity, 2,3-diphosphoglycerate (2,3-DPG) concentration, free hemoglobin (Hb) level, osmotic fragility, membrane phosphatidylserine externalization, and blood gas variables in erythrocytes were determined. Pretreatment with cisplatin (50, 100, and 200 μg/ml) combined with hyperthermia (42 °C) for 60 min significantly decreased HepG2 cell viability, and completely inhibited colony formation and DNA metabolism when the HepG2 cell concentration was 5×10(4) ml(-1) in the erythrocyte (P<0.01). Erythrocytic Na(+)-K(+)-ATPase activity, 2,3-DPG level, phosphatidylserine externalization, and extra-erythrocytic free Hb were significantly altered by hyperthermia plus high concentrations of cisplatin (100 and 200 μg/ml) (P<0.05), but not by hyperthermia plus 50 μg/ml cisplatin (P>0.05). In conclusion, pretreatment with cisplatin (50 μg/ml) combined with hyperthermia (42 °C) for 60 min effectively eliminated HepG2 cells from IBS but did not significantly affect erythrocytes in vitro.

  13. Significant benefits in survival by the use of surgery combined with radiotherapy for retroperitoneal soft tissue sarcoma.

    PubMed

    Hager, Sven; Makowiec, Frank; Henne, Karl; Hopt, Ulrich T; Wittel, Uwe A

    2017-01-26

    To report the effect of intraoperative electron beam radiotherapy (IOERT) and external beam radiotherapy (EBRT) in addition to surgery as well as to evaluate the role of resectable local recurrence for long-term prognosis. In 53 patients who underwent surgery for retroperitoneal soft tissue sarcoma (RSTS) from 2001 to 2014 prognostic and epidemiologic factors were reviewed retrospectively to analyze their impact on survival and recurrence. Twenty three patients (50%) had surgery plus radiotherapy, 23 (50%) had surgery only. Histology showed 73.9% liposarcoma, 15.2% leiomyosarcoma and 6.5% pleomorphic undifferentiated sarcoma respectively. Low grade sarcoma were observed in 52.2%, high grade sarcoma in 47.8%. The latter showed a trend towards a decreased 5-year survival rate (p = 0.125). Margin status was: R0: 60.9%, R1: 23.9%, R2: 15.2%; leading to significant changes in 5-year survival rate (R0: 77.6%; R1: 70.0%; R2: 42.9%; p = 0.03). Age younger than 55 years significantly improved 5-year survival rate (p = 0.039). Patients receiving resection of multiple sarcoma recurrence showed an almost identical improved 5-year survival rate compared to patients without recurrence (no recurrence: 100.0%; single recurrence: 35.0%; multiple recurrence: 91.7%; p = 0.001). Surgery plus radiotherapy led to significantly improved survival (p = 0.04). There is a significant benefit in terms of 5-year survival after surgery plus some form of radiotherapy and a good prognosis for patients when the recurrence from RSTS was resected. Age older than 55 years and incomplete resection lowered 5-year survival rate significantly.

  14. Low-Dose-Rate Californium-252 Neutron Intracavitary Afterloading Radiotherapy Combined With Conformal Radiotherapy for Treatment of Cervical Cancer

    SciTech Connect

    Zhang Min; Xu Hongde; Pan Songdan; Lin Shan; Yue Jianhua; Liu Jianren

    2012-07-01

    Purpose: To study the efficacy of low-dose-rate californium-252 ({sup 252}Cf) neutron intracavitary afterloading radiotherapy (RT) combined with external pelvic RT for treatment of cervical cancer. Methods and Materials: The records of 96 patients treated for cervical cancer from 2006 to 2010 were retrospectively reviewed. For patients with tumors {<=}4 cm in diameter, external beam radiation was performed (1.8 Gy/day, five times/week) until the dose reached 20 Gy, and then {sup 252}Cf neutron intracavitary afterloading RT (once/week) was begun, and the frequency of external beam radiation was changed to four times/week. For patients with tumors >4 cm, {sup 252}Cf RT was performed one to two times before whole-pelvis external beam radiation. The tumor-eliminating dose was determined by using the depth limit of 5 mm below the mucosa as the reference point. In all patients, the total dose of the external beam radiation ranged from 46.8 to 50 Gy. For {sup 252}Cf RT, the dose delivered to point A was 6 Gy/fraction, once per week, for a total of seven times, and the total dose was 42 Gy. Results: The mean {+-} SD patient age was 54.7 {+-} 13.7 years. Six patients had disease assessed at stage IB, 13 patients had stage IIA, 49 patients had stage IIB, 3 patients had stage IIIA, 24 patients had stage IIIB, and 1 patient had stage IVA. All patients obtained complete tumor regression (CR). The mean {+-} SD time to CR was 23.5 {+-} 3.4 days. Vaginal bleeding was fully controlled in 80 patients within 1 to 8 days. The mean {+-} SD follow-up period was 27.6 {+-} 12.7 months (range, 6-48 months). Five patients died due to recurrence or metastasis. The 3-year survival and disease-free recurrence rates were 89.6% and 87.5 %, respectively. Nine patients experienced mild radiation proctitis, and 4 patients developed radiocystitis. Conclusions: Low-dose-rate {sup 252}Cf neutron RT combined with external pelvic RT is effective for treating cervical cancer, with a low incidence of

  15. Low-dose-rate californium-252 neutron intracavitary afterloading radiotherapy combined with conformal radiotherapy for treatment of cervical cancer.

    PubMed

    Zhang, Min; Xu, Hong-De; Pan, Song-Dan; Lin, Shan; Yue, Jian-Hua; Liu, Jian-Ren

    2012-07-01

    To study the efficacy of low-dose-rate californium-252 ((252)Cf) neutron intracavitary afterloading radiotherapy (RT) combined with external pelvic RT for treatment of cervical cancer. The records of 96 patients treated for cervical cancer from 2006 to 2010 were retrospectively reviewed. For patients with tumors ≤4 cm in diameter, external beam radiation was performed (1.8 Gy/day, five times/week) until the dose reached 20 Gy, and then (252)Cf neutron intracavitary afterloading RT (once/week) was begun, and the frequency of external beam radiation was changed to four times/week. For patients with tumors >4 cm, (252)Cf RT was performed one to two times before whole-pelvis external beam radiation. The tumor-eliminating dose was determined by using the depth limit of 5 mm below the mucosa as the reference point. In all patients, the total dose of the external beam radiation ranged from 46.8 to 50 Gy. For (252)Cf RT, the dose delivered to point A was 6 Gy/fraction, once per week, for a total of seven times, and the total dose was 42 Gy. The mean ± SD patient age was 54.7 ± 13.7 years. Six patients had disease assessed at stage IB, 13 patients had stage IIA, 49 patients had stage IIB, 3 patients had stage IIIA, 24 patients had stage IIIB, and 1 patient had stage IVA. All patients obtained complete tumor regression (CR). The mean ± SD time to CR was 23.5 ± 3.4 days. Vaginal bleeding was fully controlled in 80 patients within 1 to 8 days. The mean ± SD follow-up period was 27.6 ± 12.7 months (range, 6-48 months). Five patients died due to recurrence or metastasis. The 3-year survival and disease-free recurrence rates were 89.6% and 87.5 %, respectively. Nine patients experienced mild radiation proctitis, and 4 patients developed radiocystitis. Low-dose-rate (252)Cf neutron RT combined with external pelvic RT is effective for treating cervical cancer, with a low incidence of complications. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Effects of combined sunitinib and extracranial stereotactic radiotherapy on bone marrow hematopoiesis

    PubMed Central

    Kao, Johnny; Timmins, Jonathan; Ozao-Choy, Junko; Packer, Stuart

    2016-01-01

    There is considerable interest in deploying stereotactic body radiotherapy in combination with immune therapy for patients with extracranial oligometastases. In addition to angiogenesis inhibition, sunitinib appears to mediate antitumor immunity through effects on circulating monocytic cells. The current study investigated the effects of combined sunitinib and stereotactic radiotherapy on hematopoiesis. As part of a phase I/II clinical trial utilizing concurrent sunitinib (25–50 mg on days 1–28) and image-guided radiation therapy (40–50 Gy in 10 fractions starting on days 8–19) for patients with metastatic cancer, the complete blood count, platelet count and automatic differential were performed pretreatment and on days 8 and 19. On average, sunitinib monotherapy for 7 days resulted in a 33% decrease in monocytes and an 18% decrease in neutrophils (P<0.01 for all). Compared to sunitinib alone, combined sunitinib and radiation resulted in a further decrease in neutrophils, lymphocytes and platelets (P<0.05). Following sunitinib and radiation treatment, a greater than average decrease in monocytes (≥200/µl) was associated with a significant increase in progression-free and overall survival times. This exploratory study provides further evidence that monocytes represent a potential biomarker in patients with solid tumors treated with sunitinib. PMID:27602153

  17. Analgesic effects of epidurally administered levogyral ketamine alone or in combination with morphine on intraoperative and postoperative pain in dogs undergoing ovariohysterectomy.

    PubMed

    Acosta, Alinne Dalla-Porta; Gomar, Carmen; Correa-Natalini, Claudio; Bopp, Simone; Polydoro, Alexandre; Sala-Blanch, Xavier

    2005-01-01

    To evaluate the analgesic and adverse effects of epidurally administered levogyral (S[+]) ketamine alone or in combination with morphine on intraoperative and postoperative pain in dogs undergoing ovariohysterectomy. 30 dogs scheduled for ovariohysterectomy. Dogs were randomly allocated to 1 of 3 groups. Dogs in group 1 received S(+) ketamine (1 mg/kg), dogs in group 2 received S(+) ketamine (0.5 mg/kg) and morphine (0.05 mg/kg), and dogs in group 3 received S(+) ketamine (1 mg/kg) and morphine (0.025 mg/kg). The skin was incised 15 minutes after epidural administration of analgesics. Heart rate (HR), respiratory rate (RR), systolic blood pressure (SBP), oxygen saturation as measured by pulse oximetry, and arterial blood gases were obtained before anesthesia, 15 minutes after epidural administration of analgesics, 15 and 30 minutes after initiation of surgery, and at the end of surgery. During the intraoperative period, an increase of > or =20% in baseline values for HR, RR, and SBP was considered a sign of intraoperative pain. Signs of pain and adverse effects were assessed at 2, 4, and 8 hours postoperatively. There were no significant differences in intraoperative or postoperative measurements among the 3 groups. No dogs had intraoperative signs of pain. Mean postoperative pain assessment scores were <3.5 in all 3 groups. Salivation was the most frequent adverse effect in dogs in groups 1 and 3, and sedation occurred more frequently in dogs in groups 2 and 3. All 3 analgesic regimens provided good respiratory and cardiovascular stability intraoperatively and adequate postoperative analgesia with minimal adverse effects.

  18. Primary Closure Following Laparoscopic Common Bile Duct Exploration Combined with Intraoperative Choledochoscopy and D-J Tube Drainage for Treating Choledocholithiasis.

    PubMed

    Yu, Miao; Xue, Huanzhou; Shen, Quan; Zhang, Xiao; Li, Ke; Jia, Meng; Jia, Jiangkun; Xu, Jian

    2017-09-19

    BACKGROUND This study aimed to assess the clinical short-term results of a primary closure following laparoscopic common bile duct exploration (LCBDE) combined with intraoperative choledochoscopy and D-J tube drainage for choledocholithiasis treatment. MATERIAL AND METHODS Twenty-five patients (14 women and 11 men) who underwent LCBDE with primary duct closure and D-J tube drainage for choledocholithiasis were retrospectively enrolled. The D-J tube (4.7F×14 cm) was removed using a duodenoscope if there was no bile leakage. Before discharge, patients were examined for blood amylase. After discharge or D-J tube removal, all patients were routinely assessed for complications. RESULTS Mean operating time was 135±46 min (range, 78-195 min). Mean intraoperative blood loss was 71±24 mL (range, 25-110 mL). Total hospital stay was 6-9 days (mean, 8.04±1.37 days). Two patients experienced intraoperative bile leakage, which was stopped with re-suturing. None of these patients experienced postoperative bile leaks. Three patients had slight elevation of serum amylase before discharge but without pancreatitis signs. The successful clearance rate of stones was 100%. During 1-year follow-up, no recurrence or severe complications occurred. CONCLUSIONS A primary closure following LCBDE combined with intraoperative choledochoscopy and D-J tube drainage is safe and feasible for choledocholithiasis treatment.

  19. Diagnostic Accuracy of Combined Multimodality Somatosensory Evoked Potential and Transcranial Motor Evoked Potential Intraoperative Monitoring in Patients With Idiopathic Scoliosis.

    PubMed

    Thirumala, Parthasarathy D; Huang, Jessie; Thiagarajan, Karthy; Cheng, Hannah; Balzer, Jeffrey; Crammond, Donald J

    2016-10-01

    Systematic review. The aim of the study was to determine the predictive value of combined multimodality somatosensory evoked potential (SSEP) and transcranial motor evoked potential (TcMEP) monitoring in detecting impending neurological injury during surgery for idiopathic scoliosis. The diagnostic of motor evoked potential monitoring and SSEP monitoring have been established. However, the predictive value of combined multimodality SSEP and TcMEP monitoring in detecting impending neurological injury during surgery for idiopathic scoliosis has not been evaluated. A systematic literature search was performed using PubMed/MEDLINE, Web of Science, and EMBASE from 1974 to January 2015. All titles and abstracts were independently reviewed by the authors. We included all studies that were (1) randomized controlled trials, prospective or retrospective cohort studies; (2) included patients with idiopathic scoliosis undergoing scoliosis correction surgery; (3) included multimodality SSEP and TcMEP monitoring during spinal surgery; (4) included immediate postoperative neurological assessment; (5) idiopathic scoliosis patient population n ≥25; and (6) published in English. Seven studies comprising a total of 2052 patients with idiopathic scoliosis were included in our meta-analysis. The incidence of neurological deficit in this cohort was 0.93%. The pooled sensitivity, specificity, and Diagnostic Odds Ratio were 82.6% (95% CI 56.7%-94.5%), 94.4% (95% CI 85.1%-98.0%), and 106.16 (95% CI 24.952-451.667), respectively. The area under the curve was 0.928, indicating excellent discriminatory ability. Idiopathic scoliosis corrective surgery patients who experience a new neurological deficit are 106.16 times more likely to have had an SSEP and/or TcMEP change during corrective procedures. The results of this meta-analysis demonstrate that combined multimodality SSEP and TcMEP monitoring possess some advantage over use of each alone, and that intraoperative neurophysiological

  20. Surgical treatment for epilepsy involving language cortices: a combined process of electrical cortical stimulation mapping and intra-operative continuous language assessment.

    PubMed

    Zhang, Xi; Zhang, Guojun; Yu, Tao; Ni, Duanyu; Cai, Lixin; Qiao, Liang; Du, Wei; Li, Yongjie

    2013-11-01

    The purpose of this study was to improve the surgical treatment of epilepsy by maximising seizure control while protecting language function. A combined process of extra-operative electrical cortical stimulation (ECS) mapping, direct ECS and intra-operative continuous language assessment was performed during complicated operative cases. Of the 24 epilepsy patients, nine had a complex relationship between the seizure onset zone and the language cortices. The combined process was used in these nine patients. In the other 15 patients, surgical resection was completed based on extra-operative ECS results alone. Evaluations were performed before and after surgery to assess language function and seizure control. The intra-operative continuous language assessment provided important information at the time of the resection. Seven extra-operative ECS positive language sites were resected without obvious language deficits in two patients. Resection was interrupted by language disturbances in an area where no extra-operative ECS positive site was identified in one patient. In three other patients, functional boundary was undefined in extra-operative ECS result, epileptogenic cortices were maximally resected during the continuous language assessment. In terms of seizure control, 18 of 24 (75%) patients reached Engel's class I, including all nine patients who underwent intra-operative continuous language assessment. One patient had minor surgery-related language deficits three months after resection. Intra-operative continuous language assessment proved to be complementary to extra-operative ECS mappings. The combination of ECS mappings and intra-operative continuous language assessment can maximise the resection of epileptogenic cortices and preserve language function in difficult cases involving the language cortex. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  1. ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinase activity in combination with radiotherapy

    SciTech Connect

    Frederick, Barbara; Gustafson, Dan; Bianco, Cataldo; Ciardiello, Fortunato; Dimery, Isaiah; Raben, David . E-mail: david.raben@uchsc.edu

    2006-01-01

    Radiation enhances both epithelial growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) expression, which are a part of key pathways for tumor progression. Some tumors may not respond well to EGFR inhibitors alone or may develop resistance to EGFR inhibitors. Therefore, drug therapy targeted to VEGF receptors and EGFRs, when combined with radiotherapy (RT), may improve tumor control and provide wider applicability. This article focuses on ZD6474, an inhibitor of EGFR and VEGF receptor signaling in combination with RT. We discuss preclinical and clinical studies with RT and inhibitors of VEGF or EGFR signaling first. We then address issues associated with ZD6474 pharmacokinetic dosing, and scheduling when combined with RT. We also discuss ZD6474 in the context of anti-EGFR therapy resistance. Dual inhibition of EGFR and VEGF receptor signaling pathways shows promise in enhancing RT efficacy.

  2. Tumor Antivascular Effects of Radiotherapy Combined with Combretastatin A4 Phosphate in Human Non-Small-Cell Lung Cancer

    SciTech Connect

    Ng, Q.-S.; Goh, Vicky; Carnell, Dawn; Meer, Khalda; Padhani, Anwar R.; Saunders, Michele I.; Hoskin, Peter J. . E-mail: peterhoskin@nhs.net

    2007-04-01

    Purpose: The tumor vascular effects of radiotherapy and subsequent administration of the vascular disrupting agent combretastatin A4 phosphate (CA4P) were studied in patients with advanced non-small-cell lung cancer using volumetric dynamic contrast-enhanced computed tomography (CT). Patients and Methods: Following ethical committee approval and informed consent, 8 patients receiving palliative radiotherapy (27 Gy in six fractions, twice weekly) also received CA4P (50 mg/m{sup 2}) after the second fraction of radiotherapy. Changes in dynamic CT parameters of tumor blood volume (BV) and permeability surface area product (PS) were measured for the whole tumor volume, tumor rim, and center after radiotherapy alone and after radiotherapy in combination with CA4P. Results: After the second fraction of radiotherapy, 6 of the 8 patients showed increases in tumor PS (23.6%, p = 0.011). Four hours after CA4P, a reduction in tumor BV (22.9%, p < 0.001) was demonstrated in the same 6 patients. Increase in PS after radiotherapy correlated with reduction in BV after CA4P (r = 0.77, p = 0.026). At 72 h after CA4P, there was a sustained reduction in tumor BV of 29.4% (p < 0.001). Both increase in PS after radiotherapy and reduction in BV after CA4P were greater at the rim of the tumor. The BV reduction at the rim was sustained to 72 h (51.4%, p 0.014). Conclusion: Radiotherapy enhances the tumor antivascular activity of CA4P in human non-small-cell lung cancer, resulting in sustained tumor vascular shutdown.

  3. [New possibilities in radiotherapy of endobronchial tumors using the afterloading method in combination with laser technics].

    PubMed

    Schumacher, W; Koch, K; Frost, D; Michel, L; Plümecke, M; Lübbert, K; Mai, J; Krumhaar, D; Macha, H N; Stadler, M

    1985-11-01

    New possibilities for radiotherapy of bronchial carcinomas are provided by the combined application of the recently introduced afterloading method used hitherto in the treatment of stenosing processes of bronchial carcinomas and the neodyme-YAG laser which opens the stenosis in such a manner that the afterloading probe can be inserted. This new method allows to perform without complications or disadvantages further combined therapies such as percutaneous irradiation (telecobalt, linear accelerator or betatron). An irradiation scheme leading to a decisive tumor regression can be established due to the fast reventilation of the lung obtained by both methods. Surprisingly, three patients could be submitted despite the small-field radiotherapy to rather important lung operations such as lobectomy and pneumonectomy which were performed without complications or disadvantages. The patients were not operable without laser and afterloading therapy. This method was applied several times in the treatment of other diseases such as oesophageal cancer and stenosing cancer of the antrum. In these cases, a normal ingestion due to tumor regression was obtained rapidly.

  4. Outcomes after combined use of intraoperative MRI and 5-aminolevulinic acid in high-grade glioma surgery

    PubMed Central

    Schatlo, Bawarjan; Fandino, Javier; Smoll, Nicolas R.; Wetzel, Oliver; Remonda, Luca; Marbacher, Serge; Perrig, Wolfgang; Landolt, Hans; Fathi, Ali-Reza

    2015-01-01

    Background Previous studies have shown the individual benefits of 5-aminolevulinic acid (5-ALA) and intraoperative (i)MRI in enhancing survival for patients with high-grade glioma. In this retrospective study, we compare rates of progression-free and overall survival between patients who underwent surgical resection with the combination of 5-ALA and iMRI and a control group without iMRI. Methods In 200 consecutive patients with high-grade gliomas, we recorded age, sex, World Health Organization tumor grade, and pre- and postoperative Karnofsky performance status (good ≥80 and poor <80). A 0.15-Tesla magnet was used for iMRI; all patients operated on with iMRI received 5-ALA. Overall and progression-free survival rates were compared using multivariable regression analysis. Results Median overall survival was 13.8 months in the non-iMRI group and 17.9 months in the iMRI group (P = .043). However, on identifying confounding variables (ie, KPS and resection status) in this univariate analysis, we then adjusted for these confounders in multivariate analysis and eliminated this distinction in overall survival (hazard ratio: 1.23, P = .34, 95% CI: 0.81, 1.86). Although 5-ALA enhanced the achievement of gross total resection (odds ratio: 3.19, P = .01, 95% CI: 1.28, 7.93), it offered no effect on overall or progression-free survival when adjusted for resection status. Conclusions Gross total resection is the key surgical variable that influences progression and survival in patients with high-grade glioma and more likely when surgical adjuncts, such as iMRI in combination with 5-ALA, are used to enhance resection. PMID:25858636

  5. Outcomes after combined use of intraoperative MRI and 5-aminolevulinic acid in high-grade glioma surgery.

    PubMed

    Schatlo, Bawarjan; Fandino, Javier; Smoll, Nicolas R; Wetzel, Oliver; Remonda, Luca; Marbacher, Serge; Perrig, Wolfgang; Landolt, Hans; Fathi, Ali-Reza

    2015-12-01

    Previous studies have shown the individual benefits of 5-aminolevulinic acid (5-ALA) and intraoperative (i)MRI in enhancing survival for patients with high-grade glioma. In this retrospective study, we compare rates of progression-free and overall survival between patients who underwent surgical resection with the combination of 5-ALA and iMRI and a control group without iMRI. In 200 consecutive patients with high-grade gliomas, we recorded age, sex, World Health Organization tumor grade, and pre- and postoperative Karnofsky performance status (good ≥80 and poor <80). A 0.15-Tesla magnet was used for iMRI; all patients operated on with iMRI received 5-ALA. Overall and progression-free survival rates were compared using multivariable regression analysis. Median overall survival was 13.8 months in the non-iMRI group and 17.9 months in the iMRI group (P = .043). However, on identifying confounding variables (ie, KPS and resection status) in this univariate analysis, we then adjusted for these confounders in multivariate analysis and eliminated this distinction in overall survival (hazard ratio: 1.23, P = .34, 95% CI: 0.81, 1.86). Although 5-ALA enhanced the achievement of gross total resection (odds ratio: 3.19, P = .01, 95% CI: 1.28, 7.93), it offered no effect on overall or progression-free survival when adjusted for resection status. Gross total resection is the key surgical variable that influences progression and survival in patients with high-grade glioma and more likely when surgical adjuncts, such as iMRI in combination with 5-ALA, are used to enhance resection. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

  6. Effects of magnetic induction hyperthermia and radiotherapy alone or combined on a murine 4T1 metastatic breast cancer model.

    PubMed

    Wang, Hui; Li, Xiao; Xi, Xuping; Hu, Bingqiang; Zhao, Lingyun; Liao, Yuping; Tang, Jintian

    2011-01-01

    The purpose of this study was to explore the effects of MIH and radiotherapy alone or combined on metastatic breast cancer and the underlying mechanisms. A murine 4T1 metastatic breast cancer model was established and randomly assigned into four treatment groups: C (control), R (radiotherapy), MIH, and MIH+R. Tumour volume, lung metastasis, the expression of Bax and MMP-9, T cell subsets, serum cytokine levels, and mouse survival were evaluated. Group MIH + R showed significantly reduced tumour volume, lung metastasis, improved survival and increased Bax expression compared to group R or MIH (P<0.05). MMP-9 expression in the primary tumour tissue was significantly increased in group R compared to the other groups (P<0.05), which could be brought down by combined MIH treatment. Group MIH +R showed significantly higher CD4(+) T cell percentage as well as CD4(+)/CD8(+) cell ratio than group R (P<0.05). Group MIH+R showed significantly higher serum levels of TNF-α, IFN-γ and IL-2 than group R (P<0.05). MIH not only promotes the tumour-cell killing effect of radiotherapy through Bax-mediated cell death, but also improves cellular immunity in mice under radiotherapy and decreases the potential of radiotherapy to enhance MMP-9 expression, which leads to significant improvement in lung metastasis and overall survival of mice under combined treatment of MIH and R. This study is the first to have explored the effect of combined hyperthermia and radiotherapy on tumour metastasis and the underlying mechanisms. It provides insights into the application of MIH as an adjuvant to radiotherapy for metastatic breast cancer.

  7. [A case of locally advanced breast cancer treated with hyperthermia in combination with radiotherapy].

    PubMed

    Yamasaki, M; Yayoi, E; Kishibuchi, M; Nishi, T; Yagyu, T; Kawasaki, K; Ostapenko, V; Nishide, T

    2001-10-01

    A 59-year-old woman was admitted to our hospital because of massive bleeding from a right breast tumor. The breast tumor had existed for ten years occupied the entire right breast (23 x 20 cm), its central part forming an ulcer 17 x 15 cm in size. Radiotherapy to the right breast and medication with tamoxifen were started, after which five courses of CMF chemotherapy were given. The tumor decreased to 16 x 14 cm, and hyperthermia to the right breast was performed for a total of 87 sessions from January 1999. The irregular protruding portion of the ulcer caused the necrosis, and was sloughed off about one month after hyperthermia. No viable tumor cells were observed in a biopsy taken at 5 months after the start of treatment (40 sessions). A total of 87 hyperthermia sessions were performed, and the ulcer disappeared. For 15 months after the end of hyperthermia, the patient showed a continuous CR. Hyperthermia in combination with radiotherapy or chemotherapy for breast cancer may produce a remarkable effect as in the present case, and may become one choice for medical treatment of locally advanced or recurrent breast cancer.

  8. Intensity-Modulated Radiotherapy Might Increase Pneumonitis Risk Relative to Three-Dimensional Conformal Radiotherapy in Patients Receiving Combined Chemotherapy and Radiotherapy: A Modeling Study of Dose Dumping

    SciTech Connect

    Vogelius, Ivan S.; Westerly, David C.; Cannon, George M.; Mackie, Thomas R.; Mehta, Minesh P.; Sugie, Chikao; Bentzen, Soren M.

    2011-07-01

    Purpose: To model the possible interaction between cytotoxic chemotherapy and the radiation dose distribution with respect to the risk of radiation pneumonitis. Methods and Materials: A total of 18 non-small-cell lung cancer patients previously treated with helical tomotherapy at the University of Wisconsin were selected for the present modeling study. Three treatment plans were considered: the delivered tomotherapy plans; a three-dimensional conformal radiotherapy (3D-CRT) plan; and a fixed-field intensity-modulated radiotherapy (IMRT) plan. The IMRT and 3D-CRT plans were generated specifically for the present study. The plans were optimized without adjusting for the chemotherapy effect. The effect of chemotherapy was modeled as an independent cell killing process by considering a uniform chemotherapy equivalent radiation dose added to all voxels of the organ at risk. The risk of radiation pneumonitis was estimated for all plans using the Lyman and the critical volume models. Results: For radiotherapy alone, the critical volume model predicts that the two IMRT plans are associated with a lower risk of radiation pneumonitis than the 3D-CRT plan. However, when the chemotherapy equivalent radiation dose exceeds a certain threshold, the radiation pneumonitis risk after IMRT is greater than after 3D-CRT. This threshold dose is in the range estimated from clinical chemoradiotherapy data sets. Conclusions: Cytotoxic chemotherapy might affect the relative merit of competing radiotherapy plans. More work is needed to improve our understanding of the interaction between chemotherapy and the radiation dose distribution in clinical settings.

  9. Breast radiotherapy (RT) using tangential fields (TgF): a prospective evaluation of the dose distribution in the sentinel lymph node (SLN) area as determined intraoperatively by clip placement.

    PubMed

    Belkacemi, Yazid; Bigorie, Veronique; Pan, Qiong; Bouaita, Ryan; Pigneur, Frederic; Itti, Emmanuel; Badaoui, Hakima; Assaf, Elias; Caillet, Philippe; Calitchi, Elie; Bosc, Romain

    2014-11-01

    Randomized trials have established that patients with limited involvement of sentinel lymph node (SLN) do not require axillary lymph node dissection (ALND). The similar outcome in patients with ≤2 positive SLN with or without additional ALND is attributed, in part, to tangential fields (TgF) RT. We evaluated the dose distribution in the SLN biopsy area (SLNBa) as determined intraoperatively by clips placement for radiotherapy (RT) optimization. This prospective study included 25 patients who had breast conservation. Titanium clips were used intraoperatively to mark the SLNBa. All patients had 3D-conformal RT using standard (STgF) or high tangential fields (HTgF). Axillary levels, SLNBa, and organs at risk were contoured on a CT scan. Dose distribution and overlap between TgF and target volumes were analyzed. The average doses delivered to axilla levels I-III and SLNBa were 25, 5, 2, and 33 Gy, respectively. The average dose delivered to SLNBa was higher using HTgF with better coverage of the axilla. Only 12 of 25 patients (48 %) had their SLNBa completely covered by the TgF. There was no impact of TgF size on ipsilateral lung dose. The mean heart dose delivered using STgF was lower than HTgF. In the era of SLNB, axilla and SNLBa RT technique has to be standardized to deliver adequate dose. We recommend the use of HTgF or direct axillary RT techniques (such as in AMAROS trial) in patients with metastases in SLN without ALND completion, when only TgF are expected to cure potential residual disease in the axilla.

  10. Combination of an Integrin-Targeting NIR Tracer and an Ultrasensitive Spectroscopic Device for Intraoperative Detection of Head and Neck Tumor Margins and Metastatic Lymph Nodes

    PubMed Central

    Yoon, Younghyoun; Mohs, Aaron M.; Mancini, Michael C.; Nie, Shuming; Shim, Hyunsuk

    2016-01-01

    Despite major advances in targeted drug therapy and radiation therapy, surgery remains the most effective treatment for most solid tumors. The single most important predictor of patient survival is a complete surgical resection of the primary tumor, draining lymph nodes, and metastatic lesions. Presently, however, 20%–30% of patients with head and neck cancer who undergo surgery still leave the operating room without complete resection because of missed lesions. Thus, major opportunities exist to develop advanced imaging tracers and intraoperative instrumentation that would allow surgeons to visualize microscopic tumors during surgery. The cell adhesion molecule integrin αvβ3 is specifically expressed by tumor neovasculature and invading tumor cells, but not by quiescent vessels or normal cells. Here we report the combined use of an integrin-targeting near-infrared tracer (RGD-IRDye800CW) and a handheld spectroscopic device, an integrated point spectroscopy with wide-field imaging system, for highly sensitive detection of integrin overexpression on infiltrating cancer cells. By using an orthotopic head and neck cancer animal model, we show that this tracer–device combination allows intraoperative detection of not only invasive tumor margins but also metastatic lymph nodes. Correlated histological analysis further reveals that microscopic clusters of 50–100 tumor cells can be detected intraoperatively with high sensitivity and specificity, raising new possibilities in guiding surgical resection of microscopic tumors and metastatic lymph nodes. PMID:27738656

  11. Combined hysteroscopy-laparoscopy approach for excision of pelvic nitinol fragment from Essure contraceptive device: Role of intraoperative fluoroscopy for uterine conservation

    PubMed Central

    Palermo, Gianpiero D.

    2016-01-01

    We describe the successful removal of a pelvic contraceptive coil in a symptomatic 46-year-old patient who had Essure devices for four years, using a combined hysteroscopy-laparoscopy-fluoroscopy approach. Following normal hysteroscopy, at laparoscopy the right Essure implant was disrupted and its outer nitinol coil had perforated the fallopian tube. However, the inner rod (containing polyethylene terephthalate) had migrated to an extrapelvic location, near the proximal colon. In contrast, the left implant was situated within the corresponding tube. Intraoperative fluoroscopy was used to confirm complete removal of the device, which was further verified by postoperative computed tomography. The patient's condition improved after surgery and she continues to do well. This is the first report to describe this technique in managing Essure complications remote from time of insertion. Our case highlights the value and limitations of preoperative and intraoperative imaging to map Essure fragment location before surgery. PMID:27462605

  12. Microwave-induced local hyperthermia in combination with radiotherapy of human malignant tumors

    SciTech Connect

    U, R.; Noell, K.T.; Woodward, K.T.; Worde, B.T.; Fishburn, R.I.; Miller, L.S.

    1980-02-15

    Since 1976, two groups of patients have been treated with local microwave hyperthermia immediately following ionizing radiation. Group A patients had measurable multiple lesions assigned radiotherapy only, microwave hyperthermia only, or combined treatment. Ionizing radiation in 200 to 600 rad fractions was used 2 to 5 times per week to a total of 1800 to 4200 rad in 5 to 14 fractions. Group B patients had combination treatment only, with radiation fractions of 200 to 600 rad 2 to 5 times per week to a total of 200 to 4800 rad total in 6 to 20 fractions. Both groups received hyperthermia (42 to 44 C) 2 to 3 times per week, maximum ten sessions in four weeks. The 19 patients treated have had squamous cell carcinoma, adenocarcinoma, malignant melanoma, plasmacytoma, epithelioid sarcoma, and undifferentiated carcinoma. After more than 150 hyperthermia sessions, we find: (1) local hyperthermia with microwave alone or in combination with ionizing radiation can be used with excellent normal tissue tolerance provided local tissue temperatures are carefully monitored and controlled; (2) a higher level of heat induction in tumor tissue as compared to surrounding normal tissues; and (3) repeated hyperthermia at 42 to 43.5 C for 45 minutes per session immediately following photon irradiation yields a favorable therapeutic result, occasionally dramatic. Local microwave hyperthermia in combination withradiotherapy offers the possibility of substantial impact on clinical cancer therapy, whether of curative or palliative intent.

  13. Radiotherapy combined with hormonal therapy in prostate cancer: the state of the art.

    PubMed

    Milecki, Piotr; Martenka, Piotr; Antczak, Andrzej; Kwias, Zbigniew

    2010-10-11

    Androgen-deprivation therapy (ADT) is used routinely in combination with definitive external beam radiation therapy (EBRT) in patients with high-risk clinically localized or locally advanced disease. The combined treatment (ADT-EBRT) also seems to play a significant role in improving treatment results in the intermediate-risk group of prostate cancer patients. On the other hand, there is a growing body of evidence that treatment with ADT can be associated with serious and lifelong adverse events including osteoporosis, cardiovascular disease, diabetes, and many others. Almost all ADT adverse events are time dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, it is crucial to clearly state the optimal schedule for ADT in combination with EBRT, that maintaining the positive effect on treatment efficacy would keep the adverse events risk at reasonable level. To achieve this goal, treatment schedule may have to be highly individualized on the basis of the patient-specific potential vulnerability to adverse events. In this study, the concise and evidence-based review of current literature concerning the general rationales for combining radiotherapy and hormonal therapy, its mechanism, treatment results, and toxicity profile is presented.

  14. Whole-brain radiotherapy combined with surgery or stereotactic radiotherapy in patients with brain oligometastases: long-term analysis.

    PubMed

    D'Agostino, Giuseppe Roberto; Autorino, Rosa; Pompucci, Angelo; De Santis, Maria Carmen; Manfrida, Stefania; Di Lella, Giuseppe; Mantini, Giovanna; Frascino, Vincenzo; Chiesa, Silvia; Albanese, Alessio; Dinapoli, Nicola; Azario, Luigi; Fiorentino, Alba; Valentini, Vincenzo; Anile, Carmelo; Balducci, Mario

    2011-07-01

    To verify whether the treatment of brain oligometastases with whole-brain radiotherapy (WBRT) plus stereotactic radiotherapy (SRT) or surgical resection results in different outcomes. Files of patients affected by brain metastases submitted to surgical resection followed by WBRT (group A) or WBRT + SRT (group B) were retrospectively selected for this study. The two treatment groups were matched for the following potential prognostic factors: WBRT schedule, age, gender, performance status, tumor type, number of brain metastases, extra-cerebral metastases, and recursive partitioning analysis class (RPA). The outcomes of patients in both groups were evaluated in terms of toxicity, local control, and overall survival. Total of 97 patients were selected (56 male; 42 female) who were respectively submitted to surgical resection followed by WBRT (group A, n = 50 patients) or WBRT + SRT (Group B, n = 47 patients). Median follow-up was 95 months (range, 8-171 months). The 1-year local control rates were 46.0% and 69.0% respectively. No significant difference in local tumor control was observed between group A and B (p = 0.10). Median overall survival was 15 and 19 months in group A and B, respectively. One-year survival was 56.0% and 62%, respectively. No difference was observed in the two groups (p = 0.40). Surgery remains the main therapeutic approach in symptomatic patients; nevertheless, our data support the use of WBRT plus SRT in one or two brain metastases smaller than 3 cm.

  15. Treatment of Solitary Painful Osseous Metastases with Radiotherapy, Cryoablation or Combined Therapy: Propensity Matching Analysis in 175 Patients

    PubMed Central

    Zugaro, Luigi; Bonfili, Pierluigi; Gregori, Lorenzo; Franzese, Pietro; Marampon, Francesco; Vittorini, Francesca; Moro, Roberto; Tombolini, Vincenzo; Di Cesare, Ernesto; Masciocchi, Carlo

    2015-01-01

    Purpose aim of this study was to identify outcomes in pain relief and quality of life in patients with a solitary painful osseous metastasis treated by radiotherapy, cryoablation or the combination using a propensity score matching study design. Materials and Methods 175 patients with painful bone metastases were included in the study. Twenty-five of them underwent a radiation course (20 Gy in five daily fractions) 15 days after the cryoablation. These subjects were retrospectively matched by propensity analysis with a group of subjects treated by radiotherapy (125 subjects) and with a group treated byCryoablation (25 subjects). The pain relief in terms of complete response, rate of subjects requiring analgesics after treatments and the changes in self-rated quality of life were measured. Informed consent was obtained from the subject and the study was approved by the local Ethical Committee. Results An higher proportion of subjects treated by cryoablation (32%) or cryoablation followed by RT (72%;) experienced a complete response compared with patients treated by radiotherapy alone (11.2%). After Bonferroni correction strategy, the addition of radiotherapy to cryoablation significantly improved the rate of complete response compared with cryoablation alone (p = 0.011) and this paralleled with an improved self-rated quality of life. Seventeen subjects (13.6%) of patients in the radiotherapy group, 9 (36%) in the cryoablation group, and 19 (76)% in the cryoablation- radiotherapy group did not require narcotic medications. Conclusions The addition of radiotherapy to cryoablation favorably impacts on perceived pain, with a favorable toxicity profile. However, our data should be interpreted with caution and could serve as a framework around which to design future trials. PMID:26103516

  16. Single trial somatosensory evoked potential extraction with ARX filtering for a combined spinal cord intraoperative neuromonitoring technique

    PubMed Central

    Rossi, Lorenzo; Bianchi, Anna Maria; Merzagora, Anna; Gaggiani, Alberto; Cerutti, Sergio; Bracchi, Francesco

    2007-01-01

    Background When spinal cord functional integrity is at risk during surgery, intraoperative neuromonitoring is recommended. Tibial Single Trial Somatosensory Evoked Potentials (SEPs) and H-reflex are here used in a combined neuromonitoring method: both signals monitor the spinal cord status, though involving different nervous pathways. However, SEPs express a trial-to-trial variability that is difficult to track because of the intrinsic low signal-to-noise ratio. For this reason single trial techniques are needed to extract SEPs from the background EEG. Methods The analysis is performed off line on data recorded in eight scoliosis surgery sessions during which the spinal cord was simultaneously monitored through classical SEPs and H-reflex responses elicited by the same tibial nerve electrical stimulation. The single trial extraction of SEPs from the background EEG is here performed through AutoRegressive filter with eXogenous input (ARX). The electroencephalographic recording can be modeled as the sum of the background EEG, which can be described as an autoregressive process not related to the stimulus, and the evoked potential (EP), which can be viewed as a filtered version of a reference signal related to the stimulus. The choice of the filter optimal orders is based on the Akaike Information Criterion (AIC). The reference signal used as exogenous input in the ARX model is a weighted average of the previous SEPs trials with exponential forgetting behavior. Results The moving average exponentially weighted, used as reference signal for the ARX model, shows a better sensibility than the standard moving average in tracking SEPs fast inter-trial changes. The ability to promptly detect changes allows highlighting relations between waveform changes and surgical maneuvers. It also allows a comparative study with H-reflex trends: in particular, the two signals show different fall and recovery dynamics following stressful conditions for the spinal cord. Conclusion The ARX

  17. Pediatric urological complications with intraoperative radiation therapy

    SciTech Connect

    Ritchey, M.L.; Gunderson, L.L.; Smithson, W.A.; Kelalis, P.P.; Kaufman, B.H.; Telander, R.L.; Evans, R.G.; Kramer, S.A. )

    1990-01-01

    Intraoperative radiotherapy with variable energy electrons has been used as a supplemental boost to treat 6 children with locally advanced retroperitoneal malignancies. Of the patients 4 had treatment-related injuries to portions of the urinary tract within the intraoperative and external radiation fields. Three patients had significant renal impairment requiring surgical correction. The pathogenesis and management of treatment-induced injury to the urinary tract are discussed.

  18. Parotid Gland Function After Radiotherapy: The Combined Michigan and Utrecht Experience

    SciTech Connect

    Dijkema, Tim; Raaijmakers, Cornelis P.J.; Ten Haken, Randall K.; Roesink, Judith M.; Braam, Petra M.; Houweling, Anette C.; Moerland, Marinus A.; Eisbruch, Avraham; Terhaard, Chris H.J.

    2010-10-01

    Purpose: To analyze the combined and updated results from the University of Michigan and University Medical Center Utrecht on normal tissue complication probability (NTCP) of the parotid gland 1 year after radiotherapy (RT) for head-and-neck (HN) cancer. Patients and Methods: A total of 222 prospectively analyzed patients with various HN malignancies were treated with conventional and intensity-modulated RT. Stimulated individual parotid gland flow rates were measured before RT and 1 year after RT using Lashley cups at both centers. A flow ratio <25% of pretreatment was defined as a complication. The data were fitted to the Lyman-Kutcher-Burman model. Results: A total of 384 parotid glands (Michigan: 157; Utrecht: 227 glands) was available for analysis 1 year after RT. Combined NTCP analysis based on mean dose resulted in a TD{sub 50} (uniform dose leading to 50% complication probability) of 39.9 Gy and m (steepness of the curve) of 0.40. The resulting NTCP curve had good qualitative agreement with the combined clinical data. Mean doses of 25-30 Gy were associated with 17-26% NTCP. Conclusions: A definite NTCP curve for parotid gland function 1 year after RT is presented, based on mean dose. No threshold dose was observed, and TD{sub 50} was equal to 40 Gy.

  19. Efficacy and toxicity of nimotuzumab combined with radiotherapy in elderly patients with esophageal squamous cell carcinoma.

    PubMed

    Guo, Jin-Hua; Chen, Ming-Qiu; Chen, Cheng; Lu, Hai-Jie; Xu, Ben-Hua

    2015-09-01

    This study was conducted to assess the efficacy and toxicity of nimotuzumab combined with radiotherapy (RT) in elderly patients with esophageal squamous cell carcinoma. The clinical data of 16 esophageal squamous cell carcinoma patients, aged >70 years, who were initially treated with nimotuzumab combined with RT, were collected and retrospectively reviewed. The overall response and treatment toxicity were analyzed using SPSS software. All the patients completed the treatment schedule. The response to treatment was assessed at treatment completion and reassessed after 1-2 months: 1 patient achieved complete response (CR), 10 patients achieved partial response (PR), 4 patients exhibited stable disease and 1 patient developed disease progression and succumbed to radiation pneumonitis (RP) 1 month later. The overall response rate (CR+PR) was 68.8%. All 16 patients experienced grade 1-2 radiation esophagitis; no grade 3-4 toxicities were reported. There was one case of treatment-related mortality due to RP during the study. One patient developed a rash on the forearm. No hematological, gastrointestinal, hepatic or renal toxicities were observed. In conclusion, the toxicity of combined nimotuzumab with RT in elderly patients with esophageal cancer was tolerable. However, due to limitations associated with the retrospective nature of this study, the limited number of enrolled cases and the epidermal growth factor receptor expression determination prior to treatment, the efficacy of this treatment modality requires further investigation.

  20. Androgen deprivation therapy in combination with radiotherapy for high-risk clinically localized prostate cancer.

    PubMed

    Nishiyama, Tsutomu

    2012-04-01

    Androgen deprivation therapy (ADT) has remained the main therapeutic option for patients with advanced prostate cancer (PCa) for about 70 years. Several reports and our findings revealed that aggressive PCa can occur under a low dihydrotestosterone (DHT) level environment where the PCa of a low malignancy with high DHT dependency cannot easily occur. Low DHT levels in the prostate with aggressive PCa are probably sufficient to propagate the growth of the tumor, and the prostate with aggressive PCa can produce androgens from the adrenal precursors more autonomously than that with non-aggressive PCa does under the low testosterone environment with testicular suppression. In patients treated with ADT the pituitary-adrenal axis mediated by adrenocorticotropic hormone has a central role in the regulation of androgen synthesis. Several experimental studies have confirmed the potential benefits from the combination of ADT with radiotherapy (RT). A combination of external RT with short-term ADT is recommended based on the results of phase III randomized trials. In contrast, the combination of RT plus 6 months of ADT provides inferior survival as compared with RT plus 3 years of ADT in the treatment of locally advanced PCa. Notably, randomized trials included patients with diverse risk groups treated with older RT modalities, a variety of ADT scheduling and duration and, importantly, suboptimal RT doses. The use of ADT with higher doses of RT or newer RT modalities has to be properly assessed.

  1. 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.

  2. Tracer-cocktail injections for combined pre- and intraoperative multimodal imaging of lymph nodes in a spontaneous mouse prostate tumor model

    NASA Astrophysics Data System (ADS)

    van Leeuwen, Anne C.; Buckle, Tessa; Bendle, Gavin; Vermeeren, Lenka; Valdés Olmos, Renato; van de Poel, Henk G.; van Leeuwen, Fijs W. B.

    2011-01-01

    To improve surgical guidance toward prostate draining lymph nodes, we investigate the potential of intraoperative fluorescence imaging and combined pre- and intraoperative multimodality imaging approaches. Transgenic adenocarcinoma mouse prostate mice with spontaneous prostate tumors are injected intratumorally with: 1. a cocktail of patent blue (Pb) and indocyanine green (ICG); 2. a cocktail of albumin radiocolloids (99mTc-NanoColl), Pb, and ICG; or 3. a cocktail of radiolabeled albumin (99mTc-Vasculosis), Pb, and ICG. The distribution of these imaging agents over the lymph nodes (LNs) are studied at different time points after injection. We find that at 60-min postinjection, ICG significantly improves the detection of the LNs compared to Pb, 53 versus 7%, respectively. Moreover, a cocktail of ICG and 99mTc-NanoColl improves the fluorescent detection rate to 86%, equalling that of the clinically applied 99mTc-NanoColl. A similar overlap is observed in our initial clinical pilot data. Fluorescent detection of the LNs using a ICG with 99mTc-Vasculosis gives similar results as ``free'' ICG (58% 60 min). A 99mTc-NanoColl, Pb, and cocktail ICG enriches the standard 99mTc-NanoColl approach by adding optical detection of the sentinel lymph nodes. Furthermore, this approach improves fluorescent-based guidance and enables both accurate surgical planning and intraoperative detection, based on a single injection.

  3. Tracer-cocktail injections for combined pre- and intraoperative multimodal imaging of lymph nodes in a spontaneous mouse prostate tumor model.

    PubMed

    van Leeuwen, Anne C; Buckle, Tessa; Bendle, Gavin; Vermeeren, Lenka; Valdés Olmos, Renato; van de Poel, Henk G; van Leeuwen, Fijs W B

    2011-01-01

    To improve surgical guidance toward prostate draining lymph nodes, we investigate the potential of intraoperative fluorescence imaging and combined pre- and intraoperative multimodality imaging approaches. Transgenic adenocarcinoma mouse prostate mice with spontaneous prostate tumors are injected intratumorally with: 1. a cocktail of patent blue (Pb) and indocyanine green (ICG); 2. a cocktail of albumin radiocolloids (99mTc-NanoColl), Pb, and ICG; or 3. a cocktail of radiolabeled albumin (99mTc-Vasculosis), Pb, and ICG. The distribution of these imaging agents over the lymph nodes (LNs) are studied at different time points after injection. We find that at 60-min postinjection, ICG significantly improves the detection of the LNs compared to Pb, 53 versus 7%, respectively. Moreover, a cocktail of ICG and 99mTc-NanoColl improves the fluorescent detection rate to 86%, equalling that of the clinically applied 99mTc-NanoColl. A similar overlap is observed in our initial clinical pilot data. Fluorescent detection of the LNs using a ICG with 99mTc-Vasculosis gives similar results as "free" ICG (58%; 60 min). A 99mTc-NanoColl, Pb, and cocktail ICG enriches the standard 99mTc-NanoColl approach by adding optical detection of the sentinel lymph nodes. Furthermore, this approach improves fluorescent-based guidance and enables both accurate surgical planning and intraoperative detection, based on a single injection.

  4. Short-term clinical effect of conformal radiotherapy combined with tegafur gimeracil oteracil potassium in treating recurrent esophagus cancer

    PubMed Central

    Jiao, Yuyan; Shen, Yuzhen; Yan, Hua; Liu, Yan; Tan, Haihua; Li, Jianzhe

    2016-01-01

    Objective: To observe clinical effects of three-dimensional conformal radiotherapy combined with Tegafur Gimeracil Oteracil Potassium chemotherapy in the treatment of patients with recurrent esophagus cancer. Methods: One hundred and twelve senile patients who suffered from esophagus cancer were selected and randomly divided into two groups, namely, observation group (56 cases) and control group (56 cases). The observation group adopted three-dimensional conformal radiotherapy combined with Tegafur Gimeracil Oteracil Potassium chemotherapy and the control group adopted three-dimensional conformal radiotherapy only. Results: All patients completed the treatment, with good compliance. Effective rate of the observation group was 82.1%, which was significantly higher than the control group (67.9%), and the difference was statistically significant (P<0.05). Main toxic and side effects of patients of two groups were radiation esophagitis, gastrointestinal reaction, hematologic toxicities and radiative skin reaction. Differences of incidence rates of all types of toxic and side effects were not statistically significant (P>0.05). The one-year and two-year survival rates of patients of the observation group were 80.4% and 53.6%, respectively, while the control group was 55.4% and 30.4%; differences between two groups were statistically significant (P<0.05). Conclusion: Three-dimensional conformal radiotherapy combined with Tegafur Gimeracil Oteracil Potassium chemotherapy has definite curative effect in treating patients with recurrent esophagus cancer and can improve survival rate of patients, without increasing adverse reaction. PMID:27882010

  5. Short-term clinical effect of conformal radiotherapy combined with tegafur gimeracil oteracil potassium in treating recurrent esophagus cancer.

    PubMed

    Jiao, Yuyan; Shen, Yuzhen; Yan, Hua; Liu, Yan; Tan, Haihua; Li, Jianzhe

    2016-01-01

    To observe clinical effects of three-dimensional conformal radiotherapy combined with Tegafur Gimeracil Oteracil Potassium chemotherapy in the treatment of patients with recurrent esophagus cancer. One hundred and twelve senile patients who suffered from esophagus cancer were selected and randomly divided into two groups, namely, observation group (56 cases) and control group (56 cases). The observation group adopted three-dimensional conformal radiotherapy combined with Tegafur Gimeracil Oteracil Potassium chemotherapy and the control group adopted three-dimensional conformal radiotherapy only. All patients completed the treatment, with good compliance. Effective rate of the observation group was 82.1%, which was significantly higher than the control group (67.9%), and the difference was statistically significant (P<0.05). Main toxic and side effects of patients of two groups were radiation esophagitis, gastrointestinal reaction, hematologic toxicities and radiative skin reaction. Differences of incidence rates of all types of toxic and side effects were not statistically significant (P>0.05). The one-year and two-year survival rates of patients of the observation group were 80.4% and 53.6%, respectively, while the control group was 55.4% and 30.4%; differences between two groups were statistically significant (P<0.05). Three-dimensional conformal radiotherapy combined with Tegafur Gimeracil Oteracil Potassium chemotherapy has definite curative effect in treating patients with recurrent esophagus cancer and can improve survival rate of patients, without increasing adverse reaction.

  6. A self-assembled multimodal complex for combined pre- and intraoperative imaging of the sentinel lymph node

    NASA Astrophysics Data System (ADS)

    Buckle, Tessa; van Leeuwen, Anne C.; Chin, Patrick T. K.; Janssen, Hans; Muller, Sara H.; Jonkers, Jos; van Leeuwen, Fijs W. B.

    2010-09-01

    Specific removal of the sentinel lymph node (SLN) during breast cancer surgery presents physicians with the opportunity to detect early metastatic disease. To increase the accuracy of intraoperative SLN detection, new methods with higher sensitivity and specificity are required. We have quantitatively compared conventional preoperative lymphoscintigraphy with albumin radiocolloids (99mTc-NanoColl) with optical intraoperative guidance using the near infrared dye indocyanine green (ICG) in an orthotopic mouse model for metastatic breast cancer. Furthermore, we have applied a self-assembled multimodal complex, in which ICG is non-covalently bound to the albumin radiocolloid, to attain identical dynamics of the radioactive and optical components. The SLN specificity of the multimodal complex is similar to conventional lymphoscintigraphy, while the fluorescent signal-to-noise ratio is improved by 86% compared to ICG alone. In addition, the multimodal complex permits scintigraphic validation of the fluorescent findings. The multimodal ICG-99mTc-NanoColl complex can be used both for lymphoscintigraphy by preoperative single photon emission computed tomography/computed tomography and for surgical navigation by intraoperative fluorescence imaging.

  7. Frameless stereotactic functional neuronavigation combined with intraoperative magnetic resonance imaging as a strategy in highly eloquent located tumors causing epilepsy.

    PubMed

    Sommer, Bjoern; Grummich, Peter; Hamer, Hajo; Bluemcke, Ingmar; Coras, Roland; Buchfelder, Michael; Roessler, Karl

    2014-01-01

    Intractable epilepsy due to tumors located in highly eloquent brain regions is often considered surgically inaccessible because of a high risk of postoperative neurological deterioration. Intraoperative MRI and functional navigation contribute to overcome this problem. To retrospectively investigate the long-term results and impact of functional neuronavigation and 1.5-tesla intraoperative MRI on patients who underwent surgery of tumors associated with epilepsy located close to or within eloquent brain areas. Nineteen patients (9 female, 10 male, mean age 41.4 ± 13.4 years, 11 low-grade and 8 high-grade glial tumors) were evaluated preoperatively using BOLD imaging, diffusion-tensor imaging tractography and magnetoencephalography. Functional data were implemented into neuronavigation in this multimodal approach. In 14 of 19 patients (74%), complete resection was achieved, and in 5 patients significant tumor volume reduction was accomplished. Eight of 14 (57%) complete resections were achieved only by performing an intraoperative image update. Neurological deterioration was found permanently in 2 patients. After a mean follow-up of 43.8 ± 23.8 months, 15 patients (79%) became seizure free (Engel class Ia). Despite the highly eloquent location of tumors causing intractable epilepsy, our multimodal approach led to complete resection in more than two-thirds of patients with an acceptable neurological morbidity and excellent long-term seizure control.

  8. Combination of Vandetanib, Radiotherapy, and Irinotecan in the LoVo Human Colorectal Cancer Xenograft Model

    SciTech Connect

    Wachsberger, Phyllis; Burd, Randy; Ryan, Anderson; Daskalakis, Constantine; Dicker, Adam P.

    2009-11-01

    Purpose: The tumor growth kinetics of the human LoVo colorectal xenograft model was assessed in response to vandetanib, an orally available receptor tyrosine kinase inhibitor, radiotherapy (RT), or irinotecan (CPT-11), as single therapies and in combination. Methods and Materials: LoVo cells were injected subcutaneously into the right hind limb (5x10{sup 6} cells in 100muL phosphate-buffered saline) of athymic NCR NUM mice and tumors were grown to a volume of 200-300 mm{sup 3} before treatment. Vandetanib was administered at 50 mg/kg daily orally for 14 days starting on Day 1. RT was given as three fractions (3x3 Gy) on Days 1, 2, and 3. CPT-11 was given at 15 mg/kg intraperitoneally on Days 1 and 3. Tumor volumes were measured on a daily basis and calculated by measuring tumor diameters with digital calipers in two orthogonal dimensions. Results: All three single treatments (vandetanib, CPT-11, and radiation) significantly slowed LoVo colorectal tumor growth. Vandetanib significantly increased the antitumor effects of CPT-11 and radiation when given in combination with either of these treatments. These treatment combinations resulted in a slow tumor growth rate during the 2 weeks of vandetanib administration. The triple combination of vandetanib, CPT-11, and radiation produced the most marked improvement in response as observed by measurable shrinkage of tumors during the first week of treatment. Conclusions: The tumor growth delay kinetics observed in this study of the LoVo colorectal model suggest concurrent and sustained post-sequencing of vandetanib with cytotoxic therapy may be beneficial in tumors of this type.

  9. Prospective phase II trial of nimotuzumab in combination with radiotherapy and concurrent capecitabine in locally advanced rectal cancer.

    PubMed

    Jin, Ting; Zhu, Yuan; Luo, Jia-Lin; Zhou, Ning; Li, De-Chuan; Ju, Hai-Xin; Fan, Yong-Tian; Liu, Yong; Zhu, Yu-Ping; Feng, Hai-Yang; Liu, Lu-Ying

    2015-03-01

    The aim of the study was to evaluate the safety and efficacy of adding concurrent nimotuzumab to preoperative radiotherapy with concurrent capecitabine in locally advanced rectal cancer. Patients with rectal cancer (clinical stage T3/4 or N+) were scheduled to receive weekly nimotuzumab (400 mg; days -6, 1, 8, 15, 22, and 29). Capecitabine (825 mg/m(2)) was delivered orally twice daily for the duration of radiotherapy. Radiotherapy was administered at 50.4 Gy (45 + 5.4 Gy). The main endpoint was the pathologic complete response (pCR) rate. Twenty-one patients with T3 or T4 disease were enrolled; 66.7 % were nodal-positive; the median distance from the anal verge was 5.5 cm. A pCR was achieved in four patients (19.0 %); 71.4 % patients obtained moderate or good tumor regression (Grade 2 and 3). Downstaging occurred in 15/21 (71.4 %) patients by T stage and 11/14 (78.6 %) by N stage. The actual dose intensities (median/mean, %) were nimotuzumab (100, 100) and capecitabine (100, 99.5). The most frequent Grade 1/2 toxicities were radiation dermatitis (57.1 %), nausea/vomiting (52.4 %), leukocytopenia (47.6 %), diarrhea (47.6 %), and proctitis (38.1 %). Grade 3 diarrhea was observed in 9.5 % of patients and Grade 3 leukocytopenia in 4.8 %. These preliminary results indicate that nimotuzumab can be safely combined with radiotherapy plus concurrent capecitabine. The efficacy of this regimen (pCR = 19.0 %) was significantly higher than that observed in previous phase II trials of preoperative radiotherapy with concurrent capecitabine and cetuximab in rectal cancer. Further investigation of concurrent nimotuzumab with radiotherapy plus capecitabine is warranted.

  10. High biologically effective dose radiation therapy using brachytherapy in combination with external beam radiotherapy for high-risk prostate cancer

    PubMed Central

    Wada, Akinori; Kohno, Naoaki

    2017-01-01

    Purpose To evaluate the outcomes of high-risk prostate cancer patients treated with biologically effective dose (BED) ≥ 220 Gy of high-dose radiotherapy, using low-dose-rate (LDR) brachytherapy in combination with external beam radiotherapy (EBRT) and short-term androgen deprivation therapy (ADT). Material and methods From 2005 to 2013, a total of 143 patients with high-risk prostate cancer were treated by radiotherapy of BED ≥ 220 Gy with a combination of LDR brachytherapy, EBRT, and androgen deprivation therapy (ADT). The high-risk patients in the present study included both high-risk and very high-risk prostate cancer. The number of high-risk features were: 60 patients with 1 high-risk factor (42%), 61 patients with 2 high-risk factors (43%), and 22 patients with 3 high-risk factors (15%) including five N1 disease. External beam radiotherapy fields included prostate and seminal vesicles only or whole pelvis depending on the extension of the disease. Biochemical failure was defined by the Phoenix definition. Results Six patients developed biochemical failure, thus providing a 5-year actual biochemical failure-free survival (BFFS) rate of 95.2%. Biochemical failure was observed exclusively in cases with distant metastasis in the present study. All six patients with biochemical relapse had clinical failure due to bone metastasis, thus yielding a 5-year freedom from clinical failure (FFCF) rate of 93.0%. None of the cases with N1 disease experienced biochemical failure. We observed four deaths, including one death from prostate cancer, therefore yielding a cause-specific survival (CSS) rate of 97.2%, and an overall survival (OS) rate of 95.5%. Conclusions High-dose (BED ≥ 220 Gy) radiotherapy by LDR in combination with EBRT has shown an excellent outcome on BFFS in high-risk and very high-risk cancer, although causal relationship between BED and BFFS remain to be explained further. PMID:28344597

  11. Prognostic factors for tumour response and skin damage to combined radiotherapy and hyperthermia in superficial recurrent breast carcinomas.

    PubMed

    Lindholm, C E; Kjellén, E; Nilsson, P; Weber, L; Hill, S

    1995-01-01

    Prognostic factors for complete tumour response and acute skin damage to combined hyperthermia and radiotherapy were analysed in material of patients with breast cancer, recurrent in previously irradiated areas. Radiotherapy was given daily to a total absorbed dose of 30.0 Gy in 2 weeks or 34.5 Gy in 3 weeks. The first radiotherapy schedule was combined with heat twice weekly, a total of four heat treatments (schedule A). The second radiotherapy schedule was combined with heat either once or twice a week resulting in a total of three (schedule B) or six (schedule C) heat treatments. Heat was induced with microwaves (2450, 915 or 434 MHz) via external applicators and always given after the radiotherapy fraction. The complete response (CR) rate in evaluable patients was 71% (49/69). There was no significant difference in CR rate between the three different hyperthermia schedules. The CR rates were 74% (14/19), 65% (15/23) and 74% (20/27) for schedules A, B and C respectively. The only factor predicting CR, evaluated both uni- and multivariately, was the CRE-value for the present radiotherapy dose (p = 0.02). If only tumours treated with 915 MHz were taken into account, however, then the highest minimum temperature at a given heat session predicted complete response (p = 0.03). This was true also in a multivariate analysis of this subgroup of tumours. A Kaplan-Meier analysis (log rank test) showed no significant difference in duration of CR between the different treatment schedules. Cox's proportional hazards method revealed three significant factors: tumour size (negatively correlated, p = 0.007), the time interval between the diagnosis of the primary tumour and the present treatment (p = 0.02) and the average temperature (0.03). Maximum acute skin reactions in the treatment field were scored according to an ordinal scale of 0-8, modified after WHO 1979. Twenty-six treatment areas (32%) expressed more severe skin damage (score > or = 5) in terms of desquamation with

  12. Novel radiotherapy approaches for lung cancer: combining radiation therapy with targeted and immunotherapies

    PubMed Central

    Simone, Charles B.; Burri, Stuart H.

    2015-01-01

    Targeted therapies and immunotherapies have quickly become fixtures in the treatment armamentarium for metastatic non-small cell lung cancer (NSCLC). Targeted therapies directed against epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) translocations, and ROS-1 rearrangements have demonstrated improved progression free survival (PFS) and, in selected populations, improved overall survival (OS) compared with cytotoxic chemotherapy. Immunotherapies, including checkpoint inhibitor monoclonal antibodies against programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1), have now also demonstrated improved survival compared with chemotherapy. The use of these novel systemic agents in non-metastatic patient populations and in combination with radiation therapy is not well defined. As radiation therapy has become more effective and more conformal with fewer toxicities, it has increasingly been used in the oligometastatic or oligoprogression setting. This has allowed improvement in PFS and potentially OS, and in the oligoprogressive setting may overcome acquired drug resistance of a specific lesion(s) to allow patients to remain on their targeted therapies. Molecularly targeted therapies and immunotherapies for patients with metastatic NSCLC have demonstrated much success. Advances in radiation therapy and stereotactic body radiotherapy, radiation therapy have led to combination strategies with targeted therapies among patients with lung cancer. Radiation therapy has also been combined with immunotherapies predominantly in the metastatic setting. In the metastatic population, radiation therapy has the ability to provide durable local control and also augment the immune response of systemic agents, which may lead to an abscopal effect of immune-mediated tumor response in disease sites outside of the radiation field in select patients. PMID:26629423

  13. Intensity-Modulated Radiotherapy Causes Fewer Side Effects than Three-Dimensional Conformal Radiotherapy When Used in Combination With Brachytherapy for the Treatment of Prostate Cancer

    SciTech Connect

    Forsythe, Kevin; Blacksburg, Seth; Stone, Nelson; Stock, Richard G.

    2012-06-01

    Purpose: To measure the benefits of intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3D-CRT) when used in combination with brachytherapy for the treatment of prostate cancer. Methods and Materials: We conducted a retrospective review of all patients with localized prostate cancer who received external-beam radiotherapy (EBRT) in combination with brachytherapy with at least 1 year follow-up (n = 812). Combination therapy consisted of {sup 103}Pd or {sup 125}I implant, followed by a course of EBRT. From 1993 to March 2003 521 patients were treated with 3D-CRT, and from April 2003 to March 2009 291 patients were treated with IMRT. Urinary symptoms were prospectively measured with the International Prostate Symptom Score questionnaire with a single quality of life (QOL) question; rectal bleeding was assessed per the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Schema. The Pearson {chi}{sup 2} test was used to compare toxicities experienced by patients who were treated with either IMRT or 3D-CRT. Logistic regression analyses were also performed to rule out possible confounding factors. Results: Within the first 3 months after treatment, patients treated with 3D-CRT scored their urinary symptoms as follows: 19% mild, 44% moderate, and 37% severe; patients treated with IMRT scored their urinary symptoms as follows: 36% mild, 47% moderate, and 17% severe (p < 0.001). The 3D-CRT patients rated their QOL as follows: 35% positive, 20% neutral, and 45% negative; IMRT patients rated their QOL as follows: 51% positive, 18% neutral, and 31% negative (p < 0.001). After 1 year of follow-up there was no longer any difference in urinary morbidity between the two groups. Logistic regression confirmed the differences in International Prostate Symptom Score and QOL in the acute setting (p < 0.001 for both). Grade {>=}2 rectal bleeding was reported by 11% of 3D

  14. X-Ray Induced Photodynamic Therapy: A Combination of Radiotherapy and Photodynamic Therapy

    PubMed Central

    Wang, Geoffrey D.; Nguyen, Ha T.; Chen, Hongmin; Cox, Phillip B.; Wang, Lianchun; Nagata, Koichi; Hao, Zhonglin; Wang, Andrew; Li, Zibo; Xie, Jin

    2016-01-01

    Conventional photodynamic therapy (PDT)'s clinical application is limited by depth of penetration by light. To address the issue, we have recently developed X-ray induced photodynamic therapy (X-PDT) which utilizes X-ray as an energy source to activate a PDT process. In addition to breaking the shallow tissue penetration dogma, our studies found more efficient tumor cell killing with X-PDT than with radiotherapy (RT) alone. The mechanisms behind the cytotoxicity, however, have not been elucidated. In the present study, we investigate the mechanisms of action of X-PDT on cancer cells. Our results demonstrate that X-PDT is more than just a PDT derivative but is essentially a PDT and RT combination. The two modalities target different cellular components (cell membrane and DNA, respectively), leading to enhanced therapy effects. As a result, X-PDT not only reduces short-term viability of cancer cells but also their clonogenecity in the long-run. From this perspective, X-PDT can also be viewed as a unique radiosensitizing method, and as such it affords clear advantages over RT in tumor therapy, especially for radioresistant cells. This is demonstrated not only in vitro but also in vivo with H1299 tumors that were either subcutaneously inoculated or implanted into the lung of mice. These findings and advances are of great importance to the developments of X-PDT as a novel treatment modality against cancer. PMID:27877235

  15. Hypofractionated Proton Boost Combined with External Beam Radiotherapy for Treatment of Localized Prostate Cancer

    PubMed Central

    Johansson, Silvia; Åström, Lennart; Sandin, Fredrik; Isacsson, Ulf; Montelius, Anders; Turesson, Ingela

    2012-01-01

    Proton boost of 20 Gy in daily 5 Gy fractions followed by external beam radiotherapy (EBRT) of 50 Gy in daily 2 Gy fractions were given to 278 patients with prostate cancer with T1b to T4N0M0 disease. Fifty-three percent of the patients received neoadjuvant androgen deprivation therapy (N-ADT). The medium followup was 57 months. The 5-year PSA progression-free survival was 100%, 95%, and 74% for low-, intermediate-, and high-risk patients, respectively. The toxicity evaluation was supported by a patient-reported questionnaire before every consultant visit. Cumulative probability and actuarial prevalence of genitourinary (GU) and gastrointestinal (GI) toxicities are presented according to the RTOG classification. N-ADT did not influence curability. Mild pretreatment GU-symptoms were found to be a strong predictive factor for GU-toxicity attributable to treatment. The actuarial prevalence declined over 3 to 5 years for both GU and GI toxicities, indicating slow resolution of epithelial damage to the genitourinary and gastrointestinal tract. Bladder toxicities rather than gastrointestinal toxicities seem to be dose limiting. More than 5-year followup is necessary to reveal any sign of true progressive late side effects of the given treatment. Hypofractionated proton-boost combined with EBRT is associated with excellent curability of localized PC and acceptable frequencies of treatment toxicity. PMID:22848840

  16. Regional hyperthermia combined with radiotherapy for esophageal squamous cell carcinoma with supraclavicular lymph node metastasis

    PubMed Central

    Liming, Sheng; Yongling, Ji; Qiner, Wu; Xianghui, Du

    2017-01-01

    To assess the efficacy and toxicity of Intensity-modulated radiotherapy (IMRT) and hyperthermia for upper and middle thoracic esophageal squamous cell carcinoma (UMT-ESCC) with supraclavicular lymph node metastasis. A total of 50 patients with UMT-ESCC with supraclavicular lymph node metastasis were evaluated in this retrospective study. All patients received IMRT. Hyperthermia was delivered simultaneously with irradiation, in 45 minutes twice a week for 5-6 weeks. Hyperthermia included supraclavicular lymph node metastasis. Forty-four patients (88.0%) received concurrent chemoradiotherapy based on cisplatin regimens. The most common types of hematological toxicities were anemia (62.0%) and leukopenia (60.0%). Most of these events were grade 1-2 and transient. The 3-year progression-free survival (PFS) rate and overall survival (OS) rate were 34.9% and 42.5%, respectively. Cox regression revealed that tumor length and number of supraclavicular lymph node metastasis were two independent predictors of OS (tumor length: HR=3.65, p=0.008; nodal stage: HR=8.07, p=0.019). The IMRT combined with supraclavicular regional hyperthermia has low toxicity and well tolerated with excellent local control in UMT-ESCC with supraclavicular lymph node metastasis. PMID:28029663

  17. Interstitial microwave hyperthermia combined with iridium-192 radiotherapy for recurrent tumors

    SciTech Connect

    Petrovich, Z.; Langholz, B.; Lam, K.; Luxton, G.; Cohen, D.; Jepson, J.; Astrahan, M.

    1989-06-01

    From 1985 through 1987, 44 tumors in 39 patients with recurrent cancer were treated with interstitial microwave hyperthermia (HT) combined with interstitial /sup 192/Ir radiotherapy (RT). All patients had unresectable and previously treated tumors (mean RT dose 57.6 Gy). Diagnoses were squamous cell carcinoma in 27 (62%), adenocarcinoma in 11 (25%), melanoma in 5 (11%), and soft tissue sarcoma in 1 (2%) site. Interstitial RT dose was from 25 to 50 Gy (mean 38.3 Gy). The first HT session was scheduled immediately before the loading of /sup 192/Ir, and the second was scheduled following its removal. Each session lasted 45-60 min at therapeutic temperature (42.5 degrees C). Complete response (CR) was obtained in 28 (64%) sites and partial response (PR) in 15 (34%) sites. None of the CR patients had local recurrence. Tumor volume was the most important factor influencing CR (p less than 0.001). The treated site, radiation dose, and thermal dose were not significant factors for CR (p = 0.03). The overall median survival was 39 weeks, with a 2-year survival of 22%. The treatment was well tolerated, with two patients developing focal skin necrosis.

  18. Hypofractionated proton boost combined with external beam radiotherapy for treatment of localized prostate cancer.

    PubMed

    Johansson, Silvia; Aström, Lennart; Sandin, Fredrik; Isacsson, Ulf; Montelius, Anders; Turesson, Ingela

    2012-01-01

    Proton boost of 20 Gy in daily 5 Gy fractions followed by external beam radiotherapy (EBRT) of 50 Gy in daily 2 Gy fractions were given to 278 patients with prostate cancer with T1b to T4N0M0 disease. Fifty-three percent of the patients received neoadjuvant androgen deprivation therapy (N-ADT). The medium followup was 57 months. The 5-year PSA progression-free survival was 100%, 95%, and 74% for low-, intermediate-, and high-risk patients, respectively. The toxicity evaluation was supported by a patient-reported questionnaire before every consultant visit. Cumulative probability and actuarial prevalence of genitourinary (GU) and gastrointestinal (GI) toxicities are presented according to the RTOG classification. N-ADT did not influence curability. Mild pretreatment GU-symptoms were found to be a strong predictive factor for GU-toxicity attributable to treatment. The actuarial prevalence declined over 3 to 5 years for both GU and GI toxicities, indicating slow resolution of epithelial damage to the genitourinary and gastrointestinal tract. Bladder toxicities rather than gastrointestinal toxicities seem to be dose limiting. More than 5-year followup is necessary to reveal any sign of true progressive late side effects of the given treatment. Hypofractionated proton-boost combined with EBRT is associated with excellent curability of localized PC and acceptable frequencies of treatment toxicity.

  19. Intraoperative direct subcortical stimulation for identification of the internal capsule, combined with an image-guided stereotactic system during surgery for basal ganglia lesions.

    PubMed

    Duffau, H

    2000-03-01

    The two main problems of surgery for basal ganglia lesions are: first, the difficulty of accurately localizing the lesion in this deep location; and second, the proximity to the internal capsule, with the risk of permanent postoperative sequelae. The author describes the use of intraoperative direct electrical subcortical stimulation in the identification and preservation of the internal capsule, combined with an image-guided stereotactic system for the selection of the best surgical approach in a case of deep cavernoma. A 33-year-old man was admitted to our institution with a history of three episodes of transitory left hemiparesia in the last 12 years. Neurological examination revealed a mild left weakness. Magnetic resonance imaging (MRI) showed typical features of a right posterior capsular-lentiform cavernoma. To prevent another hemorrhagic event, surgery was performed via a right transdistal sylvian approach, using a computer-assisted stereotactic method that allowed us to reach the lesion directly and direct stimulations to detect the subcortical pyramidal pathways. The patient had a transitory worsening with complete recovery in 10 days. Control MRI showed total resection. As described at the cortical level, the intraoperative direct subcortical stimulations seem also to represent an easy, safe, accurate, and reliable method of real-time functional identification of the internal capsule during surgery for basal ganglia lesions. The combination with an image-guided stereotactic system to accurately localize the lesion minimizes the risk of postoperative sequelae, and seems to warrant an increase of the surgical indications in this location.

  20. Intraoperative combined color and fluorescent images-based sentinel node mapping in the porcine lung: comparison of indocyanine green with or without albumin premixing.

    PubMed

    Oh, Yujin; Quan, Yu Hua; Choi, Yeonho; Kim, Choong Ki; Kim, Heezoo; Kim, Hyun Koo; Kim, Beop-Min

    2013-12-01

    We developed a multimodal optical imaging system for intraoperative visualization of sentinel lymph nodes (SLNs). This study is to validate our system by showing SLNs in the lung through combined optical color and fluorescent image with indocyanine green (ICG) and ICG with human serum albumin (HSA). Identical ICG concentrations of ICG only or ICG:HSA was injected into the rat footpad and porcine lung. Absolute amounts of the fluorescents were scaled on the basis of animal weights. The entire procedures were recorded using color and near-infrared (NIR) charge-coupled device (CCD) cameras simultaneously, and the 2 images were merged by real-time image processing software. All fluorescence intensity signals to background ratio (SBR) and retention rates at SLN for both fluorescents were estimated and compared. This newly developed intraoperative color and fluorescence optical imaging system successfully visualized the SLNs in animal experiments. The SLNs were identified 100% for both rat and pig under in vivo conditions. Real-time image processing software overcame the low signal of NIR fluorescence images. ICG and ICG:HSA provided no significantly different SBR in the SLN images for both rat thigh and pig lung. The intraoperative optical imaging system enabled real-time image-guided surgery during SLN mapping in lung in an animal model. The ICG retention rate was similar to ICG:HSA. ICG alone can be useful for SLN imaging during lung cancer surgery. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  1. Intraoperative Period and Breast Cancer: Review

    PubMed Central

    Akan, Arzu; Şimsek, Şerife

    2014-01-01

    Intraoperative radiation therapy in breast cancer (IORT) delivers a concentrated dose of radiation therapy to a tumor bed during surgery. IORT offers some of the following advantages with typically fewer complications like; maximum effect, sparing healthy tissues and organs, to help the patients finish treatment and get back to their normal activities. The goal of IORT is to improve local tumor control and survival rates for patients with breast cancer. IORT can both be performed with electron beams (ELIOT) and X-rays. Two main randomised trials testing intraoperative partial breast radiotherapy are TARGIT trial and the ELIOT (intraoperative radiotherapy with electrons) trial, but the techniques are fundamentally different. Whereas TARGIT delivers radiation from within the undisturbed tumour bed, for ELIOT, the mammary gland is mobilised, a prepectoral lead shield is inserted, the edges of the tumour bed are apposed, and radiation is delivered from without.

  2. High-dose-rate Three-dimensional Conformal Radiotherapy Combined with Active Breathing Control for Stereotactic Body Radiotherapy of Early-stage Non-small-cell Lung Cancer.

    PubMed

    Wang, Ruozheng; Yin, Yong; Qin, Yonghui; Yu, Jinming

    2015-12-01

    The purpose of this study was to evaluate the feasibility and benefits of using high-dose-rate three-dimensional conformal radiotherapy (3D-CRT) combined with active breathing control (ABC) for stereotactic body radiotherapy (SBRT) of patients with early-stage non-small-cell lung cancer (NSCLC). Eight patients with early-stage NSCLC underwent CT scans under standard free-breathing (FB) and moderately deep inspiration breath-hold (mDIBH) with ABC. Two high-dose-rate 3D-CRT plans (1000 Mu/min) were designed based on the CT scans with FB and mDIBH. The maximal dose (D1%), minimal dose (D99%), conformity index (CI), and homogeneity index (HI) of the planning target volume (PTV), and dose-volume indices of the organs at risk between each plan were compared. The mean PTV volume decreased from 158.04 cm(3) with FB to 76.90 cm(3) with mDIBH (p < 0.05). When mDIBH was used, increases in the affected lung volume (by 47%), contralateral lung volume (by 55%), and total lung volume (by 50%) were observed compared to FB (p < 0.05). The V5-V40 of the affected lung (Vx represented the percentage volume of organs receiving at least the x Gy), V5-V40 and the mean dose for the total lung, V5-V40 and mean dose of the chest wall, and the maximum dose of the spinal cord were less for mDIBH than FB (p < 0.05). There were no significant differences in CI, HI, D1%, or D99% for the PTV between the plans. In conclusion, high-dose-rate 3D-CRT combined with ABC reduced the radiation dose to the lungs and chest wall without affecting the dose distribution in SBRT of early-stage NSCLC patients.

  3. [Intraoperative high-field magnetic resonance imaging combined with functional neuronavigation in resection of low-grade temporal lobe tumors involving optic radiation].

    PubMed

    Bai, Shaocong; Chen, Xiaolei; Geng, Jiefeng; Wu, Dongdong; Yu, Xinguang; Xu, Bainan

    2015-05-01

    To investigate the clinical value of high-field-strength intraoperative magnetic resonance imaging (iMRI) combined with optic radiation neuro-navigation for the resection of temporal lobe low-grade gliomas. From April 2009 to September 2013, 65 patients with temporal lobe low-grade gliomas (WHO grade II) involving optic radiation were operated with iMRI and functional neuro-navigation. Diffusion tensor imaging (DTI) based fiber tracking was used to delineate optic radiation. The reconstructed optic radiations were integrated into a navigation system, in order to achieve intraoperative microscopic-based functional neuro-navigation. iMRI was used to update the images for both optic radiations and residual tumors. Volumetric analyses were performed using 3D Slicer for pre- and intra-operative tumor volumes in all cases. All patients were evaluated for visual field deficits preoperatively and postoperatively. The Student t test was used to evaluate the average rate of extent of resection between groups. Spearman rank correlation analysis was used to assess correlations between predictors and epilepsy prognosis. Preoperative tumor volumes were (78±40) cm3. In 29 cases, iMRI scan detected residual tumor that could be further resected, and extent of resection were increased from 76.2% to 92.7% (t=7.314, P<0.01). In 19 cases (29.2%), gross total resection was accomplished, and iMRI contributed directly to 8 of these cases. Postsurgical follow-up period varied from 13 months to 59 months, mean (33±13) months. Tumor progression were observed in 3 patients, newly developed or deteriorated visual field defects occurred in 4 patients (6.2%). For patients with pre-operative seizures, Engel Class I were achieved for 89.7% of them. Spearman rank correlation analysis revealed that seizure outcome (Engel Class) was related to increased excision of ratio (r=-0.452, P=0.004, 95% CI: -0.636--0.261) and larger tumors (r=0.391, P=0.014, 95% CI: 0.178-0.484). With iMRI and functional

  4. Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy

    SciTech Connect

    De Crevoisier, Renaud . E-mail: rdecrevo@mdanderson.org; Baudin, Eric; Bachelot, Anne; Leboulleux, Sophie; Travagli, Jean-Paul; Caillou, Bernard; Schlumberger, Martin

    2004-11-15

    Purpose: To analyze a prospective protocol combining surgery, chemotherapy (CT), and hyperfractionated accelerated radiotherapy (RT) in anaplastic thyroid carcinoma. Methods and materials: Thirty anaplastic thyroid carcinoma patients (mean age, 59 years) were treated during 1990-2000. Tumor extended beyond the capsule gland in 26 patients, with tracheal extension in 8. Lymph node metastases were present in 18 patients and lung metastases in 6. Surgery was performed before RT-CT in 20 patients and afterwards in 4. Two cycles of doxorubicin (60 mg/m{sup 2}) and cisplatin (120 mg/m{sup 2}) were delivered before RT and four cycles after RT. RT consisted of two daily fractions of 1.25 Gy, 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum. Results: Acute toxicity (World Health Organization criteria) was Grade 3 or 4 pharyngoesophagitis in 10 patients; Grade 4 neutropenia in 21, with infection in 13; and Grade 3 or 4 anemia and thrombopenia in 8 and 4, respectively. At the end of the treatment, a complete local response was observed in 19 patients. With a median follow-up of 45 months (range, 12-78 months), 7 patients were alive in complete remission, of whom 6 had initially received a complete tumor resection. Overall survival rate at 3 years was 27% (95% confidence interval 10-44%) and median survival 10 months. In multivariate analysis, tracheal extension and macroscopic complete tumor resection were significant factors in overall survival. Death was related to local progression in 5% of patients, to distant metastases in 68%, and to both in 27%. Conclusions: Main toxicity was hematologic. High long-term survival was obtained when RT-CT was given after complete surgery. This protocol avoided local tumor progression, and death was mainly caused by distant metastases.

  5. [Early results of combined treatment (induction chemotherapy and radiotherapy) of patients with squamous cell carcinoma of the oropharynx].

    PubMed

    Szutkowski, Z; Krzakowski, M; Hliniak, A; Wasilewski, M

    1990-01-01

    The results of combined treatment (induction chemotherapy followed by irradiation) in 23 patients with locally advanced squamous cell carcinoma of the oropharynx were presented. Chemotherapy program included Cisplatin 100 mg/m2 i.v. in day 1 and 5-fluorouracil 750 mg/m2 i.v. on day 1-5. The chemotherapy was administered every 3 weeks for maximum 3 cycles. Complete response in 15 patients (65%), stabilization in 4 patients (17%) and progressive disease was found in 3 patients (14%). 20 patients were irradiated with radical intention. Complete response was found in 9 patients (45%) after radiotherapy. Treatment was relatively well-tolerated. Out of 17 patients with at least 6 months' follow-up (range 6-24) 6 patients are alive with no evidence of disease. We estimate the postirradiation reaction as slightly more severe than after radiotherapy alone. The reaction did not influence the prescribed way of fractionation.

  6. Therapeutic responses of spontaneous canine malignancies to combinations of radiotherapy and hyperthermia.

    PubMed

    Denman, D L; Legorreta, R A; Kier, A B; Elson, H R; White, M L; Buncher, C R; Lewis, G C; Born, A M; Sundararaman, S; Aron, B S

    1991-07-01

    The goals of this ongoing Phase III study of adjuvant local hyperthermia with radiotherapy were to evaluate how tumor control and normal tissue complications were related to patient and treatment variables. Canine veterinary patients with localized malignancies were stratified by histology and anatomic site and randomized into three groups. All patients received radiotherapy (60CO) in 3.5 Gy fractions given Mon-Wed-Fri to 14 treatments (49 Gy). One group received radiotherapy alone while the others also received microwave-induced hyperthermia (44 degrees C) for 30 minutes once each week. Hyperthermia followed radiotherapy and was given to one group immediately and delayed 4-5 hours in the other. Adjuvant hyperthermia resulted in a significant (p less than .05) increase in complete response rate, reduction in the frequency of non-responders, and increased persistent local control relative to radiotherapy alone. Hyperthermia increased the complete response rate regardless of histology, site, or volume and with the current sample size control was significantly (p less than .05) greater for sarcomas, tumors of the trunk and extremities, and those with volumes less than 10 cc. Quantitative clinical assessment of the acute response of skin and oral mucosa indicated that hyperthermia significantly enhanced these acute reactions, which required roughly twice the healing time observed with radiotherapy alone. Quantitative histologic scoring of changes seen between pre- and post-therapy skin biopsies indicated that a treatment induced decline in the frequency of dermal blood vessels, sebaceous glands, and hair follicles was enhanced by adjuvant hyperthermia, particularly in the late response evaluation interval. The probability of tumor control and adverse normal tissue responses correlated with several measures of thermal dose. Thermal doses in excess of 120 equivalent minutes at 43 degrees C correlated positively with increased skin reactions and negatively with the

  7. The novel microtubule targeting agent BAL101553 in combination with radiotherapy in treatment-refractory tumor models.

    PubMed

    Sharma, Ashish; Broggini-Tenzer, Angela; Vuong, Van; Messikommer, Alessandra; Nytko, Katarzyna J; Guckenberger, Matthias; Bachmann, Felix; Lane, Heidi A; Pruschy, Martin

    2017-09-01

    Resistance to microtubule targeting agents (MTA) represents a major drawback in successful cancer therapy with MTAs. Here we investigated the combined treatment modality of the novel MTA BAL101553 in combination with radiotherapy in paclitaxel and epothilone-resistant tumor models. Multiple regimens of BAL101553, or its active moiety BAL27862 for in vitro experiments, were probed in combination with radiotherapy in P-glycoprotein-overexpressing, human colon adenocarcinoma cells (SW480) and in tubulin-mutated human NSCLC cells (A549EpoB40) and tumors thereof. BAL27862 reduced the proliferative activity of SW480 and A549EpoB40 tumor cells with similar potency as in A549 wildtype cells. Combined treatment of BAL27862 with ionizing radiation in vitro resulted in an additive reduction of clonogenicity. Moreover, treatment of paclitaxel- and epothilone-resistant tumors with fractionated irradiation and different regimens of BAL101553 (a single i.v. bolus vs. oral daily) suppressed tumor growth and resulted in an extended additive tumor growth delay with strong reduction of tumor proliferation and mean tumor vessel density. BAL101553 is a promising alternative in taxane- and epothilone-refractory tumors as part of a combined treatment modality with ionizing radiation. Its potent antitumor effect is not only tumor cell-directed but also targets the tumor microenvironment. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Combination of adjuvant chemotherapy and radiotherapy is associated with improved survival at early stage type II endometrial cancer and carcinosarcoma.

    PubMed

    Sozen, Hamdullah; Çiftçi, Rumeysa; Vatansever, Dogan; Topuz, Samet; Iyibozkurt, Ahmet Cem; Bozbey, Hamza Ugur; Yaşa, Cenk; Çali, Halime; Yavuz, Ekrem; Kucucuk, Seden; Aydiner, Adnan; Salihoglu, Yavuz

    2016-04-01

    The aim of this study was to describe the impact of postoperative adjuvant treatment modalities and identify risk factors associated with recurrence and survival rates in women diagnosed with early stage type II endometrial cancer and carcinosarcoma. In this retrospective study, patients diagnosed with early stage (stages I-II) carcinosarcoma and type II endometrial cancer were reviewed. All women underwent comprehensive surgical staging. Postoperative treatment options of chemotherapy (CT), radiotherapy (RT), observation (OBS) and chemotherapy-radiotherapy (CT-RT) combination were compared in terms of recurrence and survival outcome. In CT-RT treatment arm, recurrence rate was found as 12.5% and this result is significantly lower than the other treatment approaches (P = 0.01 CT alone: 33.3%, RT alone: 26.7%, OBS: 62.5%). Three-year disease free survival(DFS) rate and overall survival (OS) rate were statistically higher for the group of women treated with combination of CT-RT (92-95%) compared to the women treated with RT alone (65-72%), treated with CT alone (67-74%) and women who received no adjuvant therapy (38-45%). The multivariate analysis revealed that carcinosarcoma histology was associated with shortened DFS and OS (P = 0.001, P = 0.002). On the other hand, being at stage Ia (P = 0.01, P = 0.04) and receiving adjuvant treatment of CT-RT combination (P = 0.005, P = 0.002) appeared to lead to increased DFS and OS rates. We identified that a combination treatment of chemotherapy and radiotherapy is superior compared to other postoperative adjuvant treatment approaches concerning PFS, OS and recurrence rates in stages I-II of type II endometrial cancers and uterine carcinosarcoma. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  9. The value of temozolomide in combination with radiotherapy during standard treatment for newly diagnosed glioblastoma.

    PubMed

    Park, Chul-Kee; Lee, Se-Hoon; Kim, Tae Min; Choi, Seung Hong; Park, Sung-Hye; Heo, Dae Seog; Kim, Il Han; Jung, Hee-Won

    2013-04-01

    The current best standard care for glioblastoma still has limitations and unsatisfactory outcomes in patients with an unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) promoter. Whether the effects of temozolomide are primarily due to its concomitant use with radiotherapy or are also mediated by their independent use in the adjuvant phase remain unclear. To validate the concomitant use of temozolomide in the standard protocol, we compared the overall survival of two prospective patient groups: one treated with radiotherapy alone followed by adjuvant temozolomide (RT → TMZ group) and the other treated with concomitant radiotherapy and temozolomide followed by adjuvant temozolomide (CCRT-TMZ group). Each patient in the RT → TMZ group (n = 25) was matched with two patients in the CCRT-TMZ group (n = 50) with respect to age, extent of resection, MGMT promoter methylation status, and postsurgical performance status to minimize the influence of confounding factors. In patients with MGMT promoter methylation, the CCRT-TMZ group showed superior overall survival (OS; median, 41.0 months) and progression-free survival (PFS; median, 24.0 months) compared with the RT → TMZ group. However, the OS and PFS did not differ between the CCRT-TMZ and the RT → TMZ groups in the patients without MGMT promoter methylation. Although this data is from a retrospective analysis using small number of patients, the study might indicate that concomitant use of temozolomide with radiotherapy is a crucial step in the standard treatment for glioblastoma patients with MGMT promoter methylation. And the use of temozolomide, either concurrently or by adjuvant after radiotherapy, remains a questionable value for those with an unmethylated MGMT promoter.

  10. Multiple field hyperthermia combined with radiotherapy in advanced carcinoma of the breast.

    PubMed

    Engin, K; Tupchong, L; Waterman, F M; Komarnicky, L; Mansfield, C M; Hussain, N; Hoh, L L; McFarlane, J D; Leeper, D B

    1994-01-01

    Extensive recurrences on the chest wall of advanced carcinoma of the breast in 20 patients were treated with multiple field patchwork hyperthermia combined with radiation therapy between 1987-1991. The objective of the study was to evaluate the feasibility, tumour response and complications of treating extensive lesions with multiple, overlapping fields of hyperthermia. All lesions were diffuse encompassing up to 2900 cm2 in area with or without multiple nodules < or = 3 cm deep. All lesions had failed previous therapy with all but three failing previous radiotherapy. Hyperthermia consisted of 282 hyperthermia applicator fields and 357 hyperthermia treatments with external 915 MHz microwaves using commercially available applicators. Hyperthermia applicator fields were defined by the surface 50% SAR distribution of a particular applicator, and hyperthermia fields were abutted to cover the entire tumour bearing area. Radiation therapy consisted of 81 fields to a mean dose of 40 +/- 1 Gy (SE), 88% of fields received between 30 and 50 Gy. The equivalent dose was 42 +/- 1 Gy, based on the linear-quadratic model and alpha/beta = 25 (Fowler 1989). Overlapping hyperthermia fields were separated by an interval of at least three days. Up to four heat sessions per week were required to cover the entire tumour in a rotating fashion. The hyperthermia treatment time was 60 min. Hyperthermia treatments were continued for the duration of radiation therapy. Each hyperthermia applicator field was heated at least once. Patients were exposed to a mean of 14 +/- 3 hyperthermia applicator fields (range of 3-46 fields) and a mean of 18 +/- 3 hyperthermia treatments (range of 6-61) delivered over a mean of 7.5 +/- 0.9 weeks (range of 3-17 weeks). Each field was heated an average of 1.3 times. The tumour complete response rate was 95% with a recurrence rate of 5%. Nevertheless, the mean survival of patients with a complete response was only 10.8 +/- 1.7 months (range of 2-28 months

  11. A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck

    PubMed Central

    Budach, W; Hehr, T; Budach, V; Belka, C; Dietz, K

    2006-01-01

    Background Former meta-analyses have shown a survival benefit for the addition of chemotherapy (CHX) to radiotherapy (RT) and to some extent also for the use of hyperfractionated radiation therapy (HFRT) and accelerated radiation therapy (AFRT) in locally advanced squamous cell carcinoma (SCC) of the head and neck. However, the publication of new studies and the fact that many older studies that were included in these former meta-analyses used obsolete radiation doses, CHX schedules or study designs prompted us to carry out a new analysis using strict inclusion criteria. Methods Randomised trials testing curatively intended RT (≥60 Gy in >4 weeks/>50 Gy in <4 weeks) on SCC of the oral cavity, oropharynx, hypopharynx, and larynx published as full paper or in abstract form between 1975 and 2003 were eligible. Trials comparing RT alone with concurrent or alternating chemoradiation (5-fluorouracil (5-FU), cisplatin, carboplatin, mitomycin C) were analyzed according to the employed radiation schedule and the used CHX regimen. Studies comparing conventionally fractionated radiotherapy (CFRT) with either HFRT or AFRT without CHX were separately examined. End point of the meta-analysis was overall survival. Results Thirty-two trials with a total of 10 225 patients were included into the meta-analysis. An overall survival benefit of 12.0 months was observed for the addition of simultaneous CHX to either CFRT or HFRT/AFRT (p < 0.001). Separate analyses by cytostatic drug indicate a prolongation of survival of 24.0 months, 16.8 months, 6.7 months, and 4.0 months, respectively, for the simultaneous administration of 5-FU, cisplatin-based, carboplatin-based, and mitomycin C-based CHX to RT (each p < 0.01). Whereas no significant gain in overall survival was observed for AFRT in comparison to CFRT, a substantial prolongation of median survival (14.2 months, p < 0.001) was seen for HFRT compared to CFRT (both without CHX). Conclusion RT combined with simultaneous 5-FU

  12. Combined radiotherapy, 5-fluorouracil continuous infusion and weekly oxaliplatin in advanced rectal cancer: a phase I study.

    PubMed

    François, Eric; Ychou, Marc; Ducreux, Michel; Bertheault-Cvitkovic, Frédérique; Giovannini, Marc; Conroy, Thierry; Lemanski, Claire; Thomas, Olivier; Magnin, Valérie

    2005-12-01

    The aim of this study was to determine the maximum-tolerated dose (MTD) of weekly oxaliplatin combined with 5-fluorouracil (5FU) continuous infusion administered concomitantly with fractionated radiotherapy in patients presenting advanced rectal cancer. Forty-three patients with rectal cancer (stage T3/T4 (n = 24), metastatic (n = 17) and 2 with local recurrence), were included. The radiotherapy dose delivered was 45 Gy over 5 weeks (1.8 Gy/fraction/day, 5 days per week). The initial weekly oxaliplatin dosage was 30 mg/m2 and the 5FU dosage 150 mg/m2/d. The oxaliplatin and 5FU doses were escalated. Eight dose levels were tested. At dose level 8 (oxaliplatin 80 mg/m2, 5FU 225 mg/m2/d), 2 patients out of 4 presented dose-limiting toxicity (severe diarrhoea with dehydration and fatal shock, rectovesical fistula). At dose level 7, 2 further patients presented with grade 3 diarrhoea. The main toxicity of the combination was diarrhoea. The hematological and neurological toxicities were not severe and were not dose-limiting. Out of the 30 patients undergoing surgery, 4 (13.3%) presented with pathological complete response and 4 (13.3%) only presented with microscopic residual disease. The results from this study enabled determination of the recommended weekly oxaliplatin dose (60 mg/m2) combined with 5FU continuous infusion (225 mg/m2) and fractionated radiotherapy (45 Gy) in the pre-operative treatment of advanced rectal cancer. The good safety profile of the regimen, associated with promising results in terms of histological response, suggest that the regimen could be developed in future phase II/III studies.

  13. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody.

    PubMed

    Dewan, M Zahidunnabi; Galloway, Ashley E; Kawashima, Noriko; Dewyngaert, J Keith; Babb, James S; Formenti, Silvia C; Demaria, Sandra

    2009-09-01

    This study tested the hypothesis that the type of dose fractionation regimen determines the ability of radiotherapy to synergize with anti-CTLA-4 antibody. TSA mouse breast carcinoma cells were injected s.c. into syngeneic mice at two separate sites, defined as a "primary" site that was irradiated and a "secondary" site outside the radiotherapy field. When both tumors were palpable, mice were randomly assigned to eight groups receiving no radiotherapy or three distinct regimens of radiotherapy (20 Gy x 1, 8 Gy x 3, or 6 Gy x 5 fractions in consecutive days) in combination or not with 9H10 monoclonal antibody against CTLA-4. Mice were followed for tumor growth/regression. Similar experiments were conducted in the MCA38 mouse colon carcinoma model. In either of the two models tested, treatment with 9H10 alone had no detectable effect. Each of the radiotherapy regimens caused comparable growth delay of the primary tumors but had no effect on the secondary tumors outside the radiation field. Conversely, the combination of 9H10 and either fractionated radiotherapy regimens achieved enhanced tumor response at the primary site (P < 0.0001). Moreover, an abscopal effect, defined as a significant growth inhibition of the tumor outside the field, occurred only in mice treated with the combination of 9H10 and fractionated radiotherapy (P < 0.01). The frequency of CD8+ T cells showing tumor-specific IFN-gamma production was proportional to the inhibition of the secondary tumor. Fractionated but not single-dose radiotherapy induces an abscopal effect when in combination with anti-CTLA-4 antibody in two preclinical carcinoma models.

  14. Fractionated but not single dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody

    PubMed Central

    Dewan, M. Zahidunnabi; Galloway, Ashley E.; Kawashima, Noriko; Dewyngaert, J. Keith; Babb, James S.; Formenti, Silvia C.; Demaria, Sandra

    2009-01-01

    Purpose This study tested the hypothesis that the type of dose-fractionation regimen determines the ability of radiotherapy to synergize with anti-CTLA-4 antibody. Experimental design TSA mouse breast carcinoma cells were injected s.c. into syngeneic mice at two separate sites, defined as a “primary” site that was irradiated, and a “secondary” site outside the radiotherapy field. When both tumors were palpable mice were randomly assigned to 8 groups receiving no radiotherapy or 3 distinct regimens of radiotherapy (20 Gy × 1, 8 Gy × 3 or 6 Gy × 5 fractions in consecutive days) in combination or not with 9H10 mAb against CTLA-4. Mice were followed for tumors growth/regression. Similar experiments were conducted in the MCA38 mouse colon carcinoma model. Results In either of the 2 models tested treatment with 9H10 alone had no detectable effect. Each of the radiotherapy regimens caused comparable growth delay of the primary tumors, but had no effect on the secondary tumors, outside the radiation field. Conversely, the combination of 9H10 and either fractionated radiotherapy regimens achieved enhanced tumor response at the primary site (p<0.0001). Moreover, an abscopal effect, defined as a significant growth inhibition of the tumor outside the field occurred only in mice treated with the combination of 9H10 and fractionated radiotherapy (p<0.01). Frequency of CD8+ T cells showing tumor-specific IFNγ production was proportional to the inhibition of the secondary tumor. Conclusions Fractionated, but not single dose radiotherapy, induces an abscopal effect when in combination with anti-CTLA-4 antibody, in two preclinical carcinoma models. PMID:19706802

  15. Californium-252 neutron brachytherapy combined with external pelvic radiotherapy plus concurrent chemotherapy for cervical cancer: a retrospective clinical study.

    PubMed

    Qian, Shen; Ye, Ling; Tian, Yun-Hong; Wang, Li-Gen; Huang, Zuo-Ping; Li, Feng; Hou, Bing; Song, Ni; Chen, Juan; Liu, Ying; Liu, Xiao; Zhou, Tao

    2017-02-28

    Cervical cancer is the sixth most common cancer in Chinese women. A standard treatment modality for cervical cancer is the combination of surgery, chemotherapy, external-beam radiotherapy and intracavitary brachytherapy. The aim of this study was to retrospectively assess the long-term treatment outcomes of patients with cervical cancer who were treated with californium-252 neutron brachytherapy combined with external-beam radiotherapy plus concurrent chemotherapy. We retrospectively analyzed the medical records of 150 patients with primary stages IB-IVB cervical cancer who received neutron brachytherapy combined with external-beam radiotherapy concurrently with cisplatin chemotherapy. All patients were followed up. Using an actuarial analysis, patient outcomes and treatment-related adverse effects were evaluated and compared. The median overall survival (OS) was 33.2 months. The 3-year progression-free survival rates for patients with stages I-II, III, and IV diseases were 81.0% (68/84), 65.0% (39/60), and 0% (0/6), respectively; the 3-year OS rates were 90.5% (76/84), 85.0% (51/60), and 16.7% (1/6), respectively. Vaginal bleeding was controlled within the median time of 4.0 days. One month after treatment, 97.3% of patients achieved short-term local control. The local recurrence rates for patients with stages I-II, III, and IV disease were 4.8% (4/84), 11.7% (7/60), and 33.3% (2/6), respectively, and the occurrence rates of distant metastasis were 16.7% (14/84), 25.0% (15/60), and 100.0% (6/6), respectively. Cancer stage, tumor size, and lymph node metastasis were identified as prognostic risk factors, but only lymph node metastasis was found to be an independent prognostic factor. The most common adverse effects during treatment were grades 1 and 2 irradiation-related proctitis and radiocystitis. For patients with cervical cancer, neutron brachytherapy combined with external-beam radiotherapy plus concurrent chemotherapy produces a rapid response and greatly

  16. Perspectives on the combination of radiotherapy and targeted therapy with DNA repair inhibitors in the treatment of pancreatic cancer

    PubMed Central

    Yang, Shih-Hung; Kuo, Ting-Chun; Wu, Hsu; Guo, Jhe-Cyuan; Hsu, Chiun; Hsu, Chih-Hung; Tien, Yu-Wen; Yeh, Kun-Huei; Cheng, Ann-Lii; Kuo, Sung-Hsin

    2016-01-01

    Pancreatic cancer is highly lethal. Current research that combines radiation with targeted therapy may dramatically improve prognosis. Cancerous cells are characterized by unstable genomes and activation of DNA repair pathways, which are indicated by increased phosphorylation of numerous factors, including H2AX, ATM, ATR, Chk1, Chk2, DNA-PKcs, Rad51, and Ku70/Ku80 heterodimers. Radiotherapy causes DNA damage. Cancer cells can be made more sensitive to the effects of radiation (radiosensitization) through inhibition of DNA repair pathways. The synergistic effects, of two or more combined non-lethal treatments, led to co-administration of chemotherapy and radiosensitization in BRCA-defective cells and patients, with promising results. ATM/Chk2 and ATR/Chk1 pathways are principal regulators of cell cycle arrest, following DNA double-strand or single-strand breaks. DNA double-stranded breaks activate DNA-dependent protein kinase, catalytic subunit (DNA-PKcs). It forms a holoenzyme with Ku70/Ku80 heterodimers, called DNA-PK, which catalyzes the joining of nonhomologous ends. This is the primary repair pathway utilized in human cells after exposure to ionizing radiation. Radiosensitization, induced by inhibitors of ATM, ATR, Chk1, Chk2, Wee1, PP2A, or DNA-PK, has been demonstrated in preclinical pancreatic cancer studies. Clinical trials are underway. Development of agents that inhibit DNA repair pathways to be clinically used in combination with radiotherapy is warranted for the treatment of pancreatic cancer. PMID:27621574

  17. Phase II Study of Vinorelbine and Estramustine in Combination With Conformational Radiotherapy for Patients With High-Risk Prostate Cancer

    SciTech Connect

    Carles, Joan; Nogue, Miguel; Sole, Josep M.; Foro, Palmira; Domenech, Montserrat; Suarez, Marta; Gallardo, Enrique; Garcia, Dario; Ferrer, Ferran; Gelabert-Mas, Antoni; Gayo, Javier; Fabregat, Xavier

    2010-03-15

    Purpose: To evaluate the efficacy and safety profile of vinorelbine and estramustine in combination with three-dimensional conformational radiotherapy (3D-CRT) in patients with localized high-risk prostate cancer. Methods and Materials: Fifty patients received estramustine, 600 mg/m{sup 2} daily, and vinorelbine, 25 mg/m{sup 2}, on days 1 and 8 of a 21-day cycle for three cycles in combination with 8 weeks of 3D-CRT (total dose of 70.2 gray [Gy] at 1.8-Gy fractions or 70 Gy at 2.0-Gy fractions). Additionally, patients received luteinizing hormone-releasing hormone analogs for 3 years. Results: All patients were evaluated for response and toxicity. Progression-free survival at 5 years was 72% (95% confidence interval [CI]: 52-86). All patients who relapsed had only biochemical relapse. The most frequent severe toxicities were cystitis (16% of patients), leucopenia (10% of patients), diarrhea (10% of patients), neutropenia (8% of patients), and proctitis (8% of patients). Six patients (12%) did not complete study treatment due to the patient's decision (n = 1) and to adverse events such as hepatotoxicity, proctitis, paralytic ileus, and acute myocardial infarction. Conclusions: Vinorelbine and estramustine in combination with 3D-CRT is a safe and effective regimen for patients with localized high-risk prostate cancer. A randomized trial is needed to determine whether the results of this regimen are an improvement over the results obtained with radiotherapy and androgen ablation.

  18. Intraoperative and postoperative anaesthetic and analgesic effect of multipoint transcutaneous electrical acupuncture stimulation combined with sufentanil anaesthesia in patients undergoing supratentorial craniotomy.

    PubMed

    Liu, Xing; Li, Shuqin; Wang, Baoguo; An, Lixin; Ren, Xiujun; Wu, Haifeng

    2015-08-01

    To investigate the anaesthetic and analgesic effect of multipoint transcutaneous electrical acupuncture stimulation (TEAS) during supratentorial tumour resection for postoperative recovery and side effects. In a blinded clinical trial, 92 patients scheduled for supratentorial craniotomy under general anaesthesia were randomly allocated into either a multipoint TEAS (n=46) or a sham TEAS group (n=46). All patients received total intravenous anaesthesia (TIVA) with propofol and sufentanil. The target concentration of sufentanil was adjusted and recorded according to mean arterial pressure (MAP), heart rate (HR) and bispectral index (BIS). Patients in the TEAS group received TEAS 30 min before anaesthesia induction and this was maintained throughout the operation at four pairs of acupuncture points. Postoperative pain, recovery and side effects were evaluated. Eighty-eight patients completed the study. Continuous monitoring of MAP, HR and BIS showed stable values with no significant differences between the two groups (p>0.05). Sufentanil target plasma concentration in TEAS patients was significantly lower at some time points during supratentorial craniotomy, and total sufentanil consumption was significantly higher in the sham group (p<0.05). Postoperative recovery and pain were significantly improved by TEAS (p<0.001), without the postoperative side effects. Multipoint TEAS at both proximal and distal points combined with TIVA can significantly decrease intraoperative sufentanil requirements, increase pain relief on postoperative day 1 and improve postoperative recovery of patients during supratentorial tumour resection, with no significant increase of side effects. These findings suggest that multipoint TEAS may be clinically effective as an adjunct to analgesia in intraoperative anaesthesia and postoperative pain treatment and may speed recovery. Chinese Clinical Trial Registry (registration number ChiCTR-TRC-10001078). Published by the BMJ Publishing Group Limited

  19. Potential of mobile intraoperative radiotherapy technology.

    PubMed

    Goer, Donald A; Musslewhite, Chapple W; Jablons, David M

    2003-10-01

    Mobile IORT units have the potential to change the way patients who have cancer are treated. The integration of IORT into cancer treatment programs, made possible by the new technologies of mobile linear accelerators that can be used in unshielded operating rooms, makes IORT significantly less time-consuming, less costly, and less risky to administer. It is now practical for IORT to be used in early-stage disease, in addition to advanced disease, and in sites for which patient transportation in the middle of surgery is considered too risky. Preliminary results of trials for early-stage breast and rectal cancer indicate benefits of IORT. Pediatric patients and patients who have lung cancer, previously underserved by IORT therapies, can be offered potential gains when patient transport issues do not limit IORT. Furthermore, because many of these mobile systems require no shielding, it is now practical for mobile units to be shared between hospitals, making this new mobile technology much more widely available.

  20. An experimental study on cervix cancer with combination of HSV-TK/GCV suicide gene therapy system and 60Co radiotherapy

    PubMed Central

    2010-01-01

    Background To evaluate the killing effect of HSV-TK/GCV suicide gene therapy system combined with 60Co radiotherapy on human cervical cancer Hela cell line in vitro and in vivo, and to explore the radiosensitization by HSV-TK/GCV system. Methods HSV-TK/GCV suicide gene therapy system and 60Co radiotherapy were used separately or in combination on human cervical cancer Hela cell line in vitro and in vivo to compare their effects. Colony formation test and the rate of radiosensitization effect (E/O) were employed to observed the radiosensitization by HSV-TK/GCV system. Results HSV-TK/GCV suicide gene therapy system had strong therapeutic effects on Hela cells in vitro and in vivo (the inhibition rates were 45.8% and 39.5%, respectively), moreover, the combined administration of gene therapy and radiotherapy had stronger therapeutic effects in vitro and in vivo (the inhibition rate was 87.5% in vitro, and the inhibition rate was 87.9% in vivo) (P < 0.01). The inhibition rate by radiotherapy alone was 42.4% in vitro and 35.8% in vivo. The sensitivity of combined therapy to radiotherapy increased more than that of therapy alone, the ability of colony formation decreased (P < 0.01). The rate of radiosensitivity effect (E/O) was 3.17(> 1.4), indicating HSV-TK/GCV system could exert a sensitizing effect on 60Co radiotherapy of the transplanted human cervical cancer cell in nude mice. Conclusion HSV-TK/GCV system had radiosensitization. Gene therapy combined with radiotherapy may be a good supplementary method for cervix cancer synthetic treatment. PMID:21054886

  1. Effects of combined epidural and general anesthesia on intraoperative hemodynamic responses, postoperative cellular immunity, and prognosis in patients with gallbladder cancer

    PubMed Central

    Zhu, Jun; Zhang, Xue-Rong; Yang, Hu

    2017-01-01

    Abstract Background: This study is supposed to investigate the effects of combined epidural and general anesthesia on intraoperative hemodynamic responses, postoperative cellular immunity, and prognosis in patients with gallbladder cancer (GBC). Methods: One hundred forty-four GBC patients were selected and randomly divided into the general anesthesia (GA) group and the combined epidural-general anesthesia (CEGA) group. Before anesthesia induction (t0), at intubation (t1), at the beginning of surgery (t2), 5 minutes after pneumoperitoneum (t3), at the end of surgery (t4), after recovery of spontaneous breathing (t5), after regaining consciousness (t6), and after extubation (t7), the heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and the depth of anesthesia (bispectral index [BIS]) were detected. Blood samples were separately collected 30 minutes before anesthesia induction (T1), 2 hours after the beginning of surgery (T2), at the end of surgery (T3), 1 day after surgery (T4), 3 days after surgery (T5). The survival rates of T cell subsets (CD3+, CD4+, CD8+, CD4+/CD8+) and natural killer (NK) cells were determined by flow cytometry. Postoperative nausea and vomiting (PONV), visual analog scale (VAS), and sedation-agitation scale (SAS) were performed to assess postoperative adverse reactions. A 3-year follow-up was conducted. Results: Compared with the GA group, the CEGA group had significant lower SBP values at t5 and t6, lower DBP values at t1, t3, t4, and t5, lower HR values at t1 and t5, and higher BIS values at t4, t5, t6, and t7. No PONV was observed in the CEGA group. In comparison to the GA group, the VAS was markedly increased and survival rates of CD3+, CD4+, and CD4+/CD8+ cells were increased at T2, T3, T4, and T5 in the CEGA group. The 1-year, 2-year, and 3-year survival rates were not evidently different between the CEGA group and the GA group. Conclusion: Our study provides evidence that the combined epidural

  2. Gastrostomy vs nasogastric tube feeding in patients with head and neck cancer during radiotherapy alone or combined chemoradiotherapy

    PubMed

    Soria, Ainara; Santacruz, Elisa; Vega-Piñeiro, Belén; Gión, María; Molina, Javier; Villamayor, María; Mateo, Raquel; Riveiro, Javier; Nattero, Lia; Botella-Carretero, José I

    2017-06-05

    Patients with head and neck cancer (HNC) submitted to radiotherapy alone or combined chemoradiotherapy present a high prevalence of malnutrition at baseline. Prophylactic use of gastrostomy has been suggested for these patients for delivering enteral nutrition. On the other hand, other authors have failed to demonstrate the effectiveness of this measure over nasogastric tube feeding. We studied 40 patients with HNC with moderate or severe malnutrition who were offered either prophylactic percutaneous gastrostomy before starting oncologic treatment or close follow-up with nutritional counseling with the placement of a nasogastric tube when necessary. There were no significant changes throughout the study period in weight (p = 0.338), body mass index (BMI) (p = 0.314) or serum proteins (p = 0.729), and these changes showed no differences between the gastrostomy vsnasogastric tube feeding groups. The amount of delivered energy was above the estimated energy needs with both gastrostomy and nasogastric tube feeding, but there were no differences in the total energy provided by enteral nutrition between groups. Patients in the gastrostomy group received enteral nutrition support for a longer period of time (p = 0.007). Both gastrostomy and nasogastric tube feeding are effective methods of delivering enteral nutrition in patients with HNC submitted to radiotherapy alone or combined chemoradiotherapy, with no differences between them in terms of avoiding further nutritional deterioration.

  3. Recurrent myoepithelial carcinoma of the submandibular gland treated by rAd-p53 combined with radiotherapy: A case report

    PubMed Central

    Yang, Lin; Chen, Xiangxun; Wang, Hongyan; Shi, Qingming

    2016-01-01

    The aim of the present study was to report the case of a patient with recurrent myoepithelial carcinoma of the submandibular gland without progression for five years following treatment. A 71-year-old male patient presented to hospital with a painless swelling in the region of the right submandibular gland, and received a radical neck dissection on January 29, 2008. A nodule of ~7×4×2 cm was identified at the site of the right submandibular gland, and the pathological results revealed a diagnosis of myoepithelial carcinoma of the right submandibular gland with no lymph node metastasis. However, this case developed local recurrence with wide-spread metastasis in the lungs. Between April and October 2008, the patient underwent several treatment regimens and demonstrated no improvement following 6 cycles of chemotherapy. From then on, the patient was treated with recombinant adenoviral-p53 (rAd-p53) combined with radiotherapy using a 6 millivolt medical linear accelerator. The foci were relieved and the cancer demonstrated no signs of progression during the 5-year follow-up. rAd-p53 combined with radiotherapy was useful for treating myoepithelial carcinoma of the submandibular gland. PMID:27446369

  4. Mesothelioma at era of helical tomotherapy: results of two institutions in combining chemotherapy, surgery and radiotherapy.

    PubMed

    Sylvestre, Alma; Mahé, Marc-André; Lisbona, Albert; Zefkili, Sofia; Savignoni, Alexia; Bonnette, Pierre; Barthes, Françoise Le Pimpec; Paris, Edouard; Perigaud, Christian; Yassa, Michael; Giraud, Philippe

    2011-12-01

    There is a scarce clinical experience about adjuvant helical tomotherapy (HT) in patients affected by malignant pleural mesothelioma (MPM) even though it appears as a useful technique to treat complex volume as the pleural cavity, and seems to have better dose distribution than the "classic" intensity modulated radiotherapy (IMRT). Twenty-four patients received adjuvant radiotherapy (RT) by HT from August 1st, 2007 to December 1st, 2009 at Curie Institute (Paris) and René Gauducheau Cancer Center (Nantes). Thirteen patients had neoadjuvant chemotherapy. Extrapleural pleuropneumonectomy (EPP) was done in 23 patients. Median dose to PTV was 50Gy [48.7-55.9Gy] (2Gy/fraction). Acute and long term toxicities, disease free survival (DFS), overall survival (OS) and relapses are presented. Average follow up after RT was 7 months. The disease was staged mostly as T2-T3, N1-N2. Nineteen patients had epithelial type histology. Most patients tolerated radiotherapy with grade 1-2 side effects: redness of the skin, light cough or dyspnea, fatigue, nausea and odynophagia, mild increase of the post-operative thoracic pain. Grade 3 pneumonitis was suspected in 2 patients. Two grade 5 pneumonitis were also suspected. Eleven patients had a follow up of more than 6 months and no long term side effects related with HT were noted. At 24 months, 51.8% of patients were free of disease. Thirty percent of patients relapsed, with 2 patients presenting local relapses. Two patients died from recurrence. With limited follow up, HT has comparable toxicity to those observed with traditional IMRT. Higher radiation dose and good coverage results in excellent local control. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. Combined sellar fibrosarcoma and prolactinoma with neuronal metaplasia: report of a case unassociated with radiotherapy.

    PubMed

    Moro, Mario; Giannini, Caterina; Scheithauer, Bernd W; Lloyd, Ricardo V; Restall, Paul; Eagleton, Carl; Law, Andrew J; Kovacs, Kalman

    2004-01-01

    We report the occurrence of a primary pituitary fibrosarcoma causally unrelated to radiotherapy, admixed in association with a prolactin cell pituitary adenoma showing neuronal metaplasia. These unique findings were associated with multiple endocrine neoplasia type 1 (MEN 1). Primary fibrosarcoma involving the sella is a very rare tumor. The majority of cases have been associated with prior irradiation of either a pituitary adenoma or a craniopharyngioma. Pituitary adenoma with neuronal metaplasia is also rare and usually occurs in the setting of acromegaly. Despite the intimate association of both elements in our lesion, no transition of adenoma to sarcoma was demonstrable by immunohistochemistry or in situ hybridization studies.

  6. Surgery for Glioblastoma: Impact of the Combined Use of 5-Aminolevulinic Acid and Intraoperative MRI on Extent of Resection and Survival

    PubMed Central

    Coburger, Jan; Hagel, Vincent; Wirtz, Christian Rainer; König, Ralph

    2015-01-01

    Background There is rising evidence that in glioblastoma(GBM) surgery an increase of extent of resection(EoR) leads to an increase of patient’s survival. Based on histopathological assessments tumor depiction of Gd-DTPA enhancement and 5-aminolevulinic-acid-fluorescence(5-ALA) might be synergistic for intraoperative resection control. Objective To assess impact of additional use of 5-ALA in intraoperative MRI(iMRI) assisted surgery of GBMs on extent of resection(EoR), progression free survival(PFS) and overall survival(OS). Methods We prospectively enrolled 33 patients with GBMs eligible for gross-total-resection(GTR) and performed a combined approach using 5-ALA and iMRI. As a control group, we performed a retrospective matched pair assessment, based on 144 patients with iMRI-assisted surgery. Matching criteria were, MGMT promotor methylation, recurrent surgery, eloquent location, tumor size and age. Only patients with an intended GTR and primary GBMs were included. We calculated Kaplan Mayer estimates to compare OS and PFS using the Log-Rank-Test. We used the T-test to compare volumetric results of EoR and the Chi-Square-Test to compare new permanent neurological deficits(nPND) and general complications between the two groups. Results Median follow up was 31 months. No significant differences between both groups were found concerning the matching criteria. GTR was achieved significantly more often (p <0.010) using 5-ALA&iMRI (100%) compared to iMRI alone(82%). Mean EoR was significantly(p<0.004) higher in 5-ALA&iMRI-group(99.7%) than in iMRI-alone-group(97.4%) Rate of complications did not differ significantly between groups(21% iMRI-group,27%5-ALA&iMRI-group,p<0.518). nPND were found in 6% in both groups. Median PFS (6mo resp.;p<0.309) and median OS(iMRI:17mo;5-ALA&iMRI-group:18mo;p<0.708)) were not significantly different between both groups. Conclusion We found a significant increase of EoR when combining 5-ALA&iMRI compared to use of iMRI alone. Maximizing

  7. Combined intraoperative administration of a histone deacetylase inhibitor and a neurokinin-1 receptor antagonist synergistically reduces intra-abdominal adhesion formation in a rat model

    PubMed Central

    Cassidy, Michael R.; Sherburne, Alan C.; Heydrick, Stanley J.; Stucchi, Arthur F.

    2017-01-01

    Background Intra-abdominal adhesions are the most frequent postoperative complication after abdominopelvic surgery. Our laboratory has previously shown that an intraoperative peritoneal lavage containing either the histone deacetylase inhibitor valproic acid (VPA) or a neurokinin-1 receptor antagonist (NK-1RA) reduced adhesions by approximately 50%in a rat model. The objective of this study was to determine whether the combination of these 2 drugs was more effective in reducing adhesions than either alone. Methods Rats underwent laparotomy with creation of peritoneal ischemic buttons to induce adhesions. A single dose of VPA (25 mg/kg), NK-1RA (50 mg/kg), a combination of both, or 0.9% saline was lavaged intraperitoneally just before wound closure. On postoperative day 7, adhesions were quantified. To investigate early mechanisms of adhesiogenesis, adhesions were created as described and adhesive button tissue was harvested at 30 minutes and 3 hours postoperatively and fibrinogen and vascular endothelial growth factor (VEGF) protein levels, both indices of peritoneal extravasations, were determined by Western blot analysis. Peritoneal fluid was collected in similar experiments at 30 minutes, and 3 and 6 hours to measure fibrinolytic activity, an index of the ability of the peritoneum to degrade fibrinous adhesions. Results The coadministration of VPA plus NK-1RA reduces adhesions by 72.6% relative to saline (P < .001); this reduction was greater than either compound alone (P < .001). Peritoneal fibrinolytic activity was significantly increased at 3 and 6 hours postoperatively in animals administered the combination therapy versus saline (P = .01). VPA plus NK-1RA significantly decreased fibrinogen and VEGF protein levels at 3 and 6 hours compared with saline controls. Conclusion These results suggest that a combined pharmacologic approach targeting multiple adhesiogenic pathways provides optimal adhesion prevention. PMID:25726317

  8. Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas.

    PubMed

    Sylvester, Peter T; Evans, John A; Zipfel, Gregory J; Chole, Richard A; Uppaluri, Ravindra; Haughey, Bruce H; Getz, Anne E; Silverstein, Julie; Rich, Keith M; Kim, Albert H; Dacey, Ralph G; Chicoine, Michael R

    2015-02-01

    The clinical benefit of combined intraoperative magnetic resonance imaging (iMRI) and endoscopy for transsphenoidal pituitary adenoma resection has not been completely characterized. This study assessed the impact of microscopy, endoscopy, and/or iMRI on progression-free survival, extent of resection status (gross-, near-, and sub-total resection), and operative complications. Retrospective analyses were performed on 446 transsphenoidal pituitary adenoma surgeries at a single institution between 1998 and 2012. Multivariate analyses were used to control for baseline characteristics, differences during extent of resection status, and progression-free survival analysis. Additional surgery was performed after iMRI in 56/156 cases (35.9%), which led to increased extent of resection status in 15/156 cases (9.6%). Multivariate ordinal logistic regression revealed no increase in extent of resection status following iMRI or endoscopy alone; however, combining these modalities increased extent of resection status (odds ratio 2.05, 95% CI 1.21-3.46) compared to conventional transsphenoidal microsurgery. Multivariate Cox regression revealed that reduced extent of resection status shortened progression-free survival for near- versus gross-total resection [hazard ratio (HR) 2.87, 95% CI 1.24-6.65] and sub- versus near-total resection (HR 2.10; 95% CI 1.00-4.40). Complication comparisons between microscopy, endoscopy, and iMRI revealed increased perioperative deaths for endoscopy versus microscopy (4/209 and 0/237, respectively), but this difference was non-significant considering multiple post hoc comparisons (Fisher exact, p = 0.24). Combined use of endoscopy and iMRI increased pituitary adenoma extent of resection status compared to conventional transsphenoidal microsurgery, and increased extent of resection status was associated with longer progression-free survival. Treatment modality combination did not significantly impact complication rate.

  9. Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas

    PubMed Central

    Sylvester, Peter T.; Evans, John A.; Zipfel, Gregory J.; Chole, Richard A.; Uppaluri, Ravindra; Haughey, Bruce H.; Getz, Anne E.; Silverstein, Julie; Rich, Keith M.; Kim, Albert H.; Dacey, Ralph G.

    2014-01-01

    Purpose The clinical benefit of combined intraoperative magnetic resonance imaging (iMRI) and endoscopy for transsphenoidal pituitary adenoma resection has not been completely characterized. This study assessed the impact of microscopy, endoscopy, and/or iMRI on progression-free survival, extent of resection status (gross-, near-, and subtotal resection), and operative complications. Methods Retrospective analyses were performed on 446 transsphenoidal pituitary adenoma surgeries at a single institution between 1998 and 2012. Multivariate analyses were used to control for baseline characteristics, differences during extent of resection status, and progression-free survival analysis. Results Additional surgery was performed after iMRI in 56/156 cases (35.9 %), which led to increased extent of resection status in 15/156 cases (9.6 %). Multivariate ordinal logistic regression revealed no increase in extent of resection status following iMRI or endoscopy alone; however, combining these modalities increased extent of resection status (odds ratio 2.05, 95 % CI 1.21–3.46) compared to conventional transsphenoidal microsurgery. Multivariate Cox regression revealed that reduced extent of resection status shortened progression-free survival for near- versus gross-total resection [hazard ratio (HR) 2.87, 95 % CI 1.24–6.65] and sub- versus near-total resection (HR 2.10; 95 % CI 1.00–4.40). Complication comparisons between microscopy, endoscopy, and iMRI revealed increased perioperative deaths for endoscopy versus microscopy (4/209 and 0/237, respectively), but this difference was non-significant considering multiple post hoc comparisons (Fisher exact, p = 0.24). Conclusions Combined use of endoscopy and iMRI increased pituitary adenoma extent of resection status compared to conventional transsphenoidal microsurgery, and increased extent of resection status was associated with longer progression-free survival. Treatment modality combination did not significantly impact

  10. Intraoperative end-tidal concentration of isoflurane in cats undergoing ovariectomy that received tramadol, buprenorphine or a combination of both.

    PubMed

    Bellini, Luca; Mollo, Antonio; Contiero, Barbara; Busetto, Roberto

    2017-02-01

    Objectives The aim of the study was to evaluate the end-tidal concentration of isoflurane required to maintain heart and respiratory rate within ± 20% of basal measurement in cats undergoing ovariectomy that received buprenorphine, tramadol or a combination of both. Methods Thirty cats, divided into three groups, were enrolled in a simple operator-blinded, randomised study. Cats received acepromazine (0.03 mg/kg) and one of the following treatments: buprenorphine (0.02 mg/kg), tramadol (2 mg/kg) or a combination of both. Anaesthesia was induced with propofol and maintained with isoflurane titrated in order to maintain heart and respiratory rate within the target values recorded before premedication. Results Groups were similar for age, weight, dose of propofol administered, sedation and recovery scores. Cats receiving tramadol with buprenorphine were extubated earlier after isoflurane discontinuation. No statistical differences were detected in end-tidal fraction of isoflurane between buprenorphine alone or with tramadol. In cats that received tramadol or buprenorphine alone, ovarian pedicle traction caused a statistical increase in end-tidal isoflurane concentration compared with that measured during incision and suture of the skin. In cats that received the combination of tramadol plus buprenorphine no differences among surgical time points were observed. Conclusions and relevance Tramadol added to buprenorphine did not provide any advantage in decreasing the end-tidal fraction of isoflurane compared with buprenorphine alone, although it is speculated there may be an infra-additive interaction between tramadol and buprenorphine in cats.

  11. [A case of pineoblastoma successfully treated with surgery, combined chemotherapy of cisplatin and etoposide, and radiotherapy].

    PubMed

    Akiyama, Y; Akiyama, Y; Kumai, J; Nishikawa, M

    1995-10-01

    A 5-year-old girl was admitted to another clinic because of vomiting and convulsions. She was brought to our clinic after a ventriculoperitoneal shunt was inserted. CT scan on admission in our clinic showed a tumor in the pineal region with tumoral hemorrhage. Tumor markers such as HCG, AFP, CEA, P-LAP were within normal range. A biopsy of the tumor was performed and the histological diagnosis was pineoblastoma. Her recovery was excellent and disseminated metastasis was not recognized. A subtotal removal of the tumor was performed through the occipital transtentorial approach. She had no neurological deficits after surgery. She then received two 5-day cycles of chemotherapy, consisting of intravenous administration of 20 mg/m2/day cisplatin and 60 mg/m2/day etoposide, and craniospinal radiotherapy. After these therapies, the tumor responded and disappeared completely. Follow-up radiographic investigations also demonstrated no abnormal evidence except for brain atrophy. She is attending a primary school without any problems. Pineoblastoma is quite rare and remarkably malignant. Hence, aggressive therapies including surgery, radiotherapy and chemotherapy is indicated for this tumor.

  12. Liver complications in lymphomas treated with a combination of chemotherapy and radiotherapy: preliminary results

    SciTech Connect

    Haddad, E.; Le Bourgeois, J.P.; Kuentz, M.; Lobo, P.

    1983-09-01

    From May 1978 to May 1981, a total of 20 patients (18 patients with Non Hodgkin Lymphomas + 2 patients with Stage IV Hodgkin's disease) were treated with chemotherapy and whole or upper abdominal radiotherapy. All the patients were in complete remission at the time of irradiation. Shielding of the kidneys was effected at the start of treatment and the right lobe of the liver was shielded after a dose of 20 Gy was delivered. As of January 1982, 17 of the patients were alive and free of disease with a follow-up ranging from 6 to 32 months (mean follow-up of 18.5 months). Two patients were dead from their disease. Alterations in liver chemistry were observed in 5 patients, clinical jaundince or transient hepatomegaly along with changes in liver chemistry in 4 patients, classical veno-occlusive disease in 2 patients and 7 of the patients did not develop any complication. No death from complications were observed. The contribution of the following factors such as radiotherapy dose to the liver, drugs, nutritional status and associated medical conditions, towards the development of complications have been analyzed in detail.

  13. Cancer risk estimates from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy.

    PubMed

    Schneider, Uwe; Walsh, Linda

    2008-04-01

    Most information on the dose-response of radiation-induced cancer is derived from data on the A-bomb survivors who were exposed to gamma-rays and neutrons. Since, for radiation protection purposes, the dose span of main interest is between 0 and 1 Gy, the analysis of the A-bomb survivors is usually focused on this range. However, estimates of cancer risk for doses above 1 Gy are becoming more important for radiotherapy patients and for long-term manned missions in space research. Therefore in this work, emphasis is placed on doses relevant for radiotherapy with respect to radiation-induced solid cancer. The analysis of the A-bomb survivor's data was extended by including two extra high-dose categories (4-6 Sv and 6-13 Sv) and by an attempted combination with cancer data on patients receiving radiotherapy for Hodgkin's disease. In addition, since there are some recent indications for a high neutron dose contribution, the data were fitted separately for three different values for the relative biological effectiveness (RBE) of the neutrons (10, 35 and 100) and a variable RBE as a function of dose. The data were fitted using a linear, a linear-exponential and a plateau-dose-response relationship. Best agreement was found for the plateau model with a dose-varying RBE. It can be concluded that for doses above 1 Gy there is a tendency for a nonlinear dose-response curve. In addition, there is evidence of a neutron RBE greater than 10 for the A-bomb survivor data. Many problems and uncertainties are involved in combing these two datasets. However, since very little is currently known about the shape of dose-response relationships for radiation-induced cancer in the radiotherapy dose range, this approach could be regarded as a first attempt to acquire more information on this area. The work presented here also provides the first direct evidence that the bending over of the solid cancer excess risk dose response curve for the A-bomb survivors, generally observed above 2 Gy

  14. Effects of S-1 Combined with Radiotherapy in the Treatment of Nasopharyngeal Cancer: A Meta-analysis Based on Randomized Controlled Trials.

    PubMed

    Fengtong, Jin; Jiangtao, Fu; Yating, Wang; Lili, Wu; Jianbo, Chen; Xiaofei, Wang

    2017-01-01

    The aim of this meta-analysis was to evaluate the effects and toxicity of S-1 combined with radiotherapy in the treatment of nasopharyngeal cancer (NPC). Through a search of the databases of PubMed, Embase, the Chinese Biomedicine Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang system and Chongqing VIP Information (CQVIP), the efficacy and side effects data of S-1 combined with radiotherapy in the treatment of NPC patients from open published randomized controlled trials (RCTs) were collected. The pooled complete response (CR), partial response (PR), objective response rate (ORR), 2-year survival rate and treatment related toxicity were analyzed by Stata12.0 software. Eight RCTs with 599 cases were included and analyzed in this meta-analysis. The general quality of the 8 studies were deemed as having moderate risk of bias. Adequate sequence generation was reported in 4 studies. Incomplete outcome data address was reported in 7 publications. Five studies indicated to be free of selective reporting. Seven studies reported the treatment complete response (CR) between S-1 combined with radiotherapy and radiotherapy alone. With significant heterogeneity, the data was pooled by random effect model. The pooled results indicated that S-1 combined with radiotherapy can significant increase the CR rate compared to radiotherapy alone (RR=1.52, 95%CI:1.33-1.74, P<0.05). Eight studies reported the partial response (PR) rate between the combined treatment and radiotherapy alone. The pooled results showed that there was no statistical difference for PR between combined treatment and radiotherapy alone (RR=0.85, 95%CI:0.62-1.16, P>0.05). For the effect size of objective response rate (ORR), pooled results indicated that S-1 combined with radiotherapy can significantly increased the ORR by random effect model (RR=1.39, 95%CI:1.23-1.57, P<0.05). The pooled results showed that S-1 combined with radiotherapy significant increase the risk of developing bone

  15. [Current status of phase III study of combined treatment with radiotherapy and chemotherapy for head and neck cancer].

    PubMed

    Inoue, T; Inoue, T; Murayama, S

    1995-02-01

    Concerning the combined treatment with radiotherapy and chemotherapy for head and neck cancer, in general, there are many discrepancies between a single institutional pilot study and a multi-institutional prospective randomized study. Some of the differences depend on the insufficient number of patients entered into the study, since the annual incidence of head and neck cancer is relatively low, and the treatment result varies from site to site as well as the stage of the disease. Several types of bias, including patient selection and positive publications, and factors related to the design and analysis of clinical trials result in additional differences. To solve these problems, we organized the Quality Assurance Research Group in Japan, funded by the Ministry of Health and Welfare for several years. Based on much effort, it was emphasized the need for increased manpower and equipment in radiation oncology, for a quality assurance program of radiotherapy and the preparation of a standard treatment modality using decision tree and surrogate survey.

  16. Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study

    PubMed Central

    Slovin, S. F.; Higano, C. S.; Hamid, O.; Tejwani, S.; Harzstark, A.; Alumkal, J. J.; Scher, H. I.; Chin, K.; Gagnier, P.; McHenry, M. B.; Beer, T. M.

    2013-01-01

    Background This phase I/II study in patients with metastatic castration-resistant prostate cancer (mCRPC) explored ipilimumab as monotherapy and in combination with radiotherapy, based on the preclinical evidence of synergistic antitumor activity between anti-CTLA-4 antibody and radiotherapy. Patients and methods In dose escalation, 33 patients (≥6/cohort) received ipilimumab every 3 weeks × 4 doses at 3, 5, or 10 mg/kg or at 3 or 10 mg/kg + radiotherapy (8 Gy/lesion). The 10-mg/kg cohorts were expanded to 50 patients (ipilimumab monotherapy, 16; ipilimumab + radiotherapy, 34). Evaluations included adverse events (AEs), prostate-specific antigen (PSA) decline, and tumor response. Results Common immune-related AEs (irAEs) among the 50 patients receiving 10 mg/kg ± radiotherapy were diarrhea (54%), colitis (22%), rash (32%), and pruritus (20%); grade 3/4 irAEs included colitis (16%) and hepatitis (10%). One treatment-related death (5 mg/kg group) occurred. Among patients receiving 10 mg/kg ± radiotherapy, eight had PSA declines of ≥50% (duration: 3–13+ months), one had complete response (duration: 11.3+ months), and six had stable disease (duration: 2.8–6.1 months). Conclusions In mCRPC patients, ipilimumab 10 mg/kg ± radiotherapy suggested clinical antitumor activity with disease control and manageable AEs. Two phase III trials in mCRPC patients evaluating ipilimumab 10 mg/kg ± radiotherapy are ongoing. ClinicalTrials.gov identifier: NCT00323882. PMID:23535954

  17. Complications of peripherally inserted central catheters in advanced cancer patients undergoing combined radiotherapy and chemotherapy.

    PubMed

    Xie, Jun; Xu, Linjie; Xu, Xiaomin; Huang, Yunjuan

    2017-03-23

    To identify whether patients with advanced cancers were at high risk of peripherall"y inserted central catheter-related complications when treated with concurrent chemo-radiotherapy. Peripherally inserted central catheters are widely used in chemotherapy. However, catheter usage may elevate the risks of infections and thrombosis. It is important to identify the patients with high risk of peripherally inserted central catheter-related complications. To date, little is known about peripherally inserted central catheter-related complications in patients with advanced cancers and receiving concurrent chemo-radiotherapy. Five hundred and sixty-nine cancer patients with advanced cancers and treated by chemo-radiotherapy were analysed in the study. The incidences of peripherally inserted central catheter-related complications were investigated. Univariable and multivariable logistic regression analyses were employed for identification of risk factors. Eighty-six (15.1%) patients exhibited peripherally inserted central catheter-related infectious complications, of which 6.3% were local infection, 3.9% were catheter-related bloodstream infection and 4.9% were exit-site infection. Sixty-five (11.4%) developed symptomatic peripherally inserted central catheter-related thrombosis, and 52 (9.1%) were suffering from phlebitis. The overall complication rate was 53.1%. The univariable logistic regression and multivariate analysis showed that comorbidity (OR 1.51, p = .0148) and body mass index (OR 1.46, p = .0157), and duration of radio-chemotherapy (OR 1.4733, p = .0049) were significantly associated with peripherally inserted central catheter-related complications. Patients with peripherally inserted central catheter-related complications showed lower 5-year survival rate than those without peripherally inserted central catheter-related complications. Identification of risk factors for peripherally inserted central catheter-related complications in patients with advanced

  18. Hormono-radiotherapy in prostatic carcinoma: prognostic factors and implications for combined modality treatment.

    PubMed

    Cellini, Numa; Luzi, Stefano; Morganti, Alessio Giuseppe; Mantini, Giovanna; Valentini, Vincenzo; Racioppi, Marco; Leone, Mariavittoria; Mattiucci, Gian Carlo; Di Gesù, Cinzia; Giustacchini, Mario; Destito, Antonio; Smaniotto, Daniela; Alcini, Eugenio

    2002-01-01

    The aim of this study was to evaluate the prognostic role of several clinical variables in a patient population undergoing neoadjuvant hormonotherapy (NHT) with external beam radiotherapy (ERT) to identify subsets of patients with an unfavorable prognosis who require intensified therapy. Eighty-four patients (mean age, 68.2 +/- 6.1 years; range, 52-81 years) underwent ERT (45 Gy to pelvic volume; 65 Gy mean dose to prostate volume) and NHT (oral flutamide: 250 mg three times daily for 30 days; LH-RH analogue: one vial every 28 days starting two months before radiotherapy and for its entire duration). The distribution according to clinical stage was T2: 46.4%, T3: 50.0%, T4: 3.6%. The distribution according to the Gleason score was grade 2-4: 17.9%; grade 5-7: 53.6%; grade 8-10: 28.5%. The distribution according to pretreatment PSA levels (in ng/mL) was 0-4: 5.9%; 4-10: 26.2%; 10-20:16.7%; > or = 20: 51.2%. With a median follow-up of 36 months, 3.6% of patients died; hematogenous metastases and local disease progression were found in 16.7% and 6% of patients, respectively. Overall, the incidence of disease progression was 17.9%. 32.9% of patients showed biochemical failure during followup. Overall, metastasis-free, local progression-free and biochemical failure-free actuarial survival at five years was 89.2%, 66.5%, 85.0% and 41.9%, respectively. At univariate analysis (log-rank) clinical stage (cT) was shown to be significantly correlated with the incidence of metastasis (P = 0.0004), local progression (P < 0.0001) and disease-free survival (P = 0.0005). At multivariate analysis (Cox) the correlations between clinical stage and metastasis (P = 0.0175), local progression (P = 0.0200) and disease-free survival (P = 0.0175) were confirmed. Gleason score and pretreatment PSA levels did not show any significant correlation with these endpoints. These results confirm the indications of the recent literature, which, in prostate carcinoma at higher clinical stages, suggest

  19. Combining the ASA Physical Classification System and Continuous Intraoperative Surgical Apgar Score Measurement in Predicting Postoperative Risk.

    PubMed

    Jering, Monika Zdenka; Marolen, Khensani N; Shotwell, Matthew S; Denton, Jason N; Sandberg, Warren S; Ehrenfeld, Jesse Menachem

    2015-11-01

    The surgical Apgar score predicts major 30-day postoperative complications using data assessed at the end of surgery. We hypothesized that evaluating the surgical Apgar score continuously during surgery may identify patients at high risk for postoperative complications. We retrospectively identified general, vascular, and general oncology patients at Vanderbilt University Medical Center. Logistic regression methods were used to construct a series of predictive models in order to continuously estimate the risk of major postoperative complications, and to alert care providers during surgery should the risk exceed a given threshold. Area under the receiver operating characteristic curve (AUROC) was used to evaluate the discriminative ability of a model utilizing a continuously measured surgical Apgar score relative to models that use only preoperative clinical factors or continuously monitored individual constituents of the surgical Apgar score (i.e. heart rate, blood pressure, and blood loss). AUROC estimates were validated internally using a bootstrap method. 4,728 patients were included. Combining the ASA PS classification with continuously measured surgical Apgar score demonstrated improved discriminative ability (AUROC 0.80) in the pooled cohort compared to ASA (0.73) and the surgical Apgar score alone (0.74). To optimize the tradeoff between inadequate and excessive alerting with future real-time notifications, we recommend a threshold probability of 0.24. Continuous assessment of the surgical Apgar score is predictive for major postoperative complications. In the future, real-time notifications might allow for detection and mitigation of changes in a patient's accumulating risk of complications during a surgical procedure.

  20. Clinical observational study of conformal radiotherapy combined with topotecan chemotherapy in patients with platinum-resistant recurrent ovarian cancer.

    PubMed

    Wei, P; Zhang, Z H; Li, L; Du, X L; Shan, C P; Sheng, X G

    2015-04-22

    This retrospective study aimed to observe the cura-tive effect and adverse reactions of three-dimensional conformal radiotherapy combined with topotecan chemotherapy in patients with platinum-resistant recurrent epithelial ovarian carcinoma. The chemoradiotherapy group (N = 22) received 15 mv X-rays with 1.8 to 2.0 Gy/f/d radiation, 5 times per week. The total dose was 45 to 65 Gy; the median dose was 52.5 Gy. Topotecan chemotherapy (2.0 mg/m(2)) was administered after the first week of radiotherapy on days 1, 8, and 15; it was repeated every 28 days. The only che-motherapy group (N = 20) received topotecan chemotherapy (4.0 mg/m(2)) in the first week, and the dose was administered on days 1, 8, and 15; it was repeated every 28 days. The median follow-up times were 18.5 months (2 to 37.7) and 10.8 months (1.5 to 29.6) in the chemoradiotherapy and in the only chemotherapy groups, respectively. The total response rates were 42.1% (8/19) and 11.1% (2/18), respectively. The clinical benefit rates were 68.4% (13/19) and 22.2% (4/18), respectively, with significant difference (P < 0.05). The median disease progression-free periods were 9.8 and 6.6 months, respectively, with significant difference (P < 0.001). The median survival times were 19.7 and 12.5 months, respective-ly, with significant difference (P < 0.05). The degrees of digestive tract reaction rates were 26.3% (5/19) and 16.7% (3/18), whereas the hematology toxicity rates were 21.1% (4/19) and 22.2% (4/18), respectively, with no significant difference (P > 0.05). As three-dimensional conformal radiotherapy combined with topotecan che-motherapy had good curative effect on platinum-resistant recurrent epithelial ovarian cancer, with mild adverse reactions, this tech-nique can be used as a remedial measure.

  1. Combined total body X-ray irradiation and total skin electron beam radiotherapy with an improved technique for mycosis fungoides

    SciTech Connect

    Halberg, F.E.; Fu, K.K.; Weaver, K.A.; Zackheim, H.S.; Epstein, E.H. Jr.; Wintroub, B.U.

    1989-08-01

    Twelve consecutive patients with advanced stage mycosis fungoides (MF) were treated with combined total body X ray irradiation (TBI) and total skin electron beam radiotherapy (EBRT). Six had generalized plaque disease and dermatopathic nodes, three had tumor stage disease and node biopsy positive for mycosis fungoides, and three had erythroderma/Sezary syndrome. The treatment regimen consisted of split course total body X ray irradiation, given in twice weekly 15 cGy fractions to 75 cGy, then total skin electron beam radiation therapy given in once weekly 400 cGy fractions to a total dose of 2400 cGy. Underdosed areas and areas of greatest initial involvement were boosted 400 cGy twice weekly for an additional 1200 cGy. This was followed by a second course of total body X ray irradiation, to a total dose of 150 cGy. The total skin electron beam radiotherapy technique is a modification of an established six position EBRT technique for mycosis fungoides. Measurements to characterize the beam with and without a lexan scattering plate, demonstrated that the combination of no-plate beams produced better dose uniformity with a much higher dose rate. This improved technique is particularly advantageous for elderly and/or frail patients. Nine (75%) of the 12 patients achieved complete response (CR). The other three had significant improvement with greater than 80% clearing of their disease and resolution of symptoms. All six patients with generalized plaque disease achieved complete response and remained free of disease from 2 to 16 months. Two of three node positive patients also achieved complete response; one, with massive biopsy-documented mycosis fungoides nodal disease and deep open tumors, remained relapse-free over 2 years. Only one of the three patients with erythroderma/Sezary syndrome achieved a complete response, which was short lived.

  2. Characterization of in vitro radiosensitization in mammalian cells using biomathematical modelling: implications for hypofractionated radiotherapy with a combined modality approach.

    PubMed

    Seo, Yuji; Tamari, Keisuke; Yoshioka, Yasuo; Isohashi, Fumiaki; Suzuki, Osamu; Hayashi, Kazuhiko; Takahashi, Yutaka; Baek, SungJae; Otani, Keisuke; Ogawa, Kazuhiko

    2016-06-01

    It is unclear whether radiosensitization is beneficial when radiotherapy is administered at a high dose per fraction. The aim of this study was to assess the impact of radiation dose on the effectiveness of a broad range of radiosensitizers. We analyzed 653 pairs of clonogenic survival curves in 285 published articles, in which modifications of radiosensitivity were studied using the colony-forming assay. The modifications of radiosensitivity were arbitrarily classified into 20 classes. The survival curves were fitted to two biomathematical models: the linear-quadratic model and the repair-misrepair (RMR) model. We found that radiosensitization was predominantly characterized by an increase of the α value (α-sensitization) without an increase of the β value (β-sensitization). A subset analysis revealed that all 20 classes showed significant α-sensitization. In contrast, only oxygen/hypoxic sensitizers (oxygen) and poly(adenosine diphosphate-ribose) polymerase inhibition (PARPi) exhibited β-sensitization. An analysis using the RMR model revealed two major sources of radiosensitization: an increased residual DNA lesion through repair inhibition and a shift from linear repairs to quadratic misrepairs, leading to enhanced lethal chromosomal aberrations. Oxygen and PARPi were found to show β-sensitization, which was favourable for eliciting a comparable degree of sensitization in the higher dose range. Reduced fidelity of the repair was suggested to be a possible mechanism of β-sensitization. Further study targeting β-sensitization is needed to develop a novel combined modality therapy with high-dose-per-fraction radiotherapy. Radiosensitization can be classified into two groups, α- and β-sensitizations. These two phenomena may stem from distinct underlying mechanisms.

  3. Development of in situ forming thermosensitive hydrogel for radiotherapy combined with chemotherapy in a mouse model of hepatocellular carcinoma.

    PubMed

    Peng, Cheng-Liang; Shih, Ying-Hsia; Liang, Kuo-Sheng; Chiang, Ping-Fang; Yeh, Chung-Hsin; Tang, I-Chang; Yao, Cheng-Jung; Lee, Shin-Yi; Luo, Tsai-Yueh; Shieh, Ming-Jium

    2013-05-06

    This study evaluated a system for local cancer radiotherapy combined with chemotherapy. The delivery system is a thermosensitive hydrogel containing a therapeutic radionuclide ((188)Re-Tin colloid) and a chemotherapeutic drug (liposomal doxorubicin). The thermosensitive PCL-PEG-PCL copolymer was designed to spontaneously undergo a sol-gel phase transition in response to temperature, remaining liquid at room temperature and rapidly forming a gel at body temperature. A scanning electron microscope was used to observe the microstructure of the fully loaded hydrogel. Release of radionuclide and doxorubicin from the hydrogel was slow, and the system tended to remain stable for at least 10 days. After the intratumoral administration of Lipo-Dox/(188)Re-Tin hydrogel in mice with hepatocellular carcinoma (HCC), its retention by the tumor, spatiotemporal distribution, and therapeutic effect were evaluated. The residence time in the tumor was significantly longer for (188)Re-Tin loaded hydrogel than for Na (188)Re perrhenate (Na (188)ReO4). The hydrogel after thermal transition kept the radionuclide inside the tumor, whereas free (188)Re perrhenate ((188)ReO4) diffused quickly from the tumor. The tumor growth was more profoundly inhibited by treatment with Lipo-Dox/(188)Re-Tin hydrogel (with up to 80% regression of well-established tumors on day 32) than treatment with either (188)Re-Tin hydrogel or Lipo-Dox hydrogel. Therefore, this injectable and biodegradable hydrogel may offer the advantage of focusing radiotherapy and chemotherapy locally to maximize their effects on hepatocellular carcinoma.

  4. Stereotactic Ablative Radiotherapy Should Be Combined With a Hypoxic Cell Radiosensitizer

    SciTech Connect

    Brown, J. Martin; Diehn, Maximilian; Loo, Billy W.

    2010-10-01

    Purpose: To evaluate the effect of tumor hypoxia on the expected level of cell killing by regimens of stereotactic ablative radiotherapy (SABR) and to determine the extent to which the negative effect of hypoxia could be prevented using a clinically available hypoxic cell radiosensitizer. Results and Discussion: We have calculated the expected level of tumor cell killing from regimens of SABR, both with and without the assumption that 20% of the tumor cells are hypoxic, using the standard linear quadratic model and the universal survival curve modification. We compare the results obtained with our own clinical data for lung tumors of different sizes and with published data from other studies. We also have calculated the expected effect on cell survival of adding the hypoxic cell sensitizer etanidazole at clinically achievable drug concentrations. Modeling tumor cell killing with any of the currently used regimens of SABR produces results that are inconsistent with the majority of clinical findings if tumor hypoxia is not considered. However, with the assumption of tumor hypoxia, the expected level of cell killing is consistent with clinical data. For only some of the smallest tumors are the clinical data consistent with no tumor hypoxia, but there could be other reasons for the sensitivity of these tumors. The addition of etanidazole at clinically achievable tumor concentrations produces a large increase in the expected level of tumor cell killing from the large radiation doses used in SABR. Conclusions: The presence of tumor hypoxia is a major negative factor in limiting the curability of tumors by SABR at radiation doses that are tolerable to surrounding normal tissues. However, this negative effect of hypoxia could be overcome by the addition of clinically tolerable doses of the hypoxic cell radiosensitizer etanidazole.

  5. Treatment complications after sequential combination chemotherapy and radiotherapy with or without surgery in previously untreated squamous cell carcinoma of the head and neck

    SciTech Connect

    Posner, M.R.; Weichselbaum, R.R.; Fitzgerald, T.J.; Clark, J.R.; Rose, C.; Fabian, R.L.; Norris, C.M. Jr.; Miller, D.; Tuttle, S.A.; Ervin, T.J.

    1985-11-01

    One hundred consecutive patients with previously untreated advanced squamous cell carcinoma of the head and neck were treated with induction combination chemotherapy followed by definitive surgery and/or radiotherapy, and were evaluated for radiotherapy related toxicity. The induction regimen consisted of cisplatin, bleomycin and methotrexate/leucovorin. Acute toxicity consisted predominantly of mucositis and weight loss, and was mild or moderate by degree in 94% of patients. Six percent of patients experienced severe or life threatening acute toxicities. Two acute toxic deaths were noted in this series, one from a combination of mucositis, weight loss and infection and one from hypoglycemia of unknown origin. Thirty-five percent of patients had radiation treatment interrupted briefly because of acute toxicity. Radiotherapy dose, surgical intervention and age did not have an impact on the presence or degree of acute toxicity. Late toxicities included: hypothyroidism in 32% of patients tested: osteoradionecrosis in 5% of patients, associated primarily with a composite resection (4 of 5 cases); and soft tissue ulcerations in 3%. Taken together, these data indicate that induction combination chemotherapy did not significantly increase the toxicity of subsequent radiotherapy with or without surgery.

  6. [Intraoperative colonoscopy: current indications].

    PubMed

    Stroppa, I; D'Antini, P; Rossi, L; Farinon, A M

    1993-01-01

    From January 1987 to December 1991, 37 patients underwent intraoperative colonoscopy for several indications; these latter can be summarized in the need to define the site or extension of the lesions treated or detected by endoscopy before surgery. This procedure is therefore necessary in those cases in whom intraoperative endoscopy is likely to be useful in planning the surgical treatment. The use of intraoperative colonoscopy should be however considered complementary, but not substitutive, of the preoperative colonoscopy.

  7. [Reoxygenation of tumors of the uterine cervix during combined radiotherapy using low dose gamma-neutron irradiation with californium-252].

    PubMed

    Tacev, T; Rasovská, O; Strnad, V; Krystof, V; Prokes, B; Vacek, A

    1989-03-01

    A polarographic method was used to follow the changes in oxygenation of a tumour of uterus cervix after intracavital irradiation by 252Cf by a physical dose of 2 Gy, applied at the beginning of a therapeutic cycle of combined radiotherapy. The results reached are compared with the results of tumour oxygenation in the course of a conventional therapeutic procedure. It has become apparent that even after the irradiation of a tumour of uterus cervix by a small dose of gamma-neutron radiation with 252Cf there is, beginning with 2nd week of therapy, a significant reoxygenation of the tumour population. The changes of oxygenation after a conventional irradiation have been less marked and reached, in the 4th week of therapy, only marginally significant increase. Differences in reoxygenation of tumours of uterus cervix were confirmed by analysis of the oxygen test. The importance of tumour reoxygenation after the application of 252Cf source of radiation for facilitation of its regression in a combined treatment with Californium-252 and gamma irradiation is discussed.

  8. Mitomycin C in combination with radiotherapy as a potent inhibitor of tumour cell repopulation in a human squamous cell carcinoma

    PubMed Central

    Budach, W; Paulsen, F; Welz, S; Classen, J; Scheithauer, H; Marini, P; Belka, C; Bamberg, M

    2002-01-01

    The potential of Mitomycin C in combination with fractionated irradiation to inhibit tumour cell repopulation of a fast growing squamous cell carcinoma after fractionated radiotherapy was investigated in vivo. A rapidly growing human squamous cell carcinoma (FaDudd) was used for the study. For experiments, NMRI (nu/nu) mice with subcutaneously growing tumours were randomly allocated to no treatment, Mitomycin C, fractionated irradiation (ambient: 11x4.5 Gy in 15 days), or fractionated irradiation combined with Mitomycin C. Graded top up doses (clamped blood flow: 0–57 Gy) were given at day 16, 23, 30 or 37. End point of the study was the time to local tumour progression. Data were examined by multiple regression analysis (Cox). Mitomycin C alone resulted in a median time to local tumour progression of 23 (95% confidence limits: 17–43) days, fractionated irradiation in 31 (25–35) days and combined Mitomycin C plus fractionated irradiation in 65 (58–73) days (P=0.02). Mitomycin C decreased the relative risk of local recurrence by 94% (P<<0.001) equivalent to 31.7 Gy top up dose. Repopulation accounted for 1.33 (0.95–1.72) Gy per day top up dose after fractionated irradiation alone and for 0.68 (0.13–1.22) Gy per day after fractionated irradiation+Mitomycin C (P=0.018). Mitomycin C significantly reduces the risk of local recurrence and inhibits tumour cell repopulation in combination with fractionated irradiation in vivo in the tested tumour model. British Journal of Cancer (2002) 86, 470–476. DOI: 10.1038/sj/bjc/6600081 www.bjcancer.com © 2002 The Cancer Research Campaign PMID:11875717

  9. Tumor control and therapeutic gain with different schedules of combined radiotherapy and local external hyperthermia in human cancer

    SciTech Connect

    Arcangeli, G.; Cividalli, A.; Nervi, C.; Creton, G.; Lovisolo, G.; Mauro, F.

    1983-08-01

    Tumor control and therapeutic gain have been evaluated in a series of studies on patients with multiple lesions employing different protocols of combined radiotherapy (RT) and local external hyperthermia (HT). Tumor response has been evaluated during a follow-up ranging 6 to 18 months. Local tumor control was constantly better in lesions treated with any combined modalities in comparison with RT alone. The use of high RT dose per fraction appeared to increase tumor control only in the combined modalities groups, the immediate (so called simultaneous) schedule (HT at 42.5/sup 0/C/45 min, applied immediately after each RT fraction, twice a week) being more effective than the delayed (so called sequential) treatment (HT at 42.5/sup 0/C/45 min, delivered 4 h after each RT fraction, twice a week). The combination of high RT dose per fraction with high temperature HT (45/sup 0/C for 30 min) achieved the best tumor control. Consequently, a good therapeutic enhancement factor (TEF) (1.58) was obtained when conventional RT doses per fraction were used in association with 42.5/sup 0/C HT. TEF values of 1.40 and 1.15 were observed when high RT doses per fraction were employed in association with the delayed and immediate 42.5/sup 0/C HT, respectively. HT at 45/sup 0/C can be safely employed only when tumors can be heated selectively or at least preferentially in comparison with normal tissue; in the lesions treated with such a schedule a TEF of 2.10 was obtained.

  10. Californium-252 neutron brachytherapy combined with external beam radiotherapy for esophageal cancer: long-term treatment results.

    PubMed

    Liu, Huiming; Wang, Qifeng; Wan, Xin; Jia, Xitang; Liu, Bo; Wang, C-K Chris

    2014-01-01

    The aim of this study was to retrospectively observe and analyze the long-term treatment outcomes for a total of 952 esophageal cancer patients who were treated with (252)Cf neutron brachytherapy (NBT) in combination with external beam radiotherapy (EBRT). From November 2001 to March 2012, 952 patients with esophageal cancer underwent NBT in combination with EBRT. The patient numbers distributed over various cancer Stages I, IIA, IIB, III, and IVA were 9, 290, 51, 579, and 23, respectively. The total radiation dose to the reference point via NBT was 8-25 Gy-eq in three to five fractions with one fraction/week. The total dose via EBRT was 40-60 Gy delivered over a period of 5-6 weeks with normal fractionation. The overall median survival time was 20.3 months. The 1-, 3-, and 5-year survival rates were 67.1%, 36.3%, and 26.6%, respectively. These results compare favorably with the results obtained from conventional high-dose rate in combination with EBRT. Although a majority of the patients (860 or 90.3%) developed Grades 1 and 2 esophagitis during treatment, the symptoms were effectively relieved after the application of antacid and surface anesthesia. The clinical data show that NBT in combination with EBRT produced favorable local control and long-term survival rates for patients with esophageal cancer and that the side effects are tolerable. As such, we conclude that this dual-modality method is an effective and safe way for treating esophageal cancer. Published by Elsevier Inc.

  11. Epidemiology and prevalence of oropharyngeal candidiasis in Spanish patients with head and neck tumors undergoing radiotherapy treatment alone or in combination with chemotherapy.

    PubMed

    Mañas, Ana; Cerezo, Laura; de la Torre, Alejandro; García, Mariola; Alburquerque, Héctor; Ludeña, Blanca; Ruiz, Ana; Pérez, Ana; Escribano, Ana; Manso, Aurea; Glaria, Luis Alberto

    2012-10-01

    To describe the oropharyngeal candidiasis (OPC) prevalence in Spanish patients with head and neck cancer undergoing radiotherapy, alone or combined with chemotherapy. Secondary objectives were to determine the prevalence of Candida species colonization, and to explore whether different Candida species colonizing the oral cavity and the treatment were associated with a higher prevalence of OPC. This is an observational, cross-sectional, multicentre study, conducted in Spanish radiation oncology units. Patients were diagnosed with head and neck cancer and started a radiotherapy treatment alone or combined with chemotherapy at the moment of their inclusion (N = 92). The OPC prevalence was 26 %. The identification of colonizing pathogens was performed in 49 patients, and Candida albicans was the dominant yeast (69 %), while non-albicans Candida was only found in 15 patients (31 %). Patients with C. albicans colonization had a significant higher prevalence of OPC compared to patients colonized by non-albicans Candida (p = 0.0273), but no difference was found regarding the OPC prevalence in patients receiving only radiotherapy compared to patients with both radiotherapy and chemotherapy treatments. Our data represent a step further in the knowledge of Candida species present in Spanish patients with head and neck tumors under radiation therapy. This is an essential step to manage the prophylaxis and treatment of OPC, since it might lead to severe clinical complications causing treatment interruption and, thus, representing a reduction in anti-tumor efficacy.

  12. First-in-human phase I study of the DNA-repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma

    PubMed Central

    Le Tourneau, C; Dreno, B; Kirova, Y; Grob, J J; Jouary, T; Dutriaux, C; Thomas, L; Lebbé, C; Mortier, L; Saiag, P; Avril, M F; Maubec, E; Joly, P; Bey, P; Cosset, J M; Sun, J S; Asselain, B; Devun, F; Marty, M E; Dutreix, M

    2016-01-01

    Background: DT01 is a DNA-repair inhibitor preventing recruitment of DNA-repair enzymes at damage sites. Safety, pharmacokinetics and preliminary efficacy through intratumoural and peritumoural injections of DT01 were evaluated in combination with radiotherapy in a first-in-human phase I trial in patients with unresectable skin metastases from melanoma. Methods: Twenty-three patients were included and received radiotherapy (30 Gy in 10 sessions) on all selected tumour lesions, comprising of two lesions injected with DT01 three times a week during the 2 weeks of radiotherapy. DT01 dose levels of 16, 32, 48, 64 and 96 mg were used, in a 3+3 dose escalation design, with an expansion cohort at 96 mg. Results: The median follow-up was 180 days. All patients were evaluable for safety and pharmacokinetics. No dose-limiting toxicity was observed and the maximum-tolerated dose was not reached. Most frequent adverse events were reversible grades 1 and 2 injection site reactions. Pharmacokinetic analyses demonstrated a systemic passage of DT01. Twenty-one patients were evaluable for efficacy on 76 lesions. Objective response was observed in 45 lesions (59%), including 23 complete responses (30%). Conclusions: Intratumoural and peritumoural DT01 in combination with radiotherapy is safe and pharmacokinetic analyses suggest a systemic passage of DT01. PMID:27140316

  13. Survival benefit associated with adjuvant androgen deprivation therapy combined with radiotherapy for high- and low-risk patients with nonmetastatic prostate cancer

    SciTech Connect

    Zeliadt, Steven B. . E-mail: szeliadt@fhcrc.org; Potosky, Arnold L.; Penson, David F.

    2006-10-01

    Background: The use of adjuvant androgen deprivation therapy (ADT) combined with radiotherapy has become common in low-risk patients, although clinical trials have focused primarily on high-risk patients. This study examines the effectiveness of adjuvant ADT combined with radiotherapy for a wide range of patients treated in the 1990s. Methods and Materials: Prostate cancer survival was examined in a population based cohort of 31,643 patients aged 65 to 85 years who were diagnosed with nonmetastatic prostate cancer and treated with external beam radiotherapy and/or brachytherapy. Instrumental variable analysis methods were used to control for selection bias. Results: Patients with stage T3/T4 disease who received adjuvant ADT experienced improved 5-year and 8-year survival. No survival advantage was observed for men with T1/T2 disease during this interval. Conclusion: High-risk patients who receive primary radiotherapy have benefited from adjuvant ADT, whereas low-risk patients with disease confined to the prostate have not yet benefited from adjuvant therapy within the first 8 years after treatment. These findings are consistent with practice guidelines, which recommend adjuvant ADT for patients with high-risk disease.

  14. VEGF Trap in Combination With Radiotherapy Improves Tumor Control in U87 Glioblastoma

    SciTech Connect

    Wachsberger, Phyllis R. . E-mail: Phyllis.Wachsberger@mail.tju.edu; Burd, Randy; Cardi, Chris; Thakur, Mathew; Daskalakis, Constantine; Holash, Jocelyn; Yancopoulos, George D.; Dicker, Adam P.

    2007-04-01

    Purpose: To determine the effect of vascular endothelial growth factor VEGF Trap (Regeneron Pharmaceuticals, Tarrytown, NY), a humanized soluble vascular endothelial growth factor (VEGF) receptor protein, and radiation (RT) on tumor growth in U87 glioblastoma xenografts in nude mice. Methods and Materials: U87 cell suspensions were implanted subcutaneously into hind limbs of nude mice. VEGF Trap (2.5-25 mg/kg) was administered every 3 days for 3 weeks alone or in combination with a single dose of 10 Gy or fractionated RT (3 x 5 Gy). In addition, three scheduling protocols for VEGF Trap plus fractionated RT were examined. Results: Improved tumor control was seen when RT (either single dose or fractionated doses) was combined with the lowest dose of VEGF Trap (2.5 mg/kg). Scheduling did not significantly affect the efficacy of combined therapy. Although high-dose VEGF Trap (10 mg/kg or 25 mg/kg) significantly reduced tumor growth over that of RT alone, there was no additional benefit to combining high-dose VEGF Trap with RT. Conclusions: Vascular endothelial growth factor Trap plus radiation is clearly better than radiation alone in a U87 subcutaneous xenograft model. Although high doses of VEGF Trap alone are highly efficacious, it is unclear whether such high doses can be used clinically without incurring normal tissue toxicities. Thus, information on lower doses of VEGF Trap and ionizing radiation is of clinical relevance.

  15. Californium-252 Brachytherapy Combined With External-Beam Radiotherapy for Cervical Cancer: Long-Term Treatment Results

    SciTech Connect

    Lei Xin; Qian Chengyuan; Qing Yi; Zhao Kewei; Yang Zhengzhou; Dai Nan; Zhong Zhaoyang; Tang Cheng; Li Zheng; Gu Xianqing; Zhou Qian; Feng Yan; Xiong Yanli; Shan Jinlu; Wang Dong

    2011-12-01

    Purpose: To observe, by retrospective analysis, the curative effects and complications due to californium-252 ({sup 252}Cf) neutron intracavitary brachytherapy (ICBT) combined with external-beam radiotherapy (EBRT) in the treatment of cervical cancer. Methods and Materials: From February 1999 to December 2007, 696 patients with cervical cancer (Stages IB to IIIB) were treated with {sup 252}Cf-ICBT in combination of EBRT. Of all, 31 patients were at Stage IB, 104 at IIA, 363 at IIB, 64 at IIIA, and 134 at IIIB. Californium-252 ICBT was delivered at 7-12 Gy per insertion per week, with a total dose of 29-45 Gy to reference point A in three to five insertions. The whole pelvic cavity was treated with 8-MV X-ray external irradiation at 2 Gy per fraction, four times per week. After 16-38 Gy of external irradiation, the center of the whole pelvic field was blocked with a 4-cm-wide lead shield, with a total external irradiation dose of 44-56 Gy. The total treatment course was 5 to 6 weeks. Results: Overall survival rate at 3 and 5 years for all patients was 76.0% and 64.9%, respectively. Disease-free 3- and 5-year survival rates of patients were 71.2% and 58.4%, respectively. Late complications included vaginal contracture and adhesion, radiation proctitis, radiation cystitis, and inflammatory bowel, which accounted for 5.8%, 7.1%, 6.2%, and 4.9%, respectively. Univariate analysis results showed significant correlation of stage, age, histopathologic grade, and lymph node status with overall survival. Cox multiple regression analysis showed that the independent variables were stage, histopathologic grade, tumor size, and lymphatic metastasis in all patients. Conclusion: Results of this series suggest that the combined use of {sup 252}Cf-ICBT with EBRT is an effective method for treatment of cervical cancer.

  16. Californium-252 brachytherapy combined with external-beam radiotherapy for cervical cancer: long-term treatment results.

    PubMed

    Lei, Xin; Qian, Cheng-Yuan; Qing, Yi; Zhao, Ke-Wei; Yang, Zheng-Zhou; Dai, Nan; Zhong, Zhao-Yang; Tang, Cheng; Li, Zheng; Gu, Xian-Qing; Zhou, Qian; Feng, Yan; Xiong, Yan-Li; Shan, Jin-Lu; Wang, Dong

    2011-12-01

    To observe, by retrospective analysis, the curative effects and complications due to californium-252 (252Cf) neutron intracavitary brachytherapy (ICBT) combined with external-beam radiotherapy (EBRT) in the treatment of cervical cancer. From February 1999 to December 2007, 696 patients with cervical cancer (Stages IB to IIIB) were treated with 252Cf-ICBT in combination of EBRT. Of all, 31 patients were at Stage IB, 104 at IIA, 363 at IIB, 64 at IIIA, and 134 at IIIB. Californium-252 ICBT was delivered at 7-12 Gy per insertion per week, with a total dose of 29-45 Gy to reference point A in three to five insertions. The whole pelvic cavity was treated with 8-MV X-ray external irradiation at 2 Gy per fraction, four times per week. After 16-38 Gy of external irradiation, the center of the whole pelvic field was blocked with a 4-cm-wide lead shield, with a total external irradiation dose of 44-56 Gy. The total treatment course was 5 to 6 weeks. Overall survival rate at 3 and 5 years for all patients was 76.0% and 64.9%, respectively. Disease-free 3- and 5-year survival rates of patients were 71.2% and 58.4%, respectively. Late complications included vaginal contracture and adhesion, radiation proctitis, radiation cystitis, and inflammatory bowel, which accounted for 5.8%, 7.1%, 6.2%, and 4.9%, respectively. Univariate analysis results showed significant correlation of stage, age, histopathologic grade, and lymph node status with overall survival. Cox multiple regression analysis showed that the independent variables were stage, histopathologic grade, tumor size, and lymphatic metastasis in all patients. Results of this series suggest that the combined use of 252Cf-ICBT with EBRT is an effective method for treatment of cervical cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. The role of radiotherapy in the management of localized soft tissue sarcomas

    PubMed Central

    Tiong, Siaw Sze; Dickie, Colleen; Haas, Rick L.; O’Sullivan, Brian

    2016-01-01

    The combination of radiotherapy (RT) and function-preserving surgery is the most usual contemporary approach in the management of soft tissue sarcomas (STS). Pre- and postoperative RT result in similar local control rates, as shown by a landmark trial in extremity STS. In this review, the role of RT in the management of extremity STS will be discussed, but STS in other sites, including retroperitoneal STS, will also be addressed. The focus will consider various aspects of RT including strategies to reduce the volume of tissue being irradiated, dose, scheduling, and the possible of omission of RT in selected cases. Finally, technology advances through the use of intensity-modulated radiotherapy (IMRT), image-guided IMRT, intraoperative radiotherapy (IORT) and particle therapy will also be discussed. PMID:27807504

  18. GNRs@SiO2-FA in combination with radiotherapy induces the apoptosis of HepG2 cells by modulating the expression of apoptosis-related proteins

    PubMed Central

    GAO, BIN; SHEN, LEI; HE, KE-WU; XIAO, WEI-HUA

    2015-01-01

    The aim of the present study was to examine the apoptosis of the hepatocellular carcinoma cell line, HepG2, induced by treatment with folic acid-conjugated silica-coated gold nanorods (GNRs@SiO2-FA) in combination with radiotherapy, and to determine the involvement of apoptosis-related proteins. An MTT colorimetric assay was used to assess the biocompatibility of GNRs@SiO2-FA. The distribution of GNRs@SiO2-FA into the cells was observed using transmission electron microscopy (TEM). HepG2 cells cultured in vitro were divided into the following 4 groups: i)the control group (untreated), ii) the GNRs@SiO2-FA group, iii) the radiotherapy group (iodine 125 seeds) and iv) the combination group (treated with GNRs@SiO2-FA and iodine 125 seeds) groups. The apoptosis of the HepG2 cells was detected by flow cytometry. The concentration range of <40 µg/ml GNRs@SiO2-FA was found to be safe for the biological activity of the HepG2 cells. GNRs@SiO2-FA entered the cytoplasm through endocytosis. The apoptotic rates of the HepG2 cells were higher in the GNRs@SiO2-FA and radiotherapy groups than in the control group (P<0.05). The apoptotic rate was also significantly higher in the combination group than the GNRs@SiO2-FA and radiotherapy groups (P<0.05). Taken together, these findings demonstrate that the combination of GNRs@SiO2-FA and radiotherapy more effectively induces the apoptosis of HepG2 cells. These apoptotic effects are achieved by increasing the protein expression of Bax and caspase-3, and inhibiting the protein expression of Bcl-2 and Ki-67. The combination of GNRs@SiO2-FA and radiotherapy may thus prove to be a new approach in the treatment of primary liver cancer. PMID:26648274

  19. Combination effects of tissue heterogeneity and geometric targeting error in stereotactic body radiotherapy for lung cancer using CyberKnife.

    PubMed

    Kang, Ki Mun; Jeong, Bae Kwon; Choi, Hoon-Sik; Yoo, Seung Hoon; Hwang, Ui-Jung; Lim, Young Kyung; Jeong, Hojin

    2015-09-08

    We have investigated the combined effect of tissue heterogeneity and its variation associated with geometric error in stereotactic body radiotherapy (SBRT) for lung cancer. The treatment plans for eight lung cancer patients were calculated using effective path length (EPL) correction and Monte Carlo (MC) algorithms, with both having the same beam configuration for each patient. These two kinds of plans for individual patients were then subsequently recalculated with adding systematic and random geometric errors. In the ordinary treatment plans calculated with no geometric offset, the EPL calculations, compared with the MC calculations, largely overestimated the doses to PTV by ~ 21%, whereas the overestimation were markedly lower in GTV by ~ 12% due to relatively higher density of GTV than of PTV. When recalculating the plans for individual patients with assigning the systematic and random geometric errors, no significant changes in the relative dose distribution, except for overall shift, were observed in the EPL calculations, whereas largely altered in the MC calculations with a consistent increase in dose to GTV. Considering the better accuracy of MC than EPL algorithms, the present results demonstrated the strong coupling of tissue heterogeneity and geometric error, thereby emphasizing the essential need for simultaneous correction for tissue heterogeneity and geometric targeting error in SBRT of lung cancer.

  20. Lack of therapeutic gain when low dose rate interstitial radiotherapy is combined with cisplatin in an animal tumour model.

    PubMed

    Pop, L; Levendag, P; van Geel, C; Deurloo, I K; Visser, A

    1992-01-01

    The interaction of cisplatin with low dose rate interstitial radiotherapy was studied in an animal tumour model with a range of dose rats commonly used in clinical low dose rate brachytherapy. Small pieces of R1-rhabdomyosarcoma were implanted subcutaneously in the flanks of female Wag/Rij rats. When the tumour had grown to the desired treatment volume, four afterloading catheters were inserted in the tumour in a square geometry, and a fixed spacing was attained by means of a template. Subsequently, four 2 cm Ir192 wires were inserted. A range of tumour doses of 20-120 Gy at a mean dose rate of 48 cGy/h was applied; 15 mins before the implant an intraperitoneal bolus injection of 3 mg/kg cisplatin was given. For growth delay and cure rate, no modification of the effects of low dose rate brachytherapy by the addition of cisplatin was observed. The observed effects of the combination of cisplatin with low dose rate interstitial radiation in relation to the animal tumour are discussed.

  1. Experience with combination of nimotuzumab and intensity-modulated radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma.

    PubMed

    Zhai, Rui-Ping; Ying, Hong-Mei; Kong, Fang-Fang; Du, Cheng-Run; Huang, Shuang; Zhou, Jun-Jun; Hu, Chao-Su

    2015-01-01

    To evaluate the efficacy and safety of using nimotuzumab in combination with intensity-modulated radiotherapy (IMRT) in the primary treatment of locoregionally advanced nasopharyngeal carcinoma. Between December 2009 and December 2013, 38 newly diagnosed patients with stage III-IV nasopharyngeal carcinoma were treated with IMRT and nimotuzumab concomitantly. The distribution of disease was stage III in 20 (52.6%), stage IV A in 9 (23.7%), and stage IV B in 9 (23.7%). All the patients received at least two cycles of cisplatin-based neoadjuvant chemotherapy followed by nimotuzumab 200 mg/week concurrently with IMRT. Acute and late radiation-related toxicities were graded according to the Acute and Late Radiation Morbidity Scoring Criteria of Radiation Therapy Oncology Group. With a median follow-up of 39.7 months (range, 13.3-66.5 months), the estimated 3-year local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, progression failure-free survival, and overall survival rates were 92.8%, 92.9%, 89.5%, 78.7%, and 87.5%, respectively. The median cycle for nimotuzumab addition was 6 weeks. Grade 3 radiation-induced mucositis accounted for 36.8% of treated people. No skin rash and infusion reaction were observed, distinctly from what is reported in cetuximab-treated patients. Nimotuzumab plus IMRT showed promising outcomes in terms of locoregional control and survival, without increasing the incidence of radiation-related toxicities for patients.

  2. Inhibition of Tumor Growth and Metastasis by a Combination of Escherichia coli–mediated Cytolytic Therapy and Radiotherapy

    PubMed Central

    Jiang, Sheng-Nan; Phan, Thuy X; Nam, Taek-Keun; Nguyen, Vu H; Kim, Hyung-Seok; Bom, Hee-Seung; Choy, Hyon E; Hong, Yeongjin; Min, Jung-Joon

    2010-01-01

    We have reported that Escherichia coli K-12 colonizes hypoxic and necrotic tumor regions after intravenous injection into tumor-bearing mice. In this study, we established a novel strategy for cancer therapy using engineered bacteria to enhance the therapeutic effects of radiation. E. coli strain K-12 was engineered to produce cytolysin A (ClyA), and its effects on tumor growth in primary and metastatic tumor models were evaluated. A single treatment with E. coli–expressing ClyA significantly decreased tumor growth rates initially (9 days after treatment); however, the tumors tended to grow thereafter. With only radiotherapy (RT; 21 Gy), the tumor growth rates were retarded, but not the tumor sizes. A combination of therapy with E. coli–expressing ClyA and radiation [a total of 5 × 107 colony-forming units (CFU) and 21 Gy] resulted in significant tumor shrinkage and even complete disappearance of tumors in mice with tumors derived from murine CT26 colon cancer. Furthermore, treatment with E. coli–expressing ClyA markedly suppressed metastatic tumor growth and prolonged the survival time in mice. The results described here indicate that therapy with engineered E. coli could significantly improve the results of RT, and could exert a striking inhibitory effect on the development of lung metastasis. PMID:20051939

  3. Differential action on cancer and normal tissue by adrenochrome monoaminoguanidine methanesulfonate and cytochrome C combined with radiotherapy

    SciTech Connect

    Nakatsugawa, S. ); Sugahara, T. )

    1994-06-15

    The possibility that radioprotective effects on potent natural killer (NK) cells by adrenochrome monoaminoguanidine methanesulfonate (AMM) + cytochrome C during radiotherapy (RT) for lung cancer might result in the radiosensitization of human lung cancer cells in vivo is examined. Human lung cancer xenografts in the right hind legs of KSN mice (10 weeks old) were locally irradiated with 20 Gy of X ray. AMM (10 mg/kg/day) and/or cytochrome C (CCC) (5 mg/kg/day) were given intraperitoneally immediately before or after RT, followed by daily administration for 4 days. Natural killer activities of host splenocytes were also tested with the standard [sup 51]Cr releasing assay with YAC-1 cells as target cells. In a clinical study, 65 patients with lung cancer were treated with more than 50 Gy of RT with or without combination with AMM + CCC, OK-432 or AMM + CCC + OK-432. Before and after RT, lymphocyte subsets in the peripheral blood were examined with dichromatic analysis using an Ortho Spectrum IIIFCM system and fluorescent MABs. In this study, the change in the absolute number of each subset was investigated. AMM + cytochrome C augumented NK activity in KSN nude mice, protected potent NK cells in patients with lung cancer against RT and sensitized the human lung cancer xenografts to RT. AMM + cytochrome C may have potential as a differential modulator of radiosensitivity of normal tissues and of tumors. 8 refs., 2 figs., 1 tab.

  4. [Clinical analysis of combination of (252)Cf neutron intracavitary brachytherapy and external beam radiotherapy for 110 cervical cancer patients].

    PubMed

    Bu, Jie; Li, Ren; Song, Wei; Cao, Jing-xu; Wang, Ying-xuan

    2010-08-01

    To evaluate the curative effect and complication of (252)Cf brachytherapy on cervical cancer. From Nov 2002 to Nov 2007, 110 cervical cancer patients were treated by combination of (252)Cf neutron intracavitary brachytherapy and external beam radiotherapy. There were 2 cases of stage Ib, 5 stage IIa, 57 stage IIb, 2 stage IIIa, 41 stage IIIb, 2 stage IVa, and 1 stage IVb. The whole pelvic cavity was irradiated with 8 MV X-ray, 1.8 Gy/fraction, 4 - 5 times per week. The total dose of external beam radiotherapy was 40 - 50 Gy (the center of whole pelvic field was blocked by 4 cm in width after 20 - 30 Gy). (252)Cf neutron intracavitary brachytherapy was delivered at 6 - 8 Gy(i)/fraction, and the total dose of reference point A was 30-51 Gy(i). The median dose was 42 Gy(i). The overall 3-year survival rate of all patients was 79.2%, and the local control rate was 90.0%. In particular, the 3-year survival rate was 1/2 for stage I, 84.3% for stage II, 53.7% for stage III. The difference between stage II and stage III was statistically significant (P < 0.05). The 3-year survival in cervical lesions larger than or equal to 4 cm and those less than 4 cm was 68.1% and 71.2%, respectively (P > 0.05). The 3-year survival rate of patients with and without anemia was 42.4% and 78.2%, respectively (P < 0.05). The 3-year survival rate of patients with squamous cell carcinoma and adenocarcinoma was 78.5% and 76.9%, respectively (P > 0.05). The late radiation complications of rectum and bladder was 11.8% (13/110) and 2.7% (3/110), respectively. It is concluded that (252)Cf is a better source for intracavitary brachytherapy. According to our initial experience, (252)Cf has advantages of a high local control rate, especially to bulky tumor and adenocarcinoma.

  5. Oncolytic vaccinia virus combined with radiotherapy induces apoptotic cell death in sarcoma cells by down-regulating the inhibitors of apoptosis

    PubMed Central

    Wilkinson, Michelle J.; Smith, Henry G.; McEntee, Gráinne; Kyula-Currie, Joan; Mansfield, David C.; Khan, Aadil A.; Roulstone, Victoria

    2016-01-01

    Advanced extremity melanoma and sarcoma present a significant therapeutic challenge, requiring multimodality therapy to treat or even palliate disease. These aggressive tumours are relatively chemo-resistant, therefore new treatment approaches are urgently required. We have previously reported on the efficacy of oncolytic virotherapy (OV) delivered by isolated limb perfusion. In this report, we have improved therapeutic outcomes by combining OV with radiotherapy. In vitro, the combination of oncolytic vaccinia virus (GLV-1h68) and radiotherapy demonstrated synergistic cytotoxicity. This effect was not due to increased viral replication, but mediated through induction of intrinsic apoptosis. GLV-1h68 therapy downregulated the anti-apoptotic BCL-2 proteins (MCL-1 and BCL-XL) and the downstream inhibitors of apoptosis, resulting in cleavage of effector caspases 3 and 7. In an in vivo ILP model, the combination of OV and radiotherapy significantly delayed tumour growth and prolonged survival compared to single agent therapy. These data suggest that the virally-mediated down-regulation of anti-apoptotic proteins may increase the sensitivity of tumour cells to the cytotoxic effects of ionizing radiation. Oncolytic virotherapy represents an exciting candidate for clinical development when delivered by ILP. Its ability to overcome anti-apoptotic signals within tumour cells points the way to further development in combination with conventional anti-cancer therapies. PMID:27783991

  6. Seeing is believing: increasing intraoperative awareness to scattered radiation in interventional procedures by combining augmented reality, Monte Carlo simulations and wireless dosimeters.

    PubMed

    Loy Rodas, Nicolas; Padoy, Nicolas

    2015-08-01

    Surgical staff performing image-guided minimally invasive surgical procedures are chronically exposed to harmful ionizing radiation. Currently, no means exist to intraoperatively depict the 3D shape and intensity of scattered radiation fields or to assess the body-part exposure of clinicians. We propose a system for simulating and visualizing intraoperative scattered radiation using augmented reality. We use a multi-camera RGBD system to obtain a 3D point cloud reconstruction of the current room layout. The positions of the clinicians, patient, table and C-arm are used to build a radiation propagation simulation model and compute the deposited dose distribution in the room. We use wireless dosimeters to calibrate the simulation and to evaluate its accuracy at each time step. The computed 3D risk map is shown in an augmented reality manner by overlaying the simulation results onto the 3D model. Several 3D visualizations showing scattered radiation propagation, clinicians' body-part exposure and radiation risk maps under different irradiation conditions are proposed. The system is evaluated in an operating room equipped with a robotized X-ray imaging device by comparing the radiation simulation results to experimental measurements under several X-ray acquisition setups and room configurations. The proposed system is capable to display intraoperative scattered radiation intuitively in 3D by using augmented reality. This can have a strong impact on improving clinicians' awareness of their exposure to ionizing radiation and on reducing overexposure risks.

  7. Targeted therapies in combination with radiotherapy in oesophageal and gastroesophageal carcinoma.

    PubMed

    Cellini, F; Valentini, V

    2014-01-01

    Oesophageal cancer is the sixth cause of cancer-related death worldwide. Nowadays radiochemotherapy (RTCT) plays a central role in the treatment settings of such disease. Evaluation of molecular targeted therapies is an attractive opportunity for the management of oesophageal, GEJ and gastric cancers to improve outcomes as for other primary tumours. Clinical trials focused on the potential of many molecular targeted agents included in CT schedules, and also on the possibility, efficacy and tolerance of their use combined with RT. This review will focus on the over 15 more promising agents studied in combination with RT for esophagogastric tumour, describing the mechanism and target of action, evidences and potential future role on over 50 trials evaluated. Mechanisms of action, studies and evidences about Human Epidermal Growth Factor type 2 Targeting Agents (one of the more promising), Epidermal Growth Factor's Receptor Inhibitors (nowadays showing a lower potential than expected), Vascular Endothelial Growth Factor Inhibitors, Mesenchymal Epithelial Transition Factor, Hepatocyte Growth Factor and other targeting agents are reviewed.

  8. Evaluation of Acute Locoregional Toxicity in Patients With Breast Cancer Treated With Adjuvant Radiotherapy in Combination With Bevacizumab

    SciTech Connect

    Goyal, Sharad

    2011-02-01

    Purpose: Preclinical studies have shown that bevacizumab combined with radiotherapy (RT) induces a radiosensitizing effect. Published reports regarding the safety of combination therapy involving bevacizumab and RT are lacking. The purpose of this study was to analyze acute locoregional toxicity in patients with breast cancer receiving concurrent bevacizumab plus RT. Methods and Materials: After institutional review board approval was obtained, patients with breast cancer who received bevacizumab were identified; these patients were then cross-referenced with patients receiving RT. Toxicity was scored by the Common Terminology Criteria for Adverse Events. Patients were matched 1:1 with those who did not receive bevacizumab. Statistical analysis was performed to analyze toxicity between the two groups. Results: Fourteen patients were identified to have received bevacizumab plus RT. All patients receivedbevacizumab during RT without delay or treatment breaks; there were no RT treatment breaks in all patients. No patient receiving bevacizumab plus RT experienced {>=}Grade 3 toxicity; 3 matched control patients experienced a Grade 3 skin reaction. There was no difference in fatigue, radiation fibrosis, pneumonitis, or lymphedema between the two groups. Five patients (35%) developed reduction in ejection fraction; 2 with right-sided and 3 with left-sided treatment. Patients with left-sided treatment experienced a persistent reduction in ejection fraction compared with those receiving right-sided treatment. Conclusion: Concurrent bevacizumab and RT did not increase acute locoregional toxicity in comparison with matched control patients who did not receive RT alone. The addition of concurrent RT when treating the intact breast, chest wall, and associated nodal regions in breast cancer seems to be safe and well tolerated.

  9. Stereotactic body radiotherapy combined with transarterial chemoembolization for huge (≥10 cm) hepatocellular carcinomas: A clinical study.

    PubMed

    Zhong, Nan Bao; Lv, Guang Ming; Chen, Zhong Hua

    2014-09-01

    This study was conducted to evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) combined with transarterial chemoembolization (TACE) for huge (≥10 cm) hepatocellular carcinomas (HCCs). Between May, 2006 and December, 2012, 72 patients with huge HCCs were treated by SBRT following incomplete TACE. The median total dose of 35.6 Gy was delivered over 12-14 days with a fractional dose of 2.6-3.0 Gy and 6 fractions per week. The patients were classified into those with tumor encapsulation (group A, n=33) and those without tumor encapsulation (group B, n=39). The clinical outcomes of tumor response, overall cumulative survival and toxicities/complications were retrospectively analyzed. Among the 72 patients, CR, PR, SD and PD were achieved in 6 (8.3%), 51 (70.8%), 9 (12.5%) and 6 patients (8.3%), respectively, within a median follow-up of 18 months. The objective response rate was 79.1%. The overall cumulative 1-, 3- and 5-year survival rates and the median survival time were 38, 12 and 3% and 12.2 months, respectively. In group A, the overall cumulative 1-, 3- and 5-year survival rates were 56, 21 and 6%, respectively, with a median survival of 19 months; in group B, the overall cumulative 1-, 3- and 5-year survival rates were 23, 4 and 0%, respectively, with a median survival of 10.8 months (P=0.023). The treatment was well tolerated, with no severe radiation-induced liver disease and no reported > grade 3 toxicity. Tumor encapsulation was found to be a significant prognostic factor for survival. In conclusion, the combination of SBRT and TACE was shown to be a safe and effective treatment option for patients with unresectable huge HCC.

  10. 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

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

    PubMed

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

    2016-12-24

    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.

  12. Clinical assessment of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for endometrial cancer

    PubMed Central

    Zhou, Qian; Cheng Tang; Zhao, Ke-Wei; Xiong, Yan-Li; Chen, Shu; Xu, Wen-Jing; Lei, Xin

    2016-01-01

    OBJECTIVE: The aim of this study was to determine the efficacy of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for the treatment of endometrial cancer. METHODS: Thirty-one patients with stage I–III endometrial cancer were recruited for this study. The stage I patients received only 252Californium neutron intracavitary brachytherapy with a two-channel applicator. The stage II and III patients received both 252Californium neutron intracavitary brachytherapy using a two-channel applicator and parallel-opposed whole pelvic radiotherapy. RESULTS: The five-year local control rate was 80.6% (25/31), the overall survival rate was 51.6% (16/31), and the disease-free survival rate was 54.8% (17/31). The incidence of serious late complications was 12.9% (4/31). CONCLUSIONS: 252Californium neutron intracavitary brachytherapy using a two-channel applicator combined with external beam radiotherapy was effective for treating endometrial cancer and the incidence of serious late complications related to this combination was within an acceptable range. PMID:26872078

  13. Clinical assessment of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for endometrial cancer.

    PubMed

    Zhou, Qian; Tang, Cheng; Zhao, Ke-Wei; Xiong, Yan-Li; Chen, Shu; Xu, Wen-Jing; Lei, Xin

    2016-01-01

    The aim of this study was to determine the efficacy of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for the treatment of endometrial cancer. Thirty-one patients with stage I-III endometrial cancer were recruited for this study. The stage I patients received only 252Californium neutron intracavitary brachytherapy with a two-channel applicator. The stage II and III patients received both 252Californium neutron intracavitary brachytherapy using a two-channel applicator and parallel-opposed whole pelvic radiotherapy. The five-year local control rate was 80.6% (25/31), the overall survival rate was 51.6% (16/31), and the disease-free survival rate was 54.8% (17/31). The incidence of serious late complications was 12.9% (4/31). 252Californium neutron intracavitary brachytherapy using a two-channel applicator combined with external beam radiotherapy was effective for treating endometrial cancer and the incidence of serious late complications related to this combination was within an acceptable range.

  14. Combination of Palonosetron, Aprepitant, and Dexamethasone Effectively Controls Chemotherapy-induced Nausea and Vomiting in Patients Treated with Concomitant Temozolomide and Radiotherapy: Results of a Prospective Study

    PubMed Central

    MATSUDA, Masahide; YAMAMOTO, Tetsuya; ISHIKAWA, Eiichi; AKUTSU, Hiroyoshi; TAKANO, Shingo; MATSUMURA, Akira

    2016-01-01

    Concomitant use of temozolomide (TMZ) and radiotherapy, which is the standard therapy for patients with high-grade glioma, involves a unique regimen with multiple-day, long-term administration. In a previous study, we showed not only higher incidence rates of chemotherapy-induced nausea and vomiting (CINV) during the overall study period, but also substantially higher incidence rates of moderate/severe nausea and particularly severe appetite suppression during the late phase of the treatment. Here, we prospectively evaluated the efficacy of a combination of palonosetron, aprepitant, and dexamethasone for CINV in patients treated with concomitant TMZ and radiotherapy. Twenty-one consecutive patients with newly diagnosed high-grade glioma were enrolled. CINV was recorded using a daily diary and included nausea assessment, emetic episodes, degree of appetite suppression, and use of antiemetic medication. The percentage of patients with a complete response in the overall period was 76.2%. The percentages of patients with no moderate/severe nausea were 90.5, 100, and 90.5% in the early phase, late phase, and overall period, respectively. Severe appetite suppression throughout the overall period completely disappeared. The combination of palonosetron, aprepitant, and dexamethasone was highly effective and well tolerated in patients treated with concomitant TMZ and radiotherapy. This combination of antiemetic therapy focused on delayed as well as acute CINV and may have the potential to overcome CINV associated with a multiple-day, long-term chemotherapy regimen. PMID:27666343

  15. Intraoperative electron beam radiation therapy (IOEBRT) for carcinoma of the exocrine pancreas

    SciTech Connect

    Dobelbower, R.R. Jr.; Konski, A.A.; Merrick, H.W. III; Bronn, D.G.; Schifeling, D.; Kamen, C. )

    1991-01-01

    The abdominal cavities of 50 patients were explored in a specially constructed intraoperative radiotherapy operating amphitheater at the Medical College of Ohio. Twenty-six patients were treated with intraoperative and postoperative precision high dose external beam therapy, 12 with intraoperative irradiation but no external beam therapy, and 12 with palliative surgery alone. All but two patients completed the postoperative external beam radiation therapy as initially prescribed. The median survival time for patients treated with palliative surgery alone was 4 months, and that for patients treated with intraoperative radiotherapy without external beam therapy was 3.5 months. Patients undergoing intraoperative irradiation and external beam radiation therapy had a median survival time of 10.5 months. Four patients died within 30 days of surgery and two patients died of gastrointestinal hemorrhage 5 months posttreatment.

  16. Therapeutic effects and prognostic factors in three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma

    PubMed Central

    Wu, De-Hua; Liu, Li; Chen, Long-Hua

    2004-01-01

    AIM: To evaluate the therapeutic efficacy of three-dimensional conformal radiotherapy (3D-CRT) combined with transcatheter arterial chemoembolization (TACE) on the patients with hepatocellular carcinoma (HCC). METHODS: Between 1998 and 2001, 94 patients with HCC received 3D- CRT combined with TACE. A total 63 patients had a Okuda stage I lesion and 31 patients had stage II. The median tumor size was 10.7 cm (range 3.0-18 cm), and liver cirrhosis was present in all the patients. There were 43 cases of class A and 51 class B. TACE was performed using lipiodol, 5-fluorouracil, cisplatin, doxorubicin hydrochloride and mitomycin, followed by gelatin sponge cubes. Fifty- nine patients received TACE only one time, while the others 2 to 3 times. 3D-CRT was started 3-4 wk after TACE. All patients were irradiated with a stereotactic body frame and received 4-8 Gy single high-dose radiation for 8-12 times at the isocenter during a period of 17-26 d (median 22 d). RESULTS: The median follow-up was 37 mo (range 10-48 mo) after diagnosis. The response rate was 90.5%. The overall survival rate at 1-, 2-, and 3- year was 93.6%, 53.8% and 26.0% respectively, with the median survival of 25 mo. On univariate analysis, age (P = 0.026), Child-Pugh classification for cirrhosis of liver ( P = 0.010), Okuda stage (P = 0.026), tumor size (P = 0.000), tumor type (P = 0.029), albuminemia (P = 0.035), and radiation dose (P = 0.000) proved to be significant factors for survival. On multivariate analysis, age (P = 0.024), radiation dose (P = 0.001), and tumor size (P = 0.000) were the significant factors. CONCLUSION: 3D-CRT combined with TACE is an effective and feasible approach for HCC. Age, radiation dose and tumor size were found to be significant prognostic factors for survival of patients with HCC treated by 3D-CRT combined with TACE. Further study for HCC is needed to improve the treatment efficacy. PMID:15259062

  17. Phase I/II Study of Erlotinib Combined With Cisplatin and Radiotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Herchenhorn, Daniel; Dias, Fernando L.; Viegas, Celia M.P.; Federico, Miriam H.; Araujo, Carlos Manoel M.; Small, Isabelle; Bezerra, Marcos; Fontao, Karina M.D.; Knust, Renata E.; Ferreira, Carlos G.; Martins, Renato G.

    2010-11-01

    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 continuing 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.

  18. Inhibitory effect of radiotherapy combined with weekly recombinant human endostatin on the human pulmonary adenocarcinoma A549 xenografts in nude mice.

    PubMed

    Jiang, Xiao-dong; Dai, Peng; Wu, Jin; Song, Da-an; Yu, Jin-ming

    2011-05-01

    The aim of this study was to investigate the inhibitory effect of radiotherapy combined with weekly recombinant human endostatin (RHES) on the human pulmonary adenocarcinoma A549 xenografts in nude mice. The 40 A549 xenograft nude mice models were randomly divided into 4 groups (each group with 10 nude mice). Single radiotherapy group (group 1) was given a single external irradiation (6MV-X ray, 10 Gy) and peritumoral subcutaneous injection of 0.2 ml normal saline every day for 7 days. Single RHES group (group 2) was given peritumoral subcutaneous injection of 0.2 ml RHES (0.75 mg/ml) for 7 days. Combination therapy group (group 3) was given radiotherapy as the same as group 1 and RHES as the same as group 2. Control group was given normal saline as the same as group 1. The tumor volume was smaller in group 3 than in control group from the 8th day after treatment (P<0.05) and tumor regression occurred from the second week after treatment in group 3. On the 15th day after treatment, the inhibitory rates of tumor volume were 69.65%, 92.64% and 116.4% in groups 2, 1 and 3, respectively; MVD number was lower in group 3 than in group 1 (P<0.05); there was no statistical significance in VEGF expression between group 2 and control group as well as between group 3 and group 1 (P>0.05). Apoptosis was marked in group 3. Radiotherapy combined with weekly RHES can significantly inhibit tumor growth and earlier induce tumor regression, which may be related to the improvement of tumor hypoxia and the inhibition of radiation-induced tumor angiogenesis. Short-term application (1 week) of RHES is beneficial to clinical practice.

  19. Innovations in Radiotherapy Technology.

    PubMed

    Feain, I J; Court, L; Palta, J R; Beddar, S; Keall, P

    2017-02-01

    Many low- and middle-income countries, together with remote and low socioeconomic populations within high-income countries, lack the resources and services to deal with cancer. The challenges in upgrading or introducing the necessary services are enormous, from screening and diagnosis to radiotherapy planning/treatment and quality assurance. There are severe shortages not only in equipment, but also in the capacity to train, recruit and retain staff as well as in their ongoing professional development via effective international peer-review and collaboration. Here we describe some examples of emerging technology innovations based on real-time software and cloud-based capabilities that have the potential to redress some of these areas. These include: (i) automatic treatment planning to reduce physics staffing shortages, (ii) real-time image-guided adaptive radiotherapy technologies, (iii) fixed-beam radiotherapy treatment units that use patient (rather than gantry) rotation to reduce infrastructure costs and staff-to-patient ratios, (iv) cloud-based infrastructure programmes to facilitate international collaboration and quality assurance and (v) high dose rate mobile cobalt brachytherapy techniques for intraoperative radiotherapy. Copyright © 2016 The Royal College of Radiologists. All rights reserved.

  20. Patterns of Failure After Combined-Modality Approaches Incorporating Radiotherapy for Sinonasal Undifferentiated Carcinoma of the Head and Neck

    SciTech Connect

    Chen, Allen M. Daly, Megan E.; El-Sayed, Ivan; Garcia, Joaquin; Lee, Nancy Y.; Bucci, M. Kara; Kaplan, Michael J.

    2008-02-01

    Purpose: To report the clinical outcome of patients treated with combined-modality approaches for sinonasal undifferentiated carcinoma (SNUC) of the head and neck. Methods and Materials: The records of 21 patients with SNUC treated with curative intent at University of California, San Francisco between 1990 and 2004 were analyzed. Patient age ranged from 33 to 71 years (median, 47 years). Primary tumor sites included the nasal cavity (11 patients), maxillary sinus (5 patients), and ethmoid sinus (5 patients). All patients had T3 (4 patients) or T4 (17 patients) tumors. Local-regional treatment included surgery followed by postoperative radiotherapy (PORT) with or without adjuvant chemotherapy for 17 patients; neoadjuvant chemoradiotherapy followed by surgery for 2 patients; and definitive chemoradiotherapy for 2 patients. Median follow-up among surviving patients was 58 months (range, 12-70 months). Results: The 2- and 5-year estimates of local control were 60% and 56%, respectively. There was no difference in local control according to initial treatment approach, but among the 19 patients who underwent surgery the 5-year local control rate was 74% for those with gross tumor resection, compared with 24% for those with subtotal tumor resection (p = 0.001). The 5-year rates of overall and distant metastasis-free survival were 43% and 64%, respectively. Late complications included cataracts (2 patients), lacrimal stenosis (1 patient), and sino-cutaneous fistula (1 patient). Conclusion: The suboptimal outcomes suggest a need for more effective therapies. Gross total resection should be the goal of all treatments whenever possible.

  1. In vitro evaluation of combined temozolomide and radiotherapy using X  rays and high-linear energy transfer radiation for glioblastoma.

    PubMed

    Barazzuol, Lara; Jena, Raj; Burnet, Neil G; Jeynes, Jonathan C G; Merchant, Michael J; Kirkby, Karen J; Kirkby, Norman F

    2012-05-01

    High-linear energy transfer radiation offers superior biophysical properties over conventional radiotherapy and may have a great potential for treating radioresistant tumors, such as glioblastoma. However, very little pre-clinical data exists on the effects of high-LET radiation on glioblastoma cell lines and on the concomitant application of chemotherapy. This study investigates the in vitro effects of temozolomide in combination with low-energy protons and α particles. Cell survival, DNA damage and repair, and cell growth were examined in four human glioblastoma cell lines (LN18, T98G, U87 and U373) after treatment with either X rays, protons (LET 12.91 keV/μm), or α particles (LET 99.26 keV/μm) with or without concurrent temozolomide at clinically-relevant doses of 25 and 50 μM. The relative biological effectiveness at 10% survival (RBE(10)) increased as LET increased: 1.17 and 1.06 for protons, and 1.84 and 1.68 for α particles in the LN18 and U87 cell lines, respectively. Temozolomide administration increased cell killing in the O(6)-methylguanine DNA methyltransferase-methylated U87 and U373 cell lines. In contrast, temozolomide provided no therapeutic enhancement in the methylguanine DNA methyltransferase-unmethylated LN18 and T98G cell lines. In addition, the residual number of γ-H2AX foci at 24 h after treatment with radiation and concomitant temozolomide was found to be lower than or equal to that expected by DNA damage with either of the individual treatments. Kinetics of foci disappearance after X-ray and proton irradiation followed similar time courses; whereas, loss of γ-H2AX foci after α particle irradiation occurred at a slower rate than that by low-LET radiation (half-life 12.51-16.87 h). The combination of temozolomide with different radiation types causes additive rather than synergistic cytotoxicity. Nevertheless, particle therapy combined with chemotherapy may offer a promising alternative with the additional benefit of superior

  2. Dosimetric Comparison of Combined Intensity-Modulated Radiotherapy (IMRT) and Proton Therapy Versus IMRT Alone for Pelvic and Para-Aortic Radiotherapy in Gynecologic Malignancies

    SciTech Connect

    Berman Milby, Abigail; Both, Stefan; Ingram, Mark; Lin, Lilie L.

    2012-03-01

    Purpose: To perform a dosimetric comparison of intensity-modulated radiotherapy (IMRT), passive scattering proton therapy (PSPT), and intensity-modulated proton therapy (IMPT) to the para-aortic (PA) nodal region in women with locally advanced gynecologic malignancies. Methods and Materials: The CT treatment planning scans of 10 consecutive patients treated with IMRT to the pelvis and PA nodes were identified. The clinical target volume was defined by the primary tumor for patients with cervical cancer and by the vagina and paravaginal tissues for patients with endometrial cancer, in addition to the regional lymph nodes. The IMRT, PSPT, and IMPT plans were generated using the Eclipse Treatment Planning System and were analyzed for various dosimetric endpoints. Two groups of treatment plans including proton radiotherapy were created: IMRT to pelvic nodes with PSPT to PA nodes (PSPT/IMRT), and IMRT to pelvic nodes with IMPT to PA nodes (IMPT/IMRT). The IMRT and proton RT plans were optimized to deliver 50.4 Gy or Gy (relative biologic effectiveness [RBE)), respectively. Dose-volume histograms were analyzed for all of the organs at risk. The paired t test was used for all statistical comparison. Results: The small-bowel V{sub 20}, V{sub 30}, V{sub 35}, andV{sub 40} were reduced in PSPT/IMRT by 11%, 18%, 27%, and 43%, respectively (p < 0.01). Treatment with IMPT/IMRT demonstrated a 32% decrease in the small-bowel V{sub 20}. Treatment with PSPT/IMRT showed statistically significant reductions in the body V{sub 5-20}; IMPT/IMRT showed reductions in the body V{sub 5-15}. The dose received by half of both kidneys was reduced by PSPT/IMRT and by IMPT/IMRT. All plans maintained excellent coverage of the planning target volume. Conclusions: Compared with IMRT alone, PSPT/IMRT and IMPT/IMRT had a statistically significant decrease in dose to the small and large bowel and kidneys, while maintaining excellent planning target volume coverage. Further studies should be done to

  3. Postoperative radiotherapy dose requirement in standard combined-modality practice for head and neck squamous cell carcinoma: Analysis of salient surgical and radiotherapy parameters in 2 cohorts.

    PubMed

    Mohanti, Bidhu K; Thakar, Alok; Kaur, Jaspreet; Bahadur, Sudhir; Malik, Monica; Gandhi, Ajeet K; Bhasker, Suman; Sharma, Atul

    2017-09-01

    This study compared 2 sequential cohorts to identify the postoperative radiotherapy (PORT) dose requirement for head and neck squamous cell carcinoma (HNSCC). Two distinct PORT dose regimens were prescribed over 11 years; group 1 received 56 Gy or less, and group 2 received 60 Gy or more. The 2D and 3D techniques were used. Two sequential cohorts consisted of 478 patients, with mean and median follow-up for group 1 and 2 as: 37.0 versus 28.5 months and 13.8 versus 13.1 months, respectively. Grades 3-4 mucosal toxicities (11.4% vs 28.3%), hospitalization (3.2% vs 17.4%), and nasogastric feeding (11.9% vs 29.7%) were higher in group 2. The 2-year disease-free survival (DFS) was higher with PORT >60 Gy for the following factors: age ≤ 50 years (P = .041); ≥ 4 positive nodes (P = .029); and overall treatment time (OTT) ≥ 100 days (P = .042). Except for the benefit of doses >60 Gy for limited parameters, a lower PORT dose did not compromise the results and can potentially reduce the morbidities and healthcare costs. © 2017 Wiley Periodicals, Inc.

  4. Combination of 177Lu-PSMA-617 and External Radiotherapy for the Treatment of Cerebral Metastases in Patients With Castration-Resistant Metastatic Prostate Cancer.

    PubMed

    Wei, Xiao; Schlenkhoff, Carl; Schwarz, Bettina; Essler, Markus; Ahmadzadehfar, Hojjat

    2017-09-01

    Two castration-resistant prostate cancer patients, both with cerebral and visceral and lymphatic metastases, received multiple cycles of Lu-PSMA-617 treatments. The prognosis of both cases is dependent on brain metastases. Between Lu-PSMA-617 treatment cycles, local radiotherapy was also applied to the brain metastases. Prior to the combined therapy, all systemic metastases, including cerebral lesions, showed PSMA expression using Ga-PSMA PET/CT. Under the combined therapy, all the metastases, particularly the cerebral lesions, showed significant regression in size and PSMA expression over time.

  5. Tissue tolerance of normal and surgically manipulated canine liver to intraoperative radiation therapy (IORT)

    SciTech Connect

    Chromheecke, M.; Oldhoff, J.; Hoekstra, H.J.; Vermeij, J.; Grond, A.J.K. ); Konings, A.W.T. )

    1993-12-01

    The purpose of the study is to obtain dose guidelines for the delivery of intraoperative radiotherapy to the liver of patients with colorectal liver metastases. Following partial resection of the liver, a single high dose of 10, 20, 25, and 30 Gy intraoperative radiotherapy was applied to both the resection plane as well as a nonsurgically manipulated part of the liver of 25 beagles. The temporal sequence of histological and ultrastructural changes of these irradiated parts of the liver tissue was investigated. The feasibility of delivering a single large dose of intraoperative electron beam radiotherapy to the normal and partially hepatectomized liver was experimentally investigated in a canine study. There were no postoperative complications, no morbidity or mortality with a minimal follow-up of 1 year. Autopsy performed 3 months following irradiation showed only mild histopathological changes. One year following intraoperative radiotherapy more distinct histopathological changes consisting of capsular thickening, diffuse parenchymal fibrosis and subcapsular hepatocellular atrophy were found. The liver function remained intact. This study demonstrated that intraoperative radiotherapy to part of the liver in the canine model can be safely applied and doses up to 30 Gy are well tolerated. 34 refs., 6 figs., 1 tab.

  6. Prospective multicenter study of combined treatment with chemotherapy and radiotherapy in breast cancer women with the rare clinical scenario of ipsilateral supraclavicular node recurrence without distant metastases

    SciTech Connect

    Pergolizzi, Stefano . E-mail: Stefano.Pergolizzi@unime.it; Adamo, Vincenzo; Russi, Elvio; Santacaterina, Anna; Maisano, Roberto; Numico, Gianmauro; Palazzolo, Carmela; Ferrau, Francesco; Settineri, Nicola; Altavilla, Giuseppe; Girlando, Andrea; Spadaro, Pietro; Cascinu, Stefano

    2006-05-01

    Purpose: To evaluate the role of chemotherapy combined with curative radiotherapy in breast cancer patients who presented with recurrent ipsilateral supraclavicular lymph node metastases (ISLM) without 'nonregional disease,' we designed an observational study performed prospectively. Patients and Methods: Forty-four consecutive patients with ISLM from breast cancer as part of recurrent regional disease without distant metastases were included in this study. All patients received chemotherapy with doxorubicin-based schema or paclitaxel for six courses and curative radiotherapy (60 Gy/30 fractions of 2 Gy/5 days a week). An 'involved field' radiation was delivered during the interval between the third and fourth chemotherapy course; hormonal therapy was given based on receptor status. Results: The rate of overall clinical response after chemotherapy and radiotherapy was 94.9%. Median time to progression and overall survival were 28 and 40 months, respectively; the 5-year actuarial overall survival and disease-free survival rates were 35% (95% confidence interval, 19-51) and 20% (95% confidence interval, 6-34), respectively. Conclusion: A curative course of intravenous chemotherapy and radical irradiation is feasible in patients with ISLM. All patients presenting recurrence in supraclavicular nodes should be treated with definitive locoregional treatments and systemic therapy because the outcomes are better than might be historically assumed.

  7. SU-E-T-279: A Novel Electron-Beam Combined with Magnetic Field Application for Radiotherapy.

    PubMed

    Alezra, D; Nardi, E; Koren, S; Bragilovski, D; Orion, I

    2012-06-01

    The new beam and delivery system consists of an electron accelerator and a system of magnets (one or more). Introducing a transverse magnetic field in and near the tumor, causes the electrons to spiral in this region, thereby producing an effective peak in the depth dose distribution, within the tumor volume. Although the basic idea is not new, we suggest here for the first time, a viable as well as a workable, magnetic field configuration, which in addition to focusing the beam does not interfere with its propagation to the target. The electron accelerator: can be a linear accelerator or any other type electron accelerator, capable of producing different electron energies for different depths and dose absorption accumulation. The Field size can be as small as a pencil beam and as big as any of the other standard field sizes that are used in radiotherapy. The scatter filter can be used or removed. The dose rate accumulation can be as higher as possible.The magnets are able to produce magnetic fields. The order, direction, width, place, shape and number of the magnetic fields define the shape and the Percentage Depth Dose (PDD) curve of the electron beam. Prototypes were successfully tested by means of computer simulation, using:COMSOL-Multiphsics for magnetic fields calculations. FLUKA package, for electron beam MC simulation. Our results suggest that by using an electron beam at different energies, combined with magnetic fields, we could modify the delivered dose. This is caused by manipulating the electron motion via the Lorentz force. The applied magnetic field, will focus the electron beam at a given depth and deposit the energy in a given volume and depth, where otherwise the electron energy will have spread deeper. The direction and magnitude of the magnetic fields will prevent the scattering of the electron beam and its absorption in remote volumes. In practice, we get a pseudo Bragg peak depth dose distribution, applying a relatively low cost system. The

  8. TOPICAL REVIEW (Non-targeted) radioactive/fluorescent nanoparticles and their potential in combined pre- and intraoperative imaging during sentinel lymph node resection

    NASA Astrophysics Data System (ADS)

    Buckle, Tessa; Chin, Patrick T. K.; van Leeuwen, Fijs W. B.

    2010-12-01

    One clinical precedent for the use of nanosized imaging agents is the localization of the tumor draining sentinel lymph nodes. In this application, radiocolloids such as 99mTc-NanoColl are currently used to plan the surgical procedure and to provide acoustic guidance during the intervention. Additional injections of dyes are common to provide optical surgical guidance. Bimodal imaging agents, which are both radioactive and fluorescent, have the potential to be used for both surgical planning and intraoperative fluorescence guidance towards the sentinel lymph nodes. This review provides an overview of the radioactive, fluorescent, and size properties of (non-targeted) bimodal nanoparticles, and their (potential) value in sentinel lymph node detection.

  9. Intraoperative Stem Cell Therapy

    PubMed Central

    Coelho, Mónica Beato; Cabral, Joaquim M.S.; Karp, Jeffrey M.

    2013-01-01

    Stem cells hold significant promise for regeneration of tissue defects and disease-modifying therapies. Although numerous promising stem cell approaches are advancing in clinical trials, intraoperative stem cell therapies offer more immediate hope by integrating an autologous cell source with a well-established surgical intervention in a single procedure. Herein, the major developments in intraoperative stem cell approaches, from in vivo models to clinical studies, are reviewed, and the potential regenerative mechanisms and the roles of different cell populations in the regeneration process are discussed. Although intraoperative stem cell therapies have been shown to be safe and effective for several indications, there are still critical challenges to be tackled prior to adoption into the standard surgical armamentarium. PMID:22809140

  10. Intraoperative radiation therapy-induced sarcomas in dogs

    SciTech Connect

    Hoekstra, H.J.; Sindelar, W.F.; Kinsella, T.J.; Mehta, D.M. )

    1989-12-01

    In a canine model the tolerance of normal and surgically manipulated tissue to intraoperative radiotherapy (IORT) was investigated to provide guidelines for the clinical use of IORT in human cancer patients. A dose of 20 Gy IORT, with or without external beam radiotherapy, was generally well tolerated without significant increased treatment morbidity. Higher doses of IORT (over 30 Gy) have produced radiation-induced sarcomas in some animals followed over a long period. Therefore IORT should be used only in human cancer patients in well controlled studies, in which complications are well documented, and the possibility of radiation-induced malignancies in long-term survival should be considered.

  11. Monitoring of Circulating Tumor Cells and Their Expression of EGFR/Phospho-EGFR During Combined Radiotherapy Regimens in Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Tinhofer, Ingeborg; Hristozova, Tsvetana; Stromberger, Carmen; KeilhoIz, Ulrich; Budach, Volker

    2012-08-01

    Purpose: The numbers of circulating tumor cells (CTCs) and their expression/activation of epidermal growth factor receptor (EGFR) during the course of combined chemo- or bioradiotherapy regimens as potential biomarkers of treatment efficacy in squamous cell carcinoma of the head and neck (SCCHN) were determined. Methods and Materials: Peripheral blood samples from SCCHN patients with locally advanced stage IVA/B disease who were treated with concurrent radiochemotherapy or induction chemotherapy followed by bioradiation with cetuximab were included in this study. Using flow cytometry, the absolute number of CTCs per defined blood volume as well as their expression of EGFR and its phosphorylated form (pEGFR) during the course of treatment were assessed. Results: Before treatment, we detected {>=}1 CTC per 3.75 mL blood in 9 of 31 patients (29%). Basal expression of EGFR was detected in 100% and pEGFR in 55% of the CTC+ cases. The frequency of CTC detection was not influenced by induction chemotherapy. However, the number of CTC+ samples significantly increased after radiotherapy. This radiation-induced increase in CTC numbers was less pronounced when radiotherapy was combined with cetuximab compared to its combination with cisplatin/5-fluorouracil. The former treatment regimen was also more effective in reducing pEGFR expression in CTCs. Conclusions: Definitive radiotherapy regimens of locally advanced SCCHN can increase the number of CTCs and might thus contribute to a systemic spread of tumor cells. Further studies are needed to evaluate the predictive value of the radiation-induced increase in CTC numbers and the persistent activation of the EGFR signalling pathway in individual CTC+ cases.

  12. Acute Intraoperative Pulmonary Aspiration.

    PubMed

    Nason, Katie S

    2015-08-01

    Acute intraoperative aspiration is a potentially fatal complication with significant associated morbidity. Patients undergoing thoracic surgery are at increased risk for anesthesia-related aspiration, largely due to the predisposing conditions associated with this complication. Awareness of the risk factors, predisposing conditions, maneuvers to decrease risk, and immediate management options by the thoracic surgeon and the anesthesia team is imperative to reducing risk and optimizing patient outcomes associated with acute intraoperative pulmonary aspiration. Based on the root-cause analyses that many of the aspiration events can be traced back to provider factors, having an experienced anesthesiologist present for high-risk cases is also critical.

  13. Treatment of advanced stage ovarian carcinoma with a combination of chemotherapy, radiotherapy, and radiosensitizer: report of a pilot study from the National Cancer Institute

    SciTech Connect

    Lichter, A.S.; Ozols, R.F.; Myers, C.C.; Ostechega, Y.; Young, R.C.

    1987-08-01

    Twenty-eight patients with Stage III or IV ovarian carcinoma were treated with combined chemotherapy-radiotherapy employing a unique protocol. Four cycles of cyclophosphamide and hexamethylmelamine alternated with four cycles of concurrent cisplatin, whole abdominal radiotherapy, and intraperitoneal misonidazole. The entire treatment program lasted six months. Clinical complete responses were seen in 50% of the patients with an overall response rate of 61%. Pathologic complete response (PCR) confirmed at second look surgery occurred in 18% of the group (5 patients). Median survival of the entire group was 15.2 months with all PCR's alive NED. This outcome was no different than our previous experience with combination chemotherapy alone. Toxicities seen included leukopenia, thrombocytopenia, nausea, vomiting, and weight loss. However, these side effects were manageable. Two non-tumor deaths occurred. This study demonstrates the feasibility of combining drug and radiation therapy concurrently in the treatment of ovarian cancer; further research is needed to explore different sequencing and dose levels that could improve the outcome.

  14. Cracking the perfusion code?: Laser-assisted Indocyanine Green angiography and combined laser Doppler spectrophotometry for intraoperative evaluation of tissue perfusion in autologous breast reconstruction with DIEP or ms-TRAM flaps.

    PubMed

    Ludolph, Ingo; Arkudas, Andreas; Schmitz, Marweh; Boos, Anja M; Taeger, Christian D; Rother, Ulrich; Horch, Raymund E; Beier, Justus P

    2016-10-01

    The aim of this prospective study was to assess the correlation of flap perfusion analysis based on laser-assisted Indocyanine Green (ICG) angiography with combined laser Doppler spectrophotometry in autologous breast reconstruction using free DIEP/ms-TRAM flaps. Between February 2014 and July 2015, 35 free DIEP/ms-TRAM flaps were included in this study. Besides the clinical evaluation of flaps, intraoperative perfusion dynamics were assessed by means of laser-assisted ICG angiography and post-capillary oxygen saturation and relative haemoglobin content (rHb) using combined laser Doppler spectrophotometry. Correlation of the aforementioned parameters was analysed, as well as the impact on flap design and postoperative complications. Flap survival rate was 100%. There were no partial flap losses. In three cases, flap design was based on the angiography, contrary to clinical evaluation and spectrophotometry. The final decision on the inclusion of flap areas was based on the angiographic perfusion pattern. Angiography and spectrophotometry showed a correlation in most of the cases regarding tissue perfusion, post-capillary oxygen saturation and relative haemoglobin content. Laser-assisted ICG angiography is a useful tool for intraoperative evaluation of flap perfusion in autologous breast reconstruction with DIEP/ms-TRAM flaps, especially in decision making in cases where flap perfusion is not clearly assessable by clinical signs and exact determination of well-perfused flap margins is difficult to obtain. It provides an objective real-time analysis of flap perfusion, with high sensitivity for the detection of poorly perfused flap areas. Concerning the topographical mapping of well-perfused flap areas, laser-assisted angiography is superior to combined laser Doppler spectrophotometry.

  15. Pretreatment Endorectal Coil Magnetic Resonance Imaging Findings Predict Biochemical Tumor Control in Prostate Cancer Patients Treated With Combination Brachytherapy and External-Beam Radiotherapy

    SciTech Connect

    Riaz, Nadeem; Afaq, Asim; Akin, Oguz; Pei Xin; Kollmeier, Marisa A.; Cox, Brett; Hricak, Hedvig; Zelefsky, Michael J.

    2012-11-01

    Purpose: To investigate the utility of endorectal coil magenetic resonance imaging (eMRI) in predicting biochemical relapse in prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Methods and Materials: Between 2000 and 2008, 279 men with intermediate- or high-risk prostate cancer underwent eMRI of their prostate before receiving brachytherapy and supplemental intensity-modulated radiotherapy. Endorectal coil MRI was performed before treatment and retrospectively reviewed by two radiologists experienced in genitourinary MRI. Image-based variables, including tumor diameter, location, number of sextants involved, and the presence of extracapsular extension (ECE), were incorporated with other established clinical variables to predict biochemical control outcomes. The median follow-up was 49 months (range, 1-13 years). Results: The 5-year biochemical relapse-free survival for the cohort was 92%. Clinical findings predicting recurrence on univariate analysis included Gleason score (hazard ratio [HR] 3.6, p = 0.001), PSA (HR 1.04, p = 0.005), and National Comprehensive Cancer Network risk group (HR 4.1, p = 0.002). Clinical T stage and the use of androgen deprivation therapy were not correlated with biochemical failure. Imaging findings on univariate analysis associated with relapse included ECE on MRI (HR 3.79, p = 0.003), tumor size (HR 2.58, p = 0.04), and T stage (HR 1.71, p = 0.004). On multivariate analysis incorporating both clinical and imaging findings, only ECE on MRI and Gleason score were independent predictors of recurrence. Conclusions: Pretreatment eMRI findings predict for biochemical recurrence in intermediate- and high-risk prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Gleason score and the presence of ECE on MRI were the only significant predictors of biochemical relapse in this group of patients.

  16. A phase I study of nimotuzumab in combination with radiotherapy in stages IIB-IV non-small cell lung cancer unsuitable for radical therapy: Korean results.

    PubMed

    Choi, Hye Jin; Sohn, Joo Hyuk; Lee, Chang Geol; Shim, Hyo Sub; Lee, Ik-Jae; Yang, Woo Ick; Kwon, Ji Eun; Kim, Se Kyu; Park, Moo-Suk; Lee, Ju Hee; Kim, Joo Hang

    2011-01-01

    This study was undertaken to determine safety and tolerability of nimotuzumab, a humanized anti-epidermal growth factor receptor monoclonal antibody, in combination with radiotherapy in stages IIB-IV non-small cell lung cancer (NSCLC) patients who are unsuitable for radical therapy or chemotherapy. Nimotuzumab (100mg, 200mg and 400mg) was administered weekly from week 1 to week 8 with palliative radiotherapy (30-36 Gy, 3 Gy/day). If tumor control was achieved, nimotuzumab was continued every 2 weeks until unacceptable toxicity or disease progression. Serial skin biopsies were collected for pharmacodynamic assessment. Fifteen patients were enrolled in the study, with cohorts of five patients assigned in each dose level of nimotuzumab. Patients and disease characteristics included median age 73 years; Eastern Cooperative Oncology Group performance status (PS) 0-1/2 (n=3/12); female sex (n=2); adenocarcinoma (n=5); never-smoker status (n=2); and stages IIB/IIIB/IV (n=1/8/6). All patients were unable to tolerate radical therapy because of old age or multiple comorbidities. The most commonly reported adverse events were lymphopenia and asthenia (grades 1-2 in most patients). No skin rash or allergic toxicities appeared. Dose-limiting toxicity occurred with pneumonia with grade 4 neutropenia at the 200mg dose of nimotuzumab. Objective response rate and disease control rate inside the radiation field were 46.7% and 100.0%, respectively. Nimotuzumab in combination with radiotherapy is well-tolerated and feasible. Further clinical investigation of nimotuzumab in NSCLC patients is warranted. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  17. Radiotherapy for nasopharyngeal carcinoma and combined capecitabine and nimotuzumab treatment for lung metastases in a liver transplantation recipient: a case experience of sustained complete response.

    PubMed

    Yan, Senxiang; Jiang, Xue; Yang, Jinsong; Yan, Danfang; Wang, Yi-Xiang J

    2012-10-01

    The primary treatment for nasopharyngeal carcinoma (NPC) is external beam radiotherapy. However, until now, there is little experience with the management of NPC occurred after solid organ transplantation. In this report, a 60-year-old man was found to have NPC (T2N1M0; stage III) 3 years after orthotopic liver transplantation treatment for hepatocellular carcinoma. Intensity-modulated radiotherapy (IMRT) was performed for NPC. One month after IMRT, complete response of NPC was achieved. However, multiple lung metastases occurred 18 months after the IMRT with the largest lesion measuring 4.1×5.5 cm and confirmed to be originated from NPC. Combined chemo-/targeted therapy consisted of capecitabine, and nimotuzumab was administered for four cycles. One month after initiation of capecitabine plus nimotuzumab treatment, a near-complete response was achieved for lung metastases. A repeat CT scan 1 year later showed sustained resolution of the lung metastases. The patient is still alive 16 months after the combined chemo-/targeted therapy.

  18. [Short-term efficacy and toxicity of Nimotuzumab combined with simultaneous integrated boost intensity-modulated radiotherapy for locally advanced esophageal cancer].

    PubMed

    Chen, Zhiming; Xue, Qiang; Chen, Xiaojue; Shi, Jian; Ma, Jianbo; Ji, Bin; Chen, Buyou

    2016-03-01

    To evaluate the short-term efficacy and toxicity of Nimotuzumab combined with simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) in the treatment of locally advanced esophageal carcinoma. Twenty-nine patients with esophageal carcinoma were treated with SIB-IMRT. Planning gross target volume (PGTV) was given at a dose of 60 Gy/2.4 Gy/25 F and planning target volume (PTV) was given at a dose of 50 Gy/2 Gy/25 F. Nimotuzumab was given by intravenous drip at the dose of 200 mg, once a week before radiotherapy. Short-term efficacy and toxicity were evaluated in all patients. All patients completed the treatment successfully. Fourteen of them achieved a complete response (CR, 48.3%), 13 had a partial response (PR, 44.8%), 1 showed stable disease (SD, 3.6%), and 1 showed progressive disease (PD, 3.6%). The overall response rate (CR+ PR) was 93.1%. Most adverse reactions were radioactive esophagitis, radioactive dermatitis and bone marrow suppression (grade 1-2). Only 1 patient developed a slight skin rash. Nimotuzumab combined with SIB-IMRT is a safe and effective modality for locally advanced esophageal cancer. The patient is well tolerated and worthy of further clinical study.

  19. Proton-Beam, Intensity-Modulated, and/or Intraoperative Electron Radiation Therapy Combined with Aggressive Anterior Surgical Resection for Retroperitoneal Sarcomas

    PubMed Central

    Yoon, Sam S.; Chen, Yen-Lin; Kirsch, David G.; Maduekwe, Ugwuji N.; Rosenberg, Andrew E.; Nielsen, G. Petur; Sahani, Dushyant V.; Choy, Edwin; Harmon, David C.; DeLaney, Thomas F.

    2010-01-01

    Background We sought to reduce local recurrence for retroperitoneal sarcomas by using a coordinated strategy of advanced radiation techniques and aggressive en-bloc surgical resection. Methods Proton-beam radiation therapy (PBRT) and/or intensity-modulated radiation therapy (IMRT) were delivered to improve tumor target coverage and spare selected adjacent organs. Surgical resection of tumor and adjacent organs was performed to obtain a disease-free anterior margin. Intraoperative electron radiation therapy (IOERT) was delivered to any close posterior margin. Results Twenty patients had primary tumors and eight had recurrent tumors. Tumors were large (median size 9.75 cm), primarily liposarcomas and leiomyosarcomas (71%), and were mostly of intermediate or high grade (81%). PBRT and/or IMRT were delivered to all patients, preferably preoperatively (75%), to a median dose of 50 Gy. Surgical resection included up to five adjacent organs, most commonly the colon (n = 7) and kidney (n = 7). Margins were positive for disease, usually posteriorly, in 15 patients (54%). IOERT was delivered to the posterior margin in 12 patients (43%) to a median dose of 11 Gy. Surgical complications occurred in eight patients (28.6%), and radiation-related complications occurred in four patients (14%). After a median follow-up of 33 months, only two patients (10%) with primary disease experienced local recurrence, while three patients (37.5%) with recurrent disease experienced local recurrence. Conclusions Aggressive resection of retroperitoneal sarcomas can achieve a disease-negative anterior margin. PBRT and/or IMRT with IOERT may possibly deliver sufficient radiation dose to the posterior margin to control microscopic residual disease. This strategy may minimize radiation-related morbidity and reduce local recurrence, especially in patients with primary disease. PMID:20151216

  20. Stereotactic linear accelerator radiotherapy for pituitary tumors.

    PubMed

    Ajithkumar, Thankama; Brada, Michael

    2004-01-01

    Last decade has seen important advances in radiotherapy technology which combine precise tumor localization with accurate targeted delivery of radiation. This technique of high precision conformal radiotherapy, described as stereotactic radiotherapy or radiosurgery, uses modern linear accelerators available in most radiation oncology departments. The article describes the new technique as applied to the treatment of pituitary adenoma and reviews published clinical results.

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

    SciTech Connect

    Small, William; Mulcahy, Mary F.; Rademaker, Alfred; Bentrem, David J.; Benson, Al B.; Weitner, Bing Bing; Talamonti, Mark S.

    2011-06-01

    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 gemcitabine 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.

  2. Comparing long-term toxicity and efficacy of combined modality treatment including extended- or involved-field radiotherapy in early-stage Hodgkin's lymphoma.

    PubMed

    Sasse, S; Klimm, B; Görgen, H; Fuchs, M; Heyden-Honerkamp, A; Lohri, A; Koch, O; Wilhelm, M; Trenn, G; Finke, J; Müller, R P; Diehl, V; Eich, H T; Borchmann, P; Engert, A

    2012-11-01

    To evaluate long-term toxicity and efficacy of a combined modality strategy including extended-field radiotherapy (EF-RT) or involved-field radiotherapy (IF-RT), the German Hodgkin Study Group carried out a follow-up analysis in patients with early unfavorable Hodgkin's lymphoma (HL). One thousand two hundred and four patients were randomized to four cycles of chemotherapy followed by either 30 Gy EF- or 30 Gy IF-RT (HD8 trial); 532 patients in each treatment arm were eligible. At 10 years, no arm differences were revealed with respect to freedom from treatment failure (FFTF) (79.8% versus 79.7%), progression-free survival (79.8% versus 80.0%), and overall survival (86.4% versus 87.3%). Non-inferiority of IF-RT was demonstrated for the primary end point FFTF (95% confidence interval for hazard ratio 0.72-1.25). Elderly patients had a poorer outcome when treated with EF-RT. So far, 15.0% of patients in arm A and 12.2% in arm B died, mostly due to secondary malignancies (5.3% versus 3.4%) or HL (3.2% versus 3.4%). After EF-RT, there were more secondary malignancies overall (58 versus 45), especially acute myeloid leukemias (11 versus 4). Radiotherapy intensity reduction to IF-RT does not result in poorer long-term outcome but is associated with less acute toxicity and might be associated with less secondary malignancies.

  3. Cost-effectiveness of chemotherapy combined with thoracic radiotherapy versus chemotherapy alone for limited stage small cell lung cancer: A population-based propensity-score matched analysis

    PubMed Central

    Chien, Chun-Ru; Hsia, Te-Chun; Chen, Chih-Yi

    2014-01-01

    Background The addition of thoracic radiotherapy improves the outcome of limited stage small cell lung cancer (LS-SCLC), however, the cost-effectiveness of this process has never been reported. We aimed to estimate the short-term cost-effectiveness of chemotherapy combined with thoracic radiotherapy (C-TRT) versus chemotherapy alone (C/T) for LS-SCLC patients from the payer's perspective (Taiwan National Health Insurance). Methods We identified LS-SCLC patients diagnosed within 2007–2009 through a comprehensive population-based database containing cancer and death registries, and reimbursement data. The duration of interest was one year within diagnosis. We included potential confounding covariables through literature searching and our own experience, and used a propensity score to construct a 1:1 population for adjustment. We used a net benefit (NB) approach to evaluate the cost-effectiveness at various willingness-to-pay (WTP) levels. Sensitivity analysis regarding potential unmeasured confounder(s) was performed. Results Our study population constituted 74 patients. The mean cost (2013 USD) and survival (year) was higher for C-TRT (42 439 vs. 28 357; 0.94 vs. 0.88). At the common WTP level (50 000 USD/life-year), C-TRT was not cost effective (incremental NB − 11 082) and the probability for C-TRT to be cost effective (i.e. positive net benefit) was 0.005. The result was moderately sensitive to potential unmeasured confounder(s) in sensitivity analysis. Conclusions We provide evidence that when compared to C/T, C-TRT is effective in improving survival, but is not cost-effective in the short-term at a common WTP level from a payer's perspective. This information should be considered by clinicians when discussing thoracic radiotherapy with their LS-SCLC patients. PMID:26767048

  4. Combining Carbon Ion Radiotherapy and Local Injection of {alpha}-Galactosylceramide-Pulsed Dendritic Cells Inhibits Lung Metastases in an In Vivo Murine Model

    SciTech Connect

    Ohkubo, Yu; Iwakawa, Mayumi; Seino, Ken-Ichiro; Nakawatari, Miyako; Wada, Haruka; Kamijuku, Hajime; Nakamura, Etsuko; Nakano, Takashi; Imai, Takashi

    2010-12-01

    Purpose: Our previous report indicated that carbon ion beam irradiation upregulated membrane-associated immunogenic molecules, underlining the potential clinical application of radioimmunotherapy. The antimetastatic efficacy of local combination therapy of carbon ion radiotherapy and immunotherapy was examined by use of an in vivo murine model. Methods and Materials: Tumors of mouse squamous cell carcinoma (NR-S1) cells inoculated in the legs of C3H/HeSlc mice were locally irradiated with a single 6-Gy dose of carbon ions (290 MeV/nucleon, 6-cm spread-out Bragg peak). Thirty-six hours after irradiation, {alpha}-galactosylceramide-pulsed dendritic cells (DCs) were injected into the leg tumor. We investigated the effects on distant lung metastases by counting the numbers of lung tumor colonies, making pathologic observations, and assessing immunohistochemistry. Results: The mice with no treatment (control) presented with 168 {+-} 53.8 metastatic nodules in the lungs, whereas the mice that received the combination therapy of carbon ion irradiation and DCs presented with 2.6 {+-} 1.9 (P = 0.009) at 2 weeks after irradiation. Immunohistochemistry showed that intracellular adhesion molecule 1, which activates DCs, increased from 6 h to 36 h after irradiation in the local tumors of the carbon ion-irradiated group. The expression of S100A8 in lung tissue, a marker of the lung pre-metastatic phase, was decreased only in the group with a combination of carbon ions and DCs. Conclusions: The combination of carbon ion radiotherapy with the injection of {alpha}-galactosylceramide-pulsed DCs into the primary tumor effectively inhibited distant lung metastases.

  5. Intraoperative endovascular ultrasonography

    NASA Astrophysics Data System (ADS)

    Eton, Darwin; Ahn, Samuel S.; Baker, J. D.; Pensabene, Joseph; Yeatman, Lawrence S.; Moore, Wesley S.

    1991-05-01

    The early experience using intra-operative endovascular ultrasonography (EU) is reported in eight patients undergoing lower extremity revasularization. In four patients, intra-operative EU successfully characterized inflow stenoses that were inadequately imaged with pre- operative arteriography. Two patients were found to have hemodynamically significant inflow stenoses, and were treated with intra-operative balloon angioplasty followed by repeat EU. The other two patients were found to have non-hemodynamically significant inflow stenoses requiring no treatment. Additional outflow procedures were required in all four patients. In the remaining four patients, EU was used to evaluate the completeness of TEC rotary atherectomy, of Hall oscillatory endarterectomy, of thrombectomy of the superficial femoral and popliteal arteries, and of valve lysis during in situ saphenous vein grafting, respectively. In the latter case, the valve leaflets were not clearly seen. In the other cases, EU assisted the surgeon. Angioscopy and angiography were available for comparison. In one case, angioscopy failed because of inability to clear the field while inspecting retrograde the limb of an aorto-bi-femoral graft. EU however was possible. No complications of EU occurred. EU is a safe procedure indicated when characterization of a lesion is needed prior to an intervention or when evaluation of the intervention's success is desired. We did not find it useful in valve lysis for in-site grafting.

  6. Nationwide multi-institutional retrospective analysis of high-dose-rate brachytherapy combined with external beam radiotherapy for localized prostate cancer: An Asian Prostate HDR-BT Consortium.

    PubMed

    Ishiyama, Hiromichi; Kamitani, Nobuhiko; Kawamura, Hidemasa; Kato, Shingo; Aoki, Manabu; Kariya, Shinji; Matsumura, Taisei; Kaidu, Motoki; Yoshida, Ken; Hashimoto, Yaichiro; Noda, Yasutaka; Lim, Keith H C; Kawase, Takatsugu; Takahashi, Takeo; Inaba, Koji; Kumano, Motoyasu; Yoshikawa, Nobuhiko; Yoshioka, Yasuo; Nakamura, Katsumasa; Hiratsuka, Junichi; Itami, Jun; Hayakawa, Kazushige

    To report outcomes and risk factors of high-dose-rate (HDR) brachytherapy combined with external beam radiotherapy with or without androgen deprivation therapy (ADT) in prostate cancer patients. This multi-institutional retrospective analysis comprised 3424 patients with localized prostate cancer at 16 Asian hospitals. One-thirds (27.7%) of patients received only neoadjuvant ADT, whereas almost half (49.5%) of patients received both neoadjuvant and adjuvant ADT. Mean duration of neoadjuvant and adjuvant ADT were 8.6 months and 27.9 months, respectively. Biochemical failure was defined by Phoenix ASTRO consensus. Biochemical control rate, clinical disease-free survival (cDFS), cause-specific survival, and overall survival (OS) were calculated. Median followup was 66 months. Ten-year biochemical control, cDFS, cause-specific survival, and OS rate were 81.4%, 81.0%, 97.2%, and 85.6%, respectively. Receiving both neoadjuvant and adjuvant ADT was detected as a favorable factor for biochemical control, cDFS, and OS, but pelvic irradiation was detected as an adverse factor for cause-specific survival, and OS. Ten-year cumulative rates of late Grade ≥2 genitourinary and gastrointestinal toxicities were 26.8% and 4.1%, respectively; receiving both neoadjuvant and adjuvant ADT was detected as a favorable factor for preventing both toxicities. HDR combined with external beam radiotherapy was an effective and safe treatment for localized prostate cancer. Combination of long-term ADT was suggested to be necessary, even for HDR brachytherapy, and was useful in suppressing late toxicities. Meanwhile, pelvic irradiation was suggested to have an adverse effect on OS of our study population. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  7. [Outcomes and predictors of T3a prostate cancer treated by permanent interstitial brachytherapy combined with external radiotherapy and hormone therapy].

    PubMed

    Mai, Zhipeng; Yan, Weigang; Li, Hanzhong; Zhou, Yi; Zhou, Zhien; Chen, Jian

    2014-10-01

    To evaluate the outcomes of T3a prostate cancer treated by permanent interstitial brachytherapy combined with external radiotherapy and hormone therapy, and analyse the influence of preoperative factors on prognosis. From January 2003 to December 2008, 38 pactients with T3a prostate cancer aged from 48 to 81 years (mean: 71 years) were enrolled, with serum prostate specific antigen (PSA) levels ranged from 10.000 to 99.800 µg/L (mean: 56.300 µg/L), Gleason score from 5 to 9 (mean: 7.6) and percentage of positive biopsy cores from 10.0% to 100% (mean: 65.3%). All patients were treated by permanent interstitial brachytherapy combined with external radiotherapy and hormone therapy. Survival curves were calculated using the Kaplan-Meier method. The predictive factors including patient's age, prostate volume, serum pre-treatment PSA, Gleason score and percentage of positive biopsy cores were used for univariate analysis on biochemical failure-free, distant metastasis-free and overall survival. The mean follow-up was 69 months (range: 9-109 months).Nineteen patients experienced biochemical failure. The average biochemical failure time was 13.4 months (range: 1-40 months). There were 13 patients developed as distant metastatic prostate cancer since average 19.7 months (range: 1-70 months) after brachytherapy. Of all patients, 9 died of prostate cancer recurrence, while 6 passed away because of other reasons, with an average of 52.2 months (range: 9.0- 98.5 months). The 5-year biochemical failure-free survival (BFFS), distant metastasis free survival (DMFS), cancer specific survival (CSS) and overall survival (OS) rate were 44.1%, 68.6%, 82.4 and 75.8%, respectively. Twenty-nine patients experienced grade 1-2 gastrointestinal toxicity and 18 patients experienced grade 1-2 genitourinary toxicity. In univariate analysis, the percentage of positive biopsy cores was significantly correlated with BFFS (χ(2) = 17.240, P = 0.000), DMFS (χ(2) = 18.641, P = 0.000) and OS (χ(2

  8. Second malignancies following conventional or combined 252Cf neutron brachytherapy with external beam radiotherapy for breast cancer

    PubMed Central

    Valuckas, Konstantinas Povilas; Atkocius, Vydmantas; Kuzmickiene, Irena; Aleknavicius, Eduardas; Liukpetryte, Sarune; Ostapenko, Valerijus

    2013-01-01

    We retrospectively evaluated the risk of second malignancies among 832 patients with inner or central breast cancer treated with conventional external beam schedule (CRT group), or neutron brachytherapy using Californium-252 (252Cf) sources and hypofractionated external beam radiotherapy (HRTC group), between 1987 and 1996 at the Institute of Oncology, Vilnius University. Patients were observed until the occurrences of death or development of a second malignancy, or until 31 December 2009, whichever was earlier. Median follow-up time was 10.4 years (range, 1.2–24.1 years). Risk of second primary cancers was quantified using standardized incidence ratios (SIRs). Cox proportional hazards regression models were used to estimate hazard ratios (HRs). There was a significant increase in the risk of second primary cancers compared with the general population (SIR 1.3, 95% CI 1.1–1.5). The observed number of second primary cancers was also higher than expected for breast (SIR 1.8, 95% CI 1.3–2.4) and lung cancer (SIR 3.8, 95% CI 2.0–6.7). For second breast cancer, no raised relative risk was observed during the period ≥10 or more years after radiotherapy. Compared with the CRT group, HRTC patients had a not statistically significant higher risk of breast cancer. Increased relative risks were observed specifically for age at initial diagnosis of <50 years (HR 2.9, 95% CI 1.6–5.2) and for obesity (HR 2.8, 95% CI 1.1–7.2). PMID:23397075

  9. Phase I trial of cetuximab in combination with capecitabine, weekly irinotecan, and radiotherapy as neoadjuvant therapy for rectal cancer

    SciTech Connect

    Hofheinz, Ralf-Dieter . E-mail: ralf.hofheinz@med3.ma.uni-heidelberg.de; Horisberger, Karoline; Woernle, Christoph; Wenz, Frederik; Kraus-Tiefenbacher, Uta; Kaehler, Georg; Dinter, Dietmar; Grobholz, Rainer; Heeger, Steffen; Post, Stefan; Hochhaus, Andreas; Willeke, Frank

    2006-12-01

    Purpose: To establish the feasibility and efficacy of chemotherapy with capecitabine, weekly irinotecan, cetuximab, and pelvic radiotherapy for patients with locally advanced rectal cancer. Methods and materials: Twenty patients with rectal cancer (clinical Stage uT3-T4 or N+) received a standard dosing regimen of cetuximab (400 mg/m{sup 2} on Day 1 and 250 mg/m{sup 2} on Days 8, 15, 22, and 29) and escalating doses of irinotecan and capecitabine according to phase I methods: dose level I, irinotecan 40 mg/m{sup 2} on Days 1, 8, 15, 22, and 29 and capecitabine 800 mg/m{sup 2} on Days 1-38; dose level II, irinotecan 40 mg/m{sup 2} and capecitabine 1000 mg/m{sup 2}; and dose level III, irinotecan 50 mg/m{sup 2} and capecitabine 1000 mg/m{sup 2}. Radiotherapy was given to a dose of 50.4 Gy (45 Gy plus 5.4 Gy). Resection was scheduled 4-5 weeks after termination of chemoradiotherapy. Results: On dose level I, no dose-limiting toxicities occurred; however, Grade 3 diarrhea affected 1 of 6 patients on dose level II. Of 5 patients treated at dose level III, 2 exhibited dose-limiting toxicity (diarrhea in 2 and nausea/vomiting in 1). Therefore, dose level II was determined as the recommended dose for future studies. A total of 10 patients were treated on dose level II and received a mean relative dose intensity of 100% of cetuximab, 94% of irinotecan, and 95% of capecitabine. All patients underwent surgery. Five patients had a pathologically complete remission and six had microfoci of residual tumor only. Conclusion: Preoperative chemoradiotherapy with cetuximab, capecitabine, and weekly irinotecan is feasible and well tolerated. The preliminary efficacy is very promising. Larger phase II trials are ongoing.

  10. Tolerance of retroperitoneal structures to intraoperative radiation

    SciTech Connect

    Sindelar, W.F.; Tepper, J.; Travis, E.L.; Terrill, R.

    1982-11-01

    In conjunction with the clinical development of intraoperative radiotherapy, a study was undertaken in dogs to define the tolerance of normal anatomic structures in the retroperitoneum to radiation delivered during operation. Twenty adult dogs were subjected to laparotomy and intraoperative 11 MeV electron irradiation in single doses ranging from 0.to 5000 rad. Animals were followed regularly with clinical observation, blood count, serum chemistries, pyelography, and angiography. Animals were sacrificed and autopsied at regular intervals up to 12 months following treatment to assess radiation-induced complications or tissue damage. Irradiation field in all dogs consisted of a 4 X 15 cm rectangle extending in the retroperitoneum from the level of the renal vessels to the bifurcation of aorta and vena cava. The field included aorta, vena cava, inferior portion of left kidney, and distal portion of left ureter. No complications or histologic changes occurred in any animal given doses of 2000 rad, with a follow-up in excess of 18 months. A dose of 3000 rad was well tolerated, except for left ureteral occlusion in one animal. Mild vascular fibrosis was present inthe aorta and vena cava, and significant ureteral fibrosis developed by six months after doses of 4000 or 5000 rad. All animals that received 5000 rad died of radiation-related complications, including ureteral obstruction and rectal perforation. It was concluded that major vessels tolerate intraoperative irradiation well up to and including 3000 rad and that no clinically significant vascular problems develop after 4000 and 5000 rad, although some fibrosis does occur. The ureter and kidney appear to be the most radiosensitive structures inthe retroperitoneum, showing progressive changes at 300 rad or greater and showing the potential for serious complications after doses of 4000 rad or more.

  11. Intraoperative virtual brain counseling

    NASA Astrophysics Data System (ADS)

    Jiang, Zhaowei; Grosky, William I.; Zamorano, Lucia J.; Muzik, Otto; Diaz, Fernando

    1997-06-01

    Our objective is to offer online real-tim e intelligent guidance to the neurosurgeon. Different from traditional image-guidance technologies that offer intra-operative visualization of medical images or atlas images, virtual brain counseling goes one step further. It can distinguish related brain structures and provide information about them intra-operatively. Virtual brain counseling is the foundation for surgical planing optimization and on-line surgical reference. It can provide a warning system that alerts the neurosurgeon if the chosen trajectory will pass through eloquent brain areas. In order to fulfill this objective, tracking techniques are involved for intra- operativity. Most importantly, a 3D virtual brian environment, different from traditional 3D digitized atlases, is an object-oriented model of the brain that stores information about different brain structures together with their elated information. An object-oriented hierarchical hyper-voxel space (HHVS) is introduced to integrate anatomical and functional structures. Spatial queries based on position of interest, line segment of interest, and volume of interest are introduced in this paper. The virtual brain environment is integrated with existing surgical pre-planning and intra-operative tracking systems to provide information for planning optimization and on-line surgical guidance. The neurosurgeon is alerted automatically if the planned treatment affects any critical structures. Architectures such as HHVS and algorithms, such as spatial querying, normalizing, and warping are presented in the paper. A prototype has shown that the virtual brain is intuitive in its hierarchical 3D appearance. It also showed that HHVS, as the key structure for virtual brain counseling, efficiently integrates multi-scale brain structures based on their spatial relationships.This is a promising development for optimization of treatment plans and online surgical intelligent guidance.

  12. Dosimetric and delivery efficiency investigation for treating hepatic lesions with a MLC-equipped robotic radiosurgery–radiotherapy combined system

    SciTech Connect

    Jin, Lihui Price, Robert A.; Wang, Lu; Meyer, Joshua; Fan, James; Charlie Ma, Chang Ming

    2016-02-15

    Purpose: The CyberKnife M6 (CK-M6) Series introduced a multileaf collimator (MLC) for extending its capability from stereotactic radiosurgery/stereotactic radiotherapy (SBRT) to conventionally fractionated radiotherapy. This work is to investigate the dosimetric quality of plans that are generated using MLC-shaped beams on the CK-M6, as well as their delivery time, via comparisons with the intensity modulated radiotherapy plans that were clinically used on a Varian Linac for treating hepatic lesions. Methods: Nine patient cases were selected and divided into three groups with three patients in each group: (1) the group-one patients were treated conventionally (25 fractions); (2) the group-two patients were treated with SBRT-like hypofractionation (5 fractions); and (3) the group-three patients were treated similar to group-one patients, but with two planning target volumes (PTVs) and two different prescription dose levels correspondingly. The clinically used plans were generated on the ECLIPSE treatment planning system (TPS) and delivered on a Varian Linac (E-V plans). The multiplan (MP) TPS was used to replan these clinical cases with the MLC as the beam device for the CK-M6 (C-M plans). After plans were normalized to the same PTV dose coverage, comparisons between the C-M and E-V plans were performed based on D{sub 99%} (percentage of prescription dose received by 99% of the PTV), D{sub 0.1cm{sup 3}} (the percentage of prescription dose to 0.1 cm{sup 3} of the PTV), and doses received by critical structures. Then, the delivery times for the C-M plans will be obtained, which are the MP TPS generated estimations assuming having an imaging interval of 60 s. Results: The difference in D{sub 99%} between C-M and E-V plans is +0.6% on average (+ or − indicating a higher or lower dose from C-M plans than from E-V plans) with a range from −4.1% to +3.8%, and the difference in D{sub 0.1cm{sup 3}} was −1.0% on average with a range from −5.1% to +2.9%. The PTV

  13. Whole-body dose and energy measurements in radiotherapy by a combination of LiF:Mg,Cu,P and LiF:Mg,Ti.

    PubMed

    Hauri, Pascal; Schneider, Uwe

    2017-08-11

    Long-term survivors of cancer who were treated with radiotherapy are at risk of a radiation-induced tumor. Hence, it is important to model the out-of-field dose resulting from a cancer treatment. These models have to be verified with measurements, due to the small size, the high sensitivity to ionizing radiation and the tissue-equivalent composition, LiF thermoluminescence dosimeters (TLD) are well-suited for out-of-field dose measurements. However, the photon energy variation of the stray dose leads to systematic dose errors caused by the variation in response with radiation energy of the TLDs. We present a dosimeter which automatically corrects for the energy variation of the measured photons by combining LiF:Mg,Ti (TLD100) and LiF:Mg,Cu,P (TLD100H) chips. The response with radiation energy of TLD100 and TLD100H compared to (60)Co was taken from the literature. For the measurement, a TLD100H was placed on top of a TLD100 chip. The dose ratio between the TLD100 and TLD100H, combined with the ratio of the response curves was used to determine the mean energy. With the energy, the individual correction factors for TLD100 and TLD100H could be found. The accuracy in determining the in- and out-of-field dose for a nominal beam energy of 6MV using the double-TLD unit was evaluated by an end-to-end measurement. Furthermore, published Monte Carlo (M.C.) simulations of the mean photon energy for brachytherapy sources, stray radiation of a treatment machine and cone beam CT (CBCT) were compared to the measured mean energies. Finally, the photon energy distribution in an Alderson phantom was measured for different treatment techniques applied with a linear accelerator. Additionally, a treatment plan was measured with a cobalt machine combined with an MRI. For external radiotherapy, the presented double-TLD unit showed a relative type A uncertainty in doses of -1%±2% at the two standard deviation level compared to an ionization chamber. The type A uncertainty in dose was in

  14. History of intraoperative ultrasound.

    PubMed

    Makuuchi, M; Torzilli, G; Machi, J

    1998-11-01

    Intraoperative ultrasound (IOUS) using A-mode or non-real-time B-mode imaging started in the 1960s; however, it was not widely accepted mainly because of difficulty in image interpretation. In the late 1970s, IOUS became one of the topics in the surgical communities upon the introduction of high-frequency real-time B-mode ultrasound. Special probes for operative use were developed. In the 1980s, all over the world the use of IOUS spread to a variety of surgical fields, such as hepatobiliary pancreatic surgery, neurosurgery, and cardiovascular surgery. IOUS changed hepatic surgery dramatically because IOUS was the only modality that was capable of delineating and examining the interior of the liver during surgery. After 1990, color Doppler imaging and laparoscopic ultrasound were incorporated into IOUS. Currently, IOUS is considered an indispensable operative procedure for intraoperative decision-making and guidance of surgical procedures. For better surgical practice, education of surgeons in the use of ultrasound is the most important issue.

  15. Practicality of intraoperative teamwork assessments.

    PubMed

    Phitayakorn, Roy; Minehart, Rebecca; Pian-Smith, May C M; Hemingway, Maureen W; Milosh-Zinkus, Tanya; Oriol-Morway, Danika; Petrusa, Emil

    2014-07-01

    High-quality teamwork among operating room (OR) professionals is a key to efficient and safe practice. Quantification of teamwork facilitates feedback, assessment, and improvement. Several valid and reliable instruments are available for assessing separate OR disciplines and teams. We sought to determine the most feasible approach for routine documentation of teamwork in in-situ OR simulations. We compared rater agreement, hypothetical training costs, and feasibility ratings from five clinicians and two nonclinicians with instruments for assessment of separate OR groups and teams. Five teams of anesthesia or surgery residents and OR nurses (RN) or surgical technicians were videotaped in simulations of an epigastric hernia repair where the patient develops malignant hyperthermia. Two anesthesiologists, one OR clinical RN specialist, one educational psychologist, one simulation specialist, and one general surgeon discussed and then independently completed Anesthesiologists' Non-Technical Skills, Non-Technical Skills for Surgeons, Scrub Practitioners' List of Intraoperative Non-Technical Skills, and Observational Teamwork Assessment for Surgery forms to rate nontechnical performance of anesthesiologists, surgeons, nurses, technicians, and the whole team. Intraclass correlations of agreement ranged from 0.17-0.85. Clinicians' agreements were not different from nonclinicians'. Published rater training was 4 h for Anesthesiologists' Non-Technical Skills and Scrub Practitioners' List of Intraoperative Non-Technical Skills, 2.5 h for Non-Technical Skills for Surgeons, and 15.5 h for Observational Teamwork Assessment for Surgery. Estimated costs to train one rater to use all instruments ranged from $442 for a simulation specialist to $6006 for a general surgeon. Additional training is needed to achieve higher levels of agreement; however, costs may be prohibitive. The most cost-effective model for real-time OR teamwork assessment may be to use a simulation technician

  16. A phase I-II trial of multimodality management of bulky gynecologic malignancy. Combined chemoradiosensitization and radiotherapy

    SciTech Connect

    Kersh, C.R.; Constable, W.C.; Spaulding, C.A.; Hahn, S.S.; Andersen, W.A.; Taylor, P.T. )

    1990-07-01

    Between December 1983 and December 1987, there were 44 patients with bulky, nonresectable squamous cell carcinomas of the gynecologic tract (cervix, 36; vagina, eight) who were treated with concomitant chemotherapy and radiotherapy. Chemotherapy consisted of 5-fluorouracil (5-FU) 1g/m2 given by continuous intravenous infusion on days 1 through 4 and mitomycin C 10 mg/m2 given intravenously on day 1. External-beam irradiation was started on day 1 with a total calculated dose of 5000 cGy in 25 fractions employed. This was followed by brachytherapy. With a mean follow-up of 30.3 months and a median of 28 months, local control has been achieved in 32 of 44 patients (73%). The overall response rate was 88% (3-month partial response, 43%; 3-month complete response, 45%; 8-month partial response, 15%; 8-month complete response, 73%). Analysis of complications by Radiation Therapy Oncology Group (RTOG) criteria did not demonstrate an increase in acute or late complications.

  17. The Art of Intraoperative Glioma Identification

    PubMed Central

    Zhang, Zoe Z.; Shields, Lisa B. E.; Sun, David A.; Zhang, Yi Ping; Hunt, Matthew A.; Shields, Christopher B.

    2015-01-01

    A major dilemma in brain-tumor surgery is the identification of tumor boundaries to maximize tumor excision and minimize postoperative neurological damage. Gliomas, especially low-grade tumors, and normal brain have a similar color and texture, which poses a challenge to the neurosurgeon. Advances in glioma resection techniques combine the experience of the neurosurgeon and various advanced technologies. Intraoperative methods to delineate gliomas from normal tissue consist of (1) image-based navigation, (2) intraoperative sampling, (3) electrophysiological monitoring, and (4) enhanced visual tumor demarcation. The advantages and disadvantages of each technique are discussed. A combination of these methods is becoming widely accepted in routine glioma surgery. Gross total resection in conjunction with radiation, chemotherapy, or immune/gene therapy may increase the rates of cure in this devastating disease. PMID:26284196

  18. Site-specific dose-response relationships for cancer induction from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy.

    PubMed

    Schneider, Uwe; Sumila, Marcin; Robotka, Judith

    2011-07-26

    Most information on the dose-response of radiation-induced cancer is derived from data on the A-bomb survivors. Since, for radiation protection purposes, the dose span of main interest is between zero and one Gy, the analysis of the A-bomb survivors is usually focused on this range. However, estimates of cancer risk for doses larger than one Gy are becoming more important for radiotherapy patients. Therefore in this work, emphasis is placed on doses relevant for radiotherapy with respect to radiation induced solid cancer. For various organs and tissues the analysis of cancer induction was extended by an attempted combination of the linear-no-threshold model from the A-bomb survivors in the low dose range and the cancer risk data of patients receiving radiotherapy for Hodgkin's disease in the high dose range. The data were fitted using organ equivalent dose (OED) calculated for a group of different dose-response models including a linear model, a model including fractionation, a bell-shaped model and a plateau-dose-response relationship. The quality of the applied fits shows that the linear model fits best colon, cervix and skin. All other organs are best fitted by the model including fractionation indicating that the repopulation/repair ability of tissue is neither 0 nor 100% but somewhere in between. Bone and soft tissue sarcoma were fitted well by all the models. In the low dose range beyond 1 Gy sarcoma risk is negligible. For increasing dose, sarcoma risk increases rapidly and reaches a plateau at around 30 Gy. In this work OED for various organs was calculated for a linear, a bell-shaped, a plateau and a mixture between a bell-shaped and plateau dose-response relationship for typical treatment plans of Hodgkin's disease patients. The model parameters (α and R) were obtained by a fit of the dose-response relationships to these OED data and to the A-bomb survivors. For any three-dimensional inhomogenous dose distribution, cancer risk can be compared by

  19. Site-specific dose-response relationships for cancer induction from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy

    PubMed Central

    2011-01-01

    Background and Purpose Most information on the dose-response of radiation-induced cancer is derived from data on the A-bomb survivors. Since, for radiation protection purposes, the dose span of main interest is between zero and one Gy, the analysis of the A-bomb survivors is usually focused on this range. However, estimates of cancer risk for doses larger than one Gy are becoming more important for radiotherapy patients. Therefore in this work, emphasis is placed on doses relevant for radiotherapy with respect to radiation induced solid cancer. Materials and methods For various organs and tissues the analysis of cancer induction was extended by an attempted combination of the linear-no-threshold model from the A-bomb survivors in the low dose range and the cancer risk data of patients receiving radiotherapy for Hodgkin's disease in the high dose range. The data were fitted using organ equivalent dose (OED) calculated for a group of different dose-response models including a linear model, a model including fractionation, a bell-shaped model and a plateau-dose-response relationship. Results The quality of the applied fits shows that the linear model fits best colon, cervix and skin. All other organs are best fitted by the model including fractionation indicating that the repopulation/repair ability of tissue is neither 0 nor 100% but somewhere in between. Bone and soft tissue sarcoma were fitted well by all the models. In the low dose range beyond 1 Gy sarcoma risk is negligible. For increasing dose, sarcoma risk increases rapidly and reaches a plateau at around 30 Gy. Conclusions In this work OED for various organs was calculated for a linear, a bell-shaped, a plateau and a mixture between a bell-shaped and plateau dose-response relationship for typical treatment plans of Hodgkin's disease patients. The model parameters (α and R) were obtained by a fit of the dose-response relationships to these OED data and to the A-bomb survivors. For any three

  20. Combination of radiotherapy and double blockade HER2 with pertuzumab and trastuzumab for HER2-positive metastatic or locally recurrent unresectable and/or metastatic breast cancer: Assessment of early toxicity.

    PubMed

    Ajgal, Z; de Percin, S; Diéras, V; Pierga, J Y; Campana, F; Fourquet, A; Kirova, Y M

    2017-04-01

    We evaluate the early toxicity of concurrent use of radiotherapy, pertuzumab and trastuzumab in patients with HER2-positive metastatic or locally recurrent unresectable breast cancer. A retrospective study was performed in a population of 23 consecutive patients between 2013 and 2015. Radiotherapy was performed on the chest area or metastatic sites during maintenance with pertuzumab and trastuzumab after six cycles of pertuzumab, trastuzumab and docetaxel. Toxicity was assessed according to the National Cancer Institute Common Toxicity Criteria version 4. Irradiation volumes were whole breast (8 patients) and chest wall (9 patients) at 50Gy in 25 fractions, the supraclavicular nodes (16 patients), the axillary area (nine patients) and the internal mammary nodes (9 patients) at 46Gy in 23 fractions. For five patients, radiotherapy was palliative: bone irradiation (4 patients), whole brain radiotherapy (one patient). Median follow-up was 12.6 months (range: 6.1-21.6 months) since the start of pertuzumab and trastuzumab. One patient presented an asymptomatic decrease of left ventricular ejection fraction below 50%. No symptomatic cardiac events were reported. Two patients presented asymptomatic grade I radiation pneumonitis. Acute skin toxicity was grade III (one patient), grade II (6 patients), and grade I (5 patients). There were two grade II esophagitis. Combination of pertuzumab, trastuzumab and radiotherapy was well tolerated, which should be confirmed by the results of larger studies. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  1. Late toxicities and outcomes of adjuvant radiotherapy combined with concurrent bevacizumab in patients with triple-negative non-metastatic breast cancer

    PubMed Central

    Pernin, V; Belin, L; Cottu, P; Bontemps, P; Lemanski, C; De La Lande, B; Baumann, P; Missohou, F; Levy, C; Peignaux, K; Reynaud-Bougnoux, A; Denis, F; Gobillion, A; Bollet, M; Vago, N A; Dendale, R; Campana, F; Fourquet, A

    2015-01-01

    Objective: To evaluate the safety of the concurrent combination of bevacizumab with adjuvant radiotherapy (B-RT) in breast cancer (BC). Methods: Multicentre, prospective study, of the toxicity of adjuvant radiotherapy (RT) alone or B-RT in patients with non-metastatic BC enrolled in randomized Phase 3 BEATRICE trial. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events v. 3.0 during and 12 months after the completion of RT. Results: From 2007 to 2012, 39 females received adjuvant B-RT and 45 received adjuvant RT alone. Median follow-up was 21.5 months. All patients had triple-negative non-metastatic BC and received adjuvant chemotherapy followed by RT. 90% of the 39 females treated by concurrent B-RT received whole breast irradiation (WBI) with a boost and 4 (10%) received post-mastectomy RT. Lymph node RT was delivered in 49% of the females with internal mammary chain irradiation. The mean duration of bevacizumab was 11.7 months. 38 (84%) females treated by RT alone received WBI with a boost and 16% of the females received post-mastectomy RT. Lymph node RT was delivered in 47% of the females with internal mammary chain RT in 31%. Grade 3 acute dermatitis was observed in 9% of patients receiving B-RT and 5% of patients receiving RT alone with no significant difference. 1 year after the completion of RT, the most common late grade 1–2 toxicities in the B-RT group were pain (18%), fibrosis (8%) and telangiectasia (5%). Conclusion: The concurrent bevacizumab with locoregional RT is associated with acceptable early and late 1-year toxicities in patients with BC. Advances in knowledge: The largest series of this association. PMID:25645108

  2. Late toxicities and outcomes of adjuvant radiotherapy combined with concurrent bevacizumab in patients with triple-negative non-metastatic breast cancer.

    PubMed

    Pernin, V; Belin, L; Cottu, P; Bontemps, P; Lemanski, C; De La Lande, B; Baumann, P; Missohou, F; Levy, C; Peignaux, K; Reynaud-Bougnoux, A; Denis, F; Gobillion, A; Bollet, M; Vago, N A; Dendale, R; Campana, F; Fourquet, A; Kirova, Y M

    2015-04-01

    To evaluate the safety of the concurrent combination of bevacizumab with adjuvant radiotherapy (B-RT) in breast cancer (BC). Multicentre, prospective study, of the toxicity of adjuvant radiotherapy (RT) alone or B-RT in patients with non-metastatic BC enrolled in randomized Phase 3 BEATRICE trial. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events v. 3.0 during and 12 months after the completion of RT. From 2007 to 2012, 39 females received adjuvant B-RT and 45 received adjuvant RT alone. Median follow-up was 21.5 months. All patients had triple-negative non-metastatic BC and received adjuvant chemotherapy followed by RT. 90% of the 39 females treated by concurrent B-RT received whole breast irradiation (WBI) with a boost and 4 (10%) received post-mastectomy RT. Lymph node RT was delivered in 49% of the females with internal mammary chain irradiation. The mean duration of bevacizumab was 11.7 months. 38 (84%) females treated by RT alone received WBI with a boost and 16% of the females received post-mastectomy RT. Lymph node RT was delivered in 47% of the females with internal mammary chain RT in 31%. Grade 3 acute dermatitis was observed in 9% of patients receiving B-RT and 5% of patients receiving RT alone with no significant difference. 1 year after the completion of RT, the most common late grade 1-2 toxicities in the B-RT group were pain (18%), fibrosis (8%) and telangiectasia (5%). The concurrent bevacizumab with locoregional RT is associated with acceptable early and late 1-year toxicities in patients with BC. The largest series of this association.

  3. 3D Radiotherapy Can Be Safely Combined With Sandwich Systemic Gemcitabine Chemotherapy in the Management of Pancreatic Cancer: Factors Influencing Outcome

    SciTech Connect

    Spry, Nigel Harvey, Jennifer; MacLeod, Craig; Borg, Martin; Ngan, Samuel Y.; Millar, Jeremy L.; Graham, Peter; Zissiadis, Yvonne; Kneebone, Andrew; Carroll, Susan; Davies, Terri; Reece, William H.H.; Iacopetta, Barry; Goldstein, David

    2008-04-01

    Purpose: The aim of this Phase II study was to examine whether concurrent continuous infusion 5-fluorouracil (CI 5FU) plus three-dimensional conformal planning radiotherapy sandwiched between gemcitabine chemotherapy is effective, tolerable, and safe in the management of pancreatic cancer. Methods and Materials: Patients were enrolled in two strata: (1) resected pancreatic cancer at high risk of local relapse (postsurgery arm, n = 22) or (2) inoperable pancreatic cancer in head or body without metastases (locally advanced arm, n = 41). Gemcitabine was given at 1,000 mg/m{sup 2} weekly for 3 weeks followed by 1 week rest then 5-6 weeks of radiotherapy and concurrent CI 5FU (200 mg/m{sup 2}/day). After 4 weeks' rest, gemcitabine treatment was reinitiated for 12 weeks. Results: For the two arms combined, treatment-related Grade 3 and 4 toxicities were reported by 25 (39.7%) and 7 (11.1%) patients, respectively. No significant late renal or hepatic toxicity was observed. In the postsurgery arm (R1 54.5%), median time to progressive disease from surgery was 11.0 months, median time to failure of local control was 32.9 months, and median survival time was 15.6 months. The 1- and 2-year survival rates were 63.6% and 31.8%. No significant associations between outcome and mutations in K-ras or TP53 or microsatellite instability were identified. Post hoc investigation of cancer antigen 19-9 levels found baseline levels and increases postbaseline were associated with shorter survival (p = 0.0061 and p < 0.0001, respectively). Conclusions: This three-dimensional chemoradiotherapy regimen is safe and promising, with encouraging local control for a substantial proportion of patients, and merits testing in a randomized trial.

  4. Intraoperative BiPAP in OSA Patients

    PubMed Central

    Singh, Bhavna P

    2015-01-01

    Obstructive sleep apnea syndrome (OSA) is characterized by recurrent episodes of partial or complete upper airway obstructions during sleep. Severe OSA presents with a number of challenges to the anesthesiologist, the most life threatening being loss of the airway. We are reporting a case where we successfully used intraoperative bi level positive pressure ventilation (BiPAP) with moderate sedation and a regional technique in a patient with severe OSA posted for total knee replacement (TKR). A 55-year-old lady with osteoarthritis of right knee joint was posted for total knee replacement. She had severe OSA with an apnea-hypopnea index of 35. She also had moderate pulmonary hypertension due to her long standing OSA. We successfully used in her a combined spinal epidural technique with intraoperative BiPAP and sedation. She had no complications intraoperatively or post operatively and was discharged on day 5. Patients with OSA are vulnerable to sedatives, anaesthesia and analgesia which even in small doses can cause complete airway collapse. The problem, with regional techniques is that it requires excellent patient cooperation. We decided to put our patient on intraoperative BiPAP hoping that this would allow us to sedate her adequately for the surgery. As it happened we were able to successfully sedate her with slightly lesser doses of the commonly used sedatives without any episodes of desaturation, snoring or exacerbation of pulmonary hypertension. Many more trials are required before we can conclusively say that intraoperative BiPAP allows us to safely sedate OSA patients but we hope that our case report draws light on this possibility. Planning ahead and having a BiPAP machine available inside the operating may allow us to use sedatives in these patients to keep them comfortable under regional anaesthesia. PMID:26023625

  5. Nuclear probes and intraoperative gamma cameras.

    PubMed

    Heller, Sherman; Zanzonico, Pat

    2011-05-01

    Gamma probes are now an important, well-established technology in the management of cancer, particularly in the detection of sentinel lymph nodes. Intraoperative sentinel lymph node as well as tumor detection may be improved under some circumstances by the use of beta (negatron or positron), rather than gamma detection, because the very short range (∼ 1 mm or less) of such particulate radiations eliminates the contribution of confounding counts from activity other than in the immediate vicinity of the detector. This has led to the development of intraoperative beta probes. Gamma camera imaging also benefits from short source-to-detector distances and minimal overlying tissue, and intraoperative small field-of-view gamma cameras have therefore been developed as well. Radiation detectors for intraoperative probes can generally be characterized as either scintillation or ionization detectors. Scintillators used in scintillation-detector probes include thallium-doped sodium iodide, thallium- and sodium-doped cesium iodide, and cerium-doped lutecium orthooxysilicate. Alternatives to inorganic scintillators are plastic scintillators, solutions of organic scintillation compounds dissolved in an organic solvent that is subsequently polymerized to form a solid. Their combined high counting efficiency for beta particles and low counting efficiency for 511-keV annihilation γ-rays make plastic scintillators well-suited as intraoperative beta probes in general and positron probes in particular Semiconductors used in ionization-detector probes include cadmium telluride, cadmium zinc telluride, and mercuric iodide. Clinical studies directly comparing scintillation and semiconductor intraoperative probes have not provided a clear choice between scintillation and ionization detector-based probes. The earliest small field-of-view intraoperative gamma camera systems were hand-held devices having fields of view of only 1.5-2.5 cm in diameter that used conventional thallium

  6. Conformal Therapy Improves the Therapeutic Index of Patients with Anal Canal Cancer Treated with Combined Chemotherapy and External Beam Radiotherapy

    SciTech Connect

    Vuong, Te . E-mail: te.vuong@muhc.mcgill.ca; Kopek, Neil; Ducruet, Thierry; Portelance, Lorraine; Faria, Sergio; Bahoric, Boris; Devic, Slobodan

    2007-04-01

    Purpose: To evaluate the clinical outcomes of three-dimensional conformal radiotherapy (3D-CRT) in patients with anal canal cancer, in terms of local control (LC), freedom from relapse (FFR), and overall survival (OS) rates, and to estimate long-term toxicity data. Methods and Materials: Sixty historical patients, treated with conventional radiation techniques (C-RT), were used as controls, and 62 consecutive patients were treated with 3D-CRT. Patients treated with 3D-CRT received 54 Gy in 30 fractions delivered continuously, compared with 45-58.9 Gy (median dose, 54 Gy) in a split course in patients treated with C-RT. Chemotherapy consisted of 5-fluorouracil with either mitomycin-C or cis-platinum given concurrently with radiation. Survival curves were performed using the Kaplan-Meier model, and the Cox proportional hazards model was used for multivariate analysis of risk factors. Results: No differences in stage and age distribution were observed between the two groups. Patients treated with 3D-CRT and C-RT had an actuarial 5-year LC rate of 85.1% and 61.1%, respectively (p = 0.0056); the FFR rate was 70.2% and 46.1% (p = 0.0166), and the OS rate was 80.7% and 53.9% (p = 0.0171). In multivariate analysis, factors of significance for LC were nodal (N) status (p < 0.001); for OS, 3D-CRT (p = 0.038), N status (p 0.011), and T status (p = 0.012); and for FFR, 3D-CRT (p = 0.024) and N status (p < 0.001). Conclusion: The use of 3D-CRT allows patients with anal canal cancer to complete radiation and chemotherapy without interruption for toxicity, with significant improvements in LC, FFR, and OS.

  7. [Intraoperative mapping of lymph outflow tracts in colorectal carcinoma].

    PubMed

    Mel'nikov, O R; Iaitskiĭ, A N; Danilov, I N; Anishkin, M Iu; Abdurakhmonov, Iu B

    2007-01-01

    Based on an analysis of 60 cases the authors have shown that identification and target investigation of signal lymph nodes using intraoperative staining with special dyes allows correct assessment of the stage of malignant disease. The method also allows treatment of the patient with an adequate, corresponding to up-to-date standards scheme of combined and complex treatment, gives possibilities of exact intraoperative diagnosis of lymphogenic metastasis and, as a result, allows extended operative intervention up to radical volumes.

  8. [Intraoperative floppy iris syndrome].

    PubMed

    Mazal, Z

    2007-04-01

    In the year 2005, Chang and Cambell described unusual reaction of the iris during the cataract surgery in patients treated with tamsulosine. This was named as IFIS, an acronym for the Intraoperative Floppy Iris Syndrome. In its advanced stage, the syndrome is characterized by insufficient mydfiasis before the surgery, narrowing of the pupil during the surgery, its impossible dilatation during the surgery by means of stretching, unusual elasticity of the pupilar margin, surging and fluttering iris with tendency to prolapse. The same manifestations we observed in our patients and we confirm the direct connection with tamsulosine hydrochloride treatment. Tamsulosine is the antagonist of alpha 1A adrenergic receptors whose are present, except in the smooth musculature of the prostate gland and the urinary bladder, in the iris dilator as well. At the same time we observed this syndrome rarely in some patients not using tamsulosine. In most cases, these patients were treated with antipsychotic drugs.

  9. Chemotherapy response as a prognosticator for survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy

    SciTech Connect

    Eagan, R.T.; Fleming, T.R.; Lee, R.E.; Ingle, J.N.; Frytak, S.; Creagan, E.T.

    1980-07-01

    Twenty-two patients with limited unresectable squamous cell lung cancer were treated with 6 courses of combination chemotherapy consisting of cyclophosphamide, adriamycin, cisplatin, and bleomycin (CAP-Bleo) and short-course thoracic irradiation started after the first 4 weeks of chemotherapy. Of 20 patients with visible tumor who were treated with 4 weeks of chemotherapy alone, 10 (50%) had a tumor regression in that 4 week period and 10 did not. Those patients with tumor regression had significantly better progression free and overall survivals than did patients with no chemotherapy regressions (medians of 258 days vs. 136 days and 356 days vs. 150 days respectively). The original bleomycin dose had to be reduced by 50% primarily because of excessive radiation esophagitis that has not been reported with use of either the CAP regimen or bleomycin along in conjunction with thoracic irradiation. An initial chemotherapy regression seems to be a good prognosticator for progression-free and overall survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy.

  10. Preclinical evaluation of the combination of mTOR and proteasome inhibitors with radiotherapy in malignant peripheral nerve sheath tumors.

    PubMed

    Yamashita, A S; Baia, G S; Ho, J S Y; Velarde, E; Wong, J; Gallia, G L; Belzberg, A J; Kimura, E T; Riggins, G J

    2014-05-01

    About one half of malignant peripheral nerve sheath tumors (MPNST) have Neurofibromin 1 (NF1) mutations. NF1 is a tumor suppressor gene essential for negative regulation of RAS signaling. Survival for MPNST patients is poor and we sought to identify an effective combination therapy. Starting with the mTOR inhibitors rapamycin and everolimus, we screened for synergy in 542 FDA approved compounds using MPNST cells with a native NF1 loss in both alleles. We further analyzed the cell cycle and signal transduction. In vivo growth effects of the drug combination with local radiation therapy (RT) were assessed in MPNST xenografts. The synergistic combination of mTOR inhibitors with bortezomib yielded a reduction in MPNST cell proliferation. The combination of mTOR inhibitors and bortezomib also enhanced the anti-proliferative effect of radiation in vitro. In vivo, the combination of mTOR inhibitor (everolimus) and bortezomib with RT decreased tumor growth and proliferation, and augmented apoptosis. The combination of approved mTOR and proteasome inhibitors with radiation showed a significant reduction of tumor growth in an animal model and should be investigated and optimized further for MPNST therapy.

  11. The clinical effects of low-dose splenic irradiation combined with chest three-dimensional conformal radiotherapy on patients with locally advanced non-small-cell lung cancer: a randomized clinical trial

    PubMed Central

    Yu, Hongsheng; Qu, Yong; Shang, Qingjun; Yan, Chao; Jiang, Peng; Wang, Xiang; Liang, Donghai; Jiang, Tao

    2016-01-01

    Objective The objective of this study was to explore the clinical effects of low-dose splenic irradiation on locally advanced non-small-cell lung cancer (NSCLC) patients. Methods Thirty-eight patients with stage III NSCLC were randomly divided into a control group and a combined treatment group. The control group only received chest three-dimensional conformal radiotherapy, while the combined treatment group received low-dose splenic irradiation followed by chest three-dimensional conformal radiotherapy after 6 hours. T lymphocyte subsets of the blood cells were tested before, during, and after treatment once a week. The side effects induced by radiation were observed, and a follow-up was done to observe the survival statistics. Results The ratio differences in CD4+ cells, CD8+ cells, and CD4+/CD8+ before and after treatment were not statistically significant (P>0.05) in both the groups. The immune indexes were also not statistically significant (P>0.05) before and after radiotherapy in the combined treatment group. However, the numbers of CD4+ cells and CD4+/CD8+ ratios before radiotherapy were higher than after radiotherapy in the control group. There were no differences in the incidence of radiation toxicities between the two groups; however, the incidence of grade III or IV radiation toxicities was lower, and the dose at which the radiation toxicities appeared was higher in the combined treatment group. The total response rate was 63.16% (12/19) in the combined treatment group vs 42.11% (8/19) in the control group. The median 2-year progression-free survival (15 months in the combined treatment group vs 10 months in the control group) was statistically significant (P<0.05). The median 2-year overall survival (17.1 months in the combined treatment group vs 15.8 months in the control group) was not statistically significant (P>0.05). Conclusion Low-dose radiation can alleviate the radiation toxicities, improve the short-term efficacy of radiotherapy, and improve

  12. [Radiotherapy of bladder cancer].

    PubMed

    Riou, O; Chauvet, B; Lagrange, J-L; Martin, P; Llacer Moscardo, C; Charissoux, M; Lauche, O; Aillères, N; Fenoglietto, P; Azria, D

    2016-09-01

    Surgery (radical cystectomy) is the standard treatment of muscle-invasive bladder cancer. Radiochemotherapy has risen as an alternative treatment option to surgery as part as organ-sparing combined modality treatment or for patients unfit for surgery. Radiochemotherapy achieves 5-year bladder intact survival of 40 to 65% and 5-year overall survival of 40 to 50% with excellent quality of life. This article introduces the French recommendations for radiotherapy of bladder cancer: indications, exams, technique, dosimetry, delivery and image guidance.

  13. Combination treatment with transarterial chemoembolization, radiotherapy, and hyperthermia (CERT) for hepatocellular carcinoma with portal vein tumor thrombosis: Final results of a prospective phase II trial

    PubMed Central

    Yu, Jeong Il; Park, Hee Chul; Jung, Sang Hoon; Choi, Changhoon; Shin, Sung Wook; Cho, Sung Ki; Sinn, Dong Hyun; Paik, Yong-Han; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Yoo, Byung Chul; Sahinbas, Hüseyin; Paik, Seung Woon

    2017-01-01

    Background & Aims This study was designed to evaluate the efficacy and safety of combination transarterial chemoembolization (TACE) followed by radiotherapy (RT) and hyperthermia (CERT) in hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Methods This single-institution, single-arm, prospective phase II study was performed from October 2013 to February 2016. The objective response rate (ORR) was evaluated at 3 months after CERT completion, and overall ORR was the primary end point. Results During the study period, 69 of 77 patients who consented to participate underwent at least one session of hyperthermia and RT. More than half of the patients (39, 56.5%) complained of severe hyperthermia-related pain. The overall ORR was 43.5% (30/69), and the ORR of the RT target area was 69.6% (48/69). Liver function status was not significantly affected by CERT. Overall survival, local progression-free survival, and progression-free survival of all enrolled patients at 2 years was 62.9%, 47.6%, and 14.3%, respectively. Conclusions An overall ORR of 43.5% was observed after CERT, but a promising ORR of 69.6% was achieved in the RT target area. Toxicities related to CERT were manageable, and pain intolerance to hyperthermia was the main obstacle to treatment maintenance. PMID:28881759

  14. Preparation and Evaluation of Radiolabeled Antibody Recruiting Small Molecules That Target Prostate-Specific Membrane Antigen for Combined Radiotherapy and Immunotherapy.

    PubMed

    Genady, Afaf R; Janzen, Nancy; Banevicius, Laura; El-Gamal, Mahmoud; El-Zaria, Mohamed E; Valliant, John F

    2016-03-24

    The feasibility of developing a single agent that can deliver radioactive iodine and also direct cellular immune function by engaging endogenous antibodies as an antibody-recruiting small molecule (ARM) was determined. A library of new prostate-specific membrane antigen (PSMA)-binding ligands that contained antibody-recruiting 2,4-dinitrophenyl (DNP) groups and iodine were synthesized and screened in vitro and in vivo. A lead compound (9b) showed high affinity for PSMA and the ability to bind anti-DNP antibodies. Biodistribution studies of the iodine-125 analogue showed 3% ID/g in LNCaP xenograft tumors at 1 h postinjection with tumor-to-blood and tumor-to-muscle ratios of 10:1 and 44:1, respectively. The radiolabeled analogue was bound and internalized by LNCaP cells, with both functions blocked using a known PSMA inhibitor. A second candidate showed high tumor uptake (>10% ID/g) but had minimal binding to anti-DNP antibodies. The compounds reported represent the first examples of small molecules developed specifically for combination immunotherapy and radiotherapy for prostate cancer.

  15. Combination treatment with transarterial chemoembolization, radiotherapy, and hyperthermia (CERT) for hepatocellular carcinoma with portal vein tumor thrombosis: Final results of a prospective phase II trial.

    PubMed

    Yu, Jeong Il; Park, Hee Chul; Jung, Sang Hoon; Choi, Changhoon; Shin, Sung Wook; Cho, Sung Ki; Sinn, Dong Hyun; Paik, Yong-Han; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Yoo, Byung Chul; Sahinbas, Hüseyin; Paik, Seung Woon

    2017-08-08

    This study was designed to evaluate the efficacy and safety of combination transarterial chemoembolization (TACE) followed by radiotherapy (RT) and hyperthermia (CERT) in hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). This single-institution, single-arm, prospective phase II study was performed from October 2013 to February 2016. The objective response rate (ORR) was evaluated at 3 months after CERT completion, and overall ORR was the primary end point. During the study period, 69 of 77 patients who consented to participate underwent at least one session of hyperthermia and RT. More than half of the patients (39, 56.5%) complained of severe hyperthermia-related pain. The overall ORR was 43.5% (30/69), and the ORR of the RT target area was 69.6% (48/69). Liver function status was not significantly affected by CERT. Overall survival, local progression-free survival, and progression-free survival of all enrolled patients at 2 years was 62.9%, 47.6%, and 14.3%, respectively. An overall ORR of 43.5% was observed after CERT, but a promising ORR of 69.6% was achieved in the RT target area. Toxicities related to CERT were manageable, and pain intolerance to hyperthermia was the main obstacle to treatment maintenance.

  16. Effect of combined treatment with salvage radiotherapy plus androgen suppression on quality of life in patients with recurrent prostate cancer after radical prostatectomy

    SciTech Connect

    Pearce, Andrew; Choo, Richard . E-mail: choo.c@mayo.edu; Danjoux, Cyril; Morton, Gerard; Loblaw, D. Andrew; Szumacher, Ewa; Cheung, Patrick; Deboer, Gerrit; Chander, Sarat

    2006-05-01

    Purpose: To examine the effect of salvage radiotherapy (RT) plus 2-year androgen suppression (AS) on quality of life (QOL). Methods and Materials: A total of 74 patients with biopsy-proven local recurrence or PSA relapse after radical prostatectomy were treated with salvage RT plus 2-year AS, as per a phase II study. Quality of life was prospectively assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-Item Version 3.0 with the added prostate cancer-specific module at baseline and predefined follow-up visits. Results: Patients experienced a significant increase in bowel dysfunction (23%) by the end of RT (p < 0.0001). This bowel dysfunction improved after RT but remained slightly elevated (5-10%) throughout the 2-year AS period. This extent of residual bowel dysfunction would be considered of minimal clinical importance. A similar, but less pronounced, pattern of change did occur for urinary dysfunction. Erectile function showed no change during RT, but had an abrupt decline (10%) with initiation of AS that was of moderate clinical significance (p < 0.01). None of the other QOL domains demonstrated a persistent, significant change from baseline that would be considered of major clinical significance. Conclusion: The combined treatment with salvage RT plus 2-year AS had relatively minor long-term effects on QOL.

  17. Neoadjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: Defining high-risk patients who may benefit before concurrent chemotherapy combined with intensity-modulated radiotherapy

    PubMed Central

    Du, Xiao-Jing; Tang, Ling-Long; Chen, Lei; Mao, Yan-Ping; Guo, Rui; Liu, Xu; Sun, Ying; Zeng, Mu-Sheng; Kang, Tie-Bang; Shao, Jian-Yong; Lin, Ai-Hua; Ma, Jun

    2015-01-01

    The purpose of this study was to create a prognostic model for distant metastasis in patients with locally advanced NPC who accept concurrent chemotherapy combined with intensity-modulated radiotherapy (CCRT) to identify high-risk patients who may benefit from neoadjuvant chemotherapy (NACT). A total of 881 patients with newly-diagnosed, non-disseminated, biopsy-proven locoregionally advanced NPC were retrospectively reviewed; 411 (46.7%) accepted CCRT and 470 (53.3%) accepted NACT followed by CCRT. Multivariate analysis demonstrated N2–3 disease, plasma Epstein–Barr virus (EBV) DNA > 4000 copies/mL, serum albumin ≤46 g/L and platelet count >300 k/cc were independent prognostic factors for distant metastasis in the CCRT group. Using these four factors, a prognostic model was developed, as follows: 1) low-risk group: 0–1 risk factors; and 2) high-risk group: 2–4 risk factors. In the high-risk group, patients who accepted NACT + CCRT had significantly higher distant metastasis-free survival and progression-free survival rates than the CCRT group (P = 0.001; P = 0.011). This simple prognostic model for distant metastasis in locoregionally advanced NPC may facilitate with the selection of high-risk patients who may benefit from NACT prior to CCRT. PMID:26564805

  18. Triptolide Combined with Radiotherapy for the Treatment of Nasopharyngeal Carcinoma via NF-κB-Related Mechanism

    PubMed Central

    Zhang, Weiying; Kang, Min; Zhang, Tingting; Li, Bo; Liao, Xueyin; Wang, Rensheng

    2016-01-01

    Advanced nasopharyngeal carcinoma (NPC) has a poor prognosis because of the lack of an effective treatment. Here we explored the efficiency and the molecular mechanisms of combined treatment with triptolide and ionizing radiation for treating NPC. Human nasopharyngeal carcinoma (CNE) cells were treated with triptolide, ionizing radiation, or triptolide plus ionizing radiation in vitro. Tumor potency was examined in an in vivo CNE cell xenograft mouse model, which was treated as above. Our results demonstrated that triptolide caused a significant reduction in cell growth and colony number, and induced a marked apoptosis that was further enhanced with increasing doses of ionizing radiation. Combination treatment synergistically reduced tumor weight and volume without obvious toxicity. Western blot analysis in vitro and in vivo showed that triptolide induced apoptotic protein Bax expression and inhibited phosph-NF-κB p65, Bcl-2 and VEGF proteins without affecting other NF-κB related protein expression. In conclusion, our findings revealed that triptolide plus ionizing radiation had synergistic anti-tumor and anti-angiogenesis effects in NPC via down-regulating NF-κB p65 phosphorylation. The combination therapy may provide novel mechanism insights into inhibit NPC. PMID:27999372

  19. Accuracy Verification of Respiratory-gated Radiotherapy that Combines the Respiration-Monitoring Device and Respiratory-gated System.

    PubMed

    Shintani, Naoya; Monzen, Hajime; Tamura, Masaya; Asai, Yoshiyuki; Shimomura, Kouhei; Matsumoto, Kenji; Okumura, Masahiko; Nishimura, Yasumasa

    The purpose of this study is to evaluate the mechanical accuracy of a respiratory-gated radiation system that combines the Linear Indicator-equipped Abches respiration-monitoring device and the Varian Real-time Position Management system (LI-RPM system). This combined configuration, implemented for the first time in Japan, was compared with the stand-alone Varian RPM system (RPM system). The delay times, dose profiles, and output waveforms of the LI-RPM and RPM systems were evaluated using a self-produced dynamic phantom. The delay times for the LI-RPM and RPM systems were both 0.1 s for 4 s and 8 s test periods. The corresponding output waveform correlation factors (R(2)) for the 4 s and 8 s test periods were 0.9981 and 0.9975, respectively. No difference was observed in the dose profiles of the two systems. Thus, the present results indicate that the proposed LI-RPM combined respiratory-gated radiation system has similar properties to the RPM system. However, it offers several advantages in terms of its versatility, including its alignment assistance capabilities for non-coplanar treatments.

  20. Preoperative intensity-modulated radiotherapy with a simultaneous integrated boost combined with Capecitabine in locally advanced rectal cancer: short-term results of a multicentric study.

    PubMed

    Lupattelli, Marco; Matrone, Fabio; Gambacorta, Maria Antonietta; Osti, Mattia; Macchia, Gabriella; Palazzari, Elisa; Nicosia, Luca; Navarria, Federico; Chiloiro, Giuditta; Valentini, Vincenzo; Aristei, Cynthia; De Paoli, Antonino

    2017-08-22

    Preoperative radiotherapy (RT) in combination with fluoropyrimidine-based chemotherapy (CT) is the standard of care in patients with locally advanced, T3-T4 N0-2, rectal cancer (LARC). Given the correlation between RT dose-tumor response and the prognostic role of the tumor regression grade (TRG), treatment intensification represents an area of active investigation. The aim of the study was to analyze the role of RT dose-intensification in the preoperative treatment of LARC in terms of feasibility, efficacy and toxicity. We retrospectively analyzed patients with LARC treated with intensity-modulated radiotherapy (IMRT) and simultaneous integrated boost (SIB) at five Italian radiation oncology centers. Concurrent Capecitabine was administered. Treatment response was evaluated in terms of disease down-staging and TRG. Acute toxicity was evaluated according to the CTC-AE 4.0 scale. A total of 76 patients were identified for this analysis. A dose of 45 Gy was prescribed to the entire mesorectum and pelvic lymph nodes with a median SIB dose of 54 Gy (range 52.5-57.5) to the tumor and corresponding mesorectum. Overall, 74/76 (97.4%) patients completed the planned RT, whereas 64/76 (84.2%) patients completed the prescribed CT. Eight (10.5%) patients developed grade 3-4 acute toxicity. Overall, 72/76 patients underwent surgery. The tumor and nodal down-staging was documented in 51 (70.8%) and 43 (67%) patients, respectively. Twenty (27.8%) patients obtained a pathologic complete response. Surgical morbidity was reported in 13/72 patients (18.1%). Although retrospective in design, this study indicates that IMRT-SIB with a dose range of 52.5-57.5 Gy (median 54 Gy) and concomitant Capecitabine appears feasible, well tolerated and effective in terms of disease down-staging and pathological complete response. Long-term toxicity and the impact on disease control and patient survival will be evaluated with a longer follow-up time. NA.

  1. Side-effects of post-treatment biopsies in prostate cancer patients treated with endocrine therapy alone or combined with radical radiotherapy in the Scandinavian Prostate Cancer Group-7 randomized trial.

    PubMed

    Solberg, Arne; Widmark, Anders; Tasdemir, Ilker; Ahlgren, Göran; Angelsen, Anders

    2011-09-01

    Post-treatment prostate biopsy side-effects were evaluated in patients with locally advanced prostate cancer on endocrine therapy alone or combined with radiotherapy in the Scandinavian Prostate Cancer Group-7 randomized trial. One-hundred and twenty patients underwent transrectalultrasound-guided biopsy, and were requested to complete a questionnaire on side-effects occurring within 7 days' follow-up. The questionnaire was returned by 109 patients (91%) (endocrine therapy only 52%, combined endocrine therapy and radiotherapy 48%). Previous therapy had no significant influence on pain, urinary flow, haematuria or haematospermia. Pain at biopsy was reported in 63% (mild, 57%; moderate, 5.6%; severe, one patient) and pain at follow-up in 31% (mild, 27%; moderate, four patients). Haematuria (mean duration 2.2 days) was reported in 41%, and reduced urinary flow in 20% (mild, 18%; severe: four patients; no patient had urinary retention). Haematospermia was scarce. No patient reported urinary tract infection. Rectal bleeding occurred in 18% in the endocrine and 35% in the combined therapy group (p = 0.047), with a mean duration of 1.6 and 2.2 days, respectively (p = 0.031). In logistic regression analysis, a trend towards increased rectal bleeding was found in patients on combined endocrine therapy and radiotherapy (odds ratio 2.4, p = 0.050). Patient-reported post-treatment prostate biopsy side-effects were mild and self-limiting.

  2. Epidermal Growth Factor Receptor Expression Modulates Antitumor Efficacy of Vandetanib or Cediranib Combined With Radiotherapy in Human Glioblastoma Xenografts

    SciTech Connect

    Wachsberger, Phyllis R.; Lawrence, Yaacov R.; Liu Yi; Daroczi, Borbala; Xu Xia; Dicker, Adam P.

    2012-01-01

    Purpose: The purpose of this study was to determine the ability of radiation therapy (RT) combined with the tyrosine kinase inhibitors (TKI) vandetanib (antiepidermal growth factor receptor [EGFR] plus antivascular endothelial growth factor receptor [anti-VEGFR]) and cediranib (anti-VEGFR) to inhibit glioblastoma multiforme (GBM) growth. A secondary aim was to investigate how this regimen is modulated by tumor EGFR expression. Methods and Materials: Radiosensitivity was assessed by clonogenic cell survival assay. VEGF secretion was quantified by enzyme-linked immunosorbent assay. GBM (U87MG wild-type EGFR [wtEGFR] and U87MG EGFR-null) xenografts were treated with vandetanib, cediranib, and RT, alone or in combinations. Excised tumor sections were stained for proliferative and survival biomarkers. Results: In vitro, U87MG wtEGFR and U87 EGFR-null cells had similar growth kinetics. Neither TKI affected clonogenic cell survival following RT. However, in vivo, exogenous overexpression of wtEGFR decreased tumor doubling time (T2x) in U87MG xenografts (2.70 vs. 4.41 days for U87MG wtEGFR vs. U87MG vector, respectively). In U87MG EGFR-null cells, TKI combined with radiation was no better than radiation therapy alone. In U87MG wtEGFR, RT in combination with vandetanib (but not with cediranib) significantly increased tumor T2x compared with RT alone (T2x, 10.4 days vs. 4.8 days; p < 0.001). In vivo, growth delay correlated with suppression of pAkt, survivin, and Ki67 expression in tumor samples. The presence of EGFR augmented RT-stimulated VEGF release; this effect was inhibited by vandetanib. Conclusions: EGFR expression promoted tumor growth in vivo but not in vitro, suggesting a microenvironmental effect. GBM xenografts expressing EGFR exhibited greater sensitivity to both cediranib and vandetanib than EGFR-null tumors. Hence EGFR status plays a major role in determining a tumor's in vivo response to radiation combined with TKI, supporting a 'personalized' approach to

  3. Assessing intraoperative blood flow in cardiovascular surgery.

    PubMed

    Yamamoto, Masaki; Sasaguri, Shiro; Sato, Takayuki

    2011-11-01

    Off-pump coronary arterial bypass grafting and new surgical apparatus and techniques have decreased the mortality rate associated with this procedure to approximately 1.5%. If we could detect problems in the constructed coronary anastomoses by an alternative imaging system to coronary angiography during surgery, decisions to revise the surgical procedure could be made without hesitation. Meanwhile, the intraoperative direct evaluation of intestinal blood flow during abdominal aortic aneurysmal surgery is required to prevent ischemic colitis, which is a devastating complication. Indocyanine green (ICG) has recently improved ophthalmic angiography and the navigation systems of oncological surgery. The fluorescence illumination of ICG with a near-infrared light is captured on camera. In coronary arterial surgery, the ICG imaging system is also becoming increasingly useful. A new ICG imaging system, the HyperEye Medical System (HEMS), provides a clear view of the blood flow and ischemic area with color visualization. Furthermore, its combination with a quantitative blood flow assessment tool such as transit time flow measurement could improve the accuracy of intraoperative examination. In this review, we evaluate the current strategies of assessing blood flow intraoperatively with an ICG imaging system in cardiovascular surgery.

  4. Clinical outcome of protocol based image (MRI) guided adaptive brachytherapy combined with 3D conformal radiotherapy with or without chemotherapy in patients with locally advanced cervical cancer

    PubMed Central

    Pötter, Richard; Georg, Petra; Dimopoulos, Johannes C.A.; Grimm, Magdalena; Berger, Daniel; Nesvacil, Nicole; Georg, Dietmar; Schmid, Maximilian P.; Reinthaller, Alexander; Sturdza, Alina; Kirisits, Christian

    2011-01-01

    Background To analyse the overall clinical outcome and benefits by applying protocol based image guided adaptive brachytherapy combined with 3D conformal external beam radiotherapy (EBRT) ± chemotherapy (ChT). Methods Treatment schedule was EBRT with 45–50.4 Gy ± concomitant cisplatin chemotherapy plus 4 × 7 Gy High Dose Rate (HDR) brachytherapy. Patients were treated in the “protocol period” (2001–2008) with the prospective application of the High Risk CTV concept (D90) and dose volume constraints for organs at risk including biological modelling. Dose volume adaptation was performed with the aim of dose escalation in large tumours (prescribed D90 > 85 Gy), often with inserting additional interstitial needles. Dose volume constraints (D2cc) were 70–75 Gy for rectum and sigmoid and 90 Gy for bladder. Late morbidity was prospectively scored, using LENT/SOMA Score. Disease outcome and treatment related late morbidity were evaluated and compared using actuarial analysis. Findings One hundred and fifty-six consecutive patients (median age 58 years) with cervix cancer FIGO stages IB–IVA were treated with definitive radiotherapy in curative intent. Histology was squamous cell cancer in 134 patients (86%), tumour size was >5 cm in 103 patients (66%), lymph node involvement in 75 patients (48%). Median follow-up was 42 months for all patients. Interstitial techniques were used in addition to intracavitary brachytherapy in 69/156 (44%) patients. Total prescribed mean dose (D90) was 93 ± 13 Gy, D2cc 86 ± 17 Gy for bladder, 65 ± 9 Gy for rectum and 64 ± 9 Gy for sigmoid. Complete remission was achieved in 151/156 patients (97%). Overall local control at 3 years was 95%; 98% for tumours 2–5 cm, and 92% for tumours >5 cm (p = 0.04), 100% for IB, 96% for IIB, 86% for IIIB. Cancer specific survival at 3 years was overall 74%, 83% for tumours 2–5 cm, 70% for tumours >5 cm, 83% for IB, 84% for IIB, 52% for IIIB. Overall

  5. Combination of external beam radiotherapy and Californium (Cf)-252 neutron intracavity brachytherapy is more effective in control of cervical squamous cell carcinoma than that of cervical adenocarcinoma.

    PubMed

    Xiong, Yanli; Liu, Jia; Chen, Shu; Zhou, Qian; Xu, Wenjing; Tang, Chen; Chen, Yonghong; Yang, Mei; Lei, Xin

    2015-09-01

    The objective of this study was to compare the effect of combined external beam radiotherapy (EBRT) and Californium (Cf)-252 neutron intracavity brachytherapy (ICBT) on cervical squamous versus adenocarcinoma. A total of 106 patients with stage IB-IIIB cervical cancer were accrued between January 2005 and May 2011 and divided into squamous cell carcinoma (SCC) and adenocarcinoma (AC) as a pair with 53 patients in each group according to tumor size, stage, age, and hemoglobin level using matched-pair design. The whole pelvic EBRT was performed with 2 Gy/fraction, 4 fractions/week. The total dose was 48-54 Gy (the center of whole pelvic field was blocked by 4 cm in width after 20-36 Gy). Cf-252 neutron ICBT was delivered with 11 and 12 Gy-eq/f with the total dose at point A of 44 and 48 Gy-eq for SCC and AC patients, respectively. The mean follow-up time was 43 months. The 5-year LC, OS, DFS, LAC rates, and mean survival time were 66.0, 56.6, 52.8.0, 17.0%, and 76.4 ± 6.2 months, respectively, for AC patients, whereas they were 81.1, 69.8, 67.9, 11.3%, and 93.3 ± 4.3 months, respectively, for SCC patients. Furthermore, the early treatment toxicity was mild in both groups, the late treatment complications were mainly radiation-induced proctitis and cystitis, and there were no grade 3 or higher complications. Although the combination of Cf-252 neutron ICBT and EBRT was effective in both histology types of cervical cancer, a more aggressive strategy is needed to control cervical AC.

  6. Californium versus cobalt brachytherapy combined with external-beam radiotherapy for IIB stage cervical cancer: long-term experience of a single institute

    PubMed Central

    Janulionis, Ernestas; Valuckas, Konstantinas Povilas; Samerdokiene, Vitalija; Atkocius, Vydmantas

    2015-01-01

    Purpose The purpose of this paper was to observe and compare long-term curative effects and complications of FIGO stage IIB cervical cancer patients (n = 232) treated with high-dose-rate (HDR) californium (252Cf) neutron or cobalt (60Co) photon intracavitary brachytherapy (ICBT) combined with external-beam radiotherapy (EBRT). Material and methods The EBRT dose to the small pelvis was 50 Gy in both groups. The brachytherapy component of 252Cf or 60Co was added in the 3rd week of EBRT, 5 fractions were performed once per week resulting in a total ICBT dose of 40 Gy/Gyeq (point A). Results Overall survival (OS) at 5, 10 and 15 years was 63.6%, 50.4% and 38.8% in the 252Cf group and 62.2%, 50.5%, 39.9%, in the 60Co group, respectively (p = 0.74). The percentage of tumour recurrence was statistically significantly lower in the 252Cf group with 7.4% versus 17.1% in the 60Co group (p = 0.02). Second primary cancers have developed similarly 9.1% and 8.1% cases for 252Cf and 60Co groups, respectively. Conclusions Our long-term retrospective study comparing 252Cf and 60Co isotopes with brachytherapy in combined treatment of FIGO IIB stage cervix carcinoma patients shows, that overall survival in the both groups are similar. However, the recurrence of tumour was significantly lower in the 252Cf group. The incidence of second primary cancers was similar in both groups. PMID:26622239

  7. Californium versus cobalt brachytherapy combined with external-beam radiotherapy for IIB stage cervical cancer: long-term experience of a single institute.

    PubMed

    Janulionis, Ernestas; Valuckas, Konstantinas Povilas; Liukpetryte, Sarune; Samerdokiene, Vitalija; Atkocius, Vydmantas

    2015-10-01

    The purpose of this paper was to observe and compare long-term curative effects and complications of FIGO stage IIB cervical cancer patients (n = 232) treated with high-dose-rate (HDR) californium ((252)Cf) neutron or cobalt ((60)Co) photon intracavitary brachytherapy (ICBT) combined with external-beam radiotherapy (EBRT). The EBRT dose to the small pelvis was 50 Gy in both groups. The brachytherapy component of (252)Cf or (60)Co was added in the 3(rd) week of EBRT, 5 fractions were performed once per week resulting in a total ICBT dose of 40 Gy/Gyeq (point A). Overall survival (OS) at 5, 10 and 15 years was 63.6%, 50.4% and 38.8% in the (252)Cf group and 62.2%, 50.5%, 39.9%, in the (60)Co group, respectively (p = 0.74). The percentage of tumour recurrence was statistically significantly lower in the (252)Cf group with 7.4% versus 17.1% in the (60)Co group (p = 0.02). Second primary cancers have developed similarly 9.1% and 8.1% cases for (252)Cf and (60)Co groups, respectively. Our long-term retrospective study comparing (252)Cf and (60)Co isotopes with brachytherapy in combined treatment of FIGO IIB stage cervix carcinoma patients shows, that overall survival in the both groups are similar. However, the recurrence of tumour was significantly lower in the (252)Cf group. The incidence of second primary cancers was similar in both groups.

  8. Phase II Study of Weekly Intravenous Oxaliplatin Combined With Oral Daily Capecitabine and Radiotherapy With Biologic Correlates in Neoadjuvant Treatment of Rectal Adenocarcinoma

    SciTech Connect

    Fakih, Marwan G. BullardDunn, Kelli; Yang, Gary Y.; Pendyala, Lakshmi; Toth, Karoly; Andrews, Chris; Rustum, Youcef M.; Ross, Mary Ellen; LeVea, Charles; Puthillath, Ajithkumar; Park, Young-Mee; Rajput, Ashwani

    2008-11-01

    Purpose: To evaluate the efficacy of a combination of capecitabine, oxaliplatin, and radiotherapy (RT) in the neoadjuvant treatment of Stage II and III rectal cancers. Methods: Capecitabine was given at 725 mg/m{sup 2} orally twice daily Monday through Friday concurrently with RT. Oxaliplatin was given intravenously at 50 mg/m{sup 2} once weekly five times starting the first day of RT. The radiation dose was 50.4 Gy in 28 fractions (1.8 Gy/fraction), five fractions weekly. Endorectal tumor biopsies were obtained before treatment and on the third day of treatment to explore the effects of treatment on thymidine phosphorylase, thymidylate synthase, excision repair cross-complementing rodent repair deficiency complementation group 1 (ERCC1), and apoptosis. Results: A total of 25 patients were enrolled in this study; 6 patients (24%) had a complete pathologic response. T-downstaging occurred in 52% of patients, and N-downstaging occurred in 53%. Grade 3 diarrhea was the most common Grade 3-4 toxicity, occurring in 20% of patients. Only 2 patients experienced disease recurrence, with a median of 20 months of follow-up. Thymidylate synthase, thymidine phosphorylase, ERCC1, and apoptosis did not vary significantly between the pretreatment and Day 3 tumor biopsies, nor did they predict for T-downstaging or a complete pathologic response. Conclusion: Capecitabine at 725 mg/m{sup 2} orally twice daily, oxaliplatin 50 mg/m{sup 2}/wk, and RT at 50.4 Gy is an effective neoadjuvant combination for Stage II and III rectal cancer and results in a greater rate of complete pathologic responses than historically shown in fluoropyrimidine plus RT controls.

  9. Combining multiple FDG-PET radiotherapy target segmentation methods to reduce the effect of variable performance of individual segmentation methods

    PubMed Central

    McGurk, Ross J.; Bowsher, James; Lee, John A; Das, Shiva K.

    2013-01-01

    Purpose: Many approaches have been proposed to segment high uptake objects in 18F-fluoro-deoxy-glucose positron emission tomography images but none provides consistent performance across the large variety of imaging situations. This study investigates the use of two methods of combining individual segmentation methods to reduce the impact of inconsistent performance of the individual methods: simple majority voting and probabilistic estimation. Methods: The National Electrical Manufacturers Association image quality phantom containing five glass spheres with diameters 13–37 mm and two irregularly shaped volumes (16 and 32 cc) formed by deforming high-density polyethylene bottles in a hot water bath were filled with 18-fluoro-deoxyglucose and iodine contrast agent. Repeated 5-min positron emission tomography (PET) images were acquired at 4:1 and 8:1 object-to-background contrasts for spherical objects and 4.5:1 and 9:1 for irregular objects. Five individual methods were used to segment each object: 40% thresholding, adaptive thresholding, k-means clustering, seeded region-growing, and a gradient based method. Volumes were combined using a majority vote (MJV) or Simultaneous Truth And Performance Level Estimate (STAPLE) method. Accuracy of segmentations relative to CT ground truth volumes were assessed using the Dice similarity coefficient (DSC) and the symmetric mean absolute surface distances (SMASDs). Results: MJV had median DSC values of 0.886 and 0.875; and SMASD of 0.52 and 0.71 mm for spheres and irregular shapes, respectively. STAPLE provided similar results with median DSC of 0.886 and 0.871; and median SMASD of 0.50 and 0.72 mm for spheres and irregular shapes, respectively. STAPLE had significantly higher DSC and lower SMASD values than MJV for spheres (DSC, p < 0.0001; SMASD, p = 0.0101) but MJV had significantly higher DSC and lower SMASD values compared to STAPLE for irregular shapes (DSC, p < 0.0001; SMASD, p = 0.0027). DSC was not significantly

  10. Denoising techniques combined to Monte Carlo simulations for the prediction of high-resolution portal images in radiotherapy treatment verification

    NASA Astrophysics Data System (ADS)

    Lazaro, D.; Barat, E.; Le Loirec, C.; Dautremer, T.; Montagu, T.; Guérin, L.; Batalla, A.

    2013-05-01

    This work investigates the possibility of combining Monte Carlo (MC) simulations to a denoising algorithm for the accurate prediction of images acquired using amorphous silicon (a-Si) electronic portal imaging devices (EPIDs). An accurate MC model of the Siemens OptiVue1000 EPID was first developed using the penelope code, integrating a non-uniform backscatter modelling. Two already existing denoising algorithms were then applied on simulated portal images, namely the iterative reduction of noise (IRON) method and the locally adaptive Savitzky-Golay (LASG) method. A third denoising method, based on a nonparametric Bayesian framework and called DPGLM (for Dirichlet process generalized linear model) was also developed. Performances of the IRON, LASG and DPGLM methods, in terms of smoothing capabilities and computation time, were compared for portal images computed for different values of the RMS pixel noise (up to 10%) in three different configurations, a heterogeneous phantom irradiated by a non-conformal 15 × 15 cm2 field, a conformal beam from a pelvis treatment plan, and an IMRT beam from a prostate treatment plan. For all configurations, DPGLM outperforms both IRON and LASG by providing better smoothing performances and demonstrating a better robustness with respect to noise. Additionally, no parameter tuning is required by DPGLM, which makes the denoising step very generic and easy to handle for any portal image. Concerning the computation time, the denoising of 1024 × 1024 images takes about 1 h 30 min, 2 h and 5 min using DPGLM, IRON, and LASG, respectively. This paper shows the feasibility to predict within a few hours and with the same resolution as real images accurate portal images, combining MC simulations with the DPGLM denoising algorithm.

  11. Radiotherapy and local control in rectal cancer.

    PubMed

    Valentini, V; Rosetto, M E; Fares, C; Mantini, G; Salvi, G; Turriziani, A

    1998-01-01

    Recurrence is a stage in the natural history of rectal cancer. Preoperative radiotherapy or postoperative radiochemotherapy lower the rate of recurrence, improving local control. From 1980 to 1997, at the "Divisione di Radioterapia" of the "Università Cattolica del S. Cuore" of Rome 380 patients with rectal cancer of early clinical stage T2-3, candidates for surgery for cure, underwent radiation therapy. 119 patients underwent postoperative radiotherapy (45-50 Gy); 45 patients underwent "sandwich" radiotherapy (45 Gy:27 Gy before and 28 Gy after surgery), of whom 7 were treated with preoperative radiotherapy alone; 145 patients underwent preoperative concomitant radiochemotherapy according to 3 different protocols, radiotherapy (38 Gy) combined with mitomycin C and 5-FU; radiotherapy (50.4 Gy) combined with cisplatin and 5-FU; radiotherapy (45 Gy) combined with 5-FU and folinic acid. 71 patients were treated with preoperative radiotherapy (38 Gy) combined with IORT (10 Gy). Median follow-up was 6 years. Overall local control was 85% at 3 years, 83% at 5 years, 81% at 10 years. The rate of local control at 5 years was: 76% for postoperative radiotherapy, 83% for "sandwich" radiotherapy, 84% for preoperative radiochemotherapy and 93% for preoperative radiotherapy combined with IORT. Local control was shown to be significantly better with preoperative treatment as compared to postoperative treatment (p = 0.02). The incidence of metastases was 35% in the patients with local recurrence and 16% in those with local control. The difference in survival was highly significant in patients with local control as compared to those with local recurrence: at 5 years 87% and 32% respectively. Patients with local control showed a lower incidence of metastasis and a better survival.

  12. Dual Protective and Cytotoxic Benefits of Mesenchymal Stem Cell Therapy in Combination with Chemotherapy/Radiotherapy for Cancer Patients.

    PubMed

    Hendijani, Fatemeh; Javanmard, Shaghayegh Haghjooy

    2015-01-01

    Cancer is a major health problem in the world, and scientists seek innovative treatment strategies with higher efficacy and lower toxicity than the existing therapeutic agents. In this way, stem cell researchers try to reveal new pathways that will eventually benefit patients. Stem cell research has proven that mesenchymal stem cells (MSCs) possess anticancer activities, and their protein-rich secretome showed similar effects. MSCs also secrete cytokines that play an active role in healing and regeneration processes. Because of their known plasticity, MSCs display a variety of characteristics and functions in different environments, depending on their interactions with various cell types and tissues. Therefore, we hypothesize that MSC therapy in combination with anticancer medicines can potentiate cytotoxic effects on cancer cells. In addition, because of their regenerative capacity, MSCs can protect normal tissues from adverse cytotoxic drug reactions. They may also help rescue injured tissues from these toxic damages or systemic pathological events that occur during cancer treatment. MSC therapy may double the beneficial effects on cancer and normal cells. As our knowledge of systems biology and biotechnological methodology is progressing, this idea can move forward as a treatment option.

  13. [Intraoperative neuromonitoring in thyroid surgery].

    PubMed

    Motos-Micó, José Jacob; Felices-Montes, Manuel; Abad-Aguilar, Teresa

    Intraoperative neuromonitoring of the recurrent laryngeal nerve in thyroid surgery facilitates the identification of anatomical structures in cervical endocrine surgery reducing the frequency of vocal cord paralysis. To study the normal electrophysiological values of the vague and recurrent laryngeal nerves before and after thyroid surgery. To compare rates of injury of recurrent nerve before and after the introduction of the intraoperative neuromonitoring in thyroid surgery. An observational, descriptive and prospective study in which a total of 490 patients were included. Between 2003-2010, surgery was performed on 411 patients (703 nerves at risk) with systematic identification of recurrent laryngeal nerves. Between 2010-2011 neuromonitorization was also systematically performed on 79 patients. Before the introduction of intraoperative neuromonitoring of 704 nerves at risk, there were 14 recurrent laryngeal nerve injuries. Since 2010, after the introduction of the intraoperative neuromonitoring in thyroid surgery, there has been no nerve injury in 135 nerves at risk. We consider the systematic identification of the recurrent laryngeal nerve is the 'gold standard' in thyroid surgery and the intraoperative neuromonitoring of nerves can never replace surgery but can complement it. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  14. Perspectives in Intraoperative Diagnostics of Human Gliomas

    PubMed Central

    Tyurikova, O.; Dembitskaya, Y.; Yashin, K.; Mishchenko, M.; Vedunova, M.; Medyanik, I.; Kazantsev, V.

    2015-01-01

    Amongst large a variety of oncological diseases, malignant gliomas represent one of the most severe types of tumors. They are also the most common type of the brain tumors and account for over half of the astrocytic tumors. According to different sources, the average life expectancy of patients with various glioblastomas varies between 10 and 12 months and that of patients with anaplastic astrocytic tumors between 20 and 24 months. Therefore, studies of the physiology of transformed glial cells are critical for the development of treatment methods. Modern medical approaches offer complex procedures, including the microsurgical tumor removal, radiotherapy, and chemotherapy, supplemented with photodynamic therapy and immunotherapy. The most radical of them is surgical resection, which allows removing the largest part of the tumor, reduces the intracranial hypertension, and minimizes the degree of neurological deficit. However, complete removal of the tumor remains impossible. The main limitations are insufficient visualization of glioma boundaries, due to its infiltrative growth, and the necessity to preserve healthy tissue. This review is devoted to the description of advantages and disadvantages of modern intraoperative diagnostics of human gliomas and highlights potential perspectives for development of their treatment. PMID:26543495

  15. In vivo virtual intraoperative surgical photoacoustic microscopy

    SciTech Connect

    Han, Seunghoon Kim, Sehui Kim, Jeehyun E-mail: chulhong@postech.edu; Lee, Changho Jeon, Mansik; Kim, Chulhong E-mail: chulhong@postech.edu

    2013-11-11

    We developed a virtual intraoperative surgical photoacoustic microscopy system by combining with a commercial surgical microscope and photoacoustic microscope (PAM). By sharing the common optical path in the microscope and PAM system, we could acquire the PAM and microscope images simultaneously. Moreover, by employing a beam projector to back-project 2D PAM images onto the microscope view plane as augmented reality, the conventional microscopic and 2D cross-sectional PAM images are concurrently mapped on the plane via an ocular lens of the microscope in real-time. Further, we guided needle insertion into phantom ex vivo and mice skins in vivo.

  16. In vivo virtual intraoperative surgical photoacoustic microscopy

    NASA Astrophysics Data System (ADS)

    Han, Seunghoon; Lee, Changho; Kim, Sehui; Jeon, Mansik; Kim, Jeehyun; Kim, Chulhong

    2013-11-01

    We developed a virtual intraoperative surgical photoacoustic microscopy system by combining with a commercial surgical microscope and photoacoustic microscope (PAM). By sharing the common optical path in the microscope and PAM system, we could acquire the PAM and microscope images simultaneously. Moreover, by employing a beam projector to back-project 2D PAM images onto the microscope view plane as augmented reality, the conventional microscopic and 2D cross-sectional PAM images are concurrently mapped on the plane via an ocular lens of the microscope in real-time. Further, we guided needle insertion into phantom ex vivo and mice skins in vivo.

  17. Dosimetric Benefits of Intensity-Modulated Radiotherapy Combined With the Deep-Inspiration Breath-Hold Technique in Patients With Mediastinal Hodgkin's Lymphoma

    SciTech Connect

    Paumier, Amaury; Ghalibafian, Mithra; Gilmore, Jennifer; Beaudre, Anne; Blanchard, Pierre; El Nemr, Mohammed; Azoury, Farez; Al Hamokles, Hweej; Lefkopoulos, Dimitri; Girinsky, Theodore

    2012-03-15

    Purpose: To assess the additional benefits of using the deep-inspiration breath-hold (DIBH) technique with intensity-modulated radiotherapy (IMRT) in terms of the protection of organs at risk for patients with mediastinal Hodgkin's disease. Methods and Materials: Patients with early-stage Hodgkin's lymphoma with mediastinal involvement were entered into the study. Two simulation computed tomography scans were performed for each patient: one using the free-breathing (FB) technique and the other using the DIBH technique with a dedicated spirometer. The clinical target volume, planning target volume (PTV), and organs at risk were determined on both computed tomography scans according to the guidelines of the European Organization for Research and Treatment of Cancer. In both cases, 30 Gy in 15 fractions was prescribed. The dosimetric parameters retrieved for the statistical analysis were PTV coverage, mean heart dose, mean coronary artery dose, mean lung dose, and lung V20. Results: There were no significant differences in PTV coverage between the two techniques (FB vs. DIBH). The mean doses delivered to the coronary arteries, heart, and lungs were significantly reduced by 15% to 20% using DIBH compared with FB, and the lung V20 was reduced by almost one third. The dose reduction to organs at risk was greater for masses in the upper part of the mediastinum. IMRT with DIBH was partially implemented in 1 patient. This combination will be extended to other patients in the near future. Conclusions: Radiation exposure of the coronary arteries, heart, and lungs in patients with mediastinal Hodgkin's lymphoma was greatly reduced using DIBH with IMRT. The greatest benefit was obtained for tumors in the upper part of the mediastinum. The possibility of a wider use in clinical practice is currently under investigation in our department.

  18. Bowel sparing in pediatric cranio-spinal radiotherapy: a comparison of combined electron and photon and helical TomoTherapy techniques to a standard photon method

    SciTech Connect

    Harron, Elizabeth; Lewis, Joanne

    2012-07-01

    The aim of this study was to compare the dose to organs at risk (OARs) from different craniospinal radiotherapy treatment approaches available at the Northern Centre for Cancer Care (NCCC), with a particular emphasis on sparing the bowel. Method: Treatment plans were produced for a pediatric medulloblastoma patient with inflammatory bowel disease using 3D conformal 6-MV photons (3DCP), combined 3D 6-MV photons and 18-MeV electrons (3DPE), and helical photon TomoTherapy (HT). The 3DPE plan was a modification of the standard 3DCP technique, using electrons to treat the spine inferior to the level of the diaphragm. The plans were compared in terms of the dose-volume data to OARs and the nontumor integral dose. Results: The 3DPE plan was found to give the lowest dose to the bowel and the lowest nontumor integral dose of the 3 techniques. However, the coverage of the spine planning target volume (PTV) was least homogeneous using this technique, with only 74.6% of the PTV covered by 95% of the prescribed dose. HT was able to achieve the best coverage of the PTVs (99.0% of the whole-brain PTV and 93.1% of the spine PTV received 95% of the prescribed dose), but delivered a significantly higher integral dose. HT was able to spare the heart, thyroid, and eyes better than the linac-based techniques, but other OARs received a higher dose. Conclusions: Use of electrons was the best method for reducing the dose to the bowel and the integral dose, at the expense of compromised spine PTV coverage. For some patients, HT may be a viable method of improving dose homogeneity and reducing selected OAR doses.

  19. [Intraoperative navigation, with focus on the skull base].

    PubMed

    Wirtz, C R

    2016-09-01

    Intraoperative navigation systems are widely used in ENT, oral and maxillofacial, and neurosurgery. The benefits of such systems have been demonstrated in various applications, including intracranial and skull base surgery. Intraoperative shift, "brain shift" and changes in anatomy caused by the surgical procedure itself impair the accuracy of navigation and represent factors limiting its application, particularly in glioma and metastatic brain surgery. For this reason, intraoperative imaging was incorporated into neurosurgery. A specific application of navigation is thus skull base surgery, where shifts are often negligible due to the bony structures in which pathologies are embedded. Development of new systems with seamless integration into the operative workflow propagated routine use of navigation in neuro- and ENT surgery. Navigation proved especially helpful in interdisciplinary surgery with pathologies located in anatomic regions where competences of different surgical disciplines overlap, as in the skull base. While this increased radicality in tumour resection, there was a high risk of morbidity. The integration of electrophysiological function monitoring served to preserve function and reduce morbidity, and has led to less invasive and radical strategies in skull base surgery. New radiosurgical methods to adjuvantly treat possible tumour remnants have also supported this development. Systems allowing resection borders to be marked in the navigational coordinates would enable direct linking of these data to radiotherapy planning and better interpretation of follow-up imaging. Navigation is thus a valuable tool supporting interdisciplinary cooperation in skull base surgery for the benefit of patients.

  20. [The role of intraoperative ultrasonography].

    PubMed

    Matsushita, Yoko; Okayama, Yukinari; Matsuo, Shuji

    2008-06-01

    Intraoperative ultrasonography (US) is able to visualize the inside of the viscera in real time, and is also both noninvasive and simple to perform without influence of the bone or alimentary canal gas disturbing the propagation of the ultrasound. US has recently been widely used for neurosurgery or abdominal surgery, 1) to check the position and size of the tumor, which can not be directly visualized, and to evaluate the relationship between the tumor and blood vessel or tissue, 2) to search for lesions not detected before surgery, 3) to search for residual tumor, 4) to carry out ultrasound-guided biopsy or puncture. For effective intraoperative US, thorough knowledge of the US instrument and the local anatomy is necessary. The medical technologists who routinely perform US are qualified to assist with intraoperative US.

  1. Intraoperative fracture of phacoemulsification tip.

    PubMed

    Angmo, Dewang; Khokhar, Sudarshan K; Ganguly, Anasua

    2014-01-01

    Phacoemulsification (phaco) is an established procedure for cataract extraction and has undergone a significant advances in techniques, machines and phaco tips. The Aspiration Bypass System (ABS) phaco tip was introduced for phacoemulsification in 1998. The ABS tip allows fluid to be drawn through the opening when the phaco tip is occluded by nuclear material. The ABS tip allowed the safe use of high vacuum and flow rates and improved chamber stability by decreasing surge and therefore reducing intraoperative complications. To date, no disadvantages of ABS tips have been reported. We report a unique case of an intraoperative break of an ABS phaco tip during routine cataract surgery.

  2. Intraoperative Fracture of Phacoemulsification Tip

    PubMed Central

    Angmo, Dewang; Khokhar, Sudarshan K.; Ganguly, Anasua

    2014-01-01

    Phacoemulsification (phaco) is an established procedure for cataract extraction and has undergone a significant advances in techniques, machines and phaco tips. The Aspiration Bypass System (ABS) phaco tip was introduced for phacoemulsification in 1998. The ABS tip allows fluid to be drawn through the opening when the phaco tip is occluded by nuclear material. The ABS tip allowed the safe use of high vacuum and flow rates and improved chamber stability by decreasing surge and therefore reducing intraoperative complications. To date, no disadvantages of ABS tips have been reported. We report a unique case of an intraoperative break of an ABS phaco tip during routine cataract surgery. PMID:24669153

  3. Critical role of bevacizumab scheduling in combination with pre-surgical chemo-radiotherapy in MRI-defined high-risk locally advanced rectal cancer: results of the branch trial

    PubMed Central

    Avallone, Antonio; Pecori, Biagio; Bianco, Franco; Aloj, Luigi; Tatangelo, Fabiana; Romano, Carmela; Granata, Vincenza; Marone, Pietro; Leone, Alessandra; Botti, Gerardo; Petrillo, Antonella; Caracò, Corradina; Iaffaioli, Vincenzo R.; Muto, Paolo; Romano, Giovanni; Comella, Pasquale; Budillon, Alfredo; Delrio, Paolo

    2015-01-01

    Background We have previously shown that an intensified preoperative regimen including oxaliplatin plus raltitrexed and 5-fluorouracil/folinic acid (OXATOM/FUFA) during preoperative pelvic radiotherapy produced promising results in locally advanced rectal cancer (LARC). Preclinical evidence suggests that the scheduling of bevacizumab may be crucial to optimize its combination with chemo-radiotherapy. Patients and methods This non-randomized, non-comparative, phase II study was conducted in MRI-defined high-risk LARC. Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemo-radiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A) or 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B). Primary end point was pathological complete tumor regression (TRG1) rate. Results The accrual for the concomitant-schedule was early terminated because the number of TRG1 (2 out of 16 patients) was statistically inconsistent with the hypothesis of activity (30%) to be tested. Conversely, the endpoint was reached with the sequential-schedule and the final TRG1 rate among 46 enrolled patients was 50% (95% CI 35%–65%). Neutropenia was the most common grade ≥3 toxicity with both schedules, but it was less pronounced with the sequential than concomitant-schedule (30% vs. 44%). Postoperative complications occurred in 8/15 (53%) and 13/46 (28%) patients in schedule A and B, respectively. At 5 year follow-up the probability of PFS and OS was 80% (95%CI, 66%–89%) and 85% (95%CI, 69%–93%), respectively, for the sequential-schedule. Conclusions These results highlights the relevance of bevacizumab scheduling to optimize its combination with preoperative chemo-radiotherapy in the management of LARC. PMID:26320185

  4. Real-time 3D internal marker tracking during arc radiotherapy by the use of combined MV-kV imaging.

    PubMed

    Liu, W; Wiersma, R D; Mao, W; Luxton, G; Xing, L

    2008-12-21

    To minimize the adverse dosimetric effect caused by tumor motion, it is desirable to have real-time knowledge of the tumor position throughout the beam delivery process. A promising technique to realize the real-time image guided scheme in external beam radiation therapy is through the combined use of MV and onboard kV beam imaging. The success of this MV-kV triangulation approach for fixed-gantry radiation therapy has been demonstrated. With the increasing acceptance of modern arc radiotherapy in the clinics, a timely and clinically important question is whether the image guidance strategy can be extended to arc therapy to provide the urgently needed real-time tumor motion information. While conceptually feasible, there are a number of theoretical and practical issues specific to the arc delivery that need to be resolved before clinical implementation. The purpose of this work is to establish a robust procedure of system calibration for combined MV and kV imaging for internal marker tracking during arc delivery and to demonstrate the feasibility and accuracy of the technique. A commercially available LINAC equipped with an onboard kV imager and electronic portal imaging device (EPID) was used for the study. A custom built phantom with multiple ball bearings was used to calibrate the stereoscopic MV-kV imaging system to provide the transformation parameters from imaging pixels to 3D world coordinates. The accuracy of the fiducial tracking system was examined using a 4D motion phantom capable of moving in accordance with a pre-programmed trajectory. Overall, spatial accuracy of MV-kV fiducial tracking during the arc delivery process for normal adult breathing amplitude and period was found to be better than 1 mm. For fast motion, the results depended on the imaging frame rates. The RMS error ranged from approximately 0.5 mm for the normal adult breathing pattern to approximately 1.5 mm for more extreme cases with a low imaging frame rate of 3.4 Hz. In general

  5. Real-time 3D internal marker tracking during arc radiotherapy by the use of combined MV kV imaging

    NASA Astrophysics Data System (ADS)

    Liu, W.; Wiersma, R. D.; Mao, W.; Luxton, G.; Xing, L.

    2008-12-01

    To minimize the adverse dosimetric effect caused by tumor motion, it is desirable to have real-time knowledge of the tumor position throughout the beam delivery process. A promising technique to realize the real-time image guided scheme in external beam radiation therapy is through the combined use of MV and onboard kV beam imaging. The success of this MV-kV triangulation approach for fixed-gantry radiation therapy has been demonstrated. With the increasing acceptance of modern arc radiotherapy in the clinics, a timely and clinically important question is whether the image guidance strategy can be extended to arc therapy to provide the urgently needed real-time tumor motion information. While conceptually feasible, there are a number of theoretical and practical issues specific to the arc delivery that need to be resolved before clinical implementation. The purpose of this work is to establish a robust procedure of system calibration for combined MV and kV imaging for internal marker tracking during arc delivery and to demonstrate the feasibility and accuracy of the technique. A commercially available LINAC equipped with an onboard kV imager and electronic portal imaging device (EPID) was used for the study. A custom built phantom with multiple ball bearings was used to calibrate the stereoscopic MV-kV imaging system to provide the transformation parameters from imaging pixels to 3D world coordinates. The accuracy of the fiducial tracking system was examined using a 4D motion phantom capable of moving in accordance with a pre-programmed trajectory. Overall, spatial accuracy of MV-kV fiducial tracking during the arc delivery process for normal adult breathing amplitude and period was found to be better than 1 mm. For fast motion, the results depended on the imaging frame rates. The RMS error ranged from ~0.5 mm for the normal adult breathing pattern to ~1.5 mm for more extreme cases with a low imaging frame rate of 3.4 Hz. In general, highly accurate real

  6. [Water-filtered infrared-A-hyperthermia combined with radiotherapy in advanced and recurrent tumors. Initial results of a multicenter phase I-II study].

    PubMed

    Seegenschmiedt, M H; Klautke, G; Walther, E; Feldmann, H J; Katalinic, A; Stuschke, M; von Lieven, H; Vaupel, P

    1996-09-01

    Water-filtered infrared-A-radiation (IR/A-HT) can be used to heat superficial malignant tumors. A prospective multicenter phase I-II study was conducted to evaluate toxicity and efficacy of IR/A-HT combined with external beam radiotherapy (RT). From December 1991 to June 1994, a total of 53 patients with 58 malignant lesions were entered in the study. There were 14 primary, 36 recurrent and 8 metastatic tumors which were located in the head and neck region (14), chest wall (31), abdominal wall (2) and the extremities (11). The mean tumor volume was 100 cm3. IR/A-HT was applied 1 to 2 times per week with up to 3 IR/A-HT-radiators directly before or after external RT for 1 hour at 40.5 to 44 degrees C. Temperatures were controlled at various locations at the skin surface and invasively at depth. IR/A-HT was well tolerated: in 31 (53%) lesions acute (pain, pulse or blood pressure changes, increased skin reaction etc.) and in 25 (43%) chronic side-effects (atrophy, telangiectasis, fibrosis etc.) were noted; usually the toxicity was minor and temporary. At 3 months FU, 32 (55%) lesions achieved a local CR and 19 (35%) a PR; at 12 months FU, 25 (43%) had persistent CR; 16 patients (18 lesions) were deceased and 3 (4 lesions) not yet in FU. In univariate analysis the following prognostic factors for CR at 3 or 12 months FU were found: Karnofsky, metastatic status, tumor size, total RT-dose, thermal parameters T min(av) and T mean. For acute toxicity maximum temperature Tmax(av) was prognostically decisive. Significant differences were also found when considering the "quality of the HT-application". The microwave technique was superior to the infrared-A-HT-technique with regard to the penetration depth of energy deposition. Water-filtered infrared-A-radiation can be safely and effectively applied to heat localized superficial tumors (up to 1 cm depth). To increase the area of HT application multiple infrared-A-radiators have to be combined. A multi-element-system is in

  7. Long-term results for Stage IIIB cervical cancer patients receiving external beam radiotherapy combined with either HDR (252)Cf or HDR (60)Co intracavitary brachytherapy.

    PubMed

    Ulinskas, K; Janulionis, E; Valuckas, K P; Samerdokiene, V; Atkocius, V; Rivard, M J

    2016-01-01

    The aim of this work was to compare the long-term curative effects and complications of patients diagnosed with cervical cancer International Federation of Gynecology and Obstetrics IIIB (n = 430) as treated with Californium-252 ((252)Cf) or cobalt-60 ((60)Co) intracavitary brachytherapy (ICBT) combined with external beam radiotherapy (EBRT). Cervical cancer cases with a history of treatment with (252)Cf or (60)Co ICBT combined with EBRT were selected from the Lithuanian National Cancer Institute database. Complications and second primary malignancies were compared in both patients groups. Estimates of the 5-, 10-, and 15-year overall survival and disease-free survival rates were computed with the Kaplan-Meier method and a Cox proportional hazards model applied using STATA software. At 5, 10, and 15 years, the overall survival rates were 46.9%, 39.3%, and 34.6% for the (252)Cf group and 35.4%, 26.9%, and 22.5% for the (60)Co group (p = 0.004), respectively. The disease-free survival rates were 42.1%, 35.0%, and 31.0% for the (252)Cf group and 32.0%, 25.1%, and 21.4% for the (60)Co group (p = 0.009), respectively. Histopathologic type of adenocarcinoma increased the risk of death for the (252)Cf group (hazard ratio 3.62). Histopathologic tumor type (hazard ratio 7.48) and recurrence (hazard ratio 2.83) were factors that statistically and significantly influenced the patient prognosis for the (60)Co group. Applying (252)Cf ICBT with EBRT was effective for International Federation of Gynecology and Obstetrics IIIB cervical cancer patients. Moreover, long-term followup data demonstrated higher survival rates in patients treated with (252)Cf ICBT than (60)Co ICBT. Complications in patients treated with neutron ICBT were not more frequent or severe than those treated with (60)Co ICBT. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  8. Comorbidity as a predictor of overall survival in prostate cancer patients treated with external beam radiotherapy combined with HDR brachytherapy boosts.

    PubMed

    Hjälm-Eriksson, Marie; Ullén, Anders; Johansson, Hemming; Levitt, Seymoure; Nilsson, Sten; Kälkner, Karl-Mikael

    2017-01-01

    The risk stratification currently applied prior to curative treatment for localized prostate cancer (PC) does not take into account comorbidity or age. Therefore, we investigated the impact of comorbidity on overall survival (OS) in PC patients treated with external beam radiotherapy (EBRT) and high-dose rate (HDR) brachytherapy boost. At a single center, 611 consecutive patients diagnosed with localized PC from 1998 to 2004 underwent definitive EBRT (50 Gy) and HDR brachytherapy boosts (2 × 10 Gy) combined with neoadjuvant total androgen blockade. Comorbidity was assessed with the Charlson comorbidity score. The impact of risk factors on OS and disease-free survival (DFS) was calculated using Cox proportional hazard ratios. Risk groups were defined as follows: low-risk PC: PSA <10, WHO grade 1 and T stage 1; high-risk PC: PSA >20 and/or WHO grade 3 and/or T stage 3a; intermediate-risk PC representing patients who did not fit either the low- or high-risk PC group. Mean age in the study cohort was 66.4 years, and 51% of the patients reported some degree of comorbidity. Divided into risk groups 8.2% were categorized as low-risk, 64% as intermediate-risk and 27.8% as high-risk PC. Overall 10-year survival was 72.2%, and 89% of the patients were relapse-free. In the univariate and multivariate analyses using Cox proportional hazard ratios, age, comorbidity and T stage were statistically significant predictors of OS: hazard ratios 1.56, 1.44 and 1.2 (p-values .002, .04 and .05), respectively. WHO grade, PSA at diagnosis, T stage and comorbidity were also significant predictors of DFS (p-values .0001, .0001, .009 and .003, respectively). Comorbidity assessed with the Charlson score predicts OS in patients with localized PC treated with curative intent using combined EBRT and HDR brachytherapy boost, and should be considered when making decisions before radical treatment.

  9. [Intraoperative staging of colorectal tumors].

    PubMed

    Abdurakhmonov, Iu B; Mel'nikov, O R; Egorenkov, V V; Moiseenko, V M

    2007-01-01

    The effectiveness of intraoperative staging of tumor by sentinel node staining with lymphotropic dyes was evaluated in 60 patients with colorectal tumors (colon carcinoma -39, rectal cancer- 21). High sensitivity (84.6% and 87.5%, respectively) and specificity (100% and 100%, respectively) for regional lymph node assessment were identified for both colonic and rectal cancer.

  10. Intraoperative transfusion practices in Europe

    PubMed Central

    Meier, J.; Filipescu, D.; Kozek-Langenecker, S.; Llau Pitarch, J.; Mallett, S.; Martus, P.; Matot, I.

    2016-01-01

    Background. Transfusion of allogeneic blood influences outcome after surgery. Despite widespread availability of transfusion guidelines, transfusion practices might vary among physicians, departments, hospitals and countries. Our aim was to determine the amount of packed red blood cells (pRBC) and blood products transfused intraoperatively, and to describe factors determining transfusion throughout Europe. Methods. We did a prospective observational cohort study enrolling 5803 patients in 126 European centres that received at least one pRBC unit intraoperatively, during a continuous three month period in 2013. Results. The overall intraoperative transfusion rate was 1.8%; 59% of transfusions were at least partially initiated as a result of a physiological transfusion trigger- mostly because of hypotension (55.4%) and/or tachycardia (30.7%). Haemoglobin (Hb)- based transfusion trigger alone initiated only 8.5% of transfusions. The Hb concentration [mean (sd)] just before transfusion was 8.1 (1.7) g dl−1 and increased to 9.8 (1.8) g dl−1 after transfusion. The mean number of intraoperatively transfused pRBC units was 2.5 (2.7) units (median 2). Conclusion. Although European Society of Anaesthesiology transfusion guidelines are moderately implemented in Europe with respect to Hb threshold for transfusion (7–9 g dl−1), there is still an urgent need for further educational efforts that focus on the number of pRBC units to be transfused at this threshold. Clinical trial registration. NCT 01604083. PMID:26787795

  11. Intraoperative Radiation Therapy in Resected Pancreatic Carcinoma: Long-Term Analysis

    SciTech Connect

    Valentini, Vincenzo; Morganti, Alessio G.; Macchia, Gabriella Mantini, Giovanna; Mattiucci, Gian C.; Brizi, M. Gabriella; Alfieri, Sergio; Bossola, Maurizio; Pacelli, Fabio; Sofo, Luigi; Doglietto, Giovanbattista; Cellini, Numa

    2008-03-15

    Purpose: The combination of external radiotherapy (RT) plus intraoperative radiotherapy (IORT) in patients with pancreatic cancer is still debated. This study presents long-term results (minimum follow-up, 102 months) for 26 patients undergoing integrated adjuvant RT (external RT + IORT). Methods and Materials: From 1990 to 1995, a total of 17 patients with pancreatic cancer underwent IORT (10 Gy) and postoperative external RT (50.4 Gy). Preoperative 'flash' RT was included for the last 9 patients. The liver and pancreatic head received 5 Gy (two 2.5-Gy fractions) the day before surgery. In the subsequent period (1996-1998), 9 patients underwent preoperative concomitant chemoradiation (39.6 Gy) with 5-fluorouracil, IORT (10 Gy), and adjuvant chemotherapy. Results: Preoperative chemoradiation was completed in all patients, whereas postoperative therapy was completed in 13 of 17 patients. All 26 patients underwent pancreatectomy (25 R0 and one R1 resections). One patient died of postoperative complications (3.8%) not related to IORT. The 9 patients undergoing concomitant chemoradiation were candidates for adjuvant chemotherapy; however, only 4 of 9 underwent adjuvant chemotherapy. At last follow-up, 4 patients (15.4%) were alive and disease free. Disease recurrence was documented in 20 patients (76.9%). Sixteen patients (61.5%) showed distant metastasis, and 5 patients (19.2%) showed local recurrence. The incidence of local recurrence in R0 patients was 4 of 25 (16.0%). The overall 5-year survival rate was 15.4%. There was significant correlation with overall survival of tumor diameter (p = 0.019). Conclusions: The incidence of local recurrence in this long follow-up series (19.2%) was definitely less than that reported in other studies of adjuvant RT ({approx}50%), suggesting a positive impact on local control of integrated adjuvant RT (IORT + external RT)

  12. Survival outcomes of combined external beam radiotherapy and brachytherapy vs. brachytherapy alone for intermediate-risk prostate cancer patients using the National Cancer Data Base.

    PubMed

    Amini, Arya; Jones, Bernard L; Jackson, Matthew W; Rusthoven, Chad G; Maroni, Paul; Kavanagh, Brian D; Raben, David

    2016-01-01

    The purpose was to evaluate survival outcomes between external beam radiotherapy (EBRT) plus brachytherapy and brachytherapy alone for intermediate-risk prostate cancer, using the National Cancer Data Base. The National Cancer Data Base was queried for cN0M0 intermediate-risk patients treated from 2004 to 2006, with available data for Gleason score (GS), prostate-specific antigen (PSA), tumor stage, and receipt of radiation therapy (RT) and androgen deprivation therapy. RT comparison groups were the following: EBRT (40-50.4 Gy) plus brachytherapy and brachytherapy alone. A total of 10,571 patients were included: 3,148 received EBRT plus brachytherapy and 7,423 received brachytherapy alone. Median followup was 84 months (2-122 months); median age was 68 years (40-90 years). Unadjusted 5- and 7-year overall survival (OS) rates between EBRT plus brachytherapy vs. brachytherapy alone were 91.4% vs. 90.2% and 85.7% vs. 82.9%, respectively (p < 0.001). EBRT plus brachytherapy was associated with longer OS compared with brachytherapy alone under multivariate (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.75-0.93; p = 0.001) and propensity score-matched analyses (HR, 0.85; 95% CI, 0.75-0.97; p = 0.006). Further subset analysis performed based on the Radiation Therapy Oncology Group 0232 inclusion criteria (GS 7 if PSA < 10 or GS < 7 if PSA 10-20) also demonstrated longer OS with EBRT plus brachytherapy (HR, 0.87; 95% CI, 0.77-0.98; p = 0.026). EBRT plus brachytherapy is associated with a modest OS improvement compared with brachytherapy alone in this population-based analysis. Although this benefit appears statistically significant, the relatively small difference in OS raises the question of overall clinical benefit with combined modality RT for intermediate-risk prostate cancer, given the potential increased risk for toxicities. Future results from Radiation Therapy Oncology Group 0232 should provide further insight on this topic. Copyright © 2016 American

  13. SU-E-T-620: Dosimetric Compliance Study for a New Prostate Protocol of Combined High Dose Rate Brachytherapy and Stereotactic Body Radiotherapy

    SciTech Connect

    Peng, C; Giaddui, T; Den, R; Harrison, A; Yu, Y

    2014-06-15

    Purpose: To investigate the adherence of treatment plans of prostate cancer patients with the dosimetric compliance criteria of the new in house phase I trial of high dose rate (HDR) brachytherapy combined with stereotactic body radiotherapy (SBRT) for intermediate risk prostate cancer patients. Methods: Ten prostate cancer patients were treated using this trial. They received one fraction of HDR to 15Gy, followed by external beam(EB) boost of 3.2Gy(Level 1, five patients) or 3.94Gy(level 2, five patients) per fraction for 10 or 7 fractions, respectively, both equivalent to EB treatments of 113.5Gy in 2Gy fractions. The EB plans were either IMRT or VMAT plans. DVH analysis was performed to verify the adherence of treatment plans to the dosimetric criteria of the trial. Results: For Level 1 patients, target coverage were adequate, with CTV V32Gy(%) of 99.0±1.0 (mean ± 1 standard deviation), and PTV V31Gy(%) of 99.6±0.3. PTV V32.9Gy(%) is 1.4±3.1 and PTVmax is 32.9±0.2Gy. Rectum, bladder and femoral heads sparing were well within protocol criteria. For Level 2 patients, CTV V27.6Gy(%) is 98.7±1.8; PTV V26.7Gy(%) is 99.0±1.4. PTV V28.4Gy(%) is 1.3±1.4, with three patients having minor deviation from protocol. Again critical structures were spared compliant to the protocol. The analysis of HDR plans show similar results, with adequate dose coverage to the prostate and sparing of critical structures including urethra and rectum. V100(%) and V90(%) of prostate are 96.0±1.1 and 98.9±0.5. Urethra D10(%) is 113.1±2.9. Rectum V80(cc) is 1.4±0.5. Hotspot in prostate is substantially higher than what the protocol specifies. But the criteria for hotspot are only guidelines, serving to lower the dose to urethra . Conclusion: This new high biological equivalent dose prostate trial has been carried out successfully for ten patients. Based on dosimetric analysis, all HDR and external plans were compliant to the protocol criteria, with only minor deviations.

  14. Prognostic significance of 5-year PSA value for predicting prostate cancer recurrence after brachytherapy alone and combined with hormonal therapy and/or external beam radiotherapy.

    PubMed

    Stock, Richard G; Klein, Thomas J; Cesaretti, Jamie A; Stone, Nelson N

    2009-07-01

    To analyze the prognosis and outcomes of patients who remain free of biochemical failure during the first 5 years after treatment. Between 1991 and 2002, 742 patients with prostate cancer were treated with brachytherapy alone (n = 306), brachytherapy and hormonal therapy (n = 212), or combined implantation and external beam radiotherapy (with or without hormonal therapy; n = 224). These patients were free of biochemical failure (American Society for Therapeutic Radiology and Oncology [ASTRO] definition) during the first 5 post-treatment years and had a documented 5-year prostate-specific antigen (PSA) value. The median follow-up was 6.93 years. The actuarial 10-year freedom from PSA failure rate was 97% using the ASTRO definition and 95% using the Phoenix definition. The median 5-year PSA level was 0.03 ng/mL (range, 0-3.6). The 5-year PSA value was 0.01-0.10 in 31.1%, >0.10-0.2 in 10.2%, >0.2-0.5 in 7.82%, and >0.5 in 3.10%. The 5-year PSA value had prognostic significance, with a PSA value of or=0.2 ng/mL (n = 81; p < .0001). The treatment regimen had no effect on biochemical failure. None of the 742 patients in this study developed metastatic disease or died of prostate cancer. The results of this study have shown that the prognosis for patients treated with brachytherapy and who remain biochemically free of disease for >or=5 years is excellent and none developed metastatic disease during the first 10 years after treatment. The 5-year PSA value is prognostic, and patients with a PSA value <0.2 ng/mL are unlikely to develop subsequent biochemical relapse.

  15. Significant impact of biochemical recurrence on overall mortality in patients with high-risk prostate cancer after carbon-ion radiotherapy combined with androgen deprivation therapy.

    PubMed

    Kasuya, Goro; Ishikawa, Hitoshi; Tsuji, Hiroshi; Nomiya, Takuma; Makishima, Hirokazu; Kamada, Tadashi; Akakura, Koichiro; Suzuki, Hiroyoshi; Shimazaki, Jun; Haruyama, Yasuo; Kobashi, Gen; Tsujii, Hirohiko

    2016-10-15

    Whether biochemical recurrence (BR) is a significant predictive factor of mortality after definitive radiation therapy for prostate cancer remains unknown. The aim of the current study was to investigate the relation between BR and overall mortality (OAM) in high-risk prostate cancer patients who were treated with carbon-ion radiotherapy (CIRT) and had long-term follow-up in 2 prospective trials. In the 2 phase 2 clinical trials, which involved 466 prostate cancer patients who received 63.0 to 66.0 Gy of CIRT (relative biological effect) in 20 fractions between 2000 and 2007, 324 patients who were deemed to be at high risk on the basis of the modified D'Amico classification criteria and received CIRT along with androgen-deprivation therapy (ADT) were examined. The OAM rate was adjusted for the ADT duration, and multivariate analyses using a Cox proportional hazards model were performed for OAM with BR as a time-dependent covariate. The median follow-up period was 107.4 months, and the 5- and 10-year OAM rates after adjustments for the ADT duration were 7.0% (95% confidence interval [CI], 4.0%-9.4%) and 23.9% (95% CI, 16.4%-26.2%), respectively. A multivariate analysis revealed that the presence of BR (hazard ratio, 2.82; 95% Cl, 1.57-5.08; P = .001) was one of the predictive factors for OAM. On the other hand, the duration of ADT had no impact on OAM. BR after CIRT combined with ADT is an independent predictive factor for OAM in high-risk prostate cancer patients. The results of this study could be applied to other high-dose radiation therapies. Cancer 2016;122:3225-31. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2016 The

  16. Intraoperative magnetic resonance imaging during surgery for pituitary adenomas: pros and cons.

    PubMed

    Buchfelder, Michael; Schlaffer, Sven-Martin

    2012-12-01

    Surgery for pituitary adenomas still remains a mainstay in their treatment, despite all advances in sophisticated medical treatments and radiotherapy. Total tumor excision is often attempted, but there are limitations in the intraoperative assessment of the radicalism of tumor resection by the neurosurgeon. Standard postoperative imaging is usually performed with a few months delay from the surgical intervention. The purpose of this report is to review briefly the facilities and kinds of intraoperative magnetic resonance imaging for all physician and surgeons involved in the management of pituitary adenomas on the basis of current literature. To date, there are several low- and high-field magnetic resonance imaging systems available for intraoperative use and depiction of the extent of tumor removal during surgery. Recovery of vision and the morphological result of surgery can be largely predicted from the intraoperative images. A variety of studies document that depiction of residual tumor allows targeted attack of the remnant and extent the resection. Intraoperative magnetic resonance imaging offers an immediate feedback to the surgeon and is a perfect quality control for pituitary surgery. It is also used as a basis of datasets for intraoperative navigation which is particularly useful in any kind of anatomical variations and repeat operations in which primary surgery has distorted the normal anatomy. However, setting up the technology is expensive and some systems even require extensive remodeling of the operation theatre. Intraoperative imaging prolongs the operation, but may also depict evolving problems, such as hematomas in the tumor cavity. There are several artifacts in intraoperative MR images possible that must be considered. The procedures are not associated with an increased complication rate.

  17. Robust endoscopic pose estimation for intraoperative organ-mosaicking

    NASA Astrophysics Data System (ADS)

    Reichard, Daniel; Bodenstedt, Sebastian; Suwelack, Stefan; Wagner, Martin; Kenngott, Hannes; Müller-Stich, Beat Peter; Dillmann, Rüdiger; Speidel, Stefanie

    2016-03-01

    The number of minimally invasive procedures is growing every year. These procedures are highly complex and very demanding for the surgeons. It is therefore important to provide intraoperative assistance to alleviate these difficulties. For most computer-assistance systems, like visualizing target structures with augmented reality, a registration step is required to map preoperative data (e.g. CT images) to the ongoing intraoperative scene. Without additional hardware, the (stereo-) endoscope is the prime intraoperative data source and with it, stereo reconstruction methods can be used to obtain 3D models from target structures. To link reconstructed parts from different frames (mosaicking), the endoscope movement has to be known. In this paper, we present a camera tracking method that uses dense depth and feature registration which are combined with a Kalman Filter scheme. It provides a robust position estimation that shows promising results in ex vivo and in silico experiments.

  18. [Postoperative radiotherapy of prostate cancer].

    PubMed

    Guérif, S; Latorzeff, I; Lagrange, J-L; Hennequin, C; Supiot, S; Garcia, A; François, P; Soulié, M; Richaud, P; Salomon, L

    2014-10-01

    Between 10 and 40% of patients who have undergone a radical prostatectomy may have a biologic recurrence. Local or distant failure represents the possible patterns of relapse. Patients at high-risk for local relapse have extraprostatic disease, positive surgical margins or seminal vesicles infiltration or high Gleason score at pathology. Three phase-III randomized clinical trials have shown that, for these patients, adjuvant irradiation reduces the risk of tumoral progression without higher toxicity. Salvage radiotherapy for late relapse allows a disease control in 60-70% of the cases. Several research in order to improve the therapeutic ratio of the radiotherapy after prostatectomy are evaluate in the French Groupe d'Étude des Tumeurs Urogénitales (Gétug) and of the French association of urology (Afu). The Gétug-Afu 17 trial will provide answers to the question of the optimal moment for postoperative radiotherapy for pT3-4 R1 pN0 Nx patients, with the objective of comparing an immediate treatment to a differed early treatment initiated at biological recurrence. The Gétug-Afu 22 questions the place of a short hormonetherapy combined with image-guided, intensity-modulated radiotherapy (IMRT) in adjuvant situation for a detectable prostate specific antigen (PSA). The implementation of a multicenter quality control within the Gétug-Afu in order to harmonize a modern postoperative radiotherapy will allow the development of a dose escalation IMRT after surgery.

  19. [Combined concomitant chemotherapy and radiotherapy with or without surgery in the treatment of non-metastatic squamous carcinoma of the esophagus].

    PubMed

    Isla, M D; Sáenz, A; Tres, A; Escudero, P; Jara, C; Escó, R; González, M

    1993-12-01

    Between June 1986 and October 1992 two prospective non-randomized and consecutive therapeutic schemes with a curative intent of non-metastatic squamous cell carcinoma of the esophagus were developed. The first scheme consisted of concomitant administration of chemotherapy (cisplatin and 5-fluorouracil, 2 cycles) and radiotherapy (30 Gys) after surgery (esophagectomy) (14 evaluable patients). Without surgery, a higher dose of chemotherapy (4 cycles) and radiotherapy (55 Gys) was given on the second scheme (12 evaluable patients). Complete histological response was 42.6% for the first scheme and 50% for the second one. Toxicity was moderate in both schemes. Palliation was important in the second scheme. Actuarial survival was 28% at 1 year for the first scheme and 71% for the second one. Operative mortality was 27%. Concomitant chemoradiotherapy might be a therapeutic choice for locoregional control of squamous esophageal carcinoma.

  20. Intraoperative transfusion practices in Europe.

    PubMed

    Meier, J; Filipescu, D; Kozek-Langenecker, S; Llau Pitarch, J; Mallett, S; Martus, P; Matot, I

    2016-02-01

    Transfusion of allogeneic blood influences outcome after surgery. Despite widespread availability of transfusion guidelines, transfusion practices might vary among physicians, departments, hospitals and countries. Our aim was to determine the amount of packed red blood cells (pRBC) and blood products transfused intraoperatively, and to describe factors determining transfusion throughout Europe. We did a prospective observational cohort study enrolling 5803 patients in 126 European centres that received at least one pRBC unit intraoperatively, during a continuous three month period in 2013. The overall intraoperative transfusion rate was 1.8%; 59% of transfusions were at least partially initiated as a result of a physiological transfusion trigger- mostly because of hypotension (55.4%) and/or tachycardia (30.7%). Haemoglobin (Hb)- based transfusion trigger alone initiated only 8.5% of transfusions. The Hb concentration [mean (sd)] just before transfusion was 8.1 (1.7) g dl(-1) and increased to 9.8 (1.8) g dl(-1) after transfusion. The mean number of intraoperatively transfused pRBC units was 2.5 (2.7) units (median 2). Although European Society of Anaesthesiology transfusion guidelines are moderately implemented in Europe with respect to Hb threshold for transfusion (7-9 g dl(-1)), there is still an urgent need for further educational efforts that focus on the number of pRBC units to be transfused at this threshold. NCT 01604083. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia.

  1. Surgery Combined with Radiotherapy Improved Survival in Metastatic Esophageal Cancer in a Surveillance Epidemiology and End Results Population-based Study

    PubMed Central

    Wu, San-Gang; Xie, Wei-Hao; Zhang, Zhao-Qiang; Sun, Jia-Yuan; Li, Feng-Yan; Lin, Huan-Xin; Yong Bao; He, Zhen-Yu

    2016-01-01

    This retrospective study used a population-based national registry to determine the impact of local treatment modalities on survival in patients with metastatic esophageal cancer (EC). The Surveillance Epidemiology and End Results (SEER) database was used to identify patients with metastatic EC from 1988 to 2012. A total of 9,125 patients were identified. There were 426 patients underwent primary surgery, 4,786 patients were administered radiotherapy (RT) alone, 847 patients underwent surgery plus RT, and 3,066 patients without any local treatment. Multivariate analysis results indicated that year of diagnosis, age, race, histologic subtype, grade, and local treatment modalities were independent prognostic factors for overall survival (OS). The 5-year OS were 8.4%, 4.5%, 17.5%, and 3.4% in primary surgery, RT only, surgery plus RT, and no local treatment, respectively (P < 0.001). Subgroup analyses showed that the impact of RT was mainly reflected by preoperative radiotherapy, as patients received preoperative radiotherapy had significantly better OS than patients who underwent primary surgery alone and postoperative RT, the 5-year OS rates were 24.7%, 6.5%, and 7.8%, respectively, respectively (P < 0.001). Surgery plus RT, especially preoperative RT, may improve long-term survival of patients with metastatic EC. PMID:27323696

  2. Evaluation of a combined respiratory-gating system comprising the TrueBeam linear accelerator and a new real-time tumor-tracking radiotherapy system: a preliminary study.

    PubMed

    Shiinoki, Takehiro; Kawamura, Shinji; Uehara, Takuya; Yuasa, Yuki; Fujimoto, Koya; Koike, Masahiro; Sera, Tatsuhiro; Emoto, Yuki; Hanazawa, Hideki; Shibuya, Keiko

    2016-07-01

    A combined system comprising the TrueBeam linear accelerator and a new real-time, tumor-tracking radiotherapy system, SyncTraX, was installed in our institution. The goals of this study were to assess the capability of SyncTraX in measuring the position of a fiducial marker using color fluoroscopic images, and to evaluate the dosimetric and geometric accuracy of respiratory-gated radiotherapy using this combined system for the simple geometry. For the fundamental evaluation of respiratory-gated radiotherapy using SyncTraX, the following were performed: 1) determination of dosimetric and positional characteristics of sinusoidal patterns using a motor-driven base for several gating windows; 2) measurement of time delay using an oscilloscope; 3) positional verification of sinusoidal patterns and the pattern in the case of a lung cancer patient; 4) measurement of the half-value layer (HVL in mm AL), effective kVp, and air kerma, using a solid-state detector for each fluoroscopic condition, to determine the patient dose. The dose profile in a moving phantom with gated radiotherapy having a gating window ≤4 mm was in good agreement with that under static conditions for each photon beam. The total time delay between TrueBeam and SyncTraX was <227 ms for each photon beam. The mean of the positional tracking error was <0.4 mm for sinusoidal patterns and for the pattern in the case of a lung cancer patient. The air-kerma rates from one fluoroscopy direction were 1.93±0.01, 2.86±0.01, 3.92±0.04, 5.28±0.03, and 6.60±0.05 mGy/min for 70, 80, 90, 100, and 110 kV X-ray beams at 80 mA, respectively. The combined system comprising TrueBeam and SyncTraX could track the motion of the fiducial marker and control radiation delivery with reasonable accuracy; therefore, this system provides significant dosimetric improvement. However, patient exposure dose from fluoroscopy was not clinically negligible. PACS number(s): 87.53.Bn, 87.55.km, 87.55.Qr. © 2016 The Authors.

  3. Physics-based shape matching for intraoperative image guidance

    SciTech Connect

    Suwelack, Stefan Röhl, Sebastian; Bodenstedt, Sebastian; Reichard, Daniel; Dillmann, Rüdiger; Speidel, Stefanie; Santos, Thiago dos; Maier-Hein, Lena; Wagner, Martin; Wünscher, Josephine; Kenngott, Hannes; Müller, Beat P.

    2014-11-01

    Purpose: Soft-tissue deformations can severely degrade the validity of preoperative planning data during computer assisted interventions. Intraoperative imaging such as stereo endoscopic, time-of-flight or, laser range scanner data can be used to compensate these movements. In this context, the intraoperative surface has to be matched to the preoperative model. The shape matching is especially challenging in the intraoperative setting due to noisy sensor data, only partially visible surfaces, ambiguous shape descriptors, and real-time requirements. Methods: A novel physics-based shape matching (PBSM) approach to register intraoperatively acquired surface meshes to preoperative planning data is proposed. The key idea of the method is to describe the nonrigid registration process as an electrostatic–elastic problem, where an elastic body (preoperative model) that is electrically charged slides into an oppositely charged rigid shape (intraoperative surface). It is shown that the corresponding energy functional can be efficiently solved using the finite element (FE) method. It is also demonstrated how PBSM can be combined with rigid registration schemes for robust nonrigid registration of arbitrarily aligned surfaces. Furthermore, it is shown how the approach can be combined with landmark based methods and outline its application to image guidance in laparoscopic interventions. Results: A profound analysis of the PBSM scheme based on in silico and phantom data is presented. Simulation studies on several liver models show that the approach is robust to the initial rigid registration and to parameter variations. The studies also reveal that the method achieves submillimeter registration accuracy (mean error between 0.32 and 0.46 mm). An unoptimized, single core implementation of the approach achieves near real-time performance (2 TPS, 7–19 s total registration time). It outperforms established methods in terms of speed and accuracy. Furthermore, it is shown that the

  4. Is current clinical practice modified about intraoperative breast irradiation?

    PubMed

    Massa, Michela; Franchelli, Simonetta; Panizza, Renzo; Massa, Tiberio

    2016-04-01

    After the results obtained in the two randomized clinical trial, the ELIOT trial and the TARGIT-A trial, a heated debate is going on concerning the question of applying intraoperative radiotherapy (IORT) instead of postoperative whole breast irradiation (WBI) after breast conservative treatment. Currently, many centers are applying the IORT following the strict selection criteria dictated by the working groups American Society for Radiation Oncology (ASTRO) and Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) and monitoring the oncological outcome together with radiation toxicity on breast tissue. The clinical experience of the Geneva University Hospital regarding the use of the Intrabeam system is evaluated and compared with current evidences.

  5. Is current clinical practice modified about intraoperative breast irradiation?

    PubMed Central

    Massa, Michela; Franchelli, Simonetta; Panizza, Renzo; Massa, Tiberio

    2016-01-01

    After the results obtained in the two randomized clinical trial, the ELIOT trial and the TARGIT-A trial, a heated debate is going on concerning the question of applying intraoperative radiotherapy (IORT) instead of postoperative whole breast irradiation (WBI) after breast conservative treatment. Currently, many centers are applying the IORT following the strict selection criteria dictated by the working groups American Society for Radiation Oncology (ASTRO) and Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) and monitoring the oncological outcome together with radiation toxicity on breast tissue. The clinical experience of the Geneva University Hospital regarding the use of the Intrabeam system is evaluated and compared with current evidences. PMID:27199511

  6. Bystander effects and radiotherapy.

    PubMed

    Marín, Alicia; Martín, Margarita; Liñán, Olga; Alvarenga, Felipe; López, Mario; Fernández, Laura; Büchser, David; Cerezo, Laura

    2015-01-01

    Radiation-induced bystander effects are defined as biological effects expressed after irradiation by cells whose nuclei have not been directly irradiated. These effects include DNA damage, chromosomal instability, mutation, and apoptosis. There is considerable evidence that ionizing radiation affects cells located near the site of irradiation, which respond individually and collectively as part of a large interconnected web. These bystander signals can alter the dynamic equilibrium between proliferation, apoptosis, quiescence or differentiation. The aim of this review is to examine the most important biological effects of this phenomenon with regard to areas of major interest in radiotherapy. Such aspects include radiation-induced bystander effects during the cell cycle under hypoxic conditions when administering fractionated modalities or combined radio-chemotherapy. Other relevant aspects include individual variation and genetics in toxicity of bystander factors and normal tissue collateral damage. In advanced radiotherapy techniques, such as intensity-modulated radiation therapy (IMRT), the high degree of dose conformity to the target volume reduces the dose and, therefore, the risk of complications, to normal tissues. However, significant doses can accumulate out-of-field due to photon scattering and this may impact cellular response in these regions. Protons may offer a solution to reduce out-of-field doses. The bystander effect has numerous associated phenomena, including adaptive response, genomic instability, and abscopal effects. Also, the bystander effect can influence radiation protection and oxidative stress. It is essential that we understand the mechanisms underlying the bystander effect in order to more accurately assess radiation risk and to evaluate protocols for cancer radiotherapy.

  7. Bystander effects and radiotherapy

    PubMed Central

    Marín, Alicia; Martín, Margarita; Liñán, Olga; Alvarenga, Felipe; López, Mario; Fernández, Laura; Büchser, David; Cerezo, Laura

    2014-01-01

    Radiation-induced bystander effects are defined as biological effects expressed after irradiation by cells whose nuclei have not been directly irradiated. These effects include DNA damage, chromosomal instability, mutation, and apoptosis. There is considerable evidence that ionizing radiation affects cells located near the site of irradiation, which respond individually and collectively as part of a large interconnected web. These bystander signals can alter the dynamic equilibrium between proliferation, apoptosis, quiescence or differentiation. The aim of this review is to examine the most important biological effects of this phenomenon with regard to areas of major interest in radiotherapy. Such aspects include radiation-induced bystander effects during the cell cycle under hypoxic conditions when administering fractionated modalities or combined radio-chemotherapy. Other relevant aspects include individual variation and genetics in toxicity of bystander factors and normal tissue collateral damage. In advanced radiotherapy techniques, such as intensity-modulated radiation therapy (IMRT), the high degree of dose conformity to the target volume reduces the dose and, therefore, the risk of complications, to normal tissues. However, significant doses can accumulate out-of-field due to photon scattering and this may impact cellular response in these regions. Protons may offer a solution to reduce out-of-field doses. The bystander effect has numerous associated phenomena, including adaptive response, genomic instability, and abscopal effects. Also, the bystander effect can influence radiation protection and oxidative stress. It is essential that we understand the mechanisms underlying the bystander effect in order to more accurately assess radiation risk and to evaluate protocols for cancer radiotherapy. PMID:25535579

  8. Intraoperative photodynamic therapy for larynx carcinomas

    NASA Astrophysics Data System (ADS)

    Loukatch, Erwin V.; Latyshevska, Galina; Fekeshgazi, Ishtvan V.

    1995-05-01

    We made an experimental and clinical researches to examine Intraoperative Photodynamic Therapy (IPT) as a method to prevent the recidives of tumors. In experimental researches on models with radio-inducated fibrosarcomas and Erlich carcinomas of mice the best method of IPT was worked out. The therapeutic effect was studied also on patients with laryngeal cancer. In researches on C3H mice the antirecidive effect of IPT established with local administration of methylene blue and Ar-laser. We found that IPT (He-Ne laser combined with methylene blue administration) was endured by patients with laryngeal cancers without problems. We got good results of treatment 42 patients with laryngeal cancers with middle localization during three years with using IPT method. This can show the perspectives of using this method in treatment of other ENT-oncological diseases.

  9. Intra-operative robotics: NeuroArm.

    PubMed

    Lang, Michael J; Greer, Alexander D; Sutherland, Garnette R

    2011-01-01

    This manuscript describes the development and ongoing integration of neuroArm, an image-guided MR-compatible robot. A neurosurgical robotics platform was developed, including MR-compatible manipulators, or arms, with seven degrees of freedom, a main system controller, and a human-machine interface. This system was evaluated during pre-clinical trials and subsequent clinical application, combined with intra-operative MRI, at both 1.5 and 3.0 T. An MR-compatible surgical robot was successfully developed and merged with ioMRI at both 1.5 or 3.0 T. Image-guidance accuracy and microsurgical capability were established in pre-clinical trials. Early clinical experience demonstrated feasibility and showed the importance of a master-slave configuration. Surgeon-directed manipulator control improved performance and safety. NeuroArm successfully united the precision and accuracy of robotics with the executive decision-making capability of the surgeon.

  10. Hepatic arterial infusion chemotherapy using 5-fluorouracil and systemic interferon-α for advanced hepatocellular carcinoma in combination with or without three-dimensional conformal radiotherapy to venous tumor thrombosis in hepatic vein or inferior vena cava.

    PubMed

    Murakami, Eisuke; Aikata, Hiroshi; Miyaki, Daisuke; Nagaoki, Yuko; Katamura, Yoshio; Kawaoka, Tomokazu; Takaki, Shintaro; Hiramatsu, Akira; Waki, Koji; Takahashi, Shoichi; Kimura, Tomoki; Kenjo, Masahiro; Nagata, Yasushi; Ishikawa, Masaki; Kakizawa, Hideaki; Awai, Kazuo; Chayama, Kazuaki

    2012-05-01

      We investigated the efficacy of hepatic arterial infusion chemotherapy (HAIC) using 5-fluorouracil (5-FU) and systemic interferon (IFN)-α (HAIC-5-FU/IFN) for advanced hepatocellular carcinoma (HCC) with venous tumor thrombosis (VTT) in the hepatic vein trunk (Vv2) or inferior vena cava (Vv3).   Thirty-three patients with HCC/Vv2/3 underwent HAIC with 5-FU (500 mg/body weight/day, into hepatic artery on days 1-5 on the first and second weeks) and IFN-α (recombinant IFN-α-2b 3 000 000 U or natural IFN-α 5 000 000 U, intramuscularly on days 1, 3 and 5 of each week). Three-dimensional conformal radiotherapy (3D-CRT) was used in combination with HAIC-5-FU/IFN in 14 of 33 patients to reduce VTT.   The median survival time (MST) was 7.9 months, and 1- and 2-year survival rates were 30% and 20%, respectively. Evaluation of intrahepatic response after two cycles of HAIC-5-FU/IFN showed complete response (CR) in three (9%) and partial response (PR) in seven (21%), with an objective response rate of 30%. Multivariate analysis identified reduction of VTT (P = 0.0006), size of largest tumor (P = 0.013) and intrahepatic response CR/PR (P = 0.030) as determinants of survival. CR/PR correlated significantly with tumor liver occupying rate (P = 0.016) and hepatitis C virus Ab (P = 0.010). Reduction of VTT correlated significantly with radiotherapy (P = 0.021) and platelet count (P = 0.015). Radiotherapy-related reduction in VTT significantly improved survival of 16 patients with Vv3 and non-CR/PR response of HAIC-5-FU/IFN (P = 0.028).   As for advanced HCC with VTT of Vv2/3, HAIC-5-FU/IFN responsive patients could obtain favorable survival. Despite ineffective HAIC-5-FU/IFN, the combination with effective radiotherapy to VTT might improve patients' prognosis. © 2011 The Japan Society of Hepatology.

  11. [Radiotherapy of bone metastases].

    PubMed

    Thureau, S; Vieillard, M-H; Supiot, S; Lagrange, J-L

    2016-09-01

    Radiotherapy plays a major role in palliative treatment of bone metastases. Recent developments of stereotactic radiotherapy and intensity modulated radiation therapy give the possibility to treat oligometastatic diseases. The objective of this paper is to report indications and treatment modalities of radiotherapy in these situations.

  12. Phase II Trial of Combined High-Dose-Rate Brachytherapy and External Beam Radiotherapy for Adenocarcinoma of the Prostate: Preliminary Results of RTOG 0321

    SciTech Connect

    Hsu, I-Chow; Bae, Kyounghwa; Shinohara, Katsuto; Pouliot, Jean; Purdy, James; Ibbott, Geoffrey; Speight, Joycelyn; Vigneault, Eric; Ivker, Robert M.D.; Sandler, Howard M.D.

    2010-11-01

    Purpose: To estimate the rate of late Grade 3 or greater genitourinary (GU) and gastrointestinal (GI) adverse events (AEs) after treatment with external beam radiotherapy and prostate high-dose-rate (HDR) brachytherapy. Methods and Materials: Each participating institution submitted computed tomography-based HDR brachytherapy dosimetry data electronically for credentialing and for each study patient. Patients with locally confined Stage T1c-T3b prostate cancer were eligible for the present study. All patients were treated with 45 Gy in 25 fractions using external beam radiotherapy and one HDR implant delivering 19 Gy in two fractions. All AEs were graded according to the Common Terminology Criteria for Adverse Events, version 3.0. Late GU/GI AEs were defined as those occurring >9 months from the start of the protocol treatment, in patients with {>=}18 months of potential follow-up. Results: A total of 129 patients from 14 institutions were enrolled in the present study. Of the 129 patients, 125 were eligible, and AE data were available for 112 patients at analysis. The pretreatment characteristics of the patients were as follows: Stage T1c-T2c, 91%; Stage T3a-T3b, 9%; prostate-specific antigen level {<=}10 ng/mL, 70%; prostate-specific antigen level >10 but {<=}20 ng/mL, 30%; and Gleason score 2-6, 10%; Gleason score 7, 72%; and Gleason score 8-10, 18%. At a median follow-up of 29.6 months, three acute and four late Grade 3 GU/GI AEs were reported. The estimated rate of late Grade 3-5 GU and GI AEs at 18 months was 2.56%. Conclusion: This is the first prospective, multi-institutional trial of computed tomography-based HDR brachytherapy and external beam radiotherapy. The technique and doses used in the present study resulted in acceptable levels of AEs.

  13. Intraoperative laparoscopic complications for urological cancer procedures

    PubMed Central

    Montes, Sergio Fernández-Pello; Rodríguez, Ivan Gonzalez; Ugarteburu, Rodrigo Gil; Villamil, Luis Rodríguez; Mendez, Begoña Diaz; Gil, Patricio Suarez; Madera, Javier Mosquera

    2015-01-01

    AIM: To structure the rate of intraoperative complications that requires an intraoperative or perioperative resolution. METHODS: We perform a literature review of Medline database. The research was focused on intraoperative laparoscopic procedures inside the field of urological oncology. General rate of perioperative complications in laparoscopic urologic surgery is described to be around 12.4%. Most of the manuscripts published do not make differences between pure intraoperative, intraoperative with postoperative consequences and postoperative complications. RESULTS: We expose a narrative statement of complications, possible solutions and possible preventions for most frequent retroperitoneal and pelvic laparoscopic surgery. We expose the results with the following order: retroperitoneal laparoscopic surgery (radical nephrectomy, partial nephrectomy, nephroureterectomy and adrenalectomy) and pelvic laparoscopic surgery (radical prostatectomy and radical cystectomy). CONCLUSION: Intraoperative complications vary from different series. More scheduled reports should be done in order to better understand the real rates of complications. PMID:25984519

  14. Intraoperative laparoscopic complications for urological cancer procedures.

    PubMed

    Montes, Sergio Fernández-Pello; Rodríguez, Ivan Gonzalez; Ugarteburu, Rodrigo Gil; Villamil, Luis Rodríguez; Mendez, Begoña Diaz; Gil, Patricio Suarez; Madera, Javier Mosquera

    2015-05-16

    To structure the rate of intraoperative complications that requires an intraoperative or perioperative resolution. We perform a literature review of Medline database. The research was focused on intraoperative laparoscopic procedures inside the field of urological oncology. General rate of perioperative complications in laparoscopic urologic surgery is described to be around 12.4%. Most of the manuscripts published do not make differences between pure intraoperative, intraoperative with postoperative consequences and postoperative complications. We expose a narrative statement of complications, possible solutions and possible preventions for most frequent retroperitoneal and pelvic laparoscopic surgery. We expose the results with the following order: retroperitoneal laparoscopic surgery (radical nephrectomy, partial nephrectomy, nephroureterectomy and adrenalectomy) and pelvic laparoscopic surgery (radical prostatectomy and radical cystectomy). Intraoperative complications vary from different series. More scheduled reports should be done in order to better understand the real rates of complications.

  15. Fertility impairment in radiotherapy

    PubMed Central

    Kuźba-Kryszak, Tamara; Nowikiewicz, Tomasz; Żyromska, Agnieszka

    2016-01-01

    Infertility as a result of antineoplastic therapy is becoming a very important issue due to the growing incidence of neoplastic diseases. Routinely applied antineoplastic treatments and the illness itself lead to fertility disorders. Therapeutic methods used in antineoplastic treatment may cause fertility impairment or sterilization due to permanent damage to reproductive cells. The risk of sterilization depends on the patient's sex, age during therapy, type of neoplasm, radiation dose and treatment area. It is known that chemotherapy and radiotherapy can lead to fertility impairment and the combination of these two gives an additive effect. The aim of this article is to raise the issue of infertility in these patients. It is of growing importance due to the increase in the number of children and young adults who underwent radiotherapy in the past. The progress in antineoplastic therapy improves treatment results, but at the same time requires a deeper look at existential needs of the patient. Reproductive function is an integral element of self-esteem and should be taken into account during therapy planning. PMID:27647982

  16. Infusional 5-Fluorouracil and ZD1839 (Gefitinib-Iressa) in Combination With Preoperative Radiotherapy in Patients With Locally Advanced Rectal Cancer: A Phase I and II Trial (1839IL/0092)

    SciTech Connect

    Valentini, Vincenzo; De Paoli, Antonino; Gambacorta, Maria Antonietta Mantini, Giovanna; Ratto, Carlo; Vecchio, Fabio Maria; Barbaro, Brunella; Innocente, Roberto; Rossi, Carlo; Boz, Giovanni; Barba, Maria Cristina; Frattegiani, Alessandro; Lupattelli, Marco; Doglietto, Giovan Battista

    2008-11-01

    Purpose: To report the final data of a Phase I and II study (1839IL/0092) on the combination of an anti-epidermal growth factor receptor drug (gefitinib), infusional 5-fluorouracil, and preoperative radiotherapy in locally advanced, resectable rectal cancer. Methods and Materials: Patients received 45 Gy in the posterior pelvis plus a boost of 5.4 Gy on the tumor and corresponding mesorectum. Infusional 5-fluorouracil (5-FU) and gefitinib (250 and 500 mg/day) were delivered during all radiotherapy course. An IORT boost of 10 Gy was allowed. The main endpoints of the study were to establish dose-limiting toxicity (DLT) and to evaluate the rate of pathologic response according to the tumor regression grade (TRG) Mandard score. Results: A total of 41 patients were enrolled. The DLT was not reached in the 6 patients enrolled in the dose-escalation part of the study. Of the 33 patients in the Phase II, TRG 1 was recorded in 10 patients (30.3%) and TRG 2 in 7 patients (21.2 %); overall 17 of 33 patients (51.5%) had a favorable endpoint. Overall, Grade 3+ toxicity was recorded in 16 patients (41%); these included Grade 3+ gastrointestinal toxicity in 8 patients (20.5%), Grade 3+ skin toxicity in 6 (15.3%), and Grade 3+ genitourinary toxicity in 4 (10.2%). A dose reduction of gefitinib was necessary in 24 patients (61.5%). Conclusions: Gefitinib can be associated with 5-FU-based preoperative chemoradiation at the dose of 500 mg without any life-threatening toxicity and with a high pCR (30.3%). The relevant rate of Grade 3 gastrointestinal toxicity suggests that 250 mg would be more tolerable dose in a neaoadjuvant approach with radiotherapy and infusional 5-FU.

  17. Quality of life as predictor of survival: a prospective study on patients treated with combined surgery and radiotherapy for advanced oral and oropharyngeal cancer.

    PubMed

    Oskam, Inge M; Verdonck-de Leeuw, Irma M; Aaronson, Neil K; Kuik, Dirk J; de Bree, Remco; Doornaert, Patricia; Langendijk, Johannes A; Leemans, C René

    2010-11-01

    The relation between health-related quality of life (HRQOL) and survival was investigated at baseline and 6 months in 80 patients with advanced oral or oropharyngeal cancer after microvascular reconstructive surgery and (almost all) adjuvant radiotherapy. Multivariate Cox regression analyses of overall and disease-specific survival were performed including sociodemographic (age, gender, marital status, comorbidity), and clinical (tumor stage and site, radical surgical, metastasis, radiotherapy) parameters, and HRQOL (EORTC QLQ-C30 global quality of life scale). Before treatment, younger age and having a partner were predictors of disease-specific survival; younger age predicted overall survival. At 6 months post-treatment, disease-specific and overall survival was predicted by (deterioration of) global quality of life solely. Global health-related quality of life after treatment was mainly influenced by emotional functioning. Deterioration of global quality of life after treatment is an independent predictor of survival in patients with advanced oral or oropharyngeal cancer. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  18. Intraoperative monitoring of flash visual evoked potential under general anesthesia

    PubMed Central

    Hayashi, Hironobu

    2017-01-01

    In neurosurgical procedures that may cause visual impairment in the intraoperative period, the monitoring of flash visual evoked potential (VEP) is clinically used to evaluate visual function. Patients are unconscious during surgery under general anesthesia, making flash VEP monitoring useful as it can objectively evaluate visual function. The flash stimulus input to the retina is transmitted to the optic nerve, optic chiasm, optic tract, lateral geniculate body, optic radiation (geniculocalcarine tract), and visual cortical area, and the VEP waveform is recorded from the occipital region. Intraoperative flash VEP monitoring allows detection of dysfunction arising anywhere in the optic pathway, from the retina to the visual cortex. Particularly important steps to obtain reproducible intraoperative flash VEP waveforms under general anesthesia are total intravenous anesthesia with propofol, use of retinal flash stimulation devices using high-intensity light-emitting diodes, and a combination of electroretinography to confirm that the flash stimulus has reached the retina. Relatively major postoperative visual impairment can be detected by intraoperative decreases in the flash VEP amplitude. PMID:28367282

  19. Intraoperative monitoring of flash visual evoked potential under general anesthesia.

    PubMed

    Hayashi, Hironobu; Kawaguchi, Masahiko

    2017-04-01

    In neurosurgical procedures that may cause visual impairment in the intraoperative period, the monitoring of flash visual evoked potential (VEP) is clinically used to evaluate visual function. Patients are unconscious during surgery under general anesthesia, making flash VEP monitoring useful as it can objectively evaluate visual function. The flash stimulus input to the retina is transmitted to the optic nerve, optic chiasm, optic tract, lateral geniculate body, optic radiation (geniculocalcarine tract), and visual cortical area, and the VEP waveform is recorded from the occipital region. Intraoperative flash VEP monitoring allows detection of dysfunction arising anywhere in the optic pathway, from the retina to the visual cortex. Particularly important steps to obtain reproducible intraoperative flash VEP waveforms under general anesthesia are total intravenous anesthesia with propofol, use of retinal flash stimulation devices using high-intensity light-emitting diodes, and a combination of electroretinography to confirm that the flash stimulus has reached the retina. Relatively major postoperative visual impairment can be detected by intraoperative decreases in the flash VEP amplitude.

  20. Intraoperative arterial oxygenation in obese patients.

    PubMed Central

    Vaughan, R W; Wise, L

    1976-01-01

    Although obese patients have been shown to represent a particularly high risk group with respect to hypoxemia both pre and postoperatively, no data exist to delineate the intraoperative arterial oxygenation pattern of these patients. Furthermore, no one has studied the effects of a change in operative position or a subdiaphragmatic laparotomy pack on arterial oxygenation (PaO2). Sixty-four adults undergoing jejunoileal bypass for morbid exogenous obesity, with a mean weight of 142.0 +/- 31.4 kg and a mean age of 33.3 +/- 10.4 years, were studied. Twenty-five patients (Group I) were maintained in the supine position throughout the operative procedure, while the remaining 39 patients (Group II) were changed to a 15 degrees head down position 15 minutes after a control blood sample was taken. Four additional markedly obese patients were studied to determine the effect of an abdominal pack of PaO2 values. The following findings were demonstrated: 1) 40% oxygen did not uniformly produce adequate arterial oxygenation for intra-abdominal surgery in otherwise healthy obese patients; 2) placement of a subdiaphragmatic abdominal laparotomy pack without a change in operative position resulted in a consistent fall in PaO2 in each patient to less than 65 mm Hg even though 40% oxygen was being administered; and 3) a change from supine to a 15 degrees head down operative position resulted in a significant (P less than 0.001) reduction in mean PaO2 (73.0 +/- 26.3 mm Hg). Seventy-seven per cent of these patients demonstrated PaO2 values of less than 80 mm Hg on 40% oxygen. Because of these findings, serious consideration should be given to the routine use of the Trendelenberg position intraoperatively in obese patients. However, if one elects this posture, prudence would dictate careful monitoring and maintenance of arterial oxygenation. Certainly, in obese patients, the intraoperative combination of the head down position and a subdiaphragmatic laparotomy pack should be avoided

  1. Day-care for breast cancer: ambulatory surgery and intra-operative radiation. Techniques and preliminary results of the Centre Val-d'Aurelle--Montpellier.

    PubMed

    Mourregot, A; Lemanski, C; Gutowski, M; Colombo, P-E; Charissoux, M; Dubois, J-B; Azria, D; Saint-Aubert, B; Domergue, J; Mathieu-Daude, H; Rouanet, P

    2014-04-01

    One-day breast carcinoma treatment is defined as association of ambulatory surgery and intra-operative irradiation. Selection and rigorous process of patients is the key to success. The surgical technique is not changed by the radiotherapy. Patient's satisfaction index is very high. Financial loss should not be a hurdle to its implementation.

  2. External radiotherapy in thyroid cancers

    SciTech Connect

    Tubiana, M.; Haddad, E.; Schlumberger, M.; Hill, C.; Rougier, P.; Sarrazin, D.

    1985-05-01

    Surgery is the most effective treatment for thyroid cancer; however, in some subsets of patients, the role of radiotherapy (RT) is important. The main indication for external-beam RT is incomplete surgery. When neoplastic tissue is left behind at surgery, RT must be considered, but only if an experienced surgeon feels that everything that can be done has been done. Generally, in those patients, the neoplastic tissue involves the larynx, trachea, esophagus, blood vessels or mediastinum. Of 539 patients with differentiated thyroid cancer treated at Villejuif, France, until 1976, 97 were treated by external radiotherapy after an incomplete surgical excision. Fifteen years after irradiation, the survival rate is 57% and is approximately 40% at 25 years. The relapse-free survival is lower (39% at 15 years). In patients irradiated with an adequate dose (greater than or equal to 50 Gy) to residual neoplastic tissue after incomplete surgery, the incidence of local recurrence is low (actuarial probability of local recurrence 11% at 15 years versus 23% for patients treated by surgery alone, although the irradiated patients had larger and more extensive tumors). This demonstrates the efficacy of external-beam radiotherapy. The effects of radiotherapy on a residual tumor can be monitored by a serum thyroglobulin assay. With regard to local control of tumors, the effectiveness of radioiodine administration is clearly lower. However, since radioiodine facilitates early detection of distant metastases, a combination of external RT and radioiodine is indicated and is well-tolerated.

  3. Intraoperative radiation therapy in recurrent ovarian cancer

    SciTech Connect

    Yap, O.W. Stephanie . E-mail: stbeast@stanford.edu; Kapp, Daniel S.; Teng, Nelson N.H.; Husain, Amreen

    2005-11-15

    Purpose: To evaluate disease outcomes and complications in patients with recurrent ovarian cancer treated with cytoreductive surgery and intraoperative radiation therapy (IORT). Methods and Materials: A retrospective study of 24 consecutive patients with ovarian carcinoma who underwent secondary cytoreduction and intraoperative radiation therapy at our institution between 1994 and 2002 was conducted. After optimal cytoreductive surgery, IORT was delivered with orthovoltage X-rays (200 kVp) using individually sized and beveled cone applications. Outcomes measures were local control of disease, progression-free interval, overall survival, and treatment-related complications. Results: Of these 24 patients, 22 were available for follow-up analysis. Additional treatment at the time of and after IORT included whole abdominopelvic radiation, 9; pelvic or locoregional radiation, 5; chemotherapy, 6; and no adjuvant treatment, 2. IORT doses ranged from 9-14 Gy (median, 12 Gy). The anatomic sites treated were pelvis (sidewalls, vaginal cuff, presacral area, anterior pubis), para-aortic and paracaval lymph node beds, inguinal region, or porta hepatitis. At a median follow-up of 24 months, 5 patients remain free of disease, whereas 17 patients have recurred, of whom 4 are alive with disease and 13 died from disease. Five patients recurred within the radiation fields for a locoregional relapse rate of 32% and 12 patients recurred at distant sites with a median time to recurrence of 13.7 months. Five-year overall survival was 22% with a median survival of 26 months from time of IORT. Nine patients (41%) experienced Grade 3 toxicities from their treatments. Conclusion: In carefully selected patients with locally recurrent ovarian cancer, combined IORT and tumor reductive surgery is reasonably tolerated and may contribute to achieving local control and disease palliation.

  4. Quantitative effect of combined chemotherapy and fractionated radiotherapy on the incidence of radiation-induced lung damage: A prospective clinical study

    SciTech Connect

    Mah, K.; Van Dyk, J.; Braban, L.E.; Hao, Y.; Keane, T.J. ); Poon, P.Y. )

    1994-02-01

    The objective of this work was to assess the incidence of radiological changes compatible with radiation-induced lung damage as determined by computed tomography (CT), and subsequently calculate the dose effect factors (DEF) for specified chemotherapeutic regimens. Radiation treatments were administered once daily, 5 days-per-week. Six clinical protocols were evaluated: ABVD (adriamycin, bleomycin, vincristine, and DTIC) followed by 35 Gy in 20 fractions; MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) followed by 35 Gy in 20; MOPP/ABVD followed by 35 Gy in 20; CAV (cyclophosphamide, adriamycin, and vincristine) followed by 25 Gy in 10; and 5-FU (5-fluorouracil) concurrent with either 50-52 Gy in 20-21 or 30-36 Gy in 10-15 fractions. CT examinations were taken before and at predetermined intervals following radiotherapy. CT evidence for the development of radiation-induced damage was defined as an increase in lung density within the irradiated volume. The radiation dose to lung was calculated using a CT-based algorithm to account for tissue inhomogeneities. Different fractionation schedules were converted using two isoeffect models, the estimated single dose (ED) and the normalized total dose (NTD). The actuarial incidence of radiological pneumonitis was 71% for the ABVD, 49% for MOPP, 52% for MOPP/ABVD, 67% for CAV, 73% for 5-FU radical, and 58% for 5-FU palliative protocols. Depending on the isoeffect model selected and the method of analysis, the DEF was 1.11-1.14 for the ABVD, 0.96-0.97 for the MOPP, 0.96-1.02 for the MOPP/ABVD, 1.03-1.10 for the CAV, 0.74-0.79 for the 5-FU radical, and 0.94 for the 5-FU palliative protocols. DEF were measured by comparing the incidence of CT-observed lung damage in patients receiving chemotherapy and radiotherapy to those receiving radiotherapy alone. The addition of ABVD or CAV appeared to reduce the tolerance of lung to radiation. 40 refs., 3 figs., 3 tabs.

  5. [Radiotherapy for nasopharyngeal carcinoma].

    PubMed

    Maingon, P; Blanchard, P; Bidault, F; Calmels, L

    2016-09-01

    Nasapharyngeal carcinoma is a rare disease. Oftenly, the diagnostic is made for advanced disease. Localized tumors, T1 or T2 NO observed a good prognosis and are locally controlled in more than 90 % of the cases by radiotherapy alone. The standard treatment of locally advanced disease is combined chemoradiation. A special vigilance of fast decrease of the volume of the pathological lymph nodes, sometimes associated to loss of weight might indicate an adaptive dosimetric revision. The treatment of recurrent disease is of great importance. Surgical indications are limited but should be discussed in multidisciplinary tumor board when possible. Surgical nodal sampling has to be proposed for nodal recurrence as well as reirradiation, which could be indicated according to the technical issues.

  6. Impact of combined modality treatment with radiotherapy and S-1 on T2N0 laryngeal cancer: Possible improvement in survival through the prevention of second primary cancer and distant metastasis.

    PubMed

    Kitani, Yosuke; Kubota, Akira; Furukawa, Madoka; Hori, Yukiko; Nakayama, Yuko; Nonaka, Tetsuo; Mizoguchi, Nobutaka; Kitani, Yuka; Hatakeyama, Hiromitsu; Oridate, Nobuhiko

    2017-08-01

    In patients with head and neck cancer, the management of second primary cancer (SPC) is particularly important for improving survival because of its high incidence and associated mortality. We evaluated the impact of combination chemotherapy on survival and SPC. We retrospectively analyzed data from 49 patients treated with definitive radiation therapy (RT) for T2N0M0 laryngeal squamous cell carcinoma between 2003 and 2011. Among them, 22 patients received combined modality treatment with radiotherapy and S-1 (RT+CT group). The median follow-up period was 71months (32-111months). A significant difference in overall survival (OS, P<0.01) was observed between the RT+CT group (n=22) and the RT alone group (n=27) though no significant differences were observed in local control and disease specific survival. Univariate analyses showed that an older age (P<0.05) and a higher grade (P<0.05) were associated with OS. Multivariate analysis identified chemotherapy as the most significant predictor of survival (OR, 0.056; 95% CI, 0.008-0.353, P<0.01). A significantly lower incidence of distant metastasis (DM)+SPC (5-year incidence: 5% vs. 19%, P<0.05) and fewer deaths from these causes (1 vs. 8: P<0.05) were observed in the RT+CT group. Multivariate analysis showed that chemotherapy was the most significant factor for the incidence of DM+SPC (OR, 0.074; 95% CI, 0.0065-0.84; P<0.05). The findings of this study suggest the possibility that combined modality treatment with radiotherapy and S-1 improve survival by preventing distant metastasis and second primary cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Second malignancies following conventional or combined ²⁵²Cf neutron brachytherapy with external beam radiotherapy for breast cancer.

    PubMed

    Valuckas, Konstantinas Povilas; Atkocius, Vydmantas; Kuzmickiene, Irena; Aleknavicius, Eduardas; Liukpetryte, Sarune; Ostapenko, Valerijus

    2013-09-01

    We retrospectively evaluated the risk of second malignancies among 832 patients with inner or central breast cancer treated with conventional external beam schedule (CRT group), or neutron brachytherapy using Californium-252 (²⁵²Cf) sources and hypofractionated external beam radiotherapy (HRTC group), between 1987 and 1996 at the Institute of Oncology, Vilnius University. Patients were observed until the occurrences of death or development of a second malignancy, or until 31 December 2009, whichever was earlier. Median follow-up time was 10.4 years (range, 1.2-24.1 years). Risk of second primary cancers was quantified using standardized incidence ratios (SIRs). Cox proportional hazards regression models were used to estimate hazard ratios (HRs). There was a significant increase in the risk of second primary cancers compared with the general population (SIR 1.3, 95% CI 1.1-1.5). The observed number of second primary cancers was also higher than expected for breast (SIR 1.8, 95% CI 1.3-2.4) and lung cancer (SIR 3.8, 95% CI 2.0-6.7). For second breast cancer, no raised relative risk was observed during the period ≥10 or more years after radiotherapy. Compared with the CRT group, HRTC patients had a not statistically significant higher risk of breast cancer. Increased relative risks were observed specifically for age at initial diagnosis of <50 years (HR 2.9, 95% CI 1.6-5.2) and for obesity (HR 2.8, 95% CI 1.1-7.2).

  8. Potential of Adaptive Radiotherapy to Escalate the Radiation Dose in Combined Radiochemotherapy for Locally Advanced Non-Small Cell Lung Cancer

    SciTech Connect

    Guckenberger, Matthias; Wilbert, Juergen; Richter, Anne; Baier, Kurt; Flentje, Michael

    2011-03-01

    Purpose: To evaluate the potential of adaptive radiotherapy (ART) for advanced-stage non-small cell lung cancer (NSCLC) in terms of lung sparing and dose escalation. Methods and Materials: In 13 patients with locally advanced NSCLC, weekly CT images were acquired during radio- (n = 1) or radiochemotherapy (n = 12) for simulation of ART. Three-dimensional (3D) conformal treatment plans were generated: conventionally fractionated doses of 66 Gy were prescribed to the planning target volume without elective lymph node irradiation (Plan{sub 3}D). Using a surface-based algorithm of deformable image registration, accumulated doses were calculated in the CT images acquired during the treatment course (Plan{sub 4}D). Field sizes were adapted to tumor shrinkage once in week 3 or 5 and twice in weeks 3 and 5. Results: A continuous tumor regression of 1.2% per day resulted in a residual gross tumor volume (GTV) of 49% {+-} 15% after six weeks of treatment. No systematic differences between Plan{sub 3}D and Plan{sub 4}D were observed regarding doses to the GTV, lung, and spinal cord. Plan adaptation to tumor shrinkage resulted in significantly decreased lung doses without compromising GTV coverage: single-plan adaptation in Week 3 or 5 and twice-plan adaptation in Weeks 3 and 5 reduced the mean lung dose by 5.0% {+-} 4.4%, 5.6% {+-} 2.9% and 7.9% {+-} 4.8%, respectively. This lung sparing with twice ART allowed an iso-mean lung dose escalation of the GTV dose from 66.8 Gy {+-} 0.8 Gy to 73.6 Gy {+-} 3.8 Gy. Conclusions: Adaptation of radiotherapy to continuous tumor shrinkage during the treatment course reduced doses to the lung, allowed significant dose escalation and has the potential of increased local control.

  9. Treatment Outcomes of Locally Advanced Oropharyngeal Cancer: A Comparison Between Combined Modality Radio-Chemotherapy and Two Variants of Single Modality Altered Fractionation Radiotherapy

    SciTech Connect

    Kader, Hosam A.; Mydin, Aminudin R.; Wilson, Matthew; Alexander, Cheryl; Shahi, Jeevin; Pathak, Irvin; Wu, Jonn S.; Truong, Pauline T.

    2011-07-15

    Purpose: To compare outcomes in patients with locally advanced oropharyngeal cancer treated with radio-chemotherapy (RT-CT), accelerated fractionation radiotherapy (AccRT), or hypofractionated radiotherapy (HypoRT). Methods and Materials: Subjects were 321 consecutive patients with newly diagnosed oropharyngeal cancer, Stage III or IVA/B, treated between January 2001 and December 2005 at the BC Cancer Agency with RT-CT (n = 157), AccRT (n = 57), or HypoRT (n = 107). Outcomes examined were disease-specific survival (DSS), locoregional control (LRC), overall survival (OS), rate of G-tube use, and rate of hospitalization for acute complications. Results: Median follow-up was 3.4 years. Three-year Kaplan-Meier DSS with RT-CT, AccRT, and HypoRT were 80%, 81%, and 74%, respectively (p = 0.219). Cox regression analysis identified treatment modality as a significant factor affecting DSS (p = 0.038). Compared with RT-CT, the hazard ratio (HR) for DSS was 1.0 with AccRT and 2.0 with HypoRT (p = 0.021). Kaplan-Meier pairwise comparisons found no significant difference in LRC and OS between RT-CT and AccRT. HypoRT was associated with significantly lower LRC (p = 0.005) and OS (p = 0.008) compared with RT-CT. There were significant differences in the rates of G-tube use (p < 0.001) and of hospitalization (p = 0.036) among the three treatment groups, with the most frequent rates observed in the RT-CT group. Conclusions: In patients with locally advanced oropharyngeal cancer, AccRT conferred DSS, LRC, and OS comparable to that of RT-CT. Patients treated with RT-CT experienced higher rates of treatment-related acute toxicities. HypoRT was associated with the least favorable outcomes.

  10. Does ultrasongraphy predict intraoperative findings at cholecystectomy? An institutional review

    PubMed Central

    Stogryn, Shannon; Metcalfe, Jennifer; Vergis, Ashley; Hardy, Krista

    2016-01-01

    Background Ultrasonography (US) is the mainstay of biliary tract imaging, but few recent studies have tested its ability to diagnose acute cholecystitis (AC). Our objective was to determine how well a US diagnosis of AC correlates with the intraoperative diagnosis. We hypothesize that US underestimates this diagnosis, potentially leading to unexpected findings in the operating room (OR). Methods This retrospective review included all patients admitted to the acute care surgical service of a tertiary hospital in 2011 with suspected biliary pathology who underwent US and subsequent cholecystectomy. We determined the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of US using the intraoperative diagnosis as the gold standard. Further analysis identified which US findings were most predictive of an intraoperative diagnosis of AC. We used a recursive partitioning method with random forests to identify unique combinations of US findings that, together, are most predictive of AC. Results In total, 254 patients underwent US for biliary symptoms; 152 had AC diagnosed, and 143 (94%) of them underwent emergency surgery (median time to OR 23.03 hr). Ultrasonography predicted intraoperative findings with a sensitivity of 73.2%, specificity of 85.5% and PPV of 93.7%. The NPV (52.0%) was quite low. The US indicators most predictive of AC were a thick wall, a positive sonographic Murphy sign and cholelithiasis. Recursive partitioning demonstrated that a positive sonographic Murphy sign is highly predictive of intraoperative AC. Conclusion Ultrasonography is highly sensitive and specific for diagnosing AC. The poor NPV confirms our hypothesis that US can underestimate AC. PMID:26574703

  11. Intraoperative management of critical arrhythmia

    PubMed Central

    2017-01-01

    The incidence of intraoperative arrhythmia is extremely high, and some arrhythmias require clinical attention. Therefore, it is essential for the anesthesiologist to evaluate risk factors for arrhythmia and understand their etiology, electrophysiology, diagnosis, and treatment. Anesthetic agents reportedly affect normal cardiac electrical activity. In the normal cardiac cycle, the sinoatrial node initiates cardiac electrical activity through intrinsic autonomous pacemaker activity. Sequential atrial and ventricular contractions result in an effective cardiac pumping mechanism. Arrhythmia occurs due to various causes, and the cardiac pumping mechanism may be affected. A severe case may result in hemodynamic instability. In this situation, the anesthesiologist should eliminate the possible causes of arrhythmia and manage the condition, creating hemodynamic stability under proper electrocardiographic monitoring. PMID:28367281

  12. Intraoperative OCT in Surgical Oncology

    NASA Astrophysics Data System (ADS)

    South, Fredrick A.; Marjanovic, Marina; Boppart, Stephen A.

    The global incidence of cancer is rising, putting an increasingly heavy burden upon health care. The need to effectively detect and treat cancer is one of the most significant problems faced in health care today. Effective cancer treatment typically depends upon early detection and, for most solid tumors, successful removal of the cancerous tumor tissue via surgical procedures. Difficulties arise when attempting to differentiate between normal and tumor tissue during surgery. Unaided visual examination of the tissue provides only superficial, low-resolution information and often with little visual contrast. Many imaging modalities widely used for cancer screening and diagnostics are of limited use in the operating room due to low spatial resolution. OCT provides cellular resolution allowing for more precise localization of the tumor tissue. It is also relatively inexpensive and highly portable, making it well suited for intraoperative applications.

  13. Intraoperative magnification: Who uses it?

    PubMed

    Jarrett, Paul Max

    2004-01-01

    Surgeons over recent decades have made increasing use of intraoperative magnification to enhance the outcome of surgical procedures, yet no published information exists regarding the extent of magnification use within surgical specialties. A sample of surgeons consisting of 148 specialists and senior surgical trainees in the west of Scotland was surveyed by postal questionnaire regarding their frequency and types of magnification use. Patterns of use were similar within each specialty, but varied markedly between specialties. Otolaryngologists and plastic, maxillofacial, and ophthalmic surgeons use both loupes and microscopes frequently. Cardiothoracic and pediatric surgeons tend only to utilize loupes, whereas neurosurgeons tend only to use microscopes. General surgeons, urologists, orthopedic surgeons, and gynecologists are infrequent users or nonusers of magnification, and when required will utilize loupes rather than microscopes. As a clear pattern of magnification use exists, it should be possible to anticipate the equipment needs of surgeons when providing theater services.

  14. Rapid intraoperative zygoma fracture imaging.

    PubMed

    Czerwinski, Marcin; Parker, Wendy L; Beckman, Lorne; Williams, H Bruce

    2009-09-01

    A fractured zygoma frequently results in an aesthetically displeasing facial asymmetry. Open reduction and internal fixation may accurately realign the facial skeleton but often with undesirable sequelae. The authors' objective was to develop a precise technique of intraoperative zygoma fracture imaging using a C-arm to permit anatomical fracture realignment while reducing the extent of skeletal exposure required. The simplicity and accessibility of this method should allow its widespread clinical application. First, using a model skull, the relative positions of the C-arm required to adequately depict zygoma projection, width, arch contour, and zygoma rotation were defined. Second, diverse zygoma fracture types were created in six cadaver heads with a Mini Bionix machine and were repaired using C-arm guidance; accuracy was confirmed with postoperative computed tomography. Third, after defining optimal operating room setup, the accuracy in a clinical case was assessed. Two C-arm views were defined. The zygoma projection view (C-arm at 70 to 90 degrees to the skull's coronal plane) allows visualization of projection, width, and contour. The rotation view (C-arm at 70 to 90 degrees to the skull's sagittal plane) allows visualization of zygoma rotation. Postoperative computed tomographic imaging confirmed anatomical repair in all cases. Average operating room duration was less than 30 minutes, with operating room times decreasing progressively. The authors have developed an accurate technique of intraoperative zygoma fracture imaging and reduction guidance. This technique may decrease the risks of open access by potentially limiting direct skeletal exposure to buttresses where skeletal stabilization is required. In addition, this method is simple, can be learned and used rapidly, and is readily accessible.

  15. Biomarkers for DNA DSB inhibitors and radiotherapy clinical trials.

    PubMed

    Liu, Stanley K; Olive, Peggy L; Bristow, Robert G

    2008-09-01

    Major technical advances in radiotherapy, including IMRT and image-guided radiotherapy, have allowed for improved physical precision and increased dose delivery to the tumor, with better sparing of surrounding normal tissue. The development of inhibitors of the sensing and repair of DNA double-strand breaks (DSBs) is exciting and could be combined with precise radiotherapy targeting to improve local control following radiotherapy. However, caution must be exercised in order that DSB inhibitors are combined with radiotherapy in such a manner as to preserve the therapeutic ratio by exploiting repair deficiencies in malignant cells over that of normal cells. In this review, we discuss the rationale and current approaches to targeting DSB sensing and repair pathways in combined modality with radiotherapy. We also describe potential biomarkers that could be useful in detecting functional inhibition of DSB repair in a patient's tissues during clinical radiotherapy trials. Finally, we examine a number of issues relating to the use of DSB-inhibiting molecular agents and radiotherapy in the context of the tumor microenvironment, effects on normal tissues and the optimal timing and duration of the agent in relation to fractionated radiotherapy.

  16. [Radiotherapy of hypopharynx cancers].

    PubMed

    Pointreau, Y; Lafond, C; Trémolières, P; Legouté, F; Servagi-Vernat, S; Giraud, P; Maingon, P; Calais, G; Lapeyre, M

    2016-09-01

    The intensity-modulated radiotherapy is the gold standard in the treatment of hypopharynx cancers. Early T1 and T2 tumours could be treated by exclusive radiotherapy or surgery. For tumours requiring total pharyngolaryngectomy (T2 or T3), induction chemotherapy followed by exclusive radiotherapy or concurrent chemoradiotherapy are possible. For T4 tumours, surgery must be proposed. The treatment of lymph nodes is based on the initial treatment of the primary tumour. In non-surgical procedure, in case of sequential radiotherapy, curative dose is 70Gy and prophylactic dose is 50Gy. An integrated simultaneous boost radiotherapy is allowed (70Gy in 2Gy per fraction and 56Gy in 1.8Gy per fraction or 70Gy in 2.12Gy per fraction). Postoperatively, radiotherapy is used for locally advanced cancers with dose levels based on pathologic criteria (66Gy for R1 resection, 50 to 54Gy for complete resection). Volume delineation is based on guidelines.

  17. Effectiveness of pegaspargase, gemcitabine, and oxaliplatin (P-GEMOX) chemotherapy combined with radiotherapy in newly diagnosed, stage IE to IIE, nasal-type, extranodal natural killer/T-cell lymphoma.

    PubMed

    Wei, Wen; Wu, Ping; Li, Li; Zhang, Zhi-Hui

    2017-07-01

    Extranodal natural killer/T-cell lymphoma (ENKTL), nasal-type, is a distinct subtype of non-Hodgkin lymphoma. ENKTL is sensitive to radiotherapy, but the prognosis is poorer than those of other types of early stage lymphoma. To date, optimal treatment strategies for patients with early stage ENKTL have not been fully defined. We retrospectively investigated the efficacy and safety of pegaspargase, gemcitabine, and oxaliplatin (P-GEMOX) combined with different dose radiotherapy (RT) in the treatment of 35 newly diagnosed, stage IE to IIE ENKTL patients at our institution from October 2011 to September 2015. All patients were treated with RT (<54 Gy or ≥54 Gy) after an initial two cycles of P-GEMOX, and following two consolidation cycles. The primary endpoints were objective response rate and complete remission rate (CR). The secondary endpoints were 2-year overall survival (OS), 2-year progression-free survival (PFS), and toxicity. Thirty-three patients completed total therapy, which resulted in 94.3% of response rate that included 28 patients (80.0%) with CR and five patients (14.3%) with partial response (PR). Two (5.7%) patients progressed during therapy and six (17.1%) progressed during follow-up. The 2-year OS was 82.9%, and the 2-year PFS was 77.1%. Patients with CR, low circulating EBV DNA load (≤6.1 × 10(7) copies/ml), low NKIPI (score 0-1), and high RT dose (≥54 Gy) were independent predictors of better prognosis. Grade 3 toxicities were few; only four (11.4%) patients experienced grade 4 toxicities. No treatment-related deaths were observed. The research showed that the treatment of P-GEMOX combined with RT was a tolerable and effective treatment for localized nasal natural killer/T-cell lymphoma.

  18. Image-guided brachytherapy (IGBT) combined with whole pelvic intensity-modulated radiotherapy (WP-IMRT) for locally advanced cervical cancer: a prospective study from Chiang Mai University Hospital, Thailand

    PubMed Central

    Wanwilairat, Somsak; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Tippanya, Damrongsak; Nopnop, Wannapa; Galalae, Razvan; Chitapanarux, Imjai

    2013-01-01

    Purpose A report of preliminary results and toxicity profiles using image-guided brachytherapy (IGBT) combined with whole pelvic intensity-modulated radiation therapy (WP-IMRT) for locally advanced cervical cancer. Material and methods Fifteen patients with locally advanced cervical cancer were enrolled into the study. WP-IMRT was used to treat the Clinical Target Volume (CTV) with a dose of 45 Gy in 25 fractions. Concurrent cisplatin (40 mg/m2) was prescribed during radiotherapy (RT) on weekly basis. IGBT using computed tomography was performed at the dose of 7 Gy × 4 fractions to the High-Risk Clinical Target Volume (HR-CTV). Results The mean cumulative doses – in terms of equivalent dose of 2 Gy (EQD2) – of IGBT plus WP-IMRT to HR-CTV, bladder, rectum, and sigmoid colon were 88.3, 85.0, 68.2 and 73.6 Gy, respectively. In comparison with standard (point A prescription) dose-volume histograms, volume-based image-guided brachytherapy improved the cumulative doses for bladder of 67%, rectum of 47% and sigmoid of 46%. At the median follow-up time of 14 months, the local control, metastasis-free survival and overall survival rates were 93%, 100% and 93%, respectively. No grade 3-4 acute and late toxicities were observed. Conclusion The combination of image-guided brachytherapy and intensity-modulated radiotherapy improved the dose distribution to tumor volumes and avoided overdose in OARs which could be converted in excellent local control and toxicity profiles. PMID:23634150

  19. Heavy-ion radiotherapy

    NASA Astrophysics Data System (ADS)

    Kanai, Tatsuaki

    2000-11-01

    Heavy-ion radiotherapy using high-energy carbon beams has been performed at the National Institute of Radiological Sciences, Japan. The physical frame works for heavy-ion radiotherapy are established using physical understandings of radiation physics. In order to increase the accuracy of heavy-ion radiotherapy, many physical problems should be solved. Unsolved problems, such as the depth dose distributions, range of heavy-ion in patients and heavy-ion dosimetry in the radiation therapy, are discussed. .

  20. [Radiotherapy of oropharynx carcinoma].

    PubMed

    Servagi Vernat, S; Tochet, F; Vieillevigne, L; Pointreau, Y; Maingon, P; Giraud, P

    2016-09-01

    Indication, doses, technique of radiotherapy and concomitant chemotherapy for oropharynx carcinoma are presented. The recommendations for delineation of the target volumes and organs at risk are detailed.

  1. Neurophysiological intraoperative monitoring of the glossopharyngeal nerve: technical case report.

    PubMed

    Husain, Aatif M; Wright, David R; Stolp, Bret W; Friedman, Allan H; Keifer, John C

    2008-10-01

    Neurophysiological intraoperative monitoring of the glossopharyngeal nerve has been performed only with needle electrodes inserted into the pharyngeal muscles or soft palate. We describe a noninvasive method of monitoring this cranial nerve. A 30-year-old man who presented with headache, as well as speech and swallowing difficulty, underwent surgical resection of a right vagus nerve schwannoma. Neurophysiological intraoperative monitoring of multiple lower cranial nerves, including the glossopharyngeal and vagus nerves, was performed. The glossopharyngeal nerve was monitored with an adhesive surface electrode mounted on the cuff of a laryngeal mask airway, and the vagus nerve was monitored with a similar electrode mounted on the endotracheal tube. Successful monitoring allowed separation of the glossopharyngeal nerve from the tumor, and there was no postoperative swallowing deficit. Monitoring of the glossopharyngeal nerve with surface electrodes is possible and reliable, but it must be combined with vagus nerve monitoring.

  2. Relation between Birth Weight and Intraoperative Hemorrhage during Cesarean Section in Pregnancy with Placenta Previa.

    PubMed

    Soyama, Hiroaki; Miyamoto, Morikazu; Ishibashi, Hiroki; Takano, Masashi; Sasa, Hidenori; Furuya, Kenichi

    2016-01-01

    Placenta previa, one of the most severe obstetric complications, carries an increased risk of intraoperative massive hemorrhage. Several risk factors for intraoperative hemorrhage have been identified to date. However, the correlation between birth weight and intraoperative hemorrhage has not been investigated. Here we estimate the correlation between birth weight and the occurrence of intraoperative massive hemorrhage in placenta previa. We included all 256 singleton pregnancies delivered via cesarean section at our hospital because of placenta previa between 2003 and 2015. We calculated not only measured birth weights but also standard deviation values according to the Japanese standard growth curve to adjust for differences in gestational age. We assessed the correlation between birth weight and the occurrence of intraoperative massive hemorrhage (>1500 mL blood loss). Receiver operating characteristic curves were constructed to determine the cutoff value of intraoperative massive hemorrhage. Of 256 pregnant women with placenta previa, 96 (38%) developed intraoperative massive hemorrhage. Receiver-operating characteristic curves revealed that the area under the curve of the combination variables between the standard deviation of birth weight and intraoperative massive hemorrhage was 0.71. The cutoff value with a sensitivity of 81.3% and specificity of 55.6% was -0.33 standard deviation. The multivariate analysis revealed that a standard deviation of >-0.33 (odds ratio, 5.88; 95% confidence interval, 3.04-12.00), need for hemostatic procedures (odds ratio, 3.31; 95% confidence interval, 1.79-6.25), and placental adhesion (odds ratio, 12.68; 95% confidence interval, 2.85-92.13) were independent risk of intraoperative massive hemorrhage. In patients with placenta previa, a birth weight >-0.33 standard deviation was a significant risk indicator of massive hemorrhage during cesarean section. Based on this result, further studies are required to investigate whether

  3. [Radiotherapy in the combined therapy of limited stage pulmonary microcytoma. The experience of the Department of Oncologic Therapy at the Multiregional Hospital of Varese (1980-1989)].

    PubMed

    Cerizza, L; Källi, M; Reso, M; Stucchi, F; Vavassori, V; Tordiglione, M

    1991-06-01

    From January 1980 to December 1989, 86 patients with limited small cell lung carcinoma (SCLC) were treated in our Institution. Sixty-eight of them were males, 18 females; mean age was 58 years (range: 40-74); Karnofsky index was 80 or higher. All patients received induction multiagent chemotherapy (CAV or CAVE), usually fractionated into 3/4 cycles. Radiotherapy was administered by means of a 10 MV Linear Accelerator, 2-3 Gy/day, 5 days/week. Radiation dose was 60 Gy for 39 patients, 50 Gy for 25 patients, and 30 Gy for 22 patients. Parallel opposed fields (AP and PA) were used for administering the 30-Gy dose, while higher doses were delivered by multiportal arrangement (3/4 fields). Overall survival (corrected Kaplan-Meier) was 21.3% and 13.4% at 2 and 3 years, respectively; 2 years' survival according to dose was 24.5% for 60 Gy, 19.9% and 11% for 50 and 30 Gy, respectively. Mean survival time (MST) was 14 months for 60 Gy, 13 months and 10 months, respectively, for 50 and 30 Gy. Survival and disease-free survival rates were similar in patients who received 50 and 60 Gy. No major complications related to irradiation were observed, not even in the group receiving the highest dose. Our data are similar to those reported in the literature.

  4. Surgery combined with radiotherapy for the treatment of solitary plasmacytoma of the rib: a case report and review of the literature.

    PubMed

    Jia, Rui; Xue, Lei; Liang, Huagang; Gao, Kun; Li, Jian; Zhang, Zhefeng

    2015-10-13

    Solitary plasmacytoma of the bone, especially of a single rib, is a rare disease. We present the case of a 44-year-old Han Chinese man who was diagnosed with a solitary plasmacytoma of the bone located in the right sixth rib. The patient presented with a 4-year history of continuous pain in the right chest area and moderate fever lasting 7 days. A chest roentgenogram showed a solitary expanding lesion in the right thorax, and chest computed tomography revealed an osteolytic tumor in the chest wall. The patient underwent complete en-bloc resection of the chest wall, including the ribs, muscle, and parietal pleura. Histologically, the resected mass was composed of abundant neoplastic plasma cells, and the diagnosis was confirmed to be a plasmacytoma of rib. The examination of marrow cells showed 9 % normal plasma cells among karyocytes without clonal disease. On postoperative day 14, the patient underwent thoracic radiotherapy with a total dose of 50 Gy. The patient remained asymptomatic during the 6-month follow-up period. Herein, we also review previous reports on solitary plasmacytomas of the rib. In summary, this report provides further insights for the diagnosis and effective treatment of this rare disease.

  5. Intraoperative scintigraphy for active small intestinal bleeding

    SciTech Connect

    Biener, A.; Palestro, C.; Lewis, B.S.; Katz, L.B. )

    1990-11-01

    Localizing active sites of bleeding within the small intestine remains a difficult task. Endoscopic, angiographic or scintigraphic studies may point to the small intestine as the site of blood loss, but at operation, without a palpable lesion, the exact site of bleeding remains elusive. Patients are managed at laparotomy with intraoperative endoscopy, angiography, multiple enterotomies, blind resections, or placement of an enterostomy. We describe two patients in whom intraoperative scintigraphy accurately identified active sites of bleeding in the small intestine when other modalities failed. Intraoperative scintigraphy is rapid, easy to perform and is an effective means of identifying active sites of bleeding within the small intestine.

  6. The basics of intraoperative diagnosis in neuropathology.

    PubMed

    Lee, Han S; Tihan, Tarik

    2015-03-01

    Intraoperative pathologic consultation continues to be an essential tool during neurosurgical procedures, helping to ensure adequacy of material for achieving a pathologic diagnosis and to guide surgeons. For pathologists, successful consultation with central nervous system lesions involves not only a basic familiarity with the pathologic features of such lesions but also an understanding of their clinical and radiologic context. This review discusses a basic approach to intraoperative diagnosis for practicing pathologists, including preparation for, performance of, and interpretation of an intraoperative neuropathologic evaluation. The cytologic and frozen section features of select examples of common pathologic entities are described.

  7. Repeated iodine-125 seed implantations combined with external beam radiotherapy for the treatment of locally recurrent or metastatic stage III/IV non-small cell lung cancer: a retrospective study.

    PubMed

    Li, Wei; Dan, Gang; Jiang, Jianqing; Zheng, Yifeng; Zheng, Xiushan; Deng, Dan

    2016-09-13

    Recurrent or metastatic lung cancer is difficult to manage. This retrospective study aimed to assess the efficacy of repeated iodine-125 seed implantations combined with external beam radiotherapy (EBRT) for locally recurrent or metastatic stage-III/IV non-small cell lung cancer (NSCLC). Eighteen previously treated stage-III/IV NSCLC patients with local or metastatic recurrences underwent 1-to-3 iodine-125 implantations. Six of these patients received palliative EBRT and six patients received combined chemotherapy using gemcitabine and cisplatin. Near-term treatment efficacy was evaluated 3 months after seed implantation by comparing changes in tumor size on computed tomography images; the evaluated outcomes were complete response, partial response, stable disease, and local tumor control rate. Long-term efficacy was assessed based on 1- and 2-year survival rates. Patients were followed up for 6 to 50 months. The overall (i.e., complete + partial) response rate was 87.4 %. The local control rates after the first, second, and third years were 94.1, 58.8 and 41.2 %, respectively. The results of this study demonstrated that repeated implantation of radioactive particles combined with EBRT is a safe treatment that effectively controlled local recurrence and metastasis of stage III/IV NSCLC.

  8. Rectal bleeding after high-dose-rate brachytherapy combined with hypofractionated external-beam radiotherapy for localized prostate cancer: the relationship between dose-volume histogram parameters and the occurrence rate.

    PubMed

    Okamoto, Masahiko; Ishikawa, Hitoshi; Ebara, Takeshi; Kato, Hiroyuki; Tamaki, Tomoaki; Akimoto, Tetsuo; Ito, Kazuto; Miyakubo, Mai; Yamamoto, Takumi; Suzuki, Kazuhiro; Takahashi, Takeo; Nakano, Takashi

    2012-02-01

    To determine the predictive risk factors for Grade 2 or worse rectal bleeding after high-dose-rate brachytherapy (HDR-BT) combined with hypofractionated external-beam radiotherapy (EBRT) for prostate cancer using dose-volume histogram analysis. The records of 216 patients treated with HDR-BT combined with EBRT were analyzed. The treatment protocols for HDR-BT were 5 Gy × five times in 3 days or 7 Gy × three, 10.5 Gy × two, or 9 Gy × two in 2 days. The EBRT doses ranged from 45 to 51 Gy with a fractional dose of 3 Gy. In 20 patients Grade 2 or worse rectal bleeding developed, and the cumulative incidence rate was 9% at 5 years. By converting the HDR-BT and EBRT radiation doses into biologic effective doses (BED), the BED(3) at rectal volumes of 5% and 10% in the patients who experienced bleeding were significantly higher than those in the remaining 196 patients. Univariate analysis showed that a higher rectal BED(3-5%) and the use of fewer needles in brachytherapy were correlated with the incidence of bleeding, but BED(3-5%) was found to be the only significant factor on multivariate analysis. The radiation dose delivered to small rectal lesions as 5% is important for predicting Grade 2 or worse rectal bleeding after HDR-BT combined with EBRT for prostate cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Dose-Escalation Study of Thoracic Radiotherapy in Combination With Pemetrexed Plus Cisplatin in Japanese Patients With Locally Advanced Nonsquamous Non-Small Cell Lung Cancer: A Post Hoc Analysis of Survival and Recurrent Sites.

    PubMed

    Niho, Seiji; Nokihara, Hiroshi; Nihei, Keiji; Akimoto, Tetsuo; Sumi, Minako; Ito, Yoshinori; Yoh, Kiyotaka; Goto, Koichi; Ohmatsu, Hironobu; Horinouchi, Hidehito; Yamamoto, Noboru; Sekine, Ikuo; Kubota, Kaoru; Ohe, Yuichiro; Tamura, Tomohide

    2016-04-01

    We performed a post hoc analysis of progression-free survival (PFS), overall survival (OS), and recurrent sites in patients with locally advanced nonsquamous non-small cell lung cancer who were enrolled in a phase I trial of combination chemotherapy consisting of pemetrexed plus cisplatin with concurrent thoracic radiotherapy. Patients received pemetrexed (500 mg/m²) plus cisplatin (75 mg/m²) on day 1 every 3 weeks for 3 cycles plus concurrent thoracic radiotherapy consisting of 60 Gy (n=6) or 66 Gy (n=12); 4 to 6 weeks thereafter, patients received consolidation treatment with pemetrexed (500 mg/m) every 3 weeks for up to 3 cycles. We reviewed the medial records to collect data on progression, recurrent sites, late toxicity, and survival. No late radiation morbidity was observed. Thirteen patients (72%) exhibited disease progression: 8 patients had distant metastases, 8 patients had local recurrence (within the radiation field [n=6], outside the radiation field [n=2], and both [n=1]), and 3 patients had local recurrence plus distant metastases. The median PFS was 10.5 months (95% confidence interval [CI], 8.8-12.3), and the 3-year PFS rate was 28% (95% CI, 7.0-48.6). Ten of the 18 patients died of lung cancer. The median follow-up time for the censored cases was 42.8 months (range, 38.1 to 52.9 mo). The median OS was 27.3 months (95% CI, 13.1-41.6), and the 3-year OS rate was 50% (95% CI, 26.9-73.1). The median PFS and OS in our study were comparable to those of historical chemoradiotherapy controls.

  10. Development and Validation of a Prognostic Model Using Blood Biomarker Information for Prediction of Survival of Non-Small-Cell Lung Cancer Patients Treated With Combined Chemotherapy and Radiation or Radiotherapy Alone (NCT00181519, NCT00573040, and NCT00572325)

    SciTech Connect

    Dehing-Oberije, Cary; Aerts, Hugo; Yu Shipeng; De Ruysscher, Dirk; Menheere, Paul; Hilvo, Mika; Weide, Hiska van der; Rao, Bharat; Lambin, Philippe

    2011-10-01

    Purpose: Currently, prediction of survival for non-small-cell lung cancer patients treated with (chemo)radiotherapy is mainly based on clinical factors. The hypothesis of this prospective study was that blood biomarkers related to hypoxia, inflammation, and tumor load would have an added prognostic value for predicting survival. Methods and Materials: Clinical data and blood samples were collected prospectively (NCT00181519, NCT00573040, and NCT00572325) from 106 inoperable non-small-cell lung cancer patients (Stages I-IIIB), treated with curative intent with radiotherapy alone or combined with chemotherapy. Blood biomarkers, including lactate dehydrogenase, C-reactive protein, osteopontin, carbonic anhydrase IX, interleukin (IL) 6, IL-8, carcinoembryonic antigen (CEA), and cytokeratin fragment 21-1, were measured. A multivariate model, built on a large patient population (N = 322) and externally validated, was used as a baseline model. An extended model was created by selecting additional biomarkers. The model's performance was expressed as the area under the curve (AUC) of the receiver operating characteristic and assessed by use of leave-one-out cross validation as well as a validation cohort (n = 52). Results: The baseline model consisted of gender, World Health Organization performance status, forced expiratory volume, number of positive lymph node stations, and gross tumor volume and yielded an AUC of 0.72. The extended model included two additional blood biomarkers (CEA and IL-6) and resulted in a leave-one-out AUC of 0.81. The performance of the extended model was significantly better than the clinical model (p = 0.004). The AUC on the validation cohort was 0.66 and 0.76, respectively. Conclusions: The performance of the prognostic model for survival improved markedly by adding two blood biomarkers: CEA and IL-6.

  11. [Radiotherapy of skin cancers].

    PubMed

    Hennequin, C; Rio, E; Mahé, M-A

    2016-09-01

    The indications of radiotherapy for skin cancers are not clearly defined because of the lack of randomised trials or prospective studies. For basal cell carcinomas, radiotherapy frequently offers a good local control, but a randomized trial showed that surgery is more efficient and less toxic. Indications of radiotherapy are contra-indications of surgery for patients older than 60, non-sclerodermiform histology and occurring in non-sensitive areas. Adjuvant radiotherapy could be proposed to squamous cell carcinomas, in case of poor prognostic factors. Dose of 60 to 70Gy are usually required, and must be modulated to the size of the lesions. Adjuvant radiotherapy seems beneficial for desmoplastic melanomas but not for the other histological types. Prophylactic nodal irradiation (45 to 50Gy), for locally advanced tumours (massive nodal involvement), decreases the locoregional failure rate but do not increase survival. Adjuvant radiotherapy (50 to 56Gy) for Merckel cell carcinomas increases also the local control rate, as demonstrated by meta-analysis and a large epidemiological study. Nodal areas must be included, if there is no surgical exploration (sentinel lymph node dissection). Kaposi sarcomas are radiosensitive and could be treated with relatively low doses (24 to 30Gy). Also, cutaneous lymphomas are good indications for radiotherapy: B lymphomas are electively treated with limited fields. The role of total skin electron therapy for T-lymphomas is still discussed; but palliative radiotherapy is very efficient in case of cutaneous nodules.

  12. Practical intraoperative stereo camera calibration.

    PubMed

    Pratt, Philip; Bergeles, Christos; Darzi, Ara; Yang, Guang-Zhong

    2014-01-01

    Many of the currently available stereo endoscopes employed during minimally invasive surgical procedures have shallow depths of field. Consequently, focus settings are adjusted from time to time in order to achieve the best view of the operative workspace. Invalidating any prior calibration procedure, this presents a significant problem for image guidance applications as they typically rely on the calibrated camera parameters for a variety of geometric tasks, including triangulation, registration and scene reconstruction. While recalibration can be performed intraoperatively, this invariably results in a major disruption to workflow, and can be seen to represent a genuine barrier to the widespread adoption of image guidance technologies. The novel solution described herein constructs a model of the stereo endoscope across the continuum of focus settings, thereby reducing the number of degrees of freedom to one, such that a single view of reference geometry will determine the calibration uniquely. No special hardware or access to proprietary interfaces is required, and the method is ready for evaluation during human cases. A thorough quantitative analysis indicates that the resulting intrinsic and extrinsic parameters lead to calibrations as accurate as those derived from multiple pattern views.

  13. Virtual intraoperative surgical photoacoustic microscopy

    NASA Astrophysics Data System (ADS)

    Lee, Changho; Lee, Donghyun; Zhou, Qifa; Kim, Jeehyun; Kim, Chulhong

    2015-07-01

    A virtual intraoperative surgical photoacoustic microscopy at 1064 nm wavelength (VISPAM) system was designed and fabricated by integrating a commercial type surgical microscope and laser scanning photoacoustic microscopy (PAM) with a 1064 nm pulsed laser. Based on simple augmented reality device, VISPAM could simultaneously provide 2D depth-resolved photoacoustic and magnified microscope images of surgery regions on the same vision of surgeon via an eyepiece of the microscope. The invisible 1064 nm laser removed the interruption of surgical sight due to visible laser scanning of previous report, and decreased the danger of tissue damage caused by over irradiated laser. In addition, to approach the real practical surgery application, a needle-type transducer was utilized without a water bath for PA signal coupling. In order to verify our system's performance, we conducted needle guiding as ex vivo phantom study and needle guiding and injection of carbon particles mixtures into a melanoma tumor region as in vivo study. We expect that VISPAM can be essential tool of brain and ophthalmic microsurgery.

  14. Intraoperative tractography and motor evoked potential (MEP) monitoring in surgery for gliomas around the corticospinal tract.

    PubMed

    Maesawa, Satoshi; Fujii, Masazumi; Nakahara, Norimoto; Watanabe, Tadashi; Wakabayashi, Toshihiko; Yoshida, Jun

    2010-07-01

    Our goal is to indicate the importance of combining intraoperative tractography with motor-evoked potential (MEP) monitoring for glioma surgery in motor eloquent areas. Tumor removal was performed in 28 patients with gliomas in and around the corticospinal tract (CST), in an operation theater equipped with an integrated high-field intraoperative magnetic resonance imaging and a neuronavigation system. Diffusion-tensor imaging-based tractography of the CST was implemented preoperatively and intraoperatively. When the surgically manipulated area came close to the corticospinal pathway, MEP responses were elicited by subcortical stimulation. Responsive areas were compared with the locations of fibers traced by preoperative and intraoperative tractography. Imaging and functional outcomes were reviewed. Intraoperative tractography demonstrated significant inward or outward shift during surgery. MEP responses were observed around the tract at various intensities, and the distance between MEP responsive sites and intraoperative tractography was significantly correlated with the stimulation intensity (P < 0.01). The distance from preoperative tractography was not correlated. A more than subtotal resection was achieved in 24 patients (85.7%). Transient motor deterioration was seen in 12 patients (42.8%), and a permanent deficit was seen in 1 patient (3.5%). We found that intraoperative tractography demonstrated the location of the CST more accurately than preoperative tractography. The results of the linear regression between distance and stimulation intensity were informative for guiding approaches to tumor remnants without impinging on the CST. The combination of intraoperative tractography and MEP monitoring can enhance the quality of surgery for gliomas in motor eloquent areas. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. High-Dose-Rate Brachytherapy of a Single Implant With Two Fractions Combined With External Beam Radiotherapy for Hormone-Naive Prostate Cancer

    SciTech Connect

    Sato, Morio Mori, Takashi; Shirai, Shintaro; Kishi, Kazushi; Inagaki, Takeshi; Hara, Isao

    2008-11-15

    Purpose: To evaluate the preliminary outcomes of high-dose-rate (HDR) brachytherapy of a single implant with two fractions and external beam radiotherapy (EBRT) for hormone-naive prostate cancer. Methods and Materials: Between March 2000 and Sept 2003, a total of 53 patients with tumor Stage T1c-T3b N0 M0 prostate cancer were treated with HDR brachytherapy boost doses (7.5 Gy/fraction) and 50-Gy EBRT during a 5.5-week period. Median follow-up was 61 months. Patients were divided into groups with localized (T1c-T2b) and advanced disease (T3a-T3b). We used the American Society for Therapeutic Radiology and Oncology (ASTRO) definition for biochemical failure. According to recommendations of the Radiation Therapy Oncology Group-ASTRO Phoenix Consensus Conference, biochemical failure-free control rates (BF-FCRs) at 3 years were investigated as 2 years short of the median follow-up. Results: Between April 2000 and Sept 2007, Common Terminology Criteria for Adverse Events Version 2.0 late Grade 2 genitourinary and gastrointestinal toxicity rates were 0% and 3.8%, respectively. Erectile preservation was 25% at 5 years. Overall survival was 88.1% and cause-specific survival was 100%. At 3 years, ASTRO BF-FCRs of the localized and advanced groups were 100% and 42%, respectively (p = 0.001). Conclusions: The HDR brachytherapy of a single implant with two fractions plus EBRT is effective in treating patients with localized hormone-naive prostate cancer, with the least genitourinary and gastrointestinal toxicities; however, longer median BF-FCR follow-up is required to assess these findings.

  16. Development of Late Toxicity and International Prostate Symptom Score Resolution After External-Beam Radiotherapy Combined With Pulsed Dose Rate Brachytherapy for Prostate Cancer

    SciTech Connect

    Pieters, Bradley R.; Rezaie, Elisa; Geijsen, Elisabeth D.; Koedooder, Kees; Grient, Johan N.B. van der; Blank, Leo E.C.M.; Reijke, Theo M. de; Koning, Caro C.E.

    2011-11-01

    Purpose: To investigate the development of gastrointestinal (GI) toxicity, genitourinary (GU) toxicity, erectile dysfunction, and International Prostate Symptom Score (IPSS) resolution in a cohort of patients treated with external-beam radiotherapy (EBRT) followed by a brachytherapy pulsed dose rate (PDR) boost. Methods and Materials: Between 2002 and 2008, 110 patients were treated with 46-Gy EBRT followed by PDR brachytherapy (24.96-28.80 Gy). The investigated outcome variables, GI toxicity, GU toxicity, erectile dysfunction, and IPSS were prospectively scored at several time points during follow-up. Association between time (as continuous and categorical variable) and the outcome variables was assessed using generalized linear models. Results: No statistically significant association was found between time (continuous) and GI toxicity (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.89-1.06), GU toxicity (OR, 0.97; 95% CI, 0.91-1.03), erectile dysfunction (OR, 1.06; 95% CI, 0.99-1.11), and IPSS (-0.11; 95% CI, -0.41-0.20). Also, no statistically significant association was found between these variables and time as a categorical variable. GU toxicity was associated with IPSS resolution (OR, 1.16; 95% CI, 1.09-1.24). Posttreatment IPSS was associated with pretreatment IPSS (0.52; 95% CI, 0.25-0.79). Conclusions: No accumulation of high-grade toxicity over time could be established for a group of patients treated with EBRT and PDR brachytherapy for prostate cancer, probably because high-grade late toxicity resolves with time. Also, differences in IPSS values among patients are smaller after treatment than before treatment.

  17. A phase I study on combined therapy with proton-beam radiotherapy and in situ tumor vaccination for locally advanced recurrent hepatocellular carcinoma

    PubMed Central

    2013-01-01

    Background Proton-beam radiotherapy (PBT) has been shown to be effective to hepatocellular carcinoma (HCC) as a nonsurgical local treatment option. However, HCC still remains as one of the most difficult cancers to be cured because of frequent recurrences. Thus, methods to inhibit the recurrence need to be explored. To prevent the HCC recurrence, we here report on a prospective phase I study of ‘in situ’ tumor vaccination using CalTUMP, a newly developed immunoadjuvant consisting of BCG extract bound to hydroxyapatite and microparticulated tuberculin, following local PBT for HCC. Methods Patients with locally advanced recurrent HCC, which had been heavily pretreated with various treatments, were enrolled. PBT was performed with the conventional method to the target HCC. Subsequently, CalTUMP was injected into the same irradiated-tumor three times at one-week intervals. Three dose-levels of CalTUMP (1/10, 1/3, and 1/1) were administered to 3 patients each. Vital signs, blood samples, ultrasound, and computed tomographic scans were monitored to evaluate the safety. Results Three intratumoral injections of CalTUMP following PBT (median dose: 72.6 GyE) were accomplished in 9 patients. Transient low-grade fever and minor laboratory changes were observed in 7 patients after CalTUMP injections. No other treatment-related adverse events were observed. Median progression-free survival was 6.0 months (range: 2.1-14.2) and 4 patients were progression-free for more than 1 year. Conclusions Intratumoral injection of CalTUMP following PBT was feasible and safe in patients with heavily pre-treated HCC. Further clinical studies to evaluate the efficacy of this in situ tumor vaccination are warranted. PMID:24131485

  18. Radiotherapy and Concomitant Intra-Arterial Docetaxel Combined With Systemic 5-Fluorouracil and Cisplatin for Oropharyngeal Cancer: A Preliminary Report-Improvement of Locoregional Control of Oropharyngeal Cancer

    SciTech Connect

    Oikawa, Hirobumi Nakamura, Ryuji; Nakasato, Tatsuhiko; Nishimura, Kohji; Sato, Hiroaki; Ehara, Shigeru

    2009-10-01

    Purpose: To confirm the advantage of chemoradiotherapy using intra-arterial docetaxel with intravenous cisplatin and 5-fluorouracil. Patients and Methods: A total of 26 oropharyngeal cancer patients (1, 2, 2, and 21 patients had Stage I, II, III, and IVa-IVc, respectively) were treated with two sessions of this chemoradiotherapy regimen. External beam radiotherapy was delivered using large portals that included the primary site and the regional lymph nodes initially (range, 40-41.4 Gy) and the metastatic lymph nodes later (60 or 72 Gy). All tumor-supplying branches of the carotid arteries were cannulated, and 40 mg/m{sup 2} docetaxel was individually infused on Day 1. The other systemic chemotherapy agents included 60 mg/m{sup 2} cisplatin on Day 2 and 500 mg/m{sup 2} 5-fluorouracil on Days 2-6. Results: The primary response of the tumor was complete in 21 (81%), partial in 4 (15%), and progressive in 1 patient. Grade 4 mucositis, leukopenia, and dermatitis was observed in 3, 2, and 1 patients, respectively. During a median follow-up of 10 months, the disease recurred at the primary site and at a distant organ in 2 (8%) and 3 (12%) patients, respectively. Three patients died because of cancer progression. Two patients (8%) with a partial response were compromised by lethal bleeding from the tumor bed or chemotherapeutic toxicity. The 3-year locoregional control rate and the 3-year overall survival rate was 73% and 77%, respectively. Conclusion: This method resulted in an excellent primary tumor response rate (96%) and moderate acute toxicity. Additional follow-up is required to ascertain the usefulness of this modality.

  19. Preoperative or postoperative radiotherapy versus surgery alone for retroperitoneal sarcoma: a case-control, propensity score-matched analysis of a nationwide clinical oncology database.

    PubMed

    Nussbaum, Daniel P; Rushing, Christel N; Lane, Whitney O; Cardona, Diana M; Kirsch, David G; Peterson, Bercedis L; Blazer, Dan G

    2016-07-01

    Recruitment into clinical trials for retroperitoneal sarcoma has been challenging, resulting in termination of the only randomised multicentre trial in the USA investigating perioperative radiotherapy. Nonetheless, use of radiotherapy for retroperitoneal sarcoma has increased over the past decade, substantiated primarily by its established role in extremity sarcoma. In this study, we used a nationwide clinical oncology database to separately compare overall survival for patients with retroperitoneal sarcoma who had surgery and preoperative radiotherapy or surgery and postoperative radiotherapy versus surgery alone. We did two case-control, propensity score-matched analyses of the National Cancer Data Base, which included adult patients with retroperitoneal sarcoma who were diagnosed from 2003 to 2011. Patients were included if they had localised, primary retroperitoneal sarcoma. Patients were classified into three groups based on use of radiotherapy: preoperative radiotherapy, postoperative radiotherapy, and no radiotherapy (surgery alone). Patients were excluded if they received both preoperative radiotherapy and postoperative radiotherapy, or if they received intraoperative radiotherapy. Parallel propensity score-matched datasets were created for patients who received preoperative radiotherapy versus those who received no radiotherapy and for patients who received postoperative therapy versus those who received no radiotherapy. Propensity scores were calculated with logistic regression, with multiple imputation and backwards elimination, with a significance level to stay of 0·05. Matching was done with a nearest-neighbour algorithm and matched 1:2 for the preoperative radiotherapy dataset and 1:1 for the postoperative radiotherapy dataset. The primary objective of interest was overall survival for patients who received preoperative radiotherapy or postoperative radiotherapy compared with those who received no radiotherapy within the propensity score

  20. Intraoperative neurophysiological monitoring in spinal surgery

    PubMed Central

    Park, Jong-Hwa; Hyun, Seung-Jae

    2015-01-01

    Recently, many surgeons have been using intraoperative neurophysiological monitoring (IOM) in spinal surgery to reduce the incidence of postoperative neurological complications, including level of the spinal cord, cauda equina and nerve root. Several established technologies are available and combined motor and somatosensory evoked potentials are considered mandatory for practical and successful IOM. Spinal cord evoked potentials are elicited compound potentials recorded over the spinal cord. Electrical stimulation is provoked on the dorsal spinal cord from an epidural electrode. Somatosensory evoked potentials assess the functional integrity of sensory pathways from the peripheral nerve through the dorsal column and to the sensory cortex. For identification of the physiological midline, the dorsal column mapping technique can be used. It is helpful for reducing the postoperative morbidity associated with dorsal column dysfunction when distortion of the normal spinal cord anatomy caused by an intramedullary cord lesion results in confusion in localizing the midline for the myelotomy. Motor evoked potentials (MEPs) consist of spinal, neurogenic and muscle MEPs. MEPs allow selective and specific assessment of the functional integrity of descending motor pathways, from the motor cortex to peripheral muscles. Spinal surgeons should understand the concept of the monitoring techniques and interpret monitoring records adequately to use IOM for the decision making during the surgery for safe surgery and a favorable surgical outcome. PMID:26380823

  1. Value of Intraoperative Sonography in Pancreatic Surgery.

    PubMed

    Weinstein, Stefanie; Morgan, Tara; Poder, Liina; Shin, Lewis; Jeffrey, R Brooke; Aslam, Rizwan; Yee, Judy

    2015-07-01

    The utility of intraoperative sonography for pancreatic disease has been well described for detection and evaluation of neoplastic and inflammatory pancreatic disease. Intraoperative sonography can help substantially reduce surgical time as well as decrease potential injury to tissues and major structures. Imaging with sonography literally at the point of care--the surgeon's scalpel--can precisely define the location of pancreatic lesions and their direct relationship with surrounding structures in real time during surgery. This article highlights our experience with intraoperative sonography at multiple institutional sites for both open and laparoscopic surgical procedures. We use intraoperative sonography for a wide range of pancreatic disease to provide accurate localization and staging of disease, provide guidance for enucleation of nonpalpable, nonvisible tumors, and in planning the most direct and least invasive surgical approach, avoiding injury to the pancreatic duct or other vital structures. © 2015 by the American Institute of Ultrasound in Medicine.