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Sample records for locoregionally advanced head

  1. Induction Chemotherapy for Locoregionally Advanced Head and Neck Cancer: Past, Present, Future?

    PubMed Central

    Hanna, Glenn J.; Haddad, Robert I.

    2013-01-01

    The treatment of patients with locoregionally advanced squamous cell cancer of the head and neck is still evolving. Induction chemotherapy (IC) is widely used in this patient population and it is unclear how to best incorporate IC into multimodality treatment. Recently, the results of two randomized clinical trials were presented (the PARADIGM and Docetaxel Based Chemotherapy Plus or Minus Induction Chemotherapy to Decrease Events in Head and Neck Cancer trials), which showed no demonstrable benefit of IC followed by concurrent chemoradiation over concurrent chemoradiotherapy alone. However, a lower rate of distant metastatic disease was noted, suggesting that patients who are at high risk for metastatic disease may benefit from IC. This review summarizes how IC has evolved over the years, provides an update of recent developments, and discusses how IC may develop in the future. PMID:23442306

  2. Diagnosis-to-treatment interval and control of locoregionally advanced head and neck cancer.

    PubMed

    Caudell, Jimmy J; Locher, Julie L; Bonner, James A

    2011-03-01

    To assess the impact of prolonged diagnosis-to-treatment interval (DTI) that falls in the time frame associated with the increasing complexity of planning treatment for patients with locoregionally advanced head and neck cancer (LAHNC). Retrospective study. The University of Alabama at Birmingham. An institutional database was searched for all patients with LAHNC who were treated with radiotherapy between 1995 and 2007 at the University of Alabama at Birmingham. After patients with prior treatment for head and neck cancer (including surgery or neoadjuvant chemotherapy), patients younger than 18 years, and patients with stage I or II tumors were excluded, 427 patients remained for analysis. The DTI was defined as the time in days between the date that a biopsy specimen showing malignancy was obtained and the first day of radiotherapy. The median DTI was 34 days (range, 7-441 days). A longer DTI was not significantly associated with locoregional control (P = .11), distant metastases-free survival (P = .32), or overall survival (P = .07). A prolonged DTI did not appear to adversely affect outcomes in this cohort of patients with LAHNC.

  3. Factors associated with long-term speech and swallowing outcomes after chemoradiotherapy for locoregionally advanced head and neck cancer.

    PubMed

    Mouw, Kent W; Haraf, Daniel J; Stenson, Kerstin M; Cohen, Ezra E; Xi, Xi; Witt, Mary Ellyn; List, Marcy; Blair, Elizabeth A; Vokes, Everett E; Salama, Joseph K

    2010-12-01

    to identify factors that influence patient-centered measures of speech and swallowing function after successful use of chemoradiotherapy to treat cancers of the head and neck. patients previously enrolled in a phase 2 trial using induction chemotherapy consisting of carboplatin and paclitaxel followed by chemoradiotherapy with paclitaxel, fluorouracil, hydroxyurea, and 1 of 3 radiation dose levels were assigned speaking and swallowing scores at follow-up ranging from 1 to 4, with 1 representing normal speech or swallowing and 4 representing significant sustained deficits. one hundred eighty-four patients with locoregionally advanced head and neck cancer. speech and swallowing function after chemoradiotherapy. of the 222 patients originally enrolled in the trial, 184 were alive and free of locoregional recurrence at the outset of this study. Of these eligible patients, 163 (88.6%) were assigned a speaking score of 1 through 4 at an average of 34.8 (range, 1.5-76.4) months after completion of treatment, whereas 166 patients (90.2%) were assigned a swallowing score of 1 through 4 at an average of 34.5 (range, 1.0-76.4) months after completion of treatment. Most patients (84.7% with speaking scores and 63.3% with swallowing scores) had no residual deficit and were assigned scores of 1. Factors that were associated with worse speaking outcomes included female sex, smoking history, hypopharyngeal or laryngeal primary sites, and poor response to induction chemotherapy; factors associated with worse swallowing outcomes included advanced patient age, poor performance status, primary site, and neck dissection. among patients successfully treated for locoregionally advanced cancers of the head and neck, several factors correlate with speaking and swallowing outcomes. Because advances in therapy have led to improved survival in these patients, understanding and controlling adverse effects of treatment should continue to be an active area of investigation.

  4. Clinical Practice Guidance for Radiotherapy Planning After Induction Chemotherapy in Locoregionally Advanced Head-and-Neck Cancer

    SciTech Connect

    Salama, Joseph K.; Haddad, Robert I.; Kies, Merril S.; Busse, Paul M.; Dong Lei; Brizel, David M.; Eisbruch, Avraham; Tishler, Roy B.; Trotti, Andy M.; Garden, Adam S.

    2009-11-01

    Purpose: The use of induction chemotherapy (IC) for locoregionally advanced head-and-neck cancer is increasing. The response to IC often causes significant alterations in tumor volume and location and shifts in normal anatomy. Proper determination of the radiotherapy (RT) targets after IC becomes challenging, especially with the use of conformal and precision RT techniques. Therefore, a consensus conference was convened to discuss issues related to RT planning and coordination of care for patients receiving IC. Methods and Materials: Ten participants with special expertise in the various aspects of integration of IC and RT for the treatment of locoregionally advanced head-and-neck cancer, including radiation oncologists, medical oncologists, and a medical physicist, participated. The individual members were assigned topics for focused, didactic presentations. Discussion was encouraged after each presentation, and recommendations were formulated. Results: Recommendations and guidelines emerged that emphasize up-front evaluation by all members of the head-and-neck management team, high-quality baseline and postinduction planning scans with the patient in the treatment position, the use of preinduction target volumes, and the use of full-dose RT, even in the face of a complete response. Conclusion: A multidisciplinary approach is strongly encouraged. Although these recommendations were provided primarily for patients treated with IC, many of these same principles apply to concurrent chemoradiotherapy without IC. A rapid response during RT is quite common, requiring the development of two or more plans in a sizeable fraction of patients, and suggesting the need for similar guidance in the rapidly evolving area of adaptive RT.

  5. Positron Emission Tomography for Neck Evaluation Following Definitive Treatment with Chemoradiotherapy for Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Bar-Ad, Voichita; Mishra, Mark; Ohri, Nitin; Intenzo, Charles

    2013-01-01

    Objectives The objective of the current review was to assess published data on the role of Positron Emission Tomography (PET) for evaluation of nodal residual disease after definitive chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC). Methods Studies were identified by searching PubMed electronic databases. Only studies using a post-chemoradiotherapy PET for nodal residual disease evaluation were included in the present review. Both prospective and retrospective studies were included. Information regarding sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET for detecting nodal residual disease after definitive chemoradiotherapy for HNSCC was extracted and analyzed. Results Twenty published studies were included in the present review. Existing data suggest that a negative post-chemoradiotherapy PET scan is associated with a negative predictive value up to 100%. The sensitivity of PET in detecting nodal residual disease is greater for scans performed ≥ 10 weeks after definitive treatment with chemoradiotherapy for HNSCC. Conclusions Further studies are needed to quantify the reliability of PET in detecting nodal residual disease after chemoradiotherapy for locoregionally advanced HNSCC. The optimal timing of PET imaging after chemoradiotherapy remains to be defined. PMID:21864252

  6. IMRT With Simultaneous Integrated Boost and Concurrent Chemotherapy for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Montejo, Michael E.; Shrieve, Dennis C.; Bentz, Brandon G.; Hunt, Jason P.; Buchman, Luke O.; Agarwal, Neeraj; Hitchcock, Ying J.

    2011-12-01

    Purpose: To evaluate the efficacy and toxicity of accelerated radiotherapy with concurrent chemotherapy in advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between April 2003 and May 2008, 43 consecutive patients with advanced head-and-neck squamous cell carcinoma received accelerated chemoradiation with concurrent cisplatin or cetuximab. The doses for intensity-modulated radiotherapy with simultaneous integrated boost were 67.5, 60.0, and 54 Gy in 30 daily fractions of 2.25, 2.0, and 1.8 Gy to the planning target volumes for gross disease, high-risk nodes, and low-risk nodes, respectively. Results: Of the patients, 90.7% completed chemoradiotherapy as prescribed. The median treatment duration was 43 days (range, 38-55 days). The complete response rate was 74.4%. With median follow-up of 36.7 months (range, 16.8-78.1 months) in living patients, the estimated 1-, 2-, and 5-year locoregional control, overall survival, and disease-free survival rates were 82%, 82%, and 82%; 73%, 65%, and 61%; and 73%, 73%, and 70%, respectively. One treatment-related death occurred from renal failure. Grade 3 mucositis and dermatitis occurred in 13 patients (30.2%) and 3 patients (6.9%), respectively. Grade 2 xerostomia occurred in 12 patients (27.9%). In patients with adequate follow-up, 82% were feeding tube free by 6 months after therapy; 13% remained feeding tube dependent at 1 year. Grade 3 soft-tissue fibrosis, esophageal stricture, osteoradionecrosis, and trismus occurred in 3 patients (6.9%), 5 patients (11.6%), 1 patient (2.3%), and 3 patients (6.9%), respectively. Conclusions: Our results show that intensity-modulated radiotherapy with simultaneous integrated boost with concurrent chemotherapy improved local and regional control. Acute and late toxicities were tolerable and acceptable. A prospective trial of this fractionation regimen is necessary for further assessment of its efficacy and toxicity compared with other approaches.

  7. Concomitant chemoradiotherapy versus altered fractionation radiotherapy in the radiotherapeutic management of locoregionally advanced head and neck squamous cell carcinoma: An adjusted indirect comparison meta-analysis.

    PubMed

    Gupta, Tejpal; Kannan, Sadhana; Ghosh-Laskar, Sarbani; Agarwal, Jai Prakash

    2015-05-01

    Treatment intensification by using chemoradiotherapy (CRT) or altered fractionation radiotherapy (RT) improves outcomes in locoregionally advanced head and neck squamous cell carcinoma (HNSCC). Two comprehensive meta-analyses with similar control arms (conventionally fractionated RT) were compared indirectly. The hazard ratio (HR) of death with 95% confidence interval (CI) for the overall comparison of altered fractionation RT with concomitant CRT was 1.13 (95% CI, 0.97-1.29; p = .07) suggesting no significant difference between both approaches. Compared to concomitant CRT, the HR for death was 1.01 (95% CI, 0.89-1.15; p = .82); 1.22 (95% CI, 0.94-1.59; p = .13); and 1.22 (95% CI, 1.07-1.39; p = .002) for hyperfractionated RT; accelerated RT without total dose reduction; and accelerated RT with total dose reduction, respectively. Concomitant CRT and hyperfractionated RT are comparable to one another on indirect comparison in the radiotherapeutic management of locoregionally advanced HNSCC. Any form of acceleration (with or without total dose reduction) may not compensate fully for lack of chemotherapy. © 2014 Wiley Periodicals, Inc.

  8. The Older Adult With Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: Knowledge Gaps and Future Direction in Assessment and Treatment.

    PubMed

    Maggiore, Ronald; Zumsteg, Zachary S; BrintzenhofeSzoc, Karlynn; Trevino, Kelly M; Gajra, Ajeet; Korc-Grodzicki, Beatriz; Epstein, Joel B; Bond, Stewart M; Parker, Ira; Kish, Julie A; Murphy, Barbara A; VanderWalde, Noam A

    2017-07-15

    Older adults with head and neck squamous cell carcinoma (HNSCC) pose unique treatment and supportive care challenges to oncologists and other cancer care providers. The majority of patients with HNSCC present with locoregionally advanced disease, for which combined-modality treatment integrating chemotherapy and radiation therapy is often necessary to maximize tumor control. However, applying these approaches to an older population with concomitant comorbidities and a higher risk of functional impairments remains challenging and is exacerbated by the paucity of studies involving older adults. The purpose of this article is to identify knowledge gaps in the evaluation and management of older adults with HNSCC-particularly those undergoing concurrent chemoradiation therapy-and their caregivers through a review of the literature conducted by clinicians, researchers, and patient advocates. The findings highlight the importance of a geriatric assessment and the therapeutic paradigms and challenges relevant to this population. Furthermore, we identify the need for additional research and interventions related to key supportive care issues that arise during and after treatment in older adults with locoregionally advanced HNSCC. On the basis of our findings, we prioritize these issues to guide future patient-oriented research endeavors to address these knowledge gaps and thus better serve this growing patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Phase I Trial of Intravenous Oncolytic Vaccinia Virus (GL-ONC1) with Cisplatin and Radiotherapy in Patients with Locoregionally Advanced Head and Neck Carcinoma.

    PubMed

    Mell, Loren K; Brumund, Kevin T; Daniels, Gregory A; Advani, Sunil J; Zakeri, Kaveh; Wright, Mary E; Onyeama, Sara-Jane; Weisman, Robert A; Sanghvi, Parag R; Martin, Peter J; Szalay, Aladar A

    2017-10-01

    Purpose: Preclinical models have shown that the effectiveness of GL-ONC1, a modified oncolytic vaccinia virus, is enhanced by radiation and chemotherapy. The purpose of this study was to determine the safety of GL-ONC1 when delivered intravenously with chemoradiotherapy to patients with primary, nonmetastatic head and neck cancer.Experimental Design: Patients with locoregionally advanced unresected, nonmetastatic carcinoma of the head/neck, excluding stage III-IVA p16-positive oropharyngeal cancers, were treated with escalating doses and cycles of intravenous GL-ONC1, along with radiotherapy and chemotherapy. The primary aims were to define the MTD and dose-limiting toxicities, and to recommend a dose for phase II trials.Results: Between May 2012 and December 2014, 19 patients were enrolled. The most frequent adverse reactions included grade 1-2 rigors, fever, fatigue, and rash. Grade 3 adverse reactions included hypotension, mucositis, nausea, and vomiting. In 2 patients, the rash was confirmed as viral in origin by fluorescence imaging and viral plaque assay. In 4 patients, viral presence in tumor was confirmed on midtreatment biopsy by quantitative PCR. In 1 patient, live virus was confirmed in a tongue tumor 7 days after receiving the first dose of virus. The MTD was not reached. With median follow-up of 30 months, 1-year (2-year) progression-free survival and overall survival were 74.4% (64.1%) and 84.6% (69.2%), respectively.Conclusions: Delivery of GL-ONC1 is safe and feasible in patients with locoregionally advanced head/neck cancer undergoing standard chemoradiotherapy. A phase II study is warranted to further investigate this novel treatment strategy. Clin Cancer Res; 23(19); 5696-702. ©2017 AACR. ©2017 American Association for Cancer Research.

  10. Phase II clinical trial of cisplatin, 5-fluorouracil, and ifosfamide as treatment for advanced locoregional head and neck carcinoma.

    PubMed

    Sánchez Parra, M; Churruca, C; Paredes, A; Lacasta, A; López de Argumedo, G; Alvárez, I; Abad, T; Egana, L; Guimón, E; Piera, J M

    1999-02-01

    The association of ifosfamide with cisplatin and 5-fluorouracil for the management of advanced squamous cell carcinoma of the head and neck was assessed in this trial. Ifosfamide was given initially to 12 patients in combination with standard fixed doses of cisplatin and 5-fluorouracil, at 1,000 mg/m2 daily on days 2, 3, and 4. Two patients died of neutropenia and severe infection, and the authors recruited seven more patients who were treated with a lower dose of ifosfamide, 800 mg/m2 daily on days 2, 3, and 4. One of the seven patients died of neutropenia and severe infection. Three complete remission were observed in 18 patients evaluable for efficacy. The study was closed early because of the severe toxicity profile demonstrated by this scheme and because of no clear advantage in efficacy versus cisplatin plus 5-fluorouracil combinations.

  11. Concurrent Radiotherapy with Carboplatin and Cetuximab for the Treatment of Medically Compromised Patients with Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Saigal, Kunal; Santos, Edgardo S.; Tolba, Khaled; Kwon, Deukwoo; Elsayyad, Nagy; Abramowitz, Matthew C.; Mandalia, Amar; Samuels, Michael Andrew

    2014-01-01

    Background: Cetuximab (Cx) + radiation therapy (RT) is well-tolerated and has improved survival in patients (pts) with locoregionally advanced head and neck squamous cell carcinomas (LA-HNSCC). However, its efficacy when compared to HD-DDP + RT has been questioned. At our institution, low-dose weekly carboplatin is added to Cx + RT for patients unsuitable for HD-DDP. Methods: We reviewed records of 16 patients with LA-HNSCC treated with definitive Cx + carboplatin + RT at the University of Miami from 2007 to 2011. Median follow-up was 24 months (range: 1–69 months). Results: Median age: 71.5 years (range: 57–90 years); 15 male, 1 female. ECOG PS 0 = 15, 1 = 1. TNM staging was: T1 = 1, T2 = 5, T3 = 8, T4 = 2; N stage: N0 = 8, N1 = 5, N2a = 2, N2b = 1. All patients received weekly carboplatin (AUC 1.5–2), Cx given conventionally and daily conventionally fractionated RT. Median total weeks of concurrent systemic therapy = 7 (range: 3–8 weeks). RT was delivered to a median total dose of 70 Gy (range 30–74 Gy). Of the 15 evaluable patients, there were: 12 CR, 2 PR, and 1 PD. There were three local in-field failures, two regional failures, and three distant failures. At last follow-up, 8/15 patients remained with NED. Three-year locoregional recurrence was 28.3% (95% CI: 7.7–53.9%). Mean percentage of weight loss was 14% (range: 6–26%). Two patients required systemic therapy dose reduction. Three patients experienced a treatment delay and three did not finish RT as planned including a patient who received only 30 Gy due to death secondary to MI during treatment. Conclusion: In this small retrospective series, carboplatin/Cx/RT was well-tolerated and efficacious in patients unsuitable for HD-DDP having LA-HNSCC. Acute toxicities were similar to Cx + RT, likely due to the non-overlapping toxicity profiles of the two systemic agents. We hypothesize that the addition of a well

  12. Locoregionally Advanced Head and Neck Cancer Treated With Primary Radiotherapy: A Comparison of the Addition of Cetuximab or Chemotherapy and the Impact of Protocol Treatment

    SciTech Connect

    Caudell, Jimmy J.; Sawrie, Stephen M.; Spencer, Sharon A.; Desmond, Renee A.; Carroll, William R.; Peters, Glenn E.; Nabell, Lisle M.; Meredith, Ruby F.; Bonner, James A.

    2008-07-01

    Purpose: The addition of platinum-based chemotherapy (ChRT) or cetuximab (ExRT) to concurrent radiotherapy (RT) has resulted in improved survival in Phase III studies for locoregionally advanced head and neck cancer (LAHNC). However the optimal treatment regimen has not been defined. A retrospective study was performed to compare outcomes in patients who were treated definitively with ExRT or ChRT. Methods: Cetuximab with concurrent RT was used to treat 29 patients with LAHNC, all of whom had tumors of the oral cavity, oropharynx, or larynx. All patients were T2 to T4 and overall American Joint Committee on Cancer Stage III to IVB, with a Karnofsky Performance Status (KPS) score of 60 or greater. ChRT was used to treat 103 patients with similar characteristics. Patients were evaluated for locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS). Median follow-up for patients alive at last contact was 83 months for those treated with ExRT and 53 months for those treated with ChRT. Cox proportional hazard models were used to assess independent prognostic factors. Results: The LRC, DMFS, and DSS were not significantly different, with 3-year rates of 70.7%, 92.4%, and 78.6% for ExRT and 74.7%, 86.6%, and 76.5% for ChRT, respectively. The OS was significantly different between the two groups (p = 0.02), with 3-year rates of 75.9% for ExRT and 61.3% for ChRT. OS was not significant when patients who were on protocol treatments of ExRT or ChRT were compared. Also, OS was not significant when multivariate analysis was used to control for potential confounding factors. Conclusion: In our single-institution retrospective review of patients treated with ExRT or ChRT, no significant differences were found in LRC, DMFS, DSS, or OS.

  13. Correlation of p16 status, hypoxic imaging using [18F]-misonidazole positron emission tomography and outcome in patients with loco-regionally advanced head and neck cancer.

    PubMed

    Trinkaus, Mateya E; Hicks, Rodney J; Young, Richard J; Peters, Lester J; Solomon, Ben; Bressel, Mathias; Corry, June; Fisher, Richard; Binns, David; McArthur, Grant A; Rischin, Danny

    2014-02-01

    We investigated the relationship between hypoxia, human papillomavirus (HPV) status and outcome in head and neck squamous cell carcinoma. Patients with stage III and IV head and neck squamous cell carcinoma treated on phase I and II chemoradiation trials with 70-Gy radiation combined with tirapazamine/cisplatin or cisplatin/fluorouracil (5FU), hypoxic imaging using [18F]-misonidazole positron emission tomography and known HPV status (by p16 immunohistochemistry) were included in this sub-study. Separate analyses were conducted to consider the impact of tirapazamine on HPV-negative tumours in the phase II trial. Both p16-positive oropharyngeal tumours and p16-negative head and neck squamous cell carcinoma tumours had a high prevalence of tumour hypoxia; 14/19 (74%) and 35/44 (80%), respectively. The distribution of hypoxia (primary, nodal) was similar. On phase II, trial patients with p16-negative hypoxic tumours had worse loco-regional control with cisplatin and 5FU compared with tirapazamine and cisplatin (P < 0.001) and worse failure-free survival (hazard ratio = 5.18; 95% confidence interval, 1.98-13.55; P = 0.001). Only 1 out of 14 p16-positive patients on the phase II trial experienced loco-regional failure. Hypoxia, as assessed by [18F]-misonidazole positron emission tomography, is frequently present in both p16-positive and negative head and neck cancer. Further research is required to determine whether hypoxic imaging can be used to predict benefit from hypoxia-targeting therapies in patients with p16-negative tumours. © 2014 The Royal Australian and New Zealand College of Radiologists.

  14. Free and locoregional flap associations in the reconstruction of extensive head and neck defects.

    PubMed

    Bianchi, B; Ferri, A; Ferrari, S; Copelli, C; Poli, T; Sesenna, E

    2008-08-01

    Head and neck surgical defects after oncological resection of advanced carcinoma involving the oral cavity are often composite and involve bone, mucosa, soft tissues and skin. For the most extensive defects, the simultaneous association of two free flaps is the best choice to improve the function of the preserved structures. This procedure is difficult and involves prolonged surgery, therefore it is only possible in selected patients. In some composite head and neck defects the association of free and locoregional flaps seems to be indicated. This study, discusses the use of free and locoregional flap association, focusing on its aesthetic advantages and functional results. From January 1995 to December 2006, 30 patients received simultaneous locoregional and free flap transfer for closure of post-ablative oral cavity defects. Microvascular tissue transfer included the radial forearm, anterolateral thigh, rectus abdominis, and fibula and iliac crest free flaps. Locoregional flaps included the cervicofacial, cervicopectoral, deltopectoral, pectoralis major, latissimus dorsi and posterior scalp flaps. Based on the good functional and aesthetic outcome and low rate of complications, the association of free and locoregional flaps represents a good reconstructive option for patients with extensive post-oncological composite head and neck defects.

  15. Systematic Review and Meta-analysis of Conventionally Fractionated Concurrent Chemoradiotherapy versus Altered Fractionation Radiotherapy Alone in the Definitive Management of Locoregionally Advanced Head and Neck Squamous Cell Carcinoma.

    PubMed

    Gupta, T; Kannan, S; Ghosh-Laskar, S; Agarwal, J P

    2016-01-01

    Treatment intensification either by using concurrent chemoradiotherapy (CCRT) or altered fractionation radiotherapy (AFRT) improves outcomes of locoregionally advanced head and neck squamous cell carcinoma (HNSCC). The superiority of one approach over the other, however, remains to be firmly established. The aim of the present study was to compare outcomes of CCRT versus AFRT in the definitive non-surgical management of locoregionally advanced HNSCC for evidence-based decision making. An electronic search of Medline via PubMed was conducted with no language, year, or publication status restrictions. The Cochrane Central Register of Controlled Trials (CENTRAL) and Database of Abstracts of Reviews of Effectiveness (DARE) were also searched electronically. Only randomised controlled trials assigning HNSCC patients randomly to conventionally fractionated CCRT or AFRT alone were included. Data were extracted independently by two reviewers and pooled using the Cochrane methodology for meta-analysis and expressed as a hazard ratio with 95% confidence intervals. Overall survival was the primary outcome of interest, whereas disease-free survival, locoregional control and toxicity were secondary end points. Five randomised controlled trials (involving 1117 patients and 627 deaths) directly comparing conventionally fractionated CCRT with AFRT alone were included. The risk of bias in included studies was low for efficacy outcomes, but high for toxicity outcomes. The overall pooled hazard ratio of death was 0.73 (95% confidence interval = 0.62-0.86), which significantly favoured conventionally fractionated CCRT over AFRT alone (P < 0.0001). Similarly, disease-free survival (hazard ratio = 0.79, 95% confidence interval = 0.68-0.92; P = 0.002) and locoregional control (hazard ratio = 0.71, 95% confidence interval = 0.59-0.84; P < 0.0001) were significantly improved with CCRT. There were no significant differences in the incidence of severe acute toxicity (dermatitis and mucositis

  16. Salvage surgery for locoregional recurrences of advanced pharyngolaryngeal squamous cell carcinoma after organ preservation failure.

    PubMed

    López Delgado, I; Riestra Ayora, J; Arenas Brítez, O; García López, I; Martínez Guirado, T; Scola Yurrita, B

    2014-12-01

    Organ preservation treatment for advanced head and neck squamous cell carcinoma is associated with poor outcomes due to locoregional recurrences. Salvage surgery is the main therapeutic option for some of these patients. The aim of this study was to analyse the results of salvage surgery for advanced pharyngolaryngeal squamous cell carcinoma previously treated with radiochemotherapy. We performed a retrospective study on 38 patients (36 men, 2 women). The median age at diagnosis was 60 years with a mean follow-up period of 49.8 months. Recurrences were diagnosed at a mean of 395 days after finalising organ preservation treatment. Patients went under different salvage surgeries, including 22 total laryngectomies, 6 partial laryngectomies (3 transoral laser surgeries and 3 opened surgeries), 8 functional neck dissections and 2 tongue base surgeries. Nineteen patients had no postoperative complications after a mean hospital stay of 2 weeks. However, 5 patients died of significant recurrent bleedings. There were 4 salivary fistulas that responded to conservative management, while 7 patients had important pharyngostomas that required reconstruction with either regional or free flaps. The mean hospital stay was of 61.60 days for all patients. Five-year overall survival from diagnosis, overall survival after salvage surgery and survival after salvage surgery were 44.20, 37.90 and 45.70%, respectively. In summary, we conclude that salvage surgery is an optimal treatment for pharyngolaryngeal and regional recurrences and provides improvement in locoregional control and survival, despite the severe complications.

  17. Is Gemcitabine and Cisplatin Induction Chemotherapy Superior in Locoregionally Advanced Nasopharyngeal Carcinoma?

    PubMed Central

    Zheng, Wei; Qiu, Sufang; Huang, Lingling; Pan, Jianji

    2015-01-01

    Objective: To investigate the outcome of locoregionally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy followed by chemoradiotherapy. Methods: Between June 2005 and October 2007, 604 patients with locoregionally advanced NPC were analyzed, of whom 399 and 205 were treated with conventional radiotherapy and intensity-modulated radiotherapy (IMRT) respectively. Meanwhile, 153 patients received concurrent chemotherapy, and 520 were given induction chemotherapy. Results: With a median follow-up time of 65 months, the 3-, and 5-year overall survival (OS), locoregional free survival (LRFS), and distant-metastasis free survival (DMFS) rates were 82.5% vs. 72.6%, 90.6% vs. 87.1%, and 82.5% vs. 81.2%, respectively. Induction chemotherapy was not an independent prognostic factor for OS (P=0.193) or LRFS, but there was a positive tendency for DMFS (P=0.088). GP regimen (gemcitabine + cisplatin) was an independent prognostic factor for OS (P = 0.038) and it had a trend toward improved DMFS (P = 0.109). TP regimen (taxol + cisplatin) was only a significant prognostic factor for DMFS (P =0.038). Conclusions: Adding induction chemotherapy had no survival benefit, but GP regimen benefited overall survival and had a trend toward improved DMFS. GP regimen may be superior to TP/FP regimen (fluorouracil + cisplatin) in treating locoregionally advanced NPC. PMID:26430402

  18. Pretreatment Quality of Life Predicts for Locoregional Control in Head and Neck Cancer Patients: A Radiation Therapy Oncology Group Analysis

    SciTech Connect

    Siddiqui, Farzan; Pajak, Thomas F.; Watkins-Bruner, Deborah; Konski, Andre A.; Coyne, James C.; Gwede, Clement K.; Garden, Adam S.; Spencer, Sharon A.; Jones, Christopher; Movsas, Benjamin

    2008-02-01

    Purpose: To analyze the prospectively collected health-related quality-of-life (HRQOL) data from patients enrolled in two Radiation Therapy Oncology Group randomized Phase III head and neck cancer trials (90-03 and 91-11) to assess their value as an independent prognostic factor for locoregional control (LRC) and/or overall survival (OS). Methods and Materials: HRQOL questionnaires, using a validated instrument, the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H and N), version 2, were completed by patients before the start of treatment. OS and LRC were the outcome measures analyzed using a multivariate Cox proportional hazard model. Results: Baseline FACT-H and N data were available for 1,093 patients and missing for 417 patients. No significant difference in outcome was found between the patients with and without baseline FACT-H and N data (p = 0.58). The median follow-up time was 27.2 months for all patients and 49 months for surviving patients. Multivariate analyses were performed for both OS and LRC. Beyond tumor and nodal stage, Karnofsky performance status, primary site, cigarette use, use of concurrent chemotherapy, and altered fractionation schedules, the FACT-H and N score was independently predictive of LRC (but not OS), with p = 0.0038. The functional well-being component of the FACT-H and N predicted most significantly for LRC (p = 0.0004). Conclusions: This study represents, to our knowledge, the largest analysis of HRQOL as a prognostic factor in locally advanced head and neck cancer patients. The results of this study have demonstrated the importance of baseline HRQOL as a significant and independent predictor of LRC in patients with locally advanced head and neck cancer.

  19. Weekly Low-Dose Versus Three-Weekly High-Dose Cisplatin for Concurrent Chemoradiation in Locoregionally Advanced Non-Nasopharyngeal Head and Neck Cancer: A Systematic Review and Meta-Analysis of Aggregate Data.

    PubMed

    Szturz, Petr; Wouters, Kristien; Kiyota, Naomi; Tahara, Makoto; Prabhash, Kumar; Noronha, Vanita; Castro, Ana; Licitra, Lisa; Adelstein, David; Vermorken, Jan B

    2017-09-01

    Three-weekly high-dose cisplatin (100 mg/m(2)) is considered the standard systemic regimen given concurrently with postoperative or definitive radiotherapy in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, due to unsatisfactory patient tolerance, various weekly low-dose schedules have been increasingly used in clinical practice. The aim of this meta-analysis was to compare the efficacy, safety, and compliance between these two approaches. We systematically searched literature for prospective trials of patients with LA-SCCHN who received postoperative or definitive conventionally fractionated concurrent chemoradiation. Radiation doses were usually 60-66 gray (Gy) in the postoperative setting and 66-70 Gy in the definitive setting. Standard, three-weekly high-dose cisplatin (100 mg/m(2), 3 doses) was compared with the weekly low-dose protocol (≤50 mg/m(2), ≥6 doses). The primary endpoint was overall survival. Secondary outcomes comprised response rate, acute and late adverse events, and treatment compliance. Fifty-two studies with 4,209 patients were included in two separate meta-analyses according to the two clinical settings. There was no difference in treatment efficacy as measured by overall survival or response rate between the chemoradiation settings with low-dose weekly and high-dose three-weekly cisplatin regimens. In the definitive treatment setting, the weekly regimen was more compliant and significantly less toxic with respect to severe (grade 3-4) myelosuppression (leukopenia p = .0083; neutropenia p = .0024), severe nausea and/or vomiting (p < .0001), and severe nephrotoxicity (p = .0099). Although in the postoperative setting the two approaches were more equal in compliance and with clearly less differences in the cisplatin-induced toxicities, the weekly approach induced more grade 3-4 dysphagia (p = .0026) and weight loss (p < .0001). In LA-SCCHN, current evidence is insufficient to

  20. MiR-422a promotes loco-regional recurrence by targeting NT5E/CD73 in head and neck squamous cell carcinoma.

    PubMed

    Bonnin, Nathalie; Armandy, Emma; Carras, Julien; Ferrandon, Sylvain; Battiston-Montagne, Priscillia; Aubry, Marc; Guihard, Sébastien; Meyronet, David; Foy, Jean-Philippe; Saintigny, Pierre; Ledrappier, Sonia; Jung, Alain; Rimokh, Ruth; Rodriguez-Lafrasse, Claire; Poncet, Delphine

    2016-07-12

    At the time of diagnosis, 60% of patients with head and neck squamous cell carcinoma (HNSCC) present tumors in an advanced stage (III-IV) of disease and 80% will relapse within the first two years post-treatment, due to their frequent radio(chemo)resistance. To identify new molecular targets and companion biomarkers, we have investigated the miRNome of 75 stage III-IV oropharynx tumors without relapse (R) or with loco-regional relapse (non-responder, NR) within two years post-treatment. Interestingly, miR-422a was significantly downregulated in NR tumors, in agreement with the increase in cell proliferation and adhesion induced by miR-422a inhibition in vitro. Furthermore, we identified CD73/NT5E oncogene as target of miR-422a. Indeed, modulation of the endogenous level of miR-422a inversely influences the expression and the enzymatic activity of CD73. Moreover, knocking down CD73 mimics the effects of miR-422a upregulation. Importantly, in tumors, miR-422a and CD73 expression levels are inversely correlated, and both are predictive of relapse free survival - especially considering loco(regional) recurrence - in vitro two independent cohorts of advanced oropharynx or HNSCC (N=255) tumors. In all, we reported, for the first time, that MiR-422a and its target CD73 are involved in early loco(regional) recurrence of HNSCC tumors and are new targets for personalized medicine.

  1. Association of Human Papillomavirus and p16 Status With Outcomes in the IMCL-9815 Phase III Registration Trial for Patients With Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma of the Head and Neck Treated With Radiotherapy With or Without Cetuximab

    PubMed Central

    Rosenthal, David I.; Harari, Paul M.; Giralt, Jordi; Bell, Diana; Raben, David; Liu, Joyce; Schulten, Jeltje; Ang, Kian K.

    2016-01-01

    Purpose We conducted a retrospective evaluation of the IMCL-9815 study to examine the association of human papillomavirus (HPV) and p16 protein expression status with outcomes in patients with oropharyngeal carcinoma (OPC) receiving radiotherapy (RT) plus cetuximab or RT alone. Patients and Methods In the IMCL-9815 study, patients were randomly allocated to receive RT plus weekly cetuximab or RT alone. A subpopulation of patients with p16-evaluable OPC was retrospectively evaluated on the basis of locoregional control (LRC), overall survival (OS), and progression-free survival (PFS). Evaluable samples from patients with p16-positive OPC were also tested for HPV DNA. Results Tumor p16 status was evaluable in 182 patients with OPC enrolled in the IMCL-9815 study; 41% were p16 positive. When treated with RT alone or RT plus cetuximab, p16-positive patients had a longer OS than p16-negative patients (hazard ratio, 0.40; 95% CI, 0.21 to 0.74 and hazard ratio, 0.16; 95% CI, 0.07 to 0.36, respectively). The addition of cetuximab to RT increased LRC, OS, and PFS in both patients with p16-positive OPC and those with p16-negative disease. Interaction tests for LRC, OS, and PFS did not demonstrate any significant interaction between p16 status and treatment effect (P = .087, .085, and .253, respectively). Similar trends were observed when patients with p16-positive/HPV-positive OPC (n = 49) and those with p16-positive/HPV-negative OPC (n = 14) were compared. Conclusion p16 status was strongly prognostic for patients with OPC. The data suggest that the addition of cetuximab to RT improved clinical outcomes regardless of p16 or HPV status versus RT alone. PMID:26712222

  2. Association of Human Papillomavirus and p16 Status With Outcomes in the IMCL-9815 Phase III Registration Trial for Patients With Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma of the Head and Neck Treated With Radiotherapy With or Without Cetuximab.

    PubMed

    Rosenthal, David I; Harari, Paul M; Giralt, Jordi; Bell, Diana; Raben, David; Liu, Joyce; Schulten, Jeltje; Ang, Kian K; Bonner, James A

    2016-04-20

    We conducted a retrospective evaluation of the IMCL-9815 study to examine the association of human papillomavirus (HPV) and p16 protein expression status with outcomes in patients with oropharyngeal carcinoma (OPC) receiving radiotherapy (RT) plus cetuximab or RT alone. In the IMCL-9815 study, patients were randomly allocated to receive RT plus weekly cetuximab or RT alone. A subpopulation of patients with p16-evaluable OPC was retrospectively evaluated on the basis of locoregional control (LRC), overall survival (OS), and progression-free survival (PFS). Evaluable samples from patients with p16-positive OPC were also tested for HPV DNA. Tumor p16 status was evaluable in 182 patients with OPC enrolled in the IMCL-9815 study; 41% were p16 positive. When treated with RT alone or RT plus cetuximab, p16-positive patients had a longer OS than p16-negative patients (hazard ratio, 0.40; 95% CI, 0.21 to 0.74 and hazard ratio, 0.16; 95% CI, 0.07 to 0.36, respectively). The addition of cetuximab to RT increased LRC, OS, and PFS in both patients with p16-positive OPC and those with p16-negative disease. Interaction tests for LRC, OS, and PFS did not demonstrate any significant interaction between p16 status and treatment effect (P = .087, .085, and .253, respectively). Similar trends were observed when patients with p16-positive/HPV-positive OPC (n = 49) and those with p16-positive/HPV-negative OPC (n = 14) were compared. p16 status was strongly prognostic for patients with OPC. The data suggest that the addition of cetuximab to RT improved clinical outcomes regardless of p16 or HPV status versus RT alone. © 2015 by American Society of Clinical Oncology.

  3. Postoperative adjuvant radiotherapy improves loco-regional recurrence of head and neck mucosal melanoma.

    PubMed

    Wushou, Alimujiang; Hou, Jing; Zhao, Ya-Jun; Miao, Xin-chao

    2015-05-01

    Primary head and neck mucosal melanoma (HNMM) is a rare tumor with a poor prognosis. Controversy remains as to whether postoperative adjuvant radiotherapy (PORT) achieves a significant benefit in HNMM treatment. Because of the lack of available conclusive prospective data, we performed a systematic review and meta-analysis of all relevant available studies to clarify the benefits of PORT. A comprehensive literature search of PubMed and Google Scholar electronic databases was conducted to collect relevant studies until April 30, 2014. Studies published in the English language comparing surgery alone and surgery plus PORT for HNMM were included, with more than 15 study populations. All statistical analyses were performed using STATA version 12.0. A total of 423 patients were available from eight studies and the median sample size was 53 cases. The median follow-up time was 38.2 months (range 18.3-65.2 months). There was a positive association between PORT and loco-regional recurrence of HNMM (odds ratio [OR] = 0.36, 95% confidence interval [CI] = 0.22-0.60, P = 0.000). No associations were found between the PORT and 3-year and 5-year overall survival (OS) (OR = 1.41, 95% CI = 0.94-2.09, P = 0.093 and OR = 1.06, 95% CI = 0.70-1.61, P = 0.161, respectively). PORT had no impact on 3-year and 5-year OS (hazard ratio [HR] = 1.14, 95% CI = 0.80-1.61, P = 0.472 and HR = 1.34, 95% CI = 0.97-1.85, P = 0.227, respectively). PORT improved loco-regional recurrence of HNMM independent of OS.

  4. Locoregional Recurrent or Second Primary Head and Neck Cancer: Management Strategies and Challenges.

    PubMed

    Wong, Stuart J; Heron, Dwight E; Stenson, Kerstin; Ling, Diane C; Vargo, John A

    2016-01-01

    Treatment of patients with locoregional recurrent or second primary head and neck squamous cell cancer (HNSCC) has been guided by well-reasoned principles and informed by carefully tested chemotherapy and radiation regimens. However, clinical decision making for this population is complicated by many factors. Although surgery is generally considered the treatment of choice for patients with HNSCC with recurrent disease or new second primary disease in a previously irradiated field, operability of cases is not always straightforward. Postoperative treatment is frequently warranted but carries significant risk. In addition, the rapid rise in the incidence of HPV-associated HNSCC raises the question of whether established treatment paradigms should be re-examined in this population of patients with a much better prognosis than the non-HPV population. Furthermore, new radiation techniques and new systemic agents show early promising results in recent clinical studies, suggesting potential for practice-changing effects in the future management of this disease. This article examines each of the treatment modalities used in the care of patients with HNSCC with recurrent or new second primary disease and provides a perspective to aid clinicians in the management of this disease.

  5. Pretreatment nutritional status and locoregional failure of patients with head and neck cancer undergoing definitive concurrent chemoradiation therapy.

    PubMed

    Platek, Mary E; Reid, Mary E; Wilding, Gregory E; Jaggernauth, Wainwright; Rigual, Nestor R; Hicks, Wesley L; Popat, Saurin R; Warren, Graham W; Sullivan, Maureen; Thorstad, Wade L; Khan, Mohamed K; Loree, Thom R; Singh, Anurag K

    2011-11-01

    This study was carried out to determine if markers of nutritional status predict for locoregional failure following intensity-modulated radiation therapy (IMRT) with concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN). We performed a retrospective chart review of 78 patients with SCCHN who received definitive CCRT. We compared patient factors, tumor characteristics, and nutritional status indicators between patients with and without locoregional failure. Fifteen of 78 patients (19%) experienced locoregional failure. Median follow-up for live patients was 38 months. On univariate analysis, pretreatment percentage of ideal body weight (%IBW) (p < .01), pretreatment hemoglobin (p = .04), and treatment duration (p < .01) were significant predictors of failure. On multivariate analysis, pretreatment %IBW (p = .04) and treatment time (p < .01) remained statistically significant. Although treatment time is an accepted risk factor for failure, differences in outcome for patients with head and neck cancer undergoing definitive CCRT based on pretreatment %IBW should be examined further. Copyright © 2010 Wiley Periodicals, Inc.

  6. PRETREATMENT NUTRITIONAL STATUS AND LOCOREGIONAL FAILURE IN PATIENTS WITH HEAD AND NECK CANCER UNDERGOING DEFINITIVE CONCURRENT CHEMORADIATION THERAPY

    PubMed Central

    Platek, Mary E.; Reid, Mary E.; Wilding, Gregory E.; Jaggernauth, Wainwright; Rigual, Nestor R.; Hicks, Wesley L.; Popat, Saurin R.; Warren, Graham W.; Sullivan, Maureen; Thorstad, Wade L.; Khan, Mohamed K.; Loree, Thom R.; Singh, Anurag K.

    2015-01-01

    Background This study was carried out to determine if markers of nutritional status predict for locoregional failure following intensity-modulated radiation therapy (IMRT) with concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN). Methods We performed a retrospective chart review of 78 patients with SCCHN who received definitive CCRT. We compared patient factors, tumor characteristics, and nutritional status indicators between patients with and without locoregional failure. Results Fifteen of 78 patients (19%) experienced locoregional failure. Median follow-up for live patients was 38 months. On univariate analysis, pretreatment percentage of ideal body weight (%IBW) (p < .01), pretreatment hemoglobin (p = .04), and treatment duration (p < .01) were significant predictors of failure. On multivariate analysis, pretreatment %IBW (p = .04) and treatment time (p < .01) remained statistically significant. Conclusions Although treatment time is an accepted risk factor for failure, differences in outcome for patients with head and neck cancer undergoing definitive CCRT based on pre-treatment %IBW should be examined further. PMID:21990220

  7. MiR-422a promotes loco-regional recurrence by targeting NT5E/CD73 in head and neck squamous cell carcinoma

    PubMed Central

    Bonnin, Nathalie; Armandy, Emma; Carras, Julien; Ferrandon, Sylvain; Battiston-Montagne, Priscillia; Aubry, Marc; Guihard, Sébastien; Meyronet, David; Foy, Jean-Philippe; Saintigny, Pierre; Ledrappier, Sonia; Jung, Alain; Rimokh, Ruth; Rodriguez-Lafrasse, Claire; Poncet, Delphine

    2016-01-01

    At the time of diagnosis, 60% of patients with head and neck squamous cell carcinoma (HNSCC) present tumors in an advanced stage (III-IV) of disease and 80% will relapse within the first two years post-treatment, due to their frequent radio(chemo)resistance. To identify new molecular targets and companion biomarkers, we have investigated the miRNome of 75 stage III-IV oropharynx tumors without relapse (R) or with loco-regional relapse (non-responder, NR) within two years post-treatment. Interestingly, miR-422a was significantly downregulated in NR tumors, in agreement with the increase in cell proliferation and adhesion induced by miR-422a inhibition in vitro. Furthermore, we identified CD73/NT5E oncogene as target of miR-422a. Indeed, modulation of the endogenous level of miR-422a inversely influences the expression and the enzymatic activity of CD73. Moreover, knocking down CD73 mimics the effects of miR-422a upregulation. Importantly, in tumors, miR-422a and CD73 expression levels are inversely correlated, and both are predictive of relapse free survival - especially considering loco(regional) recurrence - in vitro two independent cohorts of advanced oropharynx or HNSCC (N=255) tumors. In all, we reported, for the first time, that MiR-422a and its target CD73 are involved in early loco(regional) recurrence of HNSCC tumors and are new targets for personalized medicine. PMID:27281619

  8. BRAF inhibition for advanced locoregional BRAF V600E mutant melanoma: a potential neoadjuvant strategy.

    PubMed

    Sloot, Sarah; Zager, Jonathan S; Kudchadkar, Ragini R; Messina, Jane L; Benedict, Jacob J; Gonzalez, Ricardo J; DeConti, Ronald; Turner, Leslie M; McCardle, Timothy; Smalley, Keiran S M; Weber, Jeffrey S; Sondak, Vernon K; Gibney, Geoffrey T

    2016-02-01

    Selective BRAF inhibitors (BRAFi) yield objective responses in 50% of patients with metastatic BRAF V600E mutant melanoma. Adding an MEK inhibitor increases this response rate to 70%. Limited data are available on the outcomes of unresectable stage III patients, and it remains unclear whether BRAF-targeted therapy can be utilized as a neoadjuvant strategy. Data on patients with advanced locoregional BRAF V600E mutant melanoma treated with BRAF-targeted therapy at Moffitt Cancer Center were analyzed to determine response rates, subsequent resection rates after tumor downsizing, pathologic responses, and patient survival. Fifteen patients with locoregional disease treated with BRAF-targeted therapy, either BRAFi alone (vemurafenib; 11 patients) or a combination of BRAFi and an MEK inhibitor (dabrafenib plus trametinib or placebo; four patients), were identified. The median age was 50 years; the median follow-up was 25.4 months. The median BRAF-targeted therapy treatment duration was 6.0 months (range 1.2-29.4 months). Response Evaluation Criteria In Solid Tumors-based evaluation demonstrated objective response in 11 patients (73.3%). Six patients underwent resection of the remaining disease after therapy. Pathological analysis showed complete pathologic response (n=2), partial pathologic response (n=2), or no pathologic response (n=2). Four of six patients undergoing surgery have been alive for more than 2 years, including three patients currently free from active disease. No complications attributable to BRAF-targeted therapy were observed in the perioperative period. Dose reduction or discontinuation because of toxicities occurred in 10/15 patients. Neoadjuvant BRAF-targeted therapy may be effective in advanced locoregional BRAF V600E mutant melanoma patients in increasing resectability, yielding pathological responses, and achieving prolonged survival.

  9. Inverse Planned High-Dose-Rate Brachytherapy for Locoregionally Advanced Cervical Cancer: 4-Year Outcomes

    SciTech Connect

    Tinkle, Christopher L.; Weinberg, Vivian; Chen, Lee-May; Littell, Ramey; Cunha, J. Adam M.; Sethi, Rajni A.; Chan, John K.; Hsu, I-Chow

    2015-08-01

    Purpose: Evaluate the efficacy and toxicity of image guided brachytherapy using inverse planning simulated annealing (IPSA) high-dose-rate brachytherapy (HDRB) boost for locoregionally advanced cervical cancer. Methods and Materials: From December 2003 through September 2009, 111 patients with primary cervical cancer were treated definitively with IPSA-planned HDRB boost (28 Gy in 4 fractions) after external radiation at our institution. We performed a retrospective review of our experience using image guided brachytherapy. Of the patients, 70% had a tumor size >4 cm, 38% had regional nodal disease, and 15% had clinically evident distant metastasis, including nonregional nodal disease, at the time of diagnosis. Surgical staging involving pelvic lymph node dissection was performed in 15% of patients, and 93% received concurrent cisplatin-based chemotherapy. Toxicities are reported according to the Common Terminology Criteria for Adverse Events version 4.0 guidelines. Results: With a median follow-up time of 42 months (range, 3-84 months), no acute or late toxicities of grade 4 or higher were observed, and grade 3 toxicities (both acute and late) developed in 8 patients (1 constitutional, 1 hematologic, 2 genitourinary, 4 gastrointestinal). The 4-year Kaplan-Meier estimate of late grade 3 toxicity was 8%. Local recurrence developed in 5 patients (4 to 9 months after HDRB), regional recurrence in 3 (6, 16, and 72 months after HDRB), and locoregional recurrence in 1 (4 months after HDR boost). The 4-year estimates of local, locoregional, and distant control of disease were 94.0%, 91.9%, and 69.1%, respectively. The overall and disease-free survival rates at 4 years were 64.3% (95% confidence interval [CI] of 54%-73%) and 61.0% (95% CI, 51%-70%), respectively. Conclusions: Definitive radiation by use of inverse planned HDRB boost for locoregionally advanced cervical cancer is well tolerated and achieves excellent local control of disease. However, overall

  10. A Recent Advance in Image-Guided Locoregional Therapy for Hepatocellular Carcinoma

    PubMed Central

    Shi, Yaoping; Zhai, Bo

    2016-01-01

    Background Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer-related deaths. Hepatic resection and liver transplantation are considered to be the preferred treatment for HCC. However, as novel therapeutic options such as image-guided locoregional therapies have emerged and been refined, the manner in which HCC is treated has changed dramatically compared with what it was considered just 2 decades earlier. Summary This study reviews the current results of various image-guided locoregional therapies for treating HCC, especially focusing on thermal ablative and transarterial techniques. Key Message Advances in image-guided locoregional therapies, including local ablative therapy and transarterial therapy, have led to a major breakthrough in the management of HCC. Both survival rates and cure rates of patients with HCC have improved markedly since the introduction of these techniques. Practical Implications Radiofrequency ablation is currently considered as an alternative to surgical resection for patients with early-stage HCC. A newer technique of ablation such as microwave ablation is increasingly being used, especially for large HCC. Transarterial chemoembolization has become a standard care for asymptomatic patients with multinodular tumors in intermediate-stage disease, and transarterial radioembolization has become the method of choice in HCC cases with portal vein thrombosis. Moreover, combination treatment modalities, such as thermal-based ablation combined with transarterial chemoembolization or 125I seed implant brachytherapy, may further broaden their clinical indications for HCC. Moreover, use of localized radiation in combination with thermal ablation has been reported to improve tumor control and long-term survival. PMID:27904861

  11. The effect of locoregional therapies in patients with advanced hepatocellular carcinoma treated with sorafenib

    PubMed Central

    Sarpel, Umut; Spivack, John H.; Berger, Yaniv; Heskel, Marina; Aycart, Samantha N.; Sweeney, Robert; Edwards, Martin P.; Labow, Daniel M.; Kim, Edward

    2016-01-01

    Background & aims It is unknown whether the addition of locoregional therapies (LRTx) to sorafenib improves prognosis over sorafenib alone in patients with advanced hepatocellular carcinoma (HCC). The aim of this study was to assess the effect of LRTx in this population. Methods A retrospective analysis was performed of patients with advanced HCC as defined by extrahepatic metastasis, lymphadenopathy >2 cm, or gross vascular invasion. Sorafenib therapy was required for inclusion. Survival of patients who received LRTx after progression to advanced stage was compared to those who did not receive LRTx. Results Using an intention to treat analysis of 312 eligible patients, a propensity weighted proportional hazards model demonstrated LRTx as a predictor of survival (HR = 0.505, 95% CI: 0.407–0.628; P < 0.001). The greatest benefit was seen in patients with the largest tumor burden (HR = 0.305, 95% CI: 0.236–0.393; P < 0.01). Median survival in the sorafenib arm was 143 days (95% CI: 118–161) vs. 247 days (95% CI: 220–289) in the sorafenib plus LRTx arm (P < 0.001). Conclusions These results demonstrate a survival benefit with the addition of LRTx to sorafenib for patients with advanced HCC. These findings should prompt a prospective clinical trial to further assess the role of LRTx in patients with advanced HCC. PMID:27154804

  12. Concurrent Chemotherapy and Intensity-Modulated Radiotherapy for Locoregionally Advanced Laryngeal and Hypopharyngeal Cancers

    SciTech Connect

    Lee, Nancy Y. O'Meara, William; Chan, Kelvin; Della-Bianca, Cesar; Mechalakos, James G.; Zhung, Joanne; Wolden, Suzanne L.; Narayana, Ashwatha; Kraus, Dennis; Shah, Jatin P.; Pfister, David G.

    2007-10-01

    Purpose: To perform a retrospective review of laryngeal/hypopharyngeal carcinomas treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). Methods and Materials: Between January 2002 and June 2005, 20 laryngeal and 11 hypopharyngeal carcinoma patients underwent IMRT with concurrent platinum-based chemotherapy; most patients had Stage IV disease. The prescription of the planning target volume for gross, high-risk, and low-risk subclinical disease was 70, 59.4, and 54 Gy, respectively. Acute/late toxicities were retrospectively scored using the Common Toxicity Criteria scale. The 2-year local progression-free, regional progression-free, laryngectomy-free, distant metastasis-free, and overall survival rates were calculated using the Kaplan-Meier method. Results: The median follow-up of the living patients was 26 months (range, 17-58 months). The 2-year local progression-free, regional progression-free, laryngectomy-free, distant metastasis-free, and overall survival rate was 86%, 94%, 89%, 92%, and 63%, respectively. Grade 2 mucositis or higher occurred in 48% of patients, and all experienced Grade 2 or higher pharyngitis during treatment. Xerostomia continued to decrease over time from the end of RT, with none complaining of Grade 2 toxicity at this analysis. The 2-year post-treatment percutaneous endoscopic gastrostomy-dependency rate for those with hypopharyngeal and laryngeal tumors was 31% and 15%, respectively. The most severe late complications were laryngeal necrosis, necrotizing fascitis, and a carotid rupture resulting in death 3 weeks after salvage laryngectomy. Conclusion: These preliminary results have shown that IMRT achieved encouraging locoregional control of locoregionally advanced laryngeal and hypopharyngeal carcinomas. Xerostomia improved over time. Pharyngoesophageal stricture with percutaneous endoscopic gastrostomy dependency remains a problem, particularly for patients with hypopharyngeal carcinoma and, to a lesser

  13. HPV16 DNA status is a strong prognosticator of loco-regional control after postoperative radiochemotherapy of locally advanced oropharyngeal carcinoma: results from a multicentre explorative study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG).

    PubMed

    Lohaus, Fabian; Linge, Annett; Tinhofer, Inge; Budach, Volker; Gkika, Eleni; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Avlar, Melanie; Grosu, Anca-Ligia; Abdollahi, Amir; Debus, Jürgen; Bayer, Christine; Belka, Claus; Pigorsch, Steffi; Combs, Stephanie E; Mönnich, David; Zips, Daniel; von Neubeck, Cläre; Baretton, Gustavo B; Löck, Steffen; Thames, Howard D; Krause, Mechthild; Baumann, Michael

    2014-12-01

    To investigate the impact of HPV status in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received surgery and cisplatin-based postoperative radiochemotherapy. For 221 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity treated at the 8 partner sites of the German Cancer Consortium, the impact of HPV DNA, p16 overexpression and p53 expression on outcome were retrospectively analysed. The primary endpoint was loco-regional tumour control; secondary endpoints were distant metastases and overall survival. In the total patient population, univariate analyses revealed a significant impact of HPV16 DNA positivity, p16 overexpression, p53 positivity and tumour site on loco-regional tumour control. Multivariate analysis stratified for tumour site showed that positive HPV 16 DNA status correlated with loco-regional tumour control in patients with oropharyngeal carcinoma (p=0.02) but not in the oral cavity carcinoma group. Multivariate evaluation of the secondary endpoints in the total population revealed a significant association of HPV16 DNA positivity with overall survival (p<0.01) but not with distant metastases. HPV16 DNA status appears to be a strong prognosticator of loco-regional tumour control after postoperative cisplatin-based radiochemotherapy of locally advanced oropharyngeal carcinoma and is now being explored in a prospective validation trial. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Roles and types of radiation in breast cancer treatment: early breast cancer, locoregionally advanced, and metastatic disease.

    PubMed

    McCloskey, Susan A; Lee, Steve P; Steinberg, Michael L

    2011-02-01

    To describe the current role of radiation therapy and specific types of radiation therapy used in the management of early stage, locoregionally advanced, and metastatic breast cancer. The role of radiation therapy in the management of breast cancer has not changed in recent decades, however methods of treatment delivery have advanced considerably. Hypofractionation and accelerated partial breast irradiation, which substantially reduce radiation treatment duration, have emerged as appropriate alternatives to conventional whole breast radiation in select patient subsets, and intensity modulated radiation therapy, breathing-adapted radiation therapy, and prone-positioning technique address challenging anatomic issues and reduce treatment-associated toxicity. Stereotactic radiosurgery and stereotactic body radiation therapy continue to advance the management of distant metastatic disease. Radiation therapy plays a significant role in the management of early stage, locoregionally advanced, and metastatic breast cancer. Technological advances are allowing for greater patient convenience and comfort in locoregional radiation therapy delivery and for expanded radiation therapy indications in the setting of metastatic disease.

  15. Electrochemotherapy for the Treatment of Unresectable Locoregionally Advanced Cutaneous Melanoma: A Systematic Review.

    PubMed

    Aguado-Romeo, M J; Benot-López, S; Romero-Tabares, A

    2017-03-01

    Electrochemotherapy is a therapeutic option for the treatment of cutaneous and subcutaneous metastases from melanoma and other tumors. The procedure consists of the administration of anticancer drugs followed by locally applied electrical impulses to achieve an effect known as electroporation, which facilitates entry into the cytosol of drugs that cannot cross the cell membrane. The aim of this review is to evaluate the evidence that supports the use of electrochemotherapy as a therapeutic strategy in melanoma. We conducted a qualitative systematic review of the literature using advanced searches of bibliographic databases and full text reviews. Seven studies (3 systematic reviews and 4 cases series) were selected. The quality of the evidence was not good, but the coincidence of results for certain variables supports their consistency. Results of the meta-analyses favored electrochemotherapy over chemotherapy. Electrochemotherapy appears to be an effective procedure for the local treatment of malignant tumor nodules (evidence of intermediate or low quality). This inexpensive method is simple to apply, well tolerated, and achieves objective responses under certain circumstances. There is no evidence that electrochemotherapy alters the natural course of the disease and it should therefore be considered a palliative treatment. With an evidence level of 1- (minus), electrochemotherapy can be recommended for the palliative treatment of unresectable, locoregionally advanced melanoma (grade B recommendation). Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Sequential chemoradiotherapy with gemcitabine and cisplatin for locoregionally advanced nasopharyngeal carcinoma.

    PubMed

    Gu, Mo-Fa; Liu, Li-Zhi; He, Long-Jun; Yuan, Wen-Xin; Zhang, Rong; Luo, Guang-Yu; Xu, Guo-Liang; Zhang, Hua-Man; Yan, Chao-Xian; Li, Jian-Jun

    2013-01-01

    We investigated a new chemoradiotherapy (CRT) regimen for locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 240 patients were randomly assigned to three different CRT regimens: sequential CRT [1 cycle chemotherapy + Phase I radiotherapy (RT) + 1 cycle chemotherapy + Phase II RT + 2 cycles chemotherapy] with a cisplatin-gemcitabine (GC) regimen (800 mg/m(2) gemcitabine on Days 1 and 8 and 20 mg/m(2) cisplatin on Days 1-5, every 4 weeks) (sGC-RT); sequential chemoradiotherapy with a cisplatin-fluorouracil (PF) regimen (20 mg/m(2) DDP and 500 mg/m(2) 5-FU on Days 1-5, every 4 weeks) (sPF-RT) and cisplatin-based concurrent chemoradiotherapy plus adjuvant PF chemotherapy (Con-RT + PF). The complete response rate was higher in the sGC + RT group than in the other two groups (98.75% vs. 92.50%, p < 0.01). The 3-year overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) rates in the sGC-RT group were significantly higher than those observed in the Con-RT group (OS, 95.0% vs. 76.3%, p < 0.001; DFS, 89.9% vs. 67.5%, p < 0.001; DMFS, 92.5% vs. 76.0%, p = 0.004) and in the sPF + RT group (OS, 95.0% vs. 73.6%, p < 0.001; DFS, 89.9% vs. 63.3%, p < 0.001; DMFS, 92.5% vs. 74.7%, p = 0.002). There were no significant differences in 3-year OS, DFS and MFS rates between the Con-RT and the sPF-RT groups. The GC-RT group experienced more hematologic toxicity, constipation and rash; however, there were no differences in late RT toxicity between the groups. These results demonstrate that a sGC-RT regimen is effective and well tolerated in patients with locoregionally advanced NPC.

  17. ACR Appropriateness Criteria® management of locoregionally advanced squamous cell carcinoma of the vulva.

    PubMed

    Kidd, Elizabeth; Moore, David; Varia, Mahesh A; Gaffney, David K; Elshaikh, Mohamed A; Erickson, Beth; Jhingran, Anuja; Lee, Larissa J; Mayr, Nina A; Puthawala, Ajmel A; Rao, Gautam G; Small, William; Wahl, Andrew O; Wolfson, Aaron H; Yashar, Catheryn M; Yuh, William; Cardenes, Higinia Rosa

    2013-08-01

    Locoregionally advanced vulvar cancer (LRAVC) is a rare disease that presents many challenging medical decisions. An expert panel was convened to reach consensus on the most appropriate pretreatment assessment and therapeutic interventions in LRAVC patients. The American College of Radiology Appropriateness Criteria are evidenced-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journal and the application of a well-established consensus methodology (modified Delphi) to rate appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to formulate recommendations. Three clinical variants were developed to address common scenarios in the management of LRAVC. Group members reached consensus on the appropriateness of specific evaluation and treatment approaches, with numerical ratings and descriptive commentary. In combining available medical literature and expert opinion, this manuscript may serve as an aid for other practitioners in the appropriate management of patients with LRAVC.

  18. 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.

  19. Association of Body Composition With Survival and Locoregional Control of Radiotherapy-Treated Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Grossberg, Aaron J.; Chamchod, Sasikarn; Fuller, Clifton D.; Mohamed, Abdallah SR; Heukelom, Jolien; Eichelberger, Hillary; Kantor, Michael E.; Hutcheson, Katherine A.; Gunn, G. Brandon; Garden, Adam S.; Frank, Steven; Phan, Jack; Beadle, Beth; Skinner, Heath D; Morrison, William H.; Rosenthal, David I.

    2016-01-01

    IMPORTANCE Major weight loss is common in patients with head and neck squamous cell carcinoma (HNSCC) who undergo radiotherapy (RT). How baseline and posttreatment body composition affects outcome is unknown. OBJECTIVE To determine whether lean body mass before and after RT for HNSCC predicts survival and locoregional control. DESIGN, SETTING, AND PARTICIPANT Retrospective study of 2840 patients with pathologically proven HNSCC undergoing curative RT at a single academic cancer referral center from October 1, 2003, to August 31, 2013. One hundred ninety patients had computed tomographic (CT) scans available for analysis of skeletal muscle (SM). The effect of pre-RT and post-RT SM depletion (defined as a CT-measured L3 SM index of less than 52.4 cm2 /m2 for men and less than 38.5 cm2 /m2 for women) on survival and disease control was evaluated. Final follow-up was completed on September 27, 2014, and data were analyzed from October 1, 2014, to November 29, 2015. MAIN OUTCOMES AND MEASURES Primary outcomes were overall and disease-specific survival and locoregional control. Secondary analyses included the influence of pre-RT body mass index (BMI) and interscan weight loss on survival and recurrence. RESULTS Among the 2840 consecutive patients who underwent screening, 190 had whole-body positron emission tomography–CT or abdominal CT scans before and after RT and were included for analysis. Of these, 160 (84.2%) were men and 30 (15.8%) were women; their mean (SD) age was 57.7 (9.4) years. Median follow up was 68.6 months. Skeletal muscle depletion was detected in 67 patients (35.3%) before RT and an additional 58 patients (30.5%) after RT. Decreased overall survival was predicted by SM depletion before RT (hazard ratio [HR], 1.92; 95% CI, 1.19–3.11; P = .007) and after RT (HR, 2.03; 95% CI, 1.02–4.24; P = .04). Increased BMI was associated with significantly improved survival (HR per 1-U increase in BMI, 0.91; 95% CI, 0.87–0.96; P < .001). Weight loss without

  20. Genetic Variations in Radiation and Chemotherapy Drug Action Pathways and Survival in locoregionally Advanced Nasopharyngeal Carcinoma Treated with Chemoradiotherapy

    PubMed Central

    Guo, Xiang; Tang, Lin-Quan; Chen, Qiu-Yan; Zhang, Lu; Guo, Ling; Luo, Dong-Hua; Huang, Pei-Yu; Mo, Hao-Yuan; Xiang, Yan-Qun; Qiu, Fang; Sun, Rui; Zhang, Ying; Chen, Ming-Yuan; Hua, Yi-Jun; Lv, Xing; Wang, Lin; Zhao, Chong; Cao, Ka-Jia; Qian, Chao-Nan; Hong, Ming-Huang; Mai, Hai-Qiang

    2013-01-01

    Background and Purpose Treatment outcomes vary greatly in patients with nasopharyngeal carcinoma (NPC). The purpose of this study is to evaluate the influence of radiation and chemotherapy drug action pathway gene polymorphisms on the survival of patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy. Material and Methods Four hundred twenty-one consecutive patients with locoregionally advanced NPC were prospectively recruited. We utilized a pathway approach and examined 18 polymorphisms in 13 major genes. Polymorphisms were detected using the LDR-PCR technique. Multifactor dimensionality reduction (MDR) analysis was performed to detect potential gene-gene interaction. Results After adjustment for clinicopathological characteristics, overall survival was significantly decreased in patients with the MPO rs2243828 CT/CC genotype (HR=2.453, 95% CI, 1.687-3.566, P<0.001). The ERCC1 rs3212986 CC (HR=1.711, 95% CI, 1.135-2.579, P=0.010), MDM2 rs2279744 GT/GG (HR=1.743, 95% CI, 1.086-2.798, P=0.021), MPO rs2243828 CT/CC (HR=3.184, 95% CI, 2.261-4.483, P<0.001) and ABCB1 rs2032582 AT/AA (HR=1.997, 95% CI, 1.086-3.670, P=0.026) genotypes were associated with poor progression-free survival. Prognostic score models based on independent prognostic factors successfully classified patients into low-, intermediate-, and high-risk groups. Furthermore, MDR analysis showed no significant interaction between polymorphisms. Conclusions Four single nucleotide polymorphisms were associated with survival in patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy. Combining clinical prognostic factors with genetic information was valuable in identifying patients with different risk. PMID:24340057

  1. Matched Survival Analysis in Patients With Locoregionally Advanced Resectable Oropharyngeal Carcinoma: Platinum-Based Induction and Concurrent Chemoradiotherapy Versus Primary Surgical Resection

    SciTech Connect

    Boscolo-Rizzo, Paolo; Gava, Alessandro; Baggio, Vittorio; Marchiori, Carlo; Stellin, Marco; Fuson, Roberto; Lamon, Stefano; Da Mosto, Maria Cristina

    2011-05-01

    Purpose: The outcome of a prospective case series of 47 patients with newly diagnosed resectable locoregionally advanced oropharyngeal squamous cell carcinoma treated with platinum-based induction-concurrent chemoradiotherapy (IC/CCRT) was compared with the outcome of 47 matched historical control patients treated with surgery and postoperative RT. Methods and Materials: A total of 47 control patients with locoregionally advanced oropharyngeal squamous cell carcinoma were identified from review of a prospectively compiled comprehensive computerized head-and-neck cancer database and were matched with a prospective case series of patients undergoing IC/CCRT by disease stage, nodal status, gender, and age ({+-}5 years). The IC/CCRT regimen consisted of one cycle of induction chemotherapy followed by conventionally fractionated RT to a total dose of 66-70 Gy concomitantly with two cycles of chemotherapy. Each cycle of chemotherapy consisted of cisplatinum, 100 mg/m{sup 2}, and a continuous infusion of 5-fluorouracil, 1,000 mg/m{sup 2}/d for 5 days. The survival analysis was performed using Kaplan-Meier estimates. Matched-pair survival was compared using the Cox proportional hazards model. Results: No significant difference was found in the overall survival or progression-free survival rates between the two groups. The matched analysis of survival did not show a statistically significant greater hazard ratio for overall death (hazard ratio, 1.35; 95% confidence interval, 0.65-2.80; p = .415) or progression (hazard ratio, 1.44; 95% confidence interval, 0.72-2.87; p = .301) for patients undergoing IC/CCRT. Conclusion: Although the sample size was small and not randomized, this matched-pair comparison between a prospective case series and a historical cohort treated at the same institution showed that the efficacy of IC/CCRT with salvage surgery is as good as primary surgical resection and postoperative RT.

  2. DNA Repair Biomarker Profiling of Head & Neck Cancer: Ku80 Expression Predicts Locoregional Failure and Death Following Radiotherapy

    PubMed Central

    Moeller, Benjamin J.; Yordy, John S.; Williams, Michelle D.; Giri, Uma; Raju, Uma; Molkentine, David P.; Byers, Lauren A.; Heymach, John V.; Story, Michael D.; Lee, J. Jack; Sturgis, Erich M.; Weber, Randal S.; Garden, Adam S.; Ang, K. Kian; Schwartz, David L.

    2011-01-01

    Purpose Radiotherapy plays an integral role in the treatment of head and neck squamous cell carcinoma (HNSCC). Although proteins involved in DNA repair may predict HNSCC response to radiotherapy, none has been validated in this context. We examined whether differential expression of double-strand DNA break (DSB) repair proteins in HNSCC, the chief mediators of DNA repair following irradiation, predict for treatment outcomes. Experimental Design Archival HNSCC tumor specimens (n = 89) were assembled onto a tissue microarray and stained with antibodies raised against 38 biomarkers. The biomarker set was enriched for proteins involved in DSB repair, in addition to established mechanistic markers of radioresistance. Staining was correlated with treatment response and survival alongside established clinical and pathologic covariates. Results were validated in an independent intramural cohort (n = 34). Results Ku80, a key mediator of DSB repair, correlated most closely with clinical outcomes. Ku80 was overexpressed in half of all tumors, and its expression was independent of all other covariates examined. Ku80 overexpression was an independent predictor for both locoregional failure and mortality following radiotherapy (P < 0.01). The predictive power of Ku80 overexpression was confined largely to HPV-negative HNSCC, where it conferred a 9-fold greater risk of death at 2 years. Conclusions Ku80 overexpression is a common feature of HNSCC, and is a candidate DNA repair-related biomarker for radiation treatment failure and death, particularly in patients with high-risk HPV-negative disease. It is a promising, mechanistically rational biomarker to select individual HPV-negative HNSCC patients for strategies to intensify treatment. PMID:21349997

  3. Multi-modality management for loco-regionally advanced laryngeal and hypopharyngeal cancer: balancing the benefit of efficacy and functional preservation.

    PubMed

    Qian, Wei; Zhu, Guopei; Wang, Yulong; Wang, Xiaoshen; Ji, Qinghai; Wang, Yu; Dou, Shengjin

    2014-09-01

    The 5-year overall survival (OS) of loco-regionally advanced laryngeal and hypopharyngeal carcinoma (LA-LHC) has declined over the past two decades following the wide application of non-surgical approaches. We aimed to define the new role of open surgery combined with adjuvant chemoradiotherapy in the treatment of LA-LHC for improving survival while maintaining a functional larynx. In the current study, 90 LA-LHC patients treated with open surgery followed by postoperative RT/CRT in our institute from May 2005 to December 2012 were retrospectively analyzed. OS, disease-free survival (DFS), loco-regional failure-free survival (LRFFS) and distant metastasis-free survival (DMFS) were calculated, and prognostic factors were analyzed. Functional larynx preservation results were evaluated according to the head and neck quality of life (QoL) Scale. With a median follow-up period of 37 months, the 3- and 5-year OS, DFS, LRFFS and DMFS were 71.3, 63.7, 85.9, 73.7 and 55.9, 53.0, 81.6, 71.9 %, respectively. Vascular embolism and extracapsular extension (ECE) of the lymph nodes were prognostic factors for poorer OS (p = 0.045 and 0.046, respectively). Vascular embolism was the only prognostic factor for poorer DMFS (p = 0.005). Patients who underwent a conservative partial laryngectomy (CPL) experienced a higher QoL in the domains of speech, swallowing and emotion. Functional larynx preservation was achieved in 36/45 patients (80 %) who received CPL. The results of our study demonstrated that CPL followed by adequate adjuvant therapy could achieve superior oncological results compared with non-surgical approaches in LA-LHC patients while also maintaining satisfactory functional larynx in a majority of patients.

  4. 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.

  5. Hyperbaric oxygen therapy for late radiation-associated tissue necroses: is it safe in patients with locoregionally recurrent and then successfully salvaged head-and-neck cancers?

    PubMed

    Lin, Hon-Yi; Ku, Chih-Hung; Liu, Dai-Wei; Chao, Hsing-Lung; Lin, Chun-Shu; Jen, Yee-Min

    2009-07-15

    To test, in a retrospective matched-pair study, whether necrosis-rescuing hyperbaric oxygen therapy (HBOT) increases the risk of cancer re-recurrence in patients with locoregionally recurrent and then successfully salvaged head-and-neck cancers. Between January 1995 and July 2004, we retrospectively identified 22 patients with locoregionally recurrent and then successfully salvaged head-and-neck cancers. We defined two groups: the HBOT group, 11 patients with HBOT for rescuing late radiation-associated tissue necroses; and the non-HBOT group, the other 11 matched-pair patients without HBOT. Between the two groups, the following four factors were matched for case pairing: primary cancer subsite, initial cancer stage, age, and gender. Three findings indicate that HBOT increases the risk of cancer re-recurrence. First, we observed more cancer re-recurrences in the HBOT group than in the non-HBOT group: 9 of 11 vs. 4 of 11, with 5-year disease-free survival rates after salvage of 32.7% vs. 70.0% (hazard ratio 3.2; 95% confidence interval 1.03-10.7; p = 0.048). Second, re-recurrences developed rapidly after HBOT in 6 patients. Third, 3 patients had unusual cancer re-recurrences after HBOT. Remarkably, of 9 patients with cancer re-recurrences in the HBOT group, 4 patients had cancer disease-free intervals of 9 months or less before HBOT. Necrosis-rescuing HBOT should be given with caution in patients with locoregionally recurrent and then successfully salvaged head-and-neck cancers; if it cannot be omitted entirely, deferring HBOT 9 months or longer after cancer re-treatment may be prudent.

  6. Survival Benefit of Locoregional Treatment for Hepatocellular Carcinoma with Advanced Liver Cirrhosis

    PubMed Central

    Kitai, Satoshi; Kudo, Masatoshi; Nishida, Naoshi; Izumi, Namiki; Sakamoto, Michiie; Matsuyama, Yutaka; Ichida, Takafumi; Nakashima, Osamu; Matsui, Osamu; Ku, Yonson; Kokudo, Norihiro; Makuuchi, Masatoshi

    2016-01-01

    Background & Aims Hepatocellular carcinoma (HCC) with decompensated liver cirrhosis (LC) is a life-threatening condition, which is amenable to liver transplantation (LT) as the standard first-line treatment. However, the application of LT can be limited due to a shortage of donor livers. This study aimed to clarify the effect of non-surgical therapy on the survival of patients with HCC and decompensated LC. Methods Of the 58,886 patients with HCC registered in the nationwide survey of the Liver Cancer Study Group of Japan (January 2000-December 2005), we included 1,344 patients with primary HCC and Child-Pugh (C-P) grade C for analysis in this retrospective study. Among the patients analyzed, 108 underwent LT, 273 were treated by local ablation therapy (LAT), 370 were treated by transarterial chemoembolization (TACE), and 593 received best supportive care (BSC). The effect of LT, LAT, and TACE on overall survival (OS) was analyzed using multivariate and propensity score analyses. Results Patient characteristics did not differ significantly between each treatment group and the BSC group, after propensity score matching. LAT (hazard ratio [HR]) =0.568; 95% confidence interval [CI], 0.40-0.80) and TACE (HR=0.691; 95% CI, 0.50-0.96) were identified as significant contributors to OS if the C-P score was less than 11 and tumor conditions met the Milan criteria. Conclusions For patients with HCC within the Milan criteria and with a C-P score of 10 or 11, locoregional treatment can be used as a salvage treatment if LT is not feasible. PMID:27493893

  7. Salvage surgery for locoregional recurrence or persistent tumor after high dose chemoradiotherapy for locally advanced non-small cell lung cancer.

    PubMed

    Dickhoff, C; Dahele, M; Paul, M A; van de Ven, P M; de Langen, A J; Senan, S; Smit, E F; Hartemink, K J

    2016-04-01

    Curative intent treatment options for locoregional recurrence or persistent tumor after radical chemoradiotherapy for locally-advanced non-small cell lung cancer (NSCLC) are limited. In selected patients, surgery can be technically feasible, although it is widely believed to be hazardous. As data regarding the outcome of this approach is sparse, we evaluated our institutional experience with salvage surgery. Patients with a pulmonary resection for in-field locoregional recurrence or persistent tumor after high dose chemoradiotherapy (≥60 Gy) for the treatment of non-small cell lung cancer, were identified and retrospectively analyzed. A total of 15 patients treated between January 2007 and August 2015 were eligible for evaluation. In 13 patients (87%), the indication for surgery was a locoregional recurrence, while 2 patients had persistent tumor. The prior median radiotherapy dose was 66 Gy (range 60-70). All patients underwent an anatomical resection, with 8 patients having a pneumonectomy, and all pathological specimens revealed the presence of viable tumor. The in-hospital morbidity rate was 40% (6 patients), and the 90-day mortality rate was 6.7% (1 patient). Median follow-up was 12.1 months. The estimated median overall and event-free survivals were 46 months and 43.6 months, respectively. Salvage surgery for locoregional recurrence or persistent tumor after high dose chemoradiotherapy, resulted in acceptable morbidity, mortality and promising outcome. It should be considered as a treatment option for selected patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Surrogate End Points for Overall Survival in Loco-Regionally Advanced Nasopharyngeal Carcinoma: An Individual Patient Data Meta-analysis.

    PubMed

    Rotolo, Federico; Pignon, Jean-Pierre; Bourhis, Jean; Marguet, Sophie; Leclercq, Julie; Tong Ng, Wai; Ma, Jun; Chan, Anthony T C; Huang, Pei-Yu; Zhu, Guopei; Chua, Daniel T T; Chen, Yong; Mai, Hai-Qiang; Kwong, Dora L W; Soong, Yoke Lim; Moon, James; Tung, Yuk; Chi, Kwan-Hwa; Fountzilas, George; Zhang, Li; Hui, Edwin Pun; Lee, Anne W M; Blanchard, Pierre; Michiels, Stefan

    2017-04-01

    Our objective was to evaluate progression-free survival (PFS) and distant metastasis-free survival (DMFS) as surrogate end points for overall survival (OS) in randomized trials of chemotherapy in loco-regionally advanced nasopharyngeal carcinomas (NPCs). Individual patient data were obtained from 19 trials of the updated Meta-Analysis of Chemotherapy in Nasopharyngeal Carcinoma (MAC-NPC) plus one additional trial (total = 5144 patients). Surrogacy was evaluated at the individual level using a rank correlation coefficient ρ and at the trial level using a correlation coefficient R(2) between treatment effects on the surrogate end point and OS. A sensitivity analysis was performed with two-year PFS/DMFS and five-year OS. PFS was strongly correlated with OS at the individual level (ρ = 0.93, 95% confidence interval [CI] = 0.93 to 0.94) and at the trial level (R(2) = 0.95, 95% CI = 0.47 to 1.00). For DMFS, too, the individual-level correlation with OS was strong (ρ = 0.98, 95% CI = 0.98 to 0.98); at trial level, the correlation was high but the regression adjusted for measurement error could not be computed (unadjusted R(2) = 0.96, 95% CI = 0.94 to 0.99). In the sensitivity analysis, two-year PFS was highly correlated with five-year OS at the individual level (ρ = 0.89, 95% CI = 0.88 to 0.90) and at the trial level (R(2) = 0.85, 95% CI = 0.46 to 1.00); two-year DMFS was highly correlated with five-year OS at the individual level (ρ = 0.95, 95% CI = 0.94 to 0.95) and at the trial level (R(2) = 0.78, 95% CI = 0.33 to 1.00). PFS and DMFS are valid surrogate end points for OS to assess treatment effect of chemotherapy in loco-regionally advanced NPC, while PFS can be measured earlier. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Postoperative simultaneous integrated boost-intensity modulated radiation therapy for patients with locoregionally advanced papillary thyroid carcinoma: preliminary results of a phase II trial and propensity score analysis.

    PubMed

    Lee, Eun Kyung; Lee, You Jin; Jung, Yuh-S; Ryu, Junsun; Kim, Tae Hyun; Lee, Chang Yoon; Ryu, Chang Hwan; Kim, Tae Sung; Kim, Seok Ki; Chung, Ki-Wook; Kim, Sang Soo; Kim, Dae Yong; Kim, Joo Young; Cho, Kwan Ho

    2015-03-01

    With recent technical advances in radiotherapy (RT) planning, simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) has made possible the delivery of high radiation dose to the tumor, minimizing surrounding normal tissues. This study aimed to evaluate the clinical effectiveness and safety of postoperative SIB-IMRT in patients with locoregionally advanced papillary thyroid cancer (PTC). This was a propensity score-matched case control study conducted at a tertiary referring center. This study included locoregionally advanced patients with PTC (pT4 or N1b) who underwent thyroid cancer surgery and radioactive iodine ablation (RIA) followed by postoperative SIB-IMRT (RT group) under a phase II trial or no postoperative RT (Non-RT group) Intervention: Postoperative SIB-IMRT was the intervention. locoregional relapse-free survival (LRFS) was compared between RT group and Non-RT group. Multivariate analysis showed that several factors, including sex, American Thyroid Association risk category, and use of postoperative RT were significantly associated with LRFS in all 201 patients (P < .05 each). In the 118 propensity score-matched patients, there were no significant differences in baseline characteristics between the RT and Non-RT groups, but the LRFS rate was significantly higher in the RT than in the Non-RT group (4 y: 100% vs 84.6%, P = .002). Overall, SIB-IMRT was well tolerated, with no grade ≥3 toxicity, and was completed as planned in all patients. Postoperative SIB-IMRT is feasible and effective in improving locoregional control in patients with locally advanced PTC. Large-scale randomized studies are warranted.

  10. Effect of taxanes-based induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: A large scale propensity-matched study.

    PubMed

    Zhang, Lu-Ning; Gao, Yuan-Hong; Lan, Xiao-Wen; Tang, Jie; OuYang, Pu-Yun; Xie, Fang-Yun

    2015-10-01

    The effect of taxanes-based induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) was quite contradictory in two phase II randomized controlled trials with small sample size. We aimed to investigate it in this large scale propensity-matched study. Totally, 779 LA-NPC patients who underwent intensity-modulated radiotherapy (IMRT) plus concurrent chemotherapy with or without taxanes-based IC were included. Patients in both treatment arms were matched using propensity score matching method at the ratio of 1:1. Failure-free survival (FFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test and Cox regression analysis. After matching, 534 patients were identified for analysis. In univariate analysis, both treatment arms resulted in parallel survival (4-years FFS 78.0% vs 74.1%, P = 0.304; OS 87.5% vs 87.3%, P = 0.595; DMFS 88.2% vs 84.4%, P = 0.154; and LRFS 91.2% vs 90.1%, P = 0.960). In multivariate analysis, taxanes-based IC did not improve any survival (P ⩾ 0.139). And this association remained unchanged in subgroup analysis by age, sex and histology, and among patients with stage III and T4N0M0. But among patients with T4N1-2M0 and stage IVb, taxanes-based IC significantly prolonged the 4-year DMFS by 11.2% (86.1% vs 74.9%, P = 0.034), and marginally improved FFS (P = 0.133) and OS (P = 0.215) in both univariate and multivariate analysis. In this large scale propensity-matched study, LA-NPC patients could not benefit from taxanes-based IC on the whole. But the risk of distant metastasis significantly decreased by above 10% for patients with T4N1-2M0 and stage IVb. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Prognostic value of primary gross tumor volume and standardized uptake value of (18)F-FDG in PET/CT for distant metastasis in locoregionally advanced nasopharyngeal carcinoma.

    PubMed

    Jin, Ya-Nan; Yao, Ji-Jin; Wang, Si-Yang; Zhang, Wang-Jian; Zhou, Guan-Qun; Zhang, Fan; Cheng, Zhi-Bin; Ma, Jun; Mo, Hao-Yuan; Sun, Ying

    2017-07-01

    Distant metastasis has become the predominant model of treatment failures in patients with locoregionally advanced nasopharyngeal carcinoma. Effort should therefore be made to stratify locoregionally advanced nasopharyngeal carcinoma patients into different groups based on the risk of metastasis to improve prognosis and tailor individualized treatments. This study aims to assess the value of primary gross tumor volume and the maximum standardized uptake value for predicting distant metastasis-free survival of patients with locoregionally advanced nasopharyngeal carcinoma. A total of 294 locoregionally advanced nasopharyngeal carcinoma patients who were identified from prospectively maintained database and underwent fluor-18-fluorodeoxyglucose positron emission tomography/computed tomography imaging before treatment were included. The maximum standardized uptake value was recorded for the primary tumor (SUVmax-P) and neck lymph nodes (SUVmax-N). Computed tomography-derived primary gross tumor volume was measured using the summation-of-area technique. At 5 years, the distant metastasis-free survival rate was 83.7%. The cut-off of the SUVmax-P, SUVmax-N, and primary gross tumor volume for distant metastasis-free survival was 8.95, 5.75, and 31.3 mL, respectively, by receiver operating characteristic curve. In univariate analysis, only SUVmax-N (hazard ratio: 7.01; 95% confidence interval: 1.70-28.87; p < 0.01) and clinical stage (hazard ratio: 3.03; 95% confidence interval: 1.67-5.47; p = 0.007) were confirmed as independent predictors of distant metastasis-free survival. A prognostic model was derived by SUVmax-N and clinical stage: low risk (SUVmax-N < 5.75 regardless of clinical stage), medium risk (stage III and SUVmax-N ≥ 5.75), and high risk (stage IV and SUVmax-N ≥ 5.75). Multivariate analysis revealed that SUVmax-N and the prognostic model remained independent prognostic factors for distant metastasis-free survival (p = 0

  12. Impact of Gender, Partner Status, and Race on Locoregional Failure and Overall Survival in Head and Neck Cancer Patients in Three Radiation Therapy Oncology Group Trials

    SciTech Connect

    Dilling, Thomas J.; Bae, Kyounghwa; Paulus, Rebecca; Watkins-Bruner, Deborah; Garden, Adam S.; Forastiere, Arlene; Kian Ang, K.; Movsas, Benjamin

    2011-11-01

    Purpose: We investigated the impact of race, in conjunction with gender and partner status, on locoregional control (LRC) and overall survival (OS) in three head and neck trials conducted by the Radiation Therapy Oncology Group (RTOG). Methods and Materials: Patients from RTOG studies 9003, 9111, and 9703 were included. Patients were stratified by treatment arms. Covariates of interest were partner status (partnered vs. non-partnered), race (white vs. non-white), and sex (female vs. male). Chi-square testing demonstrated homogeneity across treatment arms. Hazards ratio (HR) was used to estimate time to event outcome. Unadjusted and adjusted HRs were calculated for all covariates with associated 95% confidence intervals (CIs) and p values. Results: A total of 1,736 patients were analyzed. Unpartnered males had inferior OS rates compared to partnered females (adjusted HR = 1.22, 95% CI, 1.09-1.36), partnered males (adjusted HR = 1.20, 95% CI, 1.09-1.28), and unpartnered females (adjusted HR = 1.20, 95% CI, 1.09-1.32). White females had superior OS compared with white males, non-white females, and non-white males. Non-white males had inferior OS compared to white males. Partnered whites had improved OS relative to partnered non-white, unpartnered white, and unpartnered non-white patients. Unpartnered males had inferior LRC compared to partnered males (adjusted HR = 1.26, 95% CI, 1.09-1.46) and unpartnered females (adjusted HR = 1.30, 95% CI, 1.05-1.62). White females had LRC superior to non-white males and females. White males had improved LRC compared to non-white males. Partnered whites had improved LRC compared to partnered and unpartnered non-white patients. Unpartnered whites had improved LRC compared to unpartnered non-whites. Conclusions: Race, gender, and partner status had impacts on both OS and locoregional failure, both singly and in combination.

  13. Recurrence patterns of locally advanced head and neck squamous cell carcinoma after 3D conformal (chemo)-radiotherapy

    PubMed Central

    2011-01-01

    Background To establish recurrence patterns among locally advanced head and neck non-nasopharyngeal squamous cell carcinoma (HNSCC) patients treated with radical (chemo-) radiotherapy and to correlate the sites of loco-regional recurrence with radiotherapy doses and target volumes Method 151 locally advanced HNSCC patients were treated between 2004-2005 using radical three-dimensional conformal radiotherapy. Patients with prior surgery to the primary tumour site were excluded. The sites of locoregional relapses were correlated with radiotherapy plans by the radiologist and a planning dosimetrist. Results Median age was 59 years (range:34-89). 35 patients had stage III disease, 116 patients had stage IV A/B. 36 patients were treated with radiotherapy alone, 42 with induction chemotherapy, 63 with induction and concomitant chemoradiotherapy and 10 concomitant chemoradiotherapy. Median follow-up was 38 months (range 3-62). 3-year cause specific survival was 66.8%. 125 of 151 (82.8%) achieved a complete response to treatment. Amongst these 125 there were 20 local-regional recurrence, comprising 8 local, 5 regional and 7 simultaneous local and regional; synchronous distant metastases occurred in 7 of the 20. 9 patients developed distant metastases in the absence of locoregional failure. For the 14 local recurrences with planning data available, 12 were in-field, 1 was marginal, and 1 was out-of-field. Of the 11 regional failures with planning data available, 7 were in-field, 1 was marginal and 3 were out-of-field recurrences. Conclusion The majority of failures following non-surgical treatment for locally advanced HNSCC were loco-regional, within the radiotherapy target volume. Improving locoregional control remains a high priority. PMID:21609453

  14. Ten-year outcomes of a randomised trial for locoregionally advanced nasopharyngeal carcinoma: A single-institution experience from an endemic area.

    PubMed

    Huang, Pei-Yu; Zeng, Qi; Cao, Ka-Jia; Guo, Xiang; Guo, Ling; Mo, Hao-Yuan; Wu, Pei-Hong; Qian, Chao-Nan; Mai, Hai-Qiang; Hong, Ming-Huang

    2015-09-01

    We previously reported the five-year results of a randomised trial that compared induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) with induction chemotherapy plus radiotherapy (IC+RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). The aim of this study was to report the ten-year results and to explore potential prognostic factors. From August 2002 to April 2005, 408 patients with locoregionally advanced NPC were randomly assigned to receive either IC (carboplatin and floxuridine)+CCRT (carboplatin) or IC+RT. The survival rates were analysed using the Kaplan-Meier method and compared using the log-rank test. Multivariable analysis was performed to identify valuable prognostic factors. The ten-year overall survival, failure-free survival, locoregional failure-free survival and distant failure-free survival rates for the entire patient cohort were 49.5%, 48.0%, 80.8% and 66.9%, respectively. No significant survival differences were found between the IC+CCRT and IC+RT arms. By 3 years from the date of randomisation, 62.5% of the relapses had been detected; no recurrence occurred after 8 years. Within 3 years after randomisation, 77.0% of the metastases were detected; 0.8% was identified after 8 years. Age, Union for International Cancer Control (UICC) N-stage, serum lactate dehydrogenase (LDH) and body mass index (BMI) were independent prognostic factors that predicted death. Smoking status and total radiotherapy dose were independent prognostic factors that predicted locoregional recurrence. UICC N-stage, LDH and BMI were independent prognostic factors that predicted distant metastasis. Concurrent carboplatin chemotherapy did not significantly improve the long-term survival after inductive carboplatin and floxuridine chemotherapy in locoregionally advanced nasopharyngeal carcinoma. In addition to patient and tumour characteristics, LDH, BMI and smoking status were important baseline prognostic factors for tumour recurrence

  15. Brachytherapy boost in loco-regionally advanced nasopharyngeal carcinoma: a prospective randomized trial of the International Atomic Energy Agency

    PubMed Central

    2014-01-01

    patients) (p = 0.343). The grade 3–4 toxicity rate was 21.6% (30/139) and 24.4% (33/135) respectively (p = 0.687). Conclusions The addition of a brachytherapy boost to external beam radiotherapy and chemotherapy did not improve outcome in loco-regionally advanced nasopharyngeal carcinoma. PMID:24581393

  16. Prognostic value of microvessel density and p53 expression on the locoregional metastasis and survival of the patients with head and neck squamous cell carcinoma.

    PubMed

    de Oliveira, Marcos Vinícius M; Pereira Gomes, Erika P; Pereira, Camila S; de Souza, Ludmilla R; Barros, Lucas O; Mendes, Danilo C; Guimarães, André L S; De Paula, Alfredo M B

    2013-10-01

    Cancer cells need to develop microvessels in order to grow and to establish metastatic foci. A role for the p53 protein in the regulation of the angiogenic process is suggested. This study aimed to investigate the relationship between immunohistochemical expression of microvessel density (MVD), measured by CD31 staining, and p53 protein with clinicopathologic factors, and survival in head and neck squamous cell carcinoma (n=70). Tumor angiogenesis was estimated by determining MVD in areas with the highest number of stained microvessels (hot spots). Clinicopathologic factors and immunohistochemical data were evaluated by χ statistical test and were submitted to binary logistic regression to analyze the risk of presence of lymph node metastasis. Factors that might predict survival were investigated using Cox proportional hazards tests. Differences were considered statistically significant when P<0.05. The percentage of p53-positive cells showed no association with clinicopathologic parameters and MVD. Patients with locoregional metastasis presented statistically significant higher MVD (P=0.043). Individuals presenting head and neck squamous cell carcinoma in posterior sites (P=0.022; OR=3.644) and higher MVD (P=0.039; OR=3.247) had a significant increase in risk of metastasis occurrence. Multivariate analysis showed that presence of lymph node metastasis was statistically significant for overall survival of head and neck carcinoma patients (P=0.006; OR =2.917). The present data suggest that MVD represents a promising diagnostic tool to identify individuals with increased risk for the development of metastatic disease, which is very indicative of poor prognosis.

  17. Long-Term Improvement in Treatment Outcome After Radiotherapy and Hyperthermia in Locoregionally Advanced Cervix Cancer: An Update of the Dutch Deep Hyperthermia Trial

    SciTech Connect

    Franckena, Martine Stalpers, Lukas J.A.; Koper, Peter C.M.; Wiggenraad, Ruud G.J.; Hoogenraad, Wim J.; Dijk, Jan D.P. van; Warlam-Rodenhuis, Carla C.; Jobsen, Jan J.; Rhoon, Gerard C. van; Zee, Jacoba van der

    2008-03-15

    Purpose: The local failure rate in patients with locoregionally advanced cervical cancer is 41-72% after radiotherapy (RT) alone, whereas local control is a prerequisite for cure. The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia (HT) improved 3-year local control rates of 41-61%, as we reported earlier. In this study, we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up. Methods and Materials: From 1990 to 1996, a total of 114 women with locoregionally advanced cervical carcinoma were randomly assigned to RT or RT + HT. The RT was applied to a median total dose of 68 Gy. The HT was given once weekly. The primary end point was local control. Secondary end points were overall survival and late toxicity. Results: At the 12-year follow-up, local control remained better in the RT + HT group (37% vs. 56%; p = 0.01). Survival was persistently better after 12 years: 20% (RT) and 37% (RT + HT; p = 0.03). World Health Organization (WHO) performance status was a significant prognostic factor for local control. The WHO performance status, International Federation of Gynaecology and Obstetrics (FIGO) stage, and tumor diameter were significant for survival. The benefit of HT remained significant after correction for these factors. European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups. Conclusions: For locoregionally advanced cervical cancer, the addition of HT to RT resulted in long-term major improvement in local control and survival without increasing late toxicity. This combined treatment should be considered for patients who are unfit to receive chemotherapy. For other patients, the optimal treatment strategy is the subject of ongoing research.

  18. High-Dose Rate Brachytherapy Using Inverse Planning Simulated Annealing for Locoregionally Advanced Cervical Cancer: A Clinical Report With 2-Year Follow-Up

    SciTech Connect

    Kim, Daniel H.; Wang-Chesebro, Alice; Weinberg, Vivian; Pouliot, Jean; Chen, Lee-May; Speight, Joycelyn; Littell, Ramey; Hsu, I.-Chow

    2009-12-01

    Purpose: We present clinical outcomes of image-guided brachytherapy using inverse planning simulated annealing (IPSA) planned high-dose rate (HDR) brachytherapy boost for locoregionally advanced cervical cancer. Methods and Materials: From February 2004 through December 2006, 51 patients were treated at the University of California, San Francisco with HDR brachytherapy boost as part of definitive radiation for International Federation of Gynecology and Obstetrics Stage IB1 to Stage IVA cervical cancer. Of the patients, 46 received concurrent chemotherapy, 43 with cisplatin alone and 3 with cisplatin/5-fluorouracil. All patients had IPSA-planned HDR brachytherapy boost after whole-pelvis external radiation to a total tumor dose of 85 Gy or greater (for alpha/beta = 10). Toxicities are reported according to National Cancer Institute CTCAE v3.0 (Common Terminology Criteria for Adverse Events version 3.0) guidelines. Results: At a median follow-up of 24.3 months, there were no toxicities of Grade 4 or greater and the frequencies of Grade 3 acute and late toxicities were 4% and 2%, respectively. The proportion of patients having Grade 1 or 2 gastrointestinal and genitourinary acute toxicities was 48% and 52%, respectively. Low-grade late toxicities included Grade 1 or 2 vaginal, gastrointestinal, and hormonal toxicities in 31%, 18%, and 4% of patients, respectively. During the follow-up period, local recurrence developed in 2 patients, regional recurrence developed in 2, and new distant metastases developed in 15. The rates of locoregional control of disease and overall survival at 24 months were 91% and 86%, respectively. Conclusions: Definitive radiation by use of inverse planned HDR brachytherapy boost for locoregionally advanced cervical cancer is well tolerated and achieves excellent local control of disease.

  19. Adjuvant radiotherapy after transoral laser microsurgery for advanced squamous carcinoma of the head and neck

    SciTech Connect

    Pradier, Olivier . E-mail: opradier@gwdg.de; Christiansen, Hans; Schmidberger, Heinz; Martin, Alexios; Jaeckel, Martin C.; Steiner, Wolfgang; Ambrosch, Petra; Kahler, Elke; Hess, Clemens F.

    2005-12-01

    Purpose: To evaluate the efficacy of an adjuvant radiotherapy after transoral laser microsurgery for advanced squamous cell carcinoma of the head and neck and to show that a less invasive surgery with organ preservation in combination with radiotherapy is an alternative to a radical treatment. Patients and Methods: Between 1987 and 2000, 208 patients with advanced squamous cell carcinoma of the head and neck were treated with postoperative radiotherapy after surgical CO{sub 2} laser resection. Primary sites included oral cavity, 38; oropharynx, 88; larynx, 36; hypopharynx, 46. Disease stages were as follows: Stage III, 40 patients; Stage IV, 168 patients. Before 1994, the treatment consisted of a split-course radiotherapy with carboplatinum (Treatment A). After 1994, the patients received a conventional radiotherapy (Treatment B). Results: Patients had 5-year locoregional control and disease-specific survival (DSS) rates of 68% and 48%, respectively. The 5-year DSS was 70% and 44% for Stages III and IV, respectively (p = 0.00127). Patients treated with a hemoglobin level greater or equal to 13.5 g/dL before radiotherapy had a 5-year DSS of 55% as compared with 39% for patients treated with a hemoglobin level greater than 13.5 g/dL (p = 0.0054). Conclusion: In this series of patients with advanced head-and-neck tumors, transoral laser surgery in combination with adjuvant radiotherapy resulted in locoregional control and DSS rates similar to those reported for radical surgery followed by radiotherapy. Treatment B has clearly been superior to Treatment A. A further improvement of our treatment regimen might be expected by the combination of adjuvant radiotherapy with concomitant platinum-based chemotherapy.

  20. Induction chemotherapy followed by concurrent chemoradiation and nimotuzumab for locoregionally advanced nasopharyngeal carcinoma: preliminary results from a phase II clinical trial.

    PubMed

    Huang, Jian-Feng; Zhang, Fu-Zheng; Zou, Qin-Zhou; Zhou, Le-Yuan; Yang, Bo; Chu, Jian-Jun; Yu, Jia-Hua; Zhang, Hao-Wen; Yuan, Xiao-Peng; Tai, Guo-Mei; Liu, Fen-Ju; Ma, C-M Charlie

    2017-01-10

    Overexpression of epidermal growth factor receptor can be found in more than 80% of patients with locoregionally advanced nasopharyngeal carcinoma and is associated with shorter survival. In this work, we evaluated the feasibility of adding nimotuzumab to chemoradiation in locoregionally advanced nasopharyngeal carcinoma. Twenty-three patients with clinically staged T3-4 or any node-positive disease were enrolled. They were scheduled to receive one cycle of induction chemotherapy followed by intensity-modulated radiotherapy, weekly administration of nimotuzumab and concurrent chemotherapy. Results showed that all patients received a full course of radiotherapy, 19(82.6%)patients completed the scheduled neoadjuvant and concurrent chemotherapy, and 22(95.7%) patients received ≥6 weeks of nimotuzumab. During the period of concurrent chemoradiation and nimotuzumab, grade 3-4 toxicities occurred in 14(60.9%) patients: 8 (34.8%) had grade 3-4 oral mucositis, 6(26.1%) had grade 3 neutropenia, and 1(4.3%) had grade 3 dermatitis. No acne-like rash was observed. With a median follow-up of 24.1 months, the 2-year progression-free survival and overall survival were 83.5% and 95.0%, respectively. In conclusion, concurrent administration of chemoradiation and nimotuzumab was well-tolerated with good compliance. Preliminary clinical outcome data appear encouraging with favorable normal tissue toxicity results comparing with historical data of concurrent chemoradiation plus cetuximab.

  1. Induction chemotherapy followed by concurrent chemoradiation and nimotuzumab for locoregionally advanced nasopharyngeal carcinoma: preliminary results from a phase II clinical trial

    PubMed Central

    Zou, Qin-zhou; Zhou, Le-yuan; Yang, Bo; Chu, Jian-jun; Yu, Jia-hua; Zhang, Hao-wen; Yuan, Xiao-peng; Tai, Guo-mei; Liu, Fen-ju; Ma, C-M Charlie

    2017-01-01

    Overexpression of epidermal growth factor receptor can be found in more than 80% of patients with locoregionally advanced nasopharyngeal carcinoma and is associated with shorter survival. In this work, we evaluated the feasibility of adding nimotuzumab to chemoradiation in locoregionally advanced nasopharyngeal carcinoma. Twenty-three patients with clinically staged T3-4 or any node-positive disease were enrolled. They were scheduled to receive one cycle of induction chemotherapy followed by intensity-modulated radiotherapy, weekly administration of nimotuzumab and concurrent chemotherapy. Results showed that all patients received a full course of radiotherapy, 19(82.6%)patients completed the scheduled neoadjuvant and concurrent chemotherapy, and 22(95.7%) patients received =6 weeks of nimotuzumab. During the period of concurrent chemoradiation and nimotuzumab, grade 3-4 toxicities occurred in 14(60.9%) patients: 8 (34.8%) had grade 3-4 oral mucositis, 6(26.1%) had grade 3 neutropenia, and 1(4.3%) had grade 3 dermatitis. No acne-like rash was observed. With a median follow-up of 24.1 months, the 2-year progression-free survival and overall survival were 83.5% and 95.0%, respectively. In conclusion, concurrent administration of chemoradiation and nimotuzumab was well-tolerated with good compliance. Preliminary clinical outcome data appear encouraging with favorable normal tissue toxicity results comparing with historical data of concurrent chemoradiation plus cetuximab. PMID:27974693

  2. Predictors of competing mortality in advanced head and neck cancer.

    PubMed

    Mell, Loren K; Dignam, James J; Salama, Joseph K; Cohen, Ezra E W; Polite, Blase N; Dandekar, Virag; Bhate, Amit D; Witt, Mary Ellyn; Haraf, Daniel J; Mittal, Bharat B; Vokes, Everett E; Weichselbaum, Ralph R

    2010-01-01

    PURPOSE Death from noncancer causes (competing mortality) is an important event in head and neck cancer, but studies identifying predictors of this event are lacking. We sought to identify predictors of competing mortality and develop a risk stratification model for competing events. PATIENTS AND METHODS Cohort study of 479 patients with stage III to IV carcinoma of the head and neck diagnosed between August 1993 and November 2004. Patients were treated on consecutive prospective clinical trials involving organ-preserving chemoradiotherapy and surgery. We used multivariable competing risks regression models to analyze factors associated with the cumulative incidence of competing mortality, locoregional and distant failure, and second malignancies as first events. Results Median follow-up was 52 months median for survivors. The 5-year cumulative incidence of competing mortality was 19.6% (95% CI, 15.8 to 23.4). On multivariable analysis, competing mortality was associated with female sex (hazard ratio [HR], 1.72; 95% CI, 1.13 to 2.63), increasing age (HR, 1.30; 95% CI, 1.04 to 1.62), increasing Charlson Comorbidity Index (HR, 1.24; 95% CI, 1.05 to 1.47), decreasing body mass index (HR, 0.33; 95% CI, 0.13 to 0.84), and decreasing distance traveled to the treating center (HR, 0.65; 95% CI, 0.44 to 0.98). Patients with zero, one, two, and > or = three risk factors had 5-year competing mortality of 8.9% (95% CI, 3.0% to 14.8%), 12.4% (95% CI, 7.0% to 17.8%), 22.1% (95% CI, 14.5% to 29.7%), and 39.3% (95% CI, 28.6% to 50.1%), respectively. CONCLUSION Competing mortality in advanced head and neck cancer is associated with several demographic and health status characteristics. Analyses of risk factors for competing mortality may be useful in outcomes reporting and designing clinical trials.

  3. Lymph node ratio influence on risk of head and neck cancer locoregional recurrence after initial surgical resection: implications for adjuvant therapy.

    PubMed

    Prabhu, Roshan S; Hanasoge, Sheela; Magliocca, Kelly R; Hall, William A; Chen, Susie A; Higgins, Kristin A; Saba, Nabil F; El-Deiry, Mark; Grist, William; Wadsworth, J Trad; Chen, Amy Y; Beitler, Jonathan J

    2015-06-01

    The purpose of this study was to determine if lymph node ratio is associated with locoregional recurrence for patients with oral cavity or laryngeal cancer treated with initial surgical management. The study included 350 patients with oral cavity (73%) or laryngeal cancer (27%) who underwent initial surgery. All analyses were multivariable, adjusting for primary site, pathologic prognostic factors, and adjuvant therapy. Lymph node ratio was significantly associated with locoregional recurrence, in which each 1% increase in lymph node ratio had an adjusted hazard ratio (HR) for locoregional recurrence of 1.02 (95% confidence interval [CI], 1.002-1.042; p = .05). Lymph node ratio was also associated with OS, in which each 1% increase in lymph node ratio had an adjusted HR for death of 1.028 (95% CI, 1.012-1.045; p = .001). Adjusting for pathologic factors and adjuvant therapy, lymph node ratio was found to be an independent prognostic factor for locoregional recurrence and overall survival (OS). Patients with lymph node ratio ≥20% are at high risk of locoregional recurrence and death, and may be considered for adjuvant chemoradiation. © 2014 Wiley Periodicals, Inc.

  4. Phase II study of OSI-211 (liposomal lurtotecan) in patients with metastatic or loco-regional recurrent squamous cell carcinoma of the head and neck. An EORTC New Drug Development Group study.

    PubMed

    Duffaud, F; Borner, M; Chollet, P; Vermorken, J B; Bloch, J; Degardin, M; Rolland, F; Dittrich, C; Baron, B; Lacombe, D; Fumoleau, P

    2004-12-01

    The purpose of this study was to evaluate the activity and safety of OSI-211, the liposomal form of lurtotecan, in patients ineligible for curative surgery or radiotherapy and with metastatic/locoregional recurrent squamous cell carcinoma of the head and neck (SCCHN) and target lesions either within a previously irradiated field ("within") or outside a previously irradiated field ("outside"). OSI-211 was given intravenously over 30 min on days 1 and 8 at 2.4 mg/m2/day, repeated every 21 days (1 cycle). From July 2001 to March 2002, 32 patients from 14 institutions were enrolled in the "within" arm and 18 in the "outside" arm. In the "within" arm, two patients were ineligible because their tumour site was not allowed in the protocol (nasopharynx, skin) and two other patients never started treatment. Of the 46 eligible patients who started treatment, there was one objective response (response rate: 2.2% (95% Confidence Interval (CI): [0-11.5%]). Twelve patients in the "within" arm and 6 in the "outside" arm had stable disease, with a median duration of 18 weeks, 95% CI (12.7-25.7). The median time to progression was 6 weeks (95%CI: [5.9-12.7] weeks). Haematological toxicity was moderate in both arms. The most common haematological toxicity was grade 1-2 anaemia in 79% of patients. Non-haematological toxicity was mild in both arms. The most common grade 3-4 non-haematological toxicity was infection in 8.5% of patients. OSI-211 administered on d1 and d8, every 3 weeks, is well tolerated, but shows only minimal activity in locally advanced/metastatic SCCHN.

  5. A Phase II Study of a Paclitaxel-Based Chemoradiation Regimen With Selective Surgical Salvage for Resectable Locoregionally Advanced Esophageal Cancer: Initial Reporting of RTOG 0246

    SciTech Connect

    Swisher, Stephen G.; Winter, Kathryn A.; Komaki, Ritsuko U.; Ajani, Jaffer A.; Wu, Tsung T.; Hofstetter, Wayne L.; Konski, Andre A.; Willett, Christopher G.

    2012-04-01

    Purpose: The strategy of definitive chemoradiation with selective surgical salvage in locoregionally advanced esophageal cancer was evaluated in a Phase II trial in Radiation Therapy Oncology Group (RTOG)-affiliated sites. Methods and Materials: The study was designed to detect an improvement in 1-year survival from 60% to 77.5% ({alpha} = 0.05; power = 80%). Definitive chemoradiation involved induction chemotherapy with 5-fluorouracil (5-FU) (650 mg/mg{sup 2}/day), cisplatin (15 mg/mg{sup 2}/day), and paclitaxel (200 mg/mg{sup 2}/day) for two cycles, followed by concurrent chemoradiation with 50.4 Gy (1.8 Gy/fraction) and daily 5-FU (300 mg/mg{sup 2}/day) with cisplatin (15 mg/mg{sup 2}/day) over the first 5 days. Salvage surgical resection was considered for patients with residual or recurrent esophageal cancer who did not have systemic disease. Results: Forty-three patients with nonmetastatic resectable esophageal cancer were entered from Sept 2003 to March 2006. Forty-one patients were eligible for analysis. Clinical stage was {>=}T3 in 31 patients (76%) and N1 in 29 patients (71%), with adenocarcinoma histology in 30 patients (73%). Thirty-seven patients (90%) completed induction chemotherapy followed by concurrent chemoradiation. Twenty-eight patients (68%) experienced Grade 3+ nonhematologic toxicity. Four treatment-related deaths were noted. Twenty-one patients underwent surgery following definitive chemoradiation because of residual (17 patients) or recurrent (3 patients) esophageal cancer,and 1 patient because of choice. Median follow-up of live patients was 22 months, with an estimated 1-year survival of 71%. Conclusions: In this Phase II trial (RTOG 0246) evaluating selective surgical salvage after definitive chemoradiation in locoregionally advanced esophageal cancer, the hypothesized 1-year RTOG survival rate (77.5%) was not achieved (1 year, 71%; 95% confidence interval< 54%-82%).

  6. A PHASE II STUDY OF A PACLITAXEL-BASED CHEMORADIATION REGIMEN WITH SELECTIVE SURGICAL SALVAGE FOR RESECTABLE LOCOREGIONALLY ADVANCED ESOPHAGEAL CANCER: INITIAL REPORTING OF RTOG 0246

    PubMed Central

    Swisher, Stephen G.; Winter, Kathryn A.; Komaki, Ritsuko U.; Ajani, Jaffer A.; Wu, Tsung T.; Hofstetter, Wayne L.; Konski, Andre A.; Willett, Christopher G.

    2013-01-01

    Purpose The strategy of definitive chemoradiation with selective surgical salvage in locoregionally advanced esophageal cancer was evaluated in a Phase II trial in Radiation Therapy Oncology Group (RTOG)-affiliated sites. Methods and Materials The study was designed to detect an improvement in 1-year survival from 60% to 77.5% (α= 0.05; power = 80%). Definitive chemoradiation involved induction chemotherapy with 5-fluorouracil (5-FU) (650 mg/mg2/day), cisplatin (15 mg/mg2/day), and paclitaxel (200 mg/mg2/day) for two cycles, followed by concurrent chemoradiation with 50.4 Gy (1.8 Gy/fraction) and daily 5-FU (300 mg/mg2/day) with cisplatin (15 mg/mg2/day) over the first 5 days. Salvage surgical resection was considered for patients with residual or recurrent esophageal cancer who did not have systemic disease. Results Forty-three patients with nonmetastatic resectable esophageal cancer were entered from Sept 2003 to March 2006. Forty-one patients were eligible for analysis. Clinical stage was ≥T3 in 31 patients (76%) and N1 in 29 patients (71%), with adenocarcinoma histology in 30 patients (73%). Thirty-seven patients (90%) completed induction chemotherapy followed by concurrent chemoradiation. Twenty-eight patients (68%) experienced Grade 3+ nonhematologic toxicity. Four treatment-related deaths were noted. Twenty-one patients underwent surgery following definitive chemoradiation because of residual (17 patients) or recurrent (3 patients) esophageal cancer,and 1 patient because of choice. Median follow-up of live patients was 22 months, with an estimated 1-year survival of 71%. Conclusions In this Phase II trial (RTOG 0246) evaluating selective surgical salvage after definitive chemoradiation in locoregionally advanced esophageal cancer, the hypothesized 1-year RTOG survival rate (77.5%) was not achieved (1 year, 71%; 95% confidence interval< 54%–82%). PMID:21507583

  7. Loco-regional control after neo-adjuvant chemotherapy and conservative treatment for locally advanced breast cancer patients.

    PubMed

    Levy, Antonin; Borget, Isabelle; Bahri, Manel; Arnedos, Monica; Rivin, Eleonor; Vielh, Philippe; Balleyguier, Corinne; Rimareix, Françoise; Bourgier, Céline

    2014-01-01

    Breast-conserving treatment (BCT) has been validated for breast cancer patients receiving adjuvant chemotherapy. Our objective was to evaluate the difference in loco-regional recurrence (LRR) rates between BCT and mastectomy in patients receiving radiation therapy after neo-adjuvant chemotherapy (NCT). A retrospective data base was used to identify all patients with breast cancer undergoing NCT from 2002 to 2007. Patients with initial metastatic disease were excluded from this analysis. LRR was compared between those undergoing BCT and mastectomy. Individual variables associated with LRR were evaluated. Two hundred eighty-four patients were included, 111 (39%) underwent BCT and 173 (61%) mastectomy. Almost all patients (99%) in both groups received postoperative radiation. Pathologic complete response was seen in 37 patients, of which 28 underwent BCT (p < 0.001). Patients receiving mastectomy had more invasive lobular carcinoma (p = 0.007) and a higher American Joint Committee on Cancer (AJCC) stage (p < 0.001) at diagnosis than those with BCT. At a median follow-up of 6.3 years, the loco-regional control rate was 91% (95% CI: 86-94%). The 10-year LRR rate was similar in the BCT group (9.2% [95% CI: 4.9-16.7%]) and in the mastectomy group (10.7% [95% CI: 5.9-15.2%]; p = 0.8). Ten-year overall survival (OS) rates (63% [95% CI: 46-79%] in the BCT group; 60% [95% CI: 47-73%] in the mastectomy group, p = 0.8) were not statistically different between the two patient populations. Multivariate analysis showed that AJCC stage ≥ III (HR: 2.6; 95% CI: 1.2-5.8; p = 0.02), negative PR (HR: 6; 95% CI: 1.2-30.6, p = 0.03), and number of positive lymph nodes ≥3 (HR: 2.5; 95% CI: 1.1-5.9; p = 0.03) were independent predictors of LRR. Ten-year OS was similar in the BCT and in the mastectomy group (p = 0.1). The rate of LRR was low and did not significantly differ between the BCT and the mastectomy group after NCT. Randomized trials assessing whether mastectomy can be safely

  8. Role of concomitant chemoradiation in locally advanced head and neck cancers.

    PubMed

    Lasrado, Savita; Moras, Kuldeep; Pinto, George Jawahar Oliver; Bhat, Mahesh; Hegde, Sanath; Sathian, Brijesh; Luis, Neil Aaron

    2014-01-01

    Standard therapy for advanced head and neck cancer consists of a combination of surgery and radiation. However, survival of this patient population has not improved during the past 20 years. Many different multimodality treatment schedules have been proposed, and chemotherapy is often used with the intent of organ preservation. The present study was intended to establish the efficacy of concomitant chemoradiation with a single agent carboplatin in advanced head and neck cancers.The objectives were to investigate the feasibility of concomitant administration of carboplatin, monitor acute toxicity during radiotherapy, and determine subacute side effects, such as wound healing following surgery after chemoradiotherapy. A prospective study was conducted wherein a total of 40 patients with stage III and IV squamous cell carcinomas of oral cavity, oropharynx, hypopharynx and larynx were enrolled. All patients were treated with external beam radiotherapy and weekly carboplatin area under curve (AUC of 5). Radiotherapy was given in single daily fractions of 1.8-2 grays (Gy) to a total dose of 66-72 Gy. Salvage surgery was performed for any residual or recurrent locoregional disease. Neck dissection was recommended for all patients with neck disease showing less than a complete response after chemoradiation. A total of 40 patients were enrolled of whom 32 were males and 8 were females. Highest incidence of cancer was seen in the 5th-6th decades of life with a median age of 47.7 years. Oropharyngeal tumours constituted a maximum of 21 patients followed by hypopharynx in 10, larynx in 7 and oral cavity in 2. 80% of the patients had a neck node on presentation of which 40% had N2-N3 nodal status. TNM staging revealed that 58% of patients were in stage III and 43% in stage IV. Evaluation of acute toxicity revealed that 50% had grade II mucositis, 25% grade III mucositis, 2.5% grade IV mucositis. 50% of patients had grade I skin reactions, 65% of patients had grade I

  9. Concurrent Cisplatin and Radiation Versus Cetuximab and Radiation for Locally Advanced Head-and-Neck Cancer

    SciTech Connect

    Koutcher, Lawrence; Sherman, Eric; Fury, Matthew; Wolden, Suzanne; Zhang Zhigang; Mo Qianxing; Stewart, Laschelle; Schupak, Karen; Gelblum, Daphna; Wong, Richard; Kraus, Dennis; Shah, Jatin; Zelefsky, Michael; Pfister, David; Lee, Nancy

    2011-11-15

    Purpose: To compare concurrent cisplatin (CDDP) and radiation (RT) with cetuximab (C225) and RT for locally advanced head-and-neck cancer (LAHNC). Methods and Materials: This study retrospectively compared 174 consecutive, newly diagnosed LAHNC patients definitively treated from March 1, 2006, to April 1, 2008, with single-agent CDDP/RT (n = 125) or C225/RT (n = 49). We excluded patients who received additional concurrent, induction, or adjuvant systemic therapy; weekly cisplatin; prior head-and-neck radiotherapy; or primary surgical resection. Outcomes were analyzed by the Kaplan-Meier method, Cox model, and competing-risks analysis tools. Results: The C225/RT patients were older and had decreased creatinine clearance. At a median follow-up of 22.5 months for living patients, the 2-year locoregional failure rate was 5.7% for CDDP/RT and 39.9% for C225/RT (p < 0.0001). The 2-year failure-free survival (FFS) and overall survival (OS) rates were 87.4% vs. 44.5% (p < 0.0001) and 92.8% vs. 66.6% (p = 0.0003), respectively, in favor of CDDP/RT. When the Cox proportional hazards model was used for multivariate analysis, treatment with CDDP/RT predicted for improved locoregional control (p < 0.0001), FFS (p < 0.0001), and OS (p = 0.01). Late Grade 3 or 4 toxicity or feeding tube dependence 9 months after completion of RT was observed in 21% of patients in the CDDP/RT cohort and 24% in the C225/RT cohort (p = 0.66). Conclusions: In this study of LAHNC patients, CDDP/RT achieved better locoregional control, FFS, and OS than C225/RT. Although the results were upheld on multivariate analysis, they must be interpreted cautiously because of the retrospective nature of the study and significant differences in patient selection. There was no statistically significant difference in late Grade 3 or 4 effects or feeding tube dependence.

  10. [Combined therapy of locally advanced squamous epithelial cancers in the area of the head and neck].

    PubMed

    Fountzilas, G; Daniilidis, J; Kalogera-Fountzila, A; Apostolidis, T; Vritsios, A; Tourkantonis, A

    1988-04-01

    In an effort to improve treatment results in locally advanced squamous cell carcinoma of head and neck, we designed a multimodality treatment programme consisting of three cycles of inductive chemotherapy, after 2-3 weeks loco-regional therapy (surgery and/or radiotherapy), two more cycles of adjuvant chemotherapy with the same regimen were given finally. The chemotherapeutic regimen included cis-platinum 100 mg/m2 on day 1, 5-fluorouracil 100 mg/m2 on days 2-6 as a continuous infusion, bleomycin 15 units on days 15, 29; mitomycin-C 4 mg/m2 on day 2 and hydroxyurea 100 mg/m2 on days 22-26. From August 1984 onwards, 37 patients entered in this study. The group included 31 men and 6 women with a medium age of 54 (18-71) and a performance status of 80 (60-90). Primary sites were nasopharynx (13), oropharynx (5), hypopharynx (3), sinus (3), ethmoids (2), tongue (2), floor of the mouth (2), larynx (6) and unknown (1). 25 patients received 3 cycles of induction therapy whereas 22 completed the whole treatment programme. Following induction therapy, 28% of the patients demonstrated histologically confirmed CR, 40% PR and 32% SD, while after the full multimodality therapy 59% demonstrated CR, 36% PR and 5% SD. Follow-up is 9-36 months. Actual survival at 3 years is 80% for those with a CR post loco-regional therapy. Toxicities were leukopenia (40%), thrombocytopenia (20%), anaemia (40%), nausea and vomiting (60%), stomatitis (52%) diarrhoea (16%) and alopecia (79%). There was one death related to chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. A Comparative Study on Weekly Versus Three Weekly Cisplatinum Based Chemoradiation in Locally Advanced Head and Neck Cancers

    PubMed Central

    Sahoo, Tapan Kumar; Samanta, Dipti Rani; Parida, Karishma

    2017-01-01

    Introduction Head and Neck Cancers constitute around 30% of cancers occurring in India and majority of cases present with locoregionally advanced disease. Cisplatin based concurrent chemoradiation is the most common modality of definitive treatment in these advanced cases. However, it is unclear regarding priority of weekly versus three weekly cisplatin based concurrent chemoradiation schedule in treatment of such advanced diseases. Aim To evaluate the efficacy in terms of response, locoregional control, and disease status in both the arms, and to compare the acute and late toxicity in both arms. Materials and Methods Thirty untreated patients of locally advanced Squamous Cell Carcinoma of head and neck were randomized into two arms: Arm A (n=15) patients received injection cisplatin 30 mg/m2 weekly along with radiation; Arm B (n=15) patients received injection cisplatin 100 mg/m2 on a three weekly basis along with radiation. Radiotherapy was delivered to a total dose of 66 Gy in conventional fractionation schedule in telecobalt machine. Results Major toxicities included mucositis, dermatitis, vomiting, neutropenia, and anaemia. There was a trend towards increase in grade-III leukopenia and grade-III dermatitis in arm A compared to arm B, and increase in grade-III mucositis and grade-III vomiting in arm B in comparison to arm A although statistically not significant. Within a median follow-up of seven months, in arm A complete response was 73.33% (11/15) and partial response was 26.67%; whereas in arm B complete response was 85.71% (12/14) and partial response was 14.29%, which was not statistically significant. However, there was a trend towards better efficacy in arm B. Conclusion We conclude that, weekly cisplatin arm is as good as three weekly cisplatin arms. But efficacy is not statistically significant. However, there was a trend of three weekly cisplatin arms towards better efficacy, with comparable haematological and mucosal toxicities. PMID:28274031

  12. Comparison of the short-term efficacy between docetaxel plus carboplatin and 5-fluorouracil plus carboplatin in locoregionally advanced nasopharyngeal carcinoma

    PubMed Central

    Lv, Xing; Xia, Wei-Xiong; Ke, Liang-Ru; Yang, Jing; Qiu, Wen-Zhe; Yu, Ya-Hui; Liang, Hu; Huang, Xin-Jun; Liu, Guo-Yin; Zeng, Qi; Guo, Xiang; Xiang, Yan-Qun

    2016-01-01

    Objective Platinum-based chemotherapy in combination with radiotherapy is a standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma (NPC). This study aimed to investigate the long-term efficacy and tolerability of inductive chemotherapy with docetaxel plus carboplatin (TC) or 5-fluorouracil plus carboplatin (FC) followed by concurrent radiation therapy in patients with NPC. Methods Patients (N=88) were randomized to receive TC or FC as inductive therapy followed by concurrent radiotherapy (60–70 Gy) with two cycles of carboplatin (area under the curve =5 mg·h/L). Patients were followed up for 8 years. Primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), toxicity, tumor response, distant metastasis-free survival, and local recurrence-free survival. Results At the end of the follow-up period, 31 patients died, 32 had disease progression, eleven had cancer recurrence, and 25 had distant metastasis. Overall, there was no difference between treatment groups with regard to response or survival. We found that following induction and concurrent chemoradiotherapy, the majority of patients showed a complete response (~96%–98% for induction therapy and 82%–84% for comprehensive therapy) to both therapies. PFS and OS were also similar between groups. The rate of PFS was 63.6% for both FC and TC and that of OS was 65.9% and 63.5%, respectively. The overall incidence of grade 3–4 adverse events in the TC group (20.5%) was higher than in the FC group (10.7%). Neutropenia and leukopenia were the most common grade 3–4 adverse events in the TC group, and mucositis was the most common in the FC group. Conclusion These data indicate that TC and FC therapies have similar efficacy in treating locally advanced NPC and both are well tolerated. PMID:27574453

  13. Airway management before chemoradiation for advanced head and neck cancer.

    PubMed

    Langerman, Alexander; Patel, Riddhi M; Cohen, Ezra E W; Blair, Elizabeth A; Stenson, Kerstin M

    2012-02-01

    Patients with upper aerodigestive tract tumors can have development of airway compromise both before and during chemoradiotherapy (CRT). Tracheotomy is the classic method for securing a safe airway, but tumor debulking may also be used. This was a retrospective review of locoregionally advanced tumors of the base of tongue, larynx, or hypopharynx undergoing CRT between 1995 and 2007. Forty-two of the 109 patients presented with signs or symptoms of airway obstruction. Of these, 28 underwent tracheotomy before CRT, and 11 had tumor debulking. Two of the 11 patients who underwent debulking required tracheotomy within 1 year after CRT for persistent edema and fibrosis. Larynx tumors were more likely to require tracheotomy or debulking than other tumors (p = .01). Debulking is a safe and effective alternative to tracheotomy in select patients with tumor-related airway obstruction before CRT. Patients who undergo debulking should be monitored closely for recurrence of airway compromise during and after CRT. Copyright © 2011 Wiley Periodicals, Inc.

  14. The Effect of a Contrast Agent on Proton Beam Range in Radiotherapy Planning Using Computed Tomography for Patients With Locoregionally Advanced Lung Cancer

    SciTech Connect

    Hwang, Ui-Jung; Shin, Dong Ho; Kim, Tae Hyun; Moon, Sung Ho; Lim, Young Kyung; Jeong, Hojin; Rah, Jeong-Eun; Kim, Sang Soo; Kim, Joo-Young; Kim, Dae Yong; Park, Sung Yong; Cho, Kwan Ho

    2011-11-15

    Purpose: We evaluated the effect of a contrast agent (CA) on proton beam range in a treatment planning system (TPS) for patients with locoregionally advanced lung cancer. Methods and Materials: Two sets of computed tomography (CT) images (with and without CA) were obtained from 20 patients with lung cancer. Because the increase in Hounsfield unit ( Increment HU) value of the heart and great vessels due to the effect of CA is most prominent among thoracic structures, to evaluate the effect of CA on proton beam range in the TPS, we compared the calculated distal ranges in the plan with CA-enhanced CT with those with corrected CT, in which the HU values of the heart and great vessels in the CA-enhanced CT were replaced by average HU values obtained from the unenhanced CT. Results: The mean Increment HU value and the longest length of the heart and great vessels within the proton beam path in the field that passed through these structures were 189 {+-} 29 HU (range, 110-250 HU) and 7.1 {+-} 1.1 cm (range, 2.6-11.2 cm), respectively. The mean distal range error in the TPS because of the presence of CA was 1.0 {+-} 0.7 cm (range, 0.2-2.6 cm). Conclusion: If CA-enhanced CT images are used for radiotherapy planning using a proton beam for the treatment of lung cancer, our results suggest that the HU values of the heart and great vessels should be replaced by the average HU values of soft tissue to avoid discrepancies between planned and delivered doses.

  15. Effectiveness of CT assists for intraarterial chemotherapy: therapeutic outcome of chemoradiation for advanced head and neck cancer extending across the anatomical midline.

    PubMed

    Yunaiyama, Daisuke; Saito, Kazuhiro; Funatsu, Tomokazu; Nakayama, Hidetsugu; Shimizu, Akira; Ito, Hiroyuki; Suzuki, Mamoru; Akata, Soichi; Tokuuye, Koichi

    2014-12-01

    The purpose of this study was to evaluate the effectiveness of CT assist for intraarterial chemotherapy in relation to the therapeutic outcomes of intraarterial chemoradiation for advanced head and neck cancer with extension across the anatomical midline (EAM). This retrospective study evaluated 64 consecutive patients. In total, 26 and 38 patients had cancer with or without EAM, respectively. These patients underwent an intraarterial cisplatin infusion (200 mg/m(2), days 1 and 35) and intravenous 5-FU infusion (800 mg/m(2), days 1-5 and 36-39) concomitantly with radiotherapy. Angiography-assisted CT was performed to confirm complete coverage during the intraarterial chemotherapy. The accuracy of diagnosing tumor vessels by digital subtraction angiography (DSA) was evaluated using receiver-operating characteristic analysis by two radiologists. The overall survival and locoregional control rates were calculated by the Kaplan-Meier method. DSA was not useful for diagnosing tumor vessels. The 2-year overall survival rates for the patients with cancer with or without EAM were 83 and 90 %, while the 2-year locoregional control rates were 95 and 82 %, respectively. Locoregional control or the overall survival rates showed no significant differences. Intraarterial chemotherapy using angiography-assisted CT during chemoradiation therapy can achieve comparable therapeutic outcomes for cancer with and without EAM.

  16. Feasibility and efficacy of accelerated weekly concomitant boost postoperative radiation therapy combined with concomitant chemotherapy in patients with locally advanced head and neck cancer.

    PubMed

    Pehlivan, Berrin; Luthi, Francois; Matzinger, Oscar; Betz, Michael; Dragusanu, Daniela; Bulling, Shelley; Bron, Luc; Pasche, Philippe; Seelentag, Walter; Mirimanoff, René O; Zouhair, Abderrahim; Ozsahin, Mahmut

    2009-05-01

    The aim of this study was to assess feasibility and efficacy of weekly concomitant boost accelerated postoperative radiation therapy (PORT) with concomitant chemotherapy (CT) in patients with locally advanced head and neck cancer (LAHNC). Conformal or intensity-modulated 66-Gy RT was performed in 5.5 weeks in 40 patients. Cisplatin was given at days 1, 22, and 43. Median follow-up was 36 months. Grade 3 mucositis, dysphagia, and erythema was observed in ten (25%), nine (23%), and six (13%) patients, respectively. Grade 3 or more anemia was observed in two (6%) patients, and leukopenia in five (13%) patients. No grade 3 or 4 thrombocytopenia was observed. Grade 3 nephrotoxicity was observed in one patient (3%). No treatment-related mortality was observed. Grade 2 or more xerostomia and edema were observed in ten (25%) and one (3%) patient, respectively. Locoregional relapse occurred in eight patients, and seven patients developed distant metastases. Median time to locoregional relapse was 6 months. Three-year overall, disease-free survival, and locoregional control rates were 63%, 62%, and 81%, respectively. Multivariate analysis revealed that the only prognostic factor was nodal status. Reducing overall treatment time using accelerated PORT/CT by weekly concomitant boost (six fractions per week) combined with concomitant cisplatin CT is easily feasible with acceptable morbidity.

  17. Impact of Adding Concomitant Chemotherapy to Hyperfractionated Accelerated Radiotherapy for Advanced Head-and-Neck Squamous Cell Carcinoma

    SciTech Connect

    Nuyts, Sandra Dirix, Piet; Clement, Paul M.J.; Poorten, Vincent Vander; Delaere, Pierre; Schoenaers, Joseph; Hermans, Robert; Bogaert, Walter van den

    2009-03-15

    Purpose: To evaluate the feasibility and efficacy of a hyperfractionated accelerated radiotherapy (RT) schedule combined with concomitant chemotherapy (Cx) in patients with locally advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between 2004 and 2007, a total of 90 patients with locoregionally advanced head-and-neck squamous cell carcinoma underwent irradiation according to a hybrid fractionation schedule consisting of 20 fractions of 2 Gy (once daily) followed by 20 fractions of 1.6 Gy (twice daily) to a total dose of 72 Gy. Concomitant Cx (cisplatinum 100 mg/m{sup 2}) was administered at the start of Weeks 1 and 4. Treatment outcome and toxicity were retrospectively compared with a previous patient group (n = 73) treated with the same schedule, but without concomitant Cx, between 2001 and 2004. Results: The locoregional control (LRC) rate was 70% after 2 years. Two-year overall and 2-year disease-free survival rates were 74% and 60%, respectively. In comparison with the RT-only group, an improvement of 15% in both LRC (p = 0.03) and overall survival (p = 0.09) was observed. All patients were treated to full radiation dose according to protocol, although the Cx schedule had to be adjusted in 12 patients. No acute Grade 4 or 5 toxicity was seen, but incidences of Grade 3 acute mucositis (74.5% vs. 50.7%; p = 0.002) and dysphagia (82.2% vs. 47.9%; p < 0.001) were significantly higher in the chemoradiotherapy group compared with patients treated with RT alone. Conclusion: With this chemoradiotherapy regimen, excellent LRC and survival rates were achieved, with acceptable acute toxicity.

  18. Safety and Efficacy of Isolated Limb Infusion Chemotherapy for Advanced Locoregional Melanoma in Elderly Patients: An Australian Multicenter Study.

    PubMed

    Kroon, Hidde M; Coventry, Brendon J; Giles, Mitchell H; Henderson, Michael A; Speakman, David; Wall, Mark; Barbour, Andrew; Serpell, Jonathan; Paddle, Paul; Smithers, Bernard M; Thompson, John F

    2017-08-10

    Isolated limb infusion (ILI) offers a minimally invasive treatment option for locally advanced extremity melanoma. The aim of the current study was to evaluate the safety and efficacy of ILI in elderly patients in an Australian multicenter setting. The results of 316 first ILI procedures, performed between 1992 and 2008 in five Australian institutions, were identified and analyzed, with the main focus on elderly patients (≥75 years of age). All institutions used the same protocol: melphalan was circulated in the isolated limb for 20-30 min (±actinomycin D), and toxicity, responses, and survival were recorded. Characteristics of patients aged ≥75 years (n = 148) were similar to those aged <75 years (n = 168), except that older patients had more melanoma deposits (median 4 vs. 5; p = 0.035) and lower limb volumes (5.4 vs. 6.5 L; p = 0.001). Median drug circulation times were lower in the older group (21 vs. 24 min; p = 0.04), and older patients experienced less limb toxicity (grade III/IV in 22 and 37% of patients, respectively; p = 0.003). A complete response (CR) was seen in 27% of patients aged ≥75 years and in 38% of patients aged <75 years (p = 0.06), while overall response rates were 72 and 77%, respectively (p = 0.30). No difference in survival was seen (p = 0.69). The ILI technique proved safe and effective in elderly patients. When present, toxicity was localized, and lower compared with younger patients, possibly due to shorter drug circulation times. CR rates were higher in younger patients, although not significantly, while overall response and survival were equal. Optimization of perioperative factors in elderly patients may allow response rates to be raised further, while maintaining low toxicity.

  19. Accelerated versus conventional fractionated postoperative radiotherapy for advanced head and neck cancer: Results of a multicenter Phase III study

    SciTech Connect

    Sanguineti, Giuseppe . E-mail: gisangui@utmb.edu; Richetti, Antonella; Bignardi, Mario; Corvo, Renzo; Gabriele, Pietro; Sormani, Maria Pia; Antognoni, Paolo

    2005-03-01

    Purpose: To determine whether, in the postoperative setting, accelerated fractionation (AF) radiotherapy (RT) yields a superior locoregional control rate compared with conventional fractionation (CF) RT in locally advanced squamous cell carcinomas of the oral cavity, oropharynx, larynx, or hypopharynx. Methods and materials: Patients from four institutions with one or more high-risk features (pT4, positive resection margins, pN >1, perineural/lymphovascular invasion, extracapsular extension, subglottic extension) after surgery were randomly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF. Accelerated fractionation consisted of a 'biphasic concomitant boost' schedule, with the boost delivered during the first and last weeks of treatment, to deliver 64 Gy in 5 weeks. Informed consent was obtained. The primary endpoint of the study was locoregional control. Analysis was on an intention-to-treat basis. Results: From March 1994 to August 2000, 226 patients were randomized. At a median follow-up of 30.6 months (range, 0-110 months), 2-year locoregional control estimates were 80% {+-} 4% for CF and 78% {+-} 5% for AF (p = 0.52), and 2-year overall survival estimates were 67% {+-} 5% for CF and 64% {+-} 5% for AF (p = 0.84). The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis. However, interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF (hazard ratio = 0.5, 95% confidence interval 0.2-1.1). Fifty percent of patients treated with AF developed confluent mucositis, compared with only 27% of those treated with CF (p = 0.006). However, mucositis duration was not different between arms. Although preliminary, actuarial Grade 3+ late toxicity estimates at 2 years were 18% {+-} 4% and 27% {+-} 6% for CF

  20. Do selective radiation dose escalation and tumour hypoxia status impact the loco-regional tumour control after radio-chemotherapy of head & neck tumours? The ESCALOX protocol.

    PubMed

    Pigorsch, Steffi U; Wilkens, Jan J; Kampfer, Severin; Kehl, Victoria; Hapfelmeier, Alexander; Schläger, Christian; Bier, Henning; Schwaiger, Markus; Combs, Stephanie E

    2017-03-01

    Standard of care primary treatment of carcinoma of locally advanced squamous cell head and neck cancer (LAHNSCC) consists of platinum-based concomitant chemo-irradiation. Despite progress in the treatment of LAHNSCC using modern radiotherapy techniques the outcome remains still poor. Using IMRT with SIB the escalation of total dose to the GTV is possible with the aim to improve clinical outcome. This study tests the hypothesis if radiation dose escalation to the GTV improves 2-year-LRC and -OS after concomitant chemo-irradiation. The ESCALOX trial is a prospective randomized phase III study using cisplatin chemo-irradiation and the SIB-IMRT concept in patients with LAHNSCC of the oral cavity, oropharynx or hypopharynx to escalate the total dose to the GTV up to 80.5 Gy. Chemotherapy is planned either in the 1(st) and 5(th) week (cisplatin 20 mg/m(2)/d d 1-5 and d 29-33) or weekly (cisplatin 40 mg/m(2)/d) during RT. RT is delivered as SIB with total doses of 80.5 Gy/70.0 Gy/56.0 Gy with 2.3 Gy/2.0 Gy and 1.6 Gy in the experimental arm and in the control arm with 70.0 Gy/56.0 Gy with 2.0 Gy and 1.6 Gy. A pre-study with dose escalation up to 77.0 Gy/70.0 Gy/56.0 Gy with 2.2 Gy/2.0 Gy and 1.6 Gy is demanded by the German federal office of radiation protection (BfS). In the translational part of the trial 100 of the randomised patients will be investigated by 18-F-FMiso-PET-CT for the presence and behaviour of tumor hypoxia twice in the week before treatment start. The primary endpoint of the pre-study is acute radiation induced toxicity. Primary endpoint of the main trial is 2-year-LRC. By using the dose escalation up to 80.5 Gy to the GTV of the primary tumor and lymph nodes > 2 cm a LRC benefit of 15% at 2 years should be expected. The ESCALOX trial is supported by Deutsche Forschungsgemeinschaft (DFG); Grant No.: MO-363/4-1. ClinicalTrials.gov Identifier: NCT 01212354 , EudraCT-No.: 2010-021139-15.

  1. A Randomized Prospective Study of Concurrent Chemo-Radiotherapy vs Accelerated Hyperfractionation in Advanced Cancer of Head and Neck

    PubMed Central

    Mishra, Ritusha; Shahi, Uday Prataap; Mandal, Abhijit

    2016-01-01

    Introduction Locally advanced unresectable squamous cell carcinoma of head and neck has poor locoregional control when treated with conventionally fractionated Radiation Therapy (RT) alone. However, Concurrent Chemo-Radiotherapy (CRT) and altered fractionated RT schedules like Accelerated Hyperfractionation (AHF) are two different treatment strategies that have shown to be associated with better efficacy as compared to conventional RT alone in such cases. Aim Aim of the study was to compare these two treatment strategies i.e., CRT and AHF radiation treatment to know which is better in terms of clinical outcome and toxicity in patients of locally advanced unresectable squamous cell carcinoma of head and neck. Materials and Methods A prospective randomized trial was done to compare the effect of CRT and of AHF radiation treatment in locally advanced unresectable head and neck cancer on 15 patients in each arm and followed up over three months period. Results At the end of three months after completion of treatment protocol, complete response was 62% in CRT arm and 53% in AHF arm. In CRT arm and AHF arm, Grade 3 skin reactions were observed in 100% and 87%, grade 3 mucosal reactions were in 62% and 67% of cases, respectively. Three patients died in CRT arm (two due to myelosuppression and associated infection; one during the treatment and another after two weeks of treatment completion. The third patient expired after one month of treatment completion at his native place due to unknown reason). One patient died in AHF arm (during treatment due to cardiac event). Conclusion Efficacy of AHF was comparable to CRT with lesser toxicity. So the present study suggests that AHF should be preferred over CRT in locally advanced, unresectable, squamous cell head and neck cancer followed over three months non-treatment period. PMID:27891443

  2. Distribution and Prevalence of Locoregional Recurrence after Video-Assisted Thoracoscopic Surgery for Primary Lung Cancer.

    PubMed

    Haruki, Tomohiro; Miwa, Ken; Araki, Kunio; Taniguchi, Yuji; Nakamura, Hiroshige

    2016-09-01

    Background The aim of this study is to evaluate cases with locoregional recurrence after video-assisted thoracoscopic surgery (VATS) for primary lung cancer. Methods We reviewed 248 patients with primary lung cancer who underwent lobectomy or segmentectomy with mediastinal lymph node dissection by VATS between January 2005 and December 2011. Locoregional recurrence is defined as per its occurrence in (1) bronchial stump or lung parenchymal cut end, (2) ipsilateral pleura, and (3) ipsilateral hilar and mediastinal lymph nodes, and we analyzed recurrence rate and significant associated factors for locoregional recurrence by logistic regression analysis. Results There were 47 cases of postoperative recurrence, which consisted of 26 distant, 6 locoregional and distant, and 15 locoregional recurrences. The locoregional recurrence rate was 6.0%. Of the 15 locoregional recurrence cases, there were two cases of bronchial stump and lung parenchyma cut end (0.4%), five cases of ipsilateral pleura (2.0%), and eight cases of ipsilateral hilar and mediastinal lymph nodes (3.2%). Pleural and lymphovascular invasion and advanced stages were significant associated factors in univariate analysis. Multivariate analysis revealed that advanced stages were only a significant associated factor for locoregional recurrence (p < 0.01, odds ratio: 3.3). Conclusion Although locoregional recurrence rates of our surgical treatments for primary lung cancer by VATS might be acceptable, we should explore more effective modalities against pathologically proven local advanced lung cancer for preventing not only distant but also locoregional recurrences.

  3. Locoregional Therapies of Cholangiocarcinoma.

    PubMed

    Sommer, Christof M; Kauczor, Hans U; Pereira, Philippe L

    2016-12-01

    Cholangiocarcinoma (CC) is the second most primary liver malignancy with increasing incidence in Western countries. Currently, surgical R0 resection is regarded as the only potentially curative treatment. The results of systemic chemotherapy and best supportive care (BSC) in patients with metastatic disease are often disappointing in regard to toxicity, oncologic efficacy, and overall survival. In current practice, the use of different locoregional therapies is increasingly more accepted. A review of the literature on locoregional therapies for intrahepatic cholangiocarcinoma (ICC) was undertaken. There are no prospective randomized controlled trials. For localized ICC, either primary or recurrent, radiofrequency ablation (RFA) is by far the most commonly used thermal ablation modality. Thereby, a systematic review and meta-analysis reports major complication in 3.8% as well as 1-, 3-, and 5-year overall survival rates of 82, 47, and 24%, respectively. In selected patients (e.g. with a tumor diameter of ≤3 cm), oncologic efficacy and survival after RFA are comparable with surgical resection. For diffuse ICC, different transarterial therapies, either chemotherapy-based (hepatic artery infusion (HAI), transarterial chemoembolization (TACE)) or radiotherapy-based (transarterial radioembolization (TARE)), show extremely promising results. With regard to controlled trials (transarterial therapy versus systemic chemotherapy, BSC or no treatment), tumor control is virtually always better for transarterial therapies and very often accompanied by a dramatic survival benefit and improvement of quality of life. Of note, the latter is the case not only for patients without extrahepatic metastatic disease but also for those with liver-dominant extrahepatic metastatic disease. There are other locoregional therapies such as microwave ablation, irreversible electroporation, and chemosaturation; however, the current data support their use only in controlled trials or as last

  4. Factors Associated With Long-Term Dysphagia After Definitive Radiotherapy for Locally Advanced Head-and-Neck Cancer

    SciTech Connect

    Caudell, Jimmy J.; Schaner, Philip E.; Meredith, Ruby F.; Locher, Julie L.; Nabell, Lisle M.; Carroll, William R.; Magnuson, J. Scott; Spencer, Sharon A.; Bonner, James A.

    2009-02-01

    Purpose: The use of altered fractionation radiotherapy (RT) regimens, as well as concomitant chemotherapy and RT, to intensify therapy for locally advanced head-and-neck cancer can lead to increased rates of long-term dysphagia. Methods and Materials: We identified 122 patients who had undergone definitive RT for locally advanced head-and-neck cancer, after excluding those who had been treated for a second or recurrent head-and-neck primary, had Stage I-II disease, developed locoregional recurrence, had <12 months of follow-up, or had undergone postoperative RT. The patient, tumor, and treatment factors were correlated with a composite of 3 objective endpoints as a surrogate for severe long-term dysphagia: percutaneous endoscopic gastrostomy tube dependence at the last follow-up visit; aspiration on a modified barium swallow study or a clinical diagnosis of aspiration pneumonia; or the presence of a pharyngoesophageal stricture. Results: A composite dysphagia outcome occurred in 38.5% of patients. On univariate analysis, the primary site (p = 0.01), use of concurrent chemotherapy (p = 0.01), RT schedule (p = 0.02), and increasing age (p = 0.04) were significantly associated with development of composite long-term dysphagia. The use of concurrent chemotherapy (p = 0.01), primary site (p = 0.02), and increasing age (p = 0.02) remained significant on multivariate analysis. Conclusion: The addition of concurrent chemotherapy to RT for locally advanced head-and-neck cancer resulted in increased long-term dysphagia. Early intervention using swallowing exercises, avoidance of nothing-by-mouth periods, and the use of intensity-modulated RT to reduce the dose to the uninvolved swallowing structures should be explored further in populations at greater risk of long-term dysphagia.

  5. Prospective Pilot Study of Consolidation Chemotherapy With Docetaxel and Cisplatin After Concurrent Chemoradiotherapy for Advanced Head and Neck Cancer

    SciTech Connect

    Lee, Kyun Chan; Lee, Seok Ho; Lee, Yuna; Park, Se Hoon Park, Jinny; Cho, Eun Kyung; Shin, Dong Bok; Lee, Jae Hoon; Kim, Dong Young; Kim, Seon Tae

    2008-05-01

    Purpose: With the improvement concurrent chemoradiotherapy (CCRT) in the management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC), distant failures have become a more relevant problem in terms of survival. The primary objective of this Phase II study is to assess the feasibility of docetaxel and cisplatin consolidation after primary CCRT for patients with HNSCC. Methods and Materials: Patients with locoregionally advanced HNSCC received chemotherapy with three cycles of cisplatin, 100 mg/m{sup 2}, on Days 1, 22, and 43. Concurrent radiotherapy to the primary tumor and neck was given in a daily dose of 2 Gy to a total dose of 70-70.2 Gy over 7 weeks. After completion of CCRT, patients without evidence of disease progression received an additional four cycles of consolidation chemotherapy with docetaxel, 75 mg/m{sup 2}, and cisplatin, 75 mg/m{sup 2}, every 3 weeks. Results: Of 33 patients, 27 (81%) completed CCRT. After CCRT, three complete and 19 partial responses were recorded, giving an overall response rate of 67%. Of 19 patients who went to the consolidation phase, only 4 (21%) received all four cycles of docetaxel and cisplatin. Causes of failure of consolidation chemotherapy were toxicity in 11 patients, including three treatment-related deaths, and progression in 4 patients. Three patients died of sepsis during the consolidation phase. Median survival was 11 months for all patients and 8 months for those treated with consolidation chemotherapy. Conclusion: The poor compliance and high incidence of severe toxicities prompted no further evaluation of this consolidation chemotherapy after CCRT.

  6. Long-term follow-up after transoral laser microsurgery and adjuvant radiotherapy for advanced recurrent squamous cell carcinoma of the head and neck

    SciTech Connect

    Christiansen, Hans . E-mail: hchrist@gwdg.de; Hermann, Robert Michael; Martin, Alexios; Florez, Rodrigo; Kahler, Elke; Nitsche, Mirko; Hille, Andrea; Steiner, Wolfgang; Hess, Clemens F.; Pradier, Olivier

    2006-07-15

    Purpose: The aim of this study was to evaluate the efficacy of adjuvant radiotherapy after transoral laser microsurgery for advanced recurrent head-and-neck squamous cell carcinoma (HNSCC). Patients and Methods: Between 1988 and 2000, 37 patients with advanced local recurrences (23 local and 14 locoregional recurrences) of HNSCC without distant metastases were treated in curative intent with organ-preserving transoral laser microsurgery and adjuvant radiotherapy (before 1994 split-course radiotherapy with carboplatinum, after 1994 conventional radiotherapy). Initial therapy of the primary (8.1% oral cavity, 35.1% oropharynx, 13.5% hypopharynx, and 43.3% larynx) before relapse was organ-preserving transoral laser microsurgery without any adjuvant therapy. Results: After a median follow-up of 124 months, the 5-year overall survival rate was 21.3%, the loco-regional control rate 48.3%, respectively. In multivariate analysis, stage of original primary tumor (Stage I/II vs. Stage III/IV), and patient age (<58 years vs. {>=}58 years) showed statistically significant impact on prognosis. In laryngeal cancer, larynx preservation rate after treatment for recurrent tumor was 50% during follow-up. Conclusion: Our data show that organ-preserving transoral laser microsurgery followed by adjuvant radiotherapy is a curative option for patients who have advanced recurrence after transoral laser surgery and is an alternative to radical treatment.

  7. Comparing two lower-dose cisplatin programs for radio-chemotherapy of locally advanced head-and-neck cancers.

    PubMed

    Rades, Dirk; Seidl, Daniel; Janssen, Stefan; Strojan, Primoz; Karner, Katarina; Bajrovic, Amira; Hakim, Samer G; Wollenberg, Barbara; Schild, Steven E

    2017-02-01

    Radio-chemotherapy is a common treatment for locally advanced squamous cell head-and-neck cancers (LA-SCCHN). Cisplatin (100 mg/m(2)) every 3 weeks is very common but associated with considerable toxicity. Therefore, cisplatin programs with lower daily doses were introduced. There is a lack of studies comparing lower-dose programs. In this study, 85 patients receiving radio-chemotherapy with 20 mg/m(2) cisplatin on 5 days every 4 weeks (group A) were retrospectively compared to 85 patients receiving radio-chemotherapy with 30-40 mg/m(2) cisplatin weekly (group B). Groups were matched for nine factors including age, gender, performance score, tumor site, T-/N-category, surgery, hemoglobin before radio-chemotherapy, and radiation technique. One- and 3-year loco-regional control rates were 83 and 69 % in group A versus 74 and 63 % in group B (p = 0.12). One- and 3-year survival rates were 93 % and 73 % in group A versus 91 and 49 % in group B (p = 0.011). On multivariate analysis, survival was significantly better for group A (HR 1.17; p = 0.002). In groups A and B, 12 and 28 % of patients, respectively, did not receive a cumulative cisplatin dose ≥180 mg/m(2) (p = 0.016). Toxicity rates were not significantly different. On subgroup analyses, group A patients had better loco-regional control (p = 0.040) and survival (p = 0.005) than group B patients after definitive radio-chemotherapy. In patients receiving adjuvant radio-chemotherapy, outcomes were not significantly different. Thus, 20 mg/m(2) cisplatin on 5 days every 4 weeks resulted in better loco-regional control and survival in patients receiving definitive radio-chemotherapy and may be preferable for these patients. Confirmation of these results in a randomized trial is warranted.

  8. Advances and trends of head-up and head-down display systems in automobiles

    NASA Astrophysics Data System (ADS)

    Betancur, J. Alejandro; Osorio-Gomez, Gilberto; Agudelo, J. David

    2014-06-01

    Currently, in the automotive industry the interaction between drivers and Augmented Reality (AR) systems is a subject of analysis, especially the identification of advantages and risks that this kind of interaction represents. Consequently, this paper attempts to put in evidence the potential applications of Head-Up (Display (HUD) and Head-Down Display (HDD) systems in automotive vehicles, showing applications and trends under study. In general, automotive advances related to AR devices suggest the partial integration of the HUD and HDD in automobiles; however, the right way to do it is still a moot point.

  9. Recent advances in surgery for head and neck cancer.

    PubMed

    de Bree, Remco; Leemans, Charles René

    2010-05-01

    This paper reviews the advances in surgery in head and neck cancer patients. Sentinel node biopsy is a promising diagnostic technique to detect occult lymph node metastases, especially in oral carcinomas. Fludeoxyglucose-PET seems to be useful in detecting recurrent (laryngeal) carcinoma after radiotherapy. The role of fludeoxyglucose-PET to detect residual disease in the neck after radiotherapy with or without chemotherapy is not yet clear. The armamentarium of reconstructive surgery is still expanding. Endonasal endoscopic, robotic surgery and image-guided surgery are used as minimal invasive surgery in selected patients. Other advances include photodynamic therapy, ultrasonic surgery and mechanical sutures. New diagnostic techniques are used to avoid futile extensive surgery. Technical improvements have been made to treat head and neck cancer patients with minimal invasive surgery. Large prospective trials are needed to determine the indications for each technique.

  10. Reirradiation With Cetuximab in Locoregional Recurrent and Inoperable Squamous Cell Carcinoma of the Head and Neck: Feasibility and First Efficacy Results

    SciTech Connect

    Balermpas, Panagiotis; Keller, Christian; Hambek, Markus; Wagenblast, Jens; Seitz, Oliver; Roedel, Claus; Weiss, Christian

    2012-07-01

    Purpose: To report our experience with a prospective protocol of external beam reirradiation (Re-RT) combined with cetuximab for patients with inoperable, recurrent squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods: Between August 2008 and June 2010, 18 patients with inoperable recurrence of SCCHN after adjuvant or definitive radiotherapy (RT) and simultaneous or sequential cisplatin-based chemotherapy for primary SCCHN were enrolled. Acute and late toxicity from the experimental regimen were recorded every week during RT and every 3 months thereafter. Efficacy was assessed with repeated imaging using response evaluation criteria in solid tumors and clinical examinations 8-12 weeks after completion of the treatment and every 3 months thereafter. Results: Median follow-up time for all patients was 9.4 (range: 3.85-31.7) months and for patients alive 30.4 (range: 15.7-31.7) months. Acute toxicity was generally mild or moderate. Five patients developed a grade 3 acneiform rash related to cetuximab. Late toxicity occurred as grade 3 trismus in five and as grade 3 abacterial salivary gland inflammation in one patient, respectively. Overall response rate was 47%. Median overall and progression-free survival for all patients was 8.38 months and 7.33 months, respectively. The overall survival rate was 44% at 1 year, with a 1 year local control rate of 33%. Conclusion: Notwithstanding the limitations of our preliminary data Re-RT combined with cetuximab for recurrent and inoperable SCCHN is feasible and the integration of newer targeted agents seems to be less toxic compared to conventional chemotherapy with encouraging response rates at least for a subset of patients.

  11. Physical examination during chemoradiation predicts outcome of locally advanced head and neck cancer. Secondary results of a randomized phase III trial (SAKK 10/94).

    PubMed

    Ghadjar, Pirus; Sun, Hong; Zimmermann, Frank; Bodis, Stephan; Bernier, Jacques; Studer, Gabriela; Aebersold, Daniel M

    2013-10-01

    To analyze the prognostic value of clinical tumor response during chemoradiation for locally advanced head and neck cancer. The locoregional response at 50.4Gy was assessed by physical examination (PE) in patients treated within the randomized trial SAKK 10/94 using hyperfractionated radiotherapy (RT), median total dose 74.4Gy with or without cisplatin 20mg/m(2) chemotherapy on 5 consecutive days during weeks 1 and 5 or 6 of RT. Response was classified as a complete response (CR), complete response with uncertainty (Cru), partial response (PR), stable disease (SD), or progressive disease (PD). The primary endpoint was time to treatment failure (TTF) due to any cause. Secondary endpoints included locoregional-recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS). Univariate and multivariate Cox proportional hazards (PH) models were applied to analyze the associations between survival endpoints and clinical tumor response. A total of 136, 131 and 97 patients were evaluable for response at the primary tumor, lymph nodes and both sites combined, respectively. At 50.4Gy 57/136 (42%), 46/131 (35%) and 21/97 (22%) patients had a good response (CR/Cru vs. PR/SD) at the primary tumor, the lymph nodes, and both sites combined, respectively. The median follow-up times were 11.4, 9.6 and 11.4years for the three groups. Good responses were all significantly associated with improved TTF, LRRFS, DMFS and OS in univariate analysis whereas good response at the primary tumor and lymph nodes remained significantly associated with TTF and OS after multivariate Cox PH models. Locoregional response at 50.4Gy was identified as predictor of oncologic outcome. PE during treatment should not be underestimated in clinical practice. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Concomitant Cisplatin and Hyperfractionated Radiotherapy in Locally Advanced Head and Neck Cancer: 10-Year Follow-Up of a Randomized Phase III Trial (SAKK 10/94)

    SciTech Connect

    Ghadjar, Pirus; Simcock, Mathew; Studer, Gabriela; Allal, Abdelkarim S.; Ozsahin, Mahmut; Bernier, Jacques; Toepfer, Michael; Zimmermann, Frank; Betz, Michael; Glanzmann, Christoph; Aebersold, Daniel M.

    2012-02-01

    Purpose: To compare the long-term outcome of treatment with concomitant cisplatin and hyperfractionated radiotherapy versus treatment with hyperfractionated radiotherapy alone in patients with locally advanced head and neck cancer. Methods and Materials: From July 1994 to July 2000, a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to receive either hyperfractionated radiotherapy alone (median total dose, 74.4 Gy; 1.2 Gy twice daily; 5 days per week) or the same radiotherapy combined with two cycles of cisplatin (20 mg/m{sup 2} for 5 consecutive days during weeks 1 and 5). The primary endpoint was the time to any treatment failure; secondary endpoints were locoregional failure, metastatic failure, overall survival, and late toxicity assessed according to Radiation Therapy Oncology Group criteria. Results: Median follow-up was 9.5 years (range, 0.1-15.4 years). Median time to any treatment failure was not significantly different between treatment arms (hazard ratio [HR], 1.2 [95% confidence interval {l_brace}CI{r_brace}, 0.9-1.7; p = 0.17]). Rates of locoregional failure-free survival (HR, 1.5 [95% CI, 1.1-2.1; p = 0.02]), distant metastasis-free survival (HR, 1.6 [95% CI, 1.1-2.5; p = 0.02]), and cancer-specific survival (HR, 1.6 [95% CI, 1.0-2.5; p = 0.03]) were significantly improved in the combined-treatment arm, with no difference in major late toxicity between treatment arms. However, overall survival was not significantly different (HR, 1.3 [95% CI, 0.9-1.8; p = 0.11]). Conclusions: After long-term follow-up, combined-treatment with cisplatin and hyperfractionated radiotherapy maintained improved rates of locoregional control, distant metastasis-free survival, and cancer-specific survival compared to that of hyperfractionated radiotherapy alone, with no difference in major late toxicity.

  13. Induction Chemotherapy Improved Long-term Outcomes of Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: A Propensity Matched Analysis of 5-year Survival Outcomes in the Era of Intensity-modulated Radiotherapy

    PubMed Central

    Peng, Hao; Chen, Lei; Zhang, Jian; Li, Wen-Fei; Mao, Yan-Ping; Zhang, Yuan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2017-01-01

    Background: The aim of this study is to evaluate the long-term therapeutic gain of induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT). Methods: Data on 957 patients with stage T1-2N2-3 or T3-4N1-3 NPC treated with IMRT were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance influence of various covariates. Patient survival between IC and non-IC groups were compared. Results: For the 318 pairs selected from the original 957 patients by PSM, the median follow-up duration was 57.13 months (range, 1.27-78.1 months). The 5-year overall survival (OS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and locoregional relapse-free survival (LRRFS) rates for IC group vs. non-IC group were 87.2% vs. 80.8% (P = 0.023), 88.1% vs. 83.2% (P = 0.071), 80.7% vs. 71.4% (P = 0.011) and 92.1% vs. 86.7% (P = 0.081), respectively. Multivariate analysis identify IC as an independent prognostic factor for OS (HR, 0.595; 95% CI, 0.397-0.891; P = 0.012) and DFS (HR, 0.627; 95% CI, 0.451-0.872; P = 0.006). After excluding the patients not receiving concurrent chemotherapy, IC was found to be an independent prognostic factor for OS (HR, 0.566; 95% CI, 0.368-0.872; P = 0.01), DMFS (HR, 0.580; 95% CI, 0.367-0.916; P = 0.02) and DFS (HR, 0.633; 95% CI, 0.444-0.903; P = 0.012). Conclusions: IC is an effective treatment modality for patients with stage T1-2N2-3 and T3-4N1-3 NPC, and the incorporation of IC with standard CCRT could achieve the best therapeutic gain. PMID:28261337

  14. Advanced Stirling Convertor Heater Head Durability and Reliability Quantification

    NASA Technical Reports Server (NTRS)

    Krause, David L.; Shah, Ashwin R.; Korovaichuk, Igor; Kalluri, Sreeramesh

    2008-01-01

    The National Aeronautics and Space Administration (NASA) has identified the high efficiency Advanced Stirling Radioisotope Generator (ASRG) as a candidate power source for long duration Science missions, such as lunar applications, Mars rovers, and deep space missions, that require reliable design lifetimes of up to 17 years. Resistance to creep deformation of the MarM-247 heater head (HH), a structurally critical component of the ASRG Advanced Stirling Convertor (ASC), under high temperatures (up to 850 C) is a key design driver for durability. Inherent uncertainties in the creep behavior of the thin-walled HH and the variations in the wall thickness, control temperature, and working gas pressure need to be accounted for in the life and reliability prediction. Due to the availability of very limited test data, assuring life and reliability of the HH is a challenging task. The NASA Glenn Research Center (GRC) has adopted an integrated approach combining available uniaxial MarM-247 material behavior testing, HH benchmark testing and advanced analysis in order to demonstrate the integrity, life and reliability of the HH under expected mission conditions. The proposed paper describes analytical aspects of the deterministic and probabilistic approaches and results. The deterministic approach involves development of the creep constitutive model for the MarM-247 (akin to the Oak Ridge National Laboratory master curve model used previously for Inconel 718 (Special Metals Corporation)) and nonlinear finite element analysis to predict the mean life. The probabilistic approach includes evaluation of the effect of design variable uncertainties in material creep behavior, geometry and operating conditions on life and reliability for the expected life. The sensitivity of the uncertainties in the design variables on the HH reliability is also quantified, and guidelines to improve reliability are discussed.

  15. Nivolumab or Expectant Observation Following Ipilimumab, Nivolumab, and Surgery in Treating Patients With High Risk Localized, Locoregionally Advanced, or Recurrent Mucosal Melanoma

    ClinicalTrials.gov

    2017-09-04

    Cervical Carcinoma; Esophageal Carcinoma; Mucosal Melanoma; Mucosal Melanoma of the Head and Neck; Oral Cavity Mucosal Melanoma; Recurrent Melanoma; Stage II Vulvar Cancer; Stage III Vulvar Cancer; Stage IIIA Vulvar Cancer; Stage IIIB Vulvar Cancer; Stage IIIC Vulvar Cancer; Stage IV Oral Cavity Cancer AJCC v6 and v7; Stage IV Vulvar Cancer; Stage IVA Oral Cavity Cancer AJCC v6 and v7; Stage IVB Oral Cavity Cancer AJCC v6 and v7; Stage IVC Oral Cavity Cancer AJCC v6 and v7; Vaginal Carcinoma

  16. Race and competing mortality in advanced head and neck cancer.

    PubMed

    Zakeri, Kaveh; MacEwan, Iain; Vazirnia, Aria; Cohen, Ezra E W; Spiotto, Michael T; Haraf, Daniel J; Vokes, Everett E; Weichselbaum, Ralph R; Mell, Loren K

    2014-01-01

    Black patients with head and neck cancer (HNC) have poorer survival and disease control compared to non-black patients, but disparities in death from non-cancer causes (i.e., competing mortality) are less well-studied. We conducted an analysis of 538 patients (169 black, 369 non-black) with stage III-IV HNC treated on one of six multi-institutional protocols between 1993 and 2004 involving multi-agent chemoradiotherapy with or without surgery. Competing mortality was defined as death due to intercurrent comorbid disease, treatment-related morbidity, or unknown cause in the absence of disease recurrence, progression, or second malignancy. Cox proportional hazards and competing risks regression were used to estimate the effect of black race on competing mortality. Black race was associated with increased rates of comorbidity, smoking, heavy alcohol use, advanced tumor stage, and poorer performance status (p<.001 for all). Compared to non-black patients, black HNC patients had a higher 5 year cumulative incidence of disease progression (31.4%; 95% CI, 24.4-38.5% vs 23.4%; 95% CI, 19.1-28.1%) and competing mortality (28.1%; 95% CI, 21.2-35.3% vs 14.5%; 95% CI, 11.0-18.5%). When adjusting for age, male sex, body mass index, distance traveled, smoking and alcohol use, performance status, comorbidity, and tumor stage, the black race was associated with death from comorbid disease (Cox hazard ratio 2.13; 95% CI, 1.06-4.28, p=0.033). Black patients with advanced HNC are at increased risk of both disease progression and death from competing non-cancer mortality, particularly death from comorbid disease. Improved strategies to manage comorbid disease may increase the benefit of treatment intensification in black patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Technical Advances and Pitfalls in Head and Neck Radiotherapy

    PubMed Central

    Parvathaneni, Upendra; Laramore, George E.; Liao, Jay J.

    2012-01-01

    Intensity Modulated Radiotherapy (IMRT) is the standard of care in the treatment of head and neck squamous cell carcinomas (HNSCC) based on level 1 evidence. Technical advances in radiotherapy have revolutionized the treatment of HNSCC, with the most tangible gain being a reduction in long term morbidity. However, these benefits come with a serious and sobering price. Today, there is a greater chance of missing the target/tumor due to uncertainties in target volume definition by the clinician that is demanded by the highly conformal planning process involved with IMRT. Unless this is urgently addressed, our patients would be better served with the historically practiced non conformal radiotherapy, than IMRT which promises lesser morbidity. Image guided radiotherapy (IGRT) ensures the level of set up accuracy warranted to deliver a highly conformal treatment plan and should be utilized with IMRT, where feasible. Proton therapy has a theoretical physical advantage over photon therapy due to a lack of “exit dose”. However, clinical data supporting the routine use of this technology for HNSCC are currently sparse. The purpose of this article is to review the literature, discuss the salient issues and make recommendations that address the gaps in knowledge. PMID:22701482

  18. Advances in otolaryngology-Head and neck surgery. Volume 1

    SciTech Connect

    Myers, E.N. ); Bluestone, C.D. )

    1987-01-01

    This book consists of 14 sections. The section titles are: The impact of AIDS on otolaryngology--head and neck surgery; The management of sleep apneas and snoring; Antimicrobial agents for infections in the ear, nose, and throat--head and neck; Nasal allergy: Medical and surgical treatment; Uses of computerized tomography and magnetic resonance imaging in temporal bone imaging; Surgical management of otitis media with effusion; middle ear reconstruction: Current status; Cochlear implants: an overview; Diagnosis and management of acute facial paralysis; The use of the laser in head and neck surgery; The management and prevention of subglottic stenosis in infants and children; Management of the mass in the thyroid; Suction-assisted lipectomy of the head and neck area; and Ambulatory surgery.

  19. Heading perception in patients with advanced retinitis pigmentosa

    NASA Technical Reports Server (NTRS)

    Li, Li; Peli, Eli; Warren, William H.

    2002-01-01

    PURPOSE: We investigated whether retinis pigmentosa (RP) patients with residual visual field of < 100 degrees could perceive heading from optic flow. METHODS: Four RP patients and four age-matched normally sighted control subjects viewed displays simulating an observer walking over a ground. In experiment 1, subjects viewed either the entire display with free fixation (full-field condition) or through an aperture with a fixation point at the center (aperture condition). In experiment 2, patients viewed displays of different durations. RESULTS: RP patients' performance was comparable to that of the age-matched control subjects: heading judgment was better in the full-field condition than in the aperture condition. Increasing display duration from 0.5 s to 1 s improved patients' heading performance, but giving them more time (3 s) to gather more visual information did not consistently further improve their performance. CONCLUSIONS: RP patients use active scanning eye movements to compensate for their visual field loss in heading perception; they might be able to gather sufficient optic flow information for heading perception in about 1 s.

  20. Heading perception in patients with advanced retinitis pigmentosa

    NASA Technical Reports Server (NTRS)

    Li, Li; Peli, Eli; Warren, William H.

    2002-01-01

    PURPOSE: We investigated whether retinis pigmentosa (RP) patients with residual visual field of < 100 degrees could perceive heading from optic flow. METHODS: Four RP patients and four age-matched normally sighted control subjects viewed displays simulating an observer walking over a ground. In experiment 1, subjects viewed either the entire display with free fixation (full-field condition) or through an aperture with a fixation point at the center (aperture condition). In experiment 2, patients viewed displays of different durations. RESULTS: RP patients' performance was comparable to that of the age-matched control subjects: heading judgment was better in the full-field condition than in the aperture condition. Increasing display duration from 0.5 s to 1 s improved patients' heading performance, but giving them more time (3 s) to gather more visual information did not consistently further improve their performance. CONCLUSIONS: RP patients use active scanning eye movements to compensate for their visual field loss in heading perception; they might be able to gather sufficient optic flow information for heading perception in about 1 s.

  1. Advancements in the treatment of head lice in pediatrics.

    PubMed

    Eisenhower, Christine; Farrington, Elizabeth Anne

    2012-01-01

    Head lice infestations occur commonly each year in children of all socioeconomic statuses. However, head lice have become more of a nuisance as resistance to first-line agents, such as permethrin 1% and pyrethrins, has increased. Newer topical products provide unique mechanisms of action without current signs of resistance. As with older agents, proper application of products must be emphasized to ensure that treatment is effective. In addition, nonpharmacologic measures should be taken to avoid reinfestation in the patient and to prevent the spread of lice to close personal contacts.

  2. Primary Tumor Volume Is an Important Predictor of Clinical Outcomes Among Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck Treated With Definitive Chemoradiotherapy

    SciTech Connect

    Strongin, Anna; Yovino, Susannah; Taylor, Rodney; Wolf, Jeffrey; Cullen, Kevin; Zimrin, Ann; Strome, Scott; Regine, William; Suntharalingam, Mohan

    2012-04-01

    Purpose: The tumor volume has been established as a significant predictor of outcomes among patients with head-and-neck cancer undergoing radiotherapy alone. The present study attempted to add to the existing data on tumor volume as a prognostic factor among patients undergoing chemoradiotherapy. Methods and Materials: A total of 78 patients who had undergone definitive chemoradiotherapy for Stage III-IV squamous cell cancer of the hypopharynx, oropharynx, and larynx were identified. The primary tumor volumes were calculated from the treatment planning computed tomography scans, and these were correlated to the survival and tumor control data obtained from the retrospective analysis. Results: The interval to progression correlated with the primary tumor volume (p = .007). The critical cutoff point for the tumor volume was identified as 35 cm{sup 3}, and patients with a tumor volume <35 cm{sup 3} had a significantly better prognosis than those with a tumor volume >35 cm{sup 3} at 5 years (43% vs. 71%, p = .010). Longer survival was also correlated with smaller primary tumor volumes (p = .022). Similarly, patients with a primary tumor volume <35 cm{sup 3} had a better prognosis in terms of both progression-free survival (61% vs. 33%, p = .004) and overall survival (84% vs. 41%, p = < .001). On multivariate analysis, the primary tumor volume was the best predictor of recurrence (hazard ratio 4.7, 95% confidence interval 1.9-11.6; p = .001) and survival (hazard ratio 10.0, 95% confidence interval 2.9-35.1; p = < .001). In contrast, the T stage and N stage were not significant factors. Analysis of variance revealed that tumors with locoregional failure were on average 21.6 cm{sup 3} larger than tumors without locoregional failure (p = .028) and 27.1-cm{sup 3} larger than tumors that recurred as distant metastases (p = .020). Conclusion: The results of our study have shown that the primary tumor volume is a significant prognostic factor in patients with advanced cancer

  3. A comparison of concurrent cisplatin versus cetuximab with radiotherapy in locally-advanced head and neck cancer: A bi-institutional analysis.

    PubMed

    Stokes, William A; Sumner, Whitney A; Breggren, Kiersten L; Rathbun, John T; Raben, David; McDermott, Jessica D; Gan, Gregory; Karam, Sana D

    2017-01-01

    To present our experience comparing cisplatin- and cetuximab-based radiotherapy for locally-advanced head and neck squamous cell carcinoma. The comparative effectiveness of cisplatin-based chemoradiotherapy (CRT) versus cetuximab-based bioradiotherapy (BRT) for locally-advanced head and neck squamous cell carcinoma (LAHNSCC) continues to be explored. Outcomes of LAHNSCC patients treated with CRT (125) or BRT (34) at two institutions were compared retrospectively, with attention to overall survival (OS), cancer-specific survival (CSS), locoregional control (LRC), and distant control (DC). Univariate analysis (UVA) using Cox regression was performed to explore the association of intervention with survival and disease control, and multivariate (MVA) Cox regression was then performed to assess the association of intervention with survival. There were significant baseline differences between the CRT and BRT groups with respect to age, race, performance status, N-classification, tobacco history, and human papillomavirus status. UVA demonstrated inferiority of BRT versus CRT with respect to both OS (hazard ratio [HR] 2.19, 95% confidence interval [95%CI] 1.03-4.63, p = 0.04) and CSS (HR 3.33, 95%CI 1.42-7.78, p < 0.01), but non-significantly different outcomes in LRC (HR 0.99, 95%CI 0.37-2.61, p = 0.98) and DC (HR 2.01, 95%CI 0.78-5.37, p = 0.14). On MVA, there was no significant OS difference between interventions (HR 1.19, 95%CI 0.42-3.35, p = 0.74); there were too few events for the other outcomes to draw meaningful conclusions with MVA. In our retrospective analysis, patients undergoing CRT experienced improved OS and CSS over those receiving BRT; however, disease control did not significantly differ. These findings may inform management of LAHNSCC patients.

  4. Hsp90 Inhibitor AT13387 in Treating Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Radiation Therapy and Cisplatin

    ClinicalTrials.gov

    2017-09-15

    Human Papillomavirus Infection; Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

  5. Gene Expression Profiling to Predict Outcome After Chemoradiation in Head and Neck Cancer

    SciTech Connect

    Pramana, Jimmy; Brekel, Michiel van den; Velthuysen, Marie-Louise F. van; Wessels, Lodewijk F.A.; Nuyten, Dimitry S.; Hofland, Ingrid; Atsma, Douwe; Pimentel, Nuno; Hoebers, Frank J.P.; Rasch, Coen; Begg, Adrian C.

    2007-12-01

    Purpose: The goal of the present study was to improve prediction of outcome after chemoradiation in advanced head and neck cancer using gene expression analysis. Materials and Methods: We collected 92 biopsies from untreated head and neck cancer patients subsequently given cisplatin-based chemoradiation (RADPLAT) for advanced squamous cell carcinomas (HNSCC). After RNA extraction and labeling, we performed dye swap experiments using 35k oligo-microarrays. Supervised analyses were performed to create classifiers to predict locoregional control and disease recurrence. Published gene sets with prognostic value in other studies were also tested. Results: Using supervised classification on the whole series, gene sets separating good and poor outcome could be found for all end points. However, when splitting tumors into training and validation groups, no robust classifiers could be found. Using Gene Set Enrichment analysis, several gene sets were found to be enriched in locoregional recurrences, although with high false-discovery rates. Previously published signatures for radiosensitivity, hypoxia, proliferation, 'wound,' stem cells, and chromosomal instability were not significantly correlated with outcome. However, a recently published signature for HNSCC defining a 'high-risk' group was shown to be predictive for locoregional control in our dataset. Conclusion: Gene sets can be found with predictive potential for locoregional control after combined radiation and chemotherapy in HNSCC. How treatment-specific these gene sets are needs further study.

  6. "Head up and eyes out" advances in head mounted displays capabilities

    NASA Astrophysics Data System (ADS)

    Cameron, Alex

    2013-06-01

    There are a host of helmet and head mounted displays, flooding the market place with displays which provide what is essentially a mobile computer display. What sets aviators HMDs apart is that they provide the user with accurate conformal information embedded in the pilots real world view (see through display) where the information presented is intuitive and easy to use because it overlays the real world (mix of sensor imagery, symbolic information and synthetic imagery) and enables them to stay head up, eyes out, - improving their effectiveness, reducing workload and improving safety. Such systems are an enabling technology in the provision of enhanced Situation Awareness (SA) and reducing user workload in high intensity situations. Safety Is Key; so the addition of these HMD functions cannot detract from the aircrew protection functions of conventional aircrew helmets which also include life support and audio communications. These capabilities are finding much wider application in new types of compact man mounted audio/visual products enabled by the emergence of new families of micro displays, novel optical concepts and ultra-compact low power processing solutions. This papers attempts to capture the key drivers and needs for future head mounted systems for aviation applications.

  7. Head and Neck Cancer: An Evolving Treatment Paradigm

    PubMed Central

    Cognetti, David M.; Weber, Randal S.; Lai, Stephen Y.

    2009-01-01

    Since the inception of this journal in 1948, the understanding of etiologic factors that contribute to and the treatment of head and neck cancer has evolved dramatically. Advances in surgery, radiation therapy, and chemotherapy have improved locoregional control, survival, and quality of life. The outcomes of these treatment modalities have shifted the focus of curative efforts from radical ablation to preservation and restoration of function. This evolution has been documented in the pages of Cancer for the past 6 decades. This review focuses on the evolution of treatment approaches for head and neck cancer and future directions while recognizing the historic contributions recorded within this journal. PMID:18798532

  8. Prostaglandin inhibitor and radiotherapy in advanced head and neck cancers

    SciTech Connect

    Pillsbury, H.C. III; Webster, W.P.; Rosenman, J.

    1986-05-01

    Radiotherapy is the usual mode of treatment for unresectable head and neck cancer. To improve cure rates, extend survival, and reduce morbidity, we use accelerated hyperfractionation radiotherapy and an adjuvant drug to inhibit prostaglandin synthesis. In this study, 19 patients received 300 rad/day of radiotherapy in two equally divided doses to a total dose averaging 6,200 rad. Either indomethacin, 25 mg, or placebo was given four times a day in a double-blind fashion during therapy. Radiation mucositis was graded as 0 to 4+; pain, nutritional status, and tumor status were monitored daily and recorded biweekly. Evaluation of the data showed delayed mucositis in the experimental group for grades 1 to 3, with a significant difference at grade 3 compared with controls. The significance of a long-term comparison of cure rates would be doubtful considering the heterogeneity of the primary sites and regional disease in this group coupled with the small size of our study.

  9. [SIB-IMRT radiotherapy given concomitantly with cisplatin for locally advanced squamous cell head and neck cancer (SCHNC). Evaluation of the early results and toxicity].

    PubMed

    Kiprian, Dorota; Jarząbski, Andrzej; Pawłowska, Beata; Michalski, Wojciech; Kawecki, Andrzej

    2011-09-01

    Concomitant radiochemotherapy become the treatment of choice for locally advanced SCHNC. This strategy of treatment has a limitation, which is an acute and late toxicity. The IMRT technique provides the possibility of better sparing of healthy tissue. Radiobiological and clinical data also suggest that accelerated fractionation and higher dose per fraction given in GTV may produce better locoregional control. Therefore it might be expected that concomitant chemotherapy and SIB-IMRT radiotherapy could increase locoregional control and reduce acute and late radiation reactions. The evaluation of early results and toxicity of this treatment modality is presented. The evaluation of the early results and toxicity of SIB-IMRT radiotherapy given concomitantly with cisplatin for locally advanced squamous cell head and neck cancer (SCHNC). SIB-IMRT technique was applied. The boost volume was limited to the GTV + 3mm margin (macroscopic tumor extension was defined on the basis of CT and/or MRI examinations). Dose per fraction given to this volume was 2.25 Gy up to 67.5 Gy of total dose. The PTV-CTV + 3mm - was defined as an area of increased risk of microscopic spread. Dose per fraction given to this volume was 2 Gy up to 60 Gy. The PTV1-ETV+ 3mm (electively irradiated volume) received dose per fraction -1.8 Gy up to 54-56 Gy. Overall treatment time was 6 weeks (5 fractions per week, 30 fractions). Concomitant chemotherapy consisted of cisplatin in daily dose100mg/m2 given two times during irradiation (1 and 22 day of treatment). The evaluation of early tolerance was performed once weekly during the treatment than during the follow up every 2 months. The early reactions were scored according to the EORTC/RTOG scale. Between June 2006 and December 2009 99 patients diagnosed with III and IV clinical stage of SCHNC were treated with this method. 65 patients were diagnosed with oropharyngeal cancer, 18 with laryngeal cancer and 16 with hypopharyngeal cancer. PEG was performed at

  10. Head up and head mounted display performance improvements through advanced techniques in the manipulation of light

    NASA Astrophysics Data System (ADS)

    Wisely, Paul L.

    2009-05-01

    Since their introduction a number of years ago, head up and helmet mounted displays have undergone continuous and intensive development in aerospace applications. To date, the designs have been performed using geometric optic design techniques and have progressed to the point where very little further improvement in their characteristics is possible. This paper describes a display realised by the use of new optical design techniques based on wave-guiding principles that have enabled substantial further significant improvements to be made. These improvements are not only in respect of size, weight and volume for a given optical performance, but also in the optical characteristics that currently limit the usability of such displays in many applications. Displays that have been realised and tested through these methods are described and their performance in laboratory and flight trials discussed, together with considerations for further progress in their development.

  11. Roadmap for development of an advanced head-end reactor

    SciTech Connect

    Del Cul, G.D.; Johnson, J.A.; Spencer, B.B.; Collins, E.D.

    2013-07-01

    A novel dry treatment process for used nuclear fuel (UNF) using nitrogen dioxide is being developed to remove volatile and semi-volatile fission products and convert the monolithic fuel material to a fine powder suitable as a feed to many different separations processes. The process may be considered an advanced form of voloxidation, which was envisioned to remove tritium from the fuel prior to introduction of the fuel into the aqueous separations systems, where subsequent separation of tritium from the water would be difficult and expensive. The product from NO{sub 2} reaction can be selectively chosen to be U{sub 3}O{sub 8}, UO{sub 3}, or a nitrate by adjusting the processing conditions; all products are generated at temperatures lower than those used in standard voloxidation. All the fundamental tenants of the process have been successfully demonstrated as a proof of principle, and many aspects have been corroborated multiple times at laboratory scale. The goal of this roadmap is to define the activities required to develop the process to a technology-readiness level sufficient to an engineering-scale implementation. (authors)

  12. Trial of Postoperative Radiation, Cisplatin, and Panitumumab in Locally Advanced Head and Neck Cancer

    ClinicalTrials.gov

    2016-06-28

    Cancer of Head; Cancer of Head and Neck; Cancer of Neck; Cancer of the Head; Cancer of the Head and Neck; Cancer of the Neck; Head and Neck Cancer; Head Cancer; Head Neoplasms; Head, Neck Neoplasms; Neck Cancer; Neck Neoplasms; Neoplasms, Head; Neoplasms, Head and Neck; Neoplasms, Neck; Neoplasms, Upper Aerodigestive Tract; UADT Neoplasms; Upper Aerodigestive Tract Neoplasms

  13. Targeted genetic and viral therapy for advanced head and neck cancers.

    PubMed

    Huang, Pin-I; Chang, Ju-Fang; Kirn, David H; Liu, Ta-Chiang

    2009-06-01

    Head and neck cancers usually present with advanced disease and novel therapies are urgently needed. Genetic therapy aims at restoring malfunctioned tumor suppressor gene(s) or introducing proapoptotic genes. Oncolytic virotherapeutics induce multiple cycles of cancer-specific virus replication, followed by oncolysis, virus spreading and infection of adjacent cancer cells. Oncolytic viruses can also be armed to express therapeutic transgene(s). Recent advances in preclinical and clinical studies are revealing the potential of both therapeutic classes for advanced head and neck cancers, including the approval of two products (Gendicine and H101) by a governmental agency. This review summarizes the available clinical data to date and discusses the challenges and future directions.

  14. Lateral Load Testing of the Advanced Stirling Convertor (ASC-E2) Heater Head

    NASA Technical Reports Server (NTRS)

    Cornell, Peggy A.; Krause, David L.; Davis, Glen; Robbie, Malcolm G.; Gubics, David A.

    2010-01-01

    Free-piston Stirling convertors are fundamental to the development of NASA s next generation of radioisotope power system, the Advanced Stirling Radioisotope Generator (ASRG). The ASRG will use General Purpose Heat Source (GPHS) modules as the energy source and Advanced Stirling Convertors (ASCs) to convert heat into electrical energy, and is being developed by Lockheed Martin under contract to the Department of Energy. Achieving flight status mandates that the ASCs satisfy design as well as flight requirements to ensure reliable operation during launch. To meet these launch requirements, GRC performed a series of quasi-static mechanical tests simulating the pressure, thermal, and external loading conditions that will be experienced by an ASC E2 heater head assembly. These mechanical tests were collectively referred to as lateral load tests since a primary external load lateral to the heater head longitudinal axis was applied in combination with the other loading conditions. The heater head was subjected to the operational pressure, axial mounting force, thermal conditions, and axial and lateral launch vehicle acceleration loadings. To permit reliable prediction of the heater head s structural performance, GRC completed Finite Element Analysis (FEA) computer modeling for the stress, strain, and deformation that will result during launch. The heater head lateral load test directly supported evaluation of the analysis and validation of the design to meet launch requirements. This paper provides an overview of each element within the test and presents assessment of the modeling as well as experimental results of this task.

  15. Lateral Load Testing of the Advanced Stirling Convertor (ASC-E2) Heater Head

    NASA Technical Reports Server (NTRS)

    Cornell, Peggy A.; Krause, David L.; Davis, Glen; Robbie, Malcolm G.; Gubics, David A.

    2011-01-01

    Free-piston Stirling convertors are fundamental to the development of NASA s next generation of radioisotope power system, the Advanced Stirling Radioisotope Generator (ASRG). The ASRG will use General Purpose Heat Source (GPHS) modules as the energy source and Advanced Stirling Convertors (ASCs) to convert heat into electrical energy, and is being developed by Lockheed Martin under contract to the Department of Energy. Achieving flight status mandates that the ASCs satisfy design as well as flight requirements to ensure reliable operation during launch. To meet these launch requirements, GRC performed a series of quasi-static mechanical tests simulating the pressure, thermal, and external loading conditions that will be experienced by an ASC-E2 heater head assembly. These mechanical tests were collectively referred to as "lateral load tests" since a primary external load lateral to the heater head longitudinal axis was applied in combination with the other loading conditions. The heater head was subjected to the operational pressure, axial mounting force, thermal conditions, and axial and lateral launch vehicle acceleration loadings. To permit reliable prediction of the heater head s structural performance, GRC completed Finite Element Analysis (FEA) computer modeling for the stress, strain, and deformation that will result during launch. The heater head lateral load test directly supported evaluation of the analysis and validation of the design to meet launch requirements. This paper provides an overview of each element within the test and presents assessment of the modeling as well as experimental results of this task.

  16. Lateral Load Testing of the Advanced Stirling Convertor (ASC-E2) Heater Head

    NASA Technical Reports Server (NTRS)

    Cornell, Peggy A.; Krause, David L.; Davis, Glen; Robbie, Malcolm G.; Gubics, David A.

    2010-01-01

    Free-piston Stirling convertors are fundamental to the development of NASA s next generation of radioisotope power system, the Advanced Stirling Radioisotope Generator (ASRG). The ASRG will use General Purpose Heat Source (GPHS) modules as the energy source and Advanced Stirling Convertors (ASCs) to convert heat into electrical energy, and is being developed by Lockheed Martin under contract to the Department of Energy. Achieving flight status mandates that the ASCs satisfy design as well as flight requirements to ensure reliable operation during launch. To meet these launch requirements, GRC performed a series of quasi-static mechanical tests simulating the pressure, thermal, and external loading conditions that will be experienced by an ASC-E2 heater head assembly. These mechanical tests were collectively referred to as "lateral load tests" since a primary external load lateral to the heater head longitudinal axis was applied in combination with the other loading conditions. The heater head was subjected to the operational pressure, axial mounting force, thermal conditions, and axial and lateral launch vehicle acceleration loadings. To permit reliable prediction of the heater head s structural performance, GRC completed Finite Element Analysis (FEA) computer modeling for the stress, strain, and deformation that will result during launch. The heater head lateral load test directly supported evaluation of the analysis and validation of the design to meet launch requirements. This paper provides an overview of each element within the test and presents assessment of the modeling as well as experimental results of this task.

  17. Factors predictive of locoregional recurrence following neoadjuvant chemotherapy in patients with large operable or locally advanced breast cancer: An analysis of the EORTC 10994/BIG 1-00 study.

    PubMed

    Gillon, Pauline; Touati, Nathan; Breton-Callu, Christel; Slaets, Leen; Cameron, David; Bonnefoi, Hervé

    2017-07-01

    Identification of clinicopathological factors predicting for a locoregional recurrence (LRR) after neoadjuvant chemotherapy (NAC) could help to decide on the optimal locoregional radiotherapy. The objective of this trial is to identify those factors in the context of a phase III trial (European Organisation for Research and Treatment of Cancer 10994). Patients received NAC followed by surgery with or without radiotherapy. Radiotherapy was administered according to pre-specified guidelines. Patients with hormone receptor positive tumours received adjuvant hormonal therapy. A proportion of patients with human epidermal growth factor receptor 2 (HER2) positive cancer received adjuvant trastuzumab. The predictive factors for LRR were identified by multivariate analysis with time to LRR as first event as the primary end-point. The median follow-up was 4.4 years. In 1553 eligible patients, there were 76 LRRs with a 5-year cumulative incidence of 4.9% (95% confidence interval, CI [3.76-6.04]). In multivariate analysis, breast cancer subtype was a significant predictor of LRR (p < 0.0001): hazard ratio (HR) 6.44 (95% CI [2.83-14.69]) for triple negative, 6.26 (95% CI [2.81-13.93]) for HER2+ without trastuzumab (T) and 3.37 (95% CI [1.10-10.34]) for HER2+ with T cancers, all compared to luminal A patients. Lack of pathological response was also associated with significantly higher LRR risk in case of ≥4 pathologically positive nodes, HR 2.43 (95% CI [1.34-4.40], p < 0.0001). Breast cancer subtype and lack of pathological response are predictive factors for high LRR after NAC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Recent advances in head-mounted light field displays for virtual and augmented reality (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Hua, Hong

    2017-02-01

    Head-mounted light field displays render a true 3D scene by sampling either the projections of the 3D scene at different depths or the directions of the light rays apparently emitted by the 3D scene and viewed from different eye positions. They are capable of rendering correct or nearly correct focus cues and addressing the very well-known vergence-accommodation mismatch problem in conventional virtual and augmented reality displays. In this talk, I will focus on reviewing recent advancements of head-mounted light field displays for VR and AR applications. I will demonstrate examples of HMD systems developed in my group.

  19. A prognostic scoring system for locoregional control in nasopharyngeal carcinoma following conformal radiotherapy

    SciTech Connect

    Cheng, S.H.; Tsai, S.Y.; Horng, C.-F.; Yen, K.L.; Jian, James J.; Chan, Kwan-Yee; Lin, C.-Y.; Terng, S.-D.; Tsou, M.-H.; Chu, N.-M.; Chen, H.-H.; Hsieh, C.-I.; Tan, T.-D.; Chen, P.-L.; Chung, Y.L.; Huang, Andrew T. |

    2006-11-15

    Purpose: This study established a prognostic scoring system for nasopharyngeal carcinoma (NPC), which estimates the probability of locoregional (LR) control following definitive conformal radiotherapy. Methods and Materials: Patients with nondisseminated NPC at initial presentation (n = 630) were enrolled in this study. All patients had magnetic resonance imaging of the head and neck and were treated with conformal radiotherapy. Among them, 93% had concurrent chemotherapy, and 76% had postradiation chemotherapy. The extent of the primary tumor, age at diagnosis, primary tumor size, tumor and nodal classification, histology, and serum lactate dehydrogenase (LDH) level before treatment were included in the analysis for building a prognostic scoring system. The end point for this study was LR control. Results: The prognostic score was defined as the number of adverse prognostic factors present at diagnosis. Four factors had similarly independent prognostic effects (hazard ratio, 2.0-2.6): age >40 years, histologic WHO type I-II, serum LDH level {>=}410 U/L, and involvement of two or more sites of the following anatomic structures, i.e., sphenoid floor, clivus marrow, clivus cortex, prevertebral muscles, and petrous bone. The score predicted the 5-year probability of LR control as follows: 0 (15% of the patients), 100%; 1 (42% of the patients), 93%; 2 (29% of the patients), 83%; 3 or higher (13% of the patients), 71%. Conclusion: This scoring system is useful in the decision-making for individual patients and the design of clinical trials to improve LR control for advanced-stage NPC.

  20. Long-Term Results of Concomitant Boost Radiation Plus Concurrent Cisplatin for Advanced Head and Neck Carcinomas: A Phase II Trial of the Radiation Therapy Oncology Group (RTOG 99-14)

    SciTech Connect

    Garden, Adam S.; Harris, Jonathan M.S.; Trotti, Andy; Jones, Christopher U.; Carrascosa, Luis; Cheng, Jonathan D.; Spencer, Sharon S.; Forastiere, Arlene; Weber, Randal S.; Ang, K. Kian

    2008-08-01

    Purpose: The feasibility of combining concomitant boost-accelerated radiation regimen (AFX-C) with cisplatin was previously demonstrated in this Phase II trial. This article reports the long-term toxicity, relapse patterns, and survival in patients with advanced head and neck carcinoma. Methods and Materials: Between April and November 2000, 84 patients with Stage III-IV HNC were enrolled, and 76 patients were analyzable. Radiation consisted of 72 Gy over 6 weeks. Cisplatin dose was 100 mg/m{sup 2} on Days 1 and 22. Tumor and clinical status were assessed, and acute-late toxicities were graded. Results: The median follow-up for surviving patients is 4.3 years. The 2- and 4-year locoregional failure rates were 33% and 36%, respectively, and the 2- and 4-year survival rates were 70% and 54%, respectively. The worst overall late Grade 3 or 4 toxicity rate was 42%. The prevalence rates of a gastrostomy at any time during follow-up, at 12 months, and at 48 months were 83%, 41%, and 17%, respectively. Five of 36 patients (14%) alive and without disease at last follow-up were gastrostomy-tube dependent. Conclusion: These data of long-term follow-up of patients treated with AFX-C with cisplatin show encouraging results with regard to locoregional disease control and survival, with few recurrences after 2 years. The late toxicity rates are relatively high. However, although prolonged dysphagia was noted in our preliminary report, its prevalence does decreased over time. A Phase III trial comparing AFX-C plus cisplatin against standard radiation plus cisplatin has completed accrual.

  1. Gemcitabine-Based Chemoradiation in the Treatment of Locally Advanced Head and Neck Cancer: Systematic Review of Literature and Meta-Analysis

    PubMed Central

    Szturz, Petr; Specenier, Pol; Merlano, Marco C.; Benasso, Marco; Van Gestel, Dirk; Wouters, Kristien; Van Laer, Carl; Van den Weyngaert, Danielle; Peeters, Marc; Vermorken, Jan

    2016-01-01

    Background. Platinum-based concurrent chemoradiation (CCRT) improves locoregional control and overall survival of locoregionally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN) when compared to radiotherapy alone, but this approach is hampered by significant toxicity. Therefore, alternative ways to enhance the radiation effects are worth investigating. Gemcitabine (2′,2′-difluorodeoxycytidine), in addition to its activity against a variety of solid tumors, including SCCHN, is one of the most potent radiosensitizers, and it has an overall favorable safety profile. In this paper, the clinical experience with gemcitabine-based chemoradiation in the treatment of patients with LA-SCCHN is reviewed. Methods. We conducted a review of the literature on the clinical experience with radiotherapy combined with either single-agent gemcitabine or gemcitabine/cisplatin-based polychemotherapy for the treatment of patients with LA-SCCHN. We also searched abstracts in databases of major international oncology meetings from the last 20 years. A meta-analysis was performed to calculate pooled proportions with 95% confidence intervals (CIs) for complete response rate and grade 3–4 acute mucositis rate. Results. A total of 13 papers were eligible for the literature review. For schedules using a gemcitabine dose intensity (DI) below 50 mg/m2 per week, the complete response rate was 86% (95% CI, 74%–93%) with grade 3–4 acute mucositis rate of 38% (95% CI, 27%–50%) and acceptable late toxicity. In one of the studies employing such low DIs, survival data were provided showing a 3-year overall survival of 50%. Compared with DI ≥50 mg/m2 per week, there was no difference in the complete response rate (71%; 95% CI, 55%–83%; p = .087) but a significantly higher (p < .001) grade 3–4 acute mucositis rate of 74% (95% CI, 62%–83%), often leading to treatment interruptions (survival data provided in 8 studies; 3-year overall survival, 27%–63%). Late toxicity

  2. Preliminary oncological results of endosopic laser surgery in advanced head and neck tumors

    NASA Astrophysics Data System (ADS)

    Baker-Schreyer, Antonio; Sadick, Haneen; Juncker, Cathrine; Bergler, Wolfgang; Hoermann, Karl

    1998-01-01

    Lasersurgery has established itself in the treatment of minor tumors (T1 - T2) of the upper aerodigestive tract. However, advanced carcinomas of the head and neck (T3 - T4) are generally treated with conventional surgical procedures which include pharyngolaryngectomy. The purpose of this study was to evaluate the oncological outcome of endoscopic lasersurgery in advanced head and neck tumors and to compare the results with conventional surgical procedures. Between January 1994 to December 1996, 86 patients with advanced squamous cell carcinomas of the larynx and hypopharynx underwent endoscopic lasersurgery instead of pharyngolaryngectomy as a curative measure. Besides the recurrence and survival rate, the necessity of tracheostomy, postoperative complications and the mean duration of hospitalization were documented. The results showed that the recurrence and survival rate were similar or even better after conventional pharyngolaryngectomy, whereas the patients' postoperative rehabilitation was better after lasersurgery. In this contribution the indication for lasersurgical intervention or pharyngolaryngectomy in advanced carcinomas of the head and neck is discussed.

  3. Relationship Between Radiation Treatment Time and Overall Survival After Induction Chemotherapy for Locally Advanced Head-and-Neck Carcinoma: A Subset Analysis of TAX 324

    SciTech Connect

    Sher, David J.; Posner, Marshall R.; Sarlis, Nicholas J.; Haddad, Robert I.; Holupka, Edward J.; Devlin, Phillip M.

    2011-12-01

    Purpose: To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). Methods and Materials: TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of {>=} 70 Gy. Radiotherapy treatment time was analyzed as binary ({<=} 8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). Results: A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p = 0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p = 0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. Conclusions: In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential

  4. Concomitant Chemoradiotherapy With Mitomycin C and Cisplatin in Advanced Unresectable Carcinoma of the Head and Neck: Phase I-II Clinical Study

    SciTech Connect

    Strojan, Primoz Karner, Katarina; Smid, Lojze; Soba, Erika; Fajdiga, Igor; Jancar, Boris; Anicin, Aleksandar; Budihna, Marjan; Zakotnik, Branko

    2008-10-01

    Purpose: To evaluate the toxicity and efficacy of concomitant chemoradiotherapy with mitomycin C and cisplatin in the treatment of advanced unresectable squamous cell carcinoma of the head and neck. Patients and Methods: Treatment consisted of conventional radiotherapy (70 Gy in 35 fractions), mitomycin C 15 mg/m{sup 2} IV, applied after the delivery of 10 Gy, and cisplatin at an initial dose of 10 mg/m{sup 2}/d IV, applied during the last 10 fractions of irradiation ('chemoboost'). The cisplatin dose was escalated with respect to the toxic side effects by 2 mg/m{sup 2}/d up to the maximum tolerated dose (MTD) or at the most 14 mg/m{sup 2}/d (Phase I study), which was tested in the subsequent Phase II study. Results: All 36 patients had Stage T4 and/or N3 disease, and the majority had oropharyngeal (50%) or hypopharyngeal (39%) primary tumors. Six patients were treated at each of the three cisplatin dose levels tested (Phase I study). Dose-limiting toxicity was not reached even at 14 mg/m{sup 2}/d of cisplatin, which was determined as the MTD and tested in an additional 18 patients (Phase II study). After a median follow-up time of 48 months, 4-year locoregional control, failure-free, and overall survival rates were 30%, 14%, and 20%, respectively. In 24 patients treated at the cisplatin dose level of 14 mg/m{sup 2}/d, the corresponding rates were 40%, 20%, and 22%, respectively. Conclusion: Concomitant chemoradiotherapy with mitomycin C and cisplatin 'chemoboost' at 14 mg/m{sup 2}/d is feasible, with encouraging survival results if the extremely poor disease profile of the treated patients is considered.

  5. Comprehensive Locoregional Treatment and Systemic Therapy for Postmastectomy Isolated Locoregional Recurrence

    SciTech Connect

    Kuo, S.-H.; Huang, C.-S.; Kuo, W.-H.; Cheng, A.-L.; Chang, K.-J.; Chia-Hsien Cheng, Jason

    2008-12-01

    Purpose: To assess the impact of comprehensive locoregional therapy and systemic therapy on disease control and survival for postmastectomy patients with isolated locoregional recurrence (ILRR). Methods and Materials: A total of 115 postmastectomy breast cancer patients treated for ILRR were included. Of the patients, 98 underwent comprehensive locoregional treatment (local tumor excision plus postoperative radiotherapy), and 17 received definitive radiotherapy alone. Involved-field radiotherapy was given to 69 patients, whereas entire-field radiotherapy (both involved-field and elective-field, involving the chest wall and regional lymphatics) was given to 46 patients. Systemic therapy consisting of hormone therapy, chemotherapy, or both was given to 69% of patients. Results: Patients treated with comprehensive locoregional treatment had a significantly better 5-year invasive disease-free survival (IDFS) and overall survival (OS) after ILRR than patients treated with definitive radiotherapy alone (IDFS rate, 51% vs. 16%, p = 0.006; OS rate, 62% vs. 37%, p = 0.017). Patients with the most comprehensive locoregional treatment (recurrent tumor excision and entire-field radiotherapy) and systemic therapy had a significantly better 5-year IDFS and OS than patients given either treatment or neither treatment (IDFS rate, 52% vs. 39%, p = 0.011; OS rate, 63% vs. 50%, p = 0.026). Multivariate analysis revealed that positive axillary lymph nodes, Grade III tumor, negative estrogen and progesterone receptor status at primary diagnosis, disease-free interval of less than 2 years, and less comprehensive locoregional treatment were significantly associated with worse IDFS and OS. Conclusions: Use of comprehensive locoregional therapy and systemic therapy can achieve good survival outcome in a substantial proportion of postmastectomy patients with ILRR.

  6. Superselective embolization as palliative treatment of recurrent hemorrhage in advanced carcinoma of the head and neck.

    PubMed

    Sittel, C; Gossmann, A; Jungehülsing, M; Zähringer, M

    2001-12-01

    We report a case of recurrent major hemorrhage in a patient with advanced head and neck squamous cell carcinoma. Before and between the bleeding episodes, the functional level of the patient was remarkably high. Therefore, an attempt at bleeding control with superselective embolization with Ethibloc was made. Because of its specific characteristics, this substance is almost ideal for the purpose of palliative embolization. The material used and the technique of application are described in detail. After the procedure, no hemorrhage occurred for more than 4 months. We recommend superselective embolization, preferably with Ethibloc, for minimally invasive control of recurrent bleeding as palliative treatment in selected patients with advanced head and neck carcinoma, since significant benefit in terms of the quality of life may result.

  7. Concomitant boost chemoradiotherapy in locally advanced head and neck cancer: treatment tolerance and acute side effects.

    PubMed

    Majdaeen, Mehrsa; Kazemian, Ali; Babaei, Mohammad; Haddad, Peiman; Hashemi, Farnaz Amouzegar

    2015-01-01

    In the present study, we evaluated treatment tolerance and side effects of 6 days a week accelerated radiation therapy using concomitant boost methods with chemotherapy in locally advanced head and neck cancer. Thirty patients suffered locally advanced head and neck malignancies were included into this clinical trial. The patients were scheduled for accelerated radiotherapy with total dose of 70 Gy 6 days a week (5 days radiotherapy and 1-day concomitant boost radiotherapy) for 5 weeks and also concurrently for chemotherapy with cisplatin and also celecoxib. The average age of the patients was 51.47 ± 11.49 years. The incidence of acute mucositis at the end of the 1st week was 33.3% that was gradually increased until the end of the 5th week (93.3%) and then had a decreasing trend within the 6th week (70.0%). The incidence of acute dysphagia was estimated 23.3% at the end of the 1st week and reached 60% at completion of treatment. Scheduling a treatment approach with 6 days a week, accelerated radiation therapy using concomitant boost methods with chemotherapy, and celecoxib leads to significant reducing the incidence of complications in the final weeks of therapy in patients with locally advanced head and neck cancer.

  8. Experimental Creep Life Assessment for the Advanced Stirling Convertor Heater Head

    NASA Technical Reports Server (NTRS)

    Krause, David L.; Kalluri, Sreeramesh; Shah, Ashwin R.; Korovaichuk, Igor

    2010-01-01

    The United States Department of Energy is planning to develop the Advanced Stirling Radioisotope Generator (ASRG) for the National Aeronautics and Space Administration (NASA) for potential use on future space missions. The ASRG provides substantial efficiency and specific power improvements over radioisotope power systems of heritage designs. The ASRG would use General Purpose Heat Source modules as energy sources and the free-piston Advanced Stirling Convertor (ASC) to convert heat into electrical energy. Lockheed Martin Corporation of Valley Forge, Pennsylvania, is integrating the ASRG systems, and Sunpower, Inc., of Athens, Ohio, is designing and building the ASC. NASA Glenn Research Center of Cleveland, Ohio, manages the Sunpower contract and provides technology development in several areas for the ASC. One area is reliability assessment for the ASC heater head, a critical pressure vessel within which heat is converted into mechanical oscillation of a displacer piston. For high system efficiency, the ASC heater head operates at very high temperature (850 C) and therefore is fabricated from an advanced heat-resistant nickel-based superalloy Microcast MarM-247. Since use of MarM-247 in a thin-walled pressure vessel is atypical, much effort is required to assure that the system will operate reliably for its design life of 17 years. One life-limiting structural response for this application is creep; creep deformation is the accumulation of time-dependent inelastic strain under sustained loading over time. If allowed to progress, the deformation eventually results in creep rupture. Since creep material properties are not available in the open literature, a detailed creep life assessment of the ASC heater head effort is underway. This paper presents an overview of that creep life assessment approach, including the reliability-based creep criteria developed from coupon testing, and the associated heater head deterministic and probabilistic analyses. The approach also

  9. The association between malnutrition and psychological distress in patients with advanced head-and-neck cancer

    PubMed Central

    Ma, L.; Poulin, P.; Feldstain, A.; Chasen, M.R.

    2013-01-01

    Objective Malnutrition and psychological distress are often seen in patients with head-and-neck cancer, but little is known about the interrelationships between those two symptoms. The present study examined the relationship between malnutrition and psychological distress in patients with advanced head-and-neck cancer. Methods Using the Patient-Generated Subjective Global Assessment, 99 patients with advanced-stage head-and-neck cancer were screened for nutrition status. The patients were also screened for psychosocial distress (using the Distress Thermometer) and for psychosocial issues (using the Problem Checklist). Any relationship between malnutrition and psychosocial distress was determined by regression and correlation analysis. We also used t-tests to compare distress levels for patients with and without specific nutrition-related symptoms. Results The study group included 80 men and 19 women [mean age: 58.4 ± 10.9 years (range: 23–85 years)]. The correlation between poorer nutrition status and level of psychological distress was significant r = 0.37 (p < 0.001). Specifically, reduced food intake and symptoms were both positively associated with distress: r = 0.27 and r = 0.29 respectively, both significant at p < 0.01. After controlling for the effects of psychosocial problems and pain, nutrition status remained a significant predictor of distress, explaining 3.8% of the variance in the distress scores of the patients (p < 0.05). Conclusions Malnutrition and symptoms were strongly related to distress in patients with advanced head-and-neck cancer. Our results suggest the need for further research into the complex relationship between nutrition status and distress and into the management of both nutrition and distress in cancer care. PMID:24311956

  10. The association between malnutrition and psychological distress in patients with advanced head-and-neck cancer.

    PubMed

    Ma, L; Poulin, P; Feldstain, A; Chasen, M R

    2013-12-01

    Malnutrition and psychological distress are often seen in patients with head-and-neck cancer, but little is known about the interrelationships between those two symptoms. The present study examined the relationship between malnutrition and psychological distress in patients with advanced head-and-neck cancer. Using the Patient-Generated Subjective Global Assessment, 99 patients with advanced-stage head-and-neck cancer were screened for nutrition status. The patients were also screened for psychosocial distress (using the Distress Thermometer) and for psychosocial issues (using the Problem Checklist). Any relationship between malnutrition and psychosocial distress was determined by regression and correlation analysis. We also used t-tests to compare distress levels for patients with and without specific nutrition-related symptoms. The study group included 80 men and 19 women [mean age: 58.4 ± 10.9 years (range: 23-85 years)]. The correlation between poorer nutrition status and level of psychological distress was significant r = 0.37 (p < 0.001). Specifically, reduced food intake and symptoms were both positively associated with distress: r = 0.27 and r = 0.29 respectively, both significant at p < 0.01. After controlling for the effects of psychosocial problems and pain, nutrition status remained a significant predictor of distress, explaining 3.8% of the variance in the distress scores of the patients (p < 0.05). Malnutrition and symptoms were strongly related to distress in patients with advanced head-and-neck cancer. Our results suggest the need for further research into the complex relationship between nutrition status and distress and into the management of both nutrition and distress in cancer care.

  11. Comparison of two different radiation fractionation schedules with concurrent chemotherapy in head and neck malignancy.

    PubMed

    Alam, M S; Perween, R; Siddiqui, S A

    2016-01-01

    The worldwide incidence of head and neck malignancy exceeds half a million cases annually. In radiotherapy (RT), conventional fractionation comprises giving five fractions per week from Monday to Friday. Accelerated RT includes administration of six fractions per week is being advocated. It gives better locoregional control and the median overall treatment time is 39 days as compared to 46 days in conventional group. Our study involved comparison of conventional versus accelerated RT with concurrent chemotherapy, in evaluation of local control and toxicity in the two arms. Sixty patients of locally advanced squamous cell carcinoma head and neck region were studied. All the patients received cisplatin (30 mg/m2) weekly during the therapy. The patients received RT dose of 70 Gray (Gy) in 35 fractions (#). The patients were randomly assorted into two groups: Group 1 - Study group (n = 30) - Six fractions RT per week (Monday-Saturday). Group 2 - Control group (n = 30) - Five fractions RT per week (Monday-Friday). During and after the treatment, locoregional control, acute and late radiation toxicity were assessed. Results and Observation: There was no significant difference between the two schedules regarding locoregional control rate. The Grade 3 or higher acute toxicities were significantly higher in the accelerated arm although there was no significant difference in late toxicities between the two arms. Accelerated fractionation regimen was not more efficacious than conventional fractionation in the treatment of previously untreated head and neck carcinoma.

  12. Structural Benchmark Creep Testing for the Advanced Stirling Convertor Heater Head

    NASA Technical Reports Server (NTRS)

    Krause, David L.; Kalluri, Sreeramesh; Bowman, Randy R.; Shah, Ashwin R.

    2008-01-01

    The National Aeronautics and Space Administration (NASA) has identified the high efficiency Advanced Stirling Radioisotope Generator (ASRG) as a candidate power source for use on long duration Science missions such as lunar applications, Mars rovers, and deep space missions. For the inherent long life times required, a structurally significant design limit for the heater head component of the ASRG Advanced Stirling Convertor (ASC) is creep deformation induced at low stress levels and high temperatures. Demonstrating proof of adequate margins on creep deformation and rupture for the operating conditions and the MarM-247 material of construction is a challenge that the NASA Glenn Research Center is addressing. The combined analytical and experimental program ensures integrity and high reliability of the heater head for its 17-year design life. The life assessment approach starts with an extensive series of uniaxial creep tests on thin MarM-247 specimens that comprise the same chemistry, microstructure, and heat treatment processing as the heater head itself. This effort addresses a scarcity of openly available creep properties for the material as well as for the virtual absence of understanding of the effect on creep properties due to very thin walls, fine grains, low stress levels, and high-temperature fabrication steps. The approach continues with a considerable analytical effort, both deterministically to evaluate the median creep life using nonlinear finite element analysis, and probabilistically to calculate the heater head s reliability to a higher degree. Finally, the approach includes a substantial structural benchmark creep testing activity to calibrate and validate the analytical work. This last element provides high fidelity testing of prototypical heater head test articles; the testing includes the relevant material issues and the essential multiaxial stress state, and applies prototypical and accelerated temperature profiles for timely results in a

  13. Palliative Hypo-fractionated Radiotherapy in Locally Advanced Head and Neck Cancer with Fixed Neck Nodes.

    PubMed

    Paliwal, Rajan; Kumar-Patidar, Arvind; Walke, Rahul; Hirapara, Pushpendra; Jain, Sandeep; Raj-Bardia, Megh

    2012-01-01

    The locally advanced head and neck cancer with fixed nodes are incurable and has a short survival. This study aims to evaluate the symptom relief, disease response and acute toxicity after palliative hypo-fractionated radiotherapy. Between December 2010 to June 2011, previously untreated 50 patients who had histopathologically proved of head and neck squamous cell carcinoma with fixed node of stage IV, Eastern Cooperative Oncology Group (ECOG) performance status 2-3 were offered palliative radiotherapy (20 Gy/5Fr/5 Days). Patients were evaluated at 15th and 30th day after completion of treatment for disease response (WHO), palliation of symptoms using symptomatic response grading and acute toxicities (Radiation Therapy Oncology Group, RTOG). The most common presenting complaint was pain followed by dysphagia. Majority of patients (60-70%) had appreciable relief in their presenting symptom. In our study, we observed Partial Response (PR) in majority of patients (92 %); no patient had progressive or stable disease. None of the patients experienced radiation toxicities that required hospital admission. Almost all patients showed grade one and two acute skin and mucosal toxicities one month after completion of treatment. Advanced head and neck cancer with fixed neck node should be identified for suitable palliative hypo-fractionated radiotherapy to achieve acceptable symptom relief in great proportion of patients.

  14. Radiotherapy for the management of locally advanced squamous cell carcinoma of the head and neck

    PubMed Central

    Ko, Christine; Citrin, Deborah

    2008-01-01

    Background Squamous cell carcinomas of the head and neck (SCCHN) affect approximately 35,000 people in the United States yearly. Although survival has improved with advances in therapy, patients with advanced stages of SCCHN continue to have a poor prognosis. An understanding of rationale for treatment selection, newer developments in therapy, and treatment toxicity is critical. Methods Standard methods of treating locally advanced SCCHN are reviewed. Advances in medical and radiotherapeutic management are discussed and the toxicities of therapy are described. Results Post-operative chemoradiation is used in patients with high risk characteristics. Induction chemotherapy and altered fractionation radiation treatment have been evaluated as alternatives to definitive chemo-radiotherapy. Targeted agents such as cetuximab may prove to increase survival with minimal increase in toxicity profile. Technological improvements such as the use of intensity modulated radiation treatment (IMRT) have proven to decrease some debilitating side effects from radiation treatment. Conclusions Locally advanced SCCHN continues to present a therapeutic challenge. Survival, local control, and quality of life are all goals of treatment. The optimal method of treating locally advanced SCCHN is the subject of ongoing research. Long term side effects can be minimized with the use of newer technologies and with careful treatment planning. PMID:19036056

  15. Effectiveness of prophylactic retropharyngeal lymph node irradiation in patients with locally advanced head and neck cancer

    PubMed Central

    2012-01-01

    Background The aim of the study is to assess the effectiveness of intensity-modulated radiotherapy (IMRT) or image-guided radiotherapy (IGRT) for the prevention of retropharyngeal nodal recurrences in locally advanced head and neck cancer. Methods A retrospective review of 76 patients with head and neck cancer undergoing concurrent chemoradiation or postoperative radiotherapy with IMRT or IGRT who were at risk for retropharyngeal nodal recurrences because of anatomic site (hypopharynx, nasopharynx, oropharynx) and/or the presence of nodal metastases was undertaken. The prevalence of retropharyngeal nodal recurrences was assessed on follow-up positron emission tomography (PET)-CT scans. Results At a median follow-up of 22 months (4–53 months), no patient developed retropharyngeal nodal recurrences. Conclusion Prophylactic irradiation of retropharyngeal lymph nodes with IMRT or IGRT provides effective regional control for individuals at risk for recurrence in these nodes. PMID:22708791

  16. Combination chemotherapy for advanced squamous cell carcinoma of the head and neck.

    PubMed

    Coker, D D; Elias, E G; Chretien, P B; Gray, W C; Coleman, J J; Zentai, T A; Didolkar, M S; Morris, D M; Viravathana, T; Hebel, J R

    1981-01-01

    Fifty-one patients (32 previously untreated, 19 previously treated) with advanced squamous cell carcinoma of the head and neck received a single course of combination chemotherapy consisting of high dose cis-platinum (DDP), bleomycin (Bleo), +/- high dose methotrexate (MTX). Thirty-three (65%) patients responded to therapy; 5 (10%) of these patients had a complete response. Previously untreated patients and those who received the three drugs (DDP, Bleo and MTX) had the highest response rates. The duration of response was 8 to 12 weeks. Seven (15%) patients showed a two-year survival rate. All nonresponders were dead of disease within two years. Three (56%) of the five complete-response patients and 4 (21%) of the partial-response patients survived for two years. The role of preoperative chemotherapy in head and neck cancer is yet to be conclusively defined.

  17. Arthroscopic knee surgery using the advanced flat panel high-resolution color head-mounted display

    NASA Astrophysics Data System (ADS)

    Nelson, Scott A.; Jones, D. E. Casey; St. Pierre, Patrick; Sampson, James B.

    1997-06-01

    The first ever deployed arthroscopic knee surgeries have been performed using a high resolution color head-mounted display (HMD) developed under the DARPA Advanced Flat Panel HMD program. THese procedures and several fixed hospital procedures have allowed both the system designers and surgeons to gain new insight into the use of a HMD for medical procedures in both community and combat support hospitals scenarios. The surgeons demonstrated and reported improved head-body orientation and awareness while using the HMD and reported several advantages and disadvantages of the HMD as compared to traditional CRT monitor viewing of the arthroscopic video images. The surgeries, the surgeon's comments, and a human factors overview of HMDs for Army surgical applications are discussed here.

  18. Advances and Perspectives in the Molecular Diagnosis of Head and Neck Cancer

    PubMed Central

    Mydlarz, Wojciech K.; Hennessey, Patrick T.; Califano, Joseph A.

    2009-01-01

    Background Head and neck squamous cell carcinoma (HNSCC) is a debilitating and lethal disease. Despite significant advances in radiotherapy and surgical management, the 5-year survival rate for head and neck cancer has remained a dismal 50%. Advances in early detection have been made, but to improve patient outcomes better biomarkers and targeted therapeutic agents are needed. Novel biomarkers can improve early detection and provide data to optimize therapeutic strategy and patient survival, and could lead to potentially effective targeted therapies. Objective Report the advances in the discovery of novel biomarkers for HNSCC, and review the potential utility of biomarkers in the molecular diagnosis of HNSCC. Methods A review of the English literature (PubMed) from 1980 to 2009. Results/conclusion Currently the most widely accepted biomarker for HNSCC is high risk HPV status. EGFR is another promising biomarker, however, further research is necessary to determine its prognostic benefit. A large number of promising biomarker candidates are currently being evaluated including epigenetic, expression, and genomic based markers. Studies to validate the sensitivity and specificity of these biomarkers in clinical samples from adequately powered prospective cohorts are needed for successful translation of these findings into potential molecular diagnostic, prognostic, and therapeutic biomarkers for HNSCC. PMID:20161611

  19. Chemoradiation for Advanced Head and Neck Cancer: Potential for Improving Results to Match Those of Current Treatment Modalities for Early-Stage Tumors-Long-Term Results of Hyperfractionated Chemoradiation With Carbogen Breathing and Anemia Correction With Erythropoietin

    SciTech Connect

    Villar, Alfonso Martinez, Jose Carlos; Serdio, Jose Luis de

    2008-04-01

    Purpose: To attempt to improve results of chemoradiation for head and neck cancer. Methods and Materials: From March 1996 to April 2007, 98 patients with head and neck cancer (15 Stage III and 83 Stage IV) were treated with a twice-daily hyperfractionated schedule. Eleven patients presented with N0, 11 with N1, 13 with N2A, 17 with N2B, 24 with N2C, and 22 with N3. Each fraction of treatment consisted of 5 mg/m{sup 2} of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m{sup 2} of carboplatin plus 8050 cGy in 7 weeks. Anemia was corrected with erythropoietin. Results: Ninety-six patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Local toxicity remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Ninety-seven complete responses were achieved. After 11 years of follow-up (median, 81 months), actuarial locoregional control, cause-specific survival, overall survival, and nodal control rates at 5 and 10 years were, respectively, 83% and 83%, 68% and 68%, 57% and 55%, and 100% and 100%. Median follow-up of disease-free survivors was 80 months. No significant differences in survival were observed between the different subsites or between the pretreatment node status groups (N0 vs. N+, N0 vs. N1, N0 vs. N2A, N0 vs. N2B, N0 vs. N2C, and N0 vs. N3). Conclusions: Improving results of chemoradiation for advanced head and neck cancer up to the level obtained with current treatments for early-stage tumors is a potentially reachable goal.

  20. c-Met Expression Is a Marker of Poor Prognosis in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Treated With Chemoradiation

    SciTech Connect

    Baschnagel, Andrew M.; Williams, Lindsay; Hanna, Alaa; Chen, Peter Y.; Krauss, Daniel J.; Pruetz, Barbara L.; Akervall, Jan; Wilson, George D.

    2014-03-01

    Purpose: To examine the prognostic significance of c-Met expression in relation to p16 and epidermal growth factor receptor (EGFR) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with definitive concurrent chemoradiation. Methods and Materials: Archival tissue from 107 HNSCC patients treated with chemoradiation was retrieved, and a tissue microarray was assembled. Immunohistochemical staining of c-Met, p16, and EGFR was performed. c-Met expression was correlated with p16, EGFR, clinical characteristics, and clinical endpoints including locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS). Results: Fifty-one percent of patients were positive for p16, and 53% were positive for EGFR. Both p16-negative (P≤.001) and EGFR-positive (P=.019) status predicted for worse DFS. Ninety-three percent of patients stained positive for c-Met. Patients were divided into low (0, 1, or 2+ intensity) or high (3+ intensity) c-Met expression. On univariate analysis, high c-Met expression predicted for worse LRC (hazard ratio [HR] 2.27; 95% CI, 1.08-4.77; P=.031), DM (HR 4.41; 95% CI, 1.56-12.45; P=.005), DFS (HR 3.00; 95% CI, 1.68-5.38; P<.001), and OS (HR 4.35; 95% CI, 2.13-8.88; P<.001). On multivariate analysis, after adjustment for site, T stage, smoking history, and EGFR status, only high c-Met expression (P=.011) and negative p16 status (P=.003) predicted for worse DFS. High c-Met expression was predictive of worse DFS in both EGFR-positive (P=.032) and -negative (P=.008) patients. In the p16-negative patients, those with high c-Met expression had worse DFS (P=.036) than did those with low c-Met expression. c-Met expression was not associated with any outcome in the p16-positive patients. Conclusions: c-Met is expressed in the majority of locally advanced HNSCC cases, and high c-Met expression predicts for worse clinical outcomes. High c-Met expression predicted for worse DFS in p16

  1. Lhermitte's Sign Developing after IMRT for Head and Neck Cancer

    PubMed Central

    Lim, Dong C.; Gagnon, Patrick J.; Meranvil, Sophia; Kaurin, Darryl; Lipp, Linda; Holland, John M.

    2010-01-01

    Background. Lhermitte's sign (LS) is a benign form of myelopathy with neck flexion producing an unpleasant electric-shock sensation radiating down the extremities. Although rare, it can occur after head and neck radiotherapy. Results. We report a case of Lhermitte's developing after curative intensity-modulated radiotherapy (IMRT) for a patient with locoregionally advanced oropharyngeal cancer. IMRT delivers a conformal dose of radiation in head and neck cancer resulting in a gradient of radiation dose throughout the spinal cord. Using IMRT, more dose is delivered to the anterior spinal cord than the posterior cord. Conclusions. Lhermitte's sign can develop after IMRT for head and neck cancer. We propose an anterior spinal cord structure, the spinothalamic tract to be the target of IMRT-caused LS. PMID:20628529

  2. [Current advances in diagnosis and surgical treatment of lymph node metastasis in head and neck cancer].

    PubMed

    Teymoortash, A; Werner, J A

    2012-03-01

    Still today, the status of the cervical lymph nodes is the most important prognostic factor for head and neck cancer. So the individual treatment concept of the lymphatic drainage depends on the treatment of the primary tumor as well as on the presence or absence of suspect lymph nodes in the imaging diagnosis. Neck dissection may have either a therapeutic objective or a diagnostic one. The selective neck dissection is currently the method of choice for the treatment of patients with advanced head and neck cancers and clinical N0 neck. For oncologic reasons, this procedure is generally recommended with acceptable functional and aesthetic results, especially under the aspect of the mentioned staging procedure. In this review article, current aspects on pre- and posttherapeutic staging of the cervical lymph nodes are described and the indication and the necessary extent of neck dissection for head and neck cancer is discussed. Additionally the critical question is discussed if the lymph node metastasis bears an intrinsic risk of metastatic development and thus its removal in a most possible early stage plays an important role. © Georg Thieme Verlag KG Stuttgart · New York.

  3. Current advances in diagnosis and surgical treatment of lymph node metastasis in head and neck cancer

    PubMed Central

    Teymoortash, A.; Werner, J. A.

    2012-01-01

    Still today, the status of the cervical lymph nodes is the most important prognostic factor for head and neck cancer. So the individual treatment concept of the lymphatic drainage depends on the treatment of the primary tumor as well as on the presence or absence of suspect lymph nodes in the imaging diagnosis. Neck dissection may have either a therapeutic objective or a diagnostic one. The selective neck dissection is currently the method of choice for the treatment of patients with advanced head and neck cancers and clinical N0 neck. For oncologic reasons, this procedure is generally recommended with acceptable functional and aesthetic results, especially under the aspect of the mentioned staging procedure. In this review article, current aspects on pre- and posttherapeutic staging of the cervical lymph nodes are described and the indication and the necessary extent of neck dissection for head and neck cancer is discussed. Additionally the critical question is discussed if the lymph node metastasis bears an intrinsic risk of metastatic development and thus its removal in a most possible early stage plays an important role. PMID:23320056

  4. Advancements in the Management of HPV-Associated Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Zeitlin, Ross; Nguyen, Harrison P.; Rafferty, David; Tyring, Stephen

    2015-01-01

    Head and neck carcinomas have long been linked to alcohol and tobacco abuse; however, within the last two decades, the human papillomavirus (HPV) has emerged as a third etiology and is specifically associated with head and neck squamous cell carcinomas (HNSCC). In this anatomical region, the oncogenic HPV-16 mediates transformation and immortalization of epithelium, most commonly in the oropharynx. Nevertheless, the recent identification of novel HPV mechanisms thought to be specific to oropharyngeal carcinogenesis has coincided with observations that HPV-associated HNSCC has differing clinical behavior—in terms of natural history, therapeutic response, and prognosis—than HPV-negative head and neck tumors. Taken together with the growing incidence of HPV transmission in younger populations, these discoveries have sparked a rapid expansion in both laboratory and clinical studies on the infection and disease. Herein, we review the clinical characteristics of HPV-associated HNSCC, with particular emphasis on recent advancements in our understanding of the management of this infectious malignancy. PMID:26239449

  5. Early transient radiation-induced brachial plexopathy in locally advanced head and neck cancer

    PubMed Central

    Etiz, Durmus

    2016-01-01

    Aim of the study Early transient brachial plexopathy following radiotherapy (RT) in patients with head and neck cancer may be underreported and associated with a dose-response. Our purpose was to determine the incidence of early transient radiation-ınduced brachial plexopathy (RIBP) in patients receiving primary RT (± chemotherapy) for locally advanced head and neck cancer (HNC). Material and methods Twenty-seven locally advanced HNC patients who have no finding of brachial plexopathy at the diagnosis were evaluated 3 times by a specifically developed 13-item questionnaire for determining early transient RIBP. The 54 brachial plexus in 27 patients were delineated and dose volume histograms were calculated. Results Median follow-up period was 28 (range: 15–40) months. The mean BP volume was 7.9 ±3.6 cm3, and the mean and maximum doses to the BP were 45.3 (range: 32.3–59.3) Gy, and 59.4 (range: 41.4–70.3) Gy, respectively. Maximum dose to the BP was ≥ 70 Gy only in 2 nasopharyngeal cancer patients. Two (7%) early transient RIBP were reported at 7th and 8th month after RT under maximum 67.17 and 55.37 Gy, and mean 52.95 and 38.60 Gy RT doses. Conclusions Two (7%) early RIBP were seen in the patient group, although brachial plexus maximum doses were ≥ 66 Gy in 75% of patients. PMID:27095943

  6. Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II-III trial.

    PubMed

    Ghi, M G; Paccagnella, A; Ferrari, D; Foa, P; Alterio, D; Codecà, C; Nolè, F; Verri, E; Orecchia, R; Morelli, F; Parisi, S; Mastromauro, C; Mione, C A; Rossetto, C; Polsinelli, M; Koussis, H; Loreggian, L; Bonetti, A; Campostrini, F; Azzarello, G; D'Ambrosio, C; Bertoni, F; Casanova, C; Emiliani, E; Guaraldi, M; Bunkheila, F; Bidoli, P; Niespolo, R M; Gava, A; Massa, E; Frattegiani, A; Valduga, F; Pieri, G; Cipani, T; Da Corte, D; Chiappa, F; Rulli, E

    2017-09-01

    Platinum-based chemoradiation (CCRT) is the standard treatment for Locally Advanced Head and Neck Squamous-Cell Carcinoma (LAHNSCC). Cetuximab/RT (CET/RT) is an alternative treatment option to CCRT. The efficacy of induction chemotherapy (IC) followed by chemoradiation compared to chemoradiation alone has not been demonstrated in randomized clinical trials. The goals of this phase II-III trial were to assess: (i) the overall survival (OS) of IC versus no-induction (no-IC) and (ii) the Grade 3-4 in-field mucosal toxicity of CCRT versus CET/RT. The present paper focuses on the analysis of efficacy. Patients with LAHNSCC were randomized to receive concomitant treatment alone [CCRT (Arm A1) or CET/RT (Arm A2)], or three cycles of induction docetaxel/cisplatin/5 fluorouracil (TPF) followed by CCRT (Arm B1) or followed by CET/RT (Arm B2). The superiority hypothesis of OS comparison of IC versus no-IC (Arms B1 + B2 versus A1 + A2) required 204 deaths to detect an absolute 3-year OS difference of 12% (HR 0.675, with 80% power at two-sided 5% significance level). 414 out of 421 patients were finally analyzed: 206 in the IC and 208 in the no-IC arm. Six patients were excluded because of major violation and one because of metastatic disease at diagnosis. With a median follow-up of 44.8 months, OS was significantly higher in the IC arm (HR 0.74; 95% CI 0.56-0.97; P = 0.031). Complete Responses (P = 0.0028), Progression Free Survival (P = 0.013) and the Loco-regional Control (P = 0.036) were also significantly higher in the IC arm. Compliance to concomitant treatments was not affected by induction TPF. IC followed by concomitant treatment improved the outcome of patients with LAHNSCC without compromising compliance to the concomitant treatments. The degree of the benefit of IC could be different according to the type of the subsequent concomitant strategy. NCT01086826, www.clinicaltrials.gov.

  7. Long-Term Outcome and Morbidity After Treatment With Accelerated Radiotherapy and Weekly Cisplatin for Locally Advanced Head-and-Neck Cancer: Results of a Multidisciplinary Late Morbidity Clinic

    SciTech Connect

    Ruetten, Heidi; Pop, Lucas A.M.; Janssens, Geert O.R.J.; Takes, Robert P.; Knuijt, Simone; Berg, Manon van den; Merkx, Matthias A.; Herpen, Carla M.L. van; Kaanders, Johannes H.A.M.

    2011-11-15

    Purpose: To evaluate the long-term outcome and morbidity after intensified treatment for locally advanced head-and-neck cancer. Methods and Materials: Between May 2003 and December 2007, 77 patients with Stage III to IV head-and-neck cancer were treated with curative intent. Treatment consisted of accelerated radiotherapy to a dose of 68 Gy and concurrent cisplatin. Long-term survivors were invited to a multidisciplinary outpatient clinic for a comprehensive assessment of late morbidity with special emphasis on dysphagia, including radiological evaluation of swallowing function in all patients. Results: Compliance with the treatment protocol was high, with 87% of the patients receiving at least five cycles of cisplatin and all but 1 patient completing the radiotherapy as planned. The 5-year actuarial disease-free survival and overall survival rates were 40% and 47%, respectively. Locoregional recurrence-free survival at 5 years was 61%. The 5-year actuarial rates of overall late Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) Grade 3 and Grade 4 toxicity were 52% and 25% respectively. Radiologic evaluation after a median follow-up of 44 months demonstrated impaired swallowing in 57% of the patients, including 23% with silent aspiration. Subjective assessment using a systematic scoring system indicated normalcy of diet in only 15.6% of the patients. Conclusion: This regimen of accelerated radiotherapy with weekly cisplatin produced favorable tumor control rates and survival rates while compliance was high. However, comprehensive assessment by a multidisciplinary team of medical and paramedical specialists revealed significant long-term morbidity in the majority of the patients, with dysphagia being a major concern.

  8. Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck

    PubMed Central

    Pivot, X; Raymond, E; Laguerre, B; Degardin, M; Cals, L; Armand, J P; Lefebvre, J L; Gedouin, D; Ripoche, V; Kayitalire, L; Niyikiza, C; Johnson, R; Latz, J; Schneider, M

    2001-01-01

    This phase II study determined response rate of patients with locally advanced or metastatic head and neck cancer treated with pemetrexed disodium, a new multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. 35 patients with local or metastatic relapse of squamous cell carcinoma of the head and neck (31 male, 4 female; median age 53 years) were treated with pemetrexed 500 mg m2 administered as a 10-minute infusion on day 1 of a 21-day cycle. Patients received 1 to 8 cycles of therapy. 9 patients (26.5%) had an objective response, with a median response duration of 5.6 months (range 2.9–20 months). 15 (44.1%) had stable disease, and 8 (23.5%) had progressive disease. 2 patients were not assessable for response. Median overall survival was 6.4 months (range 0.7–28.1 months; 95% CI: 3.9–7.7 months). 24 patients (68.6%) experienced grade 3/4 neutropenia, with febrile neutropenia in 4 (11.4%). Grade 3/4 anaemia and thrombocytopenia occurred in 11 (34.3%) and 6 (17.1%) patients, respectively. The most frequent non-haematological toxicity was grade 3/4 mucositis (17.1%; 6 patients). In conclusion, pemetrexed is active in squamous cell carcinoma of the head and neck. Although substantial haematological toxicities were experienced by patients, subsequent studies have shown that these toxicities can be proactively managed by folic acid and vitamin B12 supplementation. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11531245

  9. Boron neutron capture therapy outcomes for advanced or recurrent head and neck cancer.

    PubMed

    Suzuki, Minoru; Kato, Ituro; Aihara, Teruhito; Hiratsuka, Junichi; Yoshimura, Kenichi; Niimi, Miyuki; Kimura, Yoshihiro; Ariyoshi, Yasunori; Haginomori, Shin-Ichi; Sakurai, Yoshinori; Kinashi, Yuko; Masunaga, Shin-Ichiro; Fukushima, Masanori; Ono, Koji; Maruhashi, Akira

    2014-01-01

    We retrospectively review outcomes of applying boron neutron capture therapy (BNCT) to unresectable advanced or recurrent head and neck cancers. Patients who were treated with BNCT for either local recurrent or newly diagnosed unresectable head or neck cancers between December 2001 and September 2007 were included. Clinicopathological characteristics and clinical outcomes were retrieved from hospital records. Either a combination of borocaptate sodium and boronophenylalanine (BPA) or BPA alone were used as boron compounds. In all the treatment cases, the dose constraint was set to deliver a dose <10-12 Gy-eq to the skin or oral mucosa. There was a patient cohort of 62, with a median follow-up of 18.7 months (range, 0.7-40.8). A total of 87 BNCT procedures were performed. The overall response rate was 58% within 6 months after BNCT. The median survival time was 10.1 months from the time of BNCT. The 1- and 2-year overall survival (OS) rates were 43.1% and 24.2%, respectively. The major acute Grade 3 or 4 toxicities were hyperamylasemia (38.6%), fatigue (6.5%), mucositis/stomatitis (9.7%) and pain (9.7%), all of which were manageable. Three patients died of treatment-related toxicity. Three patients experienced carotid artery hemorrhage, two of whom had coexistent infection of the carotid artery. This study confirmed the feasibility of our dose-estimation method and that controlled trials are warranted.

  10. Head and neck ultrasound: technical advances, novel applications and the role of elastography.

    PubMed

    McQueen, A S; Bhatia, K S

    2017-10-03

    High-resolution ultrasound (US) provides superb anatomical detail in the superficial anatomy of the neck and has become the first-line imaging investigation for neck lumps and a crucial component of clinical pathways. In this article, a wide range of advances in neck US are described with a focus on the emerging role of ultrasound elastography. Selected examples of clinical utility are presented across a spectrum of scenarios with discussion of newer applications, service delivery, and training issues. The changing role of the neck ultrasound practitioner and the future of the technique in the head and neck are considered. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  11. Summary of the Advanced Research Projects Agency head-mounted display programs

    NASA Astrophysics Data System (ADS)

    Girolamo, Henry J.

    1995-05-01

    In 1991, the Advanced Research Projects Agency (ARPA) established a head-mounted display (HMD) program as part of their High Definition Systems Program. The goals were to investigate, then develop new display technologies that would overcome the technical challenges of cathode-ray tubes, and satisfy DoD needs for improved HMDs. A Joint Services Working was formed to identify and define display specifications through common program goals. The technologies, Active Matrix Electroluminescent and Active Matrix Liquid Crystal Display were selected as the candidate display technologies. The Combat Vehicle Crew-HMD program resulted as the testbed for integrating the new display technologies. Many military systems leveraging the ARPA-developed technologies have emerged as a result of the ARPA HMD program. The dual-use applications of these technologies comply with ARPA and user goals to have HMD systems that will have wide acceptance meeting the requirements of the military, medical, commercial, and consumer markets.

  12. Adjuvant Ozonetherapy in Advanced Head and Neck Tumors: A Comparative Study

    PubMed Central

    2004-01-01

    Advanced head and neck (H&N) tumors have a poor prognosis, and this is worsened by the occurrence of hypoxia and ischemia in the tumors. Ozonetherapy has proved useful in the treatment of ischemic syndromes, and several studies have described a potential increase of oxygenation in tissues and tumors. The aim of this prospective study was to evaluate the clinical effect of ozonetherapy in patients with advanced H&N cancer in the course of their scheduled radiotherapy. Over a period of 3 years, 19 patients with advanced H&N tumors who were undergoing treatment in our department with non-standard fractionated radiotherapy plus oral tegafur. A group of 12 patients was additionally treated with intravenous chemotherapy before and/or during radiotherapy. In the other group of seven patients, systemic ozonetherapy was administered twice weekly during radiotherapy. The ozonetherapy group was older (64 versus 54 years old, P = 0.006), with a higher percentage of lymph node involvement (71% versus 8%, P = 0.019) and with a trend to more unfavorable tumor stage (57% versus 8% IVb + IVc stages, P = 0.073). However, there was no significant difference in overall survival between the chemotherapy (median 6 months) and ozonetherapy (8 months) groups. Although these results have to be viewed with caution because of the limited number of patients, they suggest that ozonetherapy could have had some positive effect during the treatment of our patients with advanced H&N tumors. The adjuvant administration of ozonetherapy during the chemo–radiotherapy for these tumors merits further research. PMID:15841266

  13. Adjuvant Ozonetherapy in Advanced Head and Neck Tumors: A Comparative Study.

    PubMed

    Clavo, Bernardino; Ruiz, Ana; Lloret, Marta; López, Laura; Suárez, Gerardo; Macías, David; Rodríguez, Victor; Hernández, Maria A; Martín-Oliva, Roberto; Quintero, Santiago; Cuyás, José M; Robaina, Francisco

    2004-12-01

    Advanced head and neck (H&N) tumors have a poor prognosis, and this is worsened by the occurrence of hypoxia and ischemia in the tumors. Ozonetherapy has proved useful in the treatment of ischemic syndromes, and several studies have described a potential increase of oxygenation in tissues and tumors. The aim of this prospective study was to evaluate the clinical effect of ozonetherapy in patients with advanced H&N cancer in the course of their scheduled radiotherapy. Over a period of 3 years, 19 patients with advanced H&N tumors who were undergoing treatment in our department with non-standard fractionated radiotherapy plus oral tegafur. A group of 12 patients was additionally treated with intravenous chemotherapy before and/or during radiotherapy. In the other group of seven patients, systemic ozonetherapy was administered twice weekly during radiotherapy. The ozonetherapy group was older (64 versus 54 years old, P = 0.006), with a higher percentage of lymph node involvement (71% versus 8%, P = 0.019) and with a trend to more unfavorable tumor stage (57% versus 8% IVb + IVc stages, P = 0.073). However, there was no significant difference in overall survival between the chemotherapy (median 6 months) and ozonetherapy (8 months) groups. Although these results have to be viewed with caution because of the limited number of patients, they suggest that ozonetherapy could have had some positive effect during the treatment of our patients with advanced H&N tumors. The adjuvant administration of ozonetherapy during the chemo-radiotherapy for these tumors merits further research.

  14. Comparison of locoregional versus extended locoregional radiation volumes for patients with non-metastatic gastro-esophageal junction carcinomas

    PubMed Central

    Wang, Jingya; Milton, Denái R.; He, Liru; Komaki, Ritsuko; Liao, Zhongxing; Crane, Christopher H.; Minsky, Bruce D.; Thall, Peter F.; Lin, Steven H.

    2015-01-01

    Introduction To delineate an optimal clinical target volume (CTV) for gastroesophageal junction (GEJ) cancers by comparing locoregional vs. extended locoregional radiation volumes. Materials This retrospective analysis examined 222 patients (111 matched pairs treated with locoregional vs. extended locoregional radiation) with non-metastatic GEJ carcinomas treated with concurrent chemoradiation +/- surgery. The CTV for locoregional volumes was defined as gross tumor volume (GTV) + elective coverage of first-echelon nodes and sometimes the celiac axis. The CTV for extended locoregional volumes was defined as GTV + elective coverage of celiac and splenic (+/- porta) nodes. Variables used for matching included gender, stage, performance status, histology, receipt of induction chemotherapy, type of concurrent chemotherapy, radiation modality, receipt of surgery, type of surgery, and Siewert classification. Regression models stratified by matched pairs were fit to estimate effect of radiation volume on clinical endpoints. Results Adjusting p-values for multiple testing, patients treated with extended locoregional vs. locoregional radiation had increased odds of grade 2+ acute chemoradiation-associated GI toxicity (OR 2.92, adj. p=0.0447). However, differing radiation volumes were not significantly associated with postoperative complication rates, pathologic T-stage, frequency of positive perigastric/regional nodes on surgical specimen, distant-metastases progression free survival, locoregional progression free survival, or overall survival (adj. p>0.05). Of the patients who did (N=124) and did not (N=72) receive elective celiac radiation, 2 (1.6%) and 2 (2.8%) patients, respectively, relapsed in the celiac nodes. No patients failed in the splenic or porta nodes. Conclusions Most GEJ cancers can be safely treated without elective inclusion of splenic/porta nodes. PMID:25695222

  15. Advanced Stirling Duplex Materials Assessment for Potential Venus Mission Heater Head Application

    NASA Technical Reports Server (NTRS)

    Ritzert, Frank; Nathal, Michael V.; Salem, Jonathan; Jacobson, Nathan; Nesbitt, James

    2011-01-01

    This report will address materials selection for components in a proposed Venus lander system. The lander would use active refrigeration to allow Space Science instrumentation to survive the extreme environment that exists on the surface of Venus. The refrigeration system would be powered by a Stirling engine-based system and is termed the Advanced Stirling Duplex (ASD) concept. Stirling engine power conversion in its simplest definition converts heat from radioactive decay into electricity. Detailed design decisions will require iterations between component geometries, materials selection, system output, and tolerable risk. This study reviews potential component requirements against known materials performance. A lower risk, evolutionary advance in heater head materials could be offered by nickel-base superalloy single crystals, with expected capability of approximately 1100C. However, the high temperature requirements of the Venus mission may force the selection of ceramics or refractory metals, which are more developmental in nature and may not have a well-developed database or a mature supporting technology base such as fabrication and joining methods.

  16. [Reappraisal role of locoregional radiation therapy in metastatic cancers].

    PubMed

    Rancoule, Chloé; Pacaut-Vassal, Cécile; Vallard, Alexis; Mery, Benoite; Trone, Jane-Chloé; El Meddeb Hamrouni, Anis; Magné, Nicolas

    2017-01-01

    Recent innovations in oncology area helped to improve the prognosis of certain cancers including metastatic ones with a decrease in mortality. Recommendations describe the treatment of metastatic cancer as systemic therapy or complementary care and the role of locoregional treatment in the treatment plan only occurs in a palliative context. Currently, in the clinical practice, out of "the evidence based medicine", an early locoregional therapy (surgery or radiation therapy) can be proposed in several cases of metastatic cancers. The aim of the present review is to describe the role of the primary tumor radiation therapy in metastatic disease. In metastatic breast, prostate, cervix, rectal or nasopharyngeal cancers, locoregional treatment including radiation therapy can, in some cases, be discussed and decided in MDT. Ongoing clinical trials in these locations should soon precise the benefit of this locoregional treatment. It will also be important to define the specific criteria in order to select patients who could benefit from this treatment.

  17. Modelling an advanced ManPAD with dual band detectors and a rosette scanning seeker head

    NASA Astrophysics Data System (ADS)

    Birchenall, Richard P.; Richardson, Mark A.; Butters, Brian; Walmsley, Roy

    2012-01-01

    Man Portable Air Defence Systems (ManPADs) have been a favoured anti aircraft weapon since their appearance on the military proliferation scene in the mid 1960s. Since this introduction there has been a 'cat and mouse' game of Missile Countermeasures (CMs) and the aircraft protection counter counter measures (CCMs) as missile designers attempt to defeat the aircraft platform protection equipment. Magnesium Teflon Viton (MTV) flares protected the target aircraft until the missile engineers discovered the art of flare rejection using techniques including track memory and track angle bias. These early CCMs relied upon CCM triggering techniques such as the rise rate method which would just sense a sudden increase in target energy and assume that a flare CM had been released by the target aircraft. This was not as reliable as was first thought as aspect changes (bringing another engine into the field of view) or glint from the sun could inadvertently trigger a CCM when not needed. The introduction of dual band detectors in the 1980s saw a major advance in CCM capability allowing comparisons between two distinct IR bands to be made thus allowing the recognition of an MTV flare to occur with minimal false alarms. The development of the rosette scan seeker in the 1980s complemented this advancement allowing the scene in the missile field of view (FOV) to be scanned by a much smaller (1/25) instantaneous FOV (IFOV) with the spectral comparisons being made at each scan point. This took the ManPAD from a basic IR energy detector to a pseudo imaging system capable of analysing individual elements of its overall FOV allowing more complex and robust CCM to be developed. This paper continues the work published in [1,2] and describes the method used to model an advanced ManPAD with a rosette scanning seeker head and robust CCMs similar to the Raytheon Stinger RMP.

  18. Nutritional changes in patients with locally advanced head and neck cancer during treatment.

    PubMed

    Arribas, L; Hurtós, L; Taberna, M; Peiró, I; Vilajosana, E; Lozano, A; Vazquez, S; Mesia, R; Virgili, N

    2017-08-01

    The purpose of the study is to evaluate changes in body composition and nutritional status that occur throughout the oncological treatment in head and neck cancer patients. A prospective cohort observational study in patients diagnosed with head and neck squamous cell carcinoma (HNSCC) that underwent treatment with induction chemotherapy (iCT) followed by chemoradiotherapy or bioradiotherapy were invited to participate. All patients had dietetic counseling from the diagnosis and a close monitoring throughout the treatment implementing nutritional support as needed. From June 2011 until October 2012, 20 patients were included. Nutritional and anthropometric parameters were collected at diagnosis, post iCT, after radiotherapy, 1 and 3months post radiotherapy. According to Patient Generated Subjective Global Assessment, 30% of patients were malnourished at diagnosis. After iCT there was an increase in weight, body mass index (BMI) and fat free mass (FFM) with almost complete improvement in dysphagia and odynophagia. Nevertheless a significant nutritional deterioration (p=0.0022) occurred at the end of radiotherapy with 95% of patients becoming severe or moderate malnourished. Nutritional parameters such as weight, BMI and hand grip strength also decrease significantly during treatment. Despite an intensive nutritional support from the diagnosis throughout the oncological treatment in advanced HNSCC cancer patients, nutritional status deteriorates during radiotherapy. Our findings suggest that iCT may help improve nutritional status by ameliorating the symptoms that limit the oral intake. This improvement in the nutritional status could contribute to minimize further deterioration. Further investigations are needed involving novel approaches to avoid nutritional deterioration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. An exploration of factors predicting malnutrition in patients with advanced head and neck cancer.

    PubMed

    Silander, Ewa; Nyman, Jan; Hammerlid, Eva

    2013-10-01

    Malnutrition is common among head and neck cancer patients and negatively impacts on survival and quality of life. This study aimed to identify predictors of malnutrition at time of diagnosis in order to identify patients at risk and enable early nutritional support and prevent malnutrition. A total of 134 patients with advanced oral and pharyngeal cancer were included in the study. Weight, body mass index (BMI), fat free mass (FFM), dysphagia, and quality of life were measured at diagnosis and after 6 months. Two definitions for malnutrition were applied: >10% weight loss and BMI <20 after 6 months. Six months after diagnosis, 66% of the patients were malnourished as per the >10% weight loss definition, and 26% of the patients were malnourished as per the BMI < 20 weight loss definition. In multivariate analysis, low BMI followed by low FFM and dysphagia were the strongest predictors for malnutrition using BMI <20. Chemotherapy and high BMI at diagnosis were the strongest predictors of malnutrition using the 10% weight loss definition. For patients treated with chemotherapy, the risk for malnutrition was very high both for patients with normal BMI (67%) and for patients with BMI 30 (89%). Unintended weight loss more than 10% seems to be the most reasonable definition of malnutrition for identifying predictors of this in head and neck cancer patients. The weight loss correlated significantly to a loss of FFM. Treatment with chemotherapy was a strong predictor, as was a high BMI at time of diagnosis. This is an important finding since overweight patients might not be considered at high risk for developing malnutrition, and consequently nutritional support for them might be delayed. Copyright © 2013 The American Laryngological, Rhinological, and Otological Society, Inc.

  20. Rapid hyperfractionated radiotherapy. Clinical results in 178 advanced squamous cell carcinomas of the head and neck

    SciTech Connect

    Nguyen, T.D.; Demange, L.; Froissart, D.; Panis, X.; Loirette, M.

    1985-07-01

    The authors present a series of 178 patients with Stage III or IV squamous cell carcinoma of the head and neck treated by rapid irradiation using multiple and small fractions per day. An initial group of 91 patients (G1) received a total dose of 72 Gy in 80 sessions and 10 days, according to the following split course schedule: J1 to J5, 36 Gy in 40 sessions, eight daily fractions of .9 Gy separated by 2 hours; J6 to J20, rest period; J21 to J25, same as in J1 except that the spinal cord was shielded. This protocol was altered for the following 87 patients (G2) by lessening the total dose to 60 to 66 Gy and the number of fractions to 60. The rest period was lengthened to 4 weeks. All patients but five completed the whole program and the minimal follow-up period was 24 months. At the end of irradiation, 121 patients achieved a total remission, but local recurrences occurred in 56%. Moreover, acute intolerance was considered as severe in 34% of G1 patients, and included extensive mucosal necrosis and bleeding. Although this rate was significantly reduced in G2 patients, late complications were observed in 20 of the 25 survivors, and included trismus, cervical sclerosis, and recurrent laryngeal edema. The crude survival rate is 13% at 2 years. Although this study was not randomized, this particular type of accelerated and hyperfractionated combination of irradiation did not really improve the clinical results in advanced carcinoma of the head and neck. Other schedules and probably other tumors, less extended, should be tested.

  1. Multiple nodal locoregional recurrence of pheochromocytoma

    PubMed Central

    Ramírez-Plaza, César Pablo; Cárdenas, Elena Margarita Sanchiz; Humanes, Rocío Soler

    2015-01-01

    Introduction Malignancy is present in 10% of pheochromocytomas (PCC) and is defined as local/vascular infiltration of surrounding tissues or the presence of chromaffin cells deposits in distant organs. The presence of isolated nodal recurrence is very rare and only 7 cases have been reported in the medical literature. Presentation of the case The case of a 32-y male with a symptomatic recurrence of a previously operated (2-years ago) PCC is presented. Radiological and functional imaging studies confirmed the presence of multiple nodules in the surgical site. A radical left nephrectomy with extensive lymphatic clearance in order to get an R0 resection was performed. The pathologist confirmed the diagnosis of massive locoregional nodal invasion. Discussion A detailed histological report and a thorough genetic study must be considered in every operated PCC in order to identify mutations and profiles of risk for malignancy. When recurrence or metastastic disease is suspected, imaging and functional exams are done in order to obtain a proper staging. Radical surgery for the metastatic disease is the only treatment that may provide prolonged survival. If an R0 resection is not possible, then a debulking surgery is a good option when the benefit/risk ratio is acceptable. Conclusion Isolated lymph nodal recurrence is very rare in malignant PCC, with only 7 cases previously published. The role of surgery is essential to get long-term survival because provides clinical and functional control of the disease. PMID:26117450

  2. Locoregional Flaps for Oral Cavity Reconstruction: A Review of Modern Options.

    PubMed

    Patel, Urjeet A; Hartig, Gregory K; Hanasono, Matthew M; Lin, Derrick T; Richmon, Jeremy D

    2017-08-01

    Objective To review state-of-the-art modifications and advances in soft tissue local and regional flap reconstruction of the oral cavity and to determine the role these techniques play in current practice. Data Sources Review of the literature regarding oral cavity reconstruction. Review Methods The authors describe advances in locoregional reconstructive options and assimilate data from the literature that compare recent advances to the historic standards. Conclusions Modern advances in regional reconstruction of the oral cavity offer outstanding results and demonstrate potential advance over free tissue transfer. These modifications demonstrate the prominent role that regional reconstruction can play in oral cavity reconstruction. Implications for Practice With a more complete understanding of these options, the surgeon is better able to tailor the reconstruction to the needs of the patient to provide high-quality cost-effective care.

  3. 0-7-21 hypofractionated palliative radiotherapy: an effective treatment for advanced head and neck cancers

    PubMed Central

    Doerwald-Munoz, L; Zhang, H; Kim, D-H; Sagar, S; Wright, J R; Hodson, D I

    2015-01-01

    Objective: We report our experience in providing palliative radiotherapy (RT) to patients with head and neck cancers (HNCs). Our hypofractionated regimen, “0-7-21”, treats patients with 24 Gy in three fractions. Methods: Patients, disease and response data were retrieved for candidates of 0-7-21 from 2005 to 2012. Primary end points included symptom and tumour size responses to RT based on response evaluation criteria in solid tumours (RECIST) guidelines. Secondary end points included progression-free survival (PFS) within the irradiated field, overall survival (OS) and symptomatic PFS (SPFS), calculated using Kaplan–Meier method and adverse events. Cox proportional hazards regression and logistic regression were used to investigate for prognostic factors. Results: A total of 110 patients were included. Among the patients, 40% and 31% had complete response for symptoms and tumour size, respectively; 42% and 50% had partial response for symptoms and tumour size, respectively; and 15% had stability of symptoms and tumour size. Median 6-month OS was 51%, and PFS within the irradiated field was 39%. Planning target volume was predictive of OS (p < 0.001), PFS (p < 0.001) and SPFS (p < 0.005), while higher TNM stage was associated with poorer tumour response (p = 0.02). Conclusion: 0-7-21 is an effective and well-tolerated palliative RT regimen for patients with HNC. There was excellent symptom and local control with acceptable toxicity profile in these patients. Advances in knowledge: This is the first study to describe the outcomes of 0-7-21 in treating advanced HNCs. The positive results suggest that 0-7-21 provides excellent palliation with minimal toxicity, with significantly less on-treatment time than current published palliative RT regimen. PMID:25694259

  4. Accelerated fractionation radiation therapy for advanced squamous cell carcinoma of the head and neck

    SciTech Connect

    Giri, P.G.; Gemer, L.S. )

    1991-09-01

    The authors treated 14 patients who had advanced head and neck cancer with an accelerated fractionation schedule of irradiation consisting of two fractions given 6 hours apart. In the morning a volume of 1.7 Gy was given to an area that encompassed the entire tumor, enlarged lymph nodes, and all areas at risk for microscopic disease. Six hours later, 1.1 Gy was given to an area that included only the tumor and any enlarged lymph nodes, with a 2-cm margin. The treatment was well tolerated; of the 13 patients who completed therapy, six did not require a break in therapy, and seven patients did. The median rest period was 2 days. There was no grade 4 toxicity. Grade 3 toxicity included skin changes (one case), mucositis (two), dysphagia (two), weight loss (three), and a decrease in the hemoglobin level (one case). The response rate in the 13 who completed therapy was 13/13 (100%); 11 of the 13 (83%) had a complete response. Only one of the 11 who achieved a complete response had failure at the primary site. At a median follow-up of 24 months, the absolute survival was 7/13 (54%) and the corrected survival was 7/10 (70%). This technique permits radiation therapy to be given on an accelerated schedule without a planned break in treatment. The overall response rate and survival at 2 years was excellent.

  5. Advanced Pathway Guidance Evaluations on a Synthetic Vision Head-Up Display

    NASA Technical Reports Server (NTRS)

    Kramer, Lynda J.; Prinzel, Lawrence J., III; Arthur, Jarvis J., III; Bailey, Randall E.

    2005-01-01

    NASA's Synthetic Vision Systems (SVS) project is developing technologies with practical applications to potentially eliminate low visibility conditions as a causal factor to civil aircraft accidents while replicating the operational benefits of clear day flight operations, regardless of the actual outside visibility condition. A major thrust of the SVS project involves the development/demonstration of affordable, certifiable display configurations that provide intuitive out-the-window terrain and obstacle information with advanced guidance for commercial and business aircraft. This experiment evaluated the influence of different pathway and guidance display concepts upon pilot situation awareness (SA), mental workload, and flight path tracking performance for Synthetic Vision display concepts using a Head-Up Display (HUD). Two pathway formats (dynamic and minimal tunnel presentations) were evaluated against a baseline condition (no tunnel) during simulated instrument meteorological conditions approaches to Reno-Tahoe International airport. Two guidance cues (tadpole, follow-me aircraft) were also evaluated to assess their influence. Results indicated that the presence of a tunnel on an SVS HUD had no effect on flight path performance but that it did have significant effects on pilot SA and mental workload. The dynamic tunnel concept with the follow-me aircraft guidance symbol produced the lowest workload and provided the highest SA among the tunnel concepts evaluated.

  6. Sub-100-nm trackwidth development by e-beam lithography for advanced magnetic recording heads

    NASA Astrophysics Data System (ADS)

    Chang, Jei-Wei; Chen, Chao-Peng

    2006-03-01

    Although semiconductor industry ramps the products with 90 nm much quicker than anticipated [1], magnetic recording head manufacturers still have difficulties in producing sub-100 nm read/write trackwidth. Patterning for high-aspectratio writer requires much higher depth of focus (DOF) than most advanced optical lithography, including immersion technique developed recently [2]. Self-aligning reader with its stabilized bias requires a bi-layer lift-off structure where the underlayer is narrower than the top image layer. As the reader's trackwidth is below 100nm, the underlayer becomes very difficult to control. Among available approaches, e-beam lithography remains the most promising one to overcome the challenge of progressive miniaturization. In this communication, the authors discussed several approaches using ebeam lithography to achieve sub-100 nm read/write trackwidth. Our studies indicated the suspended resist bridge design can not only widen the process window for lift-off process but also makes 65 nm trackwidth feasible to manufacture. Necked dog-bone structure seems to be the best design in this application due to less proximity effects from adjacent structures and minimum blockages for ion beam etching. The trackwidth smaller than 65 nm can be fabricated via the combination of e-beam lithography with auxiliary slimming and/or trimming. However, deposit overspray through undercut becomes dominated in such a small dimension. To minimize the overspray, the effects of underlayer thickness need to be further studied.

  7. [Clinical impact of locoregional hyperthermia in gynecological oncology].

    PubMed

    Bischoff, J; Lindner, L H; Issels, R D; Costa, S

    2006-10-01

    In the last decade progress in gynecological oncology has been achieved mainly by new cytotoxic drugs and advances in radiation technology. For example, the use of taxanes in the primary therapy of ovarian cancers and of combined radio-chemotherapy in cervical cancer has led to significant prolongations of survival. However, in case of relapse most gynaecological malignancies are associated with very poor prognosis. Efficacy of local and systemic therapy can be increased by combining radiotherapy and/or chemotherapy with locoregional hyperthermia (LRH). Increasing the temperature of the target tissue up to 41-43 degrees C leads to local hyperaemia and the tumor tissue becomes more responsive to cytotoxic interventions. In several prospective randomized studies the combination between LRH and radiotherapy was superior to radiotherapy alone in terms of local control (e. g. chest wall recurrence in breast cancer) and has led to longer overall survival in advanced cervical cancer. Platinum derivatives and other cytotoxic drugs have shown synergistic effects with LRH and the combination of both has elicited high response rates in recurrent cervical cancer. In phase-II-clinical trials the newly developed liposomal anthracyclines demonstrated synergistic effects with LRH in patients with refractory ovarian cancer. Our own experience has shown that adding LRH to radio- and/or chemotherapy is well tolerated by the patients. Despite of the fact, that the available data are still preliminary, the inclusion of LRH into multimodal cancer therapy concepts appears to be very promising. Well-designed comparative studies are still needed to evaluate the role of hyperthermia as an adjunct to conventional cancer therapy.

  8. Efficacy of concurrent cetuximab vs. 5-fluorouracil/carboplatin or high-dose cisplatin with intensity-modulated radiation therapy (IMRT) for locally-advanced head and neck cancer (LAHNSCC)

    PubMed Central

    Shapiro, Lauren Q.; Sherman, Eric J.; Riaz, Nadeem; Setton, Jeremy; Koutcher, Lawrence; Zhang, Zhigang; Shi, Weiji; Fury, Matthew G.; Wolden, Suzanne L.; Pfister, David G.; Morris, Luc; Lee, Nancy

    2016-01-01

    Summary Objectives We previously reported inferior outcomes for locally-advanced head and neck squamous cell carcinoma (LAHNSCC) patients treated with concurrent cetuximab vs. high-dose cisplatin with intensity-modulated radiation therapy (IMRT). Prior to FDA approval of cetuximab for LAHNSCC, non-cisplatin eligible patients at our institution received 5-fluorouracil (5FU)/carboplatin. We sought to compare concurrent cetuximab vs. 5FU/carboplatin vs. high-dose cisplatin with IMRT for LAHNSCC. Materials and methods Retrospective review was performed for LAHNSCC patients treated at Memorial Sloan-Kettering Cancer Center from 11/02 to 04/08 with concurrent cetuximab (n = 49), 5FU/carboplatin (n = 52), or cisplatin (n = 259) and IMRT. Overall survival (OS), locoregional failure (LRF), distant metastasis-free survival, and late toxicity were analyzed using univariate and multivariate analyses. OS analysis was confirmed by propensity score adjustment. Results Treatment groups were similar with regard to primary tumor site, overall stage, and alcohol and tobacco history. Cetuximab and 5FU/carboplatin patients were older, with lower performance status, more comorbidities, higher T classification, and worse renal function. On multivariate analysis, compared with cisplatin and 5FU/carboplatin, cetuximab was associated with inferior 4-year OS (86.9% vs. 70.2% vs. 40.9%; P < .0001) and 4-year LRF (6.3% vs. 9.7% vs. 40.2%; P < .0001). Late toxicity was highest with 5FU/carboplatin (25.0%) vs. cisplatin (8.0%) vs. cetuximab (7.7%). Conclusions Although 5FU/carboplatin patients were sicker and experienced greater toxicity than cisplatin patients, no significant difference was found in all endpoints. In contrast, despite similar pretreatment characteristics, outcomes for cetuximab vs. 5FU/carboplatin were significantly worse. We feel that caution should be used with routine use of cetuximab in the management of LAHNSCC. PMID:25132089

  9. Patterns of Treatment Failure and Postrecurrence Outcomes Among Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma After Chemoradiotherapy Using Modern Radiation Techniques.

    PubMed

    Leeman, Jonathan E; Li, Jin-Gao; Pei, Xin; Venigalla, Praveen; Zumsteg, Zachary S; Katsoulakis, Evangelia; Lupovitch, Eitan; McBride, Sean M; Tsai, Chiaojung J; Boyle, Jay O; Roman, Benjamin R; Morris, Luc G T; Dunn, Lara A; Sherman, Eric J; Lee, Nancy Y; Riaz, Nadeem

    2017-05-25

    Even though 15% to 50% of patients with head and neck squamous cell carcinoma (HNSCC) experience recurrence, relatively little is known regarding patterns of treatment failure and postrecurrence outcomes after chemoradiotherapy using modern radiation techniques (intensity-modulated radiotherapy [IMRT]). Recurrence patterns are significantly affected by variations in the quality of radiotherapy, which may confound findings from multicenter trials. To assess patterns of treatment failure and postrecurrence outcomes for patients with HNSCC treated with contemporary radiotherapy techniques. This large single-institution cohort study reviewed the outcomes of 1000 consecutive patients with stage III to IVB oropharyngeal carcinoma (n = 703), laryngeal carcinoma (n = 126), or hypopharyngeal carcinoma (n = 46) treated with definitive IMRT with or without concurrent chemotherapy, as well as patients with oral cavity carcinoma (n = 125) treated with postoperative IMRT with or without concurrent systemic therapy, from December 1, 2001, to December 31, 2013, with a median follow-up of 65.1 months among surviving patients. Data analysis was performed from January 31, 2016, to February 17, 2017. Patterns of treatment failure and overall survival following locoregional failure or distant metastasis. Among the 1000 patients (186 women and 814 men; mean [SD] age, 59.3 [10.8] years), there were no marginal or isolated out-of-radiation-field failures. Among subsites, the cumulative incidence of local failure was highest among patients with oral cavity carcinoma vs those with oropharyngeal carcinoma (hazard ratio, 5.2; 95% CI, 3.1-8.6; P < .001). Furthermore, patients with oral cavity carcinoma experienced significantly shorter survival following distant metastasis (hazard ratio, 3.66; 95% CI, 1.98-6.80; P < .001). Patients with oropharyngeal carcinoma positive for human papillomavirus or p16 lived longer after locoregional failure compared with patents with

  10. Research studies on advanced optical module/head designs for optical devices

    NASA Technical Reports Server (NTRS)

    Burke, James J.

    1991-01-01

    A summary is presented of research in optical data storage materials and of research at the center. The first section contains summary reports under the general headings of: (1) Magnetooptic media: modeling, design, fabrication, characterization, and testing; (2) Optical heads: holographic optical elements; and (3) Optical heads: integrated optics. The second section consist of a proposal entitled, Signal Processing Techniques for Optical Data Storage. And section three presents various publications prepared by the center.

  11. Patterns of failure in patients with locally advanced head and neck cancer treated postoperatively with irradiation or concomitant irradiation with Mitomycin C and Bleomycin

    SciTech Connect

    Zakotnik, Branko . E-mail: bzakotnik@onko-i.si; Budihna, Marjan; Smid, Lojze; Soba, Erika; Strojan, Primoz; Fajdiga, Igor; Zargi, Miha; Oblak, Irena; Lesnicar, Hotimir

    2007-03-01

    Purpose: The long term results and patterns of failure in patients with squamous cell head and neck carcinoma (SCHNC) treated in a prospective randomized trial in which concomitant postoperative radiochemotherapy with Mitomycin C and Bleomycin (CRT) was compared with radiotherapy only (RT), were analyzed. Patients and Methods: Between March 1997 and December 2001, 114 eligible patients with Stage III or IV SCHNC were randomized. Primary surgical treatment was performed with curative intent in all patients. Patients in both groups were postoperatively irradiated to the total dose of 56-70 Gy. Chemotherapy included Mitomycin C 15 mg/m{sup 2} after 10 Gy and 5 mg of Bleomycin twice weekly during irradiation. Median follow-up was 76 months (48-103 months). Results: At 5 years in the RT and CRT arms, the locoregional control was 65% and 88% (p = 0.026), disease-free survival 33% and 53% (p = 0.035), and overall survival 37% and 55% (p = 0.091) respectively. Patients who benefited from chemotherapy were those with high-risk factors. The probability of distant metastases was 22% in RT and 20% in CRT arm (p = 0.913), of grade III or higher late toxicity 19% in RT and 26% in CRT arm (p = 0.52) and of thyroid dysfunction 36% in RT and 56% in CRT arm (p = 0.24). The probability to develop a second primary malignancy (SPM) was 34% in the RT and 8% in the CRT arm (p = 0.023). One third of deaths were due to infection, but there was no difference between the 2 groups. Conclusion: With concomitant radiochemotherapy, locoregional control and disease free survival were significantly improved. Second primary malignancies in the CRT arm compared to RT arm were significantly less frequent. The high probability of post treatment hypothyroidism in both arms warrants regular laboratory evaluation.

  12. [Role and interest of induction chemotherapy for head and neck cancers].

    PubMed

    Pointreau, Y; Schick, U; Huguet, F

    2017-10-01

    Induction chemotherapy must be integrated in a global approach for locally advanced head and neck cancer. Its use has theoretical advantages but should not compromise locoregional radiotherapy. Induction chemotherapy is a standard for organ preservation with the use of the TPF scheme to avoid total laryngectomy without compromising survival data. It is more controversial in other locally advanced head and neck cancer because concurrent chemoradiotherapy is the standard of care. It may be an option for patients with significant lymph node invasion to reduce the occurrence of distant metastasis. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  13. Radiochemotherapy With Cetuximab, Cisplatin, and Amifostine for Locally Advanced Head and Neck Cancer: A Feasibility Study

    SciTech Connect

    Koukourakis, Michael I.; Karapantzos, Ilias; Daniilidis, Vassilios; Kouskoukis, Constantinos

    2010-05-01

    Purpose: Radiotherapy (RT) combined with cisplatin or cetuximab is the standard of care for patients with locally advanced head/neck cancer (LA-HNC). The feasibility of radiochemotherapy with cisplatin and cetuximab, supported with amifostine, was herein investigated. Methods and Materials: Forty-three patients with LA-HNC were recruited. Conformal hypofractionated/accelerated RT with amifostine cytoprotection (2.7 Gy/fraction, 21 fractions in 4 weeks) was combined with cisplatin (30 mg/m{sup 2}/week) and cetuximab (standard weekly regimen) therapy. The dose of amifostine was individualized according to tolerance. Results: A high daily amifostine dose (750-1,000 mg) was tolerated by 41.8% of patients, and a standard dose (500 mg) was tolerated by 34.9% of patients. A high amifostine dose was linked to reduced RT delays (p = 0.0003). Grade 3 to 4 (3-4) mucositis occurred in 7/43 (16.2%) patients, and fungal infections occurred in 18/43 (41.8%) patients. Radiation dermatitis was not aggravated. Interruption of cetuximab due to acneiform rash was necessary in 23.3% of patients, while amifostine-related fever and rash were not observed. Severe late radiation sequelae consisted of laryngeal edema (9% laryngeal cases) and cervical strictures (33% of hypopharyngeal cases). Good salivary function was preserved in 6/11 (54.5%) nasopharyngeal cancer patients. The complete response rate was 68.5%, reaching 77.2% in patients with minor radiotherapy delays. The 24-month local control and survival rates were 72.3% and 91%, respectively (median follow-up was 13 months.). Conclusions: In this feasibility study, weekly administration of cisplatin and cetuximab was safely combined with accelerated RT, supported with amifostine, at the cost of a high incidence of acneiform rash but a reduced incidence of amifostine-related fever/rash. A high daily dose of amifostine allows completion of therapy with minor delays.

  14. Brain Response to Primary Blast Wave Using Validated Finite Element Models of Human Head and Advanced Combat Helmet

    PubMed Central

    Zhang, Liying; Makwana, Rahul; Sharma, Sumit

    2013-01-01

    Blast-induced traumatic brain injury has emerged as a “signature injury” in combat casualty care. Present combat helmets are designed primarily to protect against ballistic and blunt impacts, but the current issue with helmets is protection concerning blasts. In order to delineate the blast wave attenuating capability of the Advanced Combat Helmet (ACH), a finite element (FE) study was undertaken to evaluate the head response against blast loadings with and without helmet using a partially validated FE model of the human head and ACH. Four levels of overpressures (0.27–0.66 MPa) from the Bowen’s lung iso-damage threshold curves were used to simulate blast insults. Effectiveness of the helmet with respect to head orientation was also investigated. The resulting biomechanical responses of the brain to blast threats were compared for human head with and without the helmet. For all Bowen’s cases, the peak intracranial pressures (ICP) in the head ranged from 0.68 to 1.8 MPa in the coup cortical region. ACH was found to mitigate ICP in the head by 10–35%. Helmeted head resulted in 30% lower average peak brain strains and product of strain and strain rate. Among three blast loading directions with ACH, highest reduction in peak ICP (44%) was due to backward blasts whereas the lowest reduction in peak ICP and brain strains was due to forward blast (27%). The biomechanical responses of a human head to primary blast insult exhibited directional sensitivity owing to the different geometry contours and coverage of the helmet construction and asymmetric anatomy of the head. Thus, direction-specific tolerances are needed in helmet design in order to offer omni-directional protection for the human head. The blasts of varying peak overpressures and durations that are believed to produce the same level of lung injury produce different levels of mechanical responses in the brain, and hence “iso-damage” curves for brain injury are likely different than the Bowen

  15. Advanced stitching head for making stitches in a textile article having variable thickness

    NASA Technical Reports Server (NTRS)

    Thrash, Patrick J. (Inventor); Miller, Jeffrey L. (Inventor); Codos, Richard (Inventor)

    1999-01-01

    A stitching head for a computer numerically controlled stitching machine includes a thread tensioning mechanism for automatically adjusting thread tension according to the thickness of the material being stitched. The stitching head also includes a mechanism for automatically adjusting thread path geometry according to the thickness of the material being stitched.

  16. Oxygen-modifying treatment with ARCON reduces the prognostic significance of hemoglobin in squamous cell carcinoma of the head and neck

    SciTech Connect

    Hoogsteen, Ilse J. . E-mail: i.hoogsteen@rther.umcn.nl; Pop, Lucas A.M.; Marres, Henri A.M.; Hoogen, Franciscus J.A. van den; Kaanders, Johannes H.A.M.

    2006-01-01

    Purpose: To evaluate the prognostic significance of hemoglobin (Hb) levels measured before and during treatment with accelerated radiotherapy with carbogen and nicotinamide (ARCON). Methods and Materials: Two hundred fifteen patients with locally advanced tumors of the head and neck were included in a phase II trial of ARCON. This treatment regimen combines accelerated radiotherapy for reduction of repopulation with carbogen breathing and nicotinamide to reduce hypoxia. In these patients, Hb levels were measured before, during, and after radiotherapy. Results: Preirradiation and postirradiation Hb levels were available for 206 and 195 patients respectively. Hb levels below normal were most frequently seen among patients with T4 (p < 0.001) and N2 (p < 0.01) disease. Patients with a larynx tumor had significantly higher Hb levels (p < 0.01) than other tumor sites. During radiotherapy, 69 patients experienced a decrease in Hb level. In a multivariate analysis there was no prognostic impact of Hb level on locoregional control, disease-free survival, and overall survival. Primary tumor site was independently prognostic for locoregional control (p = 0.018), and gender was the only prognostic factor for disease-free and overall survival (p < 0.05). High locoregional control rates were obtained for tumors of the larynx (77%) and oropharynx (72%). Conclusion: Hemoglobin level was not found to be of prognostic significance for outcome in patients with squamous cell carcinoma of the head and neck after oxygen-modifying treatment with ARCON.

  17. Multimodality therapy for locoregional extrahepatic cholangiocarcinoma: a population based analysis

    PubMed Central

    Fuller, Clifton D.; Wang, Samuel J.; Choi, Mehee; Czito, Brian G.; Cornell, John; Welzel, Tania M.; McGlynn, Katherine A.; Luh, Join Y.; Thomas, Charles R.

    2009-01-01

    Introduction: While surgical resection is the mainstay of treatment for extrahepatic cholangiocarcinoma (EHCC), most patients present with advanced disease. Owing in part to numerical rarity, the optimum role of radiotherapy (RT) for EHCC, as well as its relative benefit is an area of debate. The specific aim of this series is to estimate survival for EHCC patients receiving surgery and adjuvant RT using a robust population based dataset. Methods: Data was extracted from the Surveillance, Epidemiology, and End Results (SEER) limited-use dataset for selected EHCC cases. Lognormal multivariate survival analysis was implemented to estimate survival for patients for treatment cohorts based on extent of surgical intervention and RT. Results: Parametric estimated median survival for patients receiving total/radical resection+RT was 26 months, 25 months for total/radical resection alone, 25 months for subtotal/debulking resection+RT, 21 months for subtotal/debulking resection, 12 months for RT alone, and 9 months for those not receiving surgery or RT. Parametric multivariate analysis revealed age, AJCC Stage, grade, and surgical/radiation regimen as statistically significant covariates with survival. Surgery-alone and adjuvant radiotherapy cohorts showed evidence of improved survival compared to no treatment; comparatively, radiation alone was associated with survival decrement. Early improvement in survival in adjuvant cohorts was not observed at later time-points. Conclusions: Survival estimates using SEER data suggest an early survival advantage for adjuvant radiotherapy for locoregional EHCC. While future prospective series are needed to confirm these observations, SEER data represents the largest domestic population-based EHCC cohort, and may provide useful baseline survival estimates for future studies. PMID:19637356

  18. Effect of mandibular advancement on the natural position of the head: a preliminary study of 3-dimensional cephalometric analysis.

    PubMed

    Lin, Xiaozhen; Liu, Yanpu; Edwards, Sean P

    2013-10-01

    Our aim was to investigate the potential effect of advancement by bilateral sagittal split osteotomy (BSSO) on the natural position of the head by using 3-dimensional cephalomentric analysis. Seven consecutive patients who had had only BSSO advancement, and had had preoperative and 6-week postoperative cone beam computed tomography (CT) scans, were recruited to this retrospective study. Two variables, SNB and SNC2, were used to indicate the craniomandibular alignment and craniocervical inclination, respectively, in the midsagittal plane. Using 3-dimensional cephalometric analysis software, the SNB and the SNC2 were recorded in volume and measured in the midsagittal plane at 3 independent time-points. The reliability was measured and a paired t test used to assess the significance of differences between the means of SNB and SNC2 before and after operation. The 3-dimensional cephalometric measurement showed good reliability. The SNB was increased as planned in all the mandibles that were advanced, the cervical vertebrae were brought forward after BSSO, and the SNC2 was significantly increased in 6 of the 7 patients. Three-dimensional cephalometric analysis may provide an alternative way of assessing cephalometrics. After BSSO advancement, the natural position of the head changed by increasing the craniocervical inclination in an anteroposterior direction.

  19. Research Studies on Advanced Optical Module/Head Designs for Optical Disk Recording Devices

    NASA Technical Reports Server (NTRS)

    Burke, James J.; Seery, Bernard D.

    1993-01-01

    The Annual Report of the Optical Data Storage Center of the University of Arizona is presented. Summary reports on continuing projects are presented. Research areas include: magneto-optic media, optical heads, and signal processing.

  20. Current treatment options for recurrent/metastatic head and neck cancer: a post-ASCO 2011 update and review of last year's literature.

    PubMed

    Kurzweg, T; Möckelmann, N; Laban, S; Knecht, R

    2012-10-01

    The majority of patients with a squamous cell carcinoma of the head and neck present with locally advanced tumors. The first-line treatment of locally advanced tumor stages consists of a combined modality management. Despite these aggressive protocols, many patients develop locoregional recurrences or metastasis and place particularly high demands on the interdisciplinary treatment team. Treatment with a curative intent must be differentiated from a palliative one. In addition to prior treatment, resectability, age and performance status, patient wishes must be taken into consideration in treatment planning, especially considering that most therapies offer little to no overall survival benefit. Salvage surgery, chemo- and target therapies, and reirradiation are head and neck surgeon's and radiooncologist's weapons in the fight against these strong opponents. This review focuses on publications and meeting news from last year and reviews the current status of the clinical application of each treatment modality in recurrent or metastatic head and neck cancer.

  1. Environmental Loss Characterization of an Advanced Stirling Convertor (ASC-E2) Insulation Package Using a Mock Heater Head

    NASA Technical Reports Server (NTRS)

    Schifer, Nicholas A.; Briggs, Maxwell H.

    2012-01-01

    The U.S. Department of Energy (DOE) and Lockheed Martin Space Systems Company (LMSSC) have been developing the Advanced Stirling Radioisotope Generator (ASRG) for use as a power system for space science missions. This generator would use two highefficiency Advanced Stirling Convertors (ASCs), developed by Sunpower Inc. and NASA Glenn Research Center (GRC). As part of ground testing of these ASCs, different operating conditions are used to simulate expected mission conditions. These conditions require achieving a specified electrical power output for a given net heat input. While electrical power output can be precisely quantified, thermal power input to the Stirling cycle cannot be directly measured. In an effort to improve net heat input predictions, the Mock Heater Head was developed with the same relative thermal paths as a convertor using a conducting rod to represent the Stirling cycle and tested to provide a direct comparison to numerical and empirical models used to predict convertor net heat input. The Mock Heater Head also served as the pathfinder for a higher fidelity version of validation test hardware, known as the Thermal Standard. This paper describes how the Mock Heater Head was tested and utilized to validate a process for the Thermal Standard.

  2. Issues Affecting the Loco-regional and Systemic Management of Patients with Invasive Lobular Carcinoma of the Breast.

    PubMed

    Jacobs, Carmel; Clemons, Mark; Addison, Christina; Robertson, Susan; Arnaout, Angel

    2016-01-01

    Invasive lobular carcinoma (ILC) of the breast is the second most common type of invasive breast carcinoma accounting for 8-14% of all breast cancers. Traditional management of ILC has followed similar paradigms as that for invasive ductal carcinoma (IDC). However, ILC represents a pathologically, clinically and biologically unique variant of breast cancer with particular management challenges. These challenges are seen in both the loco-regional management of ILC; where ILC tumors tend to avoid detection and hence present as more clinically advanced and surgically challenging carcinomas, and the systemic management with a unique response pattern to standard systemic therapies. Because of these challenges, the outcome for patients with ILC has likely lagged behind the continued improvements seen in outcome for patients with IDC. Here, we discuss some of the unique challenges ILC presents and discuss possible management strategies to best overcome the difficulties in the loco-regional and systemic management of patients with ILC.

  3. Current Treatment of Isolated Locoregional Breast Cancer Recurrences.

    PubMed

    Harms, Wolfgang; Geretschläger, Andreas; Cescato, Corinne; Buess, Martin; Köberle, Dieter; Asadpour, Branca

    2015-08-01

    Patients with isolated locoregional breast cancer recurrences should be treated with curative intent. Mastectomy is regarded as the standard of care for patients with ipsilateral breast tumor recurrence. In a selected group of patients, partial breast irradiation after second breast-conserving surgery is a viable alternative to mastectomy. If a second breast conservation is performed, additional irradiation should be mandatory, especially in patients who had not been irradiated previously. In case of re-irradiation, the largest experience exists for multi-catheter brachytherapy. Prospective clinical trials are needed to clearly define selection criteria, long-term local control, and toxicity. In patients with resectable locoregional breast cancer recurrences after mastectomy, multi-modal therapy comprising complete resection, radiation therapy in previously unirradiated patients, and systemic therapy results in 5-year disease-free and overall survival rates of 69% and 88%, respectively. In radiation-naive patients with unresectable, isolated locoregional recurrences, radiation therapy is mandatory. In selected patients with previous irradiations and unresectable locoregional recurrences, a second irradiation as part of an individual treatment concept can be applied. The increased risk of severe toxicity should always be weighed up against the potential clinical benefit. A combination therapy with hyperthermia can further improve the treatment results.

  4. Current Treatment of Isolated Locoregional Breast Cancer Recurrences

    PubMed Central

    Harms, Wolfgang; Geretschläger, Andreas; Cescato, Corinne; Buess, Martin; Köberle, Dieter; Asadpour, Branca

    2015-01-01

    Summary Patients with isolated locoregional breast cancer recurrences should be treated with curative intent. Mastectomy is regarded as the standard of care for patients with ipsilateral breast tumor recurrence. In a selected group of patients, partial breast irradiation after second breast-conserving surgery is a viable alternative to mastectomy. If a second breast conservation is performed, additional irradiation should be mandatory, especially in patients who had not been irradiated previously. In case of re-irradiation, the largest experience exists for multi-catheter brachytherapy. Prospective clinical trials are needed to clearly define selection criteria, long-term local control, and toxicity. In patients with resectable locoregional breast cancer recurrences after mastectomy, multi-modal therapy comprising complete resection, radiation therapy in previously unirradiated patients, and systemic therapy results in 5-year disease-free and overall survival rates of 69% and 88%, respectively. In radiation-naive patients with unresectable, isolated locoregional recurrences, radiation therapy is mandatory. In selected patients with previous irradiations and unresectable locoregional recurrences, a second irradiation as part of an individual treatment concept can be applied. The increased risk of severe toxicity should always be weighed up against the potential clinical benefit. A combination therapy with hyperthermia can further improve the treatment results. PMID:26600763

  5. Functional outcomes and rehabilitation strategies in patients treated with chemoradiotherapy for advanced head and neck cancer: a systematic review.

    PubMed

    van der Molen, Lisette; van Rossum, Maya A; Burkhead, Lori M; Smeele, Ludi E; Hilgers, Frans J M

    2009-06-01

    Organ preservation with radiotherapy and concomitant chemotherapy has become an accepted treatment modality in advanced head and neck cancer. Unfortunately, organ preservation is not synonymous with function preservation. The aim of this review was to systematically assess the effects of the disease and chemoradiotherapy (CRT) on functions such as swallowing, mouth opening, nutrition, pain and quality of life in patients with head and neck cancer. Another aim was to search for (evidence-based) techniques or strategies known to alleviate or rehabilitate the loss of function(s) associated with CRT. Two databases were searched (time period, January 1997 to August 2007) for the terms head and neck cancer, chemotherapy or cisplatin and radiotherapy, and the functional outcomes swallowing, trismus, nutrition, pain and quality of life or a variation of those words. In total, 15 relevant articles were identified that met the inclusion criteria. The majority of the studies that met the criteria focused on the outcomes swallowing, quality of life, and nutrition. Two studies reported on the outcome pain, but no paper reported on the outcome trismus. Only two papers mentioned rehabilitation options, but specific information was lacking. Further long-term prospective research is essential, not only to determine the function impairment caused by the tumor and CRT, but also to assess the effects of known and newly developed rehabilitation measures. Therefore, in September 2006, the Netherlands Cancer Institute started a randomised clinical trial (RCT): Prevention of trismus, swallowing and speech problems in patients treated with chemoradiotherapy for advanced head and neck cancer. This systematic review was carried out to collect the baseline information for the future outcomes of this RCT.

  6. Locally Advanced Stage IV Squamous Cell Carcinoma of the Head and Neck: Impact of Pre-Radiotherapy Hemoglobin Level and Interruptions During Radiotherapy

    SciTech Connect

    Rades, Dirk Stoehr, Monika; Kazic, Nadja; Hakim, Samer G.; Walz, Annette; Schild, Steven E.; Dunst, Juergen

    2008-03-15

    Purpose: Stage IV head and neck cancer patients carry a poor prognosis. Clear understanding of prognostic factors can help to optimize care for the individual patient. This study investigated 11 potential prognostic factors including pre-radiotherapy hemoglobin level and interruptions during radiotherapy for overall survival (OS), metastases-free survival (MFS), and locoregional control (LC) after radiochemotherapy. Methods and Materials: Eleven factors were investigated in 153 patients receiving radiochemotherapy for Stage IV squamous cell head and neck cancer: age, gender, Karnofsky performance score (KPS), tumor site, grading, T stage, N stage, pre-radiotherapy hemoglobin level, surgery, chemotherapy type, and interruptions during radiotherapy >1 week. Results: On multivariate analysis, improved OS was associated with KPS 90-100 (relative risk [RR], 2.36; 95% confidence interval [CI], 1.20-4.93; p = .012), hemoglobin {>=}12 g/dL (RR, 1.88; 95% CI, 1.01-3.53; p = .048), and no radiotherapy interruptions (RR, 2.59; 95% CI, 1.15-5.78; p = .021). Improved LC was significantly associated with lower T stage (RR, 2.17; 95% CI, 1.16-4.63; p = .013), hemoglobin {>=}12 g/dL (RR, 4.12; 95% CI, 1.92-9.09; p < .001), surgery (RR, 2.67; 95% CI, 1.28-5.88; p = .008), and no radiotherapy interruptions (RR, 3.32; 95% CI, 1.26-8.79; p = .015). Improved MFS was associated with KPS 90-100 (RR, 3.41; 95% CI, 1.46-8.85; p = .012). Conclusions: Significant predictors for outcome in Stage IV head and neck cancer were performance status, stage, surgery, pre-radiotherapy hemoglobin level, and interruptions during radiotherapy >1 week. It appears important to avoid anemia and radiotherapy interruptions to achieve the best treatment results.

  7. Local hyperthermia in head and neck cancer: mechanism, application and advance

    PubMed Central

    Ren, Xiaohua; Tang, Yaling; Liang, Xinhua

    2016-01-01

    Local hyperthermia (HT), particularly in conjunction with surgery, radiotherapy and chemotherapy was useful for the treatment of human malignant tumors including head and neck cancer. However, at present it suffered from many limitations such as thermal dose control, target treatment regions and discrimination between healthy and cancer cells. Recent developments in nanotechnology have introduced novel and smart therapeutic nanomaterials to local HT of head and neck cancer that basically take advantage of various targeting approaches. The aim of this paper is to give a brief review of the mechanism, methods and clinical applications of local HT in head and neck cancer, mainly focusing on photothermal therapy (PTT) and nanoparticle-based hyperthermia. PMID:27384678

  8. Thermal domain stability of advanced digital recording (ADR) thin film heads

    NASA Astrophysics Data System (ADS)

    Bijker, M. D.; Draaisma, E. A.; Eisenberg, M.; Toonen, L.

    2002-04-01

    In this paper the thermal domain stability of electroplated Nickel-Iron flux guides is studied. During the thin film deposition process of ADR magnetic heads these magnetic structures are heated up to about 300°C on a few occasions and it is shown that this has a pronounced effect on the stress state of the deposited flux-guide layers. Domain observations are carried out on both NiFe strips of varying widths as well as on as-deposited test structures and annealed NiFe on product level of a data head.

  9. Research Studies on Advanced Optical Module/Head Designs for Optical Data Storage

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Preprints are presented from the recent 1992 Optical Data Storage meeting in San Jose. The papers are divided into the following topical areas: Magneto-optical media (Modeling/design and fabrication/characterization/testing); Optical heads (holographic optical elements); and Optical heads (integrated optics). Some representative titles are as follow: Diffraction analysis and evaluation of several focus and track error detection schemes for magneto-optical disk systems; Proposal for massively parallel data storage system; Transfer function characteristics of super resolving systems; Modeling and measurement of a micro-optic beam deflector; Oxidation processes in magneto-optic and related materials; and A modal analysis of lamellar diffraction gratings in conical mountings.

  10. Advances in understanding of toxicities of treatment for head and neck cancer.

    PubMed

    Logan, Richard M

    2009-10-01

    Toxicities associated with head and neck cancer treatment are common events. Despite the fact that many side effects of cancer treatment are now well controlled, some, such as mucositis and salivary gland hypofunction, continue to be almost inevitable outcomes of cancer treatment. Furthermore, improvements in cancer treatment itself as well as new modalities, such as targeted treatments, may be associated with different toxicities. In this review, common toxicities associated with head and neck cancer treatment will be discussed including those reported to occur with targeted therapies. This review also considers the concept of toxicity clusters, risk factors for toxicity (for example genetics) and individualisation of cancer treatment.

  11. Otolaryngology--head and neck surgery in undergraduate medical education: advances and innovations.

    PubMed

    Fung, Kevin

    2015-02-01

    Medical students graduate with the knowledge and skills to be undifferentiated general physicians. Otolaryngology-head and neck surgery (OtoHNS) is an essential component of primary healthcare, but is disproportionately under-represented in undergraduate medical education (UME). Advances and innovations in educational technology may represent an exciting and creative solution to this important problem. Failure to meet this educational need will result in substantial downstream effects in primary healthcare delivery. The objectives of this study were to 1) demonstrate current deficits in OtoHNS teaching at the UME level; 2) develop, validate, and critically appraise educational innovations that may enrich OtoHNS teaching in medical school curricula; and 3) propose a process for standardization of learning objectives for OtoHNS in UME as it relates to development and deployment of such educational tools. A white paper, prepared as a Triological Society thesis, which consolidates a prospective 10-year investigation of the problem of and potential solutions for under-representation of OtoHNS in UME. Cited datasets include multicenter surveys, cohort studies, and prospective, randomized controlled trials. A series of published and unpublished data were synthesized that addresses the following: 1) the current state of OtoHNS teaching at the UME level with respect to content, volume, structure, and methods; and 2) educational innovations including e-learning and simulation with emphasis on validity and learning effectiveness. Educational innovations specific to postgraduate (residency) training were excluded. Data support the observation that there is uniformly disproportionate under-representation of OtoHNS within UME curricula. Medical school graduates, especially those pursuing primary care specialties, report poor overall comfort levels in managing OtoHNS problems. A series of novel teaching methods were developed and validated using e-learning and simulation

  12. Induction Chemotherapy with Cisplatin and 5-Fluorouracil in Advanced Head and Neck Cancers: A Short Term Response Evaluation

    PubMed Central

    Rao, Raghavendra; Shenoy, Vijendra; Hegde, Mahesh Chandra; Prasad, Vishnu; Prasad, Krishna

    2015-01-01

    Background Considering the uprising number of Head and neck cancer in the state with limited options of medical and surgical treatment, the focus of this study involved on chemotherapy in advanced Head and neck cancers. The aim of this study was to evaluate the efficacy and toxicity of combination of Cisplatin and 5-Fluorouracil (PF) as induction chemotherapy in patients in locally advanced squamous cell cancer of head and neck. Materials and Methods Forty four patients with previously untreated stage III -IV advanced and inoperable cases were included in this prospective study. Induction chemotherapy consisted of 3 cycles of Cisplatin 100mg/mt2 as infusion on day 1, 5-Fluorouracil of 750mg/mt2 on day 2, 5-Fluorouracil of 1000mg/mt2 as infusion on day 3 in an inpatient basis. Cycles were repeated with an interval of 21 days. Patients were evaluated within a period of 3 weeks at the end of completion of third cycle of chemotherapy. Post chemotherapy local therapy was individualized based on the response, site and stage of the tumour. Results Out of 44 eligible and evaluable patients, major dominance was noted in male group constituting 68%. After induction chemotherapy 58.8% of stage III experienced stable response, & 44% had partial response. In stage IV, 44% showed a stable response and 33.3% had partial response. But in comparison to primary tumour response and nodal response, which had a significant clinical response, the overall response of malignancy with respect to stage and site specificity was clinically insignificant. Moderate adverse reaction was noted in 47.6% and 42.1% had mild reactions. Majority of patients experienced grade 3 adverse events, of which anaemia in females and leucopenia in males pre-dominated. Conclusion With the use of cisplatin and 5-FU as induction chemotherapy agents in advanced and inoperable squamous cell carcinoma of head and neck, a distinct benefit was seen in stabilizing the tumour from progression. But achieving a significant

  13. Surgical resection of late solitary locoregional gastric cancer recurrence in stomach bed.

    PubMed

    Watanabe, Masanori; Suzuki, Hideyuki; Maejima, Kentaro; Komine, Osamu; Mizutani, Satoshi; Yoshino, Masanori; Bo, Hideki; Kitayama, Yasuhiko; Uchida, Eiji

    2012-07-01

    Late-onset and solitary recurrence of gastric signet ring cell (SRC) carcinoma is rare. We report a successful surgical resection of late solitary locoregional recurrence after curative gastrectomy for gastric SRC carcinoma. The patient underwent total gastrectomy for advanced gastric carcinoma at age 52. Seven years after the primary operation, he visited us again with sudden onset of abdominal pain and vomiting. We finally decided to perform an operation, based on a diagnosis of colon obstruction due to the recurrence of gastric cancer by clinical findings and instrumental examinations. The laparotomic intra-abdominal findings showed that the recurrent tumor existed in the region surrounded by the left diaphragm, colon of splenic flexure, and pancreas tail. There was no evidence of peritoneal dissemination, and peritoneal lavage fluid cytology was negative. We performed complete resection of the recurrent tumor with partial colectomy, distal pancreatectomy, and partial diaphragmectomy. Histological examination of the resected specimen revealed SRC carcinoma, identical in appearance to the previously resected gastric cancer. We confirmed that the intra-abdominal tumor was a locoregional gastric cancer recurrence in the stomach bed. The patient showed a long-term survival of 27 months after the second operation. In the absence of effective alternative treatment for recurrent gastric carcinoma, surgical options should be pursued, especially for late and solitary recurrence.

  14. Gall bladder carcinoma: Aggressive malignancy with protean loco-regional and distant spread.

    PubMed

    Dwivedi, Amit Nandan Dhar; Jain, Shivi; Dixit, Ruhi

    2015-03-16

    The most common malignancy of biliary tract is gallbladder cancer (GBC) which is the third most common cancer in gastrointestinal tract. It is a lethal disease for most patients in spite of growing awareness and improved diagnostic techniques. GBC has a very poor prognosis and the 5 year survival rate is < 10%. Although etiology of the carcinoma of the gallbladder is still obscure, various factors have been implicated, cholelithiasis being the most frequent. The incidence of GBC worldwide is based on the gender, geography and ethnicity which suggest that both genetic and environmental factors can cause GBC. The major route of spread of gallbladder cancer (GC) is loco-regional rather than distant. It spreads by lymphatic, vascular, neural, intraperitoneal, and intraductal routes. Sonography is usually the most common imaging test to evaluate symptoms of biliary tract disease including suspected GC. With recent advances in imaging modalities like multi-detector computed tomography (CT) scanners, magnetic resonance imaging-positron emission tomography/CT diagnosis of gallbladder cancer has improved. Studies have also targeted molecular and genetic pathways. Treatment options have included extended and radical surgeries and adjuvant chemotherapy. This review article deals in detail with important aspects of carcinoma gallbladder and its manifestations and challenges. Role of various imaging modalities in characterization and accurate staging has been discussed. The loco-regional spread of this aggressive malignancy is dealt explicitly.

  15. [Combined radiochemotherapy in locally advanced nasopharyngeal carcinoma].

    PubMed

    Daniilidis, J; Constantinidis, J; Fountzilas, G

    2001-09-01

    Nasopharyngeal cancer (NPC) is a tumor of epidermoid origin with an entirely different biological behavior than other carcinoma of the head and neck region. A retrospective analysis was performed in 93 cases with locally advanced NPC treated with induction chemotherapy followed by radiation therapy (RT; 79 patients) or concomitant RT and chemotherapy. Totally 66 patients (71%) achieved a complete response (CR), 68% of the patients treated with induction chemotherapy followed by RT, 86% with concomitant chemoradiotherapy. After a median follow-up of 5.5 years 28 out of these 66 relapsed, 25 of them locoregionally. Median time to progression was 22.5 months, median overall survival (OS) 45 months, 5-year actuarial survival was 41.5%. Age, T and N classification, histological type and type of chemotherapy were independent significant factors for OS. Combined chemotherapy and RT in patients with locally advanced NPC result in a high CR rate. The main problem remains the locoregional control. Randomized studies are needed in order to define the optimal use of chemotherapy in combination with RT.

  16. Domain decomposition and matching for time-domain analysis of motions of ships advancing in head sea

    NASA Astrophysics Data System (ADS)

    Tang, Kai; Zhu, Ren-chuan; Miao, Guo-ping; Fan, Ju

    2014-08-01

    A domain decomposition and matching method in the time-domain is outlined for simulating the motions of ships advancing in waves. The flow field is decomposed into inner and outer domains by an imaginary control surface, and the Rankine source method is applied to the inner domain while the transient Green function method is used in the outer domain. Two initial boundary value problems are matched on the control surface. The corresponding numerical codes are developed, and the added masses, wave exciting forces and ship motions advancing in head sea for Series 60 ship and S175 containership, are presented and verified. A good agreement has been obtained when the numerical results are compared with the experimental data and other references. It shows that the present method is more efficient because of the panel discretization only in the inner domain during the numerical calculation, and good numerical stability is proved to avoid divergence problem regarding ships with flare.

  17. Efficacy of External Beam Radiation-Based Treatment plus Locoregional Therapy for Hepatocellular Carcinoma Associated with Portal Vein Tumor Thrombosis

    PubMed Central

    Chen, Ming-Yang; Wang, Yu-Chao; Wu, Tsung-Han; Lee, Chen-Fang; Wu, Ting-Jung; Chou, Hong-Shiue; Tsang, Ngan-Ming; Lee, Wei-Chen

    2016-01-01

    Background. Portal vein tumor thrombosis (PVTT) is a common event in advanced hepatocellular carcinoma (HCC). The optimal treatment for these patients remains controversial. Methods. A retrospective review of 149 patients who had unresectable HCC associated with PVTT between January 2005 and December 2012 was performed. Outcomes related to external beam radiation-based treatment were measured, and clinicopathological features and parameters affecting prognosis were analyzed as well. Results. The radiotherapeutic response of PVTT was an important element that affected the overall treatment response of HCC. Serum α-fetoprotein < 400 ng/mL, the presence of a radiotherapeutic response on PVTT, and receiving additional locoregional therapy were significant prognostic factors affecting the survival of patients. Patients who had received additional locoregional therapy obtained a better outcome, and six of them were eventually able to undergo surgical management with curative intent. Conclusion. The outcome of HCC associated with PVTT remains pessimistic. In addition to the current recommended treatment using sorafenib, a combination of external beam radiotherapy targeting PVTT and locoregional therapy for intrahepatic HCC might be a promising strategy for patients who had unresectable HCC with PVTT. This approach could perhaps offer patients a favorable outcome as well as a possible cure with following surgical management. PMID:27999803

  18. Postoperative radiotherapy for lung cancer: improvement in locoregional control using three-dimensional compared with two-dimensional technique.

    PubMed

    Masson-Côté, Laurence; Couture, Christian; Fortin, André; Dagnault, Anne

    2011-07-01

    To determine whether lung cancer patients treated with three-dimensional (3D) postoperative radiotherapy (PORT) have more favorable outcomes than those treated with two-dimensional (2D) PORT. We retrospectively analyzed the charts of 153 lung cancer patients who underwent PORT with curative intent at our center between 1995 and 2007. The patients were grouped according to the RT technique; 66 patients were in the 2D group and 87 in the 3D group. The outcomes included locoregional control, survival, and secondary effects. All patients were treated using a linear accelerator at a total dose of approximately 50 Gy and 2 Gy/fraction. A few patients (21%) also received chemotherapy. Most tumors were in the advanced stage, either Stage II (30%) or Stage III (65%). The main clinical indications for PORT were positive resection margins (23%) and Stage pN2 (52%) and pN1 (22%). The patient characteristics were comparable in both groups. Kaplan-Meier analysis showed that the 3D technique significantly improved the locoregional control rate at 5 years compared with the 2D technique (81% vs. 56%, p = .007 [Cox]). The 2D technique was associated with a more than twofold increased risk of locoregional recurrence (hazard ratio, 2.7; 95% confidence interval, 1.3-5.5; p = .006). The overall survival rate did not differ at 5 years (38% vs. 20%, p = .3 [Cox]). The toxicities were also similar and acceptable in both groups. The 3D technique for conformal PORT for lung cancer improved the locoregional control rates of patients compared with the 2D technique. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Postoperative Radiotherapy for Lung Cancer: Improvement in Locoregional Control Using Three-Dimensional Compared With Two-Dimensional Technique

    SciTech Connect

    Masson-Cote, Laurence; Couture, Christian; Fortin, Andre; Dagnault, Anne

    2011-07-01

    Purpose: To determine whether lung cancer patients treated with three-dimensional (3D) postoperative radiotherapy (PORT) have more favorable outcomes than those treated with two-dimensional (2D) PORT. Patients and Methods: We retrospectively analyzed the charts of 153 lung cancer patients who underwent PORT with curative intent at our center between 1995 and 2007. The patients were grouped according to the RT technique; 66 patients were in the 2D group and 87 in the 3D group. The outcomes included locoregional control, survival, and secondary effects. All patients were treated using a linear accelerator at a total dose of approximately 50 Gy and 2 Gy/fraction. A few patients (21%) also received chemotherapy. Most tumors were in the advanced stage, either Stage II (30%) or Stage III (65%). The main clinical indications for PORT were positive resection margins (23%) and Stage pN2 (52%) and pN1 (22%). The patient characteristics were comparable in both groups. Results: Kaplan-Meier analysis showed that the 3D technique significantly improved the locoregional control rate at 5 years compared with the 2D technique (81% vs. 56%, p = .007 [Cox]). The 2D technique was associated with a more than twofold increased risk of locoregional recurrence (hazard ratio, 2.7; 95% confidence interval, 1.3-5.5; p = .006). The overall survival rate did not differ at 5 years (38% vs. 20%, p = .3 [Cox]). The toxicities were also similar and acceptable in both groups. Conclusion: The 3D technique for conformal PORT for lung cancer improved the locoregional control rates of patients compared with the 2D technique.

  20. Functional Outcomes of the Retromaxillary-Infratemporal Fossa Dissection for Advanced Head and Neck/Skull Base Lesions

    PubMed Central

    Shibuya, Terry Y.; Doerr, Timothy D.; Mathog, Robert H.; Burgio, Don L.; Meleca, Robert J.; Yoo, George H.; Guthikonda, Murali

    2000-01-01

    The retromaxillary-infratemporal fossa (RM-ITF) dissection, using a preauricular incision, was initially popularized for the treatment of temporomandibular joint disorders, facial fractures, and orbital tumors. This approach has been expanded for the treatment of advanced head and neck and skull base tumors extending into the infratemporal fossa. We studied prospectively eight consecutive patients requiring a RM-ITF dissection. Pre- and postoperative functional outcomes measured were mastication, speech, swallowing, cranial nerve function, pain, and cosmesis. A significant reduction in pain was noted postoperatively in all patients studied. Limited changes were identified in mastication, speech, swallowing, vision, hearing, or cosmesis postoperatively. The RM-ITF dissection should be considered when resecting advanced head and neck/skull base lesions that extend into this region. We have found minimal morbidity associated with this dissection. This procedure may have a useful place in palliation of patients with incurable pain caused by tumor invasion into the infratemporal fossa. ImagesFigure 2Figure 3Figure 4 PMID:17171134

  1. A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas.

    PubMed

    Medina, José Antonio; Rueda, Antonio; de Pasos, Antonio Sacchetti; Contreras, Jorge; Cobo, Manuel; Moreno, Paloma; Benavides, Manuel; Villanueva, Asunción; Alba, Emilio

    2006-04-01

    This phase II study evaluated the efficacy and toxicity of weekly cisplatin along with concomitant boost accelerated radiation regimen in patients with locally advanced unresectable head and neck carcinoma. A total of 94 patients (median age, 58 years) with UICC stage III (n = 19) and IV (n = 75) cancer of the oropharynx, larynx, hypopharynx and oral cavity were included. Patients received radiotherapy with a concomitant boost scheme (1.8 Gy on days 1-40 and 1.5 Gy boost on days 25-40 with a total dose of 72 Gy) and concurrent cisplatin, 40 mg/m(2) weekly, for the first 4 weeks. Most patients (95%) received both radiation and chemotherapy according to protocol. Toxicity was manageable with grade III mucositis and pharyngeal-oesophageal toxicity in 85 and 50% of patients, respectively. Haematological toxicity was mild. Four patients (4%) died due to complications. With a median follow of 41 months, median overall survival and time to progression were 27 and 25 months, respectively. The estimated overall survival at 4 years was 41%. Concomitant boost accelerated radiation plus concurrent weekly cisplatin is a feasible schedule in patients with locally advanced unresectable head and neck carcinoma, with acceptable toxicity and survival data.

  2. Radial Extracorporeal Shock Wave Therapy in a Person With Advanced Osteonecrosis of the Femoral Head.

    PubMed

    Ma, Yue Wen; Jiang, Dong Lei; Zhang, Dai; Wang, Xiao Bei; Yu, Xiao Tong

    2016-09-01

    This case report describes the first patient with avascular necrosis of the femoral head of Association Research Circulation Osseous stage IV, treated with radial extracorporeal shock wave therapy. By contrast, previous studies demonstrated the efficacy of a single treatment of focused extracorporeal shock wave therapy in improving pain and Harris Hip Scale in patients with avascular necrosis of the femoral head of Association Research Circulation Osseous stage I to III. The affected hip was treated with 6000 impulses of radial extracorporeal shock wave therapy at 10 Hz and an intensity ranging from 2.5 to 4.0 bar at 7-day intervals for 24 mos. The Harris Hip Scale values were 33, 43, 56, 77, 81, 88, and 92 at baseline and 1, 3, 6, 12, 18, and 24 mos, respectively. The radiographs showed that the subluxation of the right hip was slightly aggravated. Joint effusion was reduced, bone marrow edema disappeared, the density became more uniform, and the gluteal muscles were more developed based on magnetic resonance imaging. Increased tracer uptake was evident along the joint margin and superolateral aspect of the head both before and after radial extracorporeal shock wave therapy. This case report demonstrates the feasibility of long-term radial extracorporeal shock wave therapy in Association Research Circulation Osseous stage IV patients.

  3. Radial Extracorporeal Shock Wave Therapy in a Person With Advanced Osteonecrosis of the Femoral Head

    PubMed Central

    Ma, Yue Wen; Jiang, Dong Lei; Zhang, Dai; Wang, Xiao Bei; Yu, Xiao Tong

    2016-01-01

    ABSTRACT This case report describes the first patient with avascular necrosis of the femoral head of Association Research Circulation Osseous stage IV, treated with radial extracorporeal shock wave therapy. By contrast, previous studies demonstrated the efficacy of a single treatment of focused extracorporeal shock wave therapy in improving pain and Harris Hip Scale in patients with avascular necrosis of the femoral head of Association Research Circulation Osseous stage I to III. The affected hip was treated with 6000 impulses of radial extracorporeal shock wave therapy at 10 Hz and an intensity ranging from 2.5 to 4.0 bar at 7-day intervals for 24 mos. The Harris Hip Scale values were 33, 43, 56, 77, 81, 88, and 92 at baseline and 1, 3, 6, 12, 18, and 24 mos, respectively. The radiographs showed that the subluxation of the right hip was slightly aggravated. Joint effusion was reduced, bone marrow edema disappeared, the density became more uniform, and the gluteal muscles were more developed based on magnetic resonance imaging. Increased tracer uptake was evident along the joint margin and superolateral aspect of the head both before and after radial extracorporeal shock wave therapy. This case report demonstrates the feasibility of long-term radial extracorporeal shock wave therapy in Association Research Circulation Osseous stage IV patients. PMID:27003206

  4. Voice outcomes after concurrent chemoradiotherapy for advanced nonlaryngeal head and neck cancer: a prospective study.

    PubMed

    Paleri, Vinidh; Carding, Paul; Chatterjee, Sanjoy; Kelly, Charles; Wilson, Janet Ann; Welch, Andrew; Drinnan, Michael

    2012-12-01

    The voice impact of treatment for nonlaryngeal head and neck primary sites remains unknown. We conducted a prospective study of a consecutive sample of patients undergoing chemoradiation for nonlaryngeal head and neck cancer. The Voice Symptom Scale (VoiSS) was completed, and voice recordings were made at 3 time-points. Of 42 recruited patients, 34 completed the measures before and in the early posttreatment phase (mean 16.5 weeks), while 21 patients were assessed at the final time-point (mean, 20.4 months). VoiSS scores showed statistically significant progressive deterioration in the total score (p = .02) and impairment subscale (p < .0001) through to the final assessment. Acoustic measures and perceptual ratings deteriorated significantly (p < .001) in the early posttreatment weeks and improved at the final assessment, but not to the baseline. Interrater agreement was excellent for expert measures. To the best of our knowledge, this is the first prospective study to show that chemoradiation therapy for nonlaryngeal head and neck cancer has a significant effect on the patients' self-reported voice quality, even in the long term. Copyright © 2012 Wiley Periodicals, Inc.

  5. Distant metastases in head and neck cancer.

    PubMed

    Duprez, Fréderic; Berwouts, Dieter; De Neve, Wilfried; Bonte, Katrien; Boterberg, Tom; Deron, Philippe; Huvenne, Wouter; Rottey, Sylvie; Mareel, Marc

    2017-09-01

    Most trials in head and neck cancer emphasize locoregional control, as this is the main pattern of therapy failure. However, up to 15% of patients develop distant metastases. The purpose of this study was to present the investigated factors associated with distant metastasis in a single-center patient cohort. A retrospective analysis of a single-center patient cohort over an 18-year period has been performed. We report on prevalence and incidence of distant metastasis, timing in relation to locoregional failure, Kaplan-Meier analysis for actuarial distant control rates, and univariate analysis taking into account histological, etiologic, surgical, site-dependent, stage-dependent characteristics, modality of primary therapy, and locoregional control. Of 1022 patients, 141 (13.8%) were diagnosed with distant metastases involving 283 sites. Actuarial rates of distant control were 88%, 84%, 80%, and 79% at 1, 2, 5, and 10 years, respectively. Factors associated with distant metastasis are stage grouping and regional node positivity, extranodal extension, locoregional residual disease, and human papillomavirus (HPV) negative status in oropharyngeal squamous cell carcinoma. Distant metastases in head and neck cancer led to dismal prognosis. Factors associated with distant metastasis are related to characteristics of the primary tumor. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1733-1743, 2017. © 2017 Wiley Periodicals, Inc.

  6. Role of hypofractionated radiotherapy in breast locoregional radiation.

    PubMed

    Caudrelier, J-M; Truong, P T

    2015-06-01

    Long-term results of randomised trials have confirmed the safety and efficacy of hypofractionated radiotherapy using approximately 2.6 Gy per fraction to lower total doses of 40-42.6 Gy delivered over 3 weeks, for postoperative treatment of early breast cancer. In these trials, hypofractionated radiotherapy was predominantly used for breast only treatment, while there are fewer trials that specifically examined hypofractionated radiotherapy to the breast plus regional nodes. Hypofractionated locoregional radiation is considered a standard of care in the United Kingdom and in some parts of Canada. We aim to review the radiobiology and normal tissue effects of hypofractionated locoregional radiation and to summarize available published clinical experiences using this treatment strategy as adjuvant therapy after breast conserving surgery or mastectomy for women with early breast cancer.

  7. [Loco-regional anesthesia in minor surgery of the breast].

    PubMed

    Luchini, L; Marchesi, P; Arcidiacono, G; Cecchini, G M; Barbara, E; Amadori, C

    1990-01-01

    Breast minor surgical operations, either demolitive or reconstructive, are more frequently effected by day-hospital modalities, to obviate to room scarcity and to meet patients requirements. Several patients, due to age or to concomitant pathologies, show risks caused by premature dismissal after having general anaesthesia. This problem led Authors to find an alternative loco-regional anaesthesia. Good results encouraged them to extend this method.

  8. Decreasing loco-regional recurrence for oral cavity cancer with total Mohs margins technique.

    PubMed

    Bergeron, Mathieu; Gauthier, Pierre; Audet, Nathalie

    2016-12-01

    The conventional technique for cancer resection margin analysis studies only 0.1% of the surgical margins. Complete frozen section margins - also known as Mohs margins - allows for analysis of 100% of the surgical margins. The objective of our study is to compare oral cavity cancer loco-regional recurrence rates when treated by total frozen sections technique (Total Mohs margins) versus conventional margins. We conducted a multicenter retrospective cohort chart review. Loco-regional oral cancer recurrence rates were compared between patients treated with total Mohs margins (2007-2013) and patients treated with conventional margins techniques (2002-2007). After applying inclusion criteria, a total of 60 patients treated by total Mohs margins and 57 patients with conventional margins were identified. Patients had similar baseline cancer stages, pathological types, past head and neck cancers and comorbidities (all p > 0.05). One-year recurrence rate was lower (10.0% vs 21.1%, p = 0.019) in favor of Mohs total margins and stayed significantly lower at 5 years of follow-up. When adjusted for T grade with N0 disease, Mohs technique was still beneficial in loco-regional recurrence for Tis-T4N0 up to 2 years (10.5% vs 25.7%, z-score 1.849, p = 0.032). The Number Needed to Treat at 2 years of follow-up for this subgroup of patients (Tis-T4N0) is 6.6. Margins had to be retaken more often intra-operatively in Mohs technique (68.3% vs 12.3%, p < 0.0001), mainly for positive deep margins (48.6% of all margins, p = 0.028). Duration of surgery was not increased with Mohs vs conventional technique (380 min vs 475 min respectively, p = 0.025). Mohs total margins may result in a significant reduction in cancer recurrence rate at 5 years compare to conventional surgery. Moreover, duration of surgery was not increased when using Mohs technique when judiciously performed.

  9. Definitive chemoradiotherapy with carboplatin for squamous cell carcinoma of the head and neck.

    PubMed

    Nagasaka, Misako; Zaki, Mark; Issa, Majd; Kim, Harold; Abrams, Judith; Sukari, Ammar

    2017-10-01

    Definitive concurrent chemoradiotherapy (CRT) is considered the standard of care for organ preservation and is the only potentially curative therapy for surgically unresectable patients with stage III to IVb locally advanced squamous cell carcinoma of the head and neck. In patients with high risks for adverse events utilizing cisplatin, carboplatin has been empirically substituted. The objective of this study was to estimate the locoregional control rate, progression-free survival, overall survival, and adverse events in locally advanced squamous cell carcinoma of the head and neck patients treated with CRT utilizing carboplatin. A retrospective single-arm analysis. Data on consecutive patients who fit the eligibility criteria were collected. Eligible patients were treated with 70 Gy of radiation therapy and at least two cycles of carboplatin (area of curve [AUC] of 5 between January 2007 to December 2013. Fifty-four patients were identified. Overall locoregional control rate was 50% (95% confidence interval [CI] 37%-63%). Median progression-free and overall survival were 21 (CI 11-33) and 40 (CI 33-NA) months, respectively. One-, 3-, and 5-year overall survival were 81% (CI 67%-89%), 59% (CI 41%-73%), and 42% (CI 22%-61%), respectively. Stage III/IVa patients (n = 45) had a median survival of 62 (CI 37-NA months) and 3 years of 71% (CI 53%-84%), whereas stage IVb (n = 9) had a median survival of 31 (CI 4-NA) months and none survived to 3 years. Definitive CRT with carboplatin for locally advanced squamous cell carcinoma of the head and neck was well tolerated and demonstrated comparable results to CRT with cisplatin. 4. Laryngoscope, 127:2260-2264, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  10. Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel: a subset analysis of EORTC 24971 study.

    PubMed

    Psyrri, A; Fortpied, C; Koutsodontis, G; Avgeris, M; Kroupis, C; Goutas, N; Menis, J; Herman, L; Giurgea, L; Remenár, É; Degardin, M; Pateras, I S; Langendijk, J A; van Herpen, C M L; Awada, A; Germà-Lluch, J R; Kienzer, H R; Licitra, L; Vermorken, J B

    2017-09-01

    EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF (docetaxel, cisplatin, 5-fluorouracil) over PF (cisplatin/5-fluorouracil), in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable head and neck squamous cell carcinomas. We conducted a retrospective analysis of prospectively collected data aiming to evaluate whether only HPV(-) patients (pts) benefit from adding docetaxel to PF, in which case deintensifying induction treatment in HPV(+) pts could be considered. Pretherapy tumor biopsies (blocks or slides) were assessed for high-risk HPV by p16 immunohistochemistry, PCR and quantitative PCR. HPV-DNA+ and/or p16+ tumors were subjected to in situ hybridization (ISH) and HPV E6 oncogene expression qRT-PCR analysis. Primary and secondary objectives were to evaluate the value of HPV/p16 status as predictive factor of treatment benefit in terms of PFS and OS. The predictive effect was analyzed based on the model used in the primary analysis of the study with the addition of a treatment by marker interaction term and tested at two-sided 5% significance level. Of 358, 119 pts had available tumor samples and 58 of them had oropharyngeal cancer. Median follow-up was 8.7 years. Sixteen of 119 (14%) evaluable samples were p16+ and 20 of 79 (25%) evaluable tumors were HPV-DNA+. 13 of 40 pts (33%) assessed with HPV-DNA ISH and 12 of 28 pts (43%) assessed for HPV E6 mRNA were positive. The preplanned analysis showed no statistical evidence of predictive value of HPV/p16 status for PFS (P = 0.287) or OS (P = 0.118). The incidence of HPV positivity was low in the subset of EORTC 24971 pts analyzed. In this analysis only powered to detect a large treatment by marker interaction, there was no statistical evidence that treatment effect found overall was different in magnitude in HPV(+) or HPV(-) pts. These results do not justify selection of TPF versus PF according to HPV status.

  11. Emerging strategies for the early detection and prevention of head and neck squamous cell cancer.

    PubMed

    Dasgupta, Santanu; Dash, Rupesh; Das, Swadesh K; Sarkar, Devanand; Fisher, Paul B

    2012-02-01

    Despite significant improvements in therapeutic protocols, head and neck squamous cell carcinoma (HNSCC) remains a major health problem worldwide. The 5-year post-therapeutic survival rate is among the lowest of the major cancers with loco-regional relapse being the main cause of death. Moreover, in most instances, the quality of life of the afflicted patient is severely compromised. The poor prognosis for HNSCC is primarily due to disease detection at advanced stages. Accordingly, development of early detection and preventive strategies are essential. Recent advances in our understanding of the molecular biology and etiology of HNSCC should facilitate development of improved intervention and therapeutic approaches. The present review discusses the potential role of such factors for developing preventive and early diagnostic strategies for HNSCC management.

  12. Ultrahigh head pump/turbine development program: Volume 2, Advanced design, hydraulic and mechanical: Final report

    SciTech Connect

    Yokoyama, T.

    1987-01-01

    This report presents details of the process and the results of Task 2, Advanced Design. This task includes all the theoretical studies, detailed designs of components, and evaluations of method and materials that result in a complete ready-to-build design. The design drawings and assessments of manufacturability and reliability are included.

  13. Parenteral Nutrition for Patients Treated for Locally Advanced Inoperable Tumors of the Head and Neck

    ClinicalTrials.gov

    2017-09-08

    Squamous Cell Carcinoma of the Hypopharynx Stage III; Squamous Cell Carcinoma of the Hypopharynx Stage IV; Laryngeal Squamous Cell Carcinoma Stage III; Laryngeal Squamous Cell Carcinoma Stage IV; Oropharyngeal Squamous Cell Carcinoma Stage III; Oropharyngeal Squamous Cell Carcinoma Stage IV; Squamous Cell Carcinoma of the Oral Cavity Stage III; Squamous Cell Carcinoma of the Oral Cavity Stage IV; Locally Advanced Malignant Neoplasm

  14. Accelerated Aging in Glaucoma: Immunohistochemical Assessment of Advanced Glycation End Products in the Human Retina and Optic Nerve Head

    PubMed Central

    Tezel, Gülgün; Luo, Cheng; Yang, Xiangjun

    2008-01-01

    PURPOSE This study aimed to determine the association between advanced glycation end products (AGEs) and glaucoma based on the known synergism between oxidative stress with AGEs and the evidence of oxidative stress during glaucomatous neurodegeneration. METHODS The extent and cellular localization of immunolabeling for AGEs and their receptor, RAGE, were determined in histologic sections of the retina and optic nerve head obtained from 38 donor eyes with glaucoma and 30 eyes from age-matched donors without glaucoma. RESULTS The extent of AGE and RAGE immunolabeling was greater in older than in younger donor eyes. However, compared with age-matched controls, an enhanced accumulation of AGEs and an up-regulation of RAGE were detectable in the glaucomatous retina and optic nerve head. Although some retinal ganglion cells (RGCs) and glia exhibited intracellular immunolabeling for AGEs, increased AGE immunolabeling in glaucomatous eyes was predominantly extracellular and included laminar cribriform plates in the optic nerve head. Some RAGE immunolabeling was detectable on RGCs; however, increased RAGE immunolabeling in glaucomatous eyes was predominant on glial cells, primarily Müller cells. CONCLUSIONS Given that the generation of AGEs is an age-dependent event, increased AGE accumulation in glaucomatous tissues supports that an accelerated aging process accompanies neurodegeneration in glaucomatous eyes. One of the potential consequences of AGE accumulation in glaucomatous eyes appears to be its contribution to increased rigidity of the lamina cribrosa. The presence of RAGE on RGCs and glia also makes them susceptible to AGE-mediated events through receptor-mediated signaling, which may promote cell death or dysfunction during glaucomatous neurodegeneration. PMID:17325164

  15. Long-Term Outcomes and Toxicity of Concurrent Paclitaxel and Radiotherapy for Locally Advanced Head-and-Neck Cancer

    SciTech Connect

    Citrin, Deborah Mansueti, John; Likhacheva, Anna; Sciuto, Linda; Albert, Paul S.; Rudy, Susan F.; Cooley-Zgela, Theresa; Cotrim, Ana; Solomon, Beth; Colevas, A. Dimitrios; Russo, Angelo; Morris, John C.; Herscher, Laurie; Smith, Sharon

    2009-07-15

    Purpose: To report the long-term outcomes and toxicity of a regimen of infusion paclitaxel delivered concurrently with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck. Patients and Methods: Between 1995 and 1999, 35 patients with nonmetastatic, Stage III or IV squamous cell carcinoma of the head and neck were treated with three cycles of paclitaxel as a 120-h continuous infusion beginning on Days 1, 21, and 42, concurrent with radiotherapy. The initial 16 patients received 105 mg/m{sup 2}/cycle, and the subsequent 19 patients received 120 mg/m{sup 2}/cycle. External beam radiotherapy was delivered to a dose of 70.2-72 Gy at five fractions weekly. Patients were followed to evaluate the disease outcomes and late toxicity of this regimen. Results: The median follow-up for all patients was 56.5 months. The median survival was 56.5 months, and the median time to local recurrence was not reached. Of the 35 patients, 15 (43%) developed hypothyroidism. Of the 33 patients who underwent percutaneous endoscopic gastrostomy tube placement, 11 were percutaneous endoscopic gastrostomy tube dependent until death or their last follow-up visit. Also, 5 patients (14%) required a tracheostomy until death, and 3 (9%) developed a severe esophageal stricture. All evaluated long-term survivors exhibited salivary hypofunction. Fibrosis in the radiation field occurred in 24 patients (69%). Conclusion: The results of our study have shown that concurrent chemoradiotherapy with a 120-h infusion of paclitaxel provides long-term local control and survival in patients with squamous cell carcinoma of the head and neck. Xerostomia, hypothyroidism, esophageal and pharyngeal complications, and subcutaneous fibrosis were common long-term toxicities; however, the vast majority of toxicities were grade 1 or 2.

  16. Recent Advances in Biomarkers and Potential Targeted Therapies in Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Yavrouian, Eric J.; Sinha, Uttam K.

    2012-01-01

    Head and neck squamous cell carcinoma (HNSCC) is a devastating tumor of the upper aerodigestive tract with no significant change in treatment modality or improvement in survival over the last several decades. Biomarkers are important biological molecules that can be utilized in tumor detection, prognosis, and as targeted therapies. There are several important biomarkers and potential targets in the forefront, including biomarkers of tumorigenesis, signal transduction molecules, proteins involved in angiogenesis, and oncogenic viruses. The clinical applications of these biomarkers are in various states from in vitro and in vivo models, phase II and III clinical trials, to accepted modes of treatment in patients with HNSCC. Given the potential improvement in prognosis that biomarkers and their targeted therapies may have on the treatment of HNSCC, their investigation is both important and essential. PMID:22523710

  17. Classification of locoregional lymph nodes in medullary and papillary thyroid cancer.

    PubMed

    Musholt, T J

    2014-02-01

    Among the various thyroid malignancies, medullary and papillary thyroid carcinomas are characterized by predominant locoregional lymph node metastases that may cause morbidity and affect patient survival. Although lymph node metastases are frequently detected, the optimal strategy aiming at the removal of all tumor tissues while minimizing the associated surgical morbidity remains a matter of debate. A uniform consented terminology and classification is a precondition in order to compare results of the surgical treatment of thyroid carcinomas. While the broad distinction between central and lateral lymph node groups is generally accepted, the exact boundaries of these neck regions vary significantly in the literature. Four different classification systems are currently used. The classification system of the American Head and Neck Society and the corresponding classification system of the Union for International Cancer Control (UICC) are based on observations of squamous cell carcinomas and appointed to needs of head and neck surgeons. The classification of the Japanese Society for Thyroid Diseases and the compartment classification acknowledge the distinctive pattern of metastasis in thyroid carcinomas. Comparison of four existing classification systems reveals underlying different treatment concepts. The compartment system meets the necessities of thyroid carcinomas and is used worldwide in studies describing the results of lymph node dissection. Therefore, the German Association of Endocrine Surgery has recommended using the latter system in their recently updated guidelines on thyroid carcinoma.

  18. Advancement of thyroid surgery video recording: A comparison between two full HD head mounted video cameras.

    PubMed

    Ortensi, Andrea; Panunzi, Andrea; Trombetta, Silvia; Cattaneo, Alberto; Sorrenti, Salvatore; D'Orazi, Valerio

    2017-05-01

    The aim of this study was to test two different video cameras and recording systems used in thyroid surgery in our Department. This is meant to be an attempt to record the real point of view of the magnified vision of surgeon, so as to make the viewer aware of the difference with the naked eye vision. In this retrospective study, we recorded and compared twenty thyroidectomies performed using loupes magnification and microsurgical technique: ten were recorded with GoPro(®) 4 Session action cam (commercially available) and ten with our new prototype of head mounted video camera. Settings were selected before surgery for both cameras. The recording time is about from 1 to 2 h for GoPro(®) and from 3 to 5 h for our prototype. The average time of preparation to fit the camera on the surgeon's head and set the functionality is about 5 min for GoPro(®) and 7-8 min for the prototype, mostly due to HDMI wiring cable. Videos recorded with the prototype require no further editing, which is mandatory for videos recorded with GoPro(®) to highlight the surgical details. the present study showed that our prototype of video camera, compared with GoPro(®) 4 Session, guarantees best results in terms of surgical video recording quality, provides to the viewer the exact perspective of the microsurgeon and shows accurately his magnified view through the loupes in thyroid surgery. These recordings are surgical aids for teaching and education and might be a method of self-analysis of surgical technique. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  19. Ifosfamide and mesna for the treatment of advanced squamous cell head and neck cancer. A GETLAC study.

    PubMed

    Cervellino, J C; Araujo, C E; Pirisi, C; Francia, A; Cerruti, R

    1991-01-01

    High-dose ifosfamide/mesna was administrated to 28 mostly pretreated patients with locally advanced and metastatic head and neck cancer who failed conventional surgery/radiation treatment. Primary sites include tongue (5), salivary gland (3), floor of mouth (5), oropharynx (2), hypopharynx (5) and larynx (8). The dose and schedule of ifosfamide (IF) was 3.5 g/m2 8 h, i.v. infusion, days 1-5, every 28 days, and mesna was given as 20% of IF dose intravenous bolus injection at 0, 2, 4, 6 and 8 h; mesna 40% of IF dose was given by oral route at 10 and 12 h, days 1-5, every 28 days. All patients were evaluable for both toxicity and response. 14 patients had received prior treatment with surgery plus radiation therapy and 14 patients radiation therapy. Following chemotherapy, 4 patients (14.2%) achieved complete remission and 8 patients (28.5%) achieved partial remission, with an overall response rate of 42.7%. Toxicity was reported for 186 cycles and ranged from mild to moderate: anemia 4, leukopenia 6, thrombopenia 1, nausea and vomiting 12, alopecia 28, microscopic hematuria 3, increased transaminase 1. No CNS symptoms and renal toxicity were registered. Median duration of survival is 11+ months (range 3+ to 18+ months). Nine patients died. We conclude that ifosfamide/mesna at this dose and schedule has a significant activity in recurrent head and neck cancer, and produces minimal toxicity.

  20. A phase II study using vinorelbine and continuous 5-fluorouracil in patients with advanced head and neck cancer.

    PubMed

    Larsen, Susanne; Serup-Hansen, Eva; Andersen, Lisbeth J; Lindeløv, Birgit; McCulloch, Tine; Adimi, Parvin; Bastholt, Lars

    2007-01-01

    Seventy patients with advanced head and neck cancer were treated with vinorelbine and continuous 5-FU administered in a central venous catheter. Over all response was 36% with 9% complete responses. The most common grade 3 and 4 toxicities were stomatitis (13), infection (5), pain related to vinorelbine infusion (4), skin toxicity (3). Thirty one patients had grade 3 or 4 leukopenia. Treatment was complicated by venous thrombosis in the central venous catheter in one case. A majority of patients experienced dose reduction of one or both drugs or treatment delays due to toxicity. Median time to progression was 4.7 months and overall median survival 6.6 months. We conclude that the regimen is feasible and tolerated with moderate toxicity. Response rates and time to progression are comparable to other studies with multi agent treatment.

  1. Practical Considerations in the Re-Irradiation of Recurrent and Second Primary Head-and-Neck Cancer: Who, Why, How, and How Much?

    SciTech Connect

    Chen, Allen M.; Phillips, Theodore L.; Lee, Nancy Y.

    2011-12-01

    Despite progress in surgical and reconstructive techniques, as well as advances in radiotherapy delivery methods, a significant proportion of patients irradiated for head-and-neck cancer develop locoregional recurrence. These patients are also at high risk of developing new second primary cancers of the head and neck. Because of the heterogeneity of this population with respect to disease-related and patient-related factors, such as previous treatment, tumor recurrence site, disease extent, and performance status, the optimal treatment of locoregionally recurrent or second primary cancers of the head and neck remains to be defined. Although surgical resection typically constitutes the mainstay of treatment, effective salvage therapy is often precluded by anatomic inaccessibility and the risk of perioperative complications. Although chemotherapy alone has traditionally been considered an alternative to surgery, the response rates have been poor, with nearly all patients dying of disease progression within months. Similarly, salvage therapy using re-irradiation has historically been avoided because of concerns regarding toxicity. Although the results of more recent studies using contemporary treatment techniques and conformal delivery methods have been somewhat more promising, the role of re-irradiation after previous full-course radiotherapy is still considered investigational by many. Numerous questions remain unanswered, and practical guidelines for clinical decision-making are sparse.

  2. Intensity modulated perioperative HDR brachytherapy for recurrent and/or advanced head and neck metastases.

    PubMed

    Teudt, Ingo U; Kovàcs, György; Ritter, Matthias; Melchert, Corinna; Soror, Tamer; Wollenberg, Barbara; Meyer, Jens E

    2016-09-01

    Recurrent neck metastases following surgery and full dose adjuvant radiotherapy of squamous cell head and neck cancer remain a clinical challenge. After revision neck dissection and chemotherapy re-irradiation dosage is often limited and survival prognosis deteriorates. Here, adjuvant high-dose rate intensity modulated perioperative brachytherapy (HDR IMBT) offers a second full radiation dose with a limited volume of normal tissue radiation in the neck. In this retrospective study patients were identified who underwent revision surgery and perioperative HDR IMBT for recurrent neck metastases. Survival rates were estimated and the scarce literature on interstitial brachytherapy of the neck was reviewed. From 2006 to 2014, nine patients were treated for recurrent or palliative neck metastases using salvage surgery and HDR IMBT. Eight patients received previous surgery and external beam radiotherapy with or without chemotherapy. Two and five year overall survival was calculated to be 78 and 67 %, respectively. HDR IMBT is a salvage treatment option for selected cases in the neck following surgical revision or last-line treatment strategies. In the literature and this small cohort radiation toxicity and the risk of "carotid blow-out" seemed to be low.

  3. Treatment Outcomes of Patients with Locally Advanced Synchronous Esophageal and Head/Neck Squamous Cell Carcinoma Receiving Curative Concurrent Chemoradiotherapy

    PubMed Central

    Chen, Yen-Hao; Lu, Hung-I.; Chien, Chih-Yen; Lo, Chien-Ming; Wang, Yu-Ming; Chou, Shang-Yu; Su, Yan-Ye; Shih, Li-Hsueh; Li, Shau-Hsuan

    2017-01-01

    The present study investigated clinical outcomes and prognostic factors of patients with locally advanced synchronous esophageal squamous cell carcinoma (ESCC) and head/neck squamous cell carcinoma (HNSCC) receiving curative concurrent chemoradiotherapy (CCRT), and determined whether synchronous ESCC/HNSCC patients had worse prognosis compared to isolated ESCC patients. Using propensity score matching method, we compared 60 locally advanced synchronous ESCC/HNSCC patients with 60 matched isolated ESCC patients. Compared to 60 matched isolated ESCC patients, synchronous ESCC/HNSCC patients had significantly worse prognosis (13.5 months versus 17.2 months, P = 0.01), more grade 3–4 CCRT toxicity, and higher percentage of CCRT interruption. For synchronous ESCC/HNSCC group, the 1-year and 2-year survival rates were 52% and 13%, respectively. Univariate analysis showed that early ESCC stage, non-T4b disease, and salvage operations were significantly associated with superior survival. In multivariate analysis, ESCC stage represented an independent prognosticator. For chemotherapy regimen during CCRT, cisplatin/5-fluorouracil had significantly more grade 3–4 mucositis/esophagitis and neutropenia than weekly cisplatin. In conclusion, synchronous ESCC/HNSCC patients receiving curative CCRT have worse prognosis and poorer compliance of CCRT compared to isolated ESCC patients. For these patients, ESCC stage and T4b disease were significantly associated with clinical outcomes, and salvage operation may improve overall survival. PMID:28134308

  4. Sequential chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil in patients with locally advanced head and neck cancer.

    PubMed

    Janinis, J; Papadakou, M; Panagos, G; Panousaki, A; Georgoulias, V; Hatzidaki, D; Lefantzis, D; Dokianakis, G

    2001-06-01

    The purpose of this phase II trial was to evaluate the toxicity of a sequential chemoradiotherapy approach using docetaxel, cisplatin, and 5-fluorouracil (5-FU) (DCF) with granulocyte colony-stimulating factor support in previously untreated patients with locally advanced head and neck cancer (HNC). Secondary endpoints included preliminary assessment of response. Patients with locally advanced HNC, a World Health Organization performance status 0 to 2, and no prior history of chemotherapy or radiotherapy were included. Treatment consisted of docetaxel 80 mg/m2 (1-hour infusion) on day 1, cisplatin 40 mg/m2 (1-hour infusion) on days 2 and 3, and 5-fluorouracil 1,000 mg/m2 (24-hour continuous infusion), on days 1 to 3, repeated every 28 days for a maximum of 4 cycles per patient. All patients received granulocyte colony stimulating factors subcutaneously between days 4 and 9. Radiation therapy (RT) to the primary tumor site and neck lymph nodes was planned within 5 weeks of the last cycle of chemotherapy. The primary tumor site received 60 to 70 Gy. Twenty patients (median age 56 years, range: 40-72 years) received a total of 60 cycles of DCF. The median number of cycles was 3 (range: 1-4 cycles). All patients were evaluable for toxicity and response. The most common acute nonhematologic toxicities from DCF induction chemotherapy included alopecia, mucositis, peripheral sensory neuropathy, onycholysis, and asthenia. Febrile neutropenia developed in two patients and grade IV diarrhea in one patient. There were no treatment-related deaths. The overall response rate (RR) after DCF induction chemotherapy was 90% (95% confidence interval [CI]: 76.8-103.1%). After the completion of RT, the overall RR was 95% with a complete response rate of 73% (95% CI: 49.9-90.1%). Organ preservation was achieved in eight patients with laryngeal cancer and one patient with base of tongue involvement. After a median follow-up of 36 months (range: 5-43 months) the median disease-free and

  5. Intraoperative radiation therapy (IORT) in head and neck cancer

    PubMed Central

    Kyrgias, George; Hajiioannou, Jiannis; Tolia, Maria; Kouloulias, Vassilios; Lachanas, Vasileios; Skoulakis, Charalambos; Skarlatos, Ioannis; Rapidis, Alexandros; Bizakis, Ioannis

    2016-01-01

    Abstract Background: Multimodality therapy constitutes the standard treatment of advanced and recurrent head and neck cancer. Since locoregional recurrence comprises a major obstacle in attaining cure, the role of intraoperative radiation therapy (IORT) as an add-on in improving survival and local control of the disease has been investigated. IORT allows delivery of a single tumoricidal dose of radiation to areas of potential residual microscopic disease while minimizing doses to normal tissues. Advantages of IORT include the conformal delivery of a large dose of radiation in an exposed and precisely defined tumor bed, minimizing the risk of a geographic miss creating the potential for subsequent dose reduction of external beam radiation therapy (EBRT). This strategy allows for shortening overall treatment time and dose escalation. The aim of this review is to summarize recent published work on the use of IORT as an adjuvant modality to treat common head and neck cancer in the primary or recurrent setting. Methods: We searched the Medline, Scopus, Ovid, Cochrane, Embase, and ISI Web of Science databases for articles published from 1980 up to March 2016. Results: Based on relevant publications it appears that including IORT in the multimodal treatment may contribute to improved local control. However, the benefit in overall survival is not so clear. Conclusion: IORT seems to be a safe, promising adjunct in the management of head and neck cancer and yet further well organized clinical trials are required to determine its role more precisely. PMID:27977569

  6. Locoregional small cell carcinoma of the bladder: clinical characteristics and treatment patterns.

    PubMed

    Patel, Sanjay G; Stimson, C J; Zaid, Harras B; Resnick, Matthew J; Cookson, Michael S; Barocas, Daniel A; Chang, Sam S

    2014-02-01

    Because small cell carcinoma of the bladder is a relatively rare tumor type, literature about its treatment remains limited. We determined patterns of care and survival after treatment in what is to our knowledge the largest series to date of patients with locoregional small cell carcinoma of the bladder. We identified patients with localized/locally advanced (cTis-cT4, cN0 or cM0) bladder small cell carcinoma diagnosed between 1998 and 2010 from the National Cancer Database (NCDB). Treatment was categorized as bladder preservation therapy, radical cystectomy alone, bladder preservation therapy with multimodal treatment or radical cystectomy plus multimodal treatment. We performed Kaplan-Meier overall survival analysis to evaluate differential survival between treatment groups. A total of 625 patients met study inclusion criteria. Median age at diagnosis was 73 years (range 36 to 90) and 65% of patients presented with cT2 disease. Patients were treated with bladder preservation therapy (174 or 27.8%), bladder preservation therapy plus multimodal treatment (333 or 53.3%), radical cystectomy alone (46 or 7.4%) and radical cystectomy plus multimodal treatment (72 or 11.5%) with a 3-year overall survival rate of 23% (95% CI 15-32), 35% (95% CI 30-45), 38% (95% CI 17-60) and 30.1% (95% CI 16-47), respectively. Overall survival was most favorable for radical cystectomy alone plus neoadjuvant chemotherapy with a 3-year rate of 53% (95% CI 19-79). In the United States locoregional small cell carcinoma of the bladder develops predominantly in white males, in whom treatment is performed at metropolitan, comprehensive community cancer centers. Most patients were treated with bladder preservation therapy and most received multimodal therapy. Patients who received neoadjuvant chemotherapy followed by radical cystectomy had the most favorable survival. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  7. Salvage reirradiation for locoregional failure after radiation therapy for prostate cancer: who, when, where and how?

    PubMed

    Créhange, G; Roach, M; Martin, E; Cormier, L; Peiffert, D; Cochet, A; Chapet, O; Supiot, S; Cosset, J-M; Bolla, M; Chung, H T

    2014-10-01

    Even in the current era of dose-escalated radiotherapy for prostate cancer, biochemical recurrence is not uncommon. Furthermore, biochemical failure is not specific to the site of recurrence. One of the major challenges in the management of prostate cancer patients with biochemical failure after radiotherapy is the early discrimination between those with locoregional recurrence only and those with metastatic disease. While the latter are generally considered incurable, patients with locoregional disease may benefit from emerging treatment options. Ultimately, the objective of salvage therapy is to control disease while ensuring minimal collateral damage, thereby optimizing both cancer and toxicity outcomes. Advances in functional imaging, including multiparametric prostate MRI, abdominopelvic lymphangio-MRI, sentinel node SPECT-CT and/or whole-body PET/CT have paved the way for salvage radiotherapy in patients with local recurrence, microscopic nodal disease limited to the pelvis or oligometastatic disease. These patients may be considered for salvage reirradiation using different techniques: prostate low-dose or high-dose rate brachytherapy, pelvic and/or lomboaortic image-guided radiotherapy with elective nodal irradiation, focal nodal or bone stereotactic body radiation therapy (SBRT). An individualized approach is recommended. The decision about which treatment, if any, to use will be based on the initial characteristics of the disease, relapse patterns and the natural history of the rising prostate specific antigen (PSA). Preliminary results suggest that more than 50% of patients who have undergone salvage reirradiation are biochemically relapse-free with very low rates of severe toxicity. Large prospective studies with a longer follow-up are needed to confirm the promising benefit/risk ratio observed with salvage brachytherapy and or salvage nodal radiotherapy and/or bone oligometastatic SBRT when compared with life-long palliative hormones.

  8. Clinical Value of High Mobility Group Box 1 and the Receptor for Advanced Glycation End-products in Head and Neck Cancer: A Systematic Review.

    PubMed

    Nguyen, Austin; Bhavsar, Sheila; Riley, Erinn; Caponetti, Gabriel; Agrawal, Devendra

    2016-10-01

    Introduction High mobility group box 1 is a versatile protein involved in gene transcription, extracellular signaling, and response to inflammation. Extracellularly, high mobility group box 1 binds to several receptors, notably the receptor for advanced glycation end-products. Expression of high mobility group box 1 and the receptor for advanced glycation end-products has been described in many cancers. Objectives To systematically review the available literature using PubMed and Web of Science to evaluate the clinical value of high mobility group box 1 and the receptor for advanced glycation end-products in head and neck squamous cell carcinomas. Data synthesis A total of eleven studies were included in this review. High mobility group box 1 overexpression is associated with poor prognosis and many clinical and pathological characteristics of head and neck squamous cell carcinomas patients. Additionally, the receptor for advanced glycation end-products demonstrates potential value as a clinical indicator of tumor angiogenesis and advanced staging. In diagnosis, high mobility group box 1 demonstrates low sensitivity. Conclusion High mobility group box 1 and the receptor for advanced glycation end-products are associated with clinical and pathological characteristics of head and neck squamous cell carcinomas. Further investigation of the prognostic and diagnostic value of these molecules is warranted.

  9. Melanoma targeting with the loco-regional chemotherapeutic, Melphalan: From cell death to immunotherapeutic efficacy.

    PubMed

    Dudek-Perić, Aleksandra Maria; Gołąb, Jakub; Garg, Abhishek D; Agostinis, Patrizia

    2015-12-01

    All immunoregulatory chemotherapeutics are chiefly applied in a systemic setting for anticancer therapy. However, immune responses following loco-regional application of chemotherapy may differ from those after systemic application. We recently found that Melphalan, a prototypical loco-regionally applied chemotherapeutic agent, exhibits the ability to increase the immunogenicity of dying melanoma cells.

  10. Role of Hyperthermia in Breast Cancer Locoregional Recurrence: A Review

    PubMed Central

    Maluta, Sergio; Kolff, Merel Willemijn

    2015-01-01

    Summary In patients with locoregional recurrences of breast cancer not suitable for resection, subsequent local control is difficult to maintain in previously irradiated areas when reirradiation alone or reirradiation with chemotherapy is used. Due to the limited number of treatment options there is a high risk of subsequent failure and uncontrollable local disease. In this group of patients, local hyperthermia combined with radiotherapy increases the clinical response and local control, adding limited acute and late toxicity, as has been shown in randomized trials. Hyperthermia is an artificial elevation of tissue temperature (range 40-44°C for 30-60 min). If hyperthermia is applied shortly before or after radiation, the effect of radiation is enhanced by influencing intratumoral hypoxia and by inhibiting sublethal damage repair in the tumor. Moreover, hyperthermia combined with radiation reduces the total dose of radiation needed compared to radiation alone, of which a higher dose is needed to obtain the same effect. Few data are available on the combination of radiotherapy and hyperthermia with chemotherapy, although the results of trimodality treatment consisting of reirradiation and hyperthermia together with liposomal doxorubicin are promising. Therefore, this literature review was performed to provide more comprehensive data on the mechanism and use of hyperthermia in locoregional recurrence of breast cancer. PMID:26989361

  11. 'Hitting you over the head': oncologists' disclosure of prognosis to advanced cancer patients.

    PubMed

    Gordon, Elisa J; Daugherty, Christopher K

    2003-04-01

    The disclosure of prognosis to terminally ill patients has emerged as a recent concern given greater demands for patient involvement in medical decision-making in the United States. As part of the informed consent process, American physicians are legally and ethically obligated to provide information to such patients about risks, benefits, and alternatives of all available treatment options including the use of experimental therapies. Although not legally required, the disclosure of terminal prognosis is ethically justified because it upholds the principle of self-determination and enables patients to make treatment decisions consistent with their life goals. To understand oncologists' attitudes about disclosing prognostic information to cancer patients with advanced disease, we interviewed fourteen oncologists and conducted one focus group of medical fellows. Although oncologists reported to disclose prognosis in terms of cancer not being curable, they tend to avoid using percentages to convey prognosis. Oncologists' reported reluctance to disclosing prognosis was conveyed through the use of metaphors depicting the perceived violent impact of such information on patients. Oncologists' reluctance to disclose prognosis and preserve patient hope are held in check by their need to ensure that patients have 'realistic expectations' about therapy. We discuss these data in light of the cultural, ethical, and legal dimensions of prognosis disclosure, patient hope and the doctor-patient relationship, and recommend ways to enhance the communication process.

  12. Functional results of endoscopic laser surgery in advanced head and neck tumors

    NASA Astrophysics Data System (ADS)

    Sadick, Haneen; Baker-Schreyer, Antonio; Bergler, Wolfgang; Maurer, Joachim; Hoermann, Karl

    1998-01-01

    Functional results following lasersurgery of minor laryngeal carcinomas were very encouraging. The indication for lasersurgical intervention was then extended to larger carcinomas of the larynx and hypopharynx. The purpose of this study was to assess vocal function and swallowing ability after endoscopic lasersurgery and to compare the results with conventional surgical procedures. From January 1994 to December 1996, 72 patients with advanced squamous cell carcinoma of the larynx and hypopharynx were examined prospectively. The patients underwent endoscopic lasersurgery instead of laryngopharyngectomy. The voice quality was evaluated pre- and postoperatively by subjective assessment, registration of voice parameters and sonegraphic classification. The swallowing ability was judged according to individual scores. The necessity of tracheostomy and nasogastric tube were registered and the duration of hospitalization was documented. The results showed that laryngeal phonation and swallowing ability were significantly better 12 months after lasersurgery compared to the preoperative findings whereas the recurrence rate was similar or even better after conventional pharyngolaryngectomy. Lasersurgery as an alternative surgical procedure to laryngectomy enables patients to retain a sufficient voice function and swallowing ability.

  13. American Head and Neck Society

    MedlinePlus

    American Head & Neck Society Mission Statement: Advance Education, Research, and Quality of Care for the head and neck oncology patient. American Head & Neck Society | AHNS The mission of the AHNS is ...

  14. Relation between the level of lymph node metastasis and survival in locally advanced head and neck squamous cell carcinoma.

    PubMed

    Xing, Yan; Zhang, Jianjun; Lin, Heather; Gold, Kathryn A; Sturgis, Erich M; Garden, Adam S; Lee, J Jack; William, William N

    2016-02-15

    The current head and neck squamous cell carcinoma (HNSCC) staging system may not capture the full prognostic implications of regional lymph node involvement. This study investigated the impact of the level of lymph node metastasis (LNM) on survival. The Surveillance, Epidemiology, and End Results registry was queried for oral cavity (OC), oropharynx (OP), larynx (LAR), and hypopharynx (HP) HNSCC. A multivariate Cox proportional hazards model was used to evaluate whether the level of LNM was an independent prognostic factor. Site-specific recursive-partitioning analysis was performed to classify patients into different risk groups. In all, 14,499 patients, including OC (n = 2463), OP (n = 8567), LAR (n = 2332), and HP patients (n = 1137), were analyzed. Both the American Joint Committee on Cancer (AJCC) N classification and the level of LNM showed significant effects on overall survival (OS) in patients with OC, OP, or LAR HNSCC but not in patients with HP HNSCC. In patients with N2 disease, the AJCC subclassification (N2a, N2b, or N2c) was significantly associated with the OS of patients with OP and LAR HNSCC but not with the OS of patients with OC or HP HNSCC, whereas the level of LNM (primary, secondary, or tertiary) was significantly associated with the OS of patients with OC, OP, and LAR HNSCC but not HP HNSCC. With recursive-partitioning analysis, a simple, primary site-specific prognostic tool integrating the AJCC T and N classifications and the level of LNM was designed, and it could be easily used by health care providers in clinic. The level of LNM is an independent prognostic factor for patients with locally advanced HNSCC and could add to the prognostic value of AJCC T and N classifications in patients with locally advanced HNSCC. © 2015 American Cancer Society.

  15. Classical risk factors, but not HPV status, predict survival after chemoradiotherapy in advanced head and neck cancer patients.

    PubMed

    Descamps, Géraldine; Karaca, Yasemin; Lechien, Jérôme R; Kindt, Nadège; Decaestecker, Christine; Remmelink, Myriam; Larsimont, Denis; Andry, Guy; Hassid, Samantha; Rodriguez, Alexandra; Khalife, Mohammad; Journe, Fabrice; Saussez, Sven

    2016-10-01

    Despite the advent of concomitant chemoradiotherapy (CCRT), the prognosis of advanced head and neck squamous cell carcinoma (HNSCC) patients remains particularly poor. Classically, HNSCC, especially oropharyngeal carcinomas, associated with human papillomavirus (HPV) exhibits better treatment outcomes than HNSCCs in non-infected patients, eliciting a call for the de-escalation of current therapies. To improve the management of HNSCC patients, we aimed to determine the impact of active HPV infection on patient response, recurrence and survival after CCRT in a population of heavy tobacco and alcohol consumers. Paraffin-embedded samples from 218 advanced HNSCC patients, mostly smokers and/or drinkers treated by CCRT, were tested for the presence of HPV DNA by surrogate type-specific E6/E7 qPCR and p16 immunohistochemistry. Associations between the response to CCRT and patient outcomes according to HPV status and clinical data were evaluated by Kaplan-Meier analysis and both univariate and multivariate Cox regression. Type-specific E6/E7 PCR demonstrated HPV positivity in 20 % of HNSCC. Regarding HPV status, we did not find any significant relation with response to therapy in terms of progression-free survival or overall survival. However, we observed a significantly worse prognosis for consumers of alcohol and tobacco compared to nondrinkers (p = 0.003) and non-smokers (p = 0.03). Survival analyses also revealed that the outcome is compromised in stage IV patients (p = 0.007) and, in particular, for oral cavity, hypopharynx and oropharynx carcinoma patients (p = 0.001). The risk of death from HNSCC significantly increases when patients are exposed to tobacco and alcohol during their therapy, regardless of HPV status.

  16. Relationship between level of lymph node metastasis and survival in locally advanced head and neck squamous cell carcinoma

    PubMed Central

    Xing, Yan; Zhang, Jianjun; Lin, Heather; Gold, Kathryn A.; Sturgis, Erich M.; Garden, Adam S.; Lee, J. Jack; William, William N.

    2015-01-01

    Background The current head and neck squamous cell carcinoma (HNSCC) staging system may not capture the full prognostic implications of regional lymph node involvement. We sought to investigate the impact of level of lymph node metastasis (LNM) on survival Methods The Surveillance, Epidemiology, and End Results (SEER) registry was queried for oral cavity (OC), oropharynx (OP), larynx (LAR), and hypopharynx (HP) HNSCC. Multivariate Cox proportional hazards model was used to evaluate whether level of LNM is an independent prognostic factor. Site-specific recursive-partitioning analysis (RPA) was performed to classify patients into different risk groups. Results Totally, 14,499 patients including OC (N=2,463), OP (N=8,567), LAR (N=2,332) and HP (N=1,137) were analyzed. Both AJCC N classification and level of LNM showed significant effects on overall survival (OS) in patients with OC, OP or LAR, but not in HP. In patients with N2 disease, AJCC subclassification (N2a, N2b, N2c) was significantly associated with OS of patients with OP and LAR, but not OC or HP, while level of LNM (primary, secondary, and tertiary) was significantly associated with OS in patients with OC, OP and LAR, but not HP. Using RPA, we designed a simple, primary site-specific prognostic tool integrating AJCC T classification, N classification, and level of LNM that can be easily utilized by health care providers in clinic. Conclusions Level of LNM is an independent prognostic factor for patients with locally advanced HNSCC and could add to the prognostic value of AJCC T and N classification in patients with locally advanced HNSCC. PMID:26554754

  17. Advanced auditory displays and head-mounted displays: advantages and disadvantages for monitoring by the distracted anesthesiologist.

    PubMed

    Sanderson, Penelope M; Watson, Marcus O; Russell, Walter John; Jenkins, Simon; Liu, David; Green, Norris; Llewelyn, Kristen; Cole, Phil; Shek, Vivian; Krupenia, Stas S

    2008-06-01

    In a full-scale anesthesia simulator study we examined the relative effectiveness of advanced auditory displays for respiratory and blood pressure monitoring and of head-mounted displays (HMDs) as supplements to standard intraoperative monitoring. Participants were 16 residents and attendings. While performing a reading-based distractor task, participants supervised the activities of a resident (an actor) who they were told was junior to them. If participants detected an event that could eventually harm the simulated patient, they told the resident, pressed a button on the computer screen, and/or informed a nearby experimenter. Participants completed four 22-min anesthesia scenarios. Displays were presented in a counterbalanced order that varied across participants and included: (1) Visual (visual monitor with variable-tone pulse oximetry), (2) HMD (Visual plus HMD), (3) Audio (Visual plus auditory displays for respiratory rate, tidal volume, end-tidal CO(2), and noninvasive arterial blood pressure), and (4) Both (Visual plus HMD plus Audio). Participants detected significantly more events with Audio (mean = 90%, median = 100%, P < 0.02) and Both (mean = 92%, median = 100%, P < 0.05) but not with HMD (mean = 75%, median = 67%, ns) compared with the Visual condition (mean = 52%, median = 50%). For events detected, there was no difference in detection times across display conditions. Participants self-rated monitoring as easier in the HMD, Audio and Both conditions and their responding as faster in the HMD and Both conditions than in the Visual condition. Advanced auditory displays help the distracted anesthesiologist maintain peripheral awareness of a simulated patient's status, whereas a HMD does not significantly improve performance. Further studies should test these findings in other intraoperative contexts.

  18. RapidArc Planning and Delivery in Patients With Locally Advanced Head-and-Neck Cancer Undergoing Chemoradiotherapy

    SciTech Connect

    Doornaert, Patricia; Verbakel, Wilko F.A.R.; Bieker, Michael; Slotman, Ben J.; Senan, Suresh

    2011-02-01

    Purpose: Volumetric modulated arc therapy (RapidArc, Varian Medical Systems) permits the delivery of highly conformal dose distributions. We studied planning and delivery in patients who underwent RapidArc for locally advanced head-and-neck cancer (HNC). Methods and Materials: A total of 35 consecutive patients who completed RapidArc with concurrent chemotherapy for Stages III-IV tumors of the oro- and hypopharynx/larynx in our center were identified. All underwent bilateral neck irradiation and 21 patients had at least N2 disease. A simultaneous integrated boost (SIB) delivered 70 Gy (in 2 Gy/fraction) to the planning target volume (PTV){sub boost} and elective nodal regions (PTV{sub elect}) received 57.75 Gy. A standard planning constraint set was used and constraints for parotid glands were individually adapted. Treatments were delivered using two arcs after all plans were verified in a solid water phantom using GafChromic External Beam Therapy films. Results: RapidArc planning generally took 1.5-2 h, which was faster than with our previous seven-field intensity-modulated radiotherapy sliding window technique. Film dosimetry revealed that 0.6% of films exceeded a combination of dose differences {>=}3% or distance to agreement {>=}2 mm. More than 99% of both PTVs received {>=}95% of the prescription dose. Average plan conformity index was 1.13 and mean dose to ipsilateral and contralateral parotid glands were 31.4 Gy and 26.1 Gy, respectively. The mean beam-on time was <3 min and mean number of monitor units was 426. Conclusions: RapidArc achieved excellent target coverage and normal tissue sparing, with delivery completed in less than 3 min. RA is currently our standard intensity-modulated radiotherapy approach for advanced HNC.

  19. Cluster analysis of dynamic contrast enhanced MRI reveals tumor subregions related to locoregional relapse for cervical cancer patients.

    PubMed

    Torheim, Turid; Groendahl, Aurora R; Andersen, Erlend K F; Lyng, Heidi; Malinen, Eirik; Kvaal, Knut; Futsaether, Cecilia M

    2016-11-01

    Solid tumors are known to be spatially heterogeneous. Detection of treatment-resistant tumor regions can improve clinical outcome, by enabling implementation of strategies targeting such regions. In this study, K-means clustering was used to group voxels in dynamic contrast enhanced magnetic resonance images (DCE-MRI) of cervical cancers. The aim was to identify clusters reflecting treatment resistance that could be used for targeted radiotherapy with a dose-painting approach. Eighty-one patients with locally advanced cervical cancer underwent DCE-MRI prior to chemoradiotherapy. The resulting image time series were fitted to two pharmacokinetic models, the Tofts model (yielding parameters K(trans) and νe) and the Brix model (ABrix, kep and kel). K-means clustering was used to group similar voxels based on either the pharmacokinetic parameter maps or the relative signal increase (RSI) time series. The associations between voxel clusters and treatment outcome (measured as locoregional control) were evaluated using the volume fraction or the spatial distribution of each cluster. One voxel cluster based on the RSI time series was significantly related to locoregional control (adjusted p-value 0.048). This cluster consisted of low-enhancing voxels. We found that tumors with poor prognosis had this RSI-based cluster gathered into few patches, making this cluster a potential candidate for targeted radiotherapy. None of the voxels clusters based on Tofts or Brix parameter maps were significantly related to treatment outcome. We identified one group of tumor voxels significantly associated with locoregional relapse that could potentially be used for dose painting. This tumor voxel cluster was identified using the raw MRI time series rather than the pharmacokinetic maps.

  20. Targeted Therapy in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (LA-R/M HNSCC)

    PubMed Central

    Echarri, María José; Lopez-Martin, Ana; Hitt, Ricardo

    2016-01-01

    Surgery and radiotherapy are the standard treatment options for patients with squamous cell carcinoma of the head and neck (SCCHN). Chemoradiotherapy is an alternative for patients with locally advanced disease. In recurrent/metastatic disease and after progression to platin-based regimens, no standard treatments other than best supportive care are currently available. Most SCCHN tumours overexpress the epidermal growth factor receptor (EGFR). This receptor is a tyrosine-kinase membrane receptor that has been implicated in angiogenesis, tumour progression and resistance to different cancer treatments. In this review, we analysed the different drugs and pathways under development to treat SCCHN, especially recurrent/metastatic disease. Until now, the EGFR signalling pathway has been considered the most important target with respect to new drugs; however, new drugs, such as immunotherapies, are currently under study. As new treatments for SCCHN are developed, the influence of therapies with respect to overall survival, progression free survival and quality of life in patients with this disease is changing. PMID:26927178

  1. Predicting response to radical (chemo)radiotherapy with circulating HPV DNA in locally advanced head and neck squamous carcinoma.

    PubMed

    Lee, Jen Y; Garcia-Murillas, Isaac; Cutts, Rosalind J; De Castro, David Gonzalez; Grove, Lorna; Hurley, Tara; Wang, Fuqiang; Nutting, Christopher; Newbold, Katie; Harrington, Kevin; Turner, Nicholas; Bhide, Shreerang

    2017-09-05

    Following chemo-radiotherapy (CCRT) for human papilloma virus positive (HPV+) locally advanced head and neck cancer, patients frequently undergo unnecessary neck dissection (ND) and/or repeated biopsies for abnormal PET-CT, which causes significant morbidity. We assessed the role of circulating HPV DNA in identifying 'true' residual disease. We prospectively recruited test (n=55) and validation (n=33) cohorts. HPV status was confirmed by E7 RT-PCR. We developed a novel amplicon-based next generation sequencing assay (HPV16-detect) to detect circulating HPV DNA. Circulating HPV DNA levels post-CCRT were correlated to disease response (PET-CT). In pre-CCRT plasma, HPV-detect demonstrated 100% sensitivity and 93% specificity, and 90% sensitivity and 100% specificity for the test (27 HPV+) and validation (20 HPV+) cohorts, respectively. Thirty-six out of 37 patients (test and validation cohort) with complete samples-set had negative HPV-detect at end of treatment. Six patients underwent ND (3) and repeat primary site biopsies (3) for positive PET-CT but had no viable tumour. One patient had positive HPV-detect and positive PET-CT and liver biopsy, indicating 100% agreement for HPV-detect and residual cancer. We demonstrate that HPV16-detect is a highly sensitive and specific test for identification of HPV DNA in plasma at diagnosis. HPV DNA post-treatment correlates with clinical response.

  2. Roof Deformation, Failure Characteristics, and Preventive Techniques of Gob-Side Entry Driving Heading Adjacent to the Advancing Working Face

    NASA Astrophysics Data System (ADS)

    Bai, Jian-biao; Shen, Wen-long; Guo, Guan-long; Wang, Xiang-yu; Yu, Yang

    2015-11-01

    In mining excavation, the roof bending subsidence of gob-side entry driving heading adjacent to the advancing working face (HAWF) can be considerable. Influenced by the original rock pressure, the front and lateral abutment pressure of the adjacent working face, and the front abutment pressure of the current working face, the support body can easily fail, leading to serious instability of the rock mass surrounding the tunnel. To study the stress state and the deformation failure mechanism of the HAWF roof structure, we use on-site survey data, numerical simulation, and theoretical calculations to fit the spatial distribution law of mining abutment pressure piecewise, and establish a dynamic mechanical model of the roof structure. We then propose a roof failure criterion and examine the roof flexure deformation behavioral pattern. We found that the central part of the roof is the main point that controls the surrounding rock. To prevent the deformation and collapse of the roof and rock surrounding the tunnel, we propose techniques that can be applied to HAWF gob-side entry driving, including setting the coal pillar width, the driving stop and restart timing, and other control concepts.

  3. TAK1 mRNA expression in the tumor tissue of locally advanced head and neck cancer patients.

    PubMed

    Honorato, Beatriz; Alcalde, Juan; Martinez-Monge, Rafael; Zabalegui, Natalia; Garcia-Foncillas, Jesús

    2008-02-14

    Resistance to radio and chemotherapy is one of the major drawbacks in the progression of head and neck squamous cell cancer (HNSCC) patients, evidencing the importance of finding optimum molecular prognosis markers to develop personalized treatment schedules. TGF-beta effector TAK1 activity has been related to a greater aggressiveness in several types of cancer (Kondo et al. 1998; Edlund et al. 2003; Kaur et al. 2005) and, although there has been described no significant implication of TAK1 in HNSCC development, we have further examined the role of its mRNA expression as a marker of prognosis in HNSCC. Fifty-nine advanced HNSCC patients were recruited for the study. The tumor expression of TAK1 mRNA was analyzed with RT-PCR using Taqman technology and its relationship with the clinical outcome of the patients studied. TAK1 mRNA expression was lower in patients that relapsed than in those that did not, but the difference was only significant between the patients that showed response to treatment (p < 0.001). ROC curve analyses pointed a 0.5 expression ratio TAK1/B2M value as an optimum cut-off point for relapse and response. Our data suggest the TAK1 mRNA analysis by Taqman RT-PCR can predict the risk of relapse in HNSCC patients.

  4. TAK1 mRNA Expression in the Tumor Tissue of Locally Advanced Head and Neck Cancer Patients

    PubMed Central

    Honorato, Beatriz; Alcalde, Juan; Martinez-Monge, Rafael; Zabalegui, Natalia; Garcia-Foncillas, Jesús

    2008-01-01

    Resistance to radio and chemotherapy is one of the major drawbacks in the progression of head and neck squamous cell cancer (HNSCC) patients, evidencing the importance of finding optimum molecular prognosis markers to develop personalized treatment schedules. TGF-β effector TAK1 activity has been related to a greater aggressiveness in several types of cancer (Kondo et al. 1998; Edlund et al. 2003; Kaur et al. 2005) and, although there has been described no significant implication of TAK1 in HNSCC development, we have further examined the role of its mRNA expression as a marker of prognosis in HNSCC. Fifty-nine advanced HNSCC patients were recruited for the study. The tumor expression of TAK1 mRNA was analyzed with RT-PCR using Taqman technology and its relationship with the clinical outcome of the patients studied. TAK1 mRNA expression was lower in patients that relapsed than in those that did not, but the difference was only significant between the patients that showed response to treatment (p < 0.001). ROC curve analyses pointed a 0.5 expression ratio TAK1/B2M value as an optimum cut-off point for relapse and response. Our data suggest the TAK1 mRNA analysis by Taqman RT-PCR can predict the risk of relapse in HNSCC patients. PMID:19787075

  5. The Experiences of Patients With Advanced Head and Neck Cancer With a Percutaneous Endoscopic Gastrostomy Tube: A Qualitative Descriptive Study.

    PubMed

    Kwong, Janna P Y; Stokes, Edith J; Posluns, Elaine C; Fitch, Margaret I; McAndrew, Alison; Vandenbussche, Katherine A

    2014-08-01

    Background: While the percutaneous endoscopic gastrostomy (PEG) tube has become an established part of the management regimen for patients with head and neck cancer (HNCA) with impaired nutrition and functional status, limited research has explored the impact and experiences of living with a PEG tube from the patient's perspective. This qualitative study serves as a follow-up investigation undertaken to describe the experiences of patients with advanced HNCA living with a PEG tube. Materials and Methods: Eligible patients from convenience sampling were invited to participate until data saturation was reached. In-depth interviews were conducted with consenting participants. Qualitative descriptive design guided the content analysis of the interview transcripts. Results: Of the 49 patients invited, a total of 15 participants' interviews were transcribed and analyzed. Each interview was 15-90 minutes in length. Four of 22 content codes were chosen to describe the overarching ideas of the progressive experience of a patient's journey from the initial decision-making process around tube insertion through to its removal. Difficulty swallowing and weight loss emerged as primary factors for PEG tube insertion, and all participants became accustomed to living with the tube. Resuming a complete oral diet was a gradual transition. All participants recognized the value of the tube, and most acknowledged its necessity for their survival. Conclusions: Results describe the overall PEG tube experience as a dichotomy. While there were issues with the PEG tube, all participants found the tube to be beneficial. This study provides invaluable insight from a practice perspective.

  6. Study of Functional Infrared Imaging for Early Detection of Mucositis in Locally Advanced Head and Neck Cancer Treated With Chemoradiotherapy

    PubMed Central

    Cohen, Ezra E.W.; Ahmed, Omar; Kocherginsky, Masha; Shustakova, Galyna; Kistner-Griffin, Emily; Salama, Joseph K.; Yefremenko, Volodymyr; Novosad, Valentyn

    2013-01-01

    Background and Purpose Chemoradiotherapy (CRT) has led to improved efficacy in treating locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) but has led to almost universal in-field mucositis. Patients treated with the same regimen often have differences in mucositis occurrence and severity. Mucositis induced via radiation is known to represent an intense inflammatory response histologically. We hypothesized that patients destined to display severe mucocutaneous toxicity would demonstrate greater alterations in thermal intensity early in therapy than identically treated counterparts. This will allow identification of patients that will require more intensive supportive care using thermal imaging technology. Materials and Methods Subjects with LA-SCCHN (oral cavity or oropharynx) being treated with the identical chemoradiotherapy regimen underwent baseline and weekly thermal imaging. Changes in skin temperature caused by mucositis and dermatitis compared with a reference area (T were calculated and correlated to grade of mucositis based on NCI-CTCAE 3.0. Results Thirty-four subjects were enrolled. Grade 3 mucositis and dermatitis was observed in 53% and 21%, respectively. We observed a statistically significant positive association between an early rise in T and mucositis grade (p value=0.03). Conclusions Thermal imaging is able to detect small and early changes in skin surface temperature that may be associated with development of mucositis in patients being treated with chemoradiotherapy. PMID:23988569

  7. Acoustic analysis of changes in articulation proficiency in patients with advanced head and neck cancer treated with chemoradiotherapy.

    PubMed

    Jacobi, Irene; van Rossum, Maya A; van der Molen, Lisette; Hilgers, Frans J M; van den Brekel, Michiel W M

    2013-12-01

    Our aim was to characterize articulation proficiency and differences between tumor sites before and after chemoradiotherapy for advanced head and neck cancer with the help of acoustic measures. Our further goal was to improve objective speech measures and gain insight into muscle functioning before and after treatment. In 34 patients with laryngeal or hypopharyngeal, nasal or nasopharyngeal, or oral or oropharyngeal cancer, we acoustically analyzed nasality, vowel space, precision, and strength of articulation in 12 speech sounds (/a/, /i/, /u/, /p/, /s/, /z/, /1/, /t/, /tj/, /k/, /x/, /r/) before treatment and 10 weeks and 1 year after treatment. Outcomes were compared between assessment points and between tumor sites. Nasality in nonlaryngeal sites was significantly reduced by treatment. Most affected in articulation were the oral or oropharyngeal cancer sites, followed by the nasal or nasopharyngeal sites. One year after treatment, vowel space had not recovered and consonant articulation had weakened. Laryngeal sites were less affected in articulation by tumor or treatment. Analyses of articulatory-acoustic features are a useful instrument for assessing articulation and speech quality objectively. Assessment of a number of sounds representing various articulation manners, places, and tongue shapes revealed patterns of speech deterioration after chemoradiotherapy. The results suggest that patients' speech could benefit from articulation exercises to address changes in muscle coordination and/or sensitivity and to counteract side effects and "underexercise" atrophy.

  8. Assessment of voice, speech, and related quality of life in advanced head and neck cancer patients 10-years+ after chemoradiotherapy.

    PubMed

    Kraaijenga, S A C; Oskam, I M; van Son, R J J H; Hamming-Vrieze, O; Hilgers, F J M; van den Brekel, M W M; van der Molen, L

    2016-04-01

    Assessment of long-term objective and subjective voice, speech, articulation, and quality of life in patients with head and neck cancer (HNC) treated with concurrent chemoradiotherapy (CRT) for advanced, stage IV disease. Twenty-two disease-free survivors, treated with cisplatin-based CRT for inoperable HNC (1999-2004), were evaluated at 10-years post-treatment. A standard Dutch text was recorded. Perceptual analysis of voice, speech, and articulation was conducted by two expert listeners (SLPs). Also an experimental expert system based on automatic speech recognition was used. Patients' perception of voice and speech and related quality of life was assessed with the Voice Handicap Index (VHI) and Speech Handicap Index (SHI) questionnaires. At a median follow-up of 11-years, perceptual evaluation showed abnormal scores in up to 64% of cases, depending on the outcome parameter analyzed. Automatic assessment of voice and speech parameters correlated moderate to strong with perceptual outcome scores. Patient-reported problems with voice (VHI>15) and speech (SHI>6) in daily life were present in 68% and 77% of patients, respectively. Patients treated with IMRT showed significantly less impairment compared to those treated with conventional radiotherapy. More than 10-years after organ-preservation treatment, voice and speech problems are common in this patient cohort, as assessed with perceptual evaluation, automatic speech recognition, and with validated structured questionnaires. There were fewer complaints in patients treated with IMRT than with conventional radiotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Treatment choice for locally advanced head and neck cancers on the basis of risk factors: biological risk factors.

    PubMed

    Braakhuis, B J M; Brakenhoff, R H; Leemans, C René

    2012-09-01

    Patients with locally advanced head and neck squamous cell carcinoma often experience relapse, the cause of poor survival statistics. Relapse occurs following the three main types of treatment, surgery with or without post-operative (chemo)radiotherapy, or chemoradiation (containing cisplatin). Cancer relapse can result from (i) outgrowth of residual tumour cells, sometimes with a number too small to be detected by routine histopathology or (ii) development of another carcinoma in a field of pre-neoplastic cells that has remained after treatment of the primary carcinoma. At this moment, clinical staging is not enough to identify patients who will develop relapse and who need tailored treatment. This review describes the latest knowledge of mechanisms of cancer relapse, addresses the biomarkers of potential interest detectable in the tissue of the tumour or its surgical margins and discusses three biomarkers, human papillomavirus, TP53 and epidermal growth receptor in more detail. Once a marker panel has been established, treatment should be focussed on the patients at risk of relapse by improved tailoring of existing treatment modalities. Also, the implementation of more targeting therapies based on the characteristics of the discovered markers should lead to better survival rates.

  10. Hypofractionated Accelerated Radiotherapy With Concurrent Chemotherapy For Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Sanghera, Paul; McConkey, Chris; Ho, Kean-Fatt; Glaholm, John; Hartley, Andrew . E-mail: andrew.hartley@uhb.nhs.uk

    2007-04-01

    Purpose: To investigate the tumor control rates in locally advanced head-and-neck cancer using accelerated hypofractionated radiotherapy with chemotherapy. Methods and Materials: The data from patients with squamous cell cancer of the larynx, oropharynx, oral cavity, and hypopharynx (International Union Against Cancer Stage II-IV), who received accelerated hypofractionated radiotherapy with chemotherapy between January 1, 1998, and April 1, 2005, were retrospectively analyzed. Two different chemotherapy schedules were used, carboplatin and methotrexate, both single agents administered on an outpatient basis. The endpoints were overall survival, local control, and disease-free survival. Results: A total of 81 patients were analyzed. The 2-year overall survival rate was 71.6% (95% confidence interval [CI], 61.5-81.8%). The 2-year disease-free survival rate was 68.6% (95% CI, 58.4-78.8%). The 2-year local control rate was 75.4% (95% CI, 65.6-85.1%). When excluding patients with Stage II oral cavity, larynx, and hypopharynx tumors, 68 patients remained. For these patients, the 2-year overall survival, local control, and disease-free survival rate was 67.6% (95% CI, 56.0-79.2%), 72.0% (95% CI, 61.0-83.0%), and 64.1% (95% CI, 52.6-75.7%), respectively. Conclusion: Accelerated hypofractionated radiotherapy and synchronous chemotherapy can achieve high tumor control rates while being resource sparing and should be the subject of prospective evaluation.

  11. Impact of initial FDG PET/CT in the management plan of patients with locally advanced head and neck cancer.

    PubMed

    Arias, F; Chicata, V; García-Velloso, M J; Asín, G; Uzcanga, M; Eito, C; Quilez, I; Viudez, A; Saenz, J; Hernández, I; Caicedo, C; Errasti, M; Barrado, M; García-Bragado, F

    2015-02-01

    To determine the impact of initial FDG PET/CT staging on clinical stage and the management plan in patients with locally advanced head and neck cancer (LAHNC). We retrospectively reviewed the records of 72 consecutive patients (2007-2010) staged with PET/CT and conventional CT with tumours of hypopharynx/larynx (26 patients, 36 %), oral cavity (17 patients, 24 %), oropharynx (16 patients, 22 %), nasopharynx (12 patients, 17 %), and others (2 %). The impact of PET/CT on management plans was considered high when PET/CT changed the planned treatment modality or treatment intent, and intramodality changes were considered as minor changes with low impact. FDG PET/CT changed the stage in 27 patients and had high impact on the management plan in 12 % of patients (detection of distant metastases in 6 patients and stage II in 2 patients). Intramodality changes were more frequent: FDG PET/CT altered the TNM stage in 18/72 (25 %) of patients, upstaging N stage in 90 % of patients with low impact. Initial FDG PET/CT staging not only improves stage but also affects the management plan in LAHNC patients.

  12. Targeted therapy in head and neck cancer.

    PubMed

    Licitra, Lisa; Bergamini, Cristiana; Mirabile, Aurora; Granata, Roberta

    2011-04-01

    Results of clinical studies on targeted cancer therapies are rapidly accumulating. This is also true in the field of head and neck cancer (HNC). Due to the unique multidisciplinary needs of the disease, it is of paramount importance that physicians who treat HNC are aware of the evolving changes that research is offering. Many targeted agents directed at inhibiting epithelial growth factor receptors (EGFRs) are under investigation in both curable loco-regional advanced disease in combination with standard treatments and in the recurrent metastatic setting. Human papilloma virus (HPV)-positive tumors present a distinct biological profile. Consequently, the role of targeted agents in this specific setting still needs to be refined. Herein we will briefly review the results of the most recent studies on targeted agents. Cetuximab and other monoclonal antibodies (panitumumab, zalotumumab and nimotumumab) have been already investigated in phase III studies; and some results are now available. Small molecules inhibiting EGFR have still to prove their efficacy. Other agents such as vascular endothelial cell growth factor receptor, vascular endoinsulin-like growth factor 1 receptor, MET, PI3KA and mammalian target of rapamycin inhibitor are in development. At present treatment options in HNC are changing and include targeted agents with demonstrated efficacy. A better selection based on biological factors of patients who are potentially responsive to such targeted agents is being actively pursued.

  13. Effect of Head-Down Bed Rest and Artificial Gravity Countermeasure on Cardiac Autonomic and Advanced Electrocardiographic Function

    NASA Technical Reports Server (NTRS)

    Schlegel, T. T.; Platts, S.; Stenger, M.; Ribeiro, C.; Natapoff, A.; Howarth, M.; Evans, J.

    2007-01-01

    To study the effects of 21 days of head-down bed rest (HDBR), with versus without an artificial gravity (AG) countermeasure, on cardiac autonomic and advanced electrocardiographic function. Fourteen healthy men participated in the study: seven experienced 21 days of HDBR alone ("HDBR controls") and seven the same degree and duration of HDBR but with approximately 1hr daily short-arm centrifugation as an AG countermeasure ("AG-treated"). Five minute supine high-fidelity 12-lead ECGs were obtained in all subjects: 1) 4 days before HDBR; 2) on the last day of HDBR; and 3) 7 days after HDBR. Besides conventional 12-lead ECG intervals and voltages, all of the following advanced ECG parameters were studied: 1) both stochastic (time and frequency domain) and deterministic heart rate variability (HRV); 2) beat-to-beat QT interval variability (QTV); 3) T-wave morphology, including signal-averaged T-wave residua (TWR) and principal component analysis ratios; 4) other SAECG-related parameters including high frequency QRS ECG and late potentials; and 5) several advanced ECG estimates of left ventricular (LV) mass. The most important results by repeated measures ANOVA were that: 1) Heart rates, Bazett-corrected QTc intervals, TWR, LF/HF power and the alpha 1 of HRV were significantly increased in both groups (i.e., by HDBR), but with no relevant HDBR*group differences; 2) All purely "vagally-mediated" parameters of HRV (e.g., RMSSD, HF power, Poincare SD1, etc.), PR intervals, and also several parameters of LV mass (Cornell and Sokolow-Lyon voltages, spatial ventricular activation times, ventricular gradients) were all significantly decreased in both groups (i.e., by HDBR), but again with no relevant HDBR*group differences); 3) All "generalized" or "vagal plus sympathetic" parameters of stochastic HRV (i.e., SDNN, total power, LF power) were significantly more decreased in the AG-treated group than in the HDBR-only group (i.e., here there was a relevant HDBR*group difference

  14. Effect of Head-Down Bed Rest and Artificial Gravity Countermeasure on Cardiac Autonomic and Advanced Electrocardiographic Function

    NASA Technical Reports Server (NTRS)

    Schlegel, T. T.; Platts, S.; Stenger, M.; Ribeiro, C.; Natapoff, A.; Howarth, M.; Evans, J.

    2007-01-01

    To study the effects of 21 days of head-down bed rest (HDBR), with versus without an artificial gravity (AG) countermeasure, on cardiac autonomic and advanced electrocardiographic function. Fourteen healthy men participated in the study: seven experienced 21 days of HDBR alone ("HDBR controls") and seven the same degree and duration of HDBR but with approximately 1hr daily short-arm centrifugation as an AG countermeasure ("AG-treated"). Five minute supine high-fidelity 12-lead ECGs were obtained in all subjects: 1) 4 days before HDBR; 2) on the last day of HDBR; and 3) 7 days after HDBR. Besides conventional 12-lead ECG intervals and voltages, all of the following advanced ECG parameters were studied: 1) both stochastic (time and frequency domain) and deterministic heart rate variability (HRV); 2) beat-to-beat QT interval variability (QTV); 3) T-wave morphology, including signal-averaged T-wave residua (TWR) and principal component analysis ratios; 4) other SAECG-related parameters including high frequency QRS ECG and late potentials; and 5) several advanced ECG estimates of left ventricular (LV) mass. The most important results by repeated measures ANOVA were that: 1) Heart rates, Bazett-corrected QTc intervals, TWR, LF/HF power and the alpha 1 of HRV were significantly increased in both groups (i.e., by HDBR), but with no relevant HDBR*group differences; 2) All purely "vagally-mediated" parameters of HRV (e.g., RMSSD, HF power, Poincare SD1, etc.), PR intervals, and also several parameters of LV mass (Cornell and Sokolow-Lyon voltages, spatial ventricular activation times, ventricular gradients) were all significantly decreased in both groups (i.e., by HDBR), but again with no relevant HDBR*group differences); 3) All "generalized" or "vagal plus sympathetic" parameters of stochastic HRV (i.e., SDNN, total power, LF power) were significantly more decreased in the AG-treated group than in the HDBR-only group (i.e., here there was a relevant HDBR*group difference

  15. Incidence, Natural History, and Patterns of Locoregional Recurrence in Gastric Cancer Patients Treated With Preoperative Chemoradiotherapy

    SciTech Connect

    Reed, Valerie K.; Krishnan, Sunil; Mansfield, Paul F.; Bhosale, Priya R.; Kim, Michelle; Das, Prajnan; Janjan, Nora A.; Delclos, Marc E.; Lowy, Andrew M.; Feig, Barry W.; Pisters, Peter W.T.; Ajani, Jaffer A.; Crane, Christopher H.

    2008-07-01

    Purpose: To retrospectively determine the incidence and patterns (in-field, marginal, or out-of-field) of locoregional gastric cancer recurrence in patients who received preoperative chemoradiotherapy and to determine the outcome in these patients. Methods and Materials: Between 1994 and 2004, 149 patients with gastric carcinoma were treated according to institutional protocols with preoperative chemoradiotherapy. Ultimately, 105 patients had an R0 resection. Of these 105 patients, 65 received preoperative chemotherapy followed by chemoradiotherapy and 40 received preoperative chemoradiotherapy. Most (96%) of these patients received 5-fluorouracil-based chemotherapy during radiotherapy, and the median radiation dose was 45 Gy. We retrospectively identified and classified the patterns of locoregional recurrence. Results: The 3-year actuarial incidence of locoregional recurrence was 13%, with locoregional disease recurring as any part of the failure pattern in 14 patients. Most (64%) of the evaluable locoregional recurrences were in-field. Of the 4 patients with a marginal recurrence, 2 had had inadequate coverage of the regional nodal volumes on their oblique fields. The pathologic complete response rate was 23%. A pathologic complete response was the only statistically significant predictor of locoregional control. Conclusion: Patients with gastric cancer who received preoperative chemoradiotherapy had low rates of locoregional recurrence. This strategy merits prospective multi-institutional and randomized evaluation.

  16. [Basic Studies on Locoregional Injection of a Newly Designed Chitin Sol].

    PubMed

    Chiba, Takehiro; Sugitachi, Akio; Kume, Kouhei; Segawa, Takenori; Nishinari, Yutaka; Ishida, Kaoru; Noda, Hironobu; Nishizuka, Satoshi; Kimura, Yusuke; Koeda, Keisuke; Sasaki, Akira

    2015-11-01

    Systemic chemotherapy in advanced cancer cases often provokes serious adverse events. We aimed to examine the fundamental properties and efficacy of a novel chitin sol, an anti-cancer agent with minor side effects designed to avoid the adverse effects of chemotherapy and enhance the QOL and ADL of patients. DAC-70 was used to create the novel agent termed DAC-70 sol. The anti-proliferative activity was assayed by the WST method using different types of cell lines. The anti-cancer efficacy of the novel agent was examined using cancer-bearing mice. DAC-70 sol was easily injectable through a 21-G needle. The sol suppressed proliferation of the cells in vitro. Intra-tumor injection of DAC-70 sol inhibited the rapid growth of solid tumors in the mice. CDDP-loaded DAC-70 sol, CDDP/DAC-70 sol, successfully controlled malignant ascites in the mice (p<0.05). Neither recurrence nor severe complications were encountered in these animals. These basic data strongly suggest that locoregional administration of our newly designed DAC-70 sol and CDDP/DAC-70 sol is clinically useful as novel cancer chemotherapy for advanced cases. This warrants further clinical studies in cancer chemotherapy.

  17. Involved-Field Radiation Therapy for Locoregionally Recurrent Ovarian Cancer

    PubMed Central

    Brown, Aaron P.; Jhingran, Anuja; Klopp, Ann H.; Schmeler, Kathleen M.; Ramirez, Pedro T.; Eifel, Patricia J.

    2015-01-01

    Objective To evaluate the effectiveness of definitive involved-field radiation therapy (IFRT) for selected patients with locoregionally-recurrent ovarian cancer. Methods We retrospectively reviewed records of 102 epithelial ovarian cancer patients treated with definitive IFRT (≥45 Gy). IFRT was directed to localized nodal (49%) and extranodal (51%) recurrences. Results The median time from diagnosis to IFRT was 36 months (range, 1–311), and the median follow-up after IFRT was 37 months (range, 1–123). Patients received a median of three chemotherapy courses before IFRT (range, 0–9). Five-year overall (OS) and progression-free survival (PFS) rates after IFRT were 40% and 24% respectively; the 5-year in-field disease control rate was 71%. Thirty-five patients (35%) had no evidence of disease at a median of 38 months after IFRT (range, 7–122), including 25 continuously without disease for a median of 61 months (range, 17–122) and 10 with salvage treatment following disease recurrence, disease-free for a median of 39 months after salvage treatment (range, 7–92). Eight clear cell carcinoma patients had higher 5-year OS (88% versus 37%; p=0.05) and PFS (75% versus 20%; p=0.01) rates than other patients. Patients sensitive to initial platinum chemotherapy had a higher 5-year OS rate than platinum-resistant patients (43% versus 27%, p=0.03). Patients who required chemotherapy for recurrence after IFRT often benefitted from longer chemotherapy-free intervals after than before IFRT. Conclusions Definitive IFRT can yield excellent local control, protracted disease-free intervals, and even cures in carefully selected patients. RT should be considered a tool in the curative management of locoregionally-recurrent ovarian cancer. PMID:23648467

  18. Receipt of locoregional therapy among young women with breast cancer.

    PubMed

    Freedman, Rachel A; Virgo, Katherine S; Labadie, Julia; He, Yulei; Partridge, Ann H; Keating, Nancy L

    2012-10-01

    Although younger women with breast cancer have the most to gain from receipt of optimal care, few data are available regarding their receipt of locoregional breast cancer treatments. We identified 317,596 women aged 18-64 who were diagnosed with invasive breast cancer at hospitals reporting to the National Cancer Database, a large national cancer registry, during 2004-2008. We used multivariable logistic regression to assess the association of patient age with mastectomy versus breast-conserving surgery (BCS), radiation with BCS, and postmastectomy radiation therapy (PMRT) with varying indications, adjusting for patient, clinical, and facility characteristics. Overall, 4 % of women were 35 years old or younger and 7 % were 36-40 years old. Women ≤age 40 were significantly more likely to have mastectomy than BCS compared with older women (57 % for age ≤35 and 52 % for ages 36-40 vs. 35 % for ages 61-64, adjusted odds ratio [OR] for age ≤35 = 2.03; 95 % confidence interval (CI) 1.93-2.14 and OR for ages 36-40 = 1.76; 95 % CI 1.69-1.84). Younger women were less likely to receive radiation if BCS was performed (69 and 73 vs. 80 %, OR for age ≤35 = 0.69; 95 % CI 0.65-0.74 and OR for ages 36-40 = 0.74; 95 % CI 0.70-0.78). For those who underwent mastectomy, overall rates of PMRT were low, although women ≤age 35 and ages 36-40 (vs. ages 61-64) were more likely to receive PMRT regardless of clinical indications. Our study suggests that young women with breast cancer may not be receiving optimal locoregional therapy. Efforts are needed to confirm these findings, further understand barriers to care, and increase the receipt of appropriate adjuvant radiation therapy among young women to improve their disease-free and overall survival.

  19. Concurrent Chemoradiotherapy With Cisplatin Versus Cetuximab for Squamous Cell Carcinoma of the Head and Neck

    PubMed Central

    Riaz, Nadeem; Sherman, Eric; Koutcher, Lawrence; Shapiro, Lauren; Katabi, Nora; Zhang, Zhigang; Shi, Weiji; Fury, Mathew; Wong, Richard; Wolden, Suzanne; Rao, Shyam; Lee, Nancy

    2016-01-01

    Objectives We previously reported inferior outcomes for locally advanced head and neck cancer treated with cetuximab (C225) versus cisplatin (CDDP). We now examine if this difference persists when accounting for HPV status and update outcomes on the entire cohort. Materials and Methods From 3/106 to 4/1/08, 174 locally advanced head and neck cancer patients received definitive treatment with RT and CDDP (n = 125) or RT and C225 (n = 49). Of these, 62 patients had tissue available for HPV analysis. Results The median follow-up was 47 months. The 3-year loco-regional failure, disease-free survival, and overall survival for CDDP versus C225 were 5.7% versus 40.2% (P < 0.0001), 85.1% versus 35.4% (P < 0.0001), and 90.0% versus 56.6% (P < 0.0001), respectively. In the subset with tissue, there was no difference in rates of HPV or p16 positivity between the 2 groups. In this subset, the 3-year loco-regional failure, disease-free survival, and overall survival for CDDP versus C225 were 5.3% versus 32.0% (P = 0.01), 86.8% versus 43.2% (P = 0.002), and 86.7% versus 76.9% (P = 0.09), respectively. Multivariate analysis continued to show a benefit for CDDP. Conclusions With longer follow-up and the inclusion of HPV and p16 status for about one third of patients where tissue was available, we continued to find superior outcomes with concurrent CDDP versus C225. PMID:24401670

  20. Hyperfractionated Accelerated Radiation Therapy (HART) of 70.6 Gy With Concurrent 5-FU/Mitomycin C Is Superior to HART of 77.6 Gy Alone in Locally Advanced Head and Neck Cancer: Long-term Results of the ARO 95-06 Randomized Phase III Trial

    SciTech Connect

    Budach, Volker; Stromberger, Carmen; Poettgen, Christoph; Baumann, Michael; Budach, Wilfried; Grabenbauer, Gerhard; Marnitz, Simone; Olze, Heidi; Wernecke, Klaus-Dieter; Ghadjar, Pirus

    2015-04-01

    Purpose: To report the long-term results of the ARO 95-06 randomized trial comparing hyperfractionated accelerated chemoradiation with mitomycin C/5-fluorouracil (C-HART) with hyperfractionated accelerated radiation therapy (HART) alone in locally advanced head and neck cancer. Patients and Methods: The primary endpoint was locoregional control (LRC). Three hundred eighty-four patients with stage III (6%) and IV (94%) oropharyngeal (59.4%), hypopharyngeal (32.3%), and oral cavity (8.3%) cancer were randomly assigned to 30 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total of 70.6 Gy concurrently with mitomycin C/5-FU (C-HART) or 16 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total dose of 77.6 Gy alone (HART). Statistical analyses were done with the log-rank test and univariate and multivariate Cox regression analyses. Results: The median follow-up time was 8.7 years (95% confidence interval [CI]: 7.8-9.7 years). At 10 years, the LRC rates were 38.0% (C-HART) versus 26.0% (HART, P=.002). The cancer-specific survival and overall survival rates were 39% and 10% (C-HART) versus 30.0% and 9% (HART, P=.042 and P=.049), respectively. According to multivariate Cox regression analysis, the combined treatment was associated with improved LRC (hazard ratio [HR]: 0.6 [95% CI: 0.5-0.8; P=.002]). The association between combined treatment arm and increased LRC appeared to be limited to oropharyngeal cancer (P=.003) as compared with hypopharyngeal or oral cavity cancer (P=.264). Conclusions: C-HART remains superior to HART in terms of LRC. However, this effect may be limited to oropharyngeal cancer patients.

  1. Ultrahigh head pump/turbine development program: Volume 4, Advanced design: Strength manufacturability, controls, and reliability: Final report

    SciTech Connect

    Yokoyama, T.

    1987-01-01

    The commercial availability of an ultrahigh head pump/turbine whose output can be regulated makes underground and ultrahigh head-pumped storage creditable options for utility use by reducing construction costs and plant complexity. This new turbine operates at double the head of existing equipment yet uses commercial materials, proven design concepts, and manageable manufacturing techniques. This volume discusses the stress analysis and fatigue evaluation, manufacturability, control system, and reliability and maintainability analyses.

  2. Reirradiation of head and neck cancer in the era of intensity-modulated radiotherapy: patient selection, practical aspects, and current evidence.

    PubMed

    Kim, Yeon Sil

    2017-03-01

    Locoregional failure is the most frequent pattern of failure in locally advanced head and neck cancer patients and it leads to death in most of the patients. Second primary tumors occurring in the other head and neck region reach up to almost 40% of long-term survivors. Recommended and preferred retreatment option in operable patients is salvage surgical resection, reporting a 5-year overall survival of up to 40%. However, because of tumor location, extent, and underlying comorbidities, salvage surgery is often limited and compromised by incomplete resection. Reirradiation with or without combined chemotherapy is an appropriate option for unresectable recurrence. Reirradiation is carefully considered with a case-by-case basis. Reirradiation protocol enrollment is highly encouraged prior to committing patient to an aggressive therapy. Radiation doses greater than 60 Gy are usually recommended for successful salvage. Despite recent technical improvement in intensity-modulated radiotherapy (IMRT), the use of concurrent chemotherapy, and the emergence of molecularly targeted agents, careful patient selection remain as the most paramount factor in reirradiation. Tumors that recur or persist despite aggressive prior chemoradiation therapy imply the presence of chemoradio-resistant clonogens. Treatment protocols that combine novel targeted radiosensitizing agents with conformal high precision radiation are required to overcome the resistance while minimizing toxicity. Recent large number of data showed that IMRT may provide better locoregional control with acceptable acute or chronic morbidities. However, additional prospective studies are required before a definitive conclusion can be drawn on safety and effectiveness of IMRT.

  3. Reirradiation of head and neck cancer in the era of intensity-modulated radiotherapy: patient selection, practical aspects, and current evidence

    PubMed Central

    Kim, Yeon Sil

    2017-01-01

    Locoregional failure is the most frequent pattern of failure in locally advanced head and neck cancer patients and it leads to death in most of the patients. Second primary tumors occurring in the other head and neck region reach up to almost 40% of long-term survivors. Recommended and preferred retreatment option in operable patients is salvage surgical resection, reporting a 5-year overall survival of up to 40%. However, because of tumor location, extent, and underlying comorbidities, salvage surgery is often limited and compromised by incomplete resection. Reirradiation with or without combined chemotherapy is an appropriate option for unresectable recurrence. Reirradiation is carefully considered with a case-by-case basis. Reirradiation protocol enrollment is highly encouraged prior to committing patient to an aggressive therapy. Radiation doses greater than 60 Gy are usually recommended for successful salvage. Despite recent technical improvement in intensity-modulated radiotherapy (IMRT), the use of concurrent chemotherapy, and the emergence of molecularly targeted agents, careful patient selection remain as the most paramount factor in reirradiation. Tumors that recur or persist despite aggressive prior chemoradiation therapy imply the presence of chemoradio-resistant clonogens. Treatment protocols that combine novel targeted radiosensitizing agents with conformal high precision radiation are required to overcome the resistance while minimizing toxicity. Recent large number of data showed that IMRT may provide better locoregional control with acceptable acute or chronic morbidities. However, additional prospective studies are required before a definitive conclusion can be drawn on safety and effectiveness of IMRT. PMID:28395502

  4. Pretreatment performance status and nutrition are associated with early mortality of locally advanced head and neck cancer patients undergoing concurrent chemoradiation.

    PubMed

    Chang, Pei-Hung; Yeh, Kun-Yun; Huang, Jen-Seng; Lai, Chien-Hong; Wu, Tsung-Han; Lan, Yii-Jenq; Tsai, Jason Chien-Sheng; Chen, Eric Yen-Chao; Yang, Shih-Wei; Wang, Cheng-Hsu

    2013-05-01

    Unexpected fatal events in patients with head and neck cancers undergoing concurrent chemoradiation therapy are a clinical concern. Malnutrition, which is reported frequently in head and neck cancer patients, are associated with immunity derangement. The purpose of this study was to identify risk factors for early death of patients undergoing chemoradiation. We retrospectively analyzed the records of 194 stage III, IVA, and IVB head and neck cancer patients who were treated with chemoradiation between 2007 and 2009. We defined early death as death while receiving chemoradiation or within 60 days of treatment completion. Risk factors for early death were tested using univariate and multivariate analyses. Fourteen patients (7.2 %) experienced early death, 78.6 % of whom died of infection. Univariate analysis revealed significant correlations between early death and several pretreatment variables, including Eastern Cooperative Oncology Group performance status (PS) >1, hemoglobin <10 g/dL, albumin <3 g/dL, body mass index (BMI) <19 kg/m(2), and peripheral blood total lymphocyte count <700/μL. Multivariate analysis showed that PS >1, BMI <19 kg/m(2), and peripheral blood total lymphocyte count <700/μL were independent variables associated with early death. Poor performance status and malnutrition before chemoradiation independently predict early death in locally advanced head and neck cancer patients undergoing chemoradiation. Cautious management of head and neck cancer patients with these risk factors is required throughout chemoradiation period.

  5. nab-Paclitaxel-based induction chemotherapy with or without cetuximab for locally advanced head and neck squamous cell carcinoma.

    PubMed

    Adkins, Douglas; Ley, Jessica; Oppelt, Peter; Wildes, Tanya M; Gay, Hiram A; Daly, Mackenzie; Rich, Jason; Paniello, Randal C; Jackson, Ryan; Pipkorn, Patrik; Nussenbaum, Brian; Trinkaus, Kathryn; Thorstad, Wade

    2017-09-01

    To explore the effect of incorporating cetuximab into induction chemotherapy in locally advanced head and neck squamous cell carcinoma (HNSCC). Retrospective comparative analysis of two consecutive prospective phase II trials was performed: trial 1 with nab-paclitaxel/cisplatin/5-FU and cetuximab (APF-C; n=30) and trial 2 with APF (n=30). Patients were scheduled to receive chemoradiation therapy (CRT) with cisplatin. T2-4 classification oropharynx (OP)/larynx/hypopharynx SCC were included. Cumulative incidence of death of disease (CIDD), overall survival (OS), and cumulative incidence of relapse were compared between APF-C and APF. No significant differences in patient or tumor characteristics were noted between the groups. Median follow-up of surviving patients was 52 (25-95) months. Relapse occurred in 5 (17%) patients treated with APF-C and in 2 (7%) treated with APF (p=0.37). In human papillomavirus (HPV)-related OPSCC (n=34), the CIDD at 52months was 3.4% with APF-C and 2.6% with APF and the two-year OSs were 94%. In HPV-unrelated HNSCC (n=25), the CIDD at 52months was 4.4% with APF-C and 3.3% with APF and two-year OSs were 83% and 92%, respectively. CIDD or OS did not differ when stratified by treatment group and HPV status (CIDD: p=0.80; OS: p=0.30). This exploratory retrospective comparative analysis demonstrated no significant difference in CIDD, OS, or cumulative incidence of relapse between patients treated with APF-C or APF. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Cost-effectiveness analysis of PET-CT-guided management for locally advanced head and neck cancer.

    PubMed

    Smith, A F; Hall, P S; Hulme, C T; Dunn, J A; McConkey, C C; Rahman, J K; McCabe, C; Mehanna, H

    2017-09-04

    A recent large United Kingdom (UK) clinical trial demonstrated that positron-emission tomography-computed tomography (PET-CT)-guided administration of neck dissection (ND) in patients with advanced head and neck cancer after primary chemo-radiotherapy treatment produces similar survival outcomes to planned ND (standard care) and is cost-effective over a short-term horizon. Further assessment of long-term outcomes is required to inform a robust adoption decision. Here we present results of a lifetime cost-effectiveness analysis of PET-CT-guided management from a UK secondary care perspective. Initial 6-month cost and health outcomes were derived from trial data; subsequent incidence of recurrence and mortality was simulated using a de novo Markov model. Health benefit was measured in quality-adjusted life years (QALYs) and costs reported in 2015 British pounds. Model parameters were derived from trial data and published literature. Sensitivity analyses were conducted to assess the impact of uncertainty and broader National Health Service (NHS) and personal social services (PSS) costs on the results. PET-CT management produced an average per-person lifetime cost saving of £1485 and an additional 0.13 QALYs. At a £20,000 willingness-to-pay per additional QALY threshold, there was a 75% probability that PET-CT was cost-effective, and the results remained cost-effective over the majority of sensitivity analyses. When adopting a broader NHS and PSS perspective, PET-CT management produced an average saving of £700 and had an 81% probability of being cost-effective. This analysis indicates that PET-CT-guided management is cost-effective in the long-term and supports the case for wide-scale adoption. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Hypopharyngeal Dose Is Associated With Severe Late Toxicity in Locally Advanced Head-and-Neck Cancer: An RTOG Analysis

    SciTech Connect

    Machtay, Mitchell; Moughan, Jennifer; Farach, Andrew; Galvin, James; Garden, Adam S.; Weber, Randal S.; Cooper, Jay S.; Forastiere, Arlene; Ang, K. Kian

    2012-11-15

    Purpose: Concurrent chemoradiation therapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases local tumor control but at the expense of increased toxicity. We recently showed that several clinical/pretreatment factors were associated with the occurrence of severe late toxicity. This study evaluated the potential relationship between radiation dose delivered to the pharyngeal wall and toxicity. Methods and Materials: This was an analysis of long-term survivors from 3 previously reported Radiation Therapy Oncology Group (RTOG) trials of CCRT for locally advanced SCCHN (RTOG trials 91-11, 97-03, and 99-14). Severe late toxicity was defined in this secondary analysis as chronic grade 3-4 pharyngeal/laryngeal toxicity and/or requirement for a feeding tube {>=}2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Radiation dosimetry (2-dimensional) analysis was performed centrally at RTOG headquarters to estimate doses to 4 regions of interest along the pharyngeal wall (superior oropharynx, inferior oropharynx, superior hypopharynx, and inferior hypopharynx). Case-control analysis was performed with a multivariate logistic regression model that included pretreatment and treatment potential factors. Results: A total of 154 patients were evaluable for this analysis, 71 cases (patients with severe late toxicities) and 83 controls; thus, 46% of evaluable patients had a severe late toxicity. On multivariate analysis, significant variables correlated with the development of severe late toxicity, including older age (odds ratio, 1.062 per year; P=.0021) and radiation dose received by the inferior hypopharynx (odds ratio, 1.023 per Gy; P=.016). The subgroup of patients receiving {<=}60 Gy to the inferior hypopharynx had a 40% rate of severe late toxicity compared with 56% for patients receiving >60 Gy. Oropharyngeal dose was not associated with this outcome. Conclusions: Severe late toxicity following CCRT is

  8. Cerebral revascularization and carotid artery resection at the skull base for treatment of advanced head and neck malignancies.

    PubMed

    Kalani, M Yashar S; Kalb, Samuel; Martirosyan, Nikolay L; Lettieri, Salvatore C; Spetzler, Robert F; Porter, Randall W; Feiz-Erfan, Iman

    2013-03-01

    Resection of cancer and the involved artery in the neck has been applied with some success, but the indications for such an aggressive approach at the skull base are less well defined. The authors therefore evaluated the outcomes of advanced skull base malignancies in patients who were treated with bypass and resection of the internal carotid artery (ICA). The authors retrospectively reviewed the charts of all patients with advanced head and neck cancers who underwent ICA sacrifice with revascularization in which an extracranial-intracranial bypass was used between 1995 and 2010 at the Barrow Neurological Institute. Eighteen patients (11 male and 7 female patients; mean age 46 years, range 7-69 years) were identified. There were 4 sarcomas and 14 carcinomas that involved the ICA at the skull base. All patients underwent ICA sacrifice with revascularization. One patient died of a stroke after revascularization. A second patient died of the effects of a fistula between the oral and cranial cavities (surgery-related mortality rate 11.1%). Eight months after the operation, 1 patient developed occlusion of the bypass and died. Complications associated with the bypass surgery included 1 case of subdural hematoma (SDH) with blindness, 1 case of status epilepticus, and 1 case of asymptomatic bypass occlusion (bypass-related morbidity 16.7%). Complications associated with tumor resection included 3 cases of CSF leakage requiring repair and shunting, 1 case of hydrocephalus requiring shunting, 1 case of SDH, and 1 case of contralateral ICA injury requiring a bypass (tumor resection morbidity rate 33.3%). In 1 patient treated with adjuvant therapy before surgery, the authors identified only a radiation effect and no tumor on resection. In a second patient the bypass was occluded, and her tumor was not resected. The other 16 patients underwent gross-total resection of their tumor. Excluding the surgery-related deaths, the mean and median lengths of survival in this series were

  9. Impact of the pretreatment Glasgow prognostic score on treatment tolerance, toxicities, and survival in patients with advanced head and neck cancer undergoing concurrent chemoradiotherapy.

    PubMed

    Chang, Pei-Hung; Yeh, Kun-Yun; Wang, Cheng-Hsu; Chen, Eric Yen-Chao; Yang, Shih-Wei; Huang, Jen-Seng; Chou, Wen-Chi; Hsieh, Jason Chia-Hsun

    2017-10-01

    The purpose of this study was to evaluate the impact of the pretreatment Glasgow prognostic score on treatment-related toxicities, tolerance, and survival in patients with advanced head and neck cancers undergoing concurrent chemoradiotherapy (CRT). We retrospectively analyzed and compared the clinical characteristics, toxicities, and survival of 143 patients with stages III, IVA, and IVB head and neck cancer treated with concurrent CRT according to their Glasgow prognostic score between 2007 and 2010. The Glasgow prognostic score was correlated with advanced tumor stage and T/N classification. Patients with a higher Glasgow prognostic score were less likely to tolerate concurrent CRT, experienced more weight loss, required tube feeding support more frequently, and had higher percentage of grade ≥3 hematological toxicities, sepsis, and toxic death. Patients with a Glasgow prognostic score of 0 had better overall and recurrence-free survival than those with a Glasgow prognostic score of 1 or 2. Pretreatment Glasgow prognostic score predicts treatment tolerance, toxicity, and survival in patients with advanced head and neck cancer undergoing concurrent CRT. © 2017 Wiley Periodicals, Inc.

  10. Efficacy of percutaneous endoscopic gastrostomy on unplanned treatment interruption and nutritional status in patients undergoing chemoradiotherapy for advanced head and neck cancer.

    PubMed

    Goda, Masakazu; Jinnouchi, Osamu; Takaoka, Tsukasa; Abe, Koji; Tamura, Koich; Nakaya, Yutaka; Furukita, Yoshihito; Takechi, Hirokazu; Tangoku, Akira; Takeda, Noriaki

    2015-01-01

    Efficacy of percutaneous endoscopic gastrostomy (PEG) on unplanned treatment interruption and nutritional status was examined in patients undergoing chemoradiotherapy (CRT) for advanced head and neck cancer. We retrospectively reviewed hospital charts of 44 patients with advanced head and neck cancer who were treated with CRT. CRT-induced mucositis of grade 3 or worse and inadequate oral intake of less than one third of their usual intake developed in 33 patients who were recommended PEG placement, but not in 11 patients. Thirteen patients accepted PEG placement and then completed CRT (compliant group). However, among 20 patients who refused both PEG and nasogastoric tube (NGT) placements (non-compliant group), 10 required unplanned interruptions of CRT at a radiation dose around 30-40 Gy (UI-CRT group) while 10 others could complete CRT without interruption (C-CRT group) CRT. Total serum protein levels were significantly decreased after CRT in all patients. It is suggested that therapeutic PEG placement is useful for preventing unplanned interruption of CRT in patients with advanced head and neck cancer. After severe mucositis and inadequate oral intake have developed during CRT, PEG placement should be considered before the radiation therapy dose of 30 Gy.

  11. Mature Results of a Randomized Trial of Accelerated Hyperfractionated Versus Conventional Radiotherapy in Head-and-Neck Cancer

    SciTech Connect

    Saunders, Michele I.; Rojas, Ana M.; Parmar, Mahesh K.B.; Dische, Stanley

    2010-05-01

    Purpose: To evaluate long-term late adverse events and treatment outcome of a randomized, multicenter Phase III trial of continuous, hyperfractionated, accelerated radiotherapy (CHART) compared with conventional radiotherapy (CRT) in 918 patients with advanced squamous cell carcinomas of the head and neck. Methods and Materials: Survival estimates were obtained for locoregional relapse-free survival, local relapse-free survival, overall survival, disease-specific survival, disease-free survival and for late adverse events. Results: The 10-year estimates (+-1 standard error) for locoregional relapse-free survival, overall survival, disease-free survival, and disease-specific survival were 43% +- 2% for CHART and 50% +- 3% with CRT (log-rank p = 0.2); 26% +- 2% and 29% +- 3% (p = 0.4), respectively; 41% +- 2% and 46% +- 3% (p = 0.3), respectively; and 56% +- 3% and 58% +- 3% (p = 0.5), respectively. There was a small but significant reduction in the incidence of slight or worse and moderate or worse epidermal adverse events with CHART (p = 0.002 to 0.05). Severe xerostomia, laryngeal edema, and mucosal necrosis were also significantly lower with CHART (p = 0.02 to 0.05). Conclusions: Despite the reduction in total dose from 66 Gy to 54 Gy, control of locoregional disease and survival with CHART were similar to those with CRT. These findings, together with the low incidence of long-term severe adverse events, suggest that CHART is a treatment option for patients with low-risk disease and for those unable to withstand the toxicity of concurrent chemoradiotherapy.

  12. Therapeutic exercises for affecting post-treatment swallowing in people treated for advanced-stage head and neck cancers.

    PubMed

    Perry, Alison; Lee, Siew Hwa; Cotton, Susan; Kennedy, Catriona

    2016-08-26

    Head and neck cancer treatment has developed over the last decade, with improved mortality and survival rates, but the treatments often result in dysphagia (a difficulty in swallowing) as a side effect. This may be acute, resolving after treatment, or remain as a long-term negative sequela of head and neck cancer (HNC) treatment. Interventions to counteract the problems associated with dysphagia include swallowing exercises or modification of diet (bolus texture, size), or both. To determine the effects of therapeutic exercises, undertaken before, during and/or immediately after HNC treatment, on swallowing, aspiration and adverse events such as chest infections, aspiration pneumonia and profound weight loss, in people treated curatively for advanced-stage (stage III, stage IV) squamous cell carcinoma of the head and neck. The Cochrane ENT Information Specialist searched the ENT Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 6); MEDLINE; PubMed; Embase; CINAHL; LILACS; KoreaMed; IndMed; PakMediNet; Web of Science; ClinicalTrials.gov; ICTRP; speechBITE; Google Scholar; Google and additional sources for published and unpublished trials. The date of the search was 1 July 2016. We selected randomised controlled trials (RCTs) of adults with head and neck cancer (stage III, stage IV) who underwent therapeutic exercises for swallowing before, during and/or immediately after HNC treatment to help produce safe and efficient swallowing. The main comparison was therapeutic exercises versus treatment as usual (TAU). Other possible comparison pairs included: therapeutic exercises versus sham exercises and therapeutic exercises plus TAU versus TAU. TAU consisted of reactive management of a patient's dysphagia, when this occurred. When severe, this included insertion of either a percutaneous endoscopic gastroscopy or nasogastric tube for non-oral feeding. We used the standard methodological procedures expected by Cochrane. Our primary

  13. Pretreatment anemia is correlated with the reduced effectiveness of radiation and concurrent chemotherapy in advanced head and neck cancer

    SciTech Connect

    Prosnitz, Robert G. . E-mail: robert.prosnitz@duke.edu; Yao, Bin M.S.; Farrell, Catherine L.; Clough, Robert; Brizel, David M.

    2005-03-15

    Purpose: Pretreatment anemia is an adverse prognostic variable in squamous cell head-and-neck cancer (HNC) patients treated with radiotherapy (RT) alone. Tumor hypoxia is an adverse parameter for treatment with RT alone or with RT and concurrent chemotherapy (CCT). Tumor hypoxia is more prevalent in patients who present with pretreatment hemoglobin (Hgb) concentrations less than 13 g/dL. RT/CCT improves survival over RT alone in advanced HNC, and its use is becoming more widespread. This study was performed to evaluate whether pretreatment Hgb less than 13 g/dL was correlated with treatment outcome in patients with advanced HNC treated with a uniform regimen of RT/CCT. Methods and materials: The study population consisted of patients with AJCC Stage III or IV, M0 HNC who were treated with 70 to 72.5 Gy accelerated hyperfractionated RT (1.25 Gy b.i.d.) and CCT consisting of 2 cycles of CDDP (12-20 mg/m{sup 2}/d x 5 days) and continuous infusion 5-FU (600 mg/m{sup 2}/d x 5 days) during Week 1 and Week 6. A planned break in RT occurred during Week 4. These patients were enrolled on the experimental arm of a prospective randomized trial that compared this regimen to hyperfractionated irradiation alone from 1990 to 1996. RT/CCT was delivered as standard therapy from 1996 to 2000. The primary endpoint was failure-free survival (FFS). Secondary endpoints included local-regional control and overall survival. Results: One hundred and fifty-nine patients were treated from 1990 to 2000. The median (25-75%) pretreatment Hgb was 13.6 (12.2-13.5) g/dL. Hgb was 13 g/dL or higher in 105 patients and less than 13 g/dL in 54 patients. Primary tumor sites included oropharynx (43%), hypopharynx/larynx (36%), oral cavity (9%), and nasopharynx (6%). Seventy-eight percent of the patients with Hgb 13 g/dL or higher and 92% of the patients with Hgb less than 13 g/dL had a primary tumor stage of T3 or T4 (p = 0.01). Node-positive disease was present in 74 of 105 (70%) of patients with Hgb

  14. Long-term results of paclitaxel plus cisplatin with concurrent radiotherapy for loco-regional esophageal squamous cell carcinoma

    PubMed Central

    Zhu, Han-Ting; Ai, Da-Shan; Tang, Hua-Rong; Badakhshi, Harun; Fan, Jian-Hong; Deng, Jia-Ying; Zhang, Jun-Hua; Chen, Yun; Zhang, Zhen; Xia, Yi; Guo, Xiao-Mao; Jiang, Guo-Liang; Zhao, Kuai-Le

    2017-01-01

    AIM To evaluate the long-term effectiveness and late toxicities of paclitaxel (PTX) plus cisplatin (DDP) with concurrent radiotherapy for locally advanced esophageal squamous cancer. METHODS Between 2008 and 2011, 76 patients were enrolled in a phase II study on the treatment of loco-regionally advanced esophageal cancer with radiotherapy (68.4 Gy/44 fractions or 61.2 Gy/34 fractions) combined with 4-cycle chemotherapy consisting of DDP (25 mg/m2 per day for 3 d) and PTX (175 mg/m2 for 3 h). The primary endpoints were overall survival and progression-free survival, and the secondary endpoints were toxicity and the treatment failure pattern. RESULTS A total of 76 patients were enrolled in this study, of whom 63.2% finished the whole regimen. The 5-year survival rates for the per-protocol population and intent-to-treat population were 25.4% and 26.4%, respectively, and the median survival rates were 23.7 mo and 28.5 mo, respectively. Grade 3 or 4 late toxicity was observed in only one patient (heart failure). In log-rank analysis, the pretreatment stage (stage II + III: 36.1 mo vs stage IV: 14.9 mo) and the completed cycle (1-3 cycles: 16.1 mo vs 4 cycles: 35.5 mo) were significant prognostic factors (P = 0.037 < 0.05 and P = 0.013 < 0.05). CONCLUSION Radiotherapy combined with chemotherapy consisting of PTX and DDP is a safe and effective definitive treatment for loco-regionally advanced esophageal squamous cancer. PMID:28210091

  15. Role of endoscopic ultrasonography in the loco-regional staging of patients with rectal cancer

    PubMed Central

    Marone, Pietro; de Bellis, Mario; D’Angelo, Valentina; Delrio, Paolo; Passananti, Valentina; Di Girolamo, Elena; Rossi, Giovanni Battista; Rega, Daniela; Tracey, Maura Claire; Tempesta, Alfonso Mario

    2015-01-01

    The prognosis of rectal cancer (RC) is strictly related to both T and N stage of the disease at the time of diagnosis. RC staging is crucial for choosing the best multimodal therapy: patients with high risk locally advanced RC (LARC) undergo surgery after neoadjuvant chemotherapy and radiotherapy (NAT); those with low risk LARC are operated on after a preoperative short-course radiation therapy; finally, surgery alone is recommended only for early RC. Several imaging methods are used for staging patients with RC: computerized tomography, magnetic resonance imaging, positron emission tomography, and endoscopic ultrasound (EUS). EUS is highly accurate for the loco-regional staging of RC, since it is capable to evaluate precisely the mural infiltration of the tumor (T), especially in early RC. On the other hand, EUS is less accurate in restaging RC after NAT and before surgery. Finally, EUS is indicated for follow-up of patients operated on for RC, where there is a need for the surveillance of the anastomosis. The aim of this review is to highlight the impact of EUS on the management of patients with RC, evaluating its role in both preoperative staging and follow-up of patients after surgery. PMID:26140096

  16. Imaging paradigms in assessment of rectal carcinoma: loco-regional and distant staging

    PubMed Central

    Liang, Thian Yee; Ang, Bertrand W.L.

    2012-01-01

    Abstract The role of imaging in the management of rectal malignancy has progressively evolved and undergone several paradigm shifts. Unlike a few decades ago when the role of a radiologist was restricted at defining the longitudinal extent of the tumour with barium enema, recent advances in imaging techniques permit highly accurate locoregional and distant staging of the disease as well as prognostication on those who are likely to have a postoperative recurrence. Computed tomography (CT) has always been the mainstay of imaging when evaluating for distant metastasis, with the advent of positron emission tomography/CT improving its specificity. In rectal malignancy, it is the local extent of the disease that often influences the surgical decision making and need for neoadjuvant therapy. Although endoscopic ultrasound has been the traditional technique for determining the depth of tumour invasion, over the last decade magnetic resonance imaging (MRI) has emerged as a very effective tool for accurate T-staging. This review intends to address the status of various imaging modalities and their advantages and limitations in detection, pretreatment staging, and assessment of therapeutic efficacy in rectal cancer, with emphasis on MRI of high spatial resolution. PMID:23033451

  17. Radiation therapy in the locoregional treatment of triple-negative breast cancer.

    PubMed

    Moran, Meena S

    2015-03-01

    This Review assesses the relevant data and controversies regarding the use of radiotherapy for, and locoregional management of, women with triple-negative breast cancer (TNBC). In view of the strong association between BRCA1 and TNBC, knowledge of baseline mutation status can be useful to guide locoregional treatment decisions. TNBC is not a contraindication for breast conservation therapy because data suggest increased locoregional recurrence risks (relative to luminal subtypes) with breast conservation therapy or mastectomy. Although a boost to the tumour bed should routinely be considered after whole breast radiation therapy, TNBC should not be the sole indication for post-mastectomy radiation, and accelerated delivery methods for TNBC should be offered on clinical trials. Preliminary data implying a relative radioresistance for TNBC do not imply radiation omission because radiation provides an absolute locoregional risk reduction. At present, the integration of subtypes in locoregional management decisions is still in its infancy. Until level 1 data supporting treatment decisions based on subtypes are available, standard locoregional management principles should be adhered to. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Predictors of loco-regional recurrence and cancer-related death after breast cancer surgery.

    PubMed

    Rausei, Stefano; Rovera, Francesca; Dionigi, Gianlorenzo; Tornese, Deborah; Fachinetti, Anna; Boni, Luigi; Dionigi, Renzo

    2010-01-01

    To determine which tumor-related factors might predispose the patient to loco-regional recurrence or death and the impact of these factors on the different types of events. We retrospectively analyzed the data of 1991 women between January 1998 and March 2010 for a first primary nonmetastatic breast cancer and treated with surgery and neo-adjuvant/adjuvant therapy. The overall survival distribution was estimated using the Kaplan-Meier method. The prognostic impact of several factors on cumulative overall and loco-regional recurrence free survival was evaluated by univariate (log-rank test) and multivariate analysis (Cox regression). At log-rank test, pT, nodal status, histotype, grading, lymphangioinvasive growth, tumor diameter, estrogen receptors (ER) status, progesterone receptors (PR) status, expression of Ki67, and expression of Her2/neu had a prognostic value on loco-regional recurrence or overall survival. In the multivariate analysis grading remained the only independent predictor of loco-regional recurrences. With regard to overall survival, the Cox model selected grading along with nodal status and PR status. Loco-regional recurrences after breast cancer surgery are not frequent events. They are markers of tumor aggressiveness and predictor of an increased likelihood of cancer-related death. However, loco-regional recurrence and systemic tumor progression are partially independent events, since some prognostic factors differ.

  19. Impact of cisplatin dose intensity on human papillomavirus-related and -unrelated locally advanced head and neck squamous cell carcinoma.

    PubMed

    Spreafico, Anna; Huang, Shao Hui; Xu, Wei; Granata, Roberta; Liu, Chen-Shin; Waldron, John N; Chen, Eric; Ringash, Jolie; Bayley, Andrew; Chan, Kelvin K W; Hope, Andrew J; Cho, John; Razak, Albiruni A R; Hansen, Aaron; Jang, Raymond; Perez-Ordonez, Bayardo; Weinreb, Ilan; Bossi, Paolo; Orlandi, Ester; Licitra, Lisa F; Song, Yuyao; O'Sullivan, Brian; Siu, Lillian L; Kim, John

    2016-11-01

    The aim is to evaluate the impact of cisplatin dose modification on outcomes of human papillomavirus (HPV)-related (HPV+) and HPV-unrelated (HPV-) locally advanced head and neck cancer (LAHNC) treated with chemoradiotherapy (CRT). A pooled analysis was conducted of stage III/IV oropharyngeal cancer (OPC), carcinoma of unknown primary (CUP) and laryngo-hypopharyngeal cancer (LHC) patients treated with single-agent cisplatin CRT in 2000-2012 from two tertiary academic cancer centres. HPV status was determined by p16 staining and/or in situ hybridisation. LHC was assumed to be HPV-. Unknown HPV status OPC/CUPs were excluded. Overall survival (OS) was calculated. Multivariable analysis (MVA) evaluated the impact of cisplatin dose intensity on survival for HPV+ and HPV- cohorts separately. A total of 404 HPV+ and 255 HPV- LAHNC (481 OPC, 18 CUP, 160 LHC) patients were included. Median follow-up was 4.3 (0.5-11.9) years. Three-year OS for cisplatin <200, =200, and >200 mg/m(2) subgroups were 52%, 60%, and 72% (P = 0.001) for the HPV- and 91%, 90%, and 91% (P = 0.30) for the HPV+ patients. MVA confirmed a survival benefit with cisplatin >200 mg/m(2) for the HPV- (hazard ratio [HR] 0.5, 95% confidence interval [CI]: 0.3-0.7, P < 0.001) but not for HPV+ (HR 0.6, 95% CI: 0.4-1.1, P = 0.104). There was a superior OS trend in the HPV+ T4 or N3 high-risk subset (N = 107) with cisplatin >200 mg/m(2) (HR 0.5, 95% CI: 0.2-1.1, P = 0.07). A survival benefit of cisplatin dose >200 mg/m(2) is evident for HPV- LAHNC patients, but not for HPV+ cohort overall, although the T4 or N3 subset may benefit from a higher cumulative cisplatin dose. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Evaluation of advanced turbomachinery for underground pumped hydroelectric storage. Part 3. Multistage unregulated pump/turbines for operating heads of 1000 to 1500 m

    SciTech Connect

    Frigo, A.A.; Pistner, C.

    1980-08-01

    This is the final report in a series of three on studies of advanced hydraulic turbomachinery for underground pumped hydroelectric storage. All three reports address Francis-type, reversible pump/turbines. The first report covered single-stage regulated units; the second report covered two-stage regulated units; the present report covers multistage unregulated units. Multistage unregulated pump/turbines offer an economically attractive option for heads of 1000 to 1500 m. The feasibility of developing such machines for capacities up to 500 MW and operating heads up to 1500 m has been evaluated. Preliminary designs have been generated for six multistage pump/turbines. The designs are for nominal capacities of 350 and 500 MW and for operating heads of 1000, 1250, and 1500 m. Mechanical, hydraulic, and economic analyses indicate that these machines will behave according to the criteria used to design them and that they can be built at a reasonable cost with no unsolvable problems. Efficiencies of 85.8% and 88.5% in the generating and pumping modes, respectively, can be expected for the 500-MW, 1500-m unit. Performances of the other five machines are at least comparable, and usually better. Over a 1000 to 1500-m head range, specific $/kW costs of the pump/turbines in mid-1978 US dollars vary from 19.0 to 23.1 for the 500-MW machines, and from 21.0 to 24.1 for the 350-MW machines.

  1. Locoregional symptoms in patients with de novo metastatic prostate cancer: Morbidity, management, and disease outcome.

    PubMed

    Patrikidou, Anna; Brureau, Laurent; Casenave, Julien; Albiges, Laurence; Di Palma, Mario; Patard, Jean-Jacques; Baumert, Hervé; Blanchard, Pierre; Bossi, Alberto; Kitikidou, Kyriaki; Massard, Christophe; Fizazi, Karim; Blanchet, Pascal; Loriot, Yohann

    2015-05-01

    The paradigm change observed over the last few years in several solid tumors emphasizes the value of locoregional treatment in the presence of metastatic disease, currently ignored in de novo prostate cancer (CaP). We investigated the effect of the primary tumor that is left untreated on prostate cancer-specific morbidity and mortality, time to castration resistance, and overall survival (OS). We performed a bicentric cohort study. The overall population included de novo metastatic CaP managed at the Genito-Urinary Oncology Unit of the Gustave Roussy Institute and the Urology Clinic of the University Hospital of Pointe-à-Pitre, France. Descriptive statistical and outcome analyses were performed in the overall cohort and also separately in the N+M0 and M+subgroups. The overall cohort included 263 patients. Approximately two-thirds of patients (64%) presented with locoregional symptoms at diagnosis, and 78% throughout the disease. Of the symptomatic patients, 59% required a locoregional procedure. Median OS of patients with locoregional symptoms at diagnosis was shorter than in those who were asymptomatic (47 vs. 86 mo, P = 0.0007); this difference was maintained in the N+M0 and M+subgroups. Median OS and time to castration resistance showed a nonsignificant trend in favor of patients undergoing a locoregional treatment at diagnosis. The presence of symptoms due to locoregional disease in de novo metastatic CaP entails significant morbidity and even mortality and requires active management. Randomized prospective trials are needed to evaluate the role of initial definite locoregional treatment in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Effect on long-term survival of psychiatric disorder, inflammation, malnutrition, and radiotherapy-related toxicity in patients with locally advanced head and neck cancer.

    PubMed

    Unal, Dilek; Eroglu, Celalettin; Ozsoy, Saliha Demirel; Besirli, Asli; Orhan, Okan; Kaplan, Bunyamin

    2015-01-01

    To evaluate the effects on the long-term survival of psychiatric disorders, inflammation, malnutrition, and radiotherapy (RT)-related toxicity in patients with locally advanced head and neck cancer. Included were 47 patients who received RT for non-metastatic locally advanced head and neck cancer. The diagnosis of psychiatric disorder was made by the Diagnostic and Statistical Manual of Mental disorders (4th edn) (DSM-IV) criteria. Malnutrition was defined as weight loss >5% of baseline during RT. Interleukin 1β (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed by enzyme-linked immunosorbent assay (ELISA). RT-related acute toxicity was evaluated once a week using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0. The mean patient age was 57.3±11.4 years (range 33-80); 42 (89.4%) patients were male. Mean disease-free (DFS) and overall survival (OS) were 53 and 55 months, respectively. Mean DFS was significantly lower in patients with psychiatric disorder compared with those without (35 vs 59 months, p=0.013) and the same applied for mean OS (41 vs 61 months, p=0.008). There was no significant difference between patients with and without malnutrition in terms of OS. Similarly, no significant difference was seen between patients with and without RT-related toxicities in terms of OS. Age, psychiatric disorder, T status, and stage differed significantly between these groups (p<0.10) in univariate analysis. The multivariate Cox regression analysis identified that the OS was significantly associated only with psychiatric disorder (odds ratio/OR: 3.22, 95% confidence interval/CI: 1.29-8.41, p=0.013). Psychiatric disorders had unfavorable effects on OS in patients with locally advanced head and neck cancer. Inflammation, malnutrition and RT-related toxicity had no significant impact on OS.

  3. Poor Prognosis After Second Locoregional Recurrences in the CALOR Trial.

    PubMed

    Wapnir, Irene L; Gelber, Shari; Anderson, Stewart J; Mamounas, Eleftherios P; Robidoux, André; Martín, Miguel; Nortier, Johan W R; Geyer, Charles E; Paterson, Alexander H G; Láng, István; Price, Karen N; Coates, Alan S; Gelber, Richard D; Rastogi, Priya; Regan, Meredith M; Wolmark, Norman; Aebi, Stefan

    2017-02-01

    Isolated locoregional recurrences (ILRRs) of breast cancer confer a significant risk for the development of distant metastasis. Management practices and second ILRR events in the Chemotherapy as Adjuvant for LOcally Recurrent breast cancer (CALOR) trial were investigated. In this study, 162 patients with ILRR were randomly assigned to receive postoperative chemotherapy or no chemotherapy. Descriptive statistics characterize outcomes according to local therapy and the influence of hormone receptor status on subsequent recurrences. Competing risk regression models, Kaplan-Meier estimates, and Cox proportional hazards models were used to evaluate associations between treatment, site of second recurrence, and outcome. The median follow-up period was 4.9 years. Of the 98 patients who received breast-conserving primary surgery 89 had an ipsilateral-breast tumor recurrence. Salvage mastectomy was performed for 73 patients and repeat lumpectomy for 16 patients. Another eight patients had nodal ILRR, and one patient had chest wall ILRR. Among 64 patients whose primary surgery was mastectomy, 52 had chest wall/skin ILRR, and 12 had nodal ILRR. For 15 patients, a second ILRR developed a median of 1.6 years (range 0.08-4.8 years) after ILRR. All second ILRRs occurred for patients with progesterone receptor-negative ILRR. Death occurred for 7 (47 %) of 15 patients with a second ILRR and 19 (51 %) of 37 patients with a distant recurrence. As shown in the multivariable analysis, the significant predictors of survival after either a second ILRR or distant recurrence were chemotherapy for the primary cancer (hazard ratio [HR], 3.55; 95 % confidence interval [CI], 1.15-10.9; p = 0.03) and the interval (continuous) from the primary surgery (HR, 0.87; 95 % CI, 0.75-1.00; p = 0.05). Second ILRRs represented about one third of all recurrence events after ILRR, and all were PR-negative. These second ILRRs and distant metastases portend an unfavorable outcome.

  4. Systemic chemotherapy followed by locoregional definitive intensity-modulated radiation therapy yields prolonged survival in nasopharyngeal carcinoma patients with distant metastasis at initial diagnosis.

    PubMed

    Hu, Shao-xuan; He, Xiao-hui; Dong, Mei; Jia, Bo; Zhou, Sheng-yu; Yang, Jian-liang; Yang, Sheng; Zhang, Chang-Gong; Liu, Peng; Qin, Yan; Gui, Lin

    2015-09-01

    Chemotherapy is the current mainstay of treatment for patients with newly diagnosed metastatic nasopharyngeal carcinoma (NPC), whereas the role of locoregional radiotherapy remains to be defined. In this study, we retrospectively evaluated the outcome of systemic chemotherapy followed by locoregional definitive intensity-modulated radiation therapy (IMRT) as first-line treatment for these patients. Forty-one patients with pathologically confirmed NPC with distant metastasis at initial diagnosis seen between March 2005 and February 2014 were included. All the patients were treated with platinum-based systemic chemotherapy followed by definitive IMRT to the primary head and neck region with or without concurrent chemotherapy. In addition, local treatment to metastatic lesions was given in 19 patients. With a median follow-up time of 25 months, 24 patients had died, and the estimated median overall survival time was 31.2 months. The 1-, 2-, 3- and 5-year estimated OS rates were 89.9, 67.4, 41.1 and 22.5%, respectively. Prognostic analyses showed that serum lactate dehydrogenase level (P = 0.021) and number of metastatic sites (single vs. multiple; P = 0.016) were significant prognostic factors. Five patients are still alive without evidence of disease after 52 to >101 months. All of them had a single metastatic lesion and received local treatment to metastatic sites. These results suggest that the use of definitive IMRT to treat the locoregional tumor in combination with systemic chemotherapy may prolong survival in patients with newly diagnosed metastatic NPC, making curability a possible consideration in selected patients with single metastasis. Further prospective clinical trials are warranted.

  5. Sir Hugh Cairns and World War II British advances in head injury management, diffuse brain injury, and concussion: an Oxford tale.

    PubMed

    Stone, James L; Patel, Vimal; Bailes, Julian E

    2016-11-01

    The authors trace the Oxford, England, roots of World War II (WWII)-related advances in head injury management, the biomechanics of concussion and brain injury, and postwar delineation of pathological findings in severe concussion and diffuse brain injury in man. The prominent figure in these developments was the charismatic and innovative Harvey Cushing-trained neurosurgeon Sir Hugh Cairns. Cairns, who was to closely emulate Cushing's surgical and scholarly approach, is credited with saving thousands of lives during WWII by introducing and implementing innovative programs such as helmets for motorcyclists, mobile neurosurgical units near battle zones, and the military usage of penicillin. In addition, he inspired and taught a generation of neurosurgeons, neurologists, and neurological nurses in the care of brain and spinal cord injuries at Oxford's Military Hospital for Head Injuries. During this time Cairns also trained the first full-time female neurosurgeon. Pivotal in supporting animal research demonstrating the critical role of acceleration in the causation of concussion, Cairns recruited the physicist Hylas Holbourn, whose research implicated rotary acceleration and shear strains as particularly damaging. Cairns' work in military medicine and head injury remain highly influential in efforts to mitigate and manage brain injury.

  6. Structural Benchmark Creep Testing for Microcast MarM-247 Advanced Stirling Convertor E2 Heater Head Test Article SN18

    NASA Technical Reports Server (NTRS)

    Krause, David L.; Brewer, Ethan J.; Pawlik, Ralph

    2013-01-01

    This report provides test methodology details and qualitative results for the first structural benchmark creep test of an Advanced Stirling Convertor (ASC) heater head of ASC-E2 design heritage. The test article was recovered from a flight-like Microcast MarM-247 heater head specimen previously used in helium permeability testing. The test article was utilized for benchmark creep test rig preparation, wall thickness and diametral laser scan hardware metrological developments, and induction heater custom coil experiments. In addition, a benchmark creep test was performed, terminated after one week when through-thickness cracks propagated at thermocouple weld locations. Following this, it was used to develop a unique temperature measurement methodology using contact thermocouples, thereby enabling future benchmark testing to be performed without the use of conventional welded thermocouples, proven problematic for the alloy. This report includes an overview of heater head structural benchmark creep testing, the origin of this particular test article, test configuration developments accomplished using the test article, creep predictions for its benchmark creep test, qualitative structural benchmark creep test results, and a short summary.

  7. Influence of haemoglobin concentration and peripheral muscle pO2 on tumour oxygenation in advanced head and neck tumours.

    PubMed

    Clavo, Bernardino; Pérez, Juan L; López, Laura; Suárez, Gerardo; Lloret, Marta; Morera, Jesús; Macías, David; Martínez, José C; Santana, Maite; Hernández, María A; Robaina, Francisco; Günderoth, Martina

    2003-01-01

    Haemoglobin concentrations and tumour-pO(2) were evaluated pre-therapy in 30 patients with head and neck cancers. Anterior tibialis muscle-pO(2) was additionally measured in 16 of these patients. Tumour-pO(2) was lower in the most anaemic patients (P=0.032) and correlated with muscle-pO(2) (r=0.809, P<0.001). These results suggest that haemoglobin concentration influences tumour-oxygenation.

  8. Ultrahigh head pump/turbine development program: Volume 3, Advanced design: Static stress analysis, main components: Final report

    SciTech Connect

    Yokoyama, T.

    1987-01-01

    This report concerns the progress of the stress and deformation analyses made during the period from August to December, 1982. The structure designed in the early period of Task 2 was used for the analyses. Analyses are made for the major components; the top stage runner, the wicket gates, the return guide, the spiral casing and speed ring, the head cover and the bottom cover.

  9. [Loco-regional chemotherapy at the outpatient clinic for gastric cancer patients with home enteral nutrition].

    PubMed

    Maruyama, Michio; Nagahama, Takeshi; Sugano, Norihide; Satoh, Eigo; Maruyama, Shouji; Tanami, Hideo; Chiba, Tetsuma; Murakata, Ayano; Mitsuhashi, Yosuke; Uehira, Daisuke; Akazawa, Naoya; Suzuki, Keiichirou

    2011-11-01

    In over the 10 years from 2000-2010, 21 gastric cancer patients received loco-regional chemotherapy with home enteral nutrition (HEN) at an outpatient clinic because of insufficient oral intake. These loco-regional chemotherapy regimens consisted of 5 intra-aortic chemotherapies, 4 hepato-arterial infusions and 12 intra-peritoneal chemotherapies. Five out of 8 cases that had measurable lesions showed PR, and 3 cases revealed PD. The patients received HEN with peptide central formula, 400-1,200 kcal/day in night time. The average duration of HEN was 12.9 months. The post-operative nutritional management was needed for continuation and securing of outpatient chemotherapy. The author reported an experience of the outpatient loco-regional chemotherapy with HEN for the gastric cancer patients who could not eat a sufficient volume of food.

  10. /sup 125/I implants as an adjuvant to surgery and external beam radiotherapy in the management of locally advanced head and neck cancer

    SciTech Connect

    Martinez, A.; Goffinet, D.R.; Fee, W.; Goode, R.; Cox, R.S.

    1983-03-15

    /sup 125/I seeds either individually placed or inserted into absorbable Vicryl suture carriers were utilized in conjunction with surgery and external beam radiotherapy in an attempt to increase local control rates in patients with advanced oropharyngeal and laryngopharyngeal cancers (T3-T4, N2-N3), massive cervical lymphadenopathy (N3) and an unknown primary site and locally recurrent head and neck cancers. Forty-eight patients were treated with 55 implants. The carotid artery was implanted in 15 patients, while seven patients had seeds inserted into the base of the skull region, and another three patients had implants near cranial nerves. Eighteen of the 48 patients were treated for cure. The actuarial survival at five years in this subgroup was 50%. The overall local control in the head and neck area was 58%. In this group no patients to date have had a local failure in the implanted volume. Seventeen patients with comparable stage of disease treated prior to 1974 with curative intent without /sup 125/I implants were analyzed retrospectively for comparison with the implanted patients. The actuarial survival of these patients was 18% and the overall head and neck control was 21%. These differences are statistically significant at a P value of 0.01 and 0.007, respectively. Seventeen patients received implants for local recurrence. The local control in the head and neck area was 50%; however, the 2.5 year actuarial survival was only 17%. The complication rate was 11% (six of 55 implants). The improved survival, the high local control, and the minimal complication rates in this series makes the intraoperative implantation of /sup 125/I seeds and effective adjunctive treatment to surgery and external beam irradiation.

  11. /sup 125/Iodine implants as an adjuvant to surgery and external beam radiotherapy in the management of locally advanced head and neck cancer

    SciTech Connect

    Martinez, A.; Goffinet, D.R.; Fee, W.; Goode, R.; Cox, R.S.

    1983-03-15

    /sup 125/Iodine seeds either individually placed or inserted into absorbable Vicryl suture carriers were utilized in conjunction with surgery and external beam radiotherapy in an attempt to increase local control rates in patients with (1) advanced oropharyngeal and laryngopharyngeal cancers (T3-T4, N2-N3), (2) massive cervical lymphadenopathy (N3) and an unknown primary site and (3) locally recurrent head and neck cancers. Forty-eight patients were treated with 55 implants. The carotid artery was implanted in 15 patients, while seven patients had seeds inserted into the base of the skull region, and another three patients had implants near cranial nerves. Eighteen of the 48 patients were treated for cure. The actuarial survival at five years in this subgroup was 50%. The overall local control in the head and neck area was 58%. In this group no patients to date have had a local failure in the implanted volume. Seventeen patients with comparable stage of disease treated prior to 1974 with curative intent without /sup 125/I implants were analyzed retrospectively for comparison with the implanted patients. The actuarial survival of these patients was 18% and the overall head and neck control was 21%. These differences are statistically significant at a P value of 0.01 and 0.007, respectively. Seventeen patients received implants for local recurrence. The local control in the head and neck area was 50%; however, the 2.5 year actuarial survival was only 17%. The complication rate was 11% (six of 55 implants). The improved survival, the high local control, and the minimal complication rates in this series makes the intraoperative implantation of /sup 125/I seeds and effective adjunctive treatment to surgery and external beam irradiation.

  12. Locoregional Tumor Progression After Radiation Therapy Influences Overall Survival in Pediatric Patients With Neuroblastoma

    SciTech Connect

    Pai Panandiker, Atmaram S.; McGregor, Lisa; Krasin, Matthew J.; Wu Shengjie; Xiong Xiaoping; Merchant, Thomas E.

    2010-03-15

    Purpose: There is renewed attention to primary site irradiation and local control for patients with high-risk neuroblastoma (NB). We conducted a retrospective review to identify factors that might predict for locoregional tumor control and its impact on overall survival. Methods and Materials: Between July 2000 through August 2006, a total of 44 pediatric patients with NB received radiation therapy (RT) with curative intent using computed tomography (CT)-based treatment planning. The median age was 3.4 years and the median cumulative dose was 23.4 Gy. Overall survival and locoregional tumor control were measured from the start of RT to the date of death or event as determined by CT/magnetic resonance imaging/meta-iodobenzylguanidine. The influence of age at irradiation, gender, race, cumulative radiation dose, International Neuroblastoma Staging System stage, treatment protocol and resection status was determined with respect to locoregional tumor control. Results: With a median follow-up of 34 months +- 21 months, locoregional tumor progression was observed in 11 (25%) and was evenly divided between primary site and adjacent nodal/visceral site failure. The influence of locoregional control reached borderline statistical significance (p = 0.06). Age (p = 0.5), dose (p = 0.6), resection status (p = 0.7), and International Neuroblastoma Staging System stage (p = 0.08) did not influence overall survival. Conclusions: Overall survival in high-risk neuroblastoma is influenced by locoregional tumor control. Despite CT-based planning, progression in adjacent nodal/visceral sites appears to be common; this requires further investigation regarding target volume definitions, dose, and the effects of systemic therapy.

  13. Ten-Year Recurrence Rates in Young Women With Breast Cancer by Locoregional Treatment Approach

    SciTech Connect

    Beadle, Beth M.; Woodward, Wendy A. Tucker, Susan L.; Outlaw, Elesyia D.; Allen, Pamela K.; Oh, Julia L.; Strom, Eric A.; Perkins, George H.; Tereffe, Welela; Yu, T.-K.; Meric-Bernstam, Funda; Litton, Jennifer K.; Buchholz, Thomas A.

    2009-03-01

    Purpose: Young women with breast cancer have higher locoregional recurrence (LRR) rates than older patients. The goal of this study is to determine the impact of locoregional treatment strategy, breast-conserving therapy (BCT), mastectomy alone (M), or mastectomy with adjuvant radiation (MXRT), on LRR for patients 35 years or younger. Methods and Materials: Data for 668 breast cancers in 652 young patients with breast cancer were retrospectively reviewed; 197 patients were treated with BCT, 237 with M, and 234 with MXRT. Results: Median follow-up for all living patients was 114 months. In the entire cohort, 10-year actuarial LRR rates varied by locoregional treatment: 19.8% for BCT, 24.1% for M, and 15.1% for MXRT (p = 0.05). In patients with Stage II disease, 10-year actuarial LRR rates by locoregional treatment strategy were 17.7% for BCT, 22.8% for M, and 5.7% for MXRT (p = 0.02). On multivariate analysis, M (hazard ratio, 4.45) and Grade III disease (hazard ratio, 2.24) predicted for increased LRR. In patients with Stage I disease, there was no difference in LRR rates based on locoregional treatment (18.0% for BCT, 19.8% for M; p = 0.56), but chemotherapy use had a statistically significant LRR benefit (13.5% for chemotherapy, 27.9% for none; p = 0.04). Conclusions: Young women have high rates of LRR after breast cancer treatment. For patients with Stage II disease, the best locoregional control rates were achieved with MXRT. For patients with Stage I disease, similar outcomes were achieved with BCT and mastectomy; however, chemotherapy provided a significant benefit to either approach.

  14. Trastuzumab improves locoregional control in HER2-positive breast cancer patients following adjuvant radiotherapy

    PubMed Central

    Cao, Lu; Cai, Gang; Xu, Fei; Yang, Zhao-Zhi; Yu, Xiao-Li; Ma, Jin-Li; Zhang, Qian; Wu, Jiong; Guo, Xiao-Mao; Chen, Jia-Yi

    2016-01-01

    Abstract The benefit of adjuvant trastuzumab in disease-free and overall survival for human epidermal receptor 2–positive (HER2+) breast cancer patients is well established. However, the effect of trastuzumab on locoregional control remains unclear, particularly in patients treated with adjuvant radiotherapy (RT). In this study, we investigated the locoregional benefit of trastuzumab in patients with HER2+ breast cancer after adjuvant RT. Using a single institutional database, we identified 278 patients with stage II/III invasive HER2+ breast tumors receiving adjuvant RT between January 2008 and July 2011. We compared the locoregional outcomes of 134 patients who received trastuzumab to 144 patients without trastuzumab within the same period. Clinical and biological factors that might impact on the locoregional benefit of trastuzumab were also assessed. At the median follow-up of 45 months, trastuzumab significantly lowered the risk of locoregional recurrence (LRR) with a 3-year LRR rate of 2.4% versus 7.5% for the cohort with and without trastuzumab (P = 0.019). Trastuzumab was associated with a more significant locoregional benefit in the hormone receptor–positive (HR+)/HER2+ subgroup, with a 3-year LRR of 0% versus 6.7% in the cohort with and without trastuzumab (P = 0.027). For HR−/HER2+ breast tumor patients, the 3-year LRR rate was still lower for the cohort with trastuzumab (4.7% vs 8.6%). However, statistical significance was not found (P = 0.179). Both univariate and multivariate analyses confirmed that trastuzumab treatment was the only significant predictive factor for LRR (hazard ratio, 4.05; 95% confidence interval, 1.07–15.35; P = 0.039). Adjuvant trastuzumab in addition to RT is associated with significant reduced LRR risk in HER2+ breast cancer. PMID:27512838

  15. Loco-regional treatment in metastatic breast cancer patients: is there a survival benefit?

    PubMed

    Ly, Bevan H; Nguyen, Nam P; Vinh-Hung, Vincent; Rapiti, Elisabetta; Vlastos, Georges

    2010-02-01

    A number of studies have recently demonstrated a survival benefit in stage IV breast cancer patients following surgical resection of the primary tumor. Here, we investigate the relationship between loco-regional treatment and survival in patients with metastatic breast cancer and evaluate the impact of different loco-regional treatments. We conducted a systematic review of the literature using PubMed to analyze studies with the following criteria: Type of loco-regional treatment (surgery alone or combined with radiation, radiotherapy), overall survival, progression-free survival, selection factors for local treatment, and complication rates. Thirteen studies evaluated the effect of loco-regional treatment on overall survival with overall median survival increasing from a range of 12.6-28.3 months among patients without surgery to a range of 25-42 months among patients with surgery. In addition, six studies reported a 3-year survival benefit of 28-95% and 17-79% in women with and without locoregional therapy respectively. Two studies did not find any improvement in overall survival. One study found an improvement in 5-year breast cancer-specific survival of 27% with negative surgical margins versus 12% with no surgery. Three studies reported an advantage in progression-free survival in the treatment group compared with the non-treatment group. Loco-regional treatment for breast cancer patients with distant metastases at diagnosis is an important issue because of possible improvement of survival or disease-free survival. The possibility of surgery and/or radiotherapy following induction chemotherapy should be weighed and left to individual practice. Participation in randomized controlled trials should be encouraged.

  16. Heading and head injuries in soccer.

    PubMed

    Kirkendall, D T; Jordan, S E; Garrett, W E

    2001-01-01

    In the world of sports, soccer is unique because of the purposeful use of the unprotected head for controlling and advancing the ball. This skill obviously places the player at risk of head injury and the game does carry some risk. Head injury can be a result of contact of the head with another head (or other body parts), ground, goal post, other unknown objects or even the ball. Such impacts can lead to contusions, fractures, eye injuries, concussions or even, in rare cases, death. Coaches, players, parents and physicians are rightly concerned about the risk of head injury in soccer. Current research shows that selected soccer players have some degree of cognitive dysfunction. It is important to determine the reasons behind such deficits. Purposeful heading has been blamed, but a closer look at the studies that focus on heading has revealed methodological concerns that question the validity of blaming purposeful heading of the ball. The player's history and age (did they play when the ball was leather and could absorb significant amounts of water), alcohol intake, drug intake, learning disabilities, concussion definition and control group use/composition are all factors that cloud the ability to blame purposeful heading. What does seem clear is that a player's history of concussive episodes is a more likely explanation for cognitive deficits. While it is likely that the subconcussive impact of purposeful heading is a doubtful factor in the noted deficits, it is unknown whether multiple subconcussive impacts might have some lingering effects. In addition, it is unknown whether the noted deficits have any affect on daily life. Proper instruction in the technique is critical because if the ball contacts an unprepared head (as in accidental head-ball contacts), the potential for serious injury is possible. To further our understanding of the relationship of heading, head injury and cognitive deficits, we need to: learn more about the actual impact of a ball on the

  17. Internal and external validation of an ESTRO delineation guideline - dependent automated segmentation tool for loco-regional radiation therapy of early breast cancer.

    PubMed

    Eldesoky, Ahmed R; Yates, Esben S; Nyeng, Tine B; Thomsen, Mette S; Nielsen, Hanne M; Poortmans, Philip; Kirkove, Carine; Krause, Mechthild; Kamby, Claus; Mjaaland, Ingvil; Blix, Egil S; Jensen, Ingelise; Berg, Martin; Lorenzen, Ebbe L; Taheri-Kadkhoda, Zahra; Offersen, Birgitte V

    2016-12-01

    To internally and externally validate an atlas based automated segmentation (ABAS) in loco-regional radiation therapy of breast cancer. Structures of 60 patients delineated according to the ESTRO consensus guideline were included in four categorized multi-atlas libraries using MIM Maestro™ software. These libraries were used for auto-segmentation in two different patient groups (50 patients from the local institution and 40 patients from other institutions). Dice Similarity Coefficient, Average Hausdorff Distance, difference in volume and time were computed to compare ABAS before and after correction against a gold standard manual segmentation (MS). ABAS reduced the time of MS before and after correction by 93% and 32%, respectively. ABAS showed high agreement for lung, heart, breast and humeral head, moderate agreement for chest wall and axillary nodal levels and poor agreement for interpectoral, internal mammary nodal regions and LADCA. Correcting ABAS significantly improved all the results. External validation of ABAS showed comparable results. ABAS is a clinically useful tool for segmenting structures in breast cancer loco-regional radiation therapy in a multi-institutional setting. However, manual correction of some structures is important before clinical use. The ABAS is now available for routine clinical use in Danish patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Magnetic resonance imaging of the liver after loco-regional and systemic therapy.

    PubMed

    Corona-Villalobos, Celia Pamela; Zhang, Yan; Zhang, Wei-Dong; Kamel, Ihab R

    2014-08-01

    Assessment of tumor response is crucial in determining the effectiveness of loco-regional and systemic therapy, and for determining the need for subsequent treatment. The ultimate goal is to improve patient's survival. Changes in tumor size and enhancement after therapy may not be detected early by the traditional response criteria. Tumor response is better assessed in the entire tumor volume rather than in a single axial plane. The purpose of this article is to familiarize the reader with early treatment response assessed by anatomic and volumetric functional magnetic resonance imaging metrics of the liver after loco-regional and systemic therapy.

  19. Enteral Feeding During Chemoradiotherapy for Advanced Head-and-Neck Cancer: A Single-Institution Experience Using a Reactive Approach

    SciTech Connect

    Clavel, Sebastien; Fortin, Bernard; Despres, Philippe; Donath, David; Soulieres, Denis; Khaouam, Nader; Charpentier, Danielle; Belair, Manon; Guertin, Louis; Nguyen-Tan, Phuc Felix

    2011-03-01

    Purpose: The optimal method for providing enteral nutrition to patients with head-and-neck cancer is unclear. The purpose of the present study was to evaluate the safety and efficacy of our reactive policy, which consists of the installation of a nasogastric (NG) feeding tube only when required by the patient's nutritional status. Methods and Materials: The records of all patients with Stage III and IV head-and-neck cancer treated with concomitant chemotherapy and radiotherapy between January 2003 and December 2006 were reviewed. The overall and disease-free survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test. Results: The present study included 253 patients, and the median follow-up was 33 months. At 3 years, the estimated overall survival and disease-free survival rate was 82.8% and 77.8%, respectively, for the whole population. No survival difference was observed when the patients were compared according to the presence and absence of a NG tube or stratified by weight loss quartile. The mean weight loss during treatment for all patients was 10.4%. The proportion of patients requiring a NG tube was 49.8%, and the NG tube remained in place for a median duration of 40 days. No major complications were associated with NG tube installation. Only 3% of the patients were still dependent on enteral feeding at 6 months. Conclusion: These results suggest that the use of a reactive NG tube with an interdisciplinary team approach is a safe and effective method to manage malnutrition in patients treated with concomitant chemotherapy and radiotherapy for head-and-neck cancer.

  20. Enteral feeding during chemoradiotherapy for advanced head-and-neck cancer: a single-institution experience using a reactive approach.

    PubMed

    Clavel, Sébastien; Fortin, Bernard; Després, Philippe; Donath, David; Soulières, Denis; Khaouam, Nader; Charpentier, Danielle; Bélair, Manon; Guertin, Louis; Nguyen-Tan, Phuc Felix

    2011-03-01

    The optimal method for providing enteral nutrition to patients with head-and-neck cancer is unclear. The purpose of the present study was to evaluate the safety and efficacy of our reactive policy, which consists of the installation of a nasogastric (NG) feeding tube only when required by the patient's nutritional status. The records of all patients with Stage III and IV head-and-neck cancer treated with concomitant chemotherapy and radiotherapy between January 2003 and December 2006 were reviewed. The overall and disease-free survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test. The present study included 253 patients, and the median follow-up was 33 months. At 3 years, the estimated overall survival and disease-free survival rate was 82.8% and 77.8%, respectively, for the whole population. No survival difference was observed when the patients were compared according to the presence and absence of a NG tube or stratified by weight loss quartile. The mean weight loss during treatment for all patients was 10.4%. The proportion of patients requiring a NG tube was 49.8%, and the NG tube remained in place for a median duration of 40 days. No major complications were associated with NG tube installation. Only 3% of the patients were still dependent on enteral feeding at 6 months. These results suggest that the use of a reactive NG tube with an interdisciplinary team approach is a safe and effective method to manage malnutrition in patients treated with concomitant chemotherapy and radiotherapy for head-and-neck cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Tumor markers for early diagnosis for brain metastasis of hepatocellular carcinoma: A case series and literature review for effective loco-regional treatment.

    PubMed

    Kamimura, Kenya; Kobayashi, Yuji; Takahashi, Yoshifumi; Abe, Hiroyuki; Kumaki, Daisuke; Yokoo, Takeshi; Kamimura, Hiroteru; Sakai, Norihiro; Sakamaki, Akira; Abe, Satoshi; Takamura, Masaaki; Kawai, Hirokazu; Yamagiwa, Satoshi; Terai, Shuji

    2017-02-01

    Intrahepatic lesions of hepatocellular carcinoma (HCC) have been controlled by significant advances in treatment using loco-regional therapies, including, surgery, ablative therapy, catheter-based chemotherapy, and embolization. Consequently, the number of patients with extrahepatic metastatic lesions has increased. Their prognosis remains poor with approximately <1 y of survival from the time of diagnosis. A molecularly targeted drug, sorafenib, have been used to treat extrahepatic lesions and shown the prolonged survival time. However, the therapeutic benefit for the brain metastasis remains unclear, since it causes intratumor bleeding leading to the severe brain damage. No guidelines for the brain metastasis of HCC have been developed to date due to the shortage of the experiences and evidences. Therefore, the development of standard therapy for brain metastasis following the early diagnosis is essential by accumulating the information of clinical courses and evidences. For this purpose, we reviewed cases of HCC brain metastasis reported to date and analyzed additional 8 cases from our hospital, reviewing 592 advanced HCC cases to estimate the possible metastatic lesions in the brain. With careful review of cases and literature, we suggest that the cases with lung metastasis with increase tendency of tumor markers within recent 3-6 months have higher risks of brain metastasis. Therefore, they should be carefully followed by imaging modalities. In addition, the loco-regional treatment, including surgical resection and radiation therapy should be performed for better prognosis by preventing re-bleeding from the tumors.

  2. Recent advances in knowledge regarding the head and neck manifestations of IgG4-related disease.

    PubMed

    Takano, Kenichi; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

    2017-02-01

    IgG4-related disease (IgG4-RD) is a chronic inflammatory disorder, characterized by elevated serum IgG4 levels as well as abundant infiltration of IgG4-positive plasmacytes and fibrosis in various organs, including the head and neck region. In particular, the salivary glands, orbit, and thyroid are common sites of disease involvement. IgG4-RD is diagnosed based on various clinical, serological, and histopathological findings, none of which are pathognomonic. Hence, various differential diagnoses, which exhibit elevated serum IgG4 levels and infiltration of IgG4-postive cells into tissues, need to be excluded, especially malignant diseases and mimicking disorders. Systemic corticosteroids are generally effective in inducing IgG4-RD remission; however, recurrent or refractory cases are common. In addition, although the pathogenic mechanisms of IgG4-RD remain unclear, an antigen-driven inflammatory condition is believed to be involved. Recent studies have indicated the important pathogenic role of B cell/T cell collaboration and innate immunity in this disease. Nevertheless, additional research and discussions are needed to resolve many remaining questions. In this review, we provide an overview of the recent insights on the history, clinical features, diagnosis, and treatment of IgG4-RD in the head and neck region. Furthermore, we have also addressed the pathogenesis of this disease.

  3. Gemcitabine and cisplatin in a concomitant alternating chemoradiotherapy program for locally advanced head-and-neck cancer: A pharmacology-guided schedule

    SciTech Connect

    Numico, Gianmauro . E-mail: gianmauro.numico@fastwebnet.it; Russi, Elvio G.; Vitiello, Raffele; Sorrentino, Raffaele; Colantonio, Ida; Cipolat, Marco; Taglianti, Riccardo Vigna; Pelissero, Antonio; Fea, Elena; Granetto, Cristina; Di Costanzo, Gianna; Gasco, Milena; Garrone, Ornella; Occelli, Marcella; Merlano, Marco

    2006-11-01

    Purpose: Administration of gemcitabine together with cisplatin at cytotoxic doses in a chemoradiotherapy regimen is hampered by a high degree of local toxicity. Using the pharmacologic properties of the drug we designed a modified schedule aimed at reducing toxicity while preserving activity. Methods and Materials: Patients with squamous cell carcinomas of the oral cavity, pharynx and larynx, bulky T4, and/or N2 to N3 were eligible. Gemcitabine was administered at a dose of 800 mg/m{sup 2} on Days 1 and 12 and cisplatin at a dose of 20 mg/m{sup 2} on Days 2 to 5, every 21 days for 3 courses. Radiotherapy, delivered with standard fractionation, was given on Days 8 to 12 and 15 to 19 and was repeated 3 times up to a total dose of {>=}60 Gy. Results: A total of 28 patients were selected. Grade 3 to 4 stomatitis was recorded in 25 patients (89%). Thirteen patients (46%) experienced Grade 3 to 4 neutropenia. Febrile neutropenia occurred in 8 patients (29%) and in 2 was complicated by infection and death. The overall complete response rate was 79%. At a median follow up of 71 months, 11 patients had a locoregional relapse (3-year locoregional control, 64%); 6 patients had distant metastases, among whom only 2 were without locoregional recurrence. The 3-year progression-free survival is 39% and 3-year overall survival has been 43%. Conclusion: The schedule modification did not attenuate local toxicity. Moreover, infections and especially pneumonia, were a major problem. The high activity of gemcitabine when combined with radiotherapy would most likely be better exploited in the context of modified radiation schemes.

  4. [Adjuvant radiotherapy for bladder cancer in patients with risk of locoregional recurrence: Who, what and how?

    PubMed

    Sargos, P; Larré, S; Chapet, O; Latorzeff, I; Fléchon, A; Roubaud, G; Orré, M; Belhomme, S; Richaud, P

    2017-02-01

    Radical cystectomy with extended pelvic lymph node dissection remains the standard of care for non-metastatic muscle-invasive bladder cancer. Locoregional control is a key factor in the outcome of patients since it is related to overall survival, metastasis-free survival and specific survival. Locoregional recurrence rate is directly correlated to pathological results and the quality of lymphadenectomy. In addition, while pre- or postoperative chemotherapy improved overall survival, it showed no impact on locoregional recurrence-free survival. Several recent publications have led to the development of a nomogram that predicts the risk of locoregional recurrence, in order to identify patients for which adjuvant radiotherapy could be beneficial. International cooperative groups have then come together to provide the rational for adjuvant radiotherapy, reinforced by recent technical developments limiting toxicity, and to develop prospective studies to reduce the risk of relapse. The aim of this critical literature review is to provide an overview of the elements in favor of adjuvant radiation for patients treated for muscle-invasive bladder cancer.

  5. [Role of loco-regional treatments for patients with breast cancer liver metastases].

    PubMed

    Raimondi, Cristina; Danova, Marco; Chatzileontiadou, Sofia; Palmeri, Laura; Vercelli, Alessandro; Palmeri, Sergio

    2009-09-01

    Breast cancer liver metastases (BCLM) are not uncommon (about 18% of cases): although some patients have been reported as still living after 25 months, median survival after hormonal- or chemotherapy is 6-14 months. In recent years, new chemotherapy regimens and molecular targeted therapies have given medical oncologists reason to believe that metastatic disease can be eradicated, or at least controlled for prolonged periods. In an attempt to improve survival, consideration has also been given to loco-regional treatments such as hepatic resection and radio-frequency ablation, which have been associated with better outcomes in selected patients. This review considers the role of two loco-regional approaches in a multidisciplinary perspective in the treatment of single or multiple breast cancer metastases limited to the liver. An expanded role for hepatic resection and ablation is being investigated. We assessed available data in the literature to determine their role on survival outcomes. They suggest that loco-regional treatments might be of significant benefit in a selected group of women with BCLM, but the role of these local treatments in multimodality treatment of liver metastases remains controversial. It can generally be said that loco-regional treatments can improve overall survival, with no mortality and less than 20% morbidity in patients at low surgical risk; however, they should only be considered cytoreductive treatments and, as such, always need to be integrated with systemic therapy.

  6. Evolving trends in the initial locoregional management of male breast cancer.

    PubMed

    Bratman, Scott V; Kapp, Daniel S; Horst, Kathleen C

    2012-06-01

    The locoregional management of breast cancer in men has evolved over time. Multimodality treatment regimens currently in use are based primarily on large randomized trials that exclusively enrolled women with breast cancer. We retrospectively reviewed cases of male breast cancer treated with radiotherapy at Stanford University Medical Center with an emphasis on 22 patients treated with surgery and locoregional radiotherapy. We report trends in the surgical techniques as well as in the use of adjuvant radiotherapy, chemotherapy, and hormonal therapy. There were no isolated locoregional failures in this cohort, and 5-year disease-free survival was 65%. The use of contemporary surgical and radiotherapeutic techniques in men is discussed. We conclude that treatment guidelines designed for women should be applied to the locoregional management of breast cancer in men. However, large international prospective registries and inclusion of men in cooperative group randomized trials will be important to confirm the safety and efficacy of modern treatment modalities for male breast cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. SU-E-T-313: The Accuracy of the Acuros XB Advanced Dose Calculation Algorithm for IMRT Dose Distributions in Head and Neck

    SciTech Connect

    Araki, F; Onizuka, R; Ohno, T; Tomiyama, Y; Hioki, K

    2014-06-01

    Purpose: To investigate the accuracy of the Acuros XB version 11 (AXB11) advanced dose calculation algorithm by comparing with Monte Caro (MC) calculations. The comparisons were performed with dose distributions for a virtual inhomogeneity phantom and intensity-modulated radiotherapy (IMRT) in head and neck. Methods: Recently, AXB based on Linear Boltzmann Transport Equation has been installed in the Eclipse treatment planning system (Varian Medical Oncology System, USA). The dose calculation accuracy of AXB11 was tested by the EGSnrc-MC calculations. In additions, AXB version 10 (AXB10) and Analytical Anisotropic Algorithm (AAA) were also used. First the accuracy of an inhomogeneity correction for AXB and AAA algorithms was evaluated by comparing with MC-calculated dose distributions for a virtual inhomogeneity phantom that includes water, bone, air, adipose, muscle, and aluminum. Next the IMRT dose distributions for head and neck were compared with the AXB and AAA algorithms and MC by means of dose volume histograms and three dimensional gamma analysis for each structure (CTV, OAR, etc.). Results: For dose distributions with the virtual inhomogeneity phantom, AXB was in good agreement with those of MC, except the dose in air region. The dose in air region decreased in order of MChead and neck were similar to those of MC in order of AXB11

  8. Three-dimensional conformal radiotherapy for locally advanced (Stage II and worse) head-and-neck cancer: Dosimetric and clinical evaluation

    SciTech Connect

    Portaluri, Maurizio . E-mail: portaluri@hotmail.com; Fucilli, Fulvio I.M.; Castagna, Roberta; Bambace, Santa; Pili, Giorgio; Tramacere, Francesco; Russo, Donatella; Francavilla, Maria Carmen

    2006-11-15

    Purpose: To evaluate the dosimetric parameters of three-dimensional conformal radiotherapy (3D-CRT) in locally advanced head-and-neck tumors (Stage II and above) and the effects on xerostomia. Methods and Materials: A total of 49 patients with histologically proven squamous cell cancer of the head and neck were consecutively treated with 3D-CRT using a one-point setup technique; 17 had larynx cancer, 12 oropharynx, 12 oral cavity, and 6 nasopharynx cancer; 2 had other sites of cancer. Of the 49 patients, 41 received postoperative RT and 8 definitive treatment. Also, 13 were treated with cisplatin-based chemotherapy before and during RT; in 6 cases, 5-fluorouracil was added. The follow-up time was 484-567 days (median, 530 days). Results: One-point setup can deliver 96% of the prescribed dose to the isocenter, to the whole planning target volume, including all node levels of the neck and without overdosages. The mean dose to the primary planning target volume was 49.54 {+-} 4.82 Gy (51.53 {+-} 5.47 Gy for larynx cases). The average dose to the contralateral parotid gland was approximately 38 Gy (30 Gy for larynx cases). The maximal dose to the spinal cord was 46 Gy. A Grade 0 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer xerostomia score corresponded to a mean dose of 30 Gy to one parotid gland. A lower xerostomia score with a lower mean parotid dose and longer follow-up seemed to give rise to a sort of functional recovery phenomenon. Conclusion: Three dimensional-CRT in head-and-neck cancers permits good coverage of the planning target volume with about 10-11 segments and one isocenter. With a mean dose of approximately 30 Gy to the contralateral parotid, we observed no or mild xerostomia.

  9. Functional and aesthetic outcome and survival after double free flap reconstruction in advanced head and neck cancer patients.

    PubMed

    Posch, Nicole A S; Mureau, Marc A M; Dumans, Antoine G; Hofer, Stefan O P

    2007-07-01

    Extensive composite defects in the head and neck area may require the use of double free flap reconstructions. These reconstructions are not only surgically challenging but also challenging to patients. A realistic perspective on general outcome for the patient seems important. From January of 2002 to August of 2003, double free flap reconstructions were used in 12 patients with extensive composite head and neck defects following malignant tumor (n = 7) and osteoradionecrosis (n = 5) resection. Six patients had a standardized interview, physical examination, and clinical photographs. All reconstructions were performed using an osteocutaneous fibula flap in combination with an anterolateral thigh flap (n = 8), a radial forearm flap (n = 1), or a lateral thigh flap (n = 1). The total flap survival rate was 96 percent. Mean mandibular bone defects were 10 cm. Mean skin island sizes of osteocutaneous fibula flaps were 67 cm. Mean external skin reconstruction flap sizes were 117 cm. Mean overall survival time was 20 months in patients with malignant tumors. Patients with osteoradionecrosis reconstruction survived free of disease for an average period of 38 months. Three patients (50 percent) were very satisfied, one was neutral, and two were very dissatisfied with their functional and aesthetic results. Objective evaluation of function showed mainly deteriorated speech (83 percent) and oral incontinence (67 percent). Objective evaluation of aesthetics showed mainly color mismatch (67 percent) and flap contracture of external flaps (50 percent). Reconstruction of these major composite through-and-through defects will often result in a modest functional and aesthetic outcome. Because selected patients require these procedures, the authors give information that matches with realistic expectations.

  10. Summary of major radiation fractionation and chemotherapy trials for organ preservation therapy in locally advanced head and neck squamous cell carcinoma.

    PubMed

    Parsons, James T; Greene, Bruce D

    2015-01-01

    To review radiation fractionation and chemotherapy trials for patients undergoing organ preservation therapy for locally advanced head and neck squamous cell carcinoma. Radiation therapy fractionation and chemotherapy trial results as well as historical evidence are systematically reviewed. Trial results, which involve nearly 30,000 patients, have been interpreted, compared, and presented in a structured manner to demonstrate the changing approaches in treatment over the years from the 1960s to the present. The review includes data from the split-course radiation therapy era, meta-analyses of chemotherapy and radiation therapy fractionation trials, cetuximab trials, "triple-drug trials," and modern trials of induction chemotherapy followed by concomitant chemotherapy and radiation therapy. This summary will be useful to clinicians making treatment decisions today and to investigators designing trials in the future. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  11. [The most important study results concerning nonsurgical primary treatment of locally advanced head and neck cancer: Highlights of the ASCO Meeting 2015].

    PubMed

    Gliese, A; Busch, C-J; Knecht, R

    2015-09-01

    At the Annual Meeting of the American Society of Clinical Oncology (ASCO) 2015, results of current trials dealing with nonsurgical primary treatment of locally advanced head and neck cancer were presented. Regarding concomitant chemoradiotherapy (CRT), studies focused on the dosage and sequence of cisplatin administration are currently particularly featured. Amongst these, a study on dosage reduction in human papilloma virus (HPV)-positive patients was presented. Other investigations addressed substances as alternatives for cisplatin, particularly carboplatin and targeted therapeutic agents. The comparison of concomitant and sequential CRT (induction chemotherapy (ICT) prior to CRT) is still one of the main topics. In addition, studies modifying the ICT regimen or combining subsequent radiotherapy (RT) with the epidermal growth factor receptor (EGFR) antibody cetuximab were presented. A selection of the most important trials are summarized in this article.

  12. Chemoradiation therapy using radiotherapy, systemic chemotherapy with 5-fluorouracil and nedaplatin, and intra-arterial infusion using carboplatin for locally advanced head and neck cancer - Phase II study.

    PubMed

    Fuwa, Nobukazu; Kodaira, Takesi; Furutani, Kazuhisa; Tachibana, Hiroyuki; Nakamura, Tatsuya; Daimon, Takasi

    2007-11-01

    To improve the treatment results for locally advanced head and neck cancer, chemoradiation therapy by radiotherapy, systemic chemotherapy with 5-fluorouracil (5FU) and nedaplatin (NDP), and intra-arterial therapy using carboplatin (CBDCA) was performed. Thirty-two patients were entered into the study between July 1997 and August 2002. According to the TNM staging (1997), 14 patients had stage III lesions, and 19 patients had stage IV (M0) lesions. Alternating chemoradiotherapy was performed by the following regimen. Initially, systemic chemotherapy was administered, followed by 4 weeks of radiotherapy (36Gy/20 fractions; wide field irradiation) starting 2 days after chemotherapy, a second course of systemic chemotherapy 2 days after radiotherapy, and a second course of a reduced field radiotherapy (30Gy/15 fractions) 2 days after chemotherapy. Arterial injection therapy was administered in the latter half of radiotherapy after the end of the second course of systemic chemotherapy. For systemic chemotherapy, 5FU at 3500mg/m(2)/120h was intravenously administered for 5 days (Days 1-5), and NDP at 120mg/m(2)/6h was administered on Day 6. An intra-arterial agent using CBDCA was continuously infused by a portable electrical pump for 4 (to 6) weeks. The total dose of CBDCA was AUC 6 as established by Calvert's formula. The 5-year local control rate was 59%. The 5-year overall survival rate was 51%. There were no clinically significant adverse effects. Chemoradiation therapy by radiotherapy, systemic chemotherapy, and intra-arterial chemotherapy for locally advanced head and neck cancer may be useful for improving treatment results.

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

    SciTech Connect

    Rekha Reddy, B.; Ravikumar, M.; Tanvir Pasha, C.R; Anil Kumar, M.R; Varatharaj, C.; Pyakuryal, A; Narayanasamy, Ganesh

    2014-06-01

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

  14. The role of induction chemotherapy in the treatment of patients with locally advanced head and neck cancers: A review.

    PubMed

    Al Sarraf, M D; El Hariry, I

    2008-07-01

    Induction CT have evolved since its introduction in the mid of 1970s for patients with previously untreated locally advanced HNC. We went from single agent cisplatin to cisplatin bleomycin combinations, to PF and now to the three drugs combination of TPF or its safer modification. We started with single cycle of induction CT, to two courses and now the best to give is the three cycles of CT. We not only improved on the effectiveness of the induction CT, but also reduced the possible side effects and improved the quality of life for those receiving such treatment. Induction CT followed by RT alone is superior to RT only in patients with previously untreated unresectable/inoperable HNC. Although, the "standard" of care of these patients today is concurrent CT+RT. Induction TPF followed by the best local treatment(s) usually concurrent CT+RT was superior to PF followed by the best local therapy in these patients. Will this mean that in patients with locally advanced unresectable/inoperable HNC induction TPF followed by concurrent CT+RT is the treatment of choice, in our opinion is yes, but this is not acceptable by the majority of investigators. This is why we do have more than four prospective randomized phase III trials trying to answer such an important question. In our opinion and strong believe that all patients with locally advanced HNC including patients with NPC not on active protocol(s) may be offered induction three drugs combination followed by concurrent CT+RT as their primary planned treatment. In those patients who are resectable/operable before any such therapy and did not respond (CR or PR) to such induction CT may offer surgical resection followed by post-operative concurrent CT + RT. Table 5 summarize the rational of the continue use of the total treatment of induction CT followed by concurrent CT+RT in patients with previously untreated and locally advanced HNC.

  15. Prediction of clinical toxicity in locally advanced head and neck cancer patients by radio-induced apoptosis in peripheral blood lymphocytes (PBLs)

    PubMed Central

    2010-01-01

    in locally advanced head and neck cancer patients. Anyhow, prospective studies with different cancer types and higher number of patients are needed to validate these results. PMID:20109191

  16. Postburn Head and Neck Reconstruction: An Algorithmic Approach.

    PubMed

    Heidekrueger, Paul Immanuel; Broer, Peter Niclas; Tanna, Neil; Ninkovic, Milomir

    2016-01-01

    Optimizing functional and aesthetic outcomes in postburn head and neck reconstruction remains a surgical challenge. Recurrent contractures, impaired range of motion, and disfigurement because of disruption of the aesthetic subunits of the face, can result in poor patient satisfaction and ultimately, contribute to social isolation of the patient. In an effort to improve the quality of life of these patients, this study evaluates different surgical approaches with an emphasis on tissue expansion of free and regional flaps. Regional and free-flap reconstruction was performed in 20 patients (26 flaps) with severe postburn head and neck contractures. To minimize donor site morbidity and obtain large amounts of thin and pliable tissue, pre-expansion was performed in all patients treated with locoregional flap reconstructions (12/12), and 62% (8/14) of patients with free-flap reconstructions. Algorithms regarding pre- and intraoperative decision-making are discussed, and complications between the techniques as well as long-term (mean follow-up 3 years) results are analyzed. Complications, including tissue expander infection with need for removal or exchange, partial or full flap loss, were evaluated and occurred in 25% (3/12) of patients with locoregional and 36% (5/14) of patients receiving free-flap reconstructions. Secondary revision surgery was performed in 33% (4/12) of locoregional flaps and 93% (13/14) of free flaps. Both locoregional as well as distant tissue transfers have their role in postburn head and neck reconstruction, whereas pre-expansion remains an invaluable tool. Paying attention to the presented principles and keeping the importance of aesthetic facial subunits in mind, range of motion, aesthetics, and patient satisfaction were improved long term in all our patients, while minimizing donor site morbidity.

  17. Analysis of carotid artery deformation in different head and neck positions for maxillofacial catheter navigation in advanced oral cancer treatment.

    PubMed

    Ohya, Takashi; Iwai, Toshinori; Luan, Kuan; Kato, Takashi; Liao, Hongen; Kobayashi, Etsuko; Mitsudo, Kenji; Fuwa, Nobukazu; Kohno, Ryuji; Sakuma, Ichiro; Tohnai, Iwai

    2012-09-04

    To improve the accuracy of catheter navigation, it is important to develop a method to predict shifts of carotid artery (CA) bifurcations caused by intraoperative deformation. An important factor affecting the accuracy of electromagnetic maxillofacial catheter navigation systems is CA deformations. We aimed to assess CA deformation in different head and neck positions. Using two sets of computed tomography angiography (CTA) images of six patients, displacements of the skull (maxillofacial segments), C1-C4 cervical vertebrae, mandible (mandibular segment), and CA along with its branches were analyzed. Segmented rigid bones around CA were considered the main causes of CA deformation. After superimposition of maxillofacial segments, C1-C4 and mandible segments were superimposed separately for displacement measurements. Five bifurcation points (vA-vE) were assessed after extracting the CA centerline. A new standardized coordinate system, regardless of patient-specific scanning positions, was employed. It was created using the principal axes of inertia of the maxillofacial bone segments of patients. Position and orientation parameters were transferred to this coordinate system. CA deformation in different head and neck positions was assessed. Absolute shifts in the center of gravity in the bone models for different segments were C1, 1.02 ± 0.9; C2, 2.18 ± 1.81; C3, 4.25 ± 3.85; C4, 5.90 ± 5.14; and mandible, 1.75 ± 2.76 mm. Shifts of CA bifurcations were vA, 5.52 ± 4.12; vB, 4.02 ± 3.27; vC, 4.39 ± 2.42; vD, 4.48 ± 1.88; and vE, 2.47 ± 1.32. Displacements, position changes, and orientation changes of C1-C4 segments as well as the displacements of all CA bifurcation points were similar in individual patients. CA deformation was objectively proven as an important factor contributing to errors in maxillofacial navigation. Our study results suggest that small movements of the bones around CA can result in small CA

  18. Expression and clinical significance of connective tissue growth factor in advanced head and neck squamous cell cancer.

    PubMed

    Kikuchi, Ryoko; Kikuchi, Yoshihiro; Tsuda, Hitoshi; Maekawa, Hitoshi; Kozaki, Ken-Ichi; Imoto, Issei; Tamai, Seiichi; Shiotani, Akihiro; Iwaya, Keiichi; Sakamoto, Masaru; Sekiya, Takao; Matsubara, Osamu

    2014-07-01

    Connective tissue growth factor (CTGF) has been reported to play critical roles in the tumorigenesis of several human malignancies. This study was performed to evaluate CTGF protein expression in head and neck squamous cell carcinoma (HNSCC). Surgical specimens from 76 primary HNSCC were obtained with written informed consents and the expression level of CTGF was immunohistochemically evaluated. The cytoplasmic immunoreactivity of CTGF in cancer cells was semiquantitatively classified into low and high expression. Among all 76 cases with or without neoadjuvant therapy, low CTGF showed significantly longer (P = 0.0282) overall survival (OS), but not disease-free survival (DFS) than high CTGF. Although low CTGF in patients with stage I, II and III did not result in any significant difference of the OS and DFS, stage IV HNSCC patients with low CTGF showed significantly longer OS (P = 0.032) and DFS (P = 0.0107) than those with high CTGF. These differences in stage IV cases were also confirmed using multivariate analyses. These results suggest that low CTGF in stage IV HNSCC is an independent prognostic factor, despite with or without neoadjuvant therapy.

  19. Role of salvage stereotactic body radiation therapy in post-surgical loco-regional recurrence in a selected population of non-small cell lung cancer patients.

    PubMed

    Agolli, Linda; Valeriani, Maurizio; Carnevale, Alessia; Falco, Teresa; Bracci, Stefano; De Sanctis, Vitaliana; Minniti, Giuseppe; Enrici, Riccardo Maurizi; Osti, Mattia Falchetto

    2015-03-01

    This is a retrospective analysis of a selected series of high-risk non-small cell lung cancer (NSCLC) patients with post-surgical loco-regional relapse treated with salvage stereotactic body radiotherapy (SBRT). Outcome and toxicity profiles were assessed. Twenty-eight patients (unfit for surgery or systemic therapy) with 30 lesions underwent salvage SBRT as an alternative therapy because of advanced age, co-morbid conditions or no response obtained from other treatments. Complete and partial responses were 16% and 70%, respectively. Local progression was observed in 3 patients. Regional relapse occurred in 5 patients. Distant progression occurred in 10 patients. The 2-year overall survival (OS) and disease-free survival (DFS) were 57.5% and 36.6%, respectively. Radiation acute pneumonitis occurred as follows: three patients developed grade 1, two patients experienced grade 2 and one patient experienced grade 3 toxicity. Stereotactic body radiotherapy could have an alternative role in isolated loco-regional relapse in patients unfit or resistant to other therapies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  20. A randomized preventive rehabilitation trial in advanced head and neck cancer patients treated with chemoradiotherapy: feasibility, compliance, and short-term effects.

    PubMed

    van der Molen, Lisette; van Rossum, Maya A; Burkhead, Lori M; Smeele, Ludi E; Rasch, Coen R N; Hilgers, Frans J M

    2011-06-01

    The aim of this study was to assess the effect of (preventive) rehabilitation on swallowing and mouth opening after concomitant chemoradiotherapy (CCRT). Forty-nine patients with advanced oral cavity, oropharynx, hypopharynx and larynx, or nasopharynx cancer treated with CCRT were randomized into a standard (S) or an experimental (E) preventive rehabilitation arm. Structured multidimensional assessment (i.e., videofluoroscopy, mouth-opening measurement, structured questionnaires) was performed before and 10 weeks after CCRT. In both S and E arms, feasibility was good (all patients could execute the exercises within a week) and compliance was satisfactory (mean days practiced per week was 4). Nevertheless, mouth opening, oral intake, and weight decreased significantly. Compared to similar CCRT studies at our institute, however, fewer patients were still tube-dependent after CCRT. Furthermore, some functional outcomes seemed less affected than those of studies in the literature that did not incorporate rehabilitation exercises. Patients in the E arm practiced significantly fewer days in total and per week, but they obtained results comparable to the S arm patients. Preventive rehabilitation (regardless of the approach, i.e., experimental or standard) in head and neck cancer patients, despite advanced stage and burdensome treatment, is feasible, and compared with historical controls, it seems helpful in reducing the extent and/or severity of various functional short-term effects of CCRT.

  1. Analysis of carotid artery deformation in different head and neck positions for maxillofacial catheter navigation in advanced oral cancer treatment

    PubMed Central

    2012-01-01

    Background To improve the accuracy of catheter navigation, it is important to develop a method to predict shifts of carotid artery (CA) bifurcations caused by intraoperative deformation. An important factor affecting the accuracy of electromagnetic maxillofacial catheter navigation systems is CA deformations. We aimed to assess CA deformation in different head and neck positions. Methods Using two sets of computed tomography angiography (CTA) images of six patients, displacements of the skull (maxillofacial segments), C1–C4 cervical vertebrae, mandible (mandibular segment), and CA along with its branches were analyzed. Segmented rigid bones around CA were considered the main causes of CA deformation. After superimposition of maxillofacial segments, C1–C4 and mandible segments were superimposed separately for displacement measurements. Five bifurcation points (vA–vE) were assessed after extracting the CA centerline. A new standardized coordinate system, regardless of patient-specific scanning positions, was employed. It was created using the principal axes of inertia of the maxillofacial bone segments of patients. Position and orientation parameters were transferred to this coordinate system. CA deformation in different head and neck positions was assessed. Results Absolute shifts in the center of gravity in the bone models for different segments were C1, 1.02 ± 0.9; C2, 2.18 ± 1.81; C3, 4.25 ± 3.85; C4, 5.90 ± 5.14; and mandible, 1.75 ± 2.76 mm. Shifts of CA bifurcations were vA, 5.52 ± 4.12; vB, 4.02 ± 3.27; vC, 4.39 ± 2.42; vD, 4.48 ± 1.88; and vE, 2.47 ± 1.32. Displacements, position changes, and orientation changes of C1–C4 segments as well as the displacements of all CA bifurcation points were similar in individual patients. Conclusions CA deformation was objectively proven as an important factor contributing to errors in maxillofacial navigation. Our study results suggest that small movements of the

  2. Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer.

    PubMed

    Bibault, J-E; Morelle, M; Perrier, L; Pommier, P; Boisselier, P; Coche-Dequéant, B; Gallocher, O; Alfonsi, M; Bardet, É; Rives, M; Calugaru, V; Chajon, E; Noël, G; Mecellem, H; Pérol, D; Dussart, S; Giraud, P

    2016-07-01

    Intensity-modulated radiation therapy (IMRT) has shown its interest for head and neck cancer treatment. In parallel, cetuximab has demonstrated its superiority against exclusive radiotherapy. The objective of this study was to assess the acute toxicity, local control and overall survival of cetuximab associated with different IMRT modalities compared to platinum-based chemotherapy and IMRT in the ARTORL study (NCT02024035). This prospective, multicenter study included patients with epidermoid or undifferentiated nasopharyngeal carcinoma, epidermoid carcinoma of oropharynx and oral cavity (T1-T4, M0, N0-N3). Acute toxicity, local control and overall survival were compared between groups (patients receiving cetuximab or not). Propensity score analysis at the ratio 1:1 was undertaken in an effort to adjust for potential bias between groups due to non-randomization. From the 180 patients included in the ARTORL study, 29 patients receiving cetuximab and 29 patients treated without cetuximab were matched for the analysis. Ten patients (34.5%) reported acute dermal toxicity of grade 3 in the cetuximab group versus three (10.3%) in the non-cetuximab group obtained after matching (P=0.0275). Cetuximab was not significantly associated with more grade 3 mucositis (P=0.2563). There were no significant differences in cutaneous or oral toxicity for patients treated with cetuximab between the different IMRT modalities (P=1.000 and P=0.5731, respectively). There was no significant difference in local relapse-free survival (P=0.0920) or overall survival (P=0.4575) between patients treated with or without cetuximab. Patients treated with cetuximab had more cutaneous toxicities, but oral toxicity was similar between groups. The different IMRT modalities did not induce different toxicity profiles. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  3. Head Lice

    MedlinePlus

    Head lice are parasitic wingless insects. They live on people's heads and feed on their blood. An adult louse ... Children ages 3-11 and their families get head lice most often. Personal hygiene has nothing to ...

  4. Head Lice

    MedlinePlus

    ... Schedules Nutrient Shortfall Questionnaire Home Diseases and Conditions Head Lice Head Lice Condition Family HealthKids and Teens Share Head Lice Table of Contents1. Overview2. Symptoms3. Causes4. Prevention5. ...

  5. Head circumference

    MedlinePlus

    ... a child's head circumference. Normal ranges for a child's sex and age (weeks, months), based on values that experts have obtained for normal growth rates of infants' and children's heads. Measurement of the head circumference is an ...

  6. Subarachnoid anesthesia for loco-regional antiblastic perfusion with circulatory block (stop-flow perfusion).

    PubMed

    Carron, M; Innocente, F; Veronese, S; Miotto, D; Pilati, P; Rossi, C R; Ori, C

    2006-01-01

    Loco-regional antiblastic perfusion with circulatory block (stop-flow perfusion, SFP) is a procedure designed to treat solid tumors of the limb and pelvis in an advanced stage, like melanoma, sarcoma of the soft tissues and colon-rectal cancer. The aim of this study was to evaluate if subarachnoid anesthesia could represent a safe and suitable anesthetic technique for this procedure. Thirty SFP procedures were performed in the angiographic room, 15 for the treatment of lower-limb neoplasias and 15 for pelvic neoplasias. The patients (ASA I-III) had a mean age of 59.1 years (range: 19-81 years). The patients were given different dosages of bupivacaine (range: 10-20 mg) in hyperbaric solution at the concentration of 0.5% and 1% by lumbar subarachnoid injection at different levels (from T12-L1 to L3-L4). Standard monitoring was set up (ECG, pulse-oximetry, and non-invasive artery pressure). The use of any anesthetic and analgesic drug, eventually used in the intra- or postoperative period, was recorded. The lumbar puncture was approached at L1-L2 and L2-L3 levels in 80% of the cases. Doses of bupivacaine between 12 mg and 14 mg were administered in 2/3 of the cases. Bupivacaine was formulated in hyperbaric solution and administered at a concentration of 0.5% (8 patients) or 1% (22 patients). Complica-tions related to the anesthetic technique were absent. Intraoperative pain control was almost complete with one exception, when the procedure lasted unusually long. Pain control was satisfying immediately after the procedure as well: only in 3 cases were non-opiod analgesics administered within the first 6 h. Spinal subarachnoid anesthesia has proven to be an effective, safe, and easy-to-manage technique for carrying out SFP procedure in a non-conventional environment such as an angiographic room. It was free of serious side effects and well tolerated even in patients in poor general conditions.

  7. High RAB25 expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma

    PubMed Central

    Téllez-Gabriel, Marta; Arroyo-Solera, Irene; León, Xavier; Gallardo, Alberto; López, Montserrat; Céspedes, Maria V; Casanova, Isolda; López-Pousa, Antonio; Quer, Miquel; Mangues, Maria A; Barnadas, Agustí; Mangues, Ramón; Pavón, Miguel A

    2013-01-01

    Currently there are no molecular markers able to predict clinical outcome in locally advanced head and neck squamous cell carcinoma (HNSCC). In a previous microarray study, RAB25 was identified as a potential prognostic marker. The aim of this study was to analyze the association between RAB25 expression and clinical outcome in patients with locally advanced HNSCC treated with standard therapy. In a retrospective immunohistochemical study (n = 97), we observed that RAB25-negative tumors had lower survival (log-rank, P = 0.01) than patients bearing positive tumors. In an independent prospective mRNA study (n = 117), low RAB25 mRNA expression was associated with poor prognosis. Using classification and regression tree analysis (CART) we established two groups of patients according to their RAB25 mRNA level and their risk of death. Low mRNA level was associated with poor local recurrence-free (log-rank, P = 0.005), progression-free (log-rank, P = 0.002) and cancer-specific (log-rank, P < 0.001) survival. Multivariate Cox model analysis showed that low expression of RAB25 was an independent poor prognostic factor for survival (hazard ratio: 3.84, 95% confidence interval: 1.93–7.62, P < 0.001). Patients whose tumors showed high RAB25 expression had a low probability of death after treatment. We also found lower RAB25 expression in tumors than in normal tissue (Mann–Whitney U, P < 0.001). Moreover, overexpression of RAB25 in the UM-SCC-74B HNSCC cell line increased cisplatin sensitivity, and reduced cell migration and invasion. Our findings support a tumor suppressor role for RAB25 in HNSCC and its potential use to identify locally advanced patients with a high probability of survival after genotoxic treatment. PMID:24403269

  8. SU-E-T-317: Dosimetric Evaluation of Acuros XB Advanced Dose Calculation Algorithm in Head and Neck Patients

    SciTech Connect

    Faught, A; Wu, Q

    2015-06-15

    Purpose: The Acuros XB photon dose calculation algorithm is a newly implemented calculation technique within the Eclipse treatment planning system using deterministic solutions to the linear Boltzmann transport equations. The goal of this study is to assess the clinical impact of dose differences arising from a retrospective comparison of calculations performed using the Analytical Anisotropic Algorithm (AAA) and Acuros XB on patients. Methods: Ten head and neck patients receiving intensity modulated radiation therapy were selected as a pilot study. Initial evaluation was based on the percentage of the planning target volume (PTV) covered by the prescription dose, minimum dose within the PTV, and dose differences in critical structures. For patients receiving boost plans, dosimetric evaluations were performed on the plan sum of the primary and boost plans. Results: Among the ten patients there were a total of 21 PTVs corresponding to primary and boost volumes. Using the same normalization within Eclipse, the average percentage of the PTVs receiving the prescription dose were 95.6% for AAA and Acuros XB. The average minimum doses within the PTVs, expressed as a percentage of the prescription to the volume, were 82.3% and 83.6% for AAA and Acuros XB respectively. Neither comparison showed differences with statistical significance when subjected to a paired t-test. Statistical significance was found in the average difference of the maximum dose for the mandible (242.5cGy, p=0.0005) and cord with a 5mm radial expansion (105.0cGy, p=0.0005) and in the median dose for the left parotid (25.0cGy, p=0.0423) and oral cavity (36.3cGy, p=0.002). Conclusion: The Acuros XB dose calculation algorithm did not exhibit significant differences in PTV coverage when compared to the AAA algorithm. Significant differences in critical structures are likely attributed to the structures proximity to high atomic number materials or air cavities, regions of known difficulty for the AAA

  9. [Anatomic changes after radical surgery and reconstruction with pedunculated or revascularized flaps in advanced head and neck tumors: computerized tomography and magnetic resonance findings].

    PubMed

    Osti, M F; Scattoni Padovan, F; Ricciardi, D; De Angelis D'Ossat, M; Sbarbati, S; Pirolli, C; Maurizi Enrici, R; Anaveri, G

    1997-04-01

    January, 1992, to October, 1995, sixty-four patients with advanced head and neck cancer underwent head and neck reconstructive surgery using myocutaneous or revascularized flaps; in the same period, all patients were consecutively examined with CT and MRI. Myocutaneous flaps wer used in 26 patients: 12 flaps were tubular and 14 linear. Revascularized flaps were used in 38 patients: to repair a large defect in 26 patients (14 latissimus dorsi flaps and 12 temporal muscle flaps) and to repair an oral damage in 12 patients (5 revascularized radial and 7 jejunal flaps). CT and MR images of myocutaneous flaps showed the flaps as fatty areas, repairing large surgical defects, hypodense at CT and hyperintense at MRI, with no post-contrast enhancement. The postoperative scar around the flap exhibited soft-tissue density with slight post-contrast enhancement at CT and slightly hypodense on T2-weighted MR images. Post-contrast CT and MRI showed slight scar enhancement with no signal changes in the fatty component. The appearance of revascularized flaps at CT and MRI depends on the characteristics of the structure used to repair the surgical defect: jejunal and radial flaps appeared as mostly fatty thickened layers with both imaging methods. Temporal and latissimus dorsi flaps are made basically of muscular tissue, fatty tissue and occasionally skin (used to repair a mucosal defect): consequently, CT showed a structure with mostly parenchymal density in all cases and MRI depicted intermediate signal intensity. MRI was useful to detect 12 revascularized jejunal or radial flaps thanks to its higher contrast resolution and multiplanar capabilities showing even such thin structures as these flaps. Moreover, MRI permitted to study skull base reconstruction with revascularized (latissimus dorsi) flaps in 5 of our patients.

  10. Economic analysis of amifostine as adjunctive support for patients with advanced head and neck cancer: preliminary results from a randomized phase II clinical trial from Germany.

    PubMed

    Bennett, C L; Lane, D; Stinson, T; Glatzel, M; Buntzel, J

    2001-01-01

    In a randomized phase II trial in Germany, we investigated the clinical and economic impact of amifostine protection against the hematological and oral toxicities of carboplatin administered concurrently with standard fractions of radiotherapy. 28 patients with squamous cell carcinomas of the head and neck received adjunctive or primary radiotherapy (5 days per week with daily fractions of 2 Gy, up to a total dose of 60 Gy) in conjunction with carboplatin (70 mg/m2) on days 1-5 and days 21-26. All patients received radiation encompassing at least 75% of the major salivary glands. Patients were randomized to receive radiation and carboplatin (RCT) alone or RCT preceded by rapid infusion of amifostine (500 mg) on days carboplatin was administered. The 14 patients who received amifostine, in comparison to 14 patients in the control arm, had significantly fewer episodes of grade 3 or 4 thrombocytopenia (p = 0.001), mucositis (p = 0.001), and xerostomia (p = 0.001). The patients receiving amifostine accrued significantly lower supportive care costs for resources related to infection ($241 vs. $1,275, p < 0.01), red blood cell and platelet support ($286 vs. $1,276 p = 0.06) alimentation ($343 vs. $894, p = .01), and hospitalization ($286 vs. $2,429, p < 0.01). Overall, including the costs of amifostine, mean per patient supportive care costs were $4,401 for the amifostine group and $5,873 (p = .02) for the control group. Our results from a randomized phase II trial indicate that selective cytoprotection with amifostine potentially offers clinical and economic benefits in patients with advanced head and neck cancer receiving radiochemotherapy. Additional economic studies alongside randomized phase III trials and from other countries are needed.

  11. Mucosal Melanoma of the Head and Neck: A Systematic Review of the Literature

    SciTech Connect

    Lazarev, Stanislav; Gupta, Vishal; Hu, Kenneth; Harrison, Louis B.; Bakst, Richard

    2014-12-01

    Primary mucosal melanoma of the head and neck (MMHN) comprises approximately 1% of all malignant melanomas. It presents more commonly in an elderly population and has no significant gender predominance. Given its rarity, most evidence of the causes, behavior, and treatment approaches for MMHN originates from isolated case reports and retrospective series. Between 1945 and 2011, at least 1951 cases of MMHN have been reported in the literature. Despite numerous technological developments in surgery and radiation therapy, as well as advances in systemic modalities, MMHN is an aggressive malignancy with a very poor prognosis. Complete surgical excision with clear margins remains the primary treatment modality. Adjuvant postoperative radiation therapy may improve locoregional control but does not appear to affect survival. Definitive particle radiation therapy promises to provide high rates of local control for nonoperable patients. Recent molecular evidence suggests that proto-oncogene KIT aberrations in a subset of mucosal melanomas may represent a potential diagnostic value and serve as a therapeutic target for tyrosine kinase inhibitors in an adjuvant setting for patients with advanced MMHN.

  12. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial.

    PubMed

    Haddad, Robert; O'Neill, Anne; Rabinowits, Guilherme; Tishler, Roy; Khuri, Fadlo; Adkins, Douglas; Clark, Joseph; Sarlis, Nicholas; Lorch, Jochen; Beitler, Jonathan J; Limaye, Sewanti; Riley, Sarah; Posner, Marshall

    2013-03-01

    The relative efficacy of the addition of induction chemotherapy to chemoradiotherapy compared with chemoradiotherapy alone for patients with head and neck cancer is unclear. The PARADIGM study is a multicentre open-label phase 3 study comparing the use of docetaxel, cisplatin, and fluorouracil (TPF) induction chemotherapy followed by concurrent chemoradiotherapy with cisplatin-based concurrent chemoradiotherapy alone in patients with locally advanced head and neck cancer. Adult patients with previously untreated, non-metastatic, newly diagnosed head and neck cancer were eligible. Patients were eligible if their tumour was either unresectable or of low surgical curability on the basis of advanced tumour stage (3 or 4) or regional-node stage (2 or 3, except T1N2), or if they were a candidate for organ preservation. Patients were randomly assigned (in a 1:1 ratio) to receive either induction chemotherapy with three cycles of TPF followed by concurrent chemoradiotherapy with either docetaxel or carboplatin or concurrent chemoradiotherapy alone with two cycles of bolus cisplatin. A computer-generated randomisation schedule using minimisation was prepared and the treatment assignment was done centrally at one of the study sites. Patients, study staff, and investigators were not masked to group assignment. Stratification factors were WHO performance status, primary disease site, and stage. The primary endpoint was overall survival. Analysis was by intention to treat. Patient accrual was terminated in December, 2008, because of slow enrolment. The trial is registered with ClinicalTrials.gov, number NCT00095875. Between Aug 24, 2004, and Dec 29, 2008, we enrolled 145 patients across 16 sites. After a median follow-up of 49 months (IQR 39-63), 41 patients had died-20 in the induction chemotherapy followed by chemoradiotherapy group and 21 in the chemoradiotherapy alone group. 3-year overall survival was 73% (95% CI 60-82) in the induction therapy followed by

  13. An overview of loco-regional treatments in patients and mouse models for hepatocellular carcinoma.

    PubMed

    Bimonte, Sabrina; Barbieri, Antonio; Palaia, Raffaele; Leongito, Maddalena; Albino, Vittorio; Piccirillo, Mauro; Arra, Claudio; Izzo, Francesco

    2015-01-01

    Hepatocellular carcinoma is a highly aggressive malignancy and is the third leading cause of cancer-related deaths worldwide. Although surgery is currently considered the most effective curative treatment for this type of cancer, it is note that most of patients have a poor prognosis due to chemioresistence and tumor recurrence. Loco-regional therapies, including radiofrequency ablation, surgical resection and transcatheter arterial chemoembolization play a major role in the clinical management of hepatocellular carcinoma. In order to improve the treatment outcome of patients diagnosed with this disease, several in vivo studies by using different techniques on cancer mouse models have been performed. This review will focus on the latest papers on the efficacy of loco-regional therapy and combined treatments in patients and mouse models of hepatocellular carcinoma.

  14. [Taxane-cisplatin-fluorouracil as induction chemotherapy for advanced head and neck cancer: a Meta-analysis of the efficacy and safety].

    PubMed

    Jian, Jiejun; Li, Guoyi; Yu, Zizhong; Tian, Lei

    2016-02-01

    To systematically review the efficacy and safety of taxane, cisplatin, and fluorouracil (Tax-PF) as induction chemotherapy for advanced head and neck cancer. Literature about the efficacy and safety of Taxane-cisplatin-fluorouracil as induction chemotherapy for advanced head and neck cancer was retrieved from digital databases of PubMed, Embase, SpringerLink, MEDLINE and the Cochrane Library before February 2015. Data extraction and quality assessment of included studies were conducted by two reviewers independently. Stata 13.0 was then used to perform Meta-analysis. A total 7 randomized controlled trials involving 2,702 were included. The 3-year OS rate [HR = 1.14, 95% CI (1.03, 1.25), P < 0.01], 3-year PFS rate [HR = 1.24, 95% CI (1.08, 1.43), P < 0.01], 5-year OS rate [HR = 1.30, 95% CI (1.09, 1. 55), P < 0. 01], 5-year PFS rate [HR = 1.39, 95% CI (1.14, 1.70), P < 0.01] and ORR to chemotherapy [OR = 1.66, 95% CI (1.35, 2.05), P < 0.01] of the patients in the Tax-PF group were statistically superior to those in the PF group. In terms of toxicities, the incidence of febrile neutropenia [OR = 2.36, 95% CI (1.62, 3.46), P < 0.01], alopecia [OR = 8.22, 95% CI (3.99, 16.92), P < 0.01], diarrhea [OR = 1.57, 95% CI (1.05, 2.36), P< 0.05] and leucopenia [OR = 2.79, 95% CI (1.86, 4.21), P < 0.01] was higher in the Tax-PF group than that in the PF group. The Tax-PF induction chemotherapy improved PFS and OS, and the ORR was better as compared to PF-based therapy regimens at the cost of a higher incidence of adverse events.

  15. [Electrochemotherapy: mechanism of action and clinical results in the locoregional treatment of patients with skin cancers and superficial metastases].

    PubMed

    Campana, Luca Giovanni; Marconato, Roberto; Sieni, Elisabetta; Valpione, Sara; Corti, Luigi; Mocellin, Simone; Rossi, Carlo Riccardo

    2016-08-01

    Electrochemotherapy (ECT) has emerged among European centers as an innovative locoregional treatment for patients with unresectable skin cancers or superficial metastases from any histotype. The combined administration of a cytotoxic agent (bleomycin or cisplatin) with properly tuned electric pulses results in locally-enhanced drug delivery (reversible electroporation) into malignant cells and sustained tumor response. Reversible electroporation represents the basis of ECT and allows the potentiation of two low permeant cytotoxic agents such as bleomycin (~8000 fold) and cisplatin (~80 fold). The procedure was standardized in 2006 - thanks to a European project - and shortly after introduced in the clinical practice. In recent years, experience with ECT has accumulated mainly in melanoma and breast cancer patients with cutaneous metastases, in whom complete response rates of 20-50% and 40-75% have been reported, respectively, depending on tumor size. Currently, this therapy is being investigated in deep-seated (i.e. bone, soft tissue) metastases and visceral malignancies (i.e. locally advanced pancreatic cancer), with encouraging results.

  16. Hyperthermia and reirradiation for locoregional recurrences in preirradiated breast cancers: a single institutional experience.

    PubMed

    Datta, Niloy R; Puric, Emsad; Heüberger, Juerg; Marder, Dietmar; Lomax, Nicoletta; Timm, Olaf; Memminger, Priska; Bodis, Stephan

    2015-01-01

    The aim of this retrospective analysis was to evaluate the safety and efficacy of local hyperthermia (HT) and reirradiation (ReRT) in the management of preirradiated locoregional recurrent breast cancers at Kantonsspital Aarau, Switzerland. Twenty-four previously irradiated patients who had developed locoregional recurrences in the chest wall or breast, with or without regional lymph node involvement, were reirradiated to a mean dose of 36.8 Gy (range 20-50 Gy) delivered at a mean dose per fraction of 2.33 Gy (range 1.8-4.0 Gy). All patients received local HT at 41 to 43 °C, once or twice a week prior to radiotherapy. Online thermometry was carried out during the hyperthermia sessions. An overall objective response rate of 91.7% (22/24) with a complete response in 66.7% (16/24) of patients and partial response in 25% (6/24) of patients was observed. Post-thermoradiotherapy follow-up ranged from 1 to 38 months (median 10 months). The 3-year actuarial local control rate was 59.7%. More patients who attained complete response had sustained locoregional control until their death or last follow-up when compared with those who were partial or non-responders (median local disease-free survival for complete responders not reached; for partial and non-responders 4 months; p <0.001). Post-retreatment median overall survival for all 24 patients was 10 months. Grade III/IV acute toxicity was seen in only one patient and no patient had any significant late morbidity. ReRT and HT is an effective and a safe modality to treat locoregional recurrences in previously irradiated breast cancers. The approach can lead to sustainable long-term palliation with minimal morbidity.

  17. DEGRO practical guidelines for radiotherapy of breast cancer VI: therapy of locoregional breast cancer recurrences.

    PubMed

    Harms, Wolfgang; Budach, W; Dunst, J; Feyer, P; Fietkau, R; Haase, W; Krug, D; Piroth, M D; Sautter-Bihl, M-L; Sedlmayer, F; Souchon, R; Wenz, F; Sauer, R

    2016-04-01

    To update the practical guidelines for radiotherapy of patients with locoregional breast cancer recurrences based on the current German interdisciplinary S3 guidelines 2012. A comprehensive survey of the literature using the search phrases "locoregional breast cancer recurrence", "chest wall recurrence", "local recurrence", "regional recurrence", and "breast cancer" was performed, using the limits "clinical trials", "randomized trials", "meta-analysis", "systematic review", and "guidelines". Patients with isolated in-breast or regional breast cancer recurrences should be treated with curative intent. Mastectomy is the standard of care for patients with ipsilateral breast tumor recurrence. In a subset of patients, a second breast conservation followed by partial breast irradiation (PBI) is an appropriate alternative to mastectomy. If a second breast conservation is performed, additional irradiation should be mandatory. The largest reirradiation experience base exists for multicatheter brachytherapy; however, prospective clinical trials are needed to clearly define selection criteria, long-term local control, and toxicity. Following primary mastectomy, patients with resectable locoregional breast cancer recurrences should receive multimodality therapy including systemic therapy, surgery, and radiation +/- hyperthermia. This approach results in high local control rates and long-term survival is achieved in a subset of patients. In radiation-naive patients with unresectable locoregional recurrences, radiation therapy is mandatory. In previously irradiated patients with a high risk of a second local recurrence after surgical resection or in patients with unresectable recurrences, reirradiation should be strongly considered. Indication and dose concepts depend on the time interval to first radiotherapy, presence of late radiation effects, and concurrent or sequential systemic treatment. Combination with hyperthermia can further improve tumor control. In patients with

  18. Hepatocellular carcinoma after locoregional therapy: Magnetic resonance imaging findings in falsely negative exams.

    PubMed

    Becker-Weidman, David; Civan, Jesse M; Deshmukh, Sandeep P; Roth, Christopher G; Herrine, Steven K; Parker, Laurence; Mitchell, Donald G

    2016-06-08

    To elucidate causes for false negative magnetic resonance imaging (MRI) exams by identifying imaging characteristics that predict viable hepatocellular carcinoma (HCC) in lesions previously treated with locoregional therapy when obvious findings of recurrence are absent. This retrospective institutional review board-approved and Health Insurance Portability and Accountability Act-compliant study included patients who underwent liver transplantation at our center between 1/1/2000 and 12/31/2012 after being treated for HCC with locoregional therapy. All selected patients had a contrast-enhanced MRI after locoregional therapy within 90 d of transplant that was prospectively interpreted as without evidence of residual or recurrent tumor. Retrospectively, 2 radiologists, blinded to clinical and pathological data, independently reviewed the pre-transplant MRIs for 7 imaging features. Liver explant histopathology provided the reference standard, with clinically significant tumor defined as viable tumor ≥ 1.0 cm in maximum dimension. Fisher's exact test was first performed to identify significant imaging features. Inclusion criteria selected for 42 patients with 65 treated lesions. Fourteen of 42 patients (33%) and 16 of 65 treated lesions (25%) had clinically significant viable tumor on explant histology. None of the 7 imaging findings examined could reliably and reproducibly determine which treated lesion had viable tumor when the exam had been prospectively read as without evidence of viable HCC. After locoregional therapy some treated lesions that do not demonstrate any MRI evidence of HCC will contain viable tumor. As such even patients with a negative MRI following treatment should receive regular short-term imaging surveillance because some have occult viable tumor. The possibility of occult tumor should be a consideration when contemplating any action which might delay liver transplant.

  19. Multicriteria Optimization in Intensity-Modulated Radiation Therapy Treatment Planning for Locally Advanced Cancer of the Pancreatic Head

    SciTech Connect

    Hong, Theodore S. Craft, David L.; Carlsson, Fredrik; Bortfeld, Thomas R.

    2008-11-15

    Purpose: Intensity-modulated radiation therapy (IMRT) affords the potential to decrease radiation therapy-associated toxicity by creating highly conformal dose distributions. However, the inverse planning process can create a suboptimal plan despite meeting all constraints. Multicriteria optimization (MCO) may reduce the time-consuming iteration loop necessary to develop a satisfactory plan while providing information regarding trade-offs between different treatment planning goals. In this exploratory study, we examine the feasibility and utility of MCO in physician plan selection in patients with locally advanced pancreatic cancer (LAPC). Methods and Materials: The first 10 consecutive patients with LAPC treated with IMRT were evaluated. A database of plans (Pareto surface) was created that met the inverse planning goals. The physician then navigated to an 'optimal' plan from the point on the Pareto surface at which kidney dose was minimized. Results: Pareto surfaces were created for all 10 patients. A physician was able to select a plan from the Pareto surface within 10 minutes for all cases. Compared with the original (treated) IMRT plans, the plan selected from the Pareto surface had a lower stomach mean dose in 9 of 10 patients, although often at the expense of higher kidney dose than with the treated plan. Conclusion: The MCO is feasible in patients with LAPC and allows the physician to choose a satisfactory plan quickly. Generally, when given the opportunity, the physician will choose a plan with a lower stomach dose. The MCO enables a physician to provide greater active clinical input into the IMRT planning process.

  20. Personalization of loco-regional care for primary breast cancer patients (part 1).

    PubMed

    Toi, Masakazu; Winer, Eric P; Benson, John R; Inamoto, Takashi; Forbes, John F; von Minckwitz, Gunter; Robertson, John F R; Grobmyer, Stephen R; Jatoi, Ismail; Sasano, Hironobu; Kunkler, Ian; Ho, Alice Y; Yamauchi, Chikako; Chow, Louis W C; Huang, Chiun-Sheng; Han, Wonshik; Noguchi, Shinzaburo; Pegram, Mark D; Yamauchi, Hideko; Lee, Eun-Sook; Larionov, Alexey A; Bevilacqua, Jose L B; Yoshimura, Michio; Sugie, Tomoharu; Yamauchi, Akira; Krop, Ian E; Noh, Dong Young; Klimberg, V Suzanne

    2015-01-01

    ABSTRACT  Kyoto Breast Cancer Consensus Conference, Kyoto, Japan, 18-20 February 2014 The loco-regional management of breast cancer is increasingly complex with application of primary systemic therapies, oncoplastic techniques and genetic testing for breast cancer susceptibility. Personalization of loco-regional treatment is integral to optimization of breast cancer care. Clinical and pathological tumor stage, biological features and host factors influence loco-regional treatment strategies and extent of surgical procedures. Key issues including axillary staging, axillary treatment, radiation therapy, primary systemic therapy (PST), preoperative hormonal therapy and genetic predisposition were identified and discussed at the Kyoto Breast Cancer Consensus Conference (KBCCC2014). In the first of a two part conference scene, consensus recommendations for axillary management are presented and focus on the following topics: indications for completion axillary lymph node dissection in primary surgical patients with ≤2 macrometastases or any sentinel nodal deposits after PST; the timing of sentinel lymph node biopsy in the context of PST; use of axillary irradiation as a component of primary treatment plans and the role of intraoperative node assessment in the post-Z0011 era.

  1. Personalization of loco-regional care for primary breast cancer patients (part 2).

    PubMed

    Toi, Masakazu; Winer, Eric P; Benson, John R; Inamoto, Takashi; Forbes, John F; von Minckwitz, Gunter; Robertson, John F R; Grobmyer, Stephen R; Jatoi, Ismail; Sasano, Hironobu; Kunkler, Ian; Ho, Alice Y; Yamauchi, Chikako; Chow, Louis W C; Huang, Chiun-Sheng; Han, Wonshik; Noguchi, Shinzaburo; Pegram, Mark D; Yamauchi, Hideko; Lee, Eun-Sook; Larionov, Alexey A; Bevilacqua, Jose L B; Yoshimura, Michio; Sugie, Tomoharu; Yamauchi, Akira; Krop, Ian E; Noh, Dong Young; Klimberg, V Suzanne

    2015-01-01

    Kyoto Breast Cancer Consensus Conference, Kyoto, Japan, 18-20 February 2014 The loco-regional management of breast cancer is increasingly complex with application of primary systemic therapies, oncoplastic techniques and genetic testing for breast cancer susceptibility. Personalization of loco-regional treatment is integral to optimization of breast cancer care. Clinical and pathological tumor stage, biological features and host factors influence loco-regional treatment strategies and extent of surgical procedures. Key issues including axillary staging, axillary treatment, radiation therapy, primary systemic therapy (PST), preoperative hormonal therapy and genetic predisposition were identified and discussed at the Kyoto Breast Cancer Consensus Conference (KBCCC2014). In the second of a two part conference scene, consensus recommendations for radiation treatment, primary systemic therapies and management of genetic predisposition are reported and focus on the following topics: influence of both clinical response to PST and stage at presentation on recommendations for postmastectomy radiotherapy; use of regional nodal irradiation in selected node-positive patients and those with adverse pathological factors; extent of surgical resection following downstaging of tumors with PST; use of preoperative hormonal therapy in premenopausal women with larger, node-negative luminal A-like tumors and managing increasing demands for contralateral prophylactic mastectomy in patients with a unilateral sporadic breast cancer.

  2. Is there a role for locoregional surgery in stage IV breast cancer?

    PubMed

    Quinn, Edel M; Kealy, Rebecca; O'Meara, Siobhan; Whelan, Maria; Ennis, Rachel; Malone, Carmel; McLaughlin, Ray; Kerin, Michael J; Sweeney, Karl J

    2015-02-01

    Current guidelines do not recommend locoregional surgery for Stage IV breast cancer at presentation despite some studies suggesting a survival benefit. We aimed to assess outcomes in patients with Stage IV breast cancer who underwent surgery. In a cohort study of all Stage IV breast cancers diagnosed at our tertiary-referral specialist centre between 2006 and 2012, we assessed patient survival in the context of demographics, histopathology, metastatic burden, and type of surgery performed. One hundred and nine patients were included; 52 underwent surgery. Patients in the surgery group had longer 5-year-survival (p = 0.003). Survival was also significantly longer in those with just one site of metastatic disease (p < 0.001). Patients with axillary cytology positive for regional metastases were less likely to proceed to surgery. Locoregional surgery does confer a survival advantage in Stage IV breast cancer. Assessment of preoperative axillary cytology may preclude some patients from proceeding to potentially beneficial locoregional surgery. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Locoregional treatment of breast cancer in women with and without preoperative magnetic resonance imaging.

    PubMed

    Ozanne, Elissa M; Weiss, Julie E; Onega, Tracy; DeMartini, Wendy; Kerlikowske, Karla; Buist, Diana S M; Henderson, Louise; Hubbard, Rebecca A; Goodrich, Martha; Tosteson, Anna N A; Virnig, Beth A; O'Donoghue, Cristina

    2017-01-01

    Preoperative magnetic resonance imaging (MRI) use has increased among older women diagnosed with breast cancer. MRI detects additional malignancy, but its impact on locoregional surgery and radiation treatment remains unclear. We examined the associations of preoperative MRI with initial locoregional treatment type (mastectomy, breast conserving surgery [BCS] with radiation therapy [RT], and BCS without RT) and BCS reoperation rates for Surveillance, Epidemiology, and End Results Medicare women diagnosed with stages 0 to III breast cancer from 2005 to 2009 (n = 55,997). We found no association of initial locoregional treatment of mastectomy (odds ratios [OR], 1.04; 95% confidence intervals, .98 to 1.11) or reoperation after initial BCS (OR, .96; 95% confidence intervals, .89 to 1.03) between women with preoperative MRI (16.2%) compared to women without MRI. However, women with MRI who had initial BCS were more likely to undergo RT (OR, 1.09 [1.02 to 1.16]). Preoperative breast MRI in Medicare-enrolled women with stages 0 to III breast cancer was not associated with increased mastectomy. However, in older women with MRI undergoing BCS, there was a greater use of RT. Copyright © 2016. Published by Elsevier Inc.

  4. Altered and Conventional Fractionated Radiotherapy in Locoregional Control and Survival of Patients with Squamous Cell Carcinoma of the Larynx, Oropharynx, and Hypopharynx

    PubMed Central

    Krstevska, Valentina; Crvenkova, Simonida

    2006-01-01

    Aim To compare the efficacy of two altered fractionation radiotherapy treatment protocols (hyperfractionation and accelerated fractionation with concomitant boost) with conventional fractionation in improvement of locoregional disease control and survival of patients with squamous cell carcinoma of the larynx, oropharynx, or hypopharynx. Methods From March 1999 to December 2000, 51 patients with previously untreated squamous cell carcinoma of the larynx, oropharynx or hypopharynx underwent conventionally fractionated radiotherapy and received 66-70 Gy in 6˝-7 weeks (2 Gy per fraction a day, 5 fractions a week). From January 2001 to June 2004, 101 patients with the same diagnoses underwent either hyperfractionated radiotherapy, with 74.4-79.2 Gy delivered in 6.2-7 weeks (1.2 Gy per fraction twice a day), or accelerated fractionation with concomitant boost, which delivered 68.7-72 Gy in 6 weeks (1.8 Gy per fraction a day and 1.5 Gy per fraction a day to a boost filed as a second daily treatment for the last 11-12 treatment days). Locoregional relapse and overall survival were recorded. Results Complete response to treatment was obtained in 31 of 51 patients treated with conventional fractionation, 33 of 50 patients treated with hyperfractionation, and 36 of 51 patients treated with accelerated fractionation. No significant differences were observed among the patients treated with conventional, hyperfractionated, or accelerated radiotherapy modalities either in locoregional control rate (41% vs 35% vs 49%, respectively; P = 0.690) or overall survival rate (50% vs 40% vs 51%, respectively; P = 0.760). The grade of acute reactions of the larynx significantly differed among the treatment groups (Fisher exact test; P = 0.039). The difference in the grade of acute side effects in the skin among the treatment groups was of borderline significance (χ22 test; P = 0.054). There was also a borderline difference among the groups in the grade of late side

  5. 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.

  6. Feasibility Study of Moderately Accelerated Intensity-Modulated Radiotherapy Plus Concurrent Weekly Cisplatin After Induction Chemotherapy in Locally Advanced Head-and Neck Cancer

    SciTech Connect

    Morganti, Alessio G.; Mignogna, Samantha; Deodato, Francesco; Massaccesi, Mariangela; Cilla, Savino; Calista, Franco; Serafini, Giovanni; Digesu, Cinzia; Macchia, Gabriella; Picardi, Vincenzo; Caravatta, Luciana; Di Lullo, Liberato; Giglio, Gianfranco; Sallustio, Giuseppina; Piermattei, Angelo

    2011-03-15

    Purpose: To evaluate the feasibility and efficacy of moderately accelerated intensity-modulated radiation therapy (IMRT) along with weekly cisplatin, after induction chemotherapy, in patients with locally advanced unresectable head and neck cancer (HNC). Methods and Materials: Patients with Stage III or IV locally advanced HNC, without progressive disease after three courses of induction chemotherapy, received concurrent chemo-IMRT (weekly cisplatin 30 mg/m{sup 2} plus simultaneous integrated boost IMRT). A total of 67.5 Gy in 30 fractions were delivered to primary tumor and involved nodes, 60 Gy in 30 fractions to high-risk nodal areas, and 55.5 Gy in 30 fractions to low-risk nodal areas. Results: In all, 36 patients (median age, 56 years) with International Union Against Cancer (UICC) Stage III (n = 5) and IV (n = 31) were included. Of the 36 patients, 17 had received CF (cisplatin and 5-fluorouracil (CF) and 19 had received docetaxel cisplatin and 5-fluorouracil (DCF). During concurrent chemoradiation, 11 of 36 patients (30.5%) experienced Grade III mucositis (CF, 47%; DCF, 15%; p < 0.04). Grade III pharyngeal-esophageal toxicity was observed in 5 of 19 patients (26.3%; CF, 0.0%; DCF, 26.3%; p = 0.02). Two patients died of complications (5.5%). After chemoradiation, the complete response rate was 63.8%. Two-year local control was 88.7%. Two-year progression free survival and overall survival were 74.5% and 60.9%, respectively. Conclusions: In our experience, a moderately accelerated chemo-IMRT was feasible after induction chemotherapy. However, a noteworthy early death rate of 5.5% was observed. Intensive supportive care strategies should be defined to better manage radiation-induced toxic effects. Longer follow-up is required to determine the incidence of late radiation toxicities and tumor control rates.

  7. Erlotinib and chemoradiation in patients with surgically resected locally advanced squamous cell carcinoma of the head and neck: a GICOR phase I trial.

    PubMed

    Arias de la Vega, F; Contreras, J; de Las Heras, M; de la Torre, A; Arrazubi, V; Herruzo, I; Prieto, I; García-Saenz, J A; Romero, J; Calvo, F A

    2012-04-01

    Standard treatment of advanced squamous cell carcinoma of the head and neck (SCCHN) is concurrent chemoradiation. Erlotinib is an oral tyrosine kinase inhibitor of epidermal growth factor receptor, which has shown activity in SCCHN. Phase I study aims to determine the maximum tolerated dose and dose-limiting toxicity (DLT) of adding erlotinib to chemoradiation therapy in patients with surgically resected locally advanced SCCHN. Inclusion criteria--SCCHN patients with T3 or T4 primary lesion (except T3N0 with negative resection margins); pathologic N2-N3 disease; poor prognostic findings; age 18-70 years; Eastern Cooperative Oncology Group performance status of zero to one; no evidence of metastasis; adequate organic function and written informed consent. Study design--dose-escalating phase I study with three cohorts of three to six patients each that received increasing doses of erlotinib (100-150 mg/day p.o.) and cisplatin (30-40 mg/m(2) i.v., day 1) for 7 weeks. Radiotherapy--standard regimen of 1.8 Gy daily (5 fractions/week) to a maximum total dose of 63 Gy in 7 weeks. Thirteen male (median age: 57 years) were enrolled. Overall, the regimen was well tolerated. Two of three patients treated at dose level III (erlotinib: 150 mg/day; cisplatin: 40 mg/m(2)) developed DLT consisting of grade 3 infection and grade 3 mucositis. Other toxic effects included diarrhea, asthenia, and rash. Recommended dose for additional studies: erlotinib 150 mg/day p.o.; cisplatin 30 mg/m(2)/week i.v. Erlotinib can be safely combined with chemoradiation without requiring dose reduction of chemo- or radiotherapy in this postsurgical population.

  8. Adjuvant chemoradiation therapy with high-dose versus weekly cisplatin for resected, locally-advanced HPV/p16-positive and negative head and neck squamous cell carcinoma.

    PubMed

    Geiger, Jessica L; Lazim, Ahmed F; Walsh, Francis J; Foote, Robert L; Moore, Eric J; Okuno, Scott H; Olsen, Kerry D; Kasperbauer, Jan L; Price, Daniel L; Garces, Yolanda I; Ma, Daniel J; Neben-Wittich, Michelle A; Molina, Julian R; Garcia, Joaquin J; Price, Katharine A R

    2014-04-01

    Standard treatment for patients with poor-risk, resected head and neck squamous cell carcinoma (HNSCC) is adjuvant radiation therapy combined with high-dose cisplatin. Many patients are treated with weekly cisplatin; it is not known whether weekly and high-dose cisplatin are equivalent. This study compares the outcomes of patients with locally-advanced HPV-negative HNSCC and HPV/p16-positive oropharynx HNSCC treated with adjuvant chemoradiation therapy with either high-dose or weekly cisplatin. Retrospective review of patients with Stage III/IV HNSCC who had surgery followed by adjuvant chemoradiation therapy at Mayo Clinic, Rochester. HPV and/or p16 status was available for all oropharynx patients. 104 Patients (51 high-dose, 53 weekly) were analyzed. The 3-year overall survival was 84% and 75% for patients who received high dose and weekly cisplatin, respectively (p=0.30). The 3-year recurrence free survival was 71% and 74% in the high dose and weekly cisplatin group, respectively (p=0.95). Patients with HPV/p16-positive oropharynx cancer who received adjuvant chemoradiation therapy with high-dose and weekly cisplatin had three-year overall survival rates of 91% and 86% (p=0.56), and 3-year recurrence free survival of 84% and 82% (p=0.93). Extracapsular extension did not affect prognosis in either group. No significant survival difference was seen between patients with locally advanced HNSCC treated with adjuvant chemoradiation therapy with high-dose or weekly cisplatin, although there was a trend for improved survival with high-dose cisplatin. Weekly cisplatin in the adjuvant setting may be a better treatment for patients with HPV-positive oropharynx cancer to preserve survival and minimize toxicity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Non-invasive prediction of the tumor growth rate using advanced diffusion models in head and neck squamous cell carcinoma patients.

    PubMed

    Fujima, Noriyuki; Sakashita, Tomohiro; Homma, Akihiro; Harada, Taisuke; Shimizu, Yukie; Tha, Khin Khin; Kudo, Kohsuke; Shirato, Hiroki

    2017-05-16

    We assessed parameters of advanced diffusion weighted imaging (DWI) models for the prediction of the tumor growth rate in 55 head and neck squamous cell carcinoma (HNSCC) patients. The DWI acquisition used single-shot spin-echo echo-planar imaging with 12 b-values (0-2000). We calculated 14 DWI parameters using mono-exponential, bi-exponential, tri-exponential, stretched exponential and diffusion kurtosis imaging models. We directly measured the tumor growth rate from two sets of different-date imaging data. We divided the patients into a discovery group (n = 40) and validation group (n = 15) based on their MR acquisition dates. In the discovery group, we performed univariate and multivariate regression analyses to establish the multiple regression equation for the prediction of the tumor growth rate using diffusion parameters. The equation obtained with the discovery group was applied to the validation group for the confirmation of the equation's accuracy. After the univariate and multivariate regression analyses in the discovery-group patients, the estimated tumor growth rate equation was established by using the significant parameters of intermediate diffusion coefficient D2 and slow diffusion coefficient D3 obtained by the tri-exponential model. The discovery group's correlation coefficient between the estimated and directly measured tumor growth rates was 0.74. In the validation group, the correlation coefficient (r = 0.66) and intra-class correlation coefficient (0.65) between the estimated and directly measured tumor growth rates were respectively good. In conclusion, advanced DWI model parameters can be a predictor for determining HNSCC patients' tumor growth rate.

  10. A Phase I Trial to Evaluate Antibody-Dependent Cellular Cytotoxicity of Cetuximab and Lenalidomide in Advanced Colorectal and Head and Neck Cancer.

    PubMed

    Bertino, Erin M; McMichael, Elizabeth L; Mo, Xiaokui; Trikha, Prashant; Davis, Melanie; Paul, Bonnie; Grever, Michael; Carson, William E; Otterson, Gregory A

    2016-09-01

    mAbs can induce antibody-dependent cellular cytotoxicity (ADCC) via the innate immune system's ability to recognize mAb-coated cancer cells and activate immune effector cells. Lenalidomide is an immunomodulatory agent with the capacity to stimulate immune cell cytokine production and ADCC activity. This phase I trial evaluated the combination of cetuximab with lenalidomide for the treatment of advanced colorectal and head and neck squamous cell cancers (HNSCC). This trial included patients with advanced colorectal cancer or HNSCC. Treatment consisted of cetuximab 500 mg/m(2) i.v. every two weeks with lenalidomide given orally days 1-21 on a 28-day cycle. Three dose levels of lenalidomide were evaluated (15, 20, 25 mg). Correlative studies included measurement of ADCC, FcγRIIIA polymorphism genotyping, measurement of serum cytokine levels, and flow cytometric analysis of immune cell subtypes. Twenty-two patients were enrolled (19 colorectal cancer, 3 HNSCC). Fatigue was the only dose-limiting toxicity. One partial response was observed and 8 patients had stable disease at least 12 weeks. The recommended phase II dose is cetuximab 500 mg/m(2) with lenalidomide 25 mg daily, days 1-21. Correlative studies demonstrated a dose-dependent increase in natural killer cytotoxic activity with increasing doses of lenalidomide. Cetuximab and lenalidomide were well tolerated. There was a lenalidomide dose-dependent increase in ADCC with higher activity in patients enrolled in cohort 3 than those enrolled in cohorts 1/2. Although response was not a primary endpoint, there was evidence of antitumor activity for the combination therapy. Further investigation of lenalidomide as an immunomodulator in solid tumors is warranted. Mol Cancer Ther; 15(9); 2244-50. ©2016 AACR.

  11. Phase III Randomized Trial of Induction Chemotherapy in Patients With N2 or N3 Locally Advanced Head and Neck Cancer

    PubMed Central

    Cohen, Ezra E.W.; Karrison, Theodore G.; Kocherginsky, Masha; Mueller, Jeffrey; Egan, Robyn; Huang, Chao H.; Brockstein, Bruce E.; Agulnik, Mark B.; Mittal, Bharat B.; Yunus, Furhan; Samant, Sandeep; Raez, Luis E.; Mehra, Ranee; Kumar, Priya; Ondrey, Frank; Marchand, Patrice; Braegas, Bettina; Seiwert, Tanguy Y.; Villaflor, Victoria M.; Haraf, Daniel J.; Vokes, Everett E.

    2014-01-01

    Purpose Induction chemotherapy (IC) before radiotherapy lowers distant failure (DF) rates in locally advanced squamous cell carcinoma of the head and neck (SCCHN). The goal of this phase III trial was to determine whether IC before chemoradiotherapy (CRT) further improves survival compared with CRT alone in patients with N2 or N3 disease. Patients and Methods Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm; docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week) versus two 21-day cycles of IC (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2 on days 1 to 5) followed by the same CRT regimen (IC + CRT arm). The primary end point was overall survival (OS). Secondary end points included DF-free survival, failure pattern, and recurrence-free survival (RFS). Results A total of 285 patients were randomly assigned. The most common grade 3 to 4 toxicities during IC were febrile neutropenia (11%) and mucositis (9%); during CRT (both arms combined), they were mucositis (49%), dermatitis (21%), and leukopenia (18%). Serious adverse events were more common in the IC arm (47% v 28%; P = .002). With a minimum follow-up of 30 months, there were no statistically significant differences in OS (hazard ratio, 0.91; 95% CI, 0.59 to 1.41), RFS, or DF-free survival. Conclusion IC did not translate into improved OS compared with CRT alone. However, the study was underpowered because it did not meet the planned accrual target, and OS was higher than predicted in both arms. IC cannot be recommended routinely in patients with N2 or N3 locally advanced SCCHN. PMID:25049329

  12. Molecular and Clinical Responses in a Pilot Study of Gefitinib With Paclitaxel and Radiation in Locally Advanced Head-and-Neck Cancer

    SciTech Connect

    Van Waes, Carter; Allen, Clint T.; Citrin, Deborah; Gius, David; Colevas, A. Dimetrios; Harold, Nancy A.; Rudy, Susan; Nottingham, Liesl; Muir, Christine; Chen, Zhong; Singh, Anurag K.; Dancey, Janet; Morris, John C.

    2010-06-01

    Purpose: Epidermal growth factor receptor (EGFR) overexpression in head-and-neck squamous cell carcinoma (HNSCC) stimulates tumor cell proliferation, inhibits apoptosis, and increases chemotherapy and radiation resistance. We examined the toxicity, safety and the effects on EGFR signaling in tumor biopsy samples from patients with locally advanced HNSCC treated with the EGFR signaling inhibitor gefitinib (GEF) combined with weekly intravenous paclitaxel (PAC) and radiation therapy (RT). Methods and Materials: This was a pilot Phase I dose-escalation study. Eligibility included Stage III to IVB HNSCC, age >=18 years, no prior RT or chemotherapy, adequate organ function, and informed consent. Endpoints included determination of maximum tolerated dose (MTD) and analysis of treatment effect on EGFR signaling, tumor cell proliferation, and apoptosis in biopsy samples. Results: Ten patients were treated. The MTD of this combination was GEF 250 mg/d with PAC 36 mg/m{sup 2} intravenously weekly x 6 with concurrent RT. Grade 3/4 toxicities included prolonged (>8 weeks) stomatitis (7 patients), infection (2 patients), and interstitial pneumonitis (1 patient). There were five complete responses (CR) and two partial responses (PR). Of 7 patients undergoing serial biopsies, only 1 patient demonstrated a reduction in phosphorylated EGFR, decreased downstream signaling, and reduced cellular proliferation after initiating GEF. Conclusions: Inhibition of EGFR by GEF was observed in only one of seven tumors studied. The addition of GEF to PAC and RT did not appear to improve the response of locally advanced HNSCC compared with our prior experience with PAC and RT alone. This treatment appeared to delay recovery from stomatitis.

  13. 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.

  14. Early Prediction of Outcome in Advanced Head-and-Neck Cancer Based on Tumor Blood Volume Alterations During Therapy: A Prospective Study

    SciTech Connect

    Cao Yue Popovtzer, Aron; Li, Diana; Chepeha, Douglas B.; Moyer, Jeffrey S.; Prince, Mark E.; Worden, Francis; Teknos, Theodoros; Bradford, Carol; Mukherji, Suresh K.; Eisbruch, Avraham

    2008-12-01

    Purpose: To assess whether alterations in tumor blood volume (BV) and blood flow (BF) during the early course of chemo-radiotherapy (chemo-RT) for head-and-neck cancer (HNC) predict treatment outcome. Methods and Materials: Fourteen patients receiving concomitant chemo-RT for nonresectable, locally advanced HNC underwent dynamic contrast-enhanced (DCE) MRI scans before therapy and 2 weeks after initiation of chemo-RT. The BV and BF were quantified from DCE MRI. Preradiotherapy BV and BF, as well as their changes during RT, were evaluated separately in the primary gross tumor volume (GTV) and nodal GTV for association with outcomes. Results: At a median follow-up of 10 months (range, 5-27 months), 9 patients had local-regional controlled disease. One patient had regional failure, 3 had local failures, and 1 had local-regional failure. Reduction in tumor volume after 2 weeks of chemo-RT did not predict for local control. In contrast, the BV in the primary GTV after 2 weeks of chemo-RT was increased significantly in the local control patients compared with the local failure patients (p < 0.03). Conclusions: Our data suggest that an increase in available primary tumor blood for oxygen extraction during the early course of RT is associated with local control, thus yielding a predictor with potential to modify treatment. These findings require validation in larger studies.

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

    SciTech Connect

    Weichselbaum, R.R.; Posner, M.R.; Ervin, T.J.; Fabian, R.L.; Miller, D.

    1982-05-01

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

  16. Head injuries, heading, and the use of headgear in soccer.

    PubMed

    Niedfeldt, Mark W

    2011-01-01

    Soccer has more than 265 million players around the world and is the only contact sport with purposeful use of the head for controlling and advancing the ball. Head contact in soccer has the potential to cause acute traumatic brain injury including concussion or, potentially, a pattern of chronic brain injury. Although early retrospective research on the effects of soccer heading seemed to suggest that purposeful heading may contribute to long-term cognitive impairment, prospective controlled studies do not support this and, in fact, suggest that purposeful heading may not be a risk factor for cognitive impairment. Headgear has not been shown to be effective in reducing ball impact but may be helpful in reducing the force of non-ball-related impacts to the head. There are concerns that universal use of headgear may cause more aggressive heading and head challenges, leading to increased risk of injury.

  17. Impact of Time Factors on Outcome in Patients with Head and Neck Cancer Treated with Definitive Radio(Chemo)Therapy.

    PubMed

    Dahlke, Sören; Steinmann, Diana; Christiansen, Hans; Durisin, Martin; Eckardt, Andre; Wegener, Gerd; Bremer, Michael; Meyer, Andreas

    2017-01-01

    To evaluate treatment-related factors such as overall treatment time (OTT) and radiation treatment time (RTT) in head-and-neck cancer. A total of 216 patients with locoregionally advanced inoperable head and neck cancer were treated with definitive radio(chemo)therapy. Mean follow-up was 37 months. Median time from diagnosis to start of radiotherapy (total waiting time) was 34 days, and comprised of referral waiting time and time for preparatory work. Median RTT was 40 days, and median OTT was 91 days. At 6, 12 and 24 months local recurrence-free survival (LRFS) was 75%, 65% and 60%; metastasis-free survival (MFS) was 84%, 77% and 70%; overall survival (OS) was 72%, 58% and 40%. Tumor stage, boost and chemotherapy were significant for OS, waiting time for preparatory work and RTT were significant for MFS, and referral waiting time and total radiotherapy dose for LRFS. RTT ≤40 days was a prognostic factor for better MFS. Prolonged waiting time had a converse effect for radiotherapy with better outcome on MFS and LRFS. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  18. Future treatment directions for HPV-associated head and neck cancer based on radiobiological rationale and current clinical evidence.

    PubMed

    Marcu, Loredana G

    2016-07-01

    A relatively new entity of head and neck squamous cell carcinoma located in the oropharynx and associated to the human papillomavirus (HPV) is on the rise. This cancer represents a distinct entity from the non-HPV tumours, holds different biological characteristics and responds differently to treatment. An outcome analysis of locoregionally-advanced oropharyngeal versus non-oropharyngeal cancers treated with chemo-radiotherapy revealed a statistically significant improvement for oropharyngeal cancers, which are thought to be due to their HPV-association. Consequently, more attention is paid to HPV-related head and neck cancers, given that HPV status serves as prognostic marker in oropharyngeal cancer patients. Yet, HPV positivity is a simplistic approach for risk stratification, thus more robust biomarkers are needed to fulfil this task. Despite differences in clinical response, HPV-related oral cancers undergo similar therapy to their non-HPV counterparts. This review discusses future treatment directions for HPV-related oropharyngeal cancers based on radiobiological rationale and current clinical evidence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Detecting Intracranial Hemorrhage Using Automatic Tube Current Modulation With Advanced Modeled Iterative Reconstruction in Unenhanced Head Single- and Dual-Energy Dual-Source CT.

    PubMed

    Scholtz, Jan-Erik; Wichmann, Julian L; Bennett, Dennis W; Leithner, Doris; Bauer, Ralf W; Vogl, Thomas J; Bodelle, Boris

    2017-05-01

    The purpose of our study was to determine diagnostic accuracy, image quality, and radiation dose of low-dose single- and dual-energy unenhanced third-generation dual-source head CT for detection of intracranial hemorrhage (ICH). A total of 123 patients with suspected ICH were examined using a dual-source 192-MDCT scanner. Standard-dose 120-kVp single-energy CT (SECT; n = 36) and 80-kVp and 150-kVp dual-energy CT (DECT; n = 30) images were compared with low-dose SECT (n = 32) and DECT (n = 25) images obtained using automated tube current modulation (ATCM). Advanced modeled iterative reconstruction (ADMIRE) was used for all protocols. Detection of ICH was performed by three readers who were blinded to the image acquisition parameters of each image series. Image quality was assessed both quantitatively and qualitatively. Interobserver agreement was calculated using the Fleiss kappa. Radiation dose was measured as dose-length product (DLP). Detection of ICH was excellent (sensitivity, 94.9-100%; specificity, 94.7-100%) in all protocols (p = 1.00) with perfect interobserver agreement (0.83-0.96). Qualitative ratings showed significantly better ratings for both standard-dose protocols regarding gray matter-to-white matter contrast (p ≤ 0.014), whereas highest gray matter-to-white matter contrast-to-noise ratio was observed with low-dose DECT images (p ≥ 0.057). The lowest posterior fossa artifact index was measured for standard-dose DECT, which showed significantly lower values compared with low-dose protocols (p ≤ 0.034). Delineation of ventricular margins and sharpness of subarachnoidal spaces were rated excellent in all protocols (p ≥ 0.096). Low-dose techniques lowered radiation dose by 26% for SECT images (DLP, 575.0 ± 72.3 mGy · cm vs 771.5 ± 146.8 mGy · cm; p < 0.001) and by 24% in DECT images (DLP, 587.0 ± 103.2 mGy · cm vs 770.6 ± 90.2 mGy · cm; p < 0.001). No significant difference was observed between the low-dose protocols (p = 1.00). Low

  20. Phase Ib Study of BKM120 With Cisplatin and XRT in High Risk Locally Advanced Squamous Cell Cancer of Head and Neck

    ClinicalTrials.gov

    2017-05-19

    Carcinoma, Squamous Cell of Head and Neck; HPV Positive Oropharyngeal Squamous Cell Carcinoma; Hypopharyngeal Cancer; Early Invasive Cervical Squamous Cell Carcinoma; Carcinoma of Larynx; Cancer of Nasopharynx

  1. Heads Up

    MedlinePlus

    ... Us HEADS UP Apps Reshaping the Culture Around Concussion in Sports Get HEADS UP on Your Web Site Concussion ... fit, and maintain the right helmet for specific sports. Concussion Laws Learn about Return to Play and other ...

  2. Head MRI

    MedlinePlus

    ... the head; MRI - cranial; NMR - cranial; Cranial MRI; Brain MRI; MRI - brain; MRI - head ... the test, tell your provider if you have: Brain aneurysm clips An artificial heart valves Heart defibrillator ...

  3. Comparative study between two different staging systems (AJCC TNM VS BALLANTYNE’S) for mucosal melanomas of the Head & Neck

    PubMed Central

    Aguilar-Romero, Madeleine; Villavicencio-Valencia, Verónica; Zepeda-Castilla, Ernesto; Vidrio-Morgado, Horacio; Peteuil, Nathalie; Mosqueda-Taylor, Adalberto

    2016-01-01

    Background Mucosal melanoma (MM) of head and neck (H &N) is a rare entity with a quite poor prognosis. Ballantyne’s staging system has been commonly used since 1970. In the 7th edition of the AJCC Staging Manual a new chapter for the staging of TNM Classification system for mucosal melanoma (MM) of the head and neck (H &N) has been introduced to reflect the particularly aggressive biological behavior of this neoplasm. The aim of this study was to analyze and compare among Ballantyne’s staging system vs TNM H &N in terms of overall survival (OS) and disease-free survival (DFS) in a consecutive population of patients with MM in a cancer centre. Material and Methods Descriptive analysis of demographic, clinical and pathological variables of MM of the Head & Neck were performed. We compared the survival curves for both systems according to the Kaplan-Meier method using the Log-rank test. Results An up-staging migration effect from Ballantyne’s localized disease to moderately and very advanced disease according to AJCC staging system. The 5-year DFS and OS for Ballantyne’s Localized Disease and AJCC Stage III were 31% and 36% vs. 47% and 50%, respectively. For locoregional disease the 5-year DFS / OS were 5% / 10% for Bal-lantyne’s system vs. 13.8% / 17.8% and 0 / 0% for AJCC Stages IVA and IVB, respectively. Conclusions In this series, the TNM staging system for MM of the H &N predicted better the prognosis of the disease when comparing with Ballantyne’s system. Key words:Head and neck, mucosal melanoma, AJCC TNM, Ballantynes´s staging system. PMID:27031071

  4. Head lice.

    PubMed

    Frankowski, Barbara L; Weiner, Leonard B

    2002-09-01

    Head lice infestation is associated with little morbidity but causes a high level of anxiety among parents of school-aged children. This statement attempts to clarify issues of diagnosis and treatment of head lice and makes recommendations for dealing with head lice in the school setting.

  5. Final results of local-regional control and late toxicity of RTOG 9003: a randomized trial of altered fractionation radiation for locally advanced head and neck cancer.

    PubMed

    Beitler, Jonathan J; Zhang, Qiang; Fu, Karen K; Trotti, Andy; Spencer, Sharon A; Jones, Christopher U; Garden, Adam S; Shenouda, George; Harris, Jonathan; Ang, Kian K

    2014-05-01

    To test whether altered radiation fractionation schemes (hyperfractionation [HFX], accelerated fractionation, continuous [AFX-C], and accelerated fractionation with split [AFX-S]) improved local-regional control (LRC) rates for patients with squamous cell cancers (SCC) of the head and neck when compared with standard fractionation (SFX) of 70 Gy. Patients with stage III or IV (or stage II base of tongue) SCC (n=1076) were randomized to 4 treatment arms: (1) SFX, 70 Gy/35 daily fractions/7 weeks; (2) HFX, 81.6 Gy/68 twice-daily fractions/7 weeks; (3) AFX-S, 67.2 Gy/42 fractions/6 weeks with a 2-week rest after 38.4 Gy; and (4) AFX-C, 72 Gy/42 fractions/6 weeks. The 3 experimental arms were to be compared with SFX. With patients censored for LRC at 5 years, only the comparison of HFX with SFX was significantly different: HFX, hazard ratio (HR) 0.79 (95% confidence interval 0.62-1.00), P=.05; AFX-C, 0.82 (95% confidence interval 0.65-1.05), P=.11. With patients censored at 5 years, HFX improved overall survival (HR 0.81, P=.05). Prevalence of any grade 3, 4, or 5 toxicity at 5 years; any feeding tube use after 180 days; or feeding tube use at 1 year did not differ significantly when the experimental arms were compared with SFX. When 7-week treatments were compared with 6-week treatments, accelerated fractionation appeared to increase grade 3, 4 or 5 toxicity at 5 years (P=.06). When the worst toxicity per patient was considered by treatment only, the AFX-C arm seemed to trend worse than the SFX arm when grade 0-2 was compared with grade 3-5 toxicity (P=.09). At 5 years, only HFX improved LRC and overall survival for patients with locally advanced SCC without increasing late toxicity. Published by Elsevier Inc.

  6. Long-Term Outcomes and Toxicity of Concurrent Paclitaxel and Radiation in the Treatment of Locally Advanced Head and Neck Cancer

    PubMed Central

    Citrin, Deborah; Mansueti, John; Likhacheva, Anna; Sciuto, Linda; Albert, Paul S.; Rudy, Susan F.; Cooley-Zgela, Theresa; Cotrim, Ana; Solomon, Beth; Colevas, A. Dimitrios; Russo, Angelo; Morris, John C.; Herscher, Laurie; Smith, Sharon; Van Waes, Carter

    2009-01-01

    Purpose To report the long-term outcomes and toxicity of a regimen of infusional paclitaxel delivered concurrently with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Methods Between 1995 and 1999, 35 patients with non-metastatic stage III or IV SCCHN were treated with 3 cycles of paclitaxel as a 120-hour continuous infusion beginning days 1, 21, and 42 concurrent with radiation. The initial 16 patients received 105 mg/m2/cycle, and the subsequent 19 patients received 120 mg/m2/cycle. External beam radiation was delivered to 70.2–72 Gy in 5 fractions per week. Patients were followed to evaluate disease outcomes and the late toxicity of this regimen. Results Median follow-up for all patients is 56.5 months. The median survival was 56.5 months and the median time to local recurrence was not reached. Fifteen patients (43%) developed hypothyroidism. Eleven of the 33 patients who underwent percutaneous endoscopic gastrostomy tube (PEG) placement were PEG-dependent until death or last follow-up. Five patients (14%) required a tracheostomy until death, while 3 patients (9%) suffered from severe esophageal stricture. All evaluated long term survivors exhibited salivary hypofunction. Fibrosis in the radiation field occurred in 24 patients (69%). Conclusion Concurrent chemo-radiation therapy with a 120-hour infusion of paclitaxel provides long-term local control and survival in patients with SCCHN.Xerostomia, hypothyroidism, esophageal and pharyngeal complications, and subcutaneous fibrosis were common long-term toxicities; however, the vast majority of toxicities were grade 1 or 2. PMID:19117692

  7. TU-AB-BRA-10: Prognostic Value of Intra-Radiation Treatment FDG-PET and CT Imaging Features in Locally Advanced Head and Neck Cancer

    SciTech Connect

    Song, J; Pollom, E; Durkee, B; Aggarwal, S; Bui, T; Le, Q; Loo, B; Hara, W; Cui, Y; Li, R

    2015-06-15

    Purpose: To predict response to radiation treatment using computational FDG-PET and CT images in locally advanced head and neck cancer (HNC). Methods: 68 patients with State III-IVB HNC treated with chemoradiation were included in this retrospective study. For each patient, we analyzed primary tumor and lymph nodes on PET and CT scans acquired both prior to and during radiation treatment, which led to 8 combinations of image datasets. From each image set, we extracted high-throughput, radiomic features of the following types: statistical, morphological, textural, histogram, and wavelet, resulting in a total of 437 features. We then performed unsupervised redundancy removal and stability test on these features. To avoid over-fitting, we trained a logistic regression model with simultaneous feature selection based on least absolute shrinkage and selection operator (LASSO). To objectively evaluate the prediction ability, we performed 5-fold cross validation (CV) with 50 random repeats of stratified bootstrapping. Feature selection and model training was solely conducted on the training set and independently validated on the holdout test set. Receiver operating characteristic (ROC) curve of the pooled Result and the area under the ROC curve (AUC) was calculated as figure of merit. Results: For predicting local-regional recurrence, our model built on pre-treatment PET of lymph nodes achieved the best performance (AUC=0.762) on 5-fold CV, which compared favorably with node volume and SUVmax (AUC=0.704 and 0.449, p<0.001). Wavelet coefficients turned out to be the most predictive features. Prediction of distant recurrence showed a similar trend, in which pre-treatment PET features of lymph nodes had the highest AUC of 0.705. Conclusion: The radiomics approach identified novel imaging features that are predictive to radiation treatment response. If prospectively validated in larger cohorts, they could aid in risk-adaptive treatment of HNC.

  8. Pre- and posttreatment voice and speech outcomes in patients with advanced head and neck cancer treated with chemoradiotherapy: expert listeners' and patient's perception.

    PubMed

    van der Molen, Lisette; van Rossum, Maya A; Jacobi, Irene; van Son, Rob J J H; Smeele, Ludi E; Rasch, Coen R N; Hilgers, Frans J M

    2012-09-01

    Perceptual judgments and patients' perception of voice and speech after concurrent chemoradiotherapy (CCRT) for advanced head and neck cancer. Prospective clinical trial. A standard Dutch text and a diadochokinetic task were recorded. Expert listeners rated voice and speech quality (based on Grade, Roughness, Breathiness, Asthenia, and Strain), articulation (overall, [p], [t], [k]), and comparative mean opinion scores of voice and speech at three assessment points calculated. A structured study-specific questionnaire evaluated patients' perception pretreatment (N=55), at 10-week (N=49) and 1-year posttreatment (N=37). At 10 weeks, perceptual voice quality is significantly affected. The parameters overall voice quality (mean, -0.24; P=0.008), strain (mean, -0.12; P=0.012), nasality (mean, -0.08; P=0.009), roughness (mean, -0.22; P=0.001), and pitch (mean, -0.03; P=0.041) improved over time but not beyond baseline levels, except for asthenia at 1-year posttreatment (voice is less asthenic than at baseline; mean, +0.20; P=0.03). Perceptual analyses of articulation showed no significant differences. Patients judge their voice quality as good (score, 18/20) at all assessment points, but at 1-year posttreatment, most of them (70%) judge their "voice not as it used to be." In the 1-year versus 10-week posttreatment comparison, the larynx-hypopharynx tumor group was more strained, whereas nonlarynx tumor voices were judged less strained (mean, -0.33 and +0.07, respectively; P=0.031). Patients' perceived changes in voice and speech quality at 10-week post- versus pretreatment correlate weakly with expert judgments. Overall, perceptual CCRT effects on voice and speech seem to peak at 10-week posttreatment but level off at 1-year posttreatment. However, at that assessment point, most patients still perceive their voice as different from baseline. Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  9. Prevalence and influence of malnutrition on quality of life and performance status in patients with locally advanced head and neck cancer before treatment.

    PubMed

    Capuano, Giorgio; Gentile, Pier Carlo; Bianciardi, Federico; Tosti, Michela; Palladino, Anna; Di Palma, Mario

    2010-04-01

    The aim of this study was to evaluate the prevalence and influence of malnutrition (unintentional weight loss >or=5% in the last 3 months) on quality of life (QoL) and performance status (PS) in head and neck cancer patients (HNC) before treatment. Sixty-one consecutive outpatients affected by locally advanced HNC (III-IVA stage) were enrolled. In all patients, nutritional intake (by diet history), nutritional status (Patient Generated Subjective Global Assessment), unintentional weight loss (UWL), serum prealbumin, hemoglobin level (Hb), C-reactive protein, QoL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 v. 3.0), and PS (Eastern Cooperative Oncology Group (ECOG) PS) were assessed before radio or concomitant chemoradiotherapy. Thirty-six percent of HNC were malnourished before treatment. The median ECOG PS in malnourished patients was 1 (0-2), whereas in nonmalnourished was 0 (0-2; p = 0.018). Physical (p = 0.043), role (p = 0.047), and social functions (p = 0.024) scores were significantly worse in malnourished than in nonmalnourished HNC. Fatigue (p < 0.001), appetite loss (p < 0.001), and nausea and vomiting (p = 0.002) scores were worse in malnourished patients than in nonmalnourished. In the multivariate analysis, UWL and Hb level independently influenced physical (p = 0.002; p = 0.005), role (p = 0.004; p = 0.001), and social functions (p = 0.024; p = 0.009). Our data suggest that an early and intensive nutritional support might reduce weight loss before, during, and after treatment completion, improving outcome, QoL, and PS.

  10. cRGD peptide installation on cisplatin-loaded nanomedicines enhances efficacy against locally advanced head and neck squamous cell carcinoma bearing cancer stem-like cells.

    PubMed

    Miyano, Kazuki; Cabral, Horacio; Miura, Yutaka; Matsumoto, Yu; Mochida, Yuki; Kinoh, Hiroaki; Iwata, Caname; Nagano, Osamu; Saya, Hideyuki; Nishiyama, Nobuhiro; Kataoka, Kazunori; Yamasoba, Tatsuya

    2017-09-10

    Recalcitrant head and neck squamous cell carcinoma (HNSCC) usually relapses after therapy due to the enrichment of drug resistant cancer stem-like cells (CSCs). Nanomedicines have shown potential for eradicating both cancer cells and CSCs by effective intratumoral navigation for reaching particular cell populations and controlling drug delivery. The installation of ligands on nanomedicines is an attractive approach for improving the delivery to CSCs within tumors, though the development of CSC-selective ligand-receptor systems has been challenging. Herein, we found that the CSC subpopulation in HNSCC cells overexpresses αvβ5 integrins, which is preferentially expressed in tumor neovasculature and cancer cells, and can be effectively targeted by using cyclic Arg-Gly-Asp (cRGD) peptide. Thus, in this study, we propose installing cRGD peptide on micellar nanomedicines incorporating cisplatin for improving their activity against CSCs and enhancing survival. Both cisplatin-loaded micelles (CDDP/m) and cRGD-installed CDDP/m (cRGD-CDDP/m) were effective against HNSCC SAS-L1-Luc cells in vitro, though cRGD-installed CDDP/m was more potent than CDDP/m against the CSC fraction. In vivo, the cRGD-CDDP/m also showed significant antitumor activity against HNSCC orthotopic tumors, i.e. SAS-L1 and HSC-2. Moreover, cRGD-CDDP/m rapidly accumulated into the lymph node metastasis of SAS-L1 tumors, effectively inhibiting their growth, and prolonging mice survival. These findings indicate cRGD-installed nanomedicines as an advantageous strategy for targeting CSCs in HNSCC, and particularly, cRGD-CDDP/m as a significant therapeutic strategy against regionally advanced HNSCC. Copyright © 2017. Published by Elsevier B.V.

  11. Advanced backcross QTL mapping of resistance to Fusarium head blight and plant morphological traits in a Triticum macha × T. aestivum population.

    PubMed

    Buerstmayr, Maria; Lemmens, Marc; Steiner, Barbara; Buerstmayr, Hermann

    2011-07-01

    While many reports on genetic analysis of Fusarium head blight (FHB) resistance in bread wheat have been published during the past decade, only limited information is available on FHB resistance derived from wheat relatives. In this contribution, we report on the genetic analysis of FHB resistance derived from Triticum macha (Georgian spelt wheat). As the origin of T. macha is in the Caucasian region, it is supposed that its FHB resistance differs from other well-investigated resistance sources. To introduce valuable alleles from the landrace T. macha into a modern genetic background, we adopted an advanced backcross QTL mapping scheme. A backcross-derived recombinant-inbred line population of 321 BC(2)F(3) lines was developed from a cross of T. macha with the Austrian winter wheat cultivar Furore. The population was evaluated for Fusarium resistance in seven field experiments during four seasons using artificial inoculations. A total of 300 lines of the population were genetically fingerprinted using SSR and AFLP markers. The resulting linkage map covered 33 linkage groups with 560 markers. Five novel FHB-resistance QTL, all descending from T. macha, were found on four chromosomes (2A, 2B, 5A, 5B). Several QTL for morphological and developmental traits were mapped in the same population, which partly overlapped with FHB-resistance QTL. Only the 2BL FHB-resistance QTL co-located with a plant height QTL. The largest-effect FHB-resistance QTL in this population mapped at the spelt-type locus on chromosome 5A and was associated with the wild-type allele q, but it is unclear whether q has a pleiotropic effect on FHB resistance or is closely linked to a nearby resistance QTL.

  12. Comparison of Intensity-modulated Radiotherapy, Adaptive Radiotherapy, Proton Radiotherapy, and Adaptive Proton Radiotherapy for Treatment of Locally Advanced Head and Neck Cancer

    PubMed Central

    Simone, Charles B.; Ly, David; Dan, Tu D.; Ondos, John; Ning, Holly; Belard, Arnaud; O'Connell, John; Miller, Robert W.; Simone, Nicole L.

    2011-01-01

    Background and Purpose Various radiotherapy planning methods for locally advanced squamous cell carcinoma of the head and neck (SCCHN) have been proposed to decrease normal tissue toxicity. We compare IMRT, adaptive IMRT, proton therapy (IMPT), and adaptive IMPT for SCCHN. Materials and Methods Initial and re-simulation CT images from 10 consecutive patients with SCCHN were used to quantify dosimetric differences between photon and proton therapy. Contouring was performed on both CTs, and plans (n=40 plans) and dose volume histograms were generated. Results The mean GTV volume decreased 53.4% with re-simulation. All plans provided comparable PTV coverage. Compared with IMRT, adaptive IMRT significantly reduced the maximum dose to the mandible (p=0.020) and mean doses to the contralateral parotid gland (p=0.049) and larynx (p=0.049). Compared with IMRT and adaptive IMRT, IMPT significantly lower the maximum doses to the spinal cord (p<0.002 for both) and brainstem (p<0.002 for both) and mean doses to the larynx (p<0.002 for both) and ipsilateral (p=0.004 IMRT, p=0.050 adaptive) and contralateral (p<0.002 IMRT, p=0.010 adaptive) parotid glands. Adaptive IMPT significantly reduced doses to all critical structures compared with IMRT and adaptive IMRT and several critical structures compared with non-adaptive IMPT. Conclusions Although adaptive IMRT reduced dose to several normal structures compared with standard IMRT, non-adaptive proton therapy had a more favorable dosimetric profile than IMRT or adaptive IMRT and may obviate the need for adaptive planning. Protons allowed significant sparing of the spinal cord, parotid glands, larynx, and brainstem and should be considered for SCCHN to decrease normal tissue toxicity while still providing optimal tumor coverage. PMID:21663988

  13. Comparison of intensity-modulated radiotherapy, adaptive radiotherapy, proton radiotherapy, and adaptive proton radiotherapy for treatment of locally advanced head and neck cancer.

    PubMed

    Simone, Charles B; Ly, David; Dan, Tu D; Ondos, John; Ning, Holly; Belard, Arnaud; O'Connell, John; Miller, Robert W; Simone, Nicole L

    2011-12-01

    Various radiotherapy planning methods for locally advanced squamous cell carcinoma of the head and neck (SCCHN) have been proposed to decrease normal tissue toxicity. We compare IMRT, adaptive IMRT, proton therapy (IMPT), and adaptive IMPT for SCCHN. Initial and re-simulation CT images from 10 consecutive patients with SCCHN were used to quantify dosimetric differences between photon and proton therapy. Contouring was performed on both CTs, and plans (n=40 plans) and dose-volume histograms were generated. The mean GTV volume decreased 53.4% with re-simulation. All plans provided comparable PTV coverage. Compared with IMRT, adaptive IMRT significantly reduced the maximum dose to the mandible (p=0.020) and mean doses to the contralateral parotid gland (p=0.049) and larynx (p=0.049). Compared with IMRT and adaptive IMRT, IMPT significantly lowered the maximum doses to the spinal cord (p<0.002 for both) and brainstem (p<0.002 for both) and mean doses to the larynx (p<0.002 for both) and ipsilateral (p=0.004 IMRT, p=0.050 adaptive) and contralateral (p<0.002 IMRT, p=0.010 adaptive) parotid glands. Adaptive IMPT significantly reduced doses to all critical structures compared with IMRT and adaptive IMRT and several critical structures compared with non-adaptive IMPT. Although adaptive IMRT reduced dose to several normal structures compared with standard IMRT, non-adaptive proton therapy had a more favorable dosimetric profile than IMRT or adaptive IMRT and may obviate the need for adaptive planning. Protons allowed significant sparing of the spinal cord, parotid glands, larynx, and brainstem and should be considered for SCCHN to decrease normal tissue toxicity while still providing optimal tumor coverage. Published by Elsevier Ireland Ltd.

  14. Evaluation of long term (10-years+) dysphagia and trismus in patients treated with concurrent chemo-radiotherapy for advanced head and neck cancer.

    PubMed

    Kraaijenga, S A C; Oskam, I M; van der Molen, L; Hamming-Vrieze, O; Hilgers, F J M; van den Brekel, M W M

    2015-08-01

    Assessment of long term (10-years+) swallowing function, mouth opening, and quality of life (QoL) in head and neck cancer (HNC) patients treated with chemo-radiotherapy (CRT) for advanced stage IV disease. Twenty-two disease-free survivors, participating in a multicenter randomized clinical trial for inoperable HNC (1999-2004), were evaluated to assess long-term morbidity. The prospective assessment protocol consisted of videofluoroscopy (VFS) for obtaining Penetration Aspiration Scale (PAS) and presence of residue scores, Functional Oral Intake Scale (FOIS) scores, maximum mouth opening measurements, and (SWAL-QOL and study-specific) questionnaires. At a median follow-up of 11-years, 22 patients were evaluable for analysis. Ten patients (46%) were able to consume a normal oral diet without restrictions (FOIS score 7), whereas 12 patients (54%) had moderate to serious swallowing issues, of whom 3 (14%) were feeding tube dependent. VFS evaluation showed 15/22 patients (68%) with penetration and/or aspiration (PAS⩾3). Fifty-five percent of patients (12/22) had developed trismus (mouth opening⩽35mm), which was significantly associated with aspiration (p=.011). Subjective swallowing function (SWAL-QOL score) was impaired across almost all QoL domains in the majority of patients. Patients treated with IMRT showed significantly less aspiration (p=.011), less trismus (p=.035), and less subjective swallowing problems than those treated with conventional radiotherapy. Functional swallowing and mouth opening problems are substantial in this patient cohort more than 10-years after organ-preservation CRT. Patients treated with IMRT had less impairment than those treated with conventional radiotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Reaching for better image quality and lower radiation dose in head and neck CT: advanced modeled and sinogram-affirmed iterative reconstruction in combination with tube voltage adaptation.

    PubMed

    Schmid, Andrea I; Uder, Michael; Lell, Michael M

    2017-01-01

    The aim of this study was to evaluate image quality and radiation dose in low-dose head and neck CT comparing two different commercially available iterative reconstruction algorithms: sinogram-affirmed iterative reconstruction (SAFIRE) and advanced modeled iterative reconstruction (ADMIRE) with fixed and automated tube voltage adaptation (TVA). CT examinations of 103 patients were analysed. 58 patients were examined on a single-source CT at fixed tube voltage of 120 kV and reconstructed with filtered back projection (FBP) and SAFIRE (Strength Level 3). 45 patients were examined in a single-source mode on a dual-source CT with automated TVA and reconstructed with FBP and ADMIRE (Strength Levels 2 and 3). Image noise was calculated in seven anatomical volumes of interest. Subjective evaluation of the CT images was performed using a four-grade scale. Mean CT numbers of FBP and the corresponding iterative reconstruction did not differ significantly (p = 0.74-0.99). Image noise was lower with both iterative reconstruction techniques than with FBP (SAFIRE 3: -22.3%; ADMIRE 2: -14.9%; ADMIRE 3: -24.2%; all p < 0.05); hence, the signal-to-noise ratio and the contrast-to-noise values were higher. Subjective image quality revealed a more favourable result for the iterative reconstruction. ADMIRE 3 in combination with automated TVA showed 14.4% (p < 0.05) less image noise with a 7.5% lower radiation dose than SAFIRE 3 with fixed tube voltage. Higher image quality at lower radiation dose can be achieved using ADMIRE in combination with automated TVA.

  16. Risk Factors of Ototoxicity After Cisplatin-Based Chemo-Irradiation in Patients With Locally Advanced Head-and-Neck Cancer: A Multivariate Analysis

    SciTech Connect

    Zuur, Charlotte L. . E-mail: cl.zuur@vumc.nl; Simis, Yvonne J.; Lansdaal, Pauline E.; Hart, Augustinus A.; Rasch, Coen R.; Schornagel, Jan H.; Dreschler, Wouter A.; Balm, Alfons J.

    2007-08-01

    Purpose: Cisplatin chemo-irradiation is increasingly used in locally advanced squamous cell carcinoma of the head and neck. The objective of this study is to determine risk factors of ototoxicity due to intra-arterial high-dose cisplatin chemoradiation. Methods and Materials: A prospective analysis of hearing thresholds at low and (ultra) high frequencies obtained before, during, and after treatment in 146 patients. Treatment consisted of intra-arterial infusion of high-dose cisplatin (150 mg/m{sup 2}, four courses) with sodium thiosulfate rescue and concurrent radiation therapy (70 Gy). Patient and chemoradiation variables were studied in a multivariate analysis. Results: After treatment, 23% of the ears were under consideration for hearing aids because of therapy. Twenty-two percent of the patients developed an increase in air-bone gap >10 dB during or after therapy. In the multivariate explanatory analysis, cumulative dose of cisplatin and radiation therapy, and young age displayed a causal relationship with increased sensorineural hearing loss during and after therapy (p < 0.001). In the multivariate prediction analysis, pretreatment hearing level of the concerning ear was identified as an independent predictive factor for hearing capability after therapy (p < 0.0001). Conclusions: Both cisplatin and radiation therapy were proven to induce sensorineural hearing loss, in this study with short-term follow-up. Of all patient and treatment variables studied, the patients pretreatment hearing level appeared to be the main predictive factor for hearing capability after high-dose intra-arterial cisplatin chemoradiation.

  17. Integrative advances for OCT-guided ophthalmic surgery and intraoperative OCT: microscope integration, surgical instrumentation, and heads-up display surgeon feedback.

    PubMed

    Ehlers, Justis P; Srivastava, Sunil K; Feiler, Daniel; Noonan, Amanda I; Rollins, Andrew M; Tao, Yuankai K

    2014-01-01

    To demonstrate key integrative advances in microscope-integrated intraoperative optical coherence tomography (iOCT) technology that will facilitate adoption and utilization during ophthalmic surgery. We developed a second-generation prototype microscope-integrated iOCT system that interfaces directly with a standard ophthalmic surgical microscope. Novel features for improved design and functionality included improved profile and ergonomics, as well as a tunable lens system for optimized image quality and heads-up display (HUD) system for surgeon feedback. Novel material testing was performed for potential suitability for OCT-compatible instrumentation based on light scattering and transmission characteristics. Prototype surgical instruments were developed based on material testing and tested using the microscope-integrated iOCT system. Several surgical maneuvers were performed and imaged, and surgical motion visualization was evaluated with a unique scanning and image processing protocol. High-resolution images were successfully obtained with the microscope-integrated iOCT system with HUD feedback. Six semi-transparent materials were characterized to determine their attenuation coefficients and scatter density with an 830 nm OCT light source. Based on these optical properties, polycarbonate was selected as a material substrate for prototype instrument construction. A surgical pick, retinal forceps, and corneal needle were constructed with semi-transparent materials. Excellent visualization of both the underlying tissues and surgical instrument were achieved on OCT cross-section. Using model eyes, various surgical maneuvers were visualized, including membrane peeling, vessel manipulation, cannulation of the subretinal space, subretinal intraocular foreign body removal, and corneal penetration. Significant iterative improvements in integrative technology related to iOCT and ophthalmic surgery are demonstrated.

  18. Residual deficits in quality of life one year after intensity-modulated radiotherapy for patients with locally advanced head and neck cancer: Results of a prospective study.

    PubMed

    Tribius, Silke; Raguse, Marieclaire; Voigt, Christian; Münscher, Adrian; Gröbe, Alexander; Petersen, Cordula; Krüll, Andreas; Bergelt, Corinna; Singer, Susanne

    2015-06-01

    Patients with locally advanced head and neck cancer (LAHNC) undergo life-changing treatments that can seriously affect quality of life (QoL). This prospective study examined the key QoL domains during the first year after intensity-modulated radiotherapy (IMRT) and identified predictors of these changes in order to improve patient outcomes. A consecutive series of patients with LAHNC completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core module (QLQ-C30) and the HNC-specific QLQ-HN35 before (t0) and at the end (t1) of definitive or adjuvant IMRT, then at 6-8 weeks (t2), 6 months (t3), and 1 year (t4) after IMRT. Patients (n = 111) completing questionnaires at all five time points were included (baseline response rate: 99%; dropout rate between t0 and t4: 5%). QoL deteriorated in all domains during IMRT and improved slowly during the first year thereafter. Many domains recovered to baseline values after 1 year but problems with smelling and tasting, dry mouth, and sticky saliva remained issues at this time. Increases in problems with sticky saliva were greater after 1 year in patients with definitive versus adjuvant IMRT (F = 3.5, P = 0.05). QoL in patients with LAHNC receiving IMRT takes approximately 1 year to return to baseline; some domains remain compromised after 1 year. Although IMRT aims to maintain function and QoL, patients experience long-term dry mouth and sticky saliva, particularly following definitive IMRT. Patients should be counseled at the start of therapy to reduce disappointment with the pace of recovery.

  19. Hypothyroidism as a Consequence of Intensity-Modulated Radiotherapy With Concurrent Taxane-Based Chemotherapy for Locally Advanced Head-and-Neck Cancer

    SciTech Connect

    Diaz, Roberto; Jaboin, Jerry J.; Morales-Paliza, Manuel; Koehler, Elizabeth; Phillips, John G.; Stinson, Scott; Gilbert, Jill; Chung, Christine H.; Murphy, Barbara A.; Murphy, Patrick B.; Shyr, Yu; Cmelak, Anthony J.

    2010-06-01

    Purpose: To conduct a retrospective review of 168 consecutively treated locally advanced head-and-neck cancer (LAHNC) patients treated with intensity-modulated radiotherapy (IMRT)/chemotherapy, to determine the rate and risk factors for developing hypothyroidism. Methods and Materials: Intensity-modulated radiotherapy was delivered in 33 daily fractions to 69.3 Gy to gross disease and 56.1 Gy to clinically normal cervical nodes. Dose-volume histograms (DVHs) of IMRT plans were used to determine radiation dose to thyroid and were compared with DVHs using conventional three-dimensional radiotherapy (3D-RT) in 10 of these same patients randomly selected for replanning and with DVHs of 16 patients in whom the thyroid was intentionally avoided during IMRT. Weekly paclitaxel (30 mg/m{sup 2}) and carboplatin area under the curve-1 were given concurrently with IMRT. Results: Sixty-one of 128 evaluable patients (47.7%) developed hypothyroidism after a median of 1.08 years after IMRT (range, 2.4 months to 3.9 years). Age and volume of irradiated thyroid were associated with hypothyroidism development after IMRT. Compared with 3D-RT, IMRT with no thyroid dose constraints resulted in significantly higher minimum, maximum, and median dose (p < 0.0001) and percentage thyroid volume receiving 10, 20, and 60 Gy (p < 0.05). Compared with 3D-RT, IMRT with thyroid dose constraints resulted in lower median dose and percentage thyroid volume receiving 30, 40, and 50 Gy (p < 0.005) but higher minimum and maximum dose (p < 0.005). Conclusions: If not protected, IMRT for LAHNC can result in higher radiation to the thyroid than with conventional 3D-RT. Techniques to reduce dose and volume of radiation to thyroid tissue with IMRT are achievable and recommended.

  20. Carotid endarterectomy: review of 10 years of practice of general and locoregional anesthesia in a tertiary care hospital in Portugal.

    PubMed

    Lobo, Mercês; Mourão, Joana; Afonso, Graça

    2015-01-01

    Retrospective and prospective randomized studies have compared general and locoregional anesthesia for carotid endarterectomy, but without definitive results. Evaluate the incidence of complications (medical, surgical, neurological, and hospital mortality) in a tertiary center in Portugal and review the literature. Retrospective analysis of patients undergoing endarterectomy between 2000 and 2011, using a software for hospital consultation. A total of 750 patients were identified, and locoregional anesthesia had to be converted to general anesthesia in 13 patients. Thus, a total of 737 patients were included in this analysis: 74% underwent locoregional anesthesia and 26% underwent general anesthesia. There was no statistically significant difference between the two groups regarding per operative variables. The use of shunt was more common in patients undergoing general anesthesia, a statistically significant difference. The difference between groups of strokes and mortality was not statistically significant. The average length of stay was shorter in patients undergoing locoregional anesthesia with a statistically significant difference. We found that our data are overlaid with the literature data. After reviewing the literature, we found that the number of studies comparing locoregional and general anesthesia and its impact on delirium, cognitive impairment, and decreased quality of life after surgery is still very small and can provide important data to compare the two techniques. Thus, some questions remain open, which indicates the need for randomized studies with larger number of patients and in new centers. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  1. Changes in Pulmonary Function Up to 10 Years After Locoregional Breast Irradiation

    SciTech Connect

    Erven, Katrien; Weltens, Caroline; Nackaerts, Kristiaan; Fieuws, Steffen; Decramer, Marc; Lievens, Yolande

    2012-02-01

    Purpose: To evaluate the long-term impact of locoregional breast radiotherapy (RT) on pulmonary function tests (PFTs). Methods and Materials: This study included 75 women who underwent postoperative locoregional breast RT. PFTs were performed before RT and 3, 6, and 12 months and 8 to 10 years after RT. By use of univariate and multivariate analyses, the impact of treatment- and patient-related factors on late changes in PFTs was evaluated. Results: During the first year after RT, all PFTs significantly worsened at 3 to 6 months after RT (p < 0.05). At 12 months, forced vital capacity (FVC), vital capacity (VC), and forced expiratory volume in 1 second (FEV{sub 1}) recovered almost to baseline values, whereas total lung capacity (TLC) and diffusion capacity of carbon monoxide (DL{sub CO}) recovered only slightly and were still found to be decreased compared with baseline (p < 0.05). At 8 to 10 years after RT, mean reductions in FEV{sub 1} of 4% (p = 0.03) and in VC, DL{sub CO}, and TLC of 5%, 9%, and 11% (all p < 0.0001), respectively, were observed compared with pre-RT values. On multivariate analysis, tamoxifen use negatively affected TLC at 8 to 10 years after RT (p = 0.033), whereas right-sided irradiation was associated with a late reduction in FEV{sub 1} (p = 0.027). For FEV{sub 1} and DL{sub CO}, an early decrease was predictive for a late decrease (p = 0.003 and p = 0.0009, respectively). Conclusions: The time course of PFT changes after locoregional RT for breast cancer follows a biphasic pattern. An early reduction in PFTs at 3 to 6 months with a partial recovery at 12 months after RT is followed by a late, more important PFT reduction up to 8 to 10 years after RT. Tamoxifen use may have an impact on this late decline in PFTs.

  2. Radiation field design and patterns of locoregional recurrence following definitive radiotherapy for breast cancer.

    PubMed

    Chen, Susie A; Schuster, David M; Mister, Donna; Liu, Tian; Godette, Karen; Torres, Mylin A

    2013-02-01

    Locoregional control is associated with breast cancer-specific and overall survival in select women with breast cancer. Although several patient, tumor, and treatment characteristics have been shown to contribute to locoregional recurrence (LRR), studies evaluating factors related to radiotherapy (XRT) technique have been limited. We investigated the relationship between LRR location and XRT fields and dose delivered to the primary breast cancer in women experiencing subsequent locoregional relapse. We identified 21 women who were previously treated definitively with surgery and XRT for breast cancer. All patients developed biopsy-result proven LRR and presented to Emory University Hospital between 2004 and 2010 for treatment. Computed tomography (CT) simulation scans with XRT dose files for the initial breast cancer were fused with (18)F-labeled fluorodeoxyglucose positron emission tomography (FDG PET)/CT images in DICOM (Digital Imaging and Communications in Medicine) format identifying the LRR. Each LRR was categorized as in-field, defined as ≥95% of the LRR volume receiving ≥95% of the prescribed whole-breast dose; marginal, defined as LRR at the field edge and/or not receiving ≥95% of the prescribed dose to ≥95% of the volume; or out-of-field, that is, LRR intentionally not treated with the original XRT plan. Of the 24 identified LRRs (3 patients experienced two LRRs), 3 were in-field, 9 were marginal, and 12 were out-of-field. Two of the 3 in-field LRRs were marginal misses of the additional boost XRT dose. Out-of-field LRRs consisted of six supraclavicular and six internal mammary nodal recurrences. Most LRRs in our study occurred in areas not fully covered by the prescribed XRT dose or were purposely excluded from the original XRT fields. Our data suggest that XRT technique, field design, and dose play a critical role in preventing LRR in women with breast cancer. Published by Elsevier Inc.

  3. Radiation Field Design and Patterns of Locoregional Recurrence Following Definitive Radiotherapy for Breast Cancer

    SciTech Connect

    Chen, Susie A.; Schuster, David M.; Mister, Donna; Liu Tian; Godette, Karen; Torres, Mylin A.

    2013-02-01

    Purpose: Locoregional control is associated with breast cancer-specific and overall survival in select women with breast cancer. Although several patient, tumor, and treatment characteristics have been shown to contribute to locoregional recurrence (LRR), studies evaluating factors related to radiotherapy (XRT) technique have been limited. We investigated the relationship between LRR location and XRT fields and dose delivered to the primary breast cancer in women experiencing subsequent locoregional relapse. Methods and Materials: We identified 21 women who were previously treated definitively with surgery and XRT for breast cancer. All patients developed biopsy-result proven LRR and presented to Emory University Hospital between 2004 and 2010 for treatment. Computed tomography (CT) simulation scans with XRT dose files for the initial breast cancer were fused with {sup 18}F-labeled fluorodeoxyglucose positron emission tomography (FDG PET)/CT images in DICOM (Digital Imaging and Communications in Medicine) format identifying the LRR. Each LRR was categorized as in-field, defined as {>=}95% of the LRR volume receiving {>=}95% of the prescribed whole-breast dose; marginal, defined as LRR at the field edge and/or not receiving {>=}95% of the prescribed dose to {>=}95% of the volume; or out-of-field, that is, LRR intentionally not treated with the original XRT plan. Results: Of the 24 identified LRRs (3 patients experienced two LRRs), 3 were in-field, 9 were marginal, and 12 were out-of-field. Two of the 3 in-field LRRs were marginal misses of the additional boost XRT dose. Out-of-field LRRs consisted of six supraclavicular and six internal mammary nodal recurrences. Conclusions: Most LRRs in our study occurred in areas not fully covered by the prescribed XRT dose or were purposely excluded from the original XRT fields. Our data suggest that XRT technique, field design, and dose play a critical role in preventing LRR in women with breast cancer.

  4. Three-dimensional conformal reirradiation for locoregionally recurrent lung cancer previously treated with radiation therapy.

    PubMed

    Huh, Gil Ja; Jang, Seong Soon; Park, Suk Young; Seo, Jae Hyuk; Cho, Eun Youn; Park, Ji Chan; Yang, Young Jun

    2014-07-01

    To evaluate the efficacy and toxicity of reirradiation using three-dimensional conformal radiotherapy (3D-CRT) in symptomatic patients with locoregionally recurrent lung cancer. Between 2005 and 2012, 15 patients with locoregionally recurrent lung cancer were retreated with 3D-CRT after previously receiving thoracic radiotherapy. The median interval between the initial irradiation and reirradiation was 12 months (range, five to 41 months). The median initial radiotherapy dose was 63 Gy (range, 45-70 Gy), and reirradiation doses ranged from 25.2 to 45.2 Gy (median, 36 Gy), with daily fractions of 1.8-4 Gy (median, 2 Gy). After reirradiation, 80% of the patients experienced resolved or diminished symptoms for one or more of their symptoms, with an 83% improvement in a total of 24 symptoms. The overall tumor response rate to reirradiation was 46.7%, with progressive disease occurring in only one patient. The median overall survival (OS) time was 11 months (range, one to 27 months), and the one-year OS rate was 47%. The progression-free survival time ranged from one to 10 months (median, five months). In univariate analysis, the use of combined chemotherapy and a higher reirradiation dose showed a trend toward improved survival after reirradiation. Treatment-induced toxicity included grade 2 radiation pneumonitis in only one patient, and there were no other complications, such as radiation esophagitis or myelopathy. Reirradiation using 3D-CRT with moderate doses for locoregionally recurrent lung cancer can provide palliative benefits without severe complications to the majority of selected patients with symptoms as a result of a regrowing tumor.

  5. Reirradiation and hyperthermia for irresectable locoregional recurrent breast cancer in previously irradiated area: Size matters.

    PubMed

    Oldenborg, Sabine; Griesdoorn, Vanessa; van Os, Rob; Kusumanto, Yoka H; Oei, Bing S; Venselaar, Jack L; Zum Vörde Sive Vörding, Paul J; Heymans, Martijn W; Kolff, Merel Willemijn; Rasch, Coen R N; Crezee, Hans; van Tienhoven, Geertjan

    2015-11-01

    Treatment options for irresectable locoregional recurrent breast cancer in previously irradiated area are limited. Hyperthermia, elevating tumor temperature to 40-45°C, sensitizes radio-and-chemotherapy. Four hundred and fourteen patients treated with reirradiation+hyperthermia (reRT+HT) in the AMC(n=301) and the BVI(n=113), from 1982 to 2005 were retrospectively analyzed for treatment response, locoregional control (LC) and prognostic factors for LC and toxicity. All patients received previous irradiation (median 50 Gy). reRT consisted of 8 × 4 Gy-2/week (AMC) or 12 × 3 Gy-4/week (BVI). Hyperthermia was added once (AMC)/twice (BVI) a week. Overall clinical response rate was 86%. The 3-year LC rate was 25%. The number of recurrence episodes, distant metastases (DM), tumor site, tumor size, time to recurrence and treatment year were significant for LC. Acute ⩾ grade 3 toxicity occurred in 24% of patients. Actuarial late ⩾ grade 3 toxicity was 23% at 3-years. In multivariable analysis reRT fraction dose was significantly related to late ⩾ grade 3 toxicity. reRT+HT is an effective curative and palliative treatment option for patients with irresectable locoregional recurrent breast cancer in previously irradiated area. Early referral, treatment of chest wall recurrences ⩽ 5 cm in the absence of distant metastases, provided the highest local control rates. The cumulative effects of past and present treatments should be accounted for by adjusting treatment protocol to minimize toxicity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Prognostic Factors for Local, Loco-regional and Systemic Recurrence in Early-stage Breast Cancer.

    PubMed

    Kümmel, A; Kümmel, S; Barinoff, J; Heitz, F; Holtschmidt, J; Weikel, W; Lorenz-Salehi, F; du Bois, A; Harter, P; Traut, A; Blohmer, J U; Ataseven, B

    2015-07-01

    Aim: The risk of recurrence in breast cancer depends on factors such as treatment but also on the intrinsic subtype. We analyzed the risk factors for local, loco-regional and systemic recurrence, evaluated the differences and analyzed the risk of recurrence for different molecular subtypes. Material and Methods: A total of 3054 breast cancer patients who underwent surgery followed by adjuvant treatment at HSK hospital or Essen Mitte Hospital between 1998 and 2011 were analyzed. Based on immunohistochemical parameters, cancers were divided into the following subgroups: luminal A, luminal B (HER2-), luminal B (HER2+), HER2+ and TNBC (triple negative breast cancer). Results: 67 % of tumors were classified as luminal A, 13 % as luminal B (HER2-), 6 % as luminal B (HER2+), 3 % as HER2+ and 11 % as TNBC. After a median follow-up time of 6.6 years there were 100 local (3.3 %), 32 loco-regional (1 %) and 248 distant recurrences (8 %). Five-year recurrence-free survival for the overall patient collective was 92 %. On multivariate analysis, positive nodal status, TNBC subtype and absence of radiation therapy were found to be independent risk factors for all forms of recurrence. Age < 50 years, tumor size, luminal B (HER2-) subtype and breast-conserving therapy were additional risk factors for local recurrence. Compared to the luminal A subtype, the risk of systemic recurrence was higher for all other subtypes; additional risk factors for systemic recurrence were lymphatic invasion, absence of systemic therapy and mastectomy. Conclusion: Overall, the risk of local and loco-regional recurrence was low. In addition to nodal status, subgroup classification was found to be an important factor affecting the risk of recurrence.

  7. Multivariate analyses of locoregional recurrences and skin complications after postmastectomy radiotherapy using electrons or photons

    SciTech Connect

    Huang, E.-Y.; Chen, H.-C.; Sun, L.-M.; Fang, F.-M.; Hsu, H.-C.; Hsiung, C.-Y.; Huang, Y.-J.; Wang, C.-Y.; Wang, C.-J. . E-mail: cjw1010@adm.cgmh.org.tw

    2006-08-01

    Purpose: We retrospectively analyzed factors of locoregional (LR) recurrence and skin complications in patients after postmastectomy radiotherapy (PMRT). Methods and Materials: From January 1988 to December 1999, a total of 246 women with Stage II and III breast cancer received PMRT. Doses of 46 to 52.2 Gy/23 to 29 fractions were delivered to the chest wall (CW) and peripheral lymphatic drainage with 12 to 15 MeV single-portal electrons or 6MV photons. Of the patients, 84 patients received an additional 6 to 20 Gy boost to the surgical scar using 9 MeV electrons. We used the Cox regression model for multivariate analyses of CW, supraclavicular nodes (SCN), and LR recurrence. Results: N3 stage (positive nodes >9) (p = 0.003) and diabetes (p = 0.004) were independent factors of CW recurrence. Analysis of ipsilateral SCN recurrence showed that N3 stage (p < 0.001) and electrons (p = 0.006) were independent factors. For LR recurrence, N3 (p < 0.001), T3 to T4 (p = 0.033) and electrons (p = 0.003) were significant factors. Analysis of skin telangiectasia revealed that electrons (p < 0.001) and surgical scar boost (p = 0.003) were independent factors. Conclusions: Photons are superior to single-portal electrons in patients receiving postmastectomy radiotherapy because of better locoregional control and less skin telangiectasia. In patients in whom the number of positive axillary nodes is >9, more aggressive treatment may be considered for better locoregional control.

  8. Docetaxel in the treatment of squamous cell carcinoma of the head and neck

    PubMed Central

    Rapidis, Alexander; Sarlis, Nicholas; Lefebvre, Jean-Louis; Kies, Merrill

    2008-01-01

    Squamous cell carcinoma of the head and neck (SCCHN) presents at a locally advanced (LA) stage in many patients. Chemotherapy has been successfully integrated into first-line treatment programs, either during or prior to radiotherapy (RT) – the cornerstone modality for local disease control of inoperable disease or when organ preservation is desired. Concomitant chemoradiotherapy (CCRT) provides an absolute survival benefit when compared with other types of locoregional therapy that exclude chemotherapy. Nonetheless, distant metastases still represent the most common cause of treatment failure. Consequently, adding induction chemotherapy (ICT) to definitive non-surgical local therapies with a curative intent has been vigorously explored in LA SCCHN. Recently, it has been shown that ICT using the combination of the taxane docetaxel with cisplatin–5-fluorouracil provides significant survival benefit over cisplatin–5-FU, when used before either definitive RT (TAX323 trial) or carboplatin-based CCRT (TAX324 trial). Docetaxel is also being investigated in metastatic or recurrent (M/R) disease, with promising initial results. It is very likely that the future management strategies of SCCHN will incorporate biologic agents as an add-on to docetaxel-containing schemas, administered either as ICT prior to CCRT in the LA setting or for the management of M/R disease. PMID:19209269

  9. Biologic Therapy in Head and Neck Cancer: A Road with Hurdles

    PubMed Central

    Specenier, Pol; Vermorken, Jan B.

    2012-01-01

    The epidermal growth factor receptor (EGFR) is overexpressed in the vast majority of cases of squamous cell carcinoma of the head and neck (SCCHN). A high EGFR expression is associated with an unfavorable prognosis. Cetuximab is a chimeric human/murine IgG1 antibody which binds with high affinity to the EGFR. It is the only targeted agent which got approval for the treatment of SCCHN from the regulatory agencies of Europe and the United States, both in locoregionally advanced disease, in association with radiation, and in recurrent/metastatic disease. The outcome of trials involving other EGFR-directed monoclonal antibodies, that is, zalutumumab and panitumumab, was consistent with the results with cetuximab. However these trials failed to meet their primary endpoint. The results with EGFR-directed tyrosine kinase inhibitors have been disappointing. Other potential targets for treatment in SCCHN include the entire ErbB family, the vascular endothelial growth factor (VEGF) and its receptor (VEGFR), the insulin-like growth factor 1 receptor (IGF-1R), the insulin receptor (IR), histone deacetylases (HDAC), the mammalian target of rapamycin (mTOR), the platelet-derived growth factor receptor (PDGFR), heat-shock protein 90 (HSP90), nuclear factor-kappa B (NF-κB), aurora A or B, and phosphatidylinositol 3-kinase (PIK3CA). PMID:22745915

  10. Annexin A1 Down-Regulation in Head and Neck Cancer Is Associated with Epithelial Differentiation Status

    PubMed Central

    Pedrero, Juana Maria Garcia; Fernandez, M. Pilar; Morgan, Reginald O.; Zapatero, Agustin Herrero; Gonzalez, Maria Victoria; Nieto, Carlos Suarez; Rodrigo, Juan Pablo

    2004-01-01

    Annexin A1 (ANXA1) protein expression was evaluated by Western blot in a series of 32 head and neck squamous cell carcinomas (HNSCCs) in a search for molecular alterations that could serve as useful diagnostic/prognostic markers. ANXA1 down-regulation was observed in 24 cases (75%) compared with patient-matched normal epithelium. In relation to clinicopathological variables, ANXA1 down-regulation was significantly associated with advanced T stages (P = 0.029), locoregional lymph node metastases (P = 0.038), advanced disease stage (P = 0.006), hypopharyngeal localization (P = 0.038), and poor histological differentiation (P = 0.005). ANXA1 expression was also analyzed by immunohistochemistry in paraffin-embedded sections from 22 of 32 HNSCCs and 8 premalignant lesions. All dysplastic tissues showed significantly reduced ANXA1 expression compared to a strong positive signal observed in adjacent normal epithelia (except basal and suprabasal cells). A close association was observed between ANXA1 expression and the histological grade in HNSCC. Well-differentiated tumors presented a positive ANXA1 signal in highly keratinized areas whereas moderately and poorly differentiated tumors exhibited very weak or negative staining. Our findings clearly identify ANXA1 as an effective differentiation marker for the histopathological grading of HNSCCs and for the detection of epithelial dysplasia. PMID:14695321

  11. [Reirradiation of head and neck cancers].

    PubMed

    Doyen, J; Lam Cham Kee, D; Krebs, L; Guigay, J; Dassonville, O; Peyrade, F; Poissonnet, G; Saâda-Bouzid, E; Sudaka, A; Bozec, A; Bénézery, K

    2017-10-01

    Locoregional relapse in previously irradiated region for head and neck tumours is associated with a bad locoregional and distant prognosis. Reirradiation might be exclusive, or feasible in addition with surgery and/or chemotherapy, according to histopronostic factors. Data show that reirradiation is feasible with some severe toxicity due to the bad prognosis of this situation. Hyperfractionnated regimen with split course or normofractionnated regimen without split course are possible with similar efficacy. If tumour size is small, stereotactic ablative radiotherapy may be considered, and if the treatment centre has proton therapy, it could be proposed because of better organs at risk sparing. There is no standard regarding reirradiation schedules and several trials have to be done in order to determine the best technique. Nevertheless, it is agreed that a total dose of 60Gy (2Gy per fraction) is needed. Other trials testing the association with new systemic agents have to be performed, among them agents targeting the PD1/PD-L1 axis. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  12. Loco-regional cancer drug therapy: present approaches and rapidly reversible hydrophobization (RRH) of therapeutic agents as the future direction.

    PubMed

    Budker, Vladimir G; Monahan, Sean D; Subbotin, Vladimir M

    2014-12-01

    Insufficient drug uptake by solid tumors remains the major problem for systemic chemotherapy. Many studies have demonstrated anticancer drug effects to be dose-dependent, although dose-escalation studies have resulted in limited survival benefit with increased systemic toxicities. One solution to this has been the idea of loco-regional drug treatments, which offer dramatically higher drug concentrations in tumor tissues while minimizing systemic toxicity. Although loco-regional delivery has been most prominent in cancers of the liver, soft tissues and serosal peritoneal malignancies, survival benefits are very far from desirable. This review discusses the evolution of loco-regional treatments, the present approaches and offers rapidly reversible hydrophobization of drugs as the new future direction.

  13. Reirradiation of head and neck cancer: Long‐term disease control and toxicity

    PubMed Central

    van den Bosch, Sven; Zwijnenburg, Ellen M.; Dijkema, Tim; van den Broek, Guido B.; Weijs, Willem L. J.; Verhoef, Lia C. G.; Kaanders, Johannes H. A. M.

    2017-01-01

    ABSTRACT Background The purpose of this study was to report long‐term disease control and late radiation toxicity for patients reirradiated for head and neck cancer. Methods We conducted a retrospective analysis of 137 patients reirradiated with a prescribed dose ≥45 Gy between 1986 and 2013 for a recurrent or second primary malignancy. Endpoints were locoregional control, overall survival (OS), and grade ≥4 late complications according to European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) criteria. Results Five‐year locoregional control rates were 46% for patients reirradiated postoperatively versus 20% for patients who underwent reirradiation as the primary treatment (p < .05). Sixteen cases of serious (grade ≥4) late toxicity were seen in 11 patients (actuarial 28% at 5 years). In patients reirradiated with intensity‐modulated radiotherapy (IMRT), a borderline improved locoregional control was observed (49% vs 36%; p = .07), whereas late complication rates did not differ. Conclusion Reirradiation should be considered for patients with a recurrent or second primary head and neck cancer, especially postoperatively, if indicated. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1122–1130, 2017 PMID:28263446

  14. Locoregional Recurrence of Breast Cancer in Patients Treated With Breast Conservation Surgery and Radiotherapy Following Neoadjuvant Chemotherapy

    SciTech Connect

    Min, Sun Young; Lee, Seung Ju; Shin, Kyung Hwan; Park, In Hae; Jung, So-Youn; Lee, Keun Seok; Ro, Jungsil; Lee, Seeyoun; Kim, Seok Won; Kim, Tae Hyun; Kang, Han-Sung; Cho, Kwan Ho

    2011-12-01

    Purpose: Breast conservation surgery (BCS) and radiotherapy (RT) following neoadjuvant chemotherapy (NCT) have been linked with high locoregional recurrence (LRR) rates and ipsilateral breast tumor recurrence (IBTR) rates. The purpose of this study was to analyze clinical outcomes in patients who exhibited LRR and IBTR after being treated by BCS and RT following NCT. Methods and Materials: In total, 251 breast cancer patients treated with BCS and RT following NCT between 2001 and 2006 were included. All patients had been shown to be clinically node-positive. Clinical stage at diagnosis (2003 AJCC) was II in 68% of patients and III in 32% of patients. Of those, 50%, 35%, and 15% of patients received anthracycline-based, taxane-based, and combined anthracycline-taxane NCT, respectively. All patients received RT. Results: During follow-up (median, 55 months), 26 (10%) patients had LRR, 19 of these patients had IBTR. Five-year actuarial rates of IBTR-free and LRR-free survival were 91% and 89%, respectively. In multivariate analyses, lack of hormone suppression therapy was found to increase both LRR and IBTR rates. Hazard ratios were 7.99 (p < 0.0001) and 4.22 (p = 0.004), respectively. Additionally, pathology stage N2 to N3 increased LRR rate (hazard ratio, 4.22; p = 0.004), and clinical AJCC stage III IBTR rate (hazard ratio, 9.05; p = 0.034). Achievement of pathological complete response and presence of multifocal tumors did not affect LRR or IBTR. Conclusions: In patients with locally advanced disease, who were clinically node-positive at presentation, BCS after NCT resulted in acceptably low rates of IBTR and LRR. Mastectomy should be considered as an option in patients who present with clinical stage III tumors or who are not treated with adjuvant hormone suppression therapy, because they exhibit high IBTR rates after NCT and BCS.

  15. High mammographic breast density predicts locoregional recurrence after modified radical mastectomy for invasive breast cancer: a case-control study.

    PubMed

    Huang, Yu-Sen; Chen, Jenny Ling-Yu; Huang, Chiun-Sheng; Kuo, Sung-Hsin; Jaw, Fu-Shan; Tseng, Yao-Hui; Ko, Wei-Chun; Chang, Yeun-Chung

    2016-12-01

    We aimed to evaluate the influence of mammographic breast density at diagnosis on the risk of cancer recurrence and survival outcomes in patients with invasive breast cancer after modified radical mastectomy. This case-control study included 121 case-control pairs of women diagnosed with invasive breast cancer between 2004 and 2009, and who had undergone modified radical mastectomy and had mammographic breast density measured before or at diagnosis. Women with known locoregional recurrence or distant metastasis were matched by pathological disease stage, age, and year of diagnosis to women without recurrence. Locoregional recurrence was defined as recurrence in the ipsilateral chest wall, or axillary, internal mammary, or supraclavicular nodes. The median follow-up duration was 84.0 months for case patients and 92.9 months for control patients. Patients with heterogeneously dense (50-75% density) and extremely dense (>75% density) breasts had an increased risk of locoregional recurrence (hazard ratios 3.1 and 5.7, 95% confidence intervals 1.1-9.8 and 1.2-34.9, p = 0.043 and 0.048, respectively) than did women with less dense breasts. Positive margins after surgery also increased the risk of locoregional recurrence (hazard ratio 3.3, 95% confidence interval 1.3-8.3, p = 0.010). Multivariate analysis that included dense breasts (>50% density), positive margin, no adjuvant radiotherapy, and no adjuvant chemotherapy revealed that dense breasts were significant factors for predicting locoregional recurrence risk (hazard ratio 3.6, 95% confidence interval 1.2-11.1, p = 0.025). Our results demonstrate that dense breast tissue (>50% density) increased the risk of locoregional recurrence after modified radical mastectomy in patients with invasive breast cancer. Additional prospective studies are necessary to validate these findings. The study is retrospectively registered with ClinicalTrials.gov, number NCT02771665 , on May 11, 2016.

  16. Validating a Prognostic Scoring System for Postmastectomy Locoregional Recurrence in Breast Cancer

    SciTech Connect

    Cheng, Skye Hung-Chun; Tsai, Stella Y.; Yu, Ben-Long; Horng, Cheng-Fang; Chen, Chii-Ming; Jian, James J.; Chu, Nan-Min; Tsou, Mei-Hua; Liu, Mei-Ching; Huang, Andrew T.; Prosnitz, Leonard R.

    2013-03-15

    Purpose: This study is designed to validate a previously developed locoregional recurrence risk (LRR) scoring system and further define which groups of patients with breast cancer would benefit from postmastectomy radiation therapy (PMRT). Methods and Materials: An LRR risk scoring system was developed previously at our institution using breast cancer patients initially treated with modified radical mastectomy between 1990 and 2001. The LRR score comprised 4 factors: patient age, lymphovascular invasion, estrogen receptor negativity, and number of involved lymph nodes. We sought to validate the original study by examining a new dataset of 1545 patients treated between 2002 and 2007. Results: The 1545 patients were scored according to the previously developed criteria: 920 (59.6%) were low risk (score 0-1), 493 (31.9%) intermediate risk (score 2-3), and 132 (8.5%) were high risk (score ≥4). The 5-year locoregional control rates with and without PMRT in low-risk, intermediate-risk, and high-risk groups were 98% versus 97% (P=.41), 97% versus 91% (P=.0005), and 89% versus 50% (P=.0002) respectively. Conclusions: This analysis of an additional 1545 patients treated between 2002 and 2007 validates our previously reported LRR scoring system and suggests appropriate patients for whom PMRT will be beneficial. Independent validation of this scoring system by other institutions is recommended.

  17. Feasibility of proton beam therapy for reirradiation of locoregionally recurrent non-small cell lung cancer.

    PubMed

    McAvoy, Sarah A; Ciura, Katherine T; Rineer, Justin M; Allen, Pamela K; Liao, Zhongxing; Chang, Joe Y; Palmer, Matthew B; Cox, James D; Komaki, Ritsuko; Gomez, Daniel R

    2013-10-01

    Options are limited for patients with intrathoracic recurrence of non-small cell lung cancer (NSCLC) who previously received radiation. We report our 5-year experience with the toxicity and efficacy of proton beam therapy (PBT) for reirradiation. Thirty-three patients underwent PBT reirradiation for intrathoracic recurrent NSCLC at a single institution. All patients had had RT for NSCLC (median initial dose 63 Gy in 33 fractions), with median interval to reirradiation of 36 months. Median reirradiation dose was 66 Gy (RBE) in 32 fractions. Toxicity was scored with CTCAE v4.0, and survival outcomes were estimated using Kaplan-Meier. Thirty-one patients (94%) completed reirradiation. At a median 11 months' follow-up, 1-year rates of overall survival, progression-free survival, locoregional control, and distant metastasis-free survival were 47%, 28%, 54%, and 39%. Rates of severe (grade ≥3) toxicity were 9% esophageal, 21% pulmonary; 1 patient had grade 4 esophagitis, and 2 had grade 4 pulmonary toxicity. Nine patients experienced a second in-field failure. PBT is an option for treating recurrent NSCLC. However, the rates of locoregional recurrence and distant metastasis are high and the potential for toxicity significant. The risks and benefits of PBT must be carefully weighed in each case. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. Locoregional treatment outcomes for breast cancer patients with ipsilateral supraclavicular metastases at diagnosis

    SciTech Connect

    Huang, Eugene H.; Strom, Eric A.; Valero, Vicente; Fornage, Bruno; Perkins, George H.; Oh, Julia L.; Yu, T.-K.; Tereffe, Welela; Woodward, Wendy A.; Hunt, Kelly K.; Meric-Bernstam, Funda; Sahin, Aysegul A.; Bedrosian, Isabelle; Hortobagyi, Gabriel N.; Buchholz, Thomas A. . E-mail: tbuchhol@mdanderson.org

    2007-02-01

    Purpose: To evaluate the locoregional efficacy of multimodality treatment for breast cancer patients who present with ipsilateral supraclavicular (SCV) disease without systemic metastases. Methods: We retrospectively reviewed the data from 71 patients with ipsilateral SCV involvement at presentation. SCV involvement in 16 patients (23%) was diagnosed by ultrasound examination only, without palpable disease. All patients were treated with curative intent using neoadjuvant chemotherapy, mastectomy or breast-conserving surgery (BCT), and radiotherapy. Results: The 5-year SCV control, locoregional control (LRC), disease-free survival, and overall survival rate was 90%, 77%, 30%, and 47%, respectively. Patients with persistent SCV disease after neoadjuvant chemotherapy by physical examination had a lower rate of LRC (64% vs. 86%, p = 0.026), as did those with persistent SCV disease by ultrasound examination (66% vs. 96%, p = 0.007). Of those with a complete response of SCV disease by physical examination after neoadjuvant chemotherapy, those with persistently abnormal ultrasound findings had significantly worse disease-free survival (0% vs. 55%, p = 0.03). BCT was not associated with lower rates of LRC (82% for BCT vs. 76% for mastectomy, p = 0.80). Conclusion: Radiotherapy achieved excellent LRC after surgery for patients with ipsilateral SCV metastases who achieved a complete response of the SCV disease after neoadjuvant chemotherapy. For patients who achieved a complete response of the SCV disease by physical examination, ultrasonography of the SCV fossa may help assess the risk of disease recurrence. SCV involvement should not be considered a contraindication for BCT.

  19. The 'three in one' block as locoregional analgesia in an emergency department.

    PubMed

    Van Leeuwen, F L; Bronselaer, K; Gilles, M; Sabbe, M B; Delooz, H H

    2000-03-01

    The 'three in one' block is a well-known locoregional technique for per- and post-operative anaesthesia. This 'three in one' block was investigated in an emergency department with three combinations of local anaesthetics as a locoregional way of pain relief for patients with fractures of the upper femur. A double-blind prospective study was conducted with 61 consecutive patients. A good regression of the linear visual analogue scale (LVAS), good haemodynamic stability and great patient satisfaction were found for all groups of patients at different times after installation of the block. Side effects were few and are avoidable by reducing the amount of local anaesthetic given to elderly patients with a low bodyweight. The technique failed in only four patients due to technical reasons. It was concluded that the 'three in one' block is a fast, safe, reliable and easy technique for pain relief in an emergency department. Good analgesia was achieved for patients with fractures of the upper femur with no need to change the position of the patient.

  20. Facile preparation of paclitaxel loaded silk fibroin nanoparticles for enhanced antitumor efficacy by locoregional drug delivery.

    PubMed

    Wu, Puyuan; Liu, Qin; Li, Rutian; Wang, Jing; Zhen, Xu; Yue, Guofeng; Wang, Huiyu; Cui, Fangbo; Wu, Fenglei; Yang, Mi; Qian, Xiaoping; Yu, Lixia; Jiang, Xiqun; Liu, Baorui

    2013-12-11

    Non-toxic, safe materials and preparation methods are among the most important factors when designing nanoparticles (NPs) for future clinical application. Here we report a novel and facile method encapsulating anticancer drug paclitaxel (PTX) into silk fibroin (SF), a biocompatible and biodegradable natural polymer, without adding any toxic organic solvents, surfactants or other toxic agents. The paclitaxel loaded silk fibroin nanoparticles (PTX-SF-NPs) with a diameter of 130 nm were formed in an aqueous solution at room temperature by self-assembling of SF protein, which demonstrated mainly silk I conformation in the NPs. In cellular uptake experiments, coumarin-6 loaded SF NPs were taken up efficiently by two human gastric cancer cell lines BGC-823 and SGC-7901. In vitro cytotoxicity studies demonstrated that PTX kept its pharmacological activity when incorporating into PTX-SF-NPs, while SF showed no cytotoxicity to cells. The in vivo antitumor effects of PTX-SF-NPs were evaluated on gastric cancer nude mice exnograft model. We found that locoregional delivery of PTX-SF-NPs demonstrated superior antitumor efficacy by delaying tumor growth and reducing tumor weights compared with systemic administration. Furthermore, the organs of mice in NP treated groups didn't show obvious toxicity, indicating the in vivo safety of SF NPs. These results suggest that SF NPs are promising drug delivery carriers, and locoregional delivery of SF NPs could be a potential future clinical cancer treatment regimen.

  1. Asian expert recommendation on management of skin and mucosal effects of radiation, with or without the addition of cetuximab or chemotherapy, in treatment of head and neck squamous cell carcinoma.

    PubMed

    Zhu, Guopei; Lin, Jin-Ching; Kim, Sung-Bae; Bernier, Jacques; Agarwal, Jai Prakash; Vermorken, Jan B; Thinh, Dang Huy Quoc; Cheng, Hoi-Ching; Yun, Hwan Jung; Chitapanarux, Imjai; Lertsanguansinchai, Prasert; Reddy, Vijay Anand; He, Xia

    2016-01-27

    With increasing numbers of patients with unresectable locoregionally advanced (LA) head and neck squamous cell carcinoma (HNSCC) receiving cetuximab/radiotherapy (RT), several guidelines on the early detection and management of skin-related toxicities have been developed. Considering the existing management guidelines for these treatment-induced conditions, clinical applicability and standardization of grading methods has remained a cause of concern globally, particularly in Asian countries. In this study, we attempted to collate the literature and clinical experience across Asian countries to compile a practical and implementable set of recommendations for Asian oncologists to manage skin- and mucosa-related toxicities arising from different types of radiation, with or without the addition of cetuximab or chemotherapy. In December 2013, an international panel of experts in the field of head and neck cancer management assembled for an Asia-Pacific head and neck cancer expert panel meeting in China. The compilation of discussion outcomes of this meeting and literature data ultimately led to the development of a set of recommendations for physicians with regards to the approach and management of dermatological conditions arising from RT, chemotherapy/RT and cetuximab/RT, and similarly for the approach and management of mucositis resulting from RT, with or without the addition of chemotherapy or cetuximab. These recommendations helped to adapt guidelines published in the literature or text books into bedside practice, and may also serve as a starting point for developing individual institutional side-effect management protocols with adequate training and education.

  2. Post-treatment PET/CT and p16 status for predicting treatment outcomes in locally advanced head and neck cancer after definitive radiation.

    PubMed

    Awan, Musaddiq J; Lavertu, Pierre; Zender, Chad; Rezaee, Rod; Fowler, Nicole; Karapetyan, Lilit; Gibson, Michael; Wasman, Jay; Faulhaber, Peter; Machtay, Mitchell; Yao, Min

    2017-06-01

    To retrospectively review post-treatment (post-tx) FDG-PET/CT scans in patients with advanced head and neck squamous cell carcinoma (HNSCC) and known p16 status, treated with definitive (chemo)radiation (RT). A total of 108 eligible patients had N2A or greater HNSCC treated with chemoRT from August 1, 2008, to February 28, 2015, with post-tx PET/CT within 6 months after RT. Kaplan-Meier curves, log-rank statistics, and Cox proportional hazards regression were used for statistical analysis. Median follow-up was 2.38 years. Sixty-eight (63.0%) patients had p16+ and 40 (37.0%) had p16- status. Two-year overall survival and recurrence-free survival were 93.4% and 77.8%, respectively. The negative predictive value (NPV) of PET/CT for local recurrence (LR) was 100%. The NPV for regional recurrence (RR) was 96.5% for all patients, 100% for p16+ patients, and 88.5% for p16- patients. The positive predictive value (PPV) of PET/CT for recurrence was 77.3% for all patients, 50.0% for p16+, and 78.6% for p16-. The PPV for LR was 72.7% for all patients, 50.0% for p16+ patients, and 72.7% for p16- patients. The PPV for RR was 50.0% for all patients, 33% for p16+, and 66.6% for p16-. Post-tx PET/CT and p16 status were independent predictors of recurrence-free survival (p < 0.01). Post-tx PET/CT predicts treatment outcomes in both p16 + and p16- patients, and does so independently of p16 status. P16- patients with negative PET have a 10% risk of nodal recurrence, and closer follow-up in these patients is warranted.

  3. Nab-paclitaxel-based compared to docetaxel-based induction chemotherapy regimens for locally advanced squamous cell carcinoma of the head and neck

    PubMed Central

    Schell, Amy; Ley, Jessica; Wu, Ningying; Trinkaus, Kathryn; Wildes, Tanya Marya; Michel, Loren; Thorstad, Wade; Gay, Hiram; Lewis, James; Rich, Jason; Diaz, Jason; Paniello, Randal C; Nussenbaum, Brian; Adkins, Douglas R

    2015-01-01

    We previously reported that nab-paclitaxel-based induction chemotherapy (IC) and concurrent chemoradiotherapy resulted in low relapse rates (13%) and excellent survival in head and neck squamous cell carcinoma (HNSCC). We compare the disease-specific survival (DSS) and overall survival (OS) between patients given nab-paclitaxel, cisplatin, and fluorouracil with cetuximab (APF-C) and historical controls given docetaxel, cisplatin, and fluorouracil with cetuximab (TPF-C). Patients with locally advanced HNSCC were treated with APF-C (n = 30) or TPF-C (n = 38). After 3 cycles of IC, patients were scheduled to receive cisplatin concurrent with definitive radiotherapy. T and N classification and smoking history were similar between the two groups and within p16-positive and p16-negative subsets. The median duration of follow-up for living patients in the APF-C group was 43.5 (range: 30–58) months versus 52 (range: 13–84) months for TPF-C. The 2-year DSS for patients treated with APF-C was 96.7% [95% Confidence Interval (CI): 85.2%, 99.8%] and with TPF-C was 77.6% (CI: 62.6%, 89.7%) (P = 0.0004). Disease progression that resulted in death was more frequent in the TPF-C group (39%) compared with the APF-C group (3%) when adjusted for competing risks of death from other causes (Gray's test, P = 0.0004). In p16 positive OPSCC, the 2-year DSS for APF-C was 100% and for TPF-C was 74.6% (CI: 47.4%, 94.6%) (P = 0.0019) and the 2-year OS for APF-C was 94.1% (CI: 65.0%, 99.2%) and for TPF-C was 74.6% (CI: 39.8%, 91.1%) (P = 0.013). In p16 negative HNSCC, the 2-year DSS for APF-C was 91.7% (CI: 67.6%, 99.6%) and for TPF-C was 82.6% (CI: 64.4%, 94.8%) (P = 0.092). A 2-year DSS and OS were significantly better with a nab-paclitaxel-based IC regimen (APF-C) compared to a docetaxel-based IC regimen (TPF-C) in p16-positive OPSCC. PMID:25619559

  4. 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

  5. Concurrent weekly docetaxel and concomitant boost radiation therapy in the treatment of locally advanced squamous cell cancer of the head and neck

    SciTech Connect

    Tishler, Roy B. . E-mail: roy_tishler@dfci.harvard.edu; Posner, Marshall R.; Norris, Charles M.; Mahadevan, Anand; Sullivan, Christopher; Goguen, Laura; Wirth, Lori J.; Costello, Rosemary; Case, MaryAnn; Stowell, Sara; Sammartino, Dan; Busse, Paul M.; Haddad, Robert I.

    2006-07-15

    Purpose: In a Phase I/II trial, we investigated concurrent weekly docetaxel and concomitant boost radiation in patients with locally advanced squamous cell cancer of the head and neck (SCCHN) after induction chemotherapy. Patients and Methods: Patients presented with American Joint Committee on Cancer Stage III/IV and were treated initially with induction chemotherapy using cisplatinum/5-fluorouracil (PF), carboplatinum-5-FU, or docetaxel-PF. Patients then received docetaxel four times weekly with concomitant boost (CB) radiation (1.8 Gy once-daily X20, 1.8/1.5 Gy twice a day). Fifteen patients each received 20 mg/M{sup 2} and 25 mg/M{sup 2}. Results: Thirty-one patients were enrolled and 30 were evaluable for response and toxicity. Median follow-up was 42 months (range, 27-63 months). Primary sites were: oropharynx 19, oral cavity 2, larynx/hypopharynx 5, and unknown primary 4. Eighty-seven percent of patients had N2/N3 disease; 60% had T3/T4 disease. Twenty percent of patients had a complete response (CR) to induction chemotherapy. After chemoradiotherapy, 21 of 30 patients had a CR, 2 had progressive disease, and 7 had partial response (PR). Nineteen of 26 patients presenting with neck disease had neck dissections, and 7 of 19 were positive. Ninety-three percent of all patients were rendered disease-free after all planned therapy. Treatment failed in 8 patients, and 7 have died of disease. An additional patient died with no evidence of disease. Twenty-one patients (70%) are currently alive with no evidence of disease. No acute dose-limiting toxicity was observed at either dose level. Conclusions: This intensive treatment regimen of concurrent docetaxel/concomitant boost radiation and surgery after induction chemotherapy in poor prognosis patients yields good local regional control and survival. Docetaxel/CB chemoradiotherapy represents an aggressive alternative regimen to platinum-based chemoradiotherapy or surgery in patients who have a poor response to

  6. Weekly Gemcitabine and Cisplatin in Combination With Radiotherapy in Patients With Locally Advanced Head-and-Neck Cancer: Phase I Study

    SciTech Connect

    Arruda Viani, Gustavo; Afonso, Sergio Luis; Cardoso Tavares, Vivian; Bernardes Godoi da Silva, Lucas; Stefano, Eduardo Jose

    2011-11-15

    Purpose: To define the maximum tolerated dose by describing the dose-limiting toxicity (DLT) of weekly gemcitabine and cisplatin in patients with locally advanced head-and-neck (LAHN) cancer concomitant to irradiation. Methods and Materials: Patients with LAHN cancer were enrolled in a prospective, dose-escalation Phase I study. Toxicity was graded according to the Common Toxicity Criteria score. Maximum tolerated dose was defined when DLT developed in 2 of 6 patients. The starting dose of cisplatin was 20 mg/m{sup 2} and that of gemcitabine was 10 mg/m{sup 2} in 3 patients, with a subsequent dose escalation of 10 mg/m{sup 2} of cisplatin only for 3 new patients. In the next levels, only a dose escalation of gemcitabine with 10 mg/m{sup 2} for each new cohort was used (Level 1, 10 mg/m{sup 2} of gemcitabine and 20 mg/m{sup 2} of cisplatin; Level 2, 10 mg/m{sup 2} of gemcitabine and 30 mg/m{sup 2} of cisplatin; and Level 3, 20 mg/m{sup 2} of gemcitabine and 30 mg/m{sup 2} of cisplatin). Radiation therapy was administered by use of a conformal technique over a period of 6 to 7 weeks in 2.0-Gy daily fractions for 5 consecutive days per week to a total dose of 70 Gy. Results: From 2008 to 2009, 12 patients completing 3 dose levels were included in the study. At Dose Level 3, 1 of 3 patients had DLT with Grade 3 mucositis. Of the next 3 required patients, 2 showed DLT with Grade 3 dermatitis. At a follow-up of 3 months, 10 of 12 evaluable patients (83.3%) obtained a complete response and 1 patient (8.3%) obtained a partial response. Among the complete responders, at a median follow-up of 10 months (range, 6-14 months), 9 patients are alive and disease free. Conclusion: Gemcitabine at low doses combined with cisplatin is a potent radiosensitizer effective in patients with LAHN cancer. The recommended Phase II dose is 10 mg/m{sup 2} of gemcitabine and 30 mg/m{sup 2} of cisplatin with an acceptable tolerability profile.

  7. Final Results of Local-Regional Control and Late Toxicity of RTOG 9003: A Randomized Trial of Altered Fractionation Radiation for Locally Advanced Head and Neck Cancer

    SciTech Connect

    Beitler, Jonathan J.; Zhang, Qiang; Fu, Karen K.; Trotti, Andy; Spencer, Sharon A.; Jones, Christopher U.; Garden, Adam S.; Shenouda, George; Harris, Jonathan; Ang, Kian K.

    2014-05-01

    Purpose: To test whether altered radiation fractionation schemes (hyperfractionation [HFX], accelerated fractionation, continuous [AFX-C], and accelerated fractionation with split [AFX-S]) improved local-regional control (LRC) rates for patients with squamous cell cancers (SCC) of the head and neck when compared with standard fractionation (SFX) of 70 Gy. Methods and Materials: Patients with stage III or IV (or stage II base of tongue) SCC (n=1076) were randomized to 4 treatment arms: (1) SFX, 70 Gy/35 daily fractions/7 weeks; (2) HFX, 81.6 Gy/68 twice-daily fractions/7 weeks; (3) AFX-S, 67.2 Gy/42 fractions/6 weeks with a 2-week rest after 38.4 Gy; and (4) AFX-C, 72 Gy/42 fractions/6 weeks. The 3 experimental arms were to be compared with SFX. Results: With patients censored for LRC at 5 years, only the comparison of HFX with SFX was significantly different: HFX, hazard ratio (HR) 0.79 (95% confidence interval 0.62-1.00), P=.05; AFX-C, 0.82 (95% confidence interval 0.65-1.05), P=.11. With patients censored at 5 years, HFX improved overall survival (HR 0.81, P=.05). Prevalence of any grade 3, 4, or 5 toxicity at 5 years; any feeding tube use after 180 days; or feeding tube use at 1 year did not differ significantly when the experimental arms were compared with SFX. When 7-week treatments were compared with 6-week treatments, accelerated fractionation appeared to increase grade 3, 4 or 5 toxicity at 5 years (P=.06). When the worst toxicity per patient was considered by treatment only, the AFX-C arm seemed to trend worse than the SFX arm when grade 0-2 was compared with grade 3-5 toxicity (P=.09). Conclusions: At 5 years, only HFX improved LRC and overall survival for patients with locally advanced SCC without increasing late toxicity.

  8. The head-mounted microscope.

    PubMed

    Chen, Ting; Dailey, Seth H; Naze, Sawyer A; Jiang, Jack J

    2012-04-01

    Microsurgical equipment has greatly advanced since the inception of the microscope into the operating room. These advancements have allowed for superior surgical precision and better post-operative results. This study focuses on the use of the Leica HM500 head-mounted microscope for the operating phonosurgeon. The head-mounted microscope has an optical zoom from 2× to 9× and provides a working distance from 300 mm to 700 mm. The headpiece, with its articulated eyepieces, adjusts easily to head shape and circumference, and offers a focus function, which is either automatic or manually controlled. We performed five microlaryngoscopic operations utilizing the head-mounted microscope with successful results. By creating a more ergonomically favorable operating posture, a surgeon may be able to obtain greater precision and success in phonomicrosurgery. Phonomicrosurgery requires the precise manipulation of long-handled cantilevered instruments through the narrow bore of a laryngoscope. The head-mounted microscope shortens the working distance compared with a stand microscope, thereby increasing arm stability, which may improve surgical precision. Also, the head-mounted design permits flexibility in head position, enabling operator comfort, and delaying musculoskeletal fatigue. A head-mounted microscope decreases the working distance and provides better ergonomics in laryngoscopic microsurgery. These advances provide the potential to promote precision in phonomicrosurgery.

  9. Prospective Assessment of Patterns of Failure After High-Precision Definitive (Chemo)Radiation in Head-and-Neck Squamous Cell Carcinoma

    SciTech Connect

    Gupta, Tejpal

    2011-06-01

    Purpose: To prospectively analyze patterns of failure in patients with head-and-neck squamous cell carcinoma treated with definitive high-precision radiotherapy with a focus on location of failure relative to target volume coverage. Methods and Materials: Sixty patients treated with three-dimensional conformal radiotherapy or intensity-modulated radiation therapy were included. Locoregional failure volume was defined on the planning data set at relapse, and dose received was analyzed by use of dose-volume histograms. Results: Thirteen patients were deemed to have had locoregional failures, of which two did not have any viable tumor on salvage neck dissection, leaving eleven patients with proven persistent or recurrent locoregional disease. Of these, 9 patients had in-field failure, 1 marginal failure, and 1 both in-field and marginal failures. Overall, only 2 of 11 patients (18%) with relapse had any marginal failure. Of the 20 sites of locoregional failure, 15 (75%) were in-field and 5 (25%) marginal. Distant metastases were detected in 3 patients, whereas a second new primary developed in 3 others. With a median follow-up of 26 months (interquartile range, 18-31 months) for surviving patients, the 3-year local control, locoregional control, disease-free survival, and overall survival rates were 75.3%, 74%, 67.2%, and 60.5%, respectively. Conclusions: Locoregional relapse remains the predominant pattern of failure in head-and-neck squamous cell carcinoma treated with high-precision definitive radiotherapy with the majority of failures occurring 'in-field' within the high-dose volume. Marginal failures can occur, particularly in the vicinity of the spared parotid gland. The therapeutic index of high-precision conformal radiotherapy is largely dependent on adequate selection and delineation of target volumes and organs at risk.

  10. pN0(i+) Breast Cancer: Treatment Patterns, Locoregional Recurrence, and Survival Outcomes

    SciTech Connect

    Karam, Irene; Lesperance, Maria F.; Berrang, Tanya; Speers, Caroline; Tyldesley, Scott; Truong, Pauline T.

    2013-11-15

    Purpose: To examine treatment patterns, recurrence, and survival outcomes in patients with pN0(i+) breast cancer. Methods and Materials: Subjects were 5999 women with AJCC (6th edition) pT1-3, pN0-N1a, M0 breast cancer diagnosed between 2003 and 2006. Of these, 4342 (72%) had pN0, 96 (2%) had pN0(i+), 349 (6%) had pNmic (micrometastases >0.2 mm to ≤2 mm), and 1212 (20%) had pN1a (1-3 positive macroscopic nodes) disease. Treatment characteristics and 5-year Kaplan-Meier local recurrence, regional recurrence (RR), locoregional recurrence (LRR), and overall survival were compared between nodal subgroups. Multivariable analysis was performed using Cox regression modeling. A 1:3 case-match analysis examined outcomes in pN0(i+) cases compared with pN0 controls matched for similar tumor and treatment characteristics. Results: Median follow-up was 4.8 years. Adjuvant systemic therapy use increased with nodal stage: 81%, 92%, 95%, and 94% in pN0, pN0(i+), pNmic, and pN1a disease, respectively (P<.001). Nodal radiation therapy (RT) use also increased with nodal stage: 1.7% in pN0, 27% in pN0(i+), 33% in pNmic, and 63% in pN1a cohorts (P<.001). Five-year Kaplan-Meier outcomes in pN0 versus pN0(i+) cases were as follows: local recurrence 1.7% versus 3.7% (P=.20), RR 0.5% versus 2.2% (P=.02), and LRR 2.1% versus 5.8% (P=.02). There were no RR events in 26 patients with pN0(i+) disease who received nodal RT and 2 RR events in 70 patients who did not receive nodal RT. On multivariable analysis, pN0(i+) was not associated with worse locoregional control or survival. On case-match analysis, LRR and overall survival were similar between pN0(i+) and matched pN0 counterparts. Conclusions: Nodal involvement with isolated tumor cells is not a significant prognostic factor for LRR or survival in this study's multivariable and case-match analyses. These data do not support the routine use of nodal RT in the setting of pN0(i+) disease. Prospective studies are needed to define optimal

  11. Molecular predictors of locoregional and distant metastases in oropharyngeal squamous cell carcinoma

    PubMed Central

    2013-01-01

    Background The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing due to fundamental changes in oncogenesis related to effects of the human papilomavirus (HPV). Virally-mediated tumours behave and respond to treatment differently than their classic, carcinogenically-mediated counterparts despite similar stage and grade of disease. This difference in behaviour has lead to investigation of etiologies of OPSCC at the molecular level. Molecular biomarkers offer potential insight into the behaviour of OPSCC. Identifying a subset of patients that are more likely to have recurrence and distant metastasis is valuable for prognostication and treatment planning. There is limited information regarding the profiles of these biomarkers in locoregional and distant metastases in OPSCC. Objective This study was designed to identify biomarker profiles predictive of locoregional and distant metastases and recurrence in OPSCC. Methods Cross-sectional study of a prospectively-collected oropharyngeal tumour database was undertaken. All patients with OPSCC presenting to the University of Alberta Hospital from 2002-2009 were included in the study. Data collection from the Alberta Cancer Registry, including demographics, nodal status, distant metastases, treatment, recurrence, and survival, was undertaken. Tissue micro-arrays (TMAs) were constructed for each tumour specimen using triplicate cores (0.6mm) of formalin-fixed, paraffin-embedded (FFPE) pre-treatment tumour tissue. TMAs were processed using immunohistochemistry for p16, EGFR, Ki67, p53, and Bcl-XL. Positivity for each biomarker was determined using quantified AQUAnalysis ® scores on histoplots. Multivariate statistics were utilized to assess the relationship between each biomarker and locoregional and distant metastases, as well as recurrence-free survival (RFS). Results High expression of p16 (p=0.000) and Bcl-XL (p=0.039) independently demonstrated a significant association with nodal disease at

  12. [Carotid endarterectomy: review of 10 years of practice of general and locoregional anesthesia in a tertiary care hospital in Portugal].

    PubMed

    Lobo, Mercês; Mourão, Joana; Afonso, Graça

    2015-01-01

    Retrospective and prospective randomized studies have compared general and locoregional anesthesia for carotid endarterectomy, but without definitive results. Evaluate the incidence of complications (medical, surgical, neurological, and hospital mortality) in a tertiary center in Portugal and review the literature. Retrospective analysis of patients undergoing endarterectomy between 2000 and 2011, using a software for hospital consultation. A total of 750 patients were identified, and locoregional anesthesia had to be converted to general anesthesia in 13 patients. Thus, a total of 737 patients were included in this analysis: 74% underwent locoregianal anesthesia and 26% underwent general anesthesia. There was no statistically significant difference between the two groups regarding perioperative variables. The use of shunt was more common in patients undergoing general anesthesia, a statistically significant difference. The difference between groups of strokes and mortality was not statistically significant. The average length of stay was shorter in patients undergoing locoregional anesthesia with a statistically significant difference. We found that our data are overlaid with the literature data. After reviewing the literature, we found that the number of studies comparing locoregional and general anesthesia and its impact on delirium, cognitive impairment, and decreased quality of life after surgery is still very small and can provide important data to compare the two techniques. Thus, some questions remain open, which indicates the need for randomized studies with larger number of patients and in new centers. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  13. Positive Factors Influencing the Advancement of Women to the Role of Head Athletic Trainer in the National Collegiate Athletic Association Divisions II and III

    PubMed Central

    Mazerolle, Stephanie M.; Eason, Christianne M.

    2016-01-01

    Context:  Research suggests that women do not pursue leadership positions in athletic training due to a variety of reasons, including family challenges, organizational constraints, and reluctance to hold the position. The literature has been focused on the National Collegiate Athletic Association Division I setting, limiting our full understanding. Objective:  To examine factors that help women as they worked toward the position of head athletic trainer. Design:  Qualitative study. Setting:  Divisions II and III. Patients or Other Participants:  Seventy-seven women who were employed as head athletic trainers at the Division II or III level participated in our study. Participants were 38 ± 9 (range = 24−57) years old and had an average of 14 ± 8 (range = 1−33) years of athletic training experience. Data Collection and Analysis:  We conducted online interviews. Participants journaled their reflections to a series of open-ended questions pertaining to their experiences as head athletic trainers. Data were analyzed using a general inductive approach. Credibility was secured by peer review and researcher triangulation. Results:  Three organizational facilitators emerged from the data, workplace atmosphere, mentors, and past work experiences. These organizational factors were directly tied to aspects within the athletic trainer's employment setting that allowed her to enter the role. One individual-level facilitator was found: personal attributes that were described as helpful for women in transitioning to the role of the head athletic trainer. Participants discussed being leaders and persisting toward their career goals. Conclusions:  Women working in Divisions II and III experience similar facilitators to assuming the role of head athletic trainer as those working in the Division I setting. Divisions II and III were viewed as more favorable for women seeking the role of head athletic trainer, but like those in the role in the Division I setting

  14. Positive Factors Influencing the Advancement of Women to the Role of Head Athletic Trainer in the National Collegiate Athletic Association Divisions II and III.

    PubMed

    Mazerolle, Stephanie M; Eason, Christianne M

    2016-07-01

    Research suggests that women do not pursue leadership positions in athletic training due to a variety of reasons, including family challenges, organizational constraints, and reluctance to hold the position. The literature has been focused on the National Collegiate Athletic Association Division I setting, limiting our full understanding. To examine factors that help women as they worked toward the position of head athletic trainer. Qualitative study. Divisions II and III. Seventy-seven women who were employed as head athletic trainers at the Division II or III level participated in our study. Participants were 38 ± 9 (range = 24-57) years old and had an average of 14 ± 8 (range = 1-33) years of athletic training experience. We conducted online interviews. Participants journaled their reflections to a series of open-ended questions pertaining to their experiences as head athletic trainers. Data were analyzed using a general inductive approach. Credibility was secured by peer review and researcher triangulation. Three organizational facilitators emerged from the data, workplace atmosphere, mentors, and past work experiences. These organizational factors were directly tied to aspects within the athletic trainer's employment setting that allowed her to enter the role. One individual-level facilitator was found: personal attributes that were described as helpful for women in transitioning to the role of the head athletic trainer. Participants discussed being leaders and persisting toward their career goals. Women working in Divisions II and III experience similar facilitators to assuming the role of head athletic trainer as those working in the Division I setting. Divisions II and III were viewed as more favorable for women seeking the role of head athletic trainer, but like those in the role in the Division I setting, women must have leadership skills.

  15. Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-small Cell Lung Cancer, or Squamous Cell Head and Neck Cancer

    ClinicalTrials.gov

    2017-09-14

    Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Renal Cell Cancer

  16. Immunohistochemical detection of osteopontin in advanced head-and-neck cancer: Prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1{alpha}-related markers, and hemoglobin levels

    SciTech Connect

    Bache, Matthias; Reddemann, Rolf; Said, Harun M.; Holzhausen, Hans-Juergen; Taubert, Helge; Becker, Axel; Kuhnt, Thomas; Haensgen, Gabriele; Dunst, Juergen; Vordermark, Dirk . E-mail: vordermark_d@klinik.uni-wuerzburg.de

    2006-12-01

    Purpose: The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma marker of tumor hypoxia. However, the association of immunohistochemical OPN expression in tumor sections with tumor oxygenation parameters (HF5, median pO{sub 2}), the hypoxia-related markers hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) and carbonic anhydrase IX (CAIX), or hemoglobin and systemic vascular endothelial growth factor (VEGF) levels has not been investigated. Methods and Materials: Tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radiotherapy were assessed by immunochemistry for the expression of OPN, HIF-1{alpha}, and CA IX. Relationship of OPN expression with tumor oxygenation parameters (HF5, median pO{sub 2}), HIF-1{alpha} and CA IX expression, hemoglobin and serum VEGF level, and clinical parameters was studied. Results: Bivariate analysis showed a significant correlation of positive OPN staining with low hemoglobin level (p = 0.02), high HIF-1{alpha} expression (p = 0.02), and high serum vascular endothelial growth factor level (p = 0.02) for advanced head-and-neck cancer. Furthermore, considering the 31 Stage IV patients, the median pO{sub 2} correlated significantly with the OPN expression (p = 0.02). OPN expression alone had only a small impact on prognosis. However, in a univariate Cox proportional hazard regression model, the expression of either OPN or HIF-1{alpha} or CA IX was associated with a 4.1-fold increased risk of death (p = 0.02) compared with negativity of all three markers. Conclusion: Osteopontin expression detected immunohistochemically is associated with oxygenation parameters in advanced head-and-neck cancer. When the results of OPN, HIF-1{alpha}, and CA IX immunohistochemistry are combined into a hypoxic profile, a strong and statistically significant impact on overall survival is found.

  17. Long-term outcomes after salvage radiotherapy for postoperative locoregionally recurrent non-small-cell lung cancer.

    PubMed

    Kim, Eunji; Song, Changhoon; Kim, Mi Young; Kim, Jae-Sung

    2017-03-01

    The outcomes and toxicities of locoregionally recurrent non-small-cell lung cancer (NSCLC) patients treated with curative radiotherapy were evaluated in the modern era. Fifty-seven patients receiving radical radiotherapy for locoregionally recurrent NSCLC without distant metastasis after surgery from 2004 to 2014 were reviewed. Forty-two patients were treated with concurrent chemoradiotherapy (CCRT), and 15 patients with radiotherapy alone. The median radiation dose was 66 Gy (range, 45 to 70 Gy). Lung function change after radiotherapy was evaluated by comparing pulmonary function tests before and at 1, 6, and 12 months after radiotherapy. Median follow-up was 53.6 months (range, 12.0 to 107.5 months) among the survivors. The median overall survival (OS) and progression-free survival (PFS) were 54.8 months (range, 3.0 to 116.9 months) and 12.2 months (range, 0.8 to 100.2 months), respectively. Multivariate analyses revealed that single locoregional recurrence focus and use of concurrent chemotherapy were significant prognostic factors for OS (p = 0.048 and p = 0.001, respectively) and PFS (p = 0.002 and p = 0.026, respectively). There was no significant change in predicted forced expiratory volume in one second after radiotherapy. Although diffusing lung capacity for carbon monoxide decreased significantly at 1 month after radiotherapy (p < 0.001), it recovered to pretreatment levels within 12 months. Acute grade 3 radiation pneumonitis and esophagitis were observed in 3 and 2 patients, respectively. There was no chronic complication observed in all patients. Salvage radiotherapy showed good survival outcomes without severe complications in postoperative locoregionally recurrent NSCLC patients. A single locoregional recurrent focus and the use of CCRT chemotherapy were associated with improved survival. CCRT should be considered as a salvage treatment in patients with good prognostic factors.

  18. Concomitant chemoradiotherapy using carboplatin, tegafur-uracil and leucovorin for stage III and IV head-and-neck cancer: results of GORTEC Phase II study.

    PubMed

    Fesneau, Melanie; Pointreau, Yoann; Chapet, Sophie; Martin, Laurent; Pommier, Pascal; Alfonsi, Marc; Laguerre, Brigitte; Feham, Nasreddine; Berger, Christine; Garaud, Pascal; Calais, Gilles

    2010-01-01

    Concomitant chemoradiotherapy is the standard treatment of locally advanced, nonresectable, head-and-neck squamous cell carcinoma. However, the optimal chemotherapy regimen is still controversial. The objective of this Phase II study was to evaluate the feasibility and efficacy of a concomitant treatment using tegafur-uracil, leucovorin, carboplatin, and radiotherapy. A total of 77 patients with head-and-neck squamous cell carcinoma Stage III and IVA were enrolled between October 2003 and July 2005. Of the 77 patients, 72 were eligible. They were treated with tegafur-uracil (300 mg/m(2)/d) and leucovorin (75 mg/d) from Days 1 to 19 and from Days 29 to 47 and carboplatin (70 mg/m(2) intravenously for 4 consecutive days), in three cycles every 21 days. Conventional radiotherapy was delivered to a total dose of 70 Gy in 35 fractions. With a mean follow-up of 22.8 months, the 3-year locoregional control, overall survival and disease-free survival actuarial rate was 33.1%, 41.9%, and 27.2%, respectively. The compliance of the treatment was correct. The main acute toxicity was mucositis, with 62% Grade 3-4. Three patients (4.2%) died of acute toxicity. The incidence and severity of late toxicity was acceptable, with 32% Grade 3 and no Grade 4 toxicity. The protocol of concomitant chemoradiotherapy using tegafur-uracil, leucovorin, and carboplatin for locally advanced unresectable head-and-neck squamous cell carcinoma is feasible. The compliance was correct. The incidence and severity of the acute and late toxicities were acceptable, but not improved. The efficacy of this regimen seems equivalent to the main protocols of concurrent chemoradiotherapy. It represents a possible alternative for patients without an intravenous catheter.

  19. Distant Metastases in Head-and-Neck Squamous Cell Carcinoma Treated With Intensity-Modulated Radiotherapy

    SciTech Connect

    Yao Min; Lu Minggen; Savvides, Panayiotis S.; Rezaee, Rod; Zender, Chad A.; Lavertu, Pierre; Buatti, John M.; Machtay, Mitchell

    2012-06-01

    Purpose: To determine the pattern and risk factors for distant metastases in head-and-neck squamous cell carcinoma (HNSCC) after curative treatment with intensity-modulated radiotherapy (IMRT). Methods and Materials: This was a retrospective study of 284 HNSCC patients treated in a single institution with IMRT. Sites included were oropharynx (125), oral cavity (70), larynx (55), hypopharynx (17), and unknown primary (17). American Joint Committee on Cancer stage distribution includes I (3), II (19), III (42), and IV (203). There were 224 males and 60 females with a median age of 57. One hundred eighty-six patients were treated with definitive IMRT and 98 postoperative IMRT. One hundred forty-nine patients also received concurrent cisplatin-based chemotherapy. Results: The median follow-up for all patients was 22.8 months (range, 0.07-77.3 months) and 29.5 months (4.23-77.3 months) for living patients. The 3-year local recurrence-free survival, regional recurrence-free survival, locoregional recurrence-free survival, distant metastasis-free survival, and overall survival were 94.6%, 96.4%, 92.5%, 84.1%, and 68.95%, respectively. There were 45 patients with distant metastasis. In multivariate analysis, distant metastasis was strongly associated with N stage (p = 0.046), T stage (p < 0.0001), and pretreatment maximum standardized uptake value of the lymph node (p = 0.006), but not associated with age, gender, disease sites, pretreatment standardized uptake value of the primary tumor, or locoregional control. The freedom from distant metastasis at 3 years was 98.1% for no factors, 88.6% for one factor, 68.3% for two factors, and 41.7% for three factors (p < 0.0001 by log-rank test). Conclusion: With advanced radiation techniques and concurrent chemotherapy, the failure pattern has changed with more patients failing distantly. The majority of patients with distant metastases had no local or regional failures, indicating that these patients might have microscopic distant

  20. Circulating biomarkers of hepatocellular carcinoma response after locoregional treatments: New insights

    PubMed Central

    Tampaki, Maria; Doumba, Polyxeni P; Deutsch, Melanie; Koskinas, John

    2015-01-01

    Hepatocellular cancer is the 5th most common cancer in the world and the third cause of death by malignant disease. Locoregional therapies are the most usual treatment of choice for patients with early or intermediate stage of disease. The main diagnostic tools for the detection of recurrence are the radiological techniques such as 4-phase computed tomography or dynamic contrast enhanced magnetic resonance imaging. However, in order to achieve best evaluation of treatment outcome and recurrence rates, there is a great need for the identification of specific and easily measured circulating biomarkers. The aim of this review is to analyze the existing data considering the prognostic significance of changes of serum diagnostic markers such as alpha-fetoprotein, des-gamma-carboxy prothrombin, alpha-fetoprotein-L3, angiogenetic factors (vascular endothelial growth factor, hypoxia inducible factor-1a) and immune parameters before and after radiofrequency ablation or transarterial chemoembolization. PMID:26207165

  1. [Surgical approach to the locoregional recurrence of cancer of the rectum].

    PubMed

    Lizarazu, Aintzane; Enríquez-Navascués, José M; Placer, Carlos; Carrillo, Alberto; Sainz-Lete, A