Publications by authors named "Nisha Ohri"

32 Publications

Hypofractionated Postmastectomy Radiation Therapy.

Adv Radiat Oncol 2021 Jan-Feb;6(1):100618. Epub 2020 Nov 21.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey.

Purpose: To provide an overview of the major randomized trials that support the use of hypofractionated post-mastectomy radiation therapy for locally advanced breast cancer patients.

Methods And Materials: PubMed was systematically reviewed for publications reporting use of of hypofractionated radiation therapy in patients requiring post-mastectomy radiation.

Results: Standard fractionation, which is typically delivered over 5 to 7 weeks, is considered the standard of care in setting of post-mastectomy radiation therapy (PMRT). Modern data has helped to establish hypofractionated whole breast irradiation, which consists of a 3- to 4-week regimen, as a new standard of care for early-stage breast cancer. Hypofractionated whole breast irradiation has also laid the groundwork for the exploration of a hypofractionated approach in the setting of hypofractionated post-mastectomy radiation therapy.

Conclusions: While standard fractionation remains the most commonly utilized regimen for PMRT, recently published trials support the safety and efficacy of a hypofractionated approach. Ongoing trials are further investigating the use of hypofractionated PMRT.
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http://dx.doi.org/10.1016/j.adro.2020.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809517PMC
November 2020

Risk of symptomatic radiation necrosis in patients treated with stereotactic radiosurgery for brain metastases.

Neurocirugia (Astur : Engl Ed) 2020 Oct 17. Epub 2020 Oct 17.

Department of Radiation Oncology, Acibadem Mehmet Ali Aydinlar University, School of Medicine, Istanbul, Turkey.

Introductio: Stereotactic radiosurgery (SRS) is a treatment option in the initial management of patients with brain metastases. While its efficacy has been demonstrated in several prior studies, treatment-related complications, particularly symptomatic radiation necrosis (RN), remains as an obstacle for wider implementation of this treatment modality. We thus examined risk factors associated with the development of symptomatic RN in patients treated with SRS for brain metastases.

Patients And Methods: We performed a retrospective review of our institutional database to identify patients with brain metastases treated with SRS. Diagnosis of symptomatic RN was determined by appearance on serial MRIs, MR spectroscopy, requirement of therapy, and the development of new neurological complaints without evidence of disease progression.

Results: We identified 323 brain metastases treated with SRS in 170 patients from 2009 to 2018. Thirteen patients (4%) experienced symptomatic RN after treatment of 23 (7%) lesions. After SRS, the median time to symptomatic RN was 8.3 months. Patients with symptomatic RN had a larger mean target volume (p<0.0001), and thus larger V100% (p<0.0001), V50% (p<0.0001), V12Gy (p<0.0001), and V10Gy (p=0.0002), compared to the rest of the cohort. Single-fraction treatment (p=0.0025) and diabetes (p=0.019) were also significantly associated with symptomatic RN.

Conclusion: SRS is an effective treatment option for patients with brain metastases; however, a subset of patients may develop symptomatic RN. We found that patients with larger tumor size, larger plan V100%, V50%, V12Gy, or V10Gy, who received single-fraction SRS, or who had diabetes were all at higher risk of symptomatic RN.
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http://dx.doi.org/10.1016/j.neucir.2020.08.009DOI Listing
October 2020

Management of symptomatic radiation necrosis after stereotactic radiosurgery and clinical factors for treatment response.

Radiat Oncol J 2020 Sep 14;38(3):176-180. Epub 2020 Jul 14.

Institute of Health Sciences, Mehmet Ali Aydinlar Acibadem University, Istanbul, Turkey.

Purpose: Approximately 10% of patients who received brain stereotactic radiosurgery (SRS) develop symptomatic radiation necrosis (RN). We sought to determine the effectiveness of treatment options for symptomatic RN, based on patient-reported outcomes.

Materials And Methods: We conducted a retrospective review of 217 patients with 414 brain metastases treated with SRS from 2009 to 2018 at our institution. Symptomatic RN was determined by appearance on serial magnetic resonance images (MRIs), MR spectroscopy, requirement of therapy, and development of new neurological complaints without evidence of disease progression. Therapeutic interventions for symptomatic RN included corticosteroids, bevacizumab and/or surgical resection. Patient-reported therapeutic outcomes were graded as complete response (CR), partial response (PR), and no response.

Results: Twenty-six patients experienced symptomatic RN after treatment of 50 separate lesions. The mean prescription dose was 22 Gy (range, 15 to 30 Gy) in 1 to 5 fractions (median, 1 fraction). Of the 12 patients managed with corticosteroids, 6 patients (50%) reported CR and 4 patients (33%) PR. Of the 6 patients managed with bevacizumab, 3 patients (50%) reported CR and 1 patient (18%) PR. Of the 8 patients treated with surgical resection, all reported CR (100%). Other than surgical resection, age ≥54 years (median, 54 years; range, 35 to 81 years) was associated with CR (odds ratio = 8.40; 95% confidence interval, 1.27-15.39; p = 0.027).

Conclusion: Corticosteroids and bevacizumab are commonly utilized treatment modalities with excellent response rate. Our results suggest that patient's age is associated with response rate and could help guide treatment decisions for unresectable symptomatic RN.
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http://dx.doi.org/10.3857/roj.2020.00171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533401PMC
September 2020

Clinical management of uveal melanoma: a comprehensive review with a treatment algorithm.

Radiat Oncol J 2020 Sep 9;38(3):162-169. Epub 2020 Jul 9.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.

Uveal melanoma (UM), the most frequently occurring non-cutaneous melanoma and most common primary intraocular malignancy in adults, arises from the melanocytes of the choroid in approximately 95% of cases. Prompt diagnosis and treatment is vital as primary tumor size is one of the key factors associated with survival. Despite recent advances in management, more than half of the patients develop metastatic disease which portends poor survival. Currently, treatment options for UM include local resection, enucleation, plaque brachytherapy, and/or particle beam radiotherapy (RT). Enucleation was initially the standard of care in the management of UM, but a shift towards eye-preserving therapeutic choices such as RT and local resection has been noted in recent decades. Plaque brachytherapy, a form of localized RT, is the most popular option and is now the preferred treatment modality for UM. In this review we discuss the etiopathogenesis, clinical presentation and diagnosis of UM and place a special emphasis on therapeutic options. Furthermore, we review the current literature on UM management and propose a functional treatment algorithm for non-metastatic disease.
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http://dx.doi.org/10.3857/roj.2020.00318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533402PMC
September 2020

Adjuvant radiation therapy alone is associated with improved overall survival compared to hormonal therapy alone in older women with estrogen receptor positive early stage breast cancer.

Cancer Med 2020 11 17;9(22):8345-8354. Epub 2020 Sep 17.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.

Background: Breast conserving surgery (BCS) and adjuvant hormonal therapy (HT) without radiation therapy (RT) is an acceptable approach for older women with early stage, estrogen receptor (ER) positive breast cancer. Toxicity and compliance remain issues with HT. Adjuvant RT alone may have better compliance, but its efficacy in the absence of HT is unclear. We aim to assess patterns of adjuvant therapy and survival outcomes among older women with early stage, ER positive (ER+) breast cancer.

Methods: The National Cancer Data Base (NCDB) was used to identify 130,194 women age ≥65 years with invasive ER+, node negative breast cancer diagnosed between 2004 and 2015. All patients underwent BCS. Kaplan-Meier survival curves were used to examine overall survival (OS). The association between adjuvant therapy and OS was assessed in multivariable Cox proportional hazards regression models.

Results: Unadjusted 5/10-year OS rates were 90.0%/64.3% for HT and RT, 84.2%/54.9% for RT alone, 78.7%/44.5% for HT alone, and 71.6%/38.0% for no treatment; p<0.001 for all. Compared to HT alone, the 10-year multivariable hazard ratio (HR) for death for RT alone was 0.86 (95% CI 0.82-0.91). In propensity-matched patients who received RT alone or HT alone (n=21,326), RT alone had significantly better survival at 5 (HR : 0.84) and 10 (HR : 0.87) years.

Conclusions: Older women with early stage ER+ breast cancer who undergo BCS and receive both HT and RT have the best survival, while RT as single-modality therapy had higher rates of OS at 5 and 10 years compared to HT alone.
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http://dx.doi.org/10.1002/cam4.3443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666745PMC
November 2020

New horizons from novel therapies in malignant pleural mesothelioma.

Adv Respir Med 2020 ;88(4):343-351

Department of Radiation Oncology, Acıbadem Maslak Hospital, Istanbul, Turkey.

Malignant pleural mesothelioma (MPM) is a relatively rare, but highly lethal cancer of the pleural mesothelial cells. Its pathoge-nesis is integrally linked to asbestos exposure. In spite of recent developments providing a more detailed understanding of the pathogenesis, the outcomes continue to be poor. To date, trimodality therapy involving surgery coupled with chemotherapy and/or radiotherapy remains the standard of therapy. The development of resistance of the tumor cells to radiation and several che-motherapeutic agents poses even greater challenges in the management of this cancer. Ionizing radiation damages cancer cell DNA and aids in therapeutic response, but it also activates cell survival signaling pathways that helps the tumor cells to overcome radiation-induced cytotoxicity. A careful evaluation of the biology involved in mesothelioma with an emphasis on the workings of pro-survival signaling pathways might offer some guidance for treatment options. This review focuses on the existing treatment options for MPM, novel treatment approaches based on recent studies combining the use of inhibitors which target different pro-survival pathways, and radiotherapy to optimize treatment.
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http://dx.doi.org/10.5603/ARM.a2020.0103DOI Listing
June 2021

Utilization of Hypofractionated Whole-Breast Radiotherapy With Concurrent Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Therapy.

Clin Breast Cancer 2021 02 29;21(1):31-36. Epub 2020 Jun 29.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ. Electronic address:

Introduction: Hypofractionated radiotherapy (Hypo-RT) is now considered the standard of care for the majority of patients receiving whole-breast irradiation (WBI). However, there are few data on the use of Hypo-RT in human epidermal growth factor receptor 2 (HER2)-positive patients receiving concurrent anti-HER2 therapy. In this study, we sought to examine patterns of WBI in HER2-positive patients.

Patients And Methods: Using the National Cancer Data Base, we identified women with nonmetastatic HER2-positive breast cancer diagnosed between 2010 and 2015 who received WBI. The Hypo-RT group was defined as those receiving 21 or fewer fractions. All other patients were in the conventional radiotherapy (RT) group. Multivariate logistic regression was used to identify predictors of Hypo-RT utilization. Five-year overall survival was estimated by the Kaplan-Meier method.

Results: The study included 15,776 patients, of whom 17.7% received Hypo-RT. The rate of Hypo-RT utilization increased from 7.4% in 2010 to 29.3% in 2015 (P = .004). Predictors of Hypo-RT use included older age (≥60 vs. < 60 years), higher median income quartile, further distance from the treatment facility (>50 vs. ≤50 miles), treatment at an academic facility, and later year of diagnosis. Unadjusted 5-year overall survival rates were similar among patients who received Hypo-RT and conventional RT (93.9% vs. 95.2%, P = .26). After adjusting for patient, facility, and tumor variables, Hypo-RT was not significantly associated with survival.

Conclusion: Although Hypo-RT was not commonly delivered in patients with HER2-positive breast cancer, the utilization rate quadrupled over the study period. Multiple socioeconomic and clinical predictors of Hypo-RT receipt were identified. Adjuvant RT regimen was not significantly associated with overall survival.
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http://dx.doi.org/10.1016/j.clbc.2020.06.007DOI Listing
February 2021

Predictors of Whole Breast Radiation Therapy Completion in Early Stage Breast Cancer Following Lumpectomy.

Clin Breast Cancer 2020 12 27;20(6):469-479. Epub 2020 Jun 27.

Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN.

Background: Whole breast radiation therapy (RT) has become standard of care in early stage breast cancer treatment following lumpectomy. Predictors of RT completion have been sparsely studied, with no previous nationwide examination of the impact of fractionation regimen on completion rate.

Patients And Methods: The National Cancer Database identified patients with early stage breast cancer having undergone lumpectomy and RT from 2004 through 2015. Fraction size of 1.8-2.0 Gray (Gy) was defined as standard fractionation (SFRT); 2.66-2.70 Gy/fraction as hypofractionation (HFRT). RT completion was defined as receipt of at least 46 Gy for SFRT and 40 Gy for HFRT. A multivariable logistic regression model characterized RT completion predictors.

Results: A total of 100,734 patients were identified where fraction size could be reliably characterized as above; more than 87% completed RT. Of these, 66.8% received SFRT, yet HFRT use significantly increased over time (5.2% increase/year; P < .0001). RT completion rates were significantly greater following HFRT (99.3%) versus SFRT (79.7%); patients receiving SFRT had higher odds of not completing RT (odds ratio, 41.5; 95% confidence interval, 36.6-47.1; P < .0001). Multivariable analysis revealed that African-American and Caucasian patients treated with SFRT versus HFRT had 22 and 43 times the odds of not completing RT, respectively (P < .0001).

Conclusions: SFRT remained the majority of RT fractionation in the studied time period, although HFRT use has increased over time. Patients residing > 10 miles from a treatment facility or of African-American race had lower odds of completing RT, as were patients treated with SFRT versus HFRT. These findings suggest compliance advantages of HFRT for patients with early stage breast cancer having undergone lumpectomy.
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http://dx.doi.org/10.1016/j.clbc.2020.06.006DOI Listing
December 2020

Racial Disparities in Treatment Patterns and Survival Among Surgically Treated Malignant Pleural Mesothelioma Patients.

J Immigr Minor Health 2020 Dec;22(6):1163-1171

Institute for Translational Epidemiology and Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1133, New York, NY, 10029, USA.

Surgery may improve survival in malignant pleural mesothelioma (MPM) patients. We examined treatment and survival in black and white surgical MPM patients using the National Cancer Database (NCDB). Among patients with pleurectomy/decortication (PD) or extrapleural pneumonectomy (EPP), multivariable logistic regressions were used to evaluate racial differences in surgical extent, additional treatment, and 30-/90-day mortality. Multivariable and propensity matched models were used to assess differences in survival. We identified 2550 patients; 2462 white (96.5%), 88 black (3.5%). Black patients were significantly less likely to receive EPP (OR 0.36, 95% CI 0.17-0.78) and trended towards worse 30-/90-day mortality (OR 1.54, 95% CI 0.59-4.03; OR 1.59, 95% CI 0.80-3.17, respectively). There was no difference in survival (HR 0.94, 95% CI 0.71-1.25). Surgery conferred a survival benefit (HR 0.77, 95% CI 0.73-0.82), but it varied by race (HR[white] 0.76, 95% CI 0.72-0.81; HR[black] 0.93, 95% CI 0.67-1.29). With the limitation of a small proportion of surgically resected black MPM patients in this population-based analysis, black patients were noted to undergo less extensive surgery. Although there was an overall survival benefit noted with surgery, this was not consistent across races, despite trends towards worse short-term mortality in black patients.
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http://dx.doi.org/10.1007/s10903-020-01038-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686121PMC
December 2020

Evaluation of response to stereotactic radiosurgery in patients with radioresistant brain metastases.

Radiat Oncol J 2019 Dec 31;37(4):265-270. Epub 2019 Dec 31.

Department of Radiation Oncology, School of Medicine, Mehmet Ali Aydinlar Acibadem University, Istanbul, Turkey.

Purpose: Renal cell carcinoma (RCC) and melanoma have been considered 'radioresistant' due to the fact that they do not respond to conventionally fractionated radiation therapy. Stereotactic radiosurgery (SRS) provides high-dose radiation to a defined target volume and a limited number of studies have suggested the potential effectiveness of SRS in radioresistant histologies. We sought to determine the effectiveness of SRS for the treatment of patients with radioresistant brain metastases.

Materials And Methods: We performed a retrospective review of our institutional database to identify patients with RCC or melanoma brain metastases treated with SRS. Treatment response were determined in accordance with the Response Evaluation Criteria in Solid Tumors.

Results: We identified 53 radioresistant brain metastases (28% RCC and 72% melanoma) treated in 18 patients. The mean target volume and coverage was 6.2 ± 9.5 mL and 95.5% ± 2.9%, respectively. The mean prescription dose was 20 ± 4.9 Gy. Forty lesions (75%) demonstrated a complete/partial response and 13 lesions (24%) with progressive/stable disease. Smaller target volume (p < 0.001), larger SRS dose (p < 0.001), and coverage (p = 0.008) were found to be positive predictors of complete response to SRS.

Conclusion: SRS is an effective management option with up to 75% response rate for radioresistant brain metastases. Tumor volume and radiation dose are predictors of response and can be used to guide the decision-making for patients with radioresistant brain metastases.
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http://dx.doi.org/10.3857/roj.2019.00409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952719PMC
December 2019

The Impact of Formal Mentorship Programs on Mentorship Experience Among Radiation Oncology Residents From the Northeast.

Front Oncol 2019 4;9:1369. Epub 2019 Dec 4.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States.

Strong mentorship has been shown to improve mentee productivity, clinical skills, medical knowledge, and career preparation. We conducted a survey to evaluate resident satisfaction with mentorship within their radiation oncology residency programs. In January 2019, 126 radiation oncology residents training at programs in the northeastern United States were asked to anonymously complete the validated Munich Evaluation of Mentoring Questionnaire (MEMeQ). Results of residents with a formal mentoring program were compared to those without a formal program. Overall response rate was 42%( = 53). Participants were 25% post-graduate year two (PGY-2), 21% PGY-3, 26% PGY-4, and 28% PGY-5. Only 38% of residents reported participation in a formal mentoring program, while 62% had no formal program, and 13% reported having no mentor at all. Residents participating in a formal mentoring program reported strikingly higher rates of overall satisfaction with mentoring compared to those who were not (90% vs. 9%, < 0.001). Overall, 38% of residents were either satisfied/very satisfied with their mentoring experience, while 49% of residents were unsatisfied/very unsatisfied. Residents participating in a formal mentorship program are significantly more likely to be satisfied with their mentoring experience than those who are not. Our results suggest that radiation oncology residency programs should strongly consider implementing formal mentorship programs.
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http://dx.doi.org/10.3389/fonc.2019.01369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904328PMC
December 2019

The evolution of adjuvant radiation therapy for early-stage and locally advanced breast cancer.

Breast J 2020 01 19;26(1):59-64. Epub 2019 Dec 19.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.

Adjuvant radiation therapy is often delivered after breast cancer surgery, both in the post-lumpectomy and post-mastectomy settings. Standard fractionation whole breast irradiation (SF-WBI), which is typically delivered over 5-7 weeks, was previously considered the standard of care. More recent data has helped to establish hypofractionated whole breast irradiation (HF-WBI), which consists of a 3-4 week regimen, as a new standard of care. This article provides an overview of the major randomized trials that support the routine use of HF-WBI for the majority of patients undergoing breast-conserving surgery for early-stage breast cancer. Newer data on the use of a hypofractionated approach in the post-mastectomy setting, as well as ongoing randomized trials addressing this topic, are also discussed.
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http://dx.doi.org/10.1111/tbj.13715DOI Listing
January 2020

Current treatment strategies in malignant pleural mesothelioma with a treatment algorithm.

Adv Respir Med 2019 ;87(5):289-297

Department of Radiation Oncology, Mehmet Ali Aydınlar Acıbadem University, School of Medicine, Istanbul, Turkey.

Malignant pleural mesothelioma (MPM) is arare disease with apoor prognosis. The main therapeutic options for MPM include surgery, chemotherapy, and radiation therapy (RT). Although multimodality therapy has been reported to improve survival, not every medically operable patient is able to undergo all recommended therapy. With improvements in surgical techniques and systemic therapies, as well as advancements in RT, there has been apotential new paradigm in the management of this disease. In this review, we discuss the current literature on MPM management and propose afunctional treatment algorithm.
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http://dx.doi.org/10.5603/ARM.2019.0051DOI Listing
April 2020

Acute Cardiotoxicity With Concurrent Trastuzumab and Hypofractionated Radiation Therapy in Breast Cancer Patients.

Front Oncol 2019 1;9:970. Epub 2019 Oct 1.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, United States.

Radiotherapy for patients with non-metastatic human epidermal growth factor receptor 2 (HER2) positive breast cancer is commonly administered concurrently with adjuvant trastuzumab. However, there is limited data on the use of concurrent trastuzumab and hypofractionated radiotherapy (Hypo-RT), which is now standard of care for the majority of women receiving whole breast irradiation. In this study, we compared acute cardiotoxicity rates in HER2-positive breast cancer patients treated with concurrent trastuzumab and Hypo-RT or conventionally fractionated radiotherapy (Conv-RT). We performed a review of our institutional database to identify HER2-positive breast cancer patients treated with trastuzumab and Hypo-RT or Conv-RT from 2005 to 2018 who underwent serial cardiac Left Ventricular Ejection Fraction (LVEF) evaluation. Decrease in LVEF was assessed by either echocardiography (ECHO) or multiple gated acquisition (MUGA) scan performed at baseline and every 3 months during trastuzumab therapy. Significant LVEF decline was defined as an absolute decrease in LVEF of ≥10% below the lower limit of normal or ≥16% from baseline value. We identified 41 patients treated with Hypo-RT and 100 patients treated with Conv-RT. Median follow-up was 32 months (range, 13-90 months). Baseline median LVEF was 62% (range, 50-81%) in Hypo-RT group and 64% (range, 51-76%) in Conv-RT group ( = 0.893). Final median LVEF was 60% (range, 50-75%) in both groups. Three patients (7%) in Hypo-RT and five (5%) in Conv-RT group developed significant asymptomatic LVEF decline ( = 0.203). There was no significant difference in mean heart dose in patients who developed significant asymptomatic LVEF decline vs. those who did not in Hypo-RT ( = 0.427) and Conv-RT ( = 0.354) groups. No symptomatic congestive heart failure was reported in either group. The rate of asymptomatic LVEF decline in patients receiving concurrent trastuzumab and Hypo-RT was low (7%) and was similar to the rate observed in patients receiving Conv-RT. Longer follow-up is warranted to assess late cardiotoxicity.
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http://dx.doi.org/10.3389/fonc.2019.00970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779787PMC
October 2019

Mastectomy First, Keeping Chemotherapy and Radiation in Reserve.

Int J Radiat Oncol Biol Phys 2019 09;105(1):20

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.

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http://dx.doi.org/10.1016/j.ijrobp.2019.05.019DOI Listing
September 2019

5-Year Results of a Prospective Phase 2 Trial Evaluating 3-Week Hypofractionated Whole Breast Radiation Therapy Inclusive of a Sequential Boost.

Int J Radiat Oncol Biol Phys 2019 10 5;105(2):267-274. Epub 2019 Jun 5.

Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey. Electronic address:

Purpose: To report 5-year outcomes of a phase 2 trial of hypofractionated whole breast irradiation (HF-WBI) completed in 3 weeks, inclusive of a sequential boost.

Methods And Materials: Women with stage 0-IIIA breast cancer (ductal carcinoma in situ through T2N2a) were enrolled on a prospective, phase 2 trial of accelerated HF-WBI. We delivered a whole breast dose of 36.63 Gy in 11 fractions of 3.33 Gy, with an equivalent dose to the regional nodes when indicated, followed by a tumor bed boost of 13.32 Gy in 4 fractions of 3.33 Gy over a total of 15 treatment days. The primary endpoint was locoregional control; secondary endpoints included acute/late toxicity and physician-assessed and patient-reported breast cosmesis.

Results: Between 2009 and 2017, we enrolled 150 patients, of whom 146 received the protocol treatment. Median age was 54 years (range, 33-82) and median follow-up was 62 months. Patients with higher-risk disease comprised 59% of the cohort, including features such as young age (33% ≤50 years), positive nodes (13%), triple-negative disease (11%), and treatment with regional nodal irradiation (11%) and/or neoadjuvant/adjuvant chemotherapy (36%). Five-year estimated locoregional and distant control were 97.7% (95% confidence interval [CI], 93.0%-99.3%) and 97.9% (95% CI, 93.6%-99.3%), respectively. Five-year breast cancer-specific and overall survival were 99.2% (95% CI, 94.6%-99.9%) and 97.3% (95% CI, 91.9%-99.1%), respectively. Acute/late grade 2 and 3 toxicities were observed in 30%/10% and 1%/3% of patients, respectively. There were no grade 4 or 5 toxicities. Physicians assessed breast cosmesis as good or excellent in 95% of patients; 85% of patients self-reported slight to no difference between the treated and untreated breast.

Conclusions: Our phase 2 trial offers one of the shortest courses of HF-WBI; at 5 years of follow-up there continues to be excellent locoregional control and low toxicity with favorable cosmetic outcomes in a heterogeneous cohort of patients.
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http://dx.doi.org/10.1016/j.ijrobp.2019.05.063DOI Listing
October 2019

Setup uncertainties and the optimal imaging schedule in the prone position whole breast radiotherapy.

Radiat Oncol 2019 May 9;14(1):76. Epub 2019 May 9.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA.

Background: To investigate the setup uncertainties and to establish an optimal imaging schedule for the prone-positioned whole breast radiotherapy.

Methods: Twenty prone-positioned breast patients treated with tangential fields from 2015 to 2017 were retrospectively enrolled in this study. The prescription dose for the whole breast treatment was 266 cGy × 16 for all of the patients and the treatments were delivered with the SSD setup technique. At every fraction of treatment, patient was firstly set up based on the body localization tattoos. MV portal imaging was then taken to confirm the setup; if discrepancy (> 3 mm) was found between the portal images and corresponding plan images, the patient positioning was adjusted accordingly with couch movement. Based on the information acquired from the daily tattoo and portal imaging setup, three sets of data, named as weekly imaging guidance (WIG), no daily imaging guidance (NIG), and initial 3 days then weekly imaging guidance (3 + WIG) were sampled, constructed, and analyzed in reference to the benchmark of the daily imaging guidance (DIG). We compared the setup uncertainties, target coverage (D, D), V of the ipsilateral lung, the mean dose of heart, the mean and max dose of the left-anterior-descending coronary artery (LAD) among the 4 imaging guidance (IG) schedules.

Results: Relative to the daily imaging guidance (IG) benchmark, the NIG schedule led to the largest residual setup uncertainties; the uncertainties were similar for the WIG and 3 + WIG schedules. Little variations were observed for D of the target among NIG, DIG and WIG. The target D also exhibited little changes among all the IG schedules. While V of the ipsilateral lung changed very little among all 4 schedules, the percent change of the mean heart dose was more pronounced; but its absolute values were still within the tolerance. However, for the left-sided breast patients, the LAD dose could be significantly impacted by the imaging schedules and could potentially exceed its tolerance criteria in some patients if NIG, WIG and 3 + WIG schedules were used.

Conclusions: For left-side whole breast treatment in the prone position using the SSD treatment technique, the daily imaging guidance can ensure dosimetric coverage of the target as well as preventing critical organs, especially LAD, from receiving unacceptable levels of dose. For right-sided whole breast treatment in the prone position, the weekly imaging setup guidance appears to be the optimal choice.
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http://dx.doi.org/10.1186/s13014-019-1282-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509791PMC
May 2019

Prognostic factors of survival in patients with malignant pleural mesothelioma: an analysis of the National Cancer Database.

Carcinogenesis 2019 06;40(4):529-536

Institute for Translational Epidemiology and Department of Population Health Science and Policy.

Malignant pleural mesothelioma (MPM) is a rare disease with a very poor prognosis. Previous studies have indicated that women experience longer survival compared with men. We analyzed 16 267 eligible patients (21.3% females) in the National Cancer Database to evaluate which clinical factors are independently predictive of longer survival. After adjusting for all covariates, survival was significantly better in females compared with males [HRadj: 0.81, 95% confidence interval (CI): 0.77-0.85]. Other factors significantly associated with better survival were younger age at diagnosis, higher income, lower comorbidity score, epithelial histology, earlier stage and receipt of surgical or medical treatment. After propensity matching, survival was significantly better for females compared with males [hazard ratio (HR): 0.86, 95% CI: 0.80-0.94]. After propensity matching within the epithelial group, survival remained significantly better for females compared with males (HR: 0.85, 95% CI: 0.74-0.97). This study adds information to the known significant gender survival difference in MPM by disentangling the effect of gender from the effect of age and histology, two known independent factors affecting survival. Circulating estrogen, present in young but not older women, and higher expression of the estrogen receptor beta in epithelial mesothelioma have been suggested to play a role in gender survival differences. These findings may lead to exploring new therapeutic options, such as targeting estrogen receptor beta, and considering hormonal therapy including estrogens for patients with otherwise limited prognosis.
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http://dx.doi.org/10.1093/carcin/bgz004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556702PMC
June 2019

Hypofractionated whole breast irradiation is cost-effective-but is that enough to change practice?

Transl Cancer Res 2018 Apr;7(Suppl 4):S469-S472

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey.

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http://dx.doi.org/10.21037/tcr.2018.03.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097715PMC
April 2018

Immortal Time Bias in Observational Studies of Time-to-Event Outcomes: Assessing Effects of Postmastectomy Radiation Therapy Using the National Cancer Database.

Cancer Control 2018 Jan-Dec;25(1):1073274818789355

1 Department of Population Health Science and Policy, Institute for Healthcare Delivery Science, Tisch Cancer Institute (TCI), Icahn School of Medicine at Mount Sinai, New York, NY, USA.

The objectives of this study are to illustrate the effects of immortal time bias (ITB) using an oncology outcomes database and quantify through simulations the magnitude and direction of ITB when different analytical techniques are used. A cohort of 11 626 women who received neoadjuvant chemotherapy and underwent mastectomy with pathologically positive lymph nodes were accrued from the National Cancer Database (2004-2008). Standard Cox regression, time-dependent (TD), and landmark models were used to compare overall survival in patients who did or did not receive postmastectomy radiation therapy (PMRT). Simulation studies showing ways to reduce the effect of ITB indicate that TD exposures should be included as variables in hazard-based analyses. Standard Cox regression models comparing overall survival in patients who did and did not receive PMRT showed a significant treatment effect (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.88-0.99). Time-dependent and landmark methods estimated no treatment effect with HR: 0.97, 95% CI: 0.92 to 1.03 and HR: 0.98, 95% CI, 0.92 to 1.04, respectively. In our simulation studies, the standard Cox regression model significantly overestimated treatment effects when no effect was present. Estimates of TD models were closest to the true treatment effect. Landmark model results were highly dependent on landmark timing. Appropriate statistical approaches that account for ITB are critical to minimize bias when examining relationships between receipt of PMRT and survival.
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http://dx.doi.org/10.1177/1073274818789355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053873PMC
December 2018

Hypofractionated radiation treatment in the management of breast cancer.

Expert Rev Anticancer Ther 2018 08 26;18(8):793-803. Epub 2018 Jun 26.

a Department of Radiation Oncology , Rutgers Cancer Institute of New Jersey , New Brunswick , NJ , USA.

Introduction: The standard treatment for early-stage breast cancer is breast conservation therapy, consisting of breast conserving surgery followed by adjuvant radiation treatment (RT). Conventionally-fractionated whole breast irradiation (CF-WBI) has been the standard RT regimen, but recently shorter courses of hypofractionated whole breast irradiation (HF-WBI) have been advocated for patient convenience and reduction in healthcare costs and resources. Areas covered: This review covers the major randomized European and Canadian trials comparing HF-WBI to CF-WBI with long-term follow-up, as well as additional recently closed randomized trials that further seek to define the applicability of HF-WBI in clinical practice. Randomized data is summarized in terms of clinical utility and for a variety of clinical applications. Recently published consensus guidelines and practical implementation of HF-WBI including its broader effect on the healthcare system are reviewed. Finally, an assessment of the emerging evidence in support of hypofractionation for locally advanced disease is presented. Expert commentary: HF-WBI has replaced CF-WBI as the accepted standard of care in most women with early-stage breast cancer who do not require regional nodal irradiation. Early data supports the continued study of hypofractionation in the locally advanced setting, however broad adoption awaits longer follow-up and additional data from ongoing clinical trials.
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http://dx.doi.org/10.1080/14737140.2018.1489245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312641PMC
August 2018

Is There a Role for Postmastectomy Radiation (PMRT) in Patients with T1-2 Tumors and One to Three Positive Lymph Nodes Treated in the Modern Era?

Ann Surg Oncol 2018 Jul 26;25(7):1788-1790. Epub 2018 Apr 26.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson and New Jersey Medical School, Rutgers, The State University of New Jersey, 195 Little Albany St., New Brunswick, NJ, 08903, USA.

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http://dx.doi.org/10.1245/s10434-018-6493-7DOI Listing
July 2018

Postmastectomy Radiation in Breast Cancer Patients With Pathologically Positive Lymph Nodes After Neoadjuvant Chemotherapy: Usage Rates and Survival Trends.

Int J Radiat Oncol Biol Phys 2017 11 28;99(3):549-559. Epub 2017 Jun 28.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address:

Purpose: To analyze postmastectomy radiation therapy (PMRT) usage and its association with overall survival (OS) in breast cancer patients with pathologically positive lymph nodes after neoadjuvant chemotherapy (NAC).

Methods And Materials: Using the National Cancer Database, we identified women with nonmetastatic breast cancer diagnosed from 2004 to 2013 who had received NAC and undergone mastectomy with macroscopic pathologically positive lymph nodes. Joinpoint regression models were used to assess temporal trends in annual PMRT usage. Multivariable regression models were used to identify factors associated with PMRT use. A time-dependent Cox model was used to evaluate the predictors of mortality.

Results: The study included 29,270 patients, of whom 62.5% received PMRT. PMRT was markedly underused among all nodal subgroups, in particular, among ypN2 (68.4%) and ypN3 (67.0%) patients. Hispanic patients and those with Medicaid or Medicare insurance were less likely to receive PMRT than were non-Hispanics and patients with other insurance carriers. The adjusted 5-year OS rates were similar in ypN1 and ypN2 patients with or without PMRT but were significantly greater in ypN3 patients receiving PMRT (66% vs 63%; P=.042). On multivariable analysis, PMRT was associated with improved survival only among ypN3 patients after adjusting for patient, facility, and tumor variables (multivariable hazard ratio 0.85; 95% confidence interval 0.74-0.97).

Conclusions: A considerable portion of breast cancer patients with advanced residual nodal disease after NAC did not receive appropriate adjuvant radiation. We also found socioeconomic disparities in national PMRT practice patterns. Patients with ypN3 disease might derive a survival benefit from PMRT.
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http://dx.doi.org/10.1016/j.ijrobp.2017.06.2458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004824PMC
November 2017

The role of postmastectomy radiotherapy in patients with stage II breast cancer.

Cancer 2018 02 12;124(3):450-452. Epub 2017 Dec 12.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

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http://dx.doi.org/10.1002/cncr.31130DOI Listing
February 2018

Alternatives to Standard Fractionation Radiation Therapy After Lumpectomy: Hypofractionated Whole-Breast Irradiation and Accelerated Partial-Breast Irradiation.

Surg Oncol Clin N Am 2018 01;27(1):181-194

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA. Electronic address:

Adjuvant whole-breast irradiation (WBI) after lumpectomy has been an established standard of care for decades. Standard-fractionation WBI delivered over 5 to 7 weeks can achieve durable tumor control with low toxicity but can be inconvenient for patients and cost ineffective. Hypofractionated WBI can be completed in 3 to 4 weeks and, based on long-term randomized data, is the preferred standard of care in select patients. Accelerated partial-breast irradiation can be delivered using even shorter treatment regimens. Although the available data on accelerated partial-breast irradiation is more limited, early results suggest it is an effective alternative to WBI in select patients.
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http://dx.doi.org/10.1016/j.soc.2017.07.006DOI Listing
January 2018

Trends and variations in postmastectomy radiation therapy for breast cancer in patients with 1 to 3 positive lymph nodes: A National Cancer Data Base analysis.

Cancer 2018 02 7;124(3):482-490. Epub 2017 Nov 7.

Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California.

Background: High-level evidence is lacking to guide treatment decisions about postmastectomy radiation therapy (PMRT) in patients who have breast cancer with 1 to 3 positive lymph nodes who receive contemporary systemic therapies, leading to potential variations in PMRT delivery. The objective of this study was to examine nationwide trends in PMRT use in this group.

Methods: The National Cancer Data Base (NCDB) was used to identify 93,372 women who had T1-T2N1 breast cancer diagnosed between 2003 and 2012. Patients who received neoadjuvant chemotherapy or radiation therapy (RT) and those who had bilateral breast cancers were excluded. Time trends were evaluated using the Cochrane-Armitage test and correlated the receipt of PMRT with various patient demographic, facility, clinicopathologic, and treatment variables using multivariable logistic regression. A second analysis was performed for patients who were diagnosed during 2010 and included radiation oncologist density as an additional covariate. P values < .0001 were considered statistically significant.

Results: Overall, 22.5% of the study population received PMRT, representing an increase from 19.1% in 2003 to 30.3% in 2012. Factors associated with greater PMRT use included younger age, lower Charlson-Deyo comorbidity scores, shorter distance to the treating facility, treatment at a comprehensive cancer program, facility location in the New England Census division, and higher density of radiation oncologists. Increased PMRT use was associated with later year of diagnosis, receipt of chemotherapy, receipt of hormone therapy, higher grade disease, larger tumor size, greater numbers of positive lymph nodes, positive margins, and absence of immediate breast reconstruction (all P < .0001).

Conclusions: The receipt of PMRT by patients with breast cancer who have 1 to 3 positive lymph nodes has increased over time, with wide variability in practice patterns in the United States. Cancer 2018;124:482-90. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.31080DOI Listing
February 2018

Predictors of Positive Margins After Definitive Resection for Gastric Adenocarcinoma and Impact of Adjuvant Therapies.

Int J Radiat Oncol Biol Phys 2017 08 31;98(5):1106-1115. Epub 2017 Mar 31.

Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address:

Purpose: Positive margins after definitive resection in gastric adenocarcinoma are associated with inferior outcomes. There are few randomized data to guide optimal adjuvant therapy after positive margins.

Methods: Using the National Cancer Database, we identified 24,619 nonmetastatic gastric adenocarcinoma patients who received diagnoses from 2004 to 2013 and underwent definitive resection to analyze for predictors of positive surgical margins. Of these patients, 2754 had positive margins (11.2%). Multivariate prevalence ratios were used to determine predictors. Survival analyses were performed with a Cox proportional hazards model by use of several methods of propensity score analysis.

Results: Increasing T and/or N category, high grade, and lymphovascular invasion predicted higher rates of positive margins. Asian race, treatment at an academic center, and robotic surgery predicted lower rates of positive margins. Among positive-margin patients with adjuvant treatment (n=1021), with a median follow-up period of 55 months, age, comorbidity score, nodal disease, and T4 disease predicted for worse overall survival (OS). Treatment at an academic center was associated with improved OS. Use of adjuvant concurrent chemoradiation therapy (CCRT) was associated with higher OS compared with chemotherapy alone after positive margins (hazard ratio, 0.72; 95% confidence interval, 0.58-0.91; P=.005) after propensity matching adjusting for predictors of OS. The 2-year and 3-year OS for positive-margin patients with chemotherapy alone was 43% and 29%, respectively, compared with 53% and 38%, respectively, with adjuvant CCRT. The log-rank P value for survival was .0015.

Conclusions: Stage, race, treatment center, and surgery approach predict for margin status after resection. Adjuvant CCRT after positive margins is associated with improved OS after accounting for available clinical variables.
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http://dx.doi.org/10.1016/j.ijrobp.2017.03.041DOI Listing
August 2017

Intracoronary brachytherapy for in-stent restenosis of drug-eluting stents.

Adv Radiat Oncol 2016 Jan-Mar;1(1):4-9. Epub 2015 Dec 19.

Department of Radiation Oncology, Mount Sinai Hospital, New York, New York.

Purpose: Given the limited salvage options for in-stent restenosis (ISR) of drug-eluting stents (DES), our high-volume cardiac catheterization laboratory has been performing intracoronary brachytherapy (ICBT) in patients with recurrent ISR of DES. This study analyzes their baseline characteristics and assesses the safety/toxicity of ICBT in this high-risk population.

Methods And Materials: A retrospective analysis of patients treated with ICBT between September 2012 and December 2014 was performed. Patients with ISR twice in a single location were eligible. Procedural complications included vessel dissection, perforation, tamponade, slow/absent blood flow, and vessel closure. Postprocedural events included myocardial infarction, coronary artery bypass graft, congestive heart failure, stroke, bleeding, thrombosis, embolism, dissection, dialysis, or death occurring within 72 hours. A control group of patients with 2 episodes of ISR at 1 location who underwent percutaneous coronary intervention without ICBT was identified. Unpaired tests and χ tests were used to compare the groups.

Results: There were 134 (78%) patients in the ICBT group with 141 treated lesions and 37 (22%) patients in the control group. There was a high prevalence of hyperlipidemia (>95%), hypertension (>95%), and diabetes (>50%) in both groups. The groups were well-balanced with respect to age, sex, and pre-existing medical conditions, with the exception of previous coronary artery bypass graft being more common the ICBT group. Procedural complication rates were low in the control and ICBT groups (0% vs 4.5%, = .190). Postprocedural event rates were low (<5%) in both groups. Readmission rate at 30 days was 3.7% in the ICBT group and 5.4% in the control group ( = .649).

Conclusions: This is the largest recent known series looking at ICBT for recurrent ISR of DES. ICBT is a safe treatment option with similarly low rates (<5%) of procedural and postprocedural complications compared with percutaneous coronary intervention alone. This study establishes the safety of ICBT in a high-risk patient cohort.
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http://dx.doi.org/10.1016/j.adro.2015.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506705PMC
December 2015

Bilateral implant reconstruction does not affect the quality of postmastectomy radiation therapy.

Med Dosim 2014 14;39(1):18-22. Epub 2013 Nov 14.

Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY.

To determine if the presence of bilateral implants, in addition to other anatomic and treatment-related variables, affects coverage of the target volume and dose to the heart and lung in patients receiving postmastectomy radiation therapy (PMRT). A total of 197 consecutive women with breast cancer underwent mastectomy and immediate tissue expander (TE) placement, with or without exchange for a permanent implant (PI) before radiation therapy at our center. PMRT was delivered with 2 tangential beams + supraclavicular lymph node field (50Gy). Patients were grouped by implant number: 51% unilateral (100) and 49% bilateral (97). The planning target volume (PTV) (defined as implant + chest wall + nodes), heart, and ipsilateral lung were contoured and the following parameters were abstracted from dose-volume histogram (DVH) data: PTV D95% > 98%, Lung V20Gy > 30%, and Heart V25Gy > 5%. Univariate (UVA) and multivariate analyses (MVA) were performed to determine the association of variables with these parameters. The 2 groups were well balanced for implant type and volume, internal mammary node (IMN) treatment, and laterality. In the entire cohort, 90% had PTV D95% > 98%, indicating excellent coverage of the chest wall. Of the patients, 27% had high lung doses (V20Gy > 30%) and 16% had high heart doses (V25Gy > 5%). No significant factors were associated with suboptimal PTV coverage. On MVA, IMN treatment was found to be highly associated with high lung and heart doses (both p < 0.0001), but implant number was not (p = 0.54). In patients with bilateral implants, IMN treatment was the only predictor of dose to the contralateral implant (p = 0.001). In conclusion, bilateral implants do not compromise coverage of the target volume or increase lung and heart dose in patients receiving PMRT. The most important predictor of high lung and heart doses in patients with implant-based reconstruction, whether unilateral or bilateral, is treatment of the IMNs. Refinement of radiation techniques in reconstructed patients who require comprehensive nodal irradiation is warranted.
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http://dx.doi.org/10.1016/j.meddos.2013.08.008DOI Listing
September 2014

Long-term regional control in the observed neck following definitive chemoradiation for node-positive oropharyngeal squamous cell cancer.

Int J Cancer 2013 Sep 29;133(5):1214-21. Epub 2013 Mar 29.

Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Traditionally, patients treated with chemoradiotherapy for node-positive oropharyngeal squamous cell carcinoma (N+ OPSCC) have undergone a planned neck dissection (ND) after treatment. Recently, negative post-treatment positron-emission tomography (PET)/computed tomography (CT) imaging has been found to have a high negative predictive value for the presence of residual disease in the neck. Here, we present the first comprehensive analysis of a large, uniform cohort of N+ OPSCC patients achieving a PET/CT-based complete response (CR) after chemoradiotherapy, and undergoing observation, rather than ND. From 2002 to 2009, 302 patients with N+ OPSCC treated with 70 Gy intensity-modulated radiation therapy and concurrent chemotherapy underwent post-treatment clinical assessment including PET/CT. CR was defined as no evidence of disease on clinical examination and post-treatment PET/CT. ND was reserved for patients with
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http://dx.doi.org/10.1002/ijc.28120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570243PMC
September 2013
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