Randomized Phase 2 Placebo-Controlled Trial of Nintedanib for the Treatment of Radiation Pneumonitis.

PURPOSE: Radiation pneumonitis (RP) is the most common dose-limiting toxicity for thoracic radiation therapy. Nintedanib is used for the treatment of idiopathic pulmonary fibrosis, which shares pathophysiological pathways with the subacute phase of RP. Our goal was to investigate the efficacy and safety of nintedanib added to a prednisone taper compared with a prednisone taper alone in reducing pulmonary exacerbations in patients with grade 2 or higher (G2+) RP. METHODS AND MATERIALS: In this phase 2, randomized, double-blinded, placebo-controlled trial, patients with newly diagnosed G2+ RP were randomized 1:1 to nintedanib or placebo in addition to a standard 8-week prednisone taper. The primary endpoint was freedom from pulmonary exacerbations at 1 year. Secondary endpoints included patient-reported outcomes and pulmonary function tests. Kaplan-Meier analysis was used to estimate the probability of freedom from pulmonary exacerbations. The study was closed early due to slow accrual. RESULTS: Thirty-four patients were enrolled between October 2015 and February 2020. Of 30 evaluable patients, 18 were randomized to the experimental Arm A (nintedanib + prednisone taper) and 12 to the control Arm B (placebo + prednisone taper). Freedom from exacerbation at 1 year was 72% (confidence interval, 54%-96%) in Arm A and 40% (confidence interval, 20%-82%) in Arm B (1-sided, P = .037). In Arm A, there were 16 G2+ adverse events possibly or probably related to treatment compared with 5 in the placebo arm. There were 3 deaths during the study period in Arm A due to cardiac failure, progressive respiratory failure, and pulmonary embolism. CONCLUSIONS: There was an improvement in pulmonary exacerbations by the addition of nintedanib to a prednisone taper. Further investigation is warranted for the use of nintedanib for the treatment of RP.

Dramatic Response to Concurrent Anti-PD-1 Therapy and Radiation in Resistant Tumors with Sarcomatoid Differentiation.

A substantial fraction of patients demonstrate resistance to immune checkpoint inhibitors, which limits their use. Use of radiation concurrently with checkpoint inhibitors has been shown to boost immune responsiveness, resulting in significant tumor regression in patients with metastatic melanoma. However, it is unknown whether radiation could play a role in reversing the inherent resistance to checkpoint inhibition in certain tumor types. Most trials testing this concurrent approach exclude such modestly responsive tumors and pursue checkpoint inhibition using anti-cytotoxic T-lymphocyte-associated protein 4 antibody (anti-CTLA-4, ipilimumab). The efficacy of anti-programmed-death-1 (anti-PD-1) therapy when used concurrently with radiation is less known but remains an attractive option due to less autoimmune toxicity compared with CTLA-4 inhibition. In this first reported experience, we have safely and effectively combined anti-PD-1 therapy (nivolumab) concurrently with radiation to treat two patients with relapsed sarcomatoid renal carcinoma and heavily pretreated pleomorphic sarcoma. Both patients experienced a dramatic response that was durable.

Effectiveness of a thoracic multidisciplinary clinic in the treatment of stage III non-small-cell lung cancer.

INTRODUCTION: The Institute of Medicine, the American Society of Clinical Oncology, and the European Society of Medical Oncology promote a multidisciplinary approach for the treatment of cancer. Stage III non-small-cell lung cancer (NSCLC) represents a heterogeneous group of diseases necessitating coordination of care among medical, radiation, and surgical oncology. The optimal care of stage III NSCLC underscores the need for a multidisciplinary approach. METHODS: From tumor registry data, we identified all cases of stage III NSCLC seen at Lehigh Valley Health Network between March 2010 and March 2013. The care received by patients when seen in the thoracic multidisciplinary clinic (MDC) was compared with the care received when not seen in the thoracic MDC. RESULTS: All patients seen in the MDC, compared to <50% of patients seen outside the MDC, were evaluated by more than one physician prior to beginning the treatment. Time to initiate treatment was shorter in MDC patients than in non-MDC patients. Patients seen in the MDC had a greater concordance with clinical pathways. A greater percentage of patients seen in the thoracic MDC had pathologic staging of their mediastinum. Patients seen in the MDC were more likely to receive all of their care at Lehigh Valley Health Network. CONCLUSION: Multidisciplinary care is essential in the treatment of patients with stage III NSCLC. Greater utilization of MDCs for this complex group of patients will result in more efficient coordination of care, pretreatment evaluation, and therapy, which in turn should translate to improve patients' outcomes.

Dysplasia at the margin? Investigating the case for subsequent therapy in 'low-risk' squamous cell carcinoma of the oral tongue.

PURPOSE: This is a retrospective analysis of the impact of moderate dysplasia at the resection margin for early stage cancer of the oral tongue. MATERIALS AND METHODS: Patients with T1-2N0 oral tongue cancer treated with surgery alone at Fox Chase Cancer Center (FCCC) from 1990 to 2010 were reviewed. Tumor and margin characteristics were abstracted from the pathology report. Overall survival (OS), disease-free survival (DFS) and local control (LC) were calculated using the Kaplan Meier method. Predictors of LC, OS and DFS were analyzed. RESULTS: 126 Patients met the inclusion criteria. Dysplasia was present at the final margin in 36% of the cases (severe: 9%, moderate: 15%, mild: 12%). Median follow-up was 52 months. 3 and 5-year actuarial LC for the entire cohort was 77% and 73%, respectively. Actuarial 5-year LC and DFS were significantly worse for patients with moderate or severe dysplasia at the margin vs. none or mild dysplasia at the margin (49% vs 82%, p=0.005 and 49% vs 80%, p=0.008, respectively); 3-year comparisons were not significant. When analyzed separately, the detrimental local effect of moderate dysplasia at the margin persisted (p=0.02) and the effect of severe dysplasia at the margin was approaching significance (p=0.1). Mild dysplasia at the margin did not significantly impair LC or DFS. Multivariate analysis demonstrated worse LC (HR: 2.99, p=0.006) and DFS (HR: 2.84, p=0.008) associated with severe or moderate dysplasia at the margin. CONCLUSIONS: Both severe and moderate dysplasia at the margin appear to be correlated with inferior LC and DFS. Additional therapy may be justified, despite added morbidity.

Effect of Bra Use during Radiotherapy for Large-Breasted Women: Acute Toxicity and Treated Heart and Lung Volumes.

PURPOSE: Large breast size presents special problems during radiation simulation, planning and patient treatment, including increased skin toxicity, in women undergoing breast-conserving surgery and radiotherapy (BCT). We report our experience using a bra during radiation in large-breasted women and its effect on acute toxicity and heart and lung dosimetry. MATERIALS AND METHODS: From 2001 to 2006, 246 consecutive large-breasted women (bra size ≥ 38 and/or ≥ D cup) were treated with BCT using either 3D conformal (3D-CRT) or Intensity Modulated Radiation (IMRT). In 58 cases, at the physicians' discretion, a custom-fit bra was used during simulation and treatment. Endpoints were acute radiation dermatitis, and dosimetric comparison of heart and lung volumes in a subgroup of 12 left-sided breast cancer patients planned with and without a bra. RESULTS: The majority of acute skin toxicities were grade 2 and were experienced by 90% of patients in a bra compared to 70% of patients not in a bra (p=0.003). On multivariate analysis significant predictors of grade 2/3 skin toxicity included 3D-CRT instead of IMRT (OR=3.9, 95% CI:1.8-8.5) and the use of a bra (OR=5.5, 95% CI:1.6-18.8). For left-sided patients, use of a bra was associated with a volume of heart in the treatment fields decreased by 63.4% (p=0.002), a volume of left lung decreased by 18.5% (p=0.25), and chest wall separation decreased by a mean of 1 cm (p=0.03). CONCLUSIONS: The use of a bra to augment breast shape and position in large-breasted women is an alternative to prone positioning and associated with reduced chest wall separation and reduced heart volume within the treatment field.

Effect of bra use during radiation therapy for large-breasted women: Acute toxicity and treated heart and lung volumes.

PURPOSE: Large breast size presents special problems during radiation simulation, planning, and patient treatment, including increased skin toxicity, in women undergoing breast-conserving surgery and radiation therapy (BCT). We report our experience using a bra during radiation in large-breasted women and its effect on acute toxicity and heart and lung dosimetry. METHODS AND MATERIALS: From 2001 to 2006, 246 consecutive large-breasted women (bra size ≥38 or ≥D cup) were treated with BCT using either 3-dimensional conformal radiation therapy (3DCRT) or intensity modulated radiation therapy (IMRT). In 58 cases, at the physicians' discretion, a custom-fit bra was used during simulation and treatment. Endpoints were acute radiation dermatitis and dosimetric comparison of heart and lung volumes in a subgroup of 12 left-sided breast cancer patients planned with and without a bra. RESULTS: The majority of acute skin toxicities were grade 2 and were experienced by 90% of patients in a bra compared with 70% of patients not in a bra (P = .003). On multivariate analysis significant predictors of grade 2 or 3 skin toxicity included the use of 3DCRT instead of IMRT (odds ratio, 3.9; 95% confidence interval, 1.8-8.5) and the use of a bra (odds ratio, 5.5; 95% confidence interval, 1.6-18.8). For left-sided patients, the use of a bra was associated with a volume of heart in the treatment fields decreased by 63.4% (P = .002), a volume of left lung decreased by 18.5% (P = .25), and chest wall separation decreased by a mean of 1 cm (P = .03). CONCLUSIONS: The use of a bra to augment breast shape and position in large-breasted women is an alternative to prone positioning and associated with reduced chest wall separation and reduced heart volume within the treatment field.

Five-year results of whole breast intensity modulated radiation therapy for the treatment of early stage breast cancer: the Fox Chase Cancer Center experience.

PURPOSE: To report the 5-year outcomes using whole-breast intensity-modulated radiation therapy (IMRT) for the treatment of early-stage-breast cancer at the Fox Chase Cancer Center. METHODS AND MATERIALS: A total of 946 women with early-stage breast cancer (stage 0, I, or II) were treated with IMRT after surgery with or without systemic therapy from 2003-2010. Whole-breast radiation was delivered via an IMRT technique with a median whole-breast radiation dose of 46 Gy and median tumor bed boost of 14 Gy. Endpoints included local-regional recurrence, cosmesis, and late complications. RESULTS: With a median follow-up of 31 months (range, 1-97 months), there were 12 ipsilateral breast tumor recurrences (IBTR) and one locoregional recurrence. The 5-year actuarial IBTR and locoregional recurrence rates were 2.0% and 2.4%. Physician-reported cosmestic outcomes were available for 645 patients: 63% were considered "excellent", 33% "good", and <1.5% "fair/poor". For physician-reported cosmesis, boost doses≥16 Gy, breast size>900 cc, or boost volumes>34 cc were significantly associated with a "fair/poor" cosmetic outcome. Fibrosis, edema, erythema, and telangectasia were also associated with "fair/poor" physician-reported cosmesis; erythema and telangectasia remained significant on multivariate analysis. Patient-reported cosmesis was available for 548 patients, and 33%, 50%, and 17% of patients reported "excellent", "good", and "fair/poor" cosmesis, respectively. The use of a boost and increased boost volume: breast volume ratio were significantly associated with "fair/poor" outcomes. No parameter for patient-reported cosmesis was significant on multivariate analysis. The chances of experiencing a treatment related effect was significantly associated with a boost dose≥16 Gy, receipt of chemotherapy and endocrine therapy, large breast size, and electron boost energy. CONCLUSIONS: Whole-breast IMRT is associated with very low rates of local recurrence at 5 years, 83%-98% "good/excellent" cosmetic outcomes, and minimal chronic toxicity, including late fibrosis.

First author research productivity of United States radiation oncology residents: 2002-2007.

PURPOSE: Participation in investigative research is a required element of radiation oncology residency in the United States. Our purpose was to quantify the first author research productivity of recent U.S. radiation oncology residents during their residency training. METHODS AND MATERIALS: We performed a computer-based search of PubMed and a manual review of the proceedings of the annual meetings of the American Society for Therapeutic Radiology and Oncology to identify all publications and presented abstracts with a radiation oncology resident as the first author between 2002 and 2007. RESULTS: Of 1,098 residents trained at 81 programs, 50% published > or =1 article (range, 0-9), and 53% presented > or =1 abstract (range, 0-3) at an American Society for Therapeutic Radiology and Oncology annual meeting. The national average was 1.01 articles published and 1.09 abstracts presented per resident during 4 years of training. Of 678 articles published, 82% represented original research and 18% were review articles. Residents contributed 15% of all abstracts at American Society for Therapeutic Radiology and Oncology annual meetings, and the resident contribution to orally presented abstracts increased from 12% to 21% during the study period. Individuals training at programs with >6 residents produced roughly twice as many articles and abstracts. Holman Research Pathway residents produced double the national average of articles and abstracts. CONCLUSION: Although variability exists among individuals and among training programs, U.S. radiation oncology residents routinely participate in investigative research suitable for publication or presentation at a scientific meeting. These data provide national research benchmarks that can assist current and future radiation oncology residents and training programs in their self-assessment and research planning.