Eli D. Scher

Proton beam radiation therapy results in significantly reduced toxicity compared with intensity-modulated radiation therapy for head and neck tumors that require ipsilateral radiation

BACKGROUND As proton beam radiation therapy (PBRT) may allow greater normal tissue sparing when compared with intensity-modulated radiation therapy (IMRT), we compared the dosimetry and treatment-related toxicities between patients treated to the ipsilateral head and neck with either PBRT or IMRT. METHODS Between 01/2011 and 03/2014, 41 consecutive patients underwent ipsilateral irradiation for major salivary gland cancer or cutaneous squamous cell carcinoma. The availability of PBRT, during this period, resulted in an immediate shift in practice from IMRT to PBRT, without any change in target delineation. Acute toxicities were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. RESULTS Twenty-three (56.1%) patients were treated with IMRT and 18 (43.9%) with PBRT. The groups were balanced in terms of baseline, treatment, and target volume characteristics. IMRT plans had a greater median maximum brainstem (29.7 Gy vs. 0.62 Gy (RBE), ​P < 0.001), maximum spinal cord (36.3 Gy vs. 1.88 Gy (RBE), ​P < 0.001), mean oral cavity (20.6 Gy vs. 0.94 Gy (RBE), ​P < 0.001), mean contralateral parotid (1.4 Gy vs. 0.0 Gy (RBE), P<0.001), and mean contralateral submandibular (4.1 Gy vs. 0.0 Gy (RBE), ​P < 0.001) dose when compared to PBRT plans. PBRT had significantly lower rates of grade 2 or greater acute dysgeusia (5.6% vs. 65.2%, P<0.001), mucositis (16.7% vs. 52.2%, P=0.019), and nausea (11.1% vs. 56.5%, P=0.003). CONCLUSIONS The unique properties of PBRT allow greater normal tissue sparing without sacrificing target coverage when irradiating the ipsilateral head and neck. This dosimetric advantage seemingly translates into lower rates of acute treatment-related toxicity.

Proton Beam Reirradiation for Recurrent Head and Neck Cancer: Multi-institutional Report on Feasibility and Early Outcomes

PURPOSE Reirradiation therapy (re-RT) is the only potentially curative treatment option for patients with locally recurrent head and neck cancer (HNC). Given the significant morbidity with head and neck re-RT, interest in proton beam radiation therapy (PBRT) has increased. We report the first multi-institutional clinical experience using curative-intent PBRT for re-RT in recurrent HNC. METHODS AND MATERIALS A retrospective analysis of ongoing prospective data registries from 2 hybrid community practice and academic proton centers was conducted. Patients with recurrent HNC who underwent at least 1 prior course of definitive-intent external beam radiation therapy (RT) were included. Acute and late toxicities were assessed with the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and the Radiation Therapy Oncology Group late radiation morbidity scoring system, respectively. The cumulative incidence of locoregional failure was calculated with death as a competing risk. The actuarial 12-month freedom-from-distant metastasis and overall survival rates were calculated with the Kaplan-Meier method. RESULTS Ninety-two consecutive patients were treated with curative-intent re-RT with PBRT between 2011 and 2014. Median follow-up among surviving patients was 13.3 months and among all patients was 10.4 months. The median time between last RT and PBRT was 34.4 months. There were 76 patients with 1 prior RT course and 16 with 2 or more courses. The median PBRT dose was 60.6 Gy (relative biological effectiveness, [RBE]). Eighty-five percent of patients underwent prior HNC RT for an oropharynx primary, and 39% underwent salvage surgery before re-RT. The cumulative incidence of locoregional failure at 12 months, with death as a competing risk, was 25.1%. The actuarial 12-month freedom-from-distant metastasis and overall survival rates were 84.0% and 65.2%, respectively. Acute toxicities of grade 3 or greater included mucositis (9.9%), dysphagia (9.1%), esophagitis (9.1%), and dermatitis (3.3%). There was 1 death during PBRT due to disease progression. Grade 3 or greater late skin and dysphagia toxicities were noted in 6 patients (8.7%) and 4 patients (7.1%), respectively. Two patients had grade 5 toxicity due to treatment-related bleeding. CONCLUSIONS Proton beam re-RT of the head and neck can provide effective tumor control with acceptable acute and late toxicity profiles likely because of the decreased dose to the surrounding normal, albeit previously irradiated, tissue, although longer follow-up is needed to confirm these findings.

Adjuvant Versus Salvage Radiation Therapy for Prostate Cancer Patients With Adverse Pathologic Features: Comparative Analysis of Long-term Outcomes.

Objectives:To compare long-term outcomes of men with adverse pathologic features after adjuvant radiation therapy (ART) versus salvage radiation therapy (SRT) after radical prostatectomy at our institution. Methods:Patients treated with postprostatectomy radiation therapy with pT3 tumors, or pT2 with positive surgical margins, were identified. Cumulative freedom from biochemical failure (FFBF), freedom from metastatic failure (FFMF), and overall survival rates were estimated utilizing the Kaplan-Meier method. Multivariate analyses were performed to determine independent prognostic factors correlated with study endpoints. Propensity score analyses were performed to adjust for confounding because of nonrandom treatment allocation. Results:A total of 186 patients with adverse pathologic features treated with ART or SRT were identified. The median follow-up time after radical prostatectomy was 103 and 88 months after completion of radiation therapy. The Kaplan-Meier estimates for 10-year FFBF was 73% and 41% after ART and SRT, respectively (log-rank, P=0.0001). Ten-year FFMF was higher for patients who received ART versus SRT (98.6% vs. 80.9%, P=0.0028). On multivariate analyses there was no significant difference with respect to treatment group in terms of FFBF, FFMF, and overall survival after adjusting for propensity score. Conclusions:Although unadjusted analyses showed improved FFBF with ART, the propensity score-adjusted analyses demonstrated that long-term outcomes of patients treated with ART and SRT do not differ significantly. These results, with decreased effect size of ART after adjusting for propensity score, demonstrate the potential impact of confounding on observational research.

Postprostatectomy radiation therapy: an evidence-based review

While the majority of men with localized prostate cancer who undergo a radical prostatectomy will remain disease free, men with certain clinical and pathological features are known to be at an increased risk for developing a biochemical recurrence and, ultimately, distant metastatic disease. The optimal management of these patients continues to be a source of controversy. To date, three randomized Phase III trials have demonstrated that adjuvant radiation therapy (ART) for patients with certain adverse pathological features results in an improvement in several clinically-relevant end points, including biochemical recurrence-free survival and overall survival. Despite the evidence from these trials showing a benefit for ART, many believe that ART results in overtreatment and unwarranted treatment morbidity for a significant number of patients. Many physicians, therefore, instead advocate for close observation followed by early salvage radiation therapy (SRT) at the time of a biochemical recurrence. The purpose of this review is to evaluate the evidence for and to distinguish between ART and early SRT. We will also highlight current and future areas of research for this patient population, including radiation treatment dose escalation, hypofractionation and androgen deprivation therapy. We will also discuss the cost-effectiveness of ART and early SRT.

What Are Medical Students in the United States Learning About Radiation Oncology? Results of a Multi-Institutional Survey

PURPOSE The purposes of this study were to assess the exposure that medical students (MSs) have to radiation oncology (RO) during the course of their medical school career, as evidenced by 2 time points in current medical training (ie, first vs fourth year; MS1s and MS4s, respectively) and to assess the knowledge of MS1s, MS4s, and primary care physicians (PCPs) about the appropriateness of RT in cancer management in comparison with RO attendings. METHODS We developed and beta tested an electronic survey divided into 3 parts: RO job descriptions, appropriateness of RT, and toxicities of RT. The surveys were distributed to 7 medical schools in the United States. A concordance of >90% (either yes or no) among RO attendings in an answer was necessary to determine the correct answer and to compare with other subgroups using a χ(2) test (P<.05 was significant). RESULTS The overall response rate for ROs, MS1s, MS4s, and PCPs was 26%; n (22 + 315 + 404 + 43)/3004. RT misconceptions decreased with increasing level of training. More than 1 of 10 MSs did not believe that RT alone could cure cancer. Emergent oncologic conditions for RT (eg, spinal cord compression, superior vena cava syndrome) could not be identified by >1 of 5 respondents. Multiple nontoxicities of RT (eg, emitting low-level radiation from the treatment site) were incorrectly identified as toxicities by >1 of 5 respondents. MS4s/PCPs with an RO rotation in medical school had improved scores in all prompts. CONCLUSIONS Although MS knowledge of general RT principles improves from the first to the fourth year, a large knowledge gap still exists between MSs, current PCPs, and ROs. Some basic misconceptions of RT persist among a minority of MSs and PCPs. We recommend implementing formal education in RO fundamentals during the core curriculum of medical school.

Definitive chemoradiation for primary oral cavity carcinoma: A single institution experience

OBJECTIVES While surgery with or without adjuvant radiation therapy (RT) is the standard of care for oral cavity cancer (OCC), a select group requires nonsurgical treatment. We provide a single-institution experience using definitive chemotherapy and RT for primary OCC. MATERIALS AND METHODS We examined 73 patients with previously untreated, non-metastatic primary OCC treated definitively from 1990 to 2011. There were 39 male and 34 female, with a median age of 63 years (range, 35-89). The disease distribution was Stage I and II (7% each), Stage III (14%), and Stage IV (73%). Oral tongue was the most common (48%), followed by floor of mouth (19%), retromolar trigone (13.7%), and others (8.2%). Median tumor dose was 70 Gy. Sixty-two percent of patients (n=45) were treated with concurrent chemotherapy, predominantly platinum-based. RESULTS Median follow-up among surviving patients was 73.1 months (interquartile range 14.2-81.4 months). Actuarial 5-year overall survival was 15%. Incidences of locoregional and distant failures were 41.1% and 20.5%, respectively. Kaplan-Meier estimated 5-year rates of locoregional control and freedom from distant metastasis were 37% and 70%, respectively. Mucositis was the most common ⩾Grade 3 acute toxicity (49%). Incidences of Grade 3 late dysphagia and trismus were 15% and 13%, respectively. CONCLUSION This study demonstrates over 20 years of experience using definitive chemoradiation for OCC at our institution. Our results illustrate the challenges in treating patients with advanced disease who are not surgical candidates, and the need for adequate and early treatment to prevent distant disease and improve survival outcomes.

Technical aspects of radiation therapy for anal cancer

Historically treated with surgery, current practice recommends anal carcinoma to be treated with a combination of chemotherapy and radiation. This review will examine the anatomy, modes of disease spread and recurrence, and evaluate the existing evidence for treatment options for these tumors. An in-depth examination of specific radiation therapy (RT) techniques-such as conventional 3D-conformal RT and intensity-modulated RT-will be discussed along with modern dose constraints. RT field arrangement, patient setup, and recommended gross and clinical target volume (CTV) contours will be considered. Areas in need of further investigation, such as the role in treatment for positron emission tomography (PET) will be explored.

Clinical characteristics and dose-volume histogram parameters associated with the development of pleural effusions in non-small cell lung cancer patients treated with chemoradiation therapy

Abstract Background: To investigate descriptive characteristics and dose metric (DM) parameters associated with development of pleural effusions (PlEf) in non-small cell lung cancer (NSCLC) treated with definitive chemoradiation therapy (CRT). Materials and methods: We retrospectively assessed treatment records and follow-up imaging of 66 NSCLC patients to identify PlEf formation after CRT. PlEf association between mean heart dose (MHD), mean lung dose (MLD), heart V5–V60 (HV), and lung V5–V60 (LV) were evaluated using Cox Proportional Hazard Models. Results: A total of 52% (34 of 66 patients) of our population developed PlEf and the actuarial rates at 6 months, 12 months, and 18 months were 7%, 30%, and 42%, respectively. Median time to diagnosis was five months (range 0.06–27 months). The majority of PlEfs were grade one (67%) and developed at a median of four (0.06–13) months, followed by grade two (15%) at a median 11 (5–12) months, and grade three (18%) at a median of 11 (3–27) months. On multivariate analysis, increasing HV5–HV50, LV5–LV50, MHD, and MLD were associated with greater risk of PlEf. Higher grade PlEf was also associated with higher doses of radiation to the heart, while lung DM parameters were not significantly associated with higher PlEf grades. At five-months post-CRT, MHD of 25 Gy was associated with a 100% chance of grade one PlEf, an 82% risk of grade two PlEf, and a 19% risk of grade three PlEf. Conclusions: Post-CRT PlEf is common in NSCLC with the majority being grade one. Increasing heart and lung irradiation was associated with increased risk of PlEf. Increasing heart irradiation also correlated with development of increasing grades of PlEf. The impact of potential cardiopulmonary toxicity and resultant PlEfs after CRT requires additional study.

Early vs. Late Chemoradiation Therapy and the Postoperative Interval to Adjuvant Therapy Do Not Correspond to Local Recurrence in Resected Pancreatic Cancer

Objective Standard postoperative therapy for pancreatic cancer consists of both chemotherapy alone and chemoradiation. We sought to investigate whether the sequence of chemotherapy and chemoradiation and overall time to initiation of adjuvant therapy would impact local vs. distant recurrence. Methods After Institutional Review Board approval, resected pancreas cancer patient charts were evaluated for medical background, surgical, pathological, chemoradiation (CRT), and follow-up. Local recurrence (LR) was defined as failures occurring in the postoperative bed and regional lymph nodes. Early vs. late CRT was defined by whether CRT was given early (within 1–2 cycles of adjuvant chemotherapy) or late in the course of adjuvant chemotherapy (after the 3rd cycle of chemotherapy). The postoperative interval variance was compared to LR factors such as progression-free survival (PFS) and overall survival (OS). Results Of the 34 eligible patients, 47% (n=16) underwent early CRT and 41% (n=14) underwent late CRT. 12% (n=14) did not undergo any induction chemotherapy. At median follow-up of 22 months, 53% (n=18) had metastases, 24% (n=8) had LR, and 24% (n=8) were disease free. Kaplan-Meier curves revealed that early vs. late CRT did not appear to significantly impact OS (p=0.63), PFS (p=0.085) or LR (p=0.19). Postoperative interval did not affect PFS (p=0.42) or OS (p=0.93). Conclusions Early vs. late CRT and the time to initiation of adjuvant therapy were not significantly associated with LR in patients with resected pancreatic cancer. Future prospective studies are required to determine if sequencing of chemotherapy, CRT, or the postoperative interval impact survival and patterns of recurrence.

Target Delineation of the Neck in Head and Neck Carcinomas

IMRT is utilized for treatment in head and neck sites to maximize target coverage and decrease normal tissue toxicity, such as xerostomia and dysphagia. The most common at-risk nodal levels for head and neck cancers typically include levels I to VII and the lateral retropharyngeal lymph nodes (RPLN).