Search

Purpose/Objective(s) The role of PORT for patients with resected stage IIIA (N2) NSCLC is controversial. Recently, the Phase III LungART trial reported a significant improvement in mediastinal control with PORT but failed to show an overall survival (OS) benefit, due in part to cardiopulmonary (CP) toxicity (7% early and 20% late grade (G) 3-5). However, LungART employed 3D conformal radiotherapy (3D-CRT) in 90% of patients as well as elective treatment of mediastinal nodal stations. We evaluated the risk of CP toxicity associated with use of postoperative IMRT for this population. Materials/Methods We conducted a retrospective study of consecutive patients with NSCLC treated with postoperative IMRT between 2008 and 2019. Patients were eligible if they were found to have incidental pN2 or an R1/2 resection. Targets of PORT for pN2 were bronchial stump, ipsilateral hilum, and involved mediastinal station(s). The primary objective was incidence of CTCAE (v4) G3+ CP toxicities. Secondary objectives were major adverse cardiac events (MACE), defined as cardiac death, myocardial infarction, coronary revascularization or hospitalization due to heart failure; disease-free survival (DFS); and OS. Cumulative incidence and Kaplan-Meier method were used as appropriate. Results 73 patients received PORT with IMRT. Median follow-up was 54 months. Median age at diagnosis was 65 years (range 36 - 81); 33 patients (45%) had pre-existing cardiovascular disease and 48 (65.8%) were current/former smokers. 50 patients had pN2 disease and 23 patients had R1/R2 resection. Among patients with pN2, the median number of involved mediastinal nodes was 1 (range 1 – 12). All patients with pN2 and 70% of patients with R1/R2 resection received chemotherapy, the majority of which was sequential (n = 52, 71.2%). Median RT dose was 54 Gy (range 45 – 66 Gy) in 27 fractions for patients with pN2 and 59.4 Gy (range 45 – 66 Gy) in 30 fractions for patients with R1/R2 resection. 3-year cumulative incidence of G3+ CP toxicity was 2.7%, with an overall incidence of 6.8% (5 events in 73 patients). The rate of G3+ CP toxicity in patients with pN2 was 8%. Three patients developed ≥1 MACE: one died of a cardiac arrest and two underwent coronary revascularization. Two of these patients had a history of coronary artery disease. Two episodes of G3+ toxicity involved valve replacements in patients with pre-existing valvular disease. 3-year DFS was 51.4% (95% CL 46.9 – 55.1%). Two patients with pN2 developed mediastinal failures. 3-year OS was 62.3% (95% CL 50.2 – 74.4%). Conclusion PORT for pN2 NSCLC using IMRT and no elective nodal irradiation is associated with a low rate of G3+ CP toxicity in patients with pN2, comparable to the chemotherapy only arm of the LungART trial. Our data suggest that highly conformal radiation techniques should be prospectively assessed for their potential to translate the known local control benefit of PORT into a survival advantage.

Importance Severe acute esophagitis occurs in up to 20% of patients with locally advanced lung cancer treated with chemoradiation therapy to at least 60 Gy once daily and represents a dose-limiting toxic event associated with poor outcomes. Objective To assess whether formalized sparing of the contralateral esophagus (CE) is associated with reduced risk of severe acute esophagitis. Design, setting, and participants This single-center phase 1 nonrandomized clinical trial assessing an empirical CE-sparing technique enrolled patients from July 2015 to January 2019. In total, 27 patients with locally advanced non-small cell lung carcinoma (with or without solitary brain metastasis) or limited-stage small cell lung carcinoma with gross tumor within 1 cm of the esophagus were eligible. Interventions Intensity-modulated radiation therapy to 70 Gy at 2 Gy/fraction concurrent with standard chemotherapy with or without adjuvant durvalumab. The esophageal wall contralateral to gross tumor was contoured as an avoidance structure to guide a steep dose falloff gradient. Target coverage was prioritized over CE sparing, and 99% of internal and planning target volumes had to be covered by 70 Gy and at least 63 Gy, respectively. Main outcomes and measures The primary end point was the rate of at least grade 3 acute esophagitis as assessed by Common Terminology Criteria for Adverse Events, version 4. Results Of 27 patients enrolled, 25 completed chemoradiation therapy. Nineteen patients had non-small cell lung carcinoma, and 6 had small cell lung carcinoma. The median age at diagnosis was 67 years (range, 51-81 years), and 15 patients (60%) were men. Thirteen patients (52%) had stage IIIA cancer, 10 (40%) had stage IIIB cancer, and 2 (8%) had stage IV cancer. The median CE maximum dose was 66 Gy (range, 44-71 Gy); the median volume of CE receiving at least 55 Gy was 1.4 cm3 (range, 0-5.3 cm3), and the median volume of CE receiving at least 45 Gy was 2.7 cm3 (range, 0-9.2 cm3). The median combined percentage of lung receiving at least 20 Gy was 25% (range, 11%-37%). The median follow-up was 33.3 months (range, 11.1-52.2 months). Among the 20 patients who had treatment breaks of 0 to 3 days and were thus evaluable for the primary end point, the rate of at least grade 3 esophagitis was 0%. Other toxic events observed among all 25 patients included 7 (28%) with grade 2 esophagitis, 3 (12%) with at least grade 2 pneumonitis (including 1 with grade 5), and 2 (8%) with at least grade 3 cardiac toxic event (including 1 with grade 5). There was no isolated local tumor failure. The 2-year progression-free survival rate was 57% (95% CI, 33%-75%), and the 2-year overall survival rate was 67% (95% CI, 45%-82%). Conclusions and relevance This phase 1 nonrandomized clinical trial found that the CE-sparing technique was associated with reduced risk of esophagitis among patients treated uniformly with chemoradiation therapy (to 70 Gy), with no grade 3 or higher esophagitis despite tumor within 1 cm of the esophagus. This technique may be translated into clinical practice. Trial registration ClinicalTrials.gov Identifier: NCT02394548.

Trimodality therapy (chemoradiation and surgery) is the standard of care for stage II/III rectal cancer but nearly one third of patients do not receive radiation therapy (RT). We examined the relationship between the density of radiation oncologists and the travel distance to receipt of RT.A retrospective study based on the National Cancer Data Base identified 26,845 patients aged 18 to 80 years with stage II/III rectal cancer diagnosed from 2007 to 2010. Radiation oncologists were identified through the Physician Compare dataset. Generalized estimating equations clustering by hospital service area was used to examine the association between geographic access and receipt of RT, controlling for patient sociodemographic and clinical characteristics.Of the 26,845 patients, 70% received RT within 180 days of diagnosis or within 90 days of surgery. Compared with a travel distance of12.5 miles, patients diagnosed at a reporting facility who traveled ≥50 miles had a decreased likelihood of receipt of RT (50-249 miles, adjusted odds ratio 0.75, P.001; ≥250 miles, adjusted odds ratio 0.46; P=.002), all else being equal. The density level of radiation oncologists was not significantly associated with the receipt of RT. Patients who were female, nonwhite, and aged ≥50 years and had comorbidities were less likely to receive RT (P.05). Patients who were uninsured but self-paid for their medical services, initially diagnosed elsewhere but treated at a reporting facility, and resided in Midwest had an increased the likelihood of receipt of RT (P.05).An increased travel burden was associated with a decreased likelihood of receiving RT for patients with stage II/III rectal cancer, all else being equal; however, radiation oncologist density was not. Further research of geographic access and establishing transportation assistance programs or lodging services for patients with an unmet need might help decrease geographic barriers and improve the quality of rectal cancer care.

Purpose Geographic access to care may be associated with receipt of chemotherapy but has not been fully examined. This study sought to evaluate the association between density of oncologists and travel distance and receipt of adjuvant chemotherapy for colon cancer within 90 days of colectomy. Patients and Methods Patients in the National Cancer Data Base with stage III colon cancer, diagnosed between 2007 and 2010, and age 18 to 80 years were selected. Generalized estimating equation clustering by hospital service area was conducted to examine the association between geographic access and receipt of oncology services, controlling for patient sociodemographic and clinical characteristics. Results Of 34,694 patients in the study cohort, 75.7% received adjuvant chemotherapy within 90 days of colectomy. Compared with travel distance less than 12.5 miles, patients who traveled 50 to 249 miles (odds ratio [OR], 0.87; P = .009) or ≥ 250 miles (OR, 0.36; P < .001) had decreased likelihood of receiving adjuvant chemotherapy. Density level of oncologists was not statistically associated with receipt of adjuvant chemotherapy (low v high density: OR, 0.98; P = .77). When stratifying analyses by insurance status, non–privately insured patients who resided in areas with low density of oncologists were less likely to receive adjuvant chemotherapy (OR, 0.85; P = .03). Conclusion Increased travel burden was associated with a decreased likelihood of receiving adjuvant chemotherapy, regardless of insurance status. Patients with nonprivate insurance who resided in low-density oncologist areas were less likely to receive adjuvant chemotherapy. If these findings are validated prospectively, interventions to decrease geographic barriers may improve the timeliness and quality of colon cancer treatment.

Purpose To determine the characteristics, needs, and concerns of the current radiation oncology workforce, evaluate best practices and opportunities for improving quality and safety, and assess what we can predict about the future workforce. Methods and Materials An online survey was distributed to 35,204 respondents from all segments of the radiation oncology workforce, including radiation oncologists, residents, medical dosimetrists, radiation therapists, medical physicists, nurse practitioners, nurses, physician assistants, and practice managers/administrators. The survey was disseminated by the American Society for Radiation Oncology (ASTRO) together with specialty societies representing other workforce segments. An overview of the methods and global results is presented in this paper. Results A total of 6765 completed surveys were received, a response rate of 19%, and the final analysis included 5257 respondents. Three-quarters of the radiation oncologists, residents, and physicists who responded were male, in contrast to the other segments in which two-thirds or more were female. The majority of respondents (58%) indicated they were hospital-based, whereas 40% practiced in a free-standing/satellite clinic and 2% in another setting. Among the practices represented in the survey, 21.5% were academic, 25.2% were hospital, and 53.3% were private. A perceived oversupply of professionals relative to demand was reported by the physicist, dosimetrist, and radiation therapist segments. An undersupply was perceived by physician's assistants, nurse practitioners, and nurses. The supply of radiation oncologists and residents was considered balanced. Conclusions This survey was unique as it attempted to comprehensively assess the radiation oncology workforce by directly surveying each segment. The results suggest there is potential to improve the diversity of the workforce and optimize the supply of the workforce segments. The survey also provides a benchmark for future studies, as many changes in the healthcare field exert pressure on the workforce.

Purpose The American Society for Radiation Oncology (ASTRO) conducted the 2012 Radiation Oncology Workforce Survey to obtain an up-to-date picture of the workforce, assess its needs and concerns, and identify quality and safety improvement opportunities. The results pertaining to radiation oncologists (ROs) and residents (RORs) are presented here. Methods The ASTRO Workforce Subcommittee, in collaboration with allied radiation oncology professional societies, conducted a survey study in early 2012. An online survey questionnaire was sent to all segments of the radiation oncology workforce. Respondents who were actively working were included in the analysis. This manuscript describes the data for ROs and RORs. Results A total of 3618 ROs and 568 RORs were surveyed. The response rate for both groups was 29%, with 1047 RO and 165 ROR responses. Among ROs, the 2 most common racial groups were white (80%) and Asian (15%), and the male-to-female ratio was 2.85 (74% male). The median age of ROs was 51. ROs averaged 253.4 new patient consults in a year and 22.9 on-treatment patients. More than 86% of ROs reported being satisfied or very satisfied overall with their career. Close to half of ROs reported having burnout feelings. There was a trend toward more frequent burnout feelings with increasing numbers of new patient consults. ROs' top concerns were related to documentation, reimbursement, and patients' health insurance coverage. Ninety-five percent of ROs felt confident when implementing new technology. Fifty-one percent of ROs thought that the supply of ROs was balanced with demand, and 33% perceived an oversupply. Conclusions This study provides a current snapshot of the 2012 radiation oncology physician workforce. There was a predominance of whites and men. Job satisfaction level was high. However a substantial fraction of ROs reported burnout feelings. Perceptions about supply and demand balance were mixed. ROs top concerns reflect areas of attention for the healthcare sector as a whole.

Severe (Radiation Therapy Oncology Group [RTOG] grade 3 or greater) esophagitis generally occurs in 15% to 25% of non-small cell lung cancer (NSCLC) patients undergoing concurrent chemotherapy and radiation therapy (CCRT), which may result in treatment breaks that compromise local tumor control and pose a barrier to dose escalation. Here, we report a novel contralateral esophagus-sparing technique (CEST) that uses intensity modulated radiation therapy (IMRT) to reduce the incidence of severe esophagitis.We reviewed consecutive patients with thoracic malignancies undergoing curative CCRT in whom CEST was used. The esophageal wall contralateral (CE) to the tumor was contoured as an avoidance structure, and IMRT was used to guide a rapid dose falloff gradient beyond the target volume in close proximity to the esophagus. Esophagitis was recorded based on the RTOG acute toxicity grading system.We identified 20 consecutive patients treated with CCRT of at least 63 Gy in whom there was gross tumor within 1 cm of the esophagus. The median radiation dose was 70.2 Gy (range, 63-72.15 Gy). In all patients, ≥99% of the planning and internal target volumes was covered by ≥90% and 100% of prescription dose, respectively. Strikingly, no patient experienced grade ≥3 esophagitis (95% confidence limits, 0%-16%) despite the high total doses delivered. The median maximum dose, V45, and V55 of the CE were 60.7 Gy, 2.1 cc, and 0.4 cc, respectively, indicating effective esophagus cross-section sparing by CEST.We report a simple yet effective method to avoid exposing the entire esophagus cross-section to high doses. By using proposed CE dose constraints of V452.5 cc and V550.5 cc, CEST may improve the esophagus toxicity profile in thoracic cancer patients receiving CCRT even at doses above the standard 60- to 63-Gy levels. Prospective testing of CEST is warranted.

To assess daily variations in delivered doses in postprostatectomy patients, using kilovoltage cone-beam CT (CBCT) datasets acquired before and after interventions to correct for observed distortions in volume/shape of rectum and bladder.Seventeen consecutive patients treated with intensity-modulated radiotherapy to the prostate bed were studied. For patients with large anatomical variations, quantified by either a rectal wall displacement of5 mm or bladder volume change of50% on the CBCT compared with the planning CT, an intervention was performed to adjust the rectum and/or bladder filling. Cumulative doses over the pre- and post-intervention fractions were calculated by tracking the position of the planning CT voxels on different CBCTs using a deformable surface-mapping algorithm. Dose and displacements vectors were projected on two-dimensional maps, the minimal dose received by the highest 95% of the planing target volume (PTV D95) and the highest 10% of the rectum volume (D10) as well as the bladder volume receiving2 Gy (V2) were evaluated.Of 544 fractions, 96 required intervention. Median (range) number of interventions per patient was 5 (2-12). Compared with the planning values, the mean (SD) pre- vs. postintervention value for PTV D95 was -2% (2%) vs. -1% (2%) (p0.12), for rectum D10 was -1% (4%) vs. +1% (4%) (p0.24), and for bladder V2 was +6% vs. +20% (p0.84).Interventions to reduce treatment volume deformations due to bladder and rectum fillings are not necessary when patients receive daily accurate CBCT localization, and the frequency of those potential interventions is low. However, for hypofractionated treatments, the relative frequency can significantly increase, and interventions can become more dosimetrically beneficial.

To evaluate the toxicity of daily gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor, with concurrent chemoradiation (CRT) in patients with locally advanced pancreatic adenocarcinoma and prospectively evaluate plasma k-ras as a potential marker of response to gefitinib and CRT.Eleven of 12 eligible patients enrolled received a 7-day induction of gefitinib (250 mg PO) followed by daily gefitinib with concurrent CRT. Patients received 50.4 Gy/28 fractions of external beam radiation with weekly paclitaxel (40 mg/m IV) followed by maintenance on gefitinib. Plasma k-ras codon 12 mutations were detected using a two-stage restriction fragment length polymorphism-polymerase chain reaction assay on patients' plasma both before and after therapy. Mutations were confirmed by direct sequencing.Common adverse events included grade 1 skin rash (63%), grade 1 to 2 gastrointestinal symptoms including anorexia, nausea, vomiting, and diarrhea occurred in 63% of patients, grade 3 nausea occurred in 45% of patients. Three patients did not complete therapy, only one was possibly associated with study drug. K-ras mutations were detected in the pre-gefitinib plasma of 5/11 patients and in the matched tumor tissue of 3/4 patients. In patients where k-ras mutations were undetectable post-treatment, survival times were favorable.Combination of daily gefitinib with concurrent CRT in this locally advanced pancreatic cancer population was reasonably tolerated. Rapid changes in serum k-ras may provide critical information as to the efficacy of a novel agent and assist in tailoring treatment for cancers of the pancreas.

Purpose Epidermal growth factor receptor (EGFR) gene copy number detected by fluorescent in situ hybridization (FISH) has proven to be useful for selection of non–small-cell lung cancer (NSCLC) patients for treatment with EGFR tyrosine kinase inhibitors. Here, we evaluate EGFR FISH as a predictive marker in NSCLC patients receiving the EGFR monoclonal antibody inhibitor cetuximab plus chemotherapy. Patients and Methods Two hundred twenty-nine chemotherapy-naive patients with advanced-stage NSCLC were enrolled onto a phase II selection trial evaluating sequential or concurrent chemotherapy (paclitaxel plus carboplatin) with cetuximab. Results EGFR FISH was assessable in 76 patients with available tumor tissue and classified as positive (four or more gene copies per cell in ≥ 40% of the cells or gene amplification) in 59.2%. Response (complete response/partial response) was numerically higher in FISH-positive (45%) versus FISH-negative (26%) patients (P = .14), whereas disease control rate (complete response/partial response plus stable disease) was statistically superior (81% v 55%, respectively; P = .02). Patients with FISH-positive tumors had a median progression-free survival time of 6 months compared with 3 months for FISH-negative patients (P = .0008). Median survival time was 15 months for the FISH-positive group compared with 7 months for patients who were FISH negative. (P = .04). Furthermore, survival favored FISH-positive patients receiving concurrent therapy. Conclusion These results are the first to suggest that EGFR FISH is a predictive factor for selection of NSCLC patients for cetuximab plus chemotherapy. Prospective validation of these findings is warranted.

Purpose: To describe the histologic and volumetric changes in normal liver tissue after stereotactic body radiotherapy (SBRT) for liver metastases. Methods and Materials: Pre- and post-SBRT imaging studies were analyzed to evaluate the effect of SBRT on normal liver volume (NLV) in 15 patients treated in a prospective clinical trial. Two other patients underwent exploratory surgery after SBRT and histologic analyses of the irradiated liver were performed to characterize the pathologic effects of SBRT. Results: In the 15 patients studied quantitatively, the total NLV had decreased transiently at 2-3 months after SBRT and then began to regenerate at 3-8 months after SBRT. The median NLV reduction at the maximal observed effect was 315 cm{sup 3} (range, 125-600) or 19% (range, 13-33%). Among the several dosimetric parameters evaluated, the strongest linear correlation was noted for the NLV percentage receiving 30 Gy as a predictor of maximal NLV reduction (r{sup 2} = 0.72). The histologic changes observed 2 and 8 months after SBRT demonstrated distinct zones of tissue injury consistent with localized veno-occlusive disease. Conclusion: The well-demarcated focal parenchymal changes after liver SBRT (demonstrated both radiographically and histologically) within the high-dose zone are consistent with a threshold dose-induced set of phenomena. Inmore » contrast, the more global effect of NLV reduction, which is roughly proportional to whole organ dose parameters, resembles more closely an effect determined from radiobiologically parallel architecture. These observations suggest that modeling of normal tissue effects after liver SBRT might require different governing equations for different classes of effects.« less