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Purpose: Bladder preservation therapy is an effective treatment for muscle-invasive urothelial carcinoma (UC). In this study we treated noncystectomy candidates with daily radiation and weekly paclitaxel for 7 weeks. Patients whose tumors showed her2/neu overexpression were additionally treated with weekly trastuzumab.Methods and Materials: Sixty-eight evaluable patients were treated with radiation therapy and either paclitaxel + trastuzumab (group 1) or paclitaxel alone (group 2). Groups were assigned on the basis of her2/neu immunohistochemistry results. Patients received 1.8-Gy fractions to a total dose of 64.8 Gy. The primary endpoint of the study was treatment-related toxicity, and secondary endpoints included complete response (CR) rate, protocol completion rate, and survival.Results: A total of 20 evaluable patients were treated in group 1 and 46 patients in group 2. Acute treatment-related adverse events (AEs) were observed in 7 of 20 patients in group 1 (35%) and 14 of 46 patients in group 2 (30.4%). Protocol therapy was completed by 60% (group 1) and 74% (group 2) of patients. Most incompletions were due to toxicity, and the majority of AEs were gastrointestinal, including 1 grade 5 AE (group 1). Two other deaths (both in group 2) were unrelated to protocol therapy. No unexpected cardiac, hematologic, or other toxicities were observed. The CR rate at 1 year was 72% for group 1 and 68% for group 2.Conclusions: In patients with muscle-invasive UC who are not candidates for cystectomy, daily radiation combined with paclitaxel is an effective treatment strategy with a high completion rate and moderate toxicity. In patients with her2/neu-positive tumors, a group generally considered to have worse outcomes, the addition of trastuzumab appears to result in comparable efficacy and toxicity. Further biomarker-driven trials should be undertaken in advancing treatment of this challenging disease. [ABSTRACT FROM AUTHOR]

Purpose: To compare 2 stereotactic body radiation therapy (SBRT) schedules for medically inoperable early-stage lung cancer to determine which produces the lowest rate of grade ≥3 protocol-specified adverse events (psAEs) at 1 year.Methods and Materials: Patients with biopsy-proven peripheral (≥2 cm from the central bronchial tree) T1 or T2, N0 (clinically node negative by positron emission tomography), M0 tumors were eligible. Patients were randomized to receive either 34 Gy in 1 fraction (arm 1) or 48 Gy in 4 consecutive daily fractions (arm 2). Rigorous central accreditation and quality assurance confirmed treatment per protocol guidelines. This study was designed to detect a psAEs rate >17% at a 10% significance level (1-sided) and 90% power. Secondary endpoints included rates of primary tumor control (PC), overall survival (OS), and disease-free survival (DFS) at 1 year. Designating the better of the 2 regimens was based on prespecified rules of psAEs and PC for each arm.Results: Ninety-four patients were accrued between September 2009 and March 2011. The median follow-up time was 30.2 months. Of 84 analyzable patients, 39 were in arm 1 and 45 in arm 2. Patient and tumor characteristics were balanced between arms. Four (10.3%) patients on arm 1 (95% confidence interval [CI] 2.9%-24.2%) and 6 (13.3%) patients on arm 2 (95% CI 5.1%-26.8%) experienced psAEs. The 2-year OS rate was 61.3% (95% CI 44.2%-74.6%) for arm 1 patients and 77.7% (95% CI 62.5%-87.3%) for arm 2. The 2-year DFS was 56.4% (95% CI 39.6%-70.2%) for arm 1 and 71.1% (95% CI 55.5%-82.1%) for arm 2. The 1-year PC rate was 97.0% (95% CI 84.2%-99.9%) for arm 1 and 92.7% (95% CI 80.1%-98.5%) for arm 2.Conclusions: 34 Gy in 1 fraction met the prespecified criteria and, of the 2 schedules, warrants further clinical research. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to assess the association between positive post-radiation therapy (RT) biopsy results and subsequent clinical outcomes in males with localized prostate cancer. Methods and Materials Radiation Therapy Oncology Group study 94-08 analyzed 1979 males with prostate cancer, stage T1b-T2b and prostate-specific antigen concentrations of ≤20 ng/dL, to investigate whether 4 months of total androgen suppression (TAS) added to RT improved survival compared to RT alone. Patients randomized to receive TAS received flutamide with luteinizing hormone releasing hormone (LHRH) agonist. According to protocol, patients without evidence of clinical recurrence or initiation of additional endocrine therapy underwent repeat prostate biopsy 2 years after RT completion. Statistical analysis was performed to evaluate the impact of positive post-RT biopsy results on clinical outcomes. Results A total of 831 patients underwent post-RT biopsy, 398 were treated with RT alone and 433 with RT plus TAS. Patients with positive post-RT biopsy results had higher rates of biochemical failure (hazard ratio [HR] = 1.7; 95% confidence interval [CI] = 1.3-2.1) and distant metastasis (HR = 2.4; 95% CI = 1.3-4.4) and inferior disease-specific survival (HR = 3.8; 95% CI = 1.9-7.5). Positive biopsy results remained predictive of such outcomes after correction for potential confounders such as Gleason score, tumor stage, and TAS administration. Prior TAS therapy did not prevent elevated risk of adverse outcome in the setting of post-RT positive biopsy results. Patients with Gleason score ≥7 with a positive biopsy result additionally had inferior overall survival compared to those with a negative biopsy result (HR = 1.56; 95% CI = 1.04-2.35). Conclusions Positive post-RT biopsy is associated with increased rates of distant metastases and inferior disease-specific survival in patients treated with definitive RT and was associated with inferior overall survival in patients with high-grade tumors. [ABSTRACT FROM AUTHOR]

Purpose Radiation Therapy Oncology Group (RTOG) 0424 was a phase 2 study of a high-risk low-grade glioma (LGG) population who were treated with temozolomide (TMZ) and radiation therapy (RT), and outcomes were compared to those of historical controls. This study was designed to detect a 43% increase in median survival time (MST) from 40.5 to 57.9 months and a 20% improvement in 3-year overall survival (OS) rate from 54% to 65% at a 10% significance level (1-sided) and 96% power. Methods and Materials Patients with LGGs with 3 or more risk factors for recurrence (age ≥40 years, astrocytoma histology, bihemispherical tumor, preoperative tumor diameter of ≥6 cm, or a preoperative neurological function status of >1) were treated with RT (54 Gy in 30 fractions) and concurrent and adjuvant TMZ. Results From 2005 to 2009, 129 evaluable patients (75 males and 54 females) were accrued. Median age was 49 years; 91% had a Zubrod score of 0 or 1; and 69%, 25%, and 6% of patients had 3, 4, and 5 risk factors, respectively. Patients had median and minimum follow-up examinations of 4.1 years and 3 years, respectively. The 3-year OS rate was 73.1% (95% confidence interval: 65.3%-80.8%), which was significantly improved compared to that of prespecified historical control values ( P <.001). Median survival time has not yet been reached. Three-year progression-free survival was 59.2%. Grades 3 and 4 adverse events occurred in 43% and 10% of patients, respectively. One patient died of herpes encephalitis. Conclusions The 3-year OS rate of 73.1% for RTOG 0424 high-risk LGG patients is higher than that reported for historical controls ( P <.001) and the study-hypothesized rate of 65%. [ABSTRACT FROM AUTHOR]

In this issue of the International Journal of Radiation Oncology • Biology • Physics, Taylor et al present a meta-analysis of published data supporting 2 findings: (1) radiation dose escalation seems to benefit patients who receive radiation alone for non-small cell lung cancer; and (2) radiation dose escalation has a detrimental effect on overall survival in the setting of concurrent chemotherapy. The latter finding is supported by data but has perplexed the oncology community. Perhaps these findings are not perplexing at all. Perhaps it is simply another lesson in the major principle in radiation oncology, to minimize radiation dose to normal tissues. [ABSTRACT FROM AUTHOR]

Purpose: To study the dosimetric risk factors for radiation-induced proximal bronchial tree (PBT) toxicity in patients treated with radiation therapy for non-small cell lung cancer (NSCLC).Methods and Materials: Patients with medically inoperable or unresectable NSCLC treated with conventionally fractionated 3-dimensional conformal radiation therapy (3DCRT) in prospective clinical trials were eligible for this study. Proximal bronchial tree (PBT) and PBT wall were contoured consistently per RTOG 1106 OAR-Atlas. The dose-volume histograms (DVHs) of physical prescription dose (DVHp) and biological effective dose (α/β = 2.5; DVH2.5) were generated, respectively. The primary endpoint was PBT toxicities, defined by CTCAE 4.0 under the terminology of bronchial stricture/atelectasis.Results: Of 100 patients enrolled, with a median follow-up of 64 months (95% confidence interval [CI], 50-78), 73% received 70 Gy or greater and 17% developed PBT toxicity (grade 1, 8%; grade 2, 6%; grade 3, 0%; and grade 4, 3%). The median time interval between RT initiation and onset of PBT toxicity was 8.4 months (95% CI, 4.7-44.1). The combined DVHs showed that no patient with a PBT maximum physical dose <65 Gy developed any PBT toxicity. Cox proportional hazards analysis and receiver operating characteristic analysis demonstrated that V75 of PBT was the most significant dosimetric parameter for both grade 1+ (P = .035) and grade 2+ (P = .037) PBT toxicities. The dosimetric thresholds for V75 of PBT were 6.8% and 11.9% for grade 1+ and grade 2+ PBT toxicity, respectively.Conclusions: V75 of PBT appeared be the most significant dosimetric parameter for PBT toxicity after conventionally fractionated thoracic 3DCRT. Constraining V75 of PBT can limit clinically significant PBT toxicity. [ABSTRACT FROM AUTHOR]

Our objective was to assess the incidence and dose-volume predictors of radiation esophagitis (RE) in patients with breast cancer undergoing hypofractionated regional nodal irradiation. Eligible patients who received intensity modulated radiation therapy (RT) at the chest wall, the supraclavicular/infraclavicular fossa, level II axilla, and/or the internal mammary chain after mastectomy were included. The prescribed dose was 43.5 Gy in 15 fractions. RE was evaluated weekly during RT and at 1 and 2 weeks, followed by 3 and 6 months after RT, and was graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0. The esophagus was contoured from the lower border level of the cricoid cartilage to the lower margin of the aortic arch. Esophageal total volume, mean dose, maximum dose, and the relative volumes (RV) and absolute volumes (AV) receiving at least 5 to 45 Gy by 5-Gy increments (RV5-RV45 and AV5-AV45) were evaluated. Univariable and multivariable logistic regression analyses were performed to determine risk factors for RE, and receiver operating characteristic curves were obtained to identify the thresholds of esophageal dosimetric parameters. In total, 298 patients were included between May 8, 2020, and January 5, 2022 (minimum post-RT follow-up: 6 months). Grade 2 and 3 RE incidence was 40.9% (122/298) and 0.3% (1/298), respectively. No grade 4 or 5 RE was observed. Esophageal RV20-RV40 and AV35-AV40 were significantly associated with the risk of grade ≥2 RE after adjusting for tumor laterality and internal mammary nodal irradiation. RV25 and AV35 were optimum dose-volume predictors for grade ≥2 RE at thresholds 20% for RV25 (35.9% vs 60.9%; P =.04) and 0.27 mL for AV35 (31.0% vs 54.6%; P =.04). RE is common in patients with breast cancer undergoing hypofractionated regional nodal irradiation. Maintaining the upper esophageal V25 at <20% and V35 at <0.27 mL may decrease the risk of RE. [ABSTRACT FROM AUTHOR]

Purpose: A pay gap between men and women has been identified in many medical specialties. However, radiation oncology has been excluded from most analyses. This study sought to determine whether such a disparity exists among physicians in US public academic radiation oncology departments.Materials and Methods: Radiation oncology physician faculty at US public academic medical schools were identified in states that report public university radiation oncology faculty salary. Information pertaining to sex, academic rank, experience, clinical volume, and academic productivity were collected. Simple (1 predictor) and multiple (more than 1 predictor) generalized linear mixed-effect models for compensation were used to simultaneously assess the impact of physician-level and institutional-level variables, while accounting for potential correlations within institutions. To minimize the impact of faculty members working less than a full-time equivalent, a Monte Carlo simulation-based sensitivity analysis was conducted, and faculty with reported salaries under $175,000 were excluded.Results: A total of 247 eligible faculty (81 women, 166 men) with public salary data were identified at 22 US public academic radiation oncology departments in 14 states. Unadjusted mean salary was 12.6% ($48,974) lower for women ($341,173; 95% confidence interval [CI], $304,581-$382,162) than it was for men ($390,147; 95% CI, $353,693-$430,358; P < .01). A $26,458 gap (6.4%) in mean salary between men ($411,829; 95% CI, $367,282-$461,780) and women ($385,371; 95% CI, $342,388-$433,749) persisted on multivariable analysis after accounting for other factors (P < .01). The salary gap remained statistically significant on sensitivity analysis.Conclusions: Mean salary for women at US public academic radiation oncology departments was lower than mean salary for men, after adjusting for confounders. Our analysis was limited to public data and could not account for relevant private personal choices and departmental factors. The salary gap may differ in other practice environments. Further research is warranted to determine the cause of this disparity, whether it exists in other practice environments, and how to successfully address it. [ABSTRACT FROM AUTHOR]

Purpose: For pediatric patients with large, high-grade, extremity nonrhabdomyosarcoma soft-tissue sarcomas, preoperative radiation therapy (RT) provides the opportunity for smaller radiation fields and tumor shrinkage resulting in less extensive surgery. The potential disadvantage is an increased risk of wound complications after surgery compared with rates after postoperative chemoradiation. We assessed the impact of preoperative RT technique on target coverage in relationship to dose to skin and adjacent joints to determine whether acute wound complications and late musculoskeletal injury might be influenced by treatment technique.Methods and Materials: Of 550 eligible patients <30 years of age, 200 were enrolled in arm D of ARST0332 and received neoadjuvant ifosfamide/doxorubicin, then chemoradiotherapy (45 Gy and ifosfamide) and surgery followed by postoperative RT if gross or microscopic positive surgical margins. One-hundred thirteen patients had extremity nonrhabdomyosarcoma soft-tissue sarcomas, of which 56 patients had preoperative RT plans for digital review. The doses to the target volume, skin (surface to 5 mm depth), adjacent joint, and extremity diameter were analyzed with respect to RT technique.Results: Thirty-eight patients (65%) received 3-dimensional conformal RT (3D-CRT) and 18 (32%) received intensity modulated RT (IMRT). There was no difference in clinical target volume (CTV) size between groups (P = .920); however, IMRT plans had improved CTV coverage to 100% of the prescription dose compared with 3D-CRT plans (median CTV coverage, 92.7% vs 98.6%; P = .011). In patients without target overlap with the skin, IMRT use was associated with reduced percent volume of skin receiving 45 Gy or more (V45Gy) compared with 3D-CRT (median, 1.6% vs 6.3%, respectively; P = .005). IMRT was also associated with reduced V45Gy to the adjacent joint compared with 3D-CRT (median, 1.1% vs 13.2%; P = .018).Conclusions: Preoperative IMRT may improve CTV coverage and reduce the volume of skin and adjacent joint treated to high doses. Future studies should assess whether these dosimetric findings produce differences in clinical and toxicity outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To explore seromarker levels for associations with outcomes in locally advanced pancreatic cancer (LAPC) patients who received chemotherapy and stereotactic body radiation therapy (SBRT).Methods and Materials: Serum from LAPC patients in 2 prospective trials of hypofractionated SBRT (5-6.6 Gy × 5) was collected before SBRT. Proximity ligation assay quantified the expression levels of 36 pancreatic cancer-specific candidate seromarkers: Axl, BMP2, CA 125, CA 19-9, CEA, CXCL-1/6/9/10, EGFR, Gas6, Her2, IGF-2, IGFBP-2/3/7, IL-6/6Ra/7/8/12, mesothelin, MMP-1/2/3/7, osteopontin, PDGFRa, PDK1, PF4, RegIV, SPARC, TGF-β, VEGF-A/D, and YKL40. Seromarker values were log transformed owing to log-normal distribution of the values, and Cox regression analysis was performed to assess for any association with overall survival. The Benjamini-Hochberg method was used to control for a false discovery rate (FDR) of only 10%.Results: Sixty-four patients with LAPC were included. No clinical factors (including surgical resection, receipt of pre-SBRT chemotherapy, receipt of post-SBRT chemotherapy, performance status, and age) or potential biomarkers in the panel were associated with improved survival in this cohort after application of the FDR correction. Potential prognostic factors for improved survival for future investigation included surgical resection (P=.007, adjusted P=.153) and the serum expression of IL-8 (P=.006, adjusted P=.153), CA 19-9 (P=.031, adjusted P=.377), and MMP-1 (P=.036, adjusted P=.377).Conclusions: These data explore the expression of a panel of proteins in pre-SBRT serum of LAPC patients in the context of a conservative FDR correction. None of the clinical factors or expression levels of the serum proteins were found to be associated with survival; however, IL-8, CA 19-9, and MMP-1 were highlighted as possible candidates warranting inclusion in future seromarker studies in the ongoing efforts to identify tools for risk stratification and treatment allocation in LAPC. [ABSTRACT FROM AUTHOR]