National Trends in Treatment for Retroperitoneal Soft Tissue Sarcoma: A Modern Appraisal of Variability in Therapeutic Strategies.

BACKGROUND: Little level 1 evidence exists to guide multimodality treatment in retroperitoneal soft tissue sarcoma (RPS), which may lead to significant variation in therapeutic approaches. This analysis aimed to describe national RPS treatment trends and explore potential variability among low-/high-volume hospitals (LVH/HVHs). PATIENTS AND METHODS: In total, 5992 patients who underwent resection for primary RPS were retrospectively identified in the National Cancer Database (2004-2017). Time trend analyses examined rates of multivisceral resection (MVR), radiation, and chemotherapy use. LVHs were defined as those carrying out fewer than ten resections per year (N = 5433), whereas HVHs were defined as those carrying out ten or more (N = 559). Descriptive statistics and logistic regression models compared trends between groups. RESULTS: MVR was more frequent at HVHs (63.7% versus 43.5%, p < 0.001). Use of radiation varied widely by hospital volume. HVHs more frequently employed preoperative radiation as compared with LVHs (14.7% versus 8.1%, p < 0.001). Throughout the study period, LVHs increased utilization of preoperative radiation (2.6% to 12.0%, p < 0.001) whereas rates at HVHs remained stable. Overall, LVHs utilized postoperative radiation significantly more frequently as compared with HVHs (14.7% versus 2.7%, respectively, p < 0.001). Postoperative radiation at LVHs remained stable until 2013 and sharply declined thereafter (16.7% to 6.9%, p < 0.001). Rates of postoperative radiation use at HVHs remained lower than those at LVHs at all time points. CONCLUSIONS: Strategies for resection and radiation use at LVHs have trended towards those of HVHs. Current national implementation of preoperative radiation, MVR, and chemotherapy remains heterogeneous. These findings inform future trial design and support standardization of care.

Initial Clinical Experience With Novel Directional Low-Dose Rate Brachytherapy for Retroperitoneal Sarcoma.

BACKGROUND: A novel Palladium-103 low-dose rate (LDR) brachytherapy device was developed to provide dose-escalation to the tumor bed after resection while shielding adjacent tissues. This multicenter report describes the initial experience with this device in patients with retroperitoneal sarcoma (RPS). MATERIALS AND METHODS: Patients with recurrent RPS, prior radiotherapy, and/or concern for positive margins were considered. An LDR brachytherapy dose of 20-60 Gy was administered, corresponding to biologically effective dose values of 15-53 Gy and equivalent dose values of 12-43 Gy. RESULTS: Six patients underwent implantation at four institutions. Of these, five had recurrent disease in the retroperitoneum or pelvic sidewall, one had untreated locally advanced leiomyosarcoma, two had prior external beam radiation therapy at the time of initial diagnosis, and four received neoadjuvant external beam radiation therapy plus brachytherapy. The device was easily implanted and conformed to the treatment area. Median follow-up was 16 mo; radiation was delivered to the at-risk margin with minimal irradiation of adjacent structures. No local recurrences at the site of implantation, device migration, or radiation-related toxicities were observed. CONCLUSIONS: The novel LDR directional brachytherapy device successfully delivered a targeted dose escalation to treat RPS high-risk margins. Lack of radiation-related toxicity demonstrates its safety.

Retroperitoneal Sarcomas: Does Laterality Matter?

BACKGROUND: Sarcomas are malignant tumors of connective tissue that can vary widely in etiology. Parameters such as grade, extent of resection, and tumor integrity have been shown to affect prognosis. Our principal aim was to examine associations between the laterality of retroperitoneal sarcomas and tumor characteristics, treatment, and patient outcomes. MATERIALS AND METHODS: We performed a retrospective study of patients treated at our tertiary referral center with a diagnosis of primary retroperitoneal sarcoma who underwent tumor resection. Categorical variables were compared using the chi-square test, whereas continuous variables were compared using one-way analysis of variance. Cox regression was used to estimate the risk of death. RESULTS: Data from 106 patients were analyzed. A greater proportion of bilateral or midline tumors were leiomyosarcomas (P = 0.02), whereas right-sided tumors were more likely to be liposarcoma (P = 0.02). There was no significant relationship between laterality and tumor grade or stage. Two-thirds of patients had at least one contiguous organ resected (n = 68, 65.4%). Patients with nephrectomy during sarcoma resection were more likely to have right-sided disease (P = 0.02). Splenectomy and pancreatectomy were associated with left-sided disease (P < 0.01; P < 0.01), and pancreaticoduodenectomies with bilateral or midline disease (P < 0.001). Adjusting for age, sex, race, grade, stage, histology, and treatment, there was no increased risk of death or recurrence based on laterality. CONCLUSIONS: Although laterality did not seem to have a measurable relationship with patient outcomes or survival, there was a significant association between laterality, tumor histology, and resection of contiguous organs. These preliminary findings warrant further investigation.

Phase I Study of Concomitant Pemetrexed and Cisplatin Plus External Beam Radiation Therapy in Patients with Locally Advanced or Metastatic Esophageal or Gastroesophageal Junction Carcinomas.

PURPOSE: To establish the maximum tolerated dose (MTD) and safety profile of bi-weekly Pemetrexed (PEM) when combined with weekly cisplatin (CDDP) and standard dose external beam radiation (EBRT) in patients with locally advanced or metastatic esophageal and gastroesophageal junction (GEJ) carcinomas. METHODS: We conducted an open label, single institution, phase I dose escalation study designed to evaluate up to 15-35 patients with advanced or metastatic esophageal and GEJ carcinomas. RESULTS: 10 patients were treated with bi-weekly PEM, weekly CDDP, and EBRT. The MTD of bi-weekly PEM was determined to be 500 mg/m(2).

External beam radiation therapy (EBRT) for asymptomatic bone metastases in patients with solid tumors reduces the risk of skeletal-related events (SREs).

BACKGROUND: The potential benefit of administering external beam radiation therapy (EBRT) to patients with asymptomatic bone metastases has rarely been addressed in clinical investigations. The aim of this study was to determine if cancer patients who were treated with EBRT for asymptomatic bone metastases experienced later onset of pain and skeletal-related events (SREs) than those who were untreated. METHODS: A retrospective chart review was conducted for prostate, breast, and lung cancer patients with asymptomatic bone metastases treated at a single cancer center from 2007 to 2017. Patients who received EBRT for asymptomatic bone metastases were compared to those who received medical or supportive therapy only. RESULTS: When all cancer groups were combined, the median time from the diagnosis of asymptomatic bone metastases to either moderate-to-severe pain or an SRE was 25 months for the untreated patients and 81 months for the patients receiving EBRT (P<0.001). The delay in the first occurrence of pain or an SRE following EBRT was observed for patients with prostate cancer (P=0.025) and lung cancer (P=0.029) but not for patients with breast cancer. In a multivariate analysis, EBRT was again shown to reduce the risk of developing pain or an SRE when all cancer types were combined (P=0.006). OS was not altered by EBRT. CONCLUSIONS: EBRT administered to a group of prostate, lung, and breast cancer patients with asymptomatic bone metastases was associated with an increase in time to the first occurrence of either pain or an SRE. These data demonstrate that there may be clinical settings in which EBRT should be used to delay or prevent late complications of bone metastases that are asymptomatic at the time of diagnosis.

Phase 2 trial of guideline-based postoperative image guided intensity modulated radiation therapy for prostate cancer: Toxicity, biochemical, and patient-reported health-related quality-of-life outcomes.

PURPOSE: The purpose of this study was to characterize treatment-related toxicities, health-related quality of life (HRQOL), and biochemical outcomes in patients treated with postoperative image guided intensity modulated radiation therapy (IMRT) for prostate cancer using a consensus guideline for defining the clinical target volume. METHODS AND MATERIALS: Between August 2007 and October 2008, patients considered for radiation therapy (RT) after prostatectomy were enrolled. The clinical target volume (prostate bed) was delineated according to published consensus guidelines, and patients were prescribed a dose of 66 Gy in 33 fractions. Radiation treatment planning prioritized rectal dose constraints over target volume coverage. Treatment was delivered by use of IMRT and daily cone beam computed tomographic guidance. Toxicity (graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events) and HRQOL assessments according to the Expanded Prostate Cancer Index Composite (EPIC) questionnaire were collected prospectively at baseline, at week 5 (during RT), at 3 months, and at yearly follow-up visits. Cumulative toxicity and biochemical relapse-free rates were calculated by the Kaplan-Meier method. Paired Student t tests with multiple testing correction were used to assess changes in HRQOL. RESULTS: A total of 68 men were evaluated, with median follow-up of 5.9 years. Fifty-three patients (77.9%) and 15 patients (22.1%) were treated with salvage and adjuvant RT, respectively. Primary planning objectives were met in most cases (97.1%), but planning target volume coverage was compromised in 40% of cases because of large planning target volumes (mean 347.6 cm(3)). There were no grade 3 or 4 acute toxicities. Cumulative 5-year incidence of late gastrointestinal and genitourinary grade 2 toxicities was 12.3% (95% confidence interval [CI], 11.1%-13.5%) and 10.6% (95% CI, 9.5%-11.6%), respectively. No grade 3 or 4 late toxicities were observed. Transient declines in EPIC gastrointestinal domain summary score (mean 87.66 at 3 months vs 92.76 at baseline; P = .006) and genitourinary irritative subscale (week 5 mean score 83.37 vs 89.45 at baseline; P = .007) were observed. Complete recovery occurred between 3 and 12 months after therapy, remaining stable compared with baseline at 5-year follow-up. Sexual HRQOL remained stable at 5 years, with an improving trend in bother subscale. Biochemical relapse-free rate at 5 years was 72.7% (95% CI, 61.9%-83.5%). CONCLUSIONS: Guideline-based postprostatectomy image guided IMRT with rigid rectal dose constraints resulted in favorable toxicity profiles; long-term stability in gastrointestinal, genitourinary, and sexual HRQOL; and expected biochemical control rates. Concerns regarding toxicity and HRQOL should not preclude recommendation for RT after prostatectomy.