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.

Treatment Patterns and Distance to Treatment Facility for Soft Tissue Sarcoma of the Extremity.

BACKGROUND: The impact that distance traveled to receive treatment has on treatments and outcomes among patients with soft tissue sarcoma (STS) of the extremity has yet to be thoroughly investigated. METHODS: Information on patients treated for STS of the extremity between 2006 and 2015 was obtained from the National Cancer Database. Patients were stratified into two groups based on median distance traveled to receive treatment. Chi-square tests assessed associations between categorical variables and distance to treatment. Kaplan-Meier survival estimates and Cox regression were used to estimate survival. RESULTS: The sample included 21,763 patients. The mean age was 59.3 y, 54.6% were men, and 83.2% were white. The median distance traveled to the treating facility was 15.6 miles. Compared with patients who traveled <15 miles, those who traveled ≥15 miles were more likely to have undifferentiated rather than well-differentiated tumors (odds ratio [OR], 1.23; 95% confidence interval [95% CI], 1.10-1.37), and stage II rather than stage I disease (OR, 1.14; 95% CI, 1.04-1.24). They were also more likely to undergo limb-sparing resection (OR, 1.58; 95% CI, 1.39-1.79) or amputation (OR, 1.72; 95% CI, 1.44-2.07) rather than no surgery and less likely to have positive margins (OR, 0.86; 95% CI, 0.79-0.93). There was no difference in the risk of death between patients who traveled ≥15 miles and those who did not (hazard ratio, 1.00; 95% CI, 0.94-1.07). CONCLUSIONS: Although clinical characteristics and treatments may differ based on distance traveled, survival appears equivalent. Further research into reasons why greater distance traveled is associated with more advanced disease, but comparable survival is warranted.

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).

Gender Equity in Radiation Oncology: Culture Change Is a Marathon, Not a Sprint.

The specialty of radiation oncology's gender diversity is lagging other medical specialties. The lack of gender diversity in radiation oncology has been demonstrated at all stages of career, from medical schools to department chairs. Multiple articles have demonstrated literature-based benefits of inclusion of a diverse group of female colleagues. This editorial is intended to note areas of progress and highlight resources available to support gender equity in the field of radiation oncology.

Radiation Oncologist Perceptions and Utilization of Digital Patient Assessment Platforms.

BACKGROUND: Patient engagement is increasing in the presence of digital patient assessment platforms, or physician rating websites. Despite this rapid growth, data remains insufficient regarding how these evaluations impact radiation oncologists. OBJECTIVES: The purpose of this study was to assess radiation oncologists worldwide on their awareness and noted effects of digital patient assessment platforms. METHODS: An electronic survey was delivered to 6,199 members of the American Society of Radiation Oncology. Subjects were radiation oncologists practicing throughout the world. The survey consisted of 14 questions focused on demographics, practice details, patient volume, institutional utilization of patient reviews, and perceptions of radiation oncologists on health care reviews provided by patients. RESULTS: There were 447 responses from practicing radiation oncologists in total, 321 (72%) of which are in the US. Most respondents (228; 51%) either agreed or strongly agreed that patients consider online reviews when deciding which physician to visit. Of all respondents, 188 (42%) reported that their institution checks their online feedback, whereas 157 (36%) and 99 (22%) respectively reported not knowing, or to their knowledge their institution does not check their online feedback. Respondents who saw more than the average number of consults per week were significantly more likely to receive negative feedback (P = 0.005). Forty-five percent of respondents agreed or strongly agreed that online virtual assessment tools contribute to physician burnout. Respondents (100; 22%) who received inappropriate or misdirected feedback were significantly more likely to report that virtual reviews contribute to burnout (P = 0.001). CONCLUSIONS: Radiation oncologists need to be aware that self-reported patient assessments are a data point in the quality of a physician and health care establishment. To best ensure appropriate feedback of a physician's capabilities as a doctor, leadership and employee alignment for patient experience are now more important than ever.

Locally Advanced Rectal Cancer Evaluation by Magnetic Resonance Imaging after Neoadjuvant Therapy on Decision Making: Cancer Center Experience and Literature Review.

PURPOSE: An accurate clinical and radiological staging is the pyramid of treatment decisions in locally advanced rectal cancer (LARC). Guidelines recommended neoadjuvant chemoradiation therapy (CRT) followed by surgical resection for fit patients with LARC. Determining the aggressiveness of intervention while avoiding needless morbidity according to patient risk remains an unmet pre-operative decision-making need. With newer magnetic resonance imaging (MRI) techniques and image acquisition available at our Cancer Center, we seek to retrospectively review the correlation between pre- and post-CRT MRI response to the surgical pathological stage in order to aide multidisciplinary team decision making. METHODS: Our Cancer Center Rectal Cancer Registry between 2011 and 2015 included 57 patients with LARC, 20 completed standard CRT with surgery, and of those 10 had repeated MRI after CRT. RESULTS: Our retrospective case series revealed that 90% of the patients had a downstage tumor response on surgical specimen compared to radiological evaluation after CRT, and furthermore, all patients who were re-staged with MRI prior to surgery correlated with the gold standard pathological stage (p = 0.02). CONCLUSIONS: Post-CRT MRI could potentially aide decision making to further avoid 20% of patients with a complete pathological response from a morbid surgery, whereas 10% of patients with an upstaged disease state may require a more aggressive neoadjuvant or planned surgical intervention. We concluded that future multidisciplinary oncology care treatment decision making would benefit from a repeat MRI after neoadjuvant CRT of LARC.

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.

Soft tissue sarcoma of the extremity: Characterizing symptom duration and outcomes.

BACKGROUND: We sought to investigate how the interval between symptom onset and diagnosis of soft tissue sarcoma (STS) of the extremity was associated with survival. METHODS: Patients treated for extremity STS years 2006-2015 were stratified by symptom duration: at least two, six or twelve months between symptom onset and diagnosis. Chi-square tests compared patient and tumor-related characteristics based on symptom duration. Survival analysis included Cox regression and Kaplan-Meier estimates. RESULTS: Of 113 patients included, mean age was 56.7 years, 52.2% were male, and 75.2% were white. Median tumor size was 75 mm, 48.7% were grade 3, and 38.1% were stage I. With symptom duration of either at least 6 or 12 months, a greater proportion of patients who experienced the specified symptom duration had lower grade tumors (p < 0.01 and p = 0.01, respectively) and lower stage disease (p < 0.01 and p = 0.02, respectively) than those who did not. Among all patients, survival estimates were similar between those who experienced a symptom duration of 2 (p = 0.12), 6 (p = 0.18) or 12 (p = 0.61) months and those who did not. CONCLUSION: Patients with extremity STS who tolerated a longer symptom duration had less advanced disease. Reasons for prolonged symptom duration and methods to address these factors warrant further investigation.

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.