Patterns of major wound complications following multidisciplinary therapy for lower extremity soft tissue sarcoma.

BACKGROUND AND OBJECTIVES: The purpose of this study was to determine the pattern and timing of major wound complications (MWCs) in patients at our institution who received multimodality treatment for lower extremity soft tissue sarcoma (LE-STS) and to evaluate the impact of MWCs on tumor control and patient outcomes. METHODS: The medical records of 102 LE-STS patients treated with limb-sparing surgery and radiation therapy were reviewed. MWCs were defined as secondary operations with anesthesia, seroma/hematoma aspiration, admission for IV antibiotics, or persistent deep packing. RESULTS: MWCs occurred in 22% of patients, with 45% of events occurring >120 days after resection. On multivariate analysis, preoperative external beam radiation therapy (EBRT) (OR 4.29, 95% CI 1.06-17.40, P = 0.042) and skin graft placement (OR 6.39, 95% CI 1.37-29.84, P = 0.018) were found to be independent predictors of MWCs. MWC occurrence did not predict for chronic toxicity and did not impact tumor control or survival. CONCLUSIONS: A considerable proportion of MWCs occur >120 days from surgical resection with preoperative EBRT and skin graft placement independent predictors for MWCs. While an additional source of morbidity, MWC occurrence did not impact tumor control, nor did it predict for chronic toxicity. J. Surg. Oncol. 2016;114:385-391. © 2016 Wiley Periodicals, Inc.

The role of modern radiation therapy in the management of extremity sarcomas.

For nearly half a decade, surgery and radiation therapy have been used in combination to achieve the goal of limb preservation in extremity soft tissue sarcoma, with success rates in excess of 90%. Common decision points in therapeutic radiation delivery for sarcoma are discussed, including preoperative versus postoperative irradiation, the postoperative boost, and when irradiation might be unnecessary. We describe specialized techniques, such as brachytherapy and intraoperative irradiation. The data driving current practice is summarized.

Computed tomography-based radiation therapy of ovarian remnants for symptomatic persistent endometriosis.

BACKGROUND: Endometriosis, a major cause of pelvic pain in women, is driven by estrogen. Ovarian remnant irradiation may alleviate pelvic pain by eliminating estrogen production in appropriately selected women with endometriosis. CASE: Three patients with endometriosis causing incapacitating pelvic pain received 3D-imaging-based external beam radiation to doses of 1,500 to 2,100 cGy. All had pre-irradiation premenopausal follicle stimulating hormone levels and imaging evidence of ovarian remnants. None were candidates for further medical or surgical interventions. By 3 months after radiation, follicle stimulating hormone levels reached postmenopausal levels in all three patients, with complete resolution of the severe pelvic pain. CONCLUSION: Radiation therapy effectively induced menopause and relieved refractory pain from endometriosis. Careful selection of patients is necessary, given the potential for an increased long-term risk of radiation-related complications.

Radiation Dose to the Thoracic Vertebral Bodies Is Associated With Acute Hematologic Toxicities in Patients Receiving Concurrent Chemoradiation for Lung Cancer: Results of a Single-Center Retrospective Analysis.

PURPOSE: To test the hypothesis that increasing radiation therapy (RT) dose to the thoracic vertebral bodies (TVBs) contributes to the development of hematologic toxicities (HTs) in patients with lung cancer. METHODS AND MATERIALS: Cases of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) treated with definitive chemoradiation with concurrent platinum-based doublet chemotherapy at our institution from 2007 to 2016 were identified. Mean TVB dose and the volume of TVBs receiving at least 5 to 60 Gy (V5-V60) were retrospectively recorded. Logistic regression was used to test associations between grade ≥3 HT (HT3+) and dosimetric/clinical parameters. Normal tissue complication probability was evaluated using the Lyman-Kutcher-Burman (LKB) model for HT3+, and receiver operating characteristics analysis was used to determine dosimetric cut-points. RESULTS: We identified 201 patients, the majority having NSCLC (n=162, 81%) and stage III to IV disease (n=179, 89%). All patients received either cisplatin/etoposide (n=107, 53%) or carboplatin/paclitaxel (n=94, 47%). Median RT dose was 60 Gy (range, 60-70 Gy). The rate of HT3+ was 49% (n=99). Increasing mean TVB dose (per Gy) was associated with higher odds of developing HT3+ (odds ratio 1.041, 95% confidence interval 1.004-1.080, P=.032), as were increasing TVB V5 to V20. These dosimetric correlates to HT3+ persisted on multivariate analysis. Constrained optimization of the LKB model for HT3+ yielded the parameters: n=1, m=1.79, and TD50=21.4 Gy. Optimal cut-points identified were V5=65%, V10=60%, V20=50%, and mean dose=23.5 Gy. Patients with values above these cut-points had an approximately 2-fold increased risk of HT3+. CONCLUSIONS: We found that mean TVB dose and low-dose parameters (V5-V20) were associated with HT3+ in chemoradiation for lung cancer. Per the LKB model, bone marrow behaves like a parallel organ (n=1), implying that mean TVB dose is a useful predictor for toxicity. These data suggest that efforts to spare dose to the TVBs may reduce rates of severe HT.

Identifying patterns of care for elderly patients with non-surgically treated stage III non-small cell lung cancer: an analysis of the national cancer database.

BACKGROUND: To compare patterns of care for elderly patients versus non-elderly patients with non-surgically treated stage III non-small cell lung cancer (NSCLC) using the National Cancer Database (NCDB). We hypothesize that elderly patients are less likely to receive curative treatments, including concurrent chemoradiation (CCRT), compared to non-elderly patients. METHODS: We identified patients from the NCDB between 2003 and 2014 with non-surgically treated stage III NSCLC. We defined elderly as ≥70 years old and non-elderly <70 years old. Treatment categories included: no treatment, palliative treatment (chemotherapy alone, radiation (RT) alone <59.4 Gy or chemoradiation (CRT) <59.4 Gy), or definitive treatment (RT alone ≥59.4 Gy or CRT ≥59.4 Gy). Differences in treatment between elderly and non-elderly were tested using the χ2 test. RESULTS: We identified 57,602 elderly and 55,928 non-elderly patients. More elderly patients received no treatment (24.5% vs. 13.2%, P < 0.0001) and the elderly were less likely to receive definitive treatment (48.5% vs. 56.3%, P < 0.0001). CCRT was delivered in a significantly smaller proportion of elderly vs. non-elderly patients (66.0% vs. 78.9%, P < 0.0001 in patients treated with definitive intent; 32.0% vs. 44.5%, P < 0.0001 in patients receiving any treatment; and 24.2% vs. 38.6%, P < 0.0001 amongst all patients). CONCLUSIONS: In this large study of patients with non-surgically treated stage III NSCLC, elderly patients were less likely to receive any treatment or treatment with definitive intent compared to the non-elderly. The lack of use of concurrent or sequential chemotherapy in the elderly with stage III NSCLC suggests that the optimal treatment approach for this vulnerable population remains undefined.

The Addition of Chemotherapy to Radiation Therapy Improves Survival in Elderly Patients with Stage III Non-Small Cell Lung Cancer.

INTRODUCTION: Elderly patients account for the majority of lung cancer diagnoses but are poorly represented in clinical trials. We evaluated the overall survival (OS) of elderly patients with stage III NSCLC treated with definitive radiation compared with that of patients treated with definitive chemoradiation. METHODS: We conducted a comparative effectiveness study of radiation therapy versus chemoradiation in elderly (≥70 years old) patients with stage III NSCLC not treated surgically diagnosed from 2003 to 2014; the patients were identified by using the National Cancer Database. Two cohorts were evaluated: patients (n = 5023) treated with definitive radiation (≥59.4 Gy) and patients (n = 18,206) treated with definitive chemoradiation. Chemoradiation was further defined as concurrent (radiation and chemotherapy started within 30 days of each other) or sequential (radiation started >30 days after chemotherapy). We compared OS between the treatment groups by using the Kaplan-Meier method and Cox proportional hazards regression before and after propensity score matching (PSM). RESULTS: Treatment with chemoradiation was associated with improved OS versus that with radiation both before PSM (hazard ratio [HR] = 0.66, 95% confidence interval [CI]: 0.64-0.68, p < 0.001) and after PSM (HR = 0.67, 95% CI: 0.64-0.70, p < 0.001). Relative to concurrent chemoradiation, sequential chemoradiation was associated with a 9% reduction in the risk for death (HR = 0.91, 95% CI: 0.85-0.96, p = 0.002). CONCLUSIONS: We found that definitive chemoradiation resulted in a survival advantage compared with definitive radiation in elderly patients. Sequential chemotherapy and radiation was superior to concurrent chemoradiation. Although prospective trials are needed, this analysis suggests that chemoradiation should be strongly considered for elderly patients and the optimal sequencing of chemotherapy and radiation remains an unanswered question for this patient population.

Intensity-modulated proton therapy for elective nodal irradiation and involved-field radiation in the definitive treatment of locally advanced non-small-cell lung cancer: a dosimetric study.

BACKGROUND: Photon involved-field (IF) radiation therapy (IFRT), the standard for locally advanced (LA) non-small cell lung cancer (NSCLC), results in favorable outcomes without increased isolated nodal failures, perhaps from scattered dose to elective nodal stations. Because of the high conformality of intensity-modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA-NSCLC. PATIENTS AND METHODS: IMPT IFRT plans were generated to the same total dose of 66.6-72 Gy received by 20 LA-NSCLC patients treated with photon IFRT. IMPT ENI plans were generated to 46 cobalt Gray equivalent (CGE) to elective nodal planning treatment volumes (PTV) plus 24 CGE to IF-PTVs. RESULTS: Proton IFRT and ENI improved the IF-PTV percentage of volume receiving 95% of the prescribed dose (D95) by 4% (P < .01) compared with photon IFRT. All evaluated dosimetric parameters improved significantly with both proton plans. The lung percentage of volume receiving 20 Gy/CGE (V20) and mean lung dose decreased 18% (P < .01) and 36% (P < .01), respectively, with proton IFRT, and 11% (P = .03) and 26% (P < .01) with ENI. The mean esophagus dose decreased 16% with IFRT and 12% with ENI; heart V25 decreased 63% with both (all P < .01). CONCLUSION: This study demonstrates the feasibility of IMPT for LA-NSCLC ENI. Potential decreased toxicity indicates that IMPT could allow ENI while maintaining a favorable therapeutic ratio compared with photon IFRT.

Recurrence patterns and survival for patients with intermediate- and high-grade myxofibrosarcoma.

PURPOSE: Myxofibrosarcoma (MFS) is a rare sarcoma with a predilection for multiple local recurrences (LR), for which optimal treatment has not been defined. We reviewed our experience to determine the impact of surgery and radiation therapy (RT) on pattern of recurrence, limb salvage, and overall survival (OS). METHODS AND MATERIALS: Between 1995 and 2005, 36 patients with localized intermediate- or high-grade MFS were treated at our institution. Data on clinicopathologic features, treatments, and patient outcomes were reviewed and analyzed. RESULTS: Median age was 72.5 years (range, 42-96 years). Median tumor size was 7.5 cm, and 34 tumors (94%) were high grade. All patients underwent surgery at our institution, including re-resections in 20 patients (56%) after initial surgery elsewhere. Margins were microscopically positive in 9 patients (25%). RT was given to 28 patients (78%) pre - and/or postoperatively. After a median follow-up of 3.5 years (range, 0.4-12.4 years), 11 patients (31%) developed LR. There were no significant predictors for LR on univariate analysis, including margin status or use of RT. Limb salvage was ultimately achieved in only 5 of 11 LRs (45%) because of multiple subsequent LRs. Distant recurrence (DR) occurred in 6 patients (17%). Median and 4-year OS were 96 months and 65%, respectively. Seven patients (19%) died of tumor-related causes, 6 of whom had DRs. On univariate analysis, tumor size was associated with OS. CONCLUSIONS: Despite aggressive surgery and RT, intermediate- and high-grade MFS are associated with a high rate of LR that adversely affects limb preservation. More aggressive local treatment strategies are necessary.