Natural history of intraosseous low-grade chondroid lesions of the proximal humerus.

Introduction: Enchondromas and grade 1 chondrosarcomas are commonly encountered low-grade chondroid tumors in the proximal humerus. While there is a concern for malignant transformation, few studies have evaluated the natural history of these lesions. The purpose of this study is to evaluate the natural history of proximal humerus low-grade chondroid lesions managed both conservatively and surgically, and to define management criteria using clinical and radiographic findings for these low-grade chondroid lesions. Methods: The patient population included 90 patients intended for conservative treatment and 22 patients proceeding directly to surgery. Data collection was based on a combination of chart review and patient imaging and descriptive statistics were calculated for each group. Results: No malignant transformations were noted amongst any group. In the conservative treatment group, 7 of 64 (11%) progressed to surgery after an average of 20.3 months of conservative treatment due to persistent pain unexplained by other shoulder pathology. Importantly, 71% experienced continued pain at a mean of 53.1 months post-operatively. The group that went directly to surgery also demonstrated pain in 41% at an average follow-up of 57.3 months. Discussion: Low-grade cartilaginous lesions of the proximal humerus without concerning imaging findings can be managed with conservative treatment and the risk of malignant transformation is very low. Patients with a clear source of their shoulder pain unrelated to their tumor and without concerning characteristics on imaging can be managed with serial annual radiographic imaging. Patients undergoing surgery for these indolent tumors are likely to experience persistent pain even after surgery.

Pathologic Complete Response and Clinical Outcomes in Patients With Localized Soft Tissue Sarcoma Treated With Neoadjuvant Chemoradiotherapy or Radiotherapy: The NRG/RTOG 9514 and 0630 Nonrandomized Clinical Trials.

Importance: Pathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS). Objective: We sought to determine the prognostic significance of pCR on survival outcomes in STS for patients receiving neoadjuvant chemoradiotherapy (CT-RT) (Radiation Therapy Oncology Group [RTOG] 9514) or preoperative image-guided radiotherapy alone (RT, RTOG 0630) and provide a long-term update of RTOG 0630. Design, Setting, and Participants: RTOG has completed 2 multi-institutional, nonrandomized phase 2 clinical trials for patients with localized STS. One hundred forty-three eligible patients from RTOG 0630 (n = 79) and RTOG 9514 (n = 64) were included in this ancillary analysis of pCR and 79 patients from RTOG 0630 were evaluated for long-term outcomes. Intervention: Patients in trial 9514 received CT interdigitated with RT, whereas those in trial 0630 received preoperative RT alone. Main Outcomes and Measures: Overall and disease-free survival (OS and DFS) rates were estimated by the Kaplan-Meier method. Hazard ratios (HRs) and P values were estimated by multivariable Cox model stratified by study, where possible; otherwise, P values were calculated by stratified log-rank test. Analysis took place between December 14, 2016, to April 13, 2017. Results: Overall there were 42 (53.2%) men; 68 (86.1%) were white; with a mean (SD) age of 59.6 (14.5) years. For RTOG 0630, at median follow-up of 6.0 years, there was 1 new in-field recurrence and 1 new distant failure since the initial report. From both studies, 123 patients were evaluable for pCR: 14 of 51 (27.5%) in trial 9514 and 14 of 72 (19.4%) in trial 0630 had pCR. Five-year OS was 100% for patients with pCR vs 76.5% (95% CI, 62.3%-90.8%) and 56.4% (95% CI, 43.3%-69.5%) for patients with less than pCR in trials 9514 and 0630, respectively. Overall, pCR was associated with improved OS (P = .01) and DFS (HR, 4.91; 95% CI, 1.51-15.93; P = .008) relative to less than pCR. Five-year local failure rate was 0% in patients with pCR vs 11.7% (95% CI, 3.6%-25.1%) and 9.1% (95% CI, 3.3%-18.5%) for patients with less than pCR in 9514 and 0630, respectively. Histologic types other than leiomyosarcoma, liposarcoma, and myxofibrosarcoma were associated with worse OS (HR, 2.24; 95% CI, 1.12-4.45). Conclusions and Relevance: This ancillary analysis of 2 nonrandomized clinical trials found that pCR was associated with improved survival in patients with STS and should be considered as a prognostic factor of clinical outcomes for future studies. Trial Registration: ClinicalTrials.gov Identifiers: RTOG 0630 (NCT00589121); RTOG 9514 (NCT00002791).

Radiation Therapy for Treatment of Soft Tissue Sarcoma in Adults: Executive Summary of an ASTRO Clinical Practice Guideline.

PURPOSE: This guideline provides evidence-based recommendations addressing the indications for radiation therapy (RT), sequencing of local therapies, and appropriate dose and planning techniques for management of primary, operable, localized, soft tissue sarcoma (STS) in adults. METHODS: The American Society for Radiation Oncology convened a task force to address 5 key questions focused on the use of RT for management of STS. These questions included indications for RT for STS of the extremity and superficial trunk; considerations for sequencing of RT with respect to surgery, dose of RT, appropriate treatment volumes and techniques; and the role of RT in management of retroperitoneal sarcoma. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: Multidisciplinary evaluation and decision making are recommended for all cases of STS. RT is recommended for patients in whom there is increased risk of local recurrence of resected STS, particularly if close or microscopically positive margins are anticipated or have occurred. When RT is indicated, preoperative RT is strongly recommended over postoperative RT. Postoperative RT is conditionally recommended in specific clinical circumstances (eg, uncontrolled pain or bleeding) or when the risk of wound complications outweighs that of late toxicity from RT. Routine use of RT in addition to oncologic resection for retroperitoneal sarcoma is conditionally not recommended. When RT is used for retroperitoneal sarcoma, preoperative RT is recommended, whereas postoperative RT is not recommended. CONCLUSIONS: Based on currently published data, the American Society for Radiation Oncology task force has proposed evidence-based recommendations regarding the use of RT for STS in adults. Future studies will ascertain whether alterations in dosing and sequencing may optimize outcomes and quality of life.

Smoking is predictive of poorer distant metastasis-free and progression free-survival in soft tissue sarcoma patients treated with pre-operative radiotherapy or chemoradiotherapy.

BACKGROUND: Soft tissue sarcomas (STS) are often treated with pre-operative radiation (RT), with or without chemotherapy, followed by wide local excision. Prognosis for these patients involves an interplay of tumor and patient characteristics. Known prognostic determinants include tumor size, grade, response to therapy, and patient characteristics such as age. While smoking is negatively correlated with outcomes in various malignancies, the impact on STS is unknown. We aimed to assess if smoking impacts overall (OS), distant metastasis-free (DMFS), and progression-free (PFS) survival in patients with STS treated with pre-operative RT. METHODS: Between 2000 and 2015, 166 patients with STS were identified from our prospective database. Patient variables were retrospectively reviewed. Smoking was defined as a ≥ 10 pack year history of current and former smokers. Survival was evaluated using the fisher exact test for univariate (UVA) and logistic regression for multivariate (MVA) analysis. RESULTS: Fifty-seven (34.3%) patients had smoking histories of ≥ 10 pack years. On UVA, smoking was associated with decreased DMFS (p = 0.0009) and PFS (p = 0.0036), but not OS (p = 0.05). Smoking held significance on MVA for both DMFS and PFS. Current smokers and patients with ≥ 24-month follow-up demonstrated decreased DMFS and PFS on UVA and MVA. CONCLUSIONS: Current smokers and patients with a significant smoking history demonstrated decreased DMFS and PFS in STS patients treated with pre-operative RT. Smoking may cause immunologic compromise and therefore lead to higher rates of progression and distant metastasis.

Overall survival after resection of retroperitoneal sarcoma at academic cancer centers versus community cancer centers: An analysis of the National Cancer Data Base.

BACKGROUND: Operative resection remains the definitive curative therapy for retroperitoneal sarcoma. Data published recently show a correlation between improved outcomes for complex oncologic operations and treatment at academic centers. For large retroperitoneal sarcomas, operative resection can be complex and require multidisciplinary care. We hypothesized that survival rates vary between type of treating center for patients undergoing resection for retroperitoneal sarcoma. METHODS: Patients with stage I to III nonmetastatic retroperitoneal sarcomas who underwent operative resection were identified from the National Cancer Database during the years 2004-2013. Treating centers were categorized as academic cancer centers or community cancer centers. Overall survival was analyzed by log-rank test and graphed using Kaplan-Meier method. RESULTS: A total of 2,762 patients were identified. A majority of patients (59.4%, n = 1,642) underwent resection at an academic cancer centers. Median age at diagnosis was 63 years old. Neoadjuvant radiotherapy was more common at academic cancer centers, while adjuvant radiotherapy was more common at community cancer centers. Improved overall survival was seen at academic cancer centers across all stages compared with community cancer centers (P = .014) but, after multivariable Cox regression analysis, was not a significant independent predictor of survival (hazard ratio = 0.91, 95% confidence interval, 0.79-1.04, P = .171). Academic cancer centers exhibited a greater rate of R0 resection (55.9% vs 47.0%, P < .001) and a lesser odds of positive margins (odds ratio 0.83, 95% confidence interval, 0.69-0.99, P = .044) after multivariable logistic regression. CONCLUSION: Resection for retroperitoneal sarcoma performed at academic cancer centers was an independent predictor of margin-negative resection but was not a statistically significant factor for survival. This observation suggests that site of care may contribute to some aspect of improved oncologic resection for retroperitoneal sarcoma.

Preoperative Radiation Therapy Followed by Reexcision May Improve Local Control and Progression-Free Survival in Unplanned Excisions of Soft Tissue Sarcomas of the Extremity and Chest-Wall.

Background. The management for unplanned excision (UE) of soft tissue sarcomas (STS) has not been established. In this study, we compare outcomes of UE versus planned excision (PE) and determine an optimal treatment for UE in STS. Methods. From 2000 to 2014 a review was performed on all patients treated with localized STS. Clinical outcomes including local recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) were evaluated using the Kaplan-Meier estimate. Univariate (UVA) and multivariate (MVA) analyses were performed to determine prognostic variables. For MVA, Cox proportional hazards model was used. Results. 245 patients were included in the analysis. 14% underwent UE. Median follow-up was 2.8 years. The LR rate was 8.6%. The LR rate in UE was 35% versus 4.2% in PE patients (p < 0.0001). 2-year PFS in UE versus PE patients was 4.2 years and 9.3 years, respectively (p = 0.08). Preoperative radiation (RT) (p = 0.01) and use of any RT for UE (p = 0.003) led to improved PFS. On MVA, preoperative RT (p = 0.04) and performance status (p = 0.01) led to improved PFS. Conclusions. UEs led to decreased LC and PFS versus PE in patients with STS. The use of preoperative RT followed by reexcision improved LC and PFS in patients who had UE of their STS.

Tumor volume is a better predictor of post-operative wound complications compared to tumor size in soft tissue sarcomas of the proximal lower extremity.

BACKGROUND: Wide local excision with or without radiation therapy (RT) and chemotherapy is widely accepted as appropriate management for soft tissue sarcomas (STS) of the extremity. Although survival and local control rates are comparable to amputation, post-operative wound complications (WC) following limb salvage can result in significant morbidity for the patient. Certain risk factors such as location, pre-operative RT, and age have been shown to increase the risk of WCs. Somewhat surprisingly, size has not consistently been shown to impact WC rates. The goal of this study is to assess whether tumor volume, as opposed to the traditional measurement of the largest dimension in one plane, correlates with the development of post-operative WCs. METHODS: Between 2000 and 2013, 81 patients with STS of the proximal lower extremity, buttock and pelvis were retrospectively identified from our prospective database. We reviewed the impact of patient, tumor, and treatment variables on postoperative WC. Predictors for WC were evaluated using the Fisher exact test for univariate analysis and logistic regression for multivariate analysis. Tumor volume was determined using the medical image merge (MIM) (®) software program (version 6.5.4, MIM Software, Cleveland, OH). Tumor size (diameter) was determined the historical way of measuring the widest dimension on the sagittal, coronal, and axial planes from the MRI scan at midplane. RESULTS: The overall WC rate within 6 months of tumor resection was 32 %. WC were more likely to occur with larger tumor volumes (p = 0.015), although not with tumor diameters ≥10 cm (p = 0.55). Neither volume of subcutaneous fat (p = 0.34) or depth of the subcutaneous fat layer (p = 0.82) significantly impacted WC rates. Tumor proximity to skin surface also did not significantly impact WC risk (p = 0.73). CONCLUSIONS: Increase in tumor volume led to a higher risk of post-operative WCs. Assessing tumor volume may allow clinicians to better counsel patients on their risk of post-operative WCs. Tumor volume, as opposed to size alone, should be considered in future sarcoma outcome studies.

Significant Reduction of Late Toxicities in Patients With Extremity Sarcoma Treated With Image-Guided Radiation Therapy to a Reduced Target Volume: Results of Radiation Therapy Oncology Group RTOG-0630 Trial.

PURPOSE: We performed a multi-institutional prospective phase II trial to assess late toxicities in patients with extremity soft tissue sarcoma (STS) treated with preoperative image-guided radiation therapy (IGRT) to a reduced target volume. PATIENTS AND METHODS: Patients with extremity STS received IGRT with (cohort A) or without (cohort B) chemotherapy followed by limb-sparing resection. Daily pretreatment images were coregistered with digitally reconstructed radiographs so that the patient position could be adjusted before each treatment. All patients received IGRT to reduced tumor volumes according to strict protocol guidelines. Late toxicities were assessed at 2 years. RESULTS: In all, 98 patients were accrued (cohort A, 12; cohort B, 86). Cohort A was closed prematurely because of poor accrual and is not reported. Seventy-nine eligible patients from cohort B form the basis of this report. At a median follow-up of 3.6 years, five patients did not have surgery because of disease progression. There were five local treatment failures, all of which were in field. Of the 57 patients assessed for late toxicities at 2 years, 10.5% experienced at least one grade ≥ 2 toxicity as compared with 37% of patients in the National Cancer Institute of Canada SR2 (CAN-NCIC-SR2: Phase III Randomized Study of Pre- vs Postoperative Radiotherapy in Curable Extremity Soft Tissue Sarcoma) trial receiving preoperative radiation therapy without IGRT (P < .001). CONCLUSION: The significant reduction of late toxicities in patients with extremity STS who were treated with preoperative IGRT and absence of marginal-field recurrences suggest that the target volumes used in the Radiation Therapy Oncology Group RTOG-0630 (A Phase II Trial of Image-Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity) study are appropriate for preoperative IGRT for extremity STS.

Mitigation of late renal and pulmonary injury after hematopoietic stem cell transplantation.

PURPOSE: To update the results of a clinical trial that assessed whether the angiotensin-converting enzyme inhibitor captopril was effective in mitigating chronic renal failure and pulmonary-related mortality in subjects undergoing total body irradiation (TBI) in preparation for hematopoietic stem cell transplantation (HSCT). METHODS AND MATERIALS: Updated records of the 55 subjects who were enrolled in this randomized controlled trial were analyzed. Twenty-eight patients received captopril, and 27 patients received placebo. Definitions of TBI-HSCT-related chronic renal failure (and relapse) were the same as those in the 2007 analysis. Pulmonary-related mortality was based on clinical or autopsy findings of pulmonary failure or infection as the primary cause of death. Follow-up data for overall and pulmonary-related mortality were supplemented by use of the National Death Index. RESULTS: The risk of TBI-HSCT-related chronic renal failure was lower in the captopril group (11% at 4 years) than in the placebo group (17% at 4 years), but this was not statistically significant (p > 0.2). Analysis of mortality was greatly extended by use of the National Death Index, and no patients were lost to follow-up for reasons other than death prior to 67 months. Patient survival was higher in the captopril group than in the placebo group, but this was not statistically significant (p > 0.2). The improvement in survival was influenced more by a decrease in pulmonary mortality (11% risk at 4 years in the captopril group vs. 26% in the placebo group, p = 0.15) than by a decrease in chronic renal failure. There was no adverse effect on relapse risk (p = 0.4). CONCLUSIONS: Captopril therapy produces no detectable adverse effects when given after TBI. Captopril therapy reduces overall and pulmonary-related mortality after radiation-based HSCT, and there is a trend toward mitigation of chronic renal failure.

Hyperfractionated accelerated radiotherapy for rectal cancer in patients with prior pelvic irradiation.

PURPOSE: To retrospectively determine rates of toxicity, freedom from local progression, and survival in rectal cancer patients treated with reirradiation. METHODS AND MATERIALS: Between February 2001 and February 2005, 50 patients with a history of pelvic radiotherapy were treated with hyperfractionated accelerated radiotherapy for primary (n = 2 patients) or recurrent (n = 48 patients) rectal adenocarcinoma. Patients were treated with 150-cGy fractions twice daily, with a total dose of 39 Gy (n = 47 patients) if the retreatment interval was >or=1 year or 30 Gy (n = 3) if the retreatment interval was <1 year. Concurrent chemotherapy was administered to 48 (96%) patients. Eighteen (36%) patients underwent surgical resection following radiotherapy. RESULTS: Two patients had grade 3 acute toxicity and 13 patients had grade 3 to 4 late toxicity. The 3-year rate of grade 3 to 4 late toxicity was 35%. The 3-year rate of freedom from local progression was 33%. The 3-year freedom from local progression rate was 47% in patients undergoing surgery and 21% in those not undergoing surgery (p = 0.057). The 3-year overall survival rate was 39%. The 3-year overall survival rate was 66% in patients undergoing surgery and 27% in those not undergoing surgery (p = 0.003). The 3-year overall survival rate was 53% in patients with a retreatment interval of >2 years and 21% in those with a retreatment interval of

Capecitabine and timing of radiotherapy during preoperative chemoradiation for rectal cancer.

BACKGROUND: Capecitabine is effective in treating colorectal cancer and is increasingly being investigated for use in preoperative chemoradiation of rectal cancer. Since capecitabine and its metabolites have a plasma half-life of 0.5-1 hour, the relative timing of capecitabine and radiotherapy may affect clinical outcomes. We retrospectively investigated whether the timing of radiotherapy affects rates of acute toxicity, pathologic response, and relapse in rectal cancer patients receiving capecitabine. METHODS: Between June 2001 and July 2004, 111 rectal cancer patients were treated with preoperative radiotherapy and concurrent capecitabine given twice daily, in the early morning and at night. Of these, 44 received at least 70% of their radiation treatments before 12 PM (AM group), and 47 received at least 70% of their radiation treatments after 12 PM (PM group). RESULTS: There were no significant differences between the AM vs. PM groups in rates of grade >/= 2 acute gastrointestinal toxicity (61% vs. 47%) or skin toxicity (23% vs. 26%) or grades >/= 1 hand-foot syndrome (27% vs. 15%). Although the PM group had numerically higher rates of pathologic complete response (28% vs. 16%) and tumor downstaging (57% vs. 39%), differences in these outcomes and in sphincter preservation were not significant. Rates of 2-year local control, distant control, and disease-free survival were nearly identical in the two groups. CONCLUSIONS: No significant differences were seen in the rates of acute toxicity, pathologic response, and relapse between patients in the AM and PM groups. The timing of radiotherapy does not appear to be critical in patients with rectal cancer receiving concurrent capecitabine.