Preoperative Protein or Methionine Restriction Preserves Wound Healing and Reduces Hyperglycemia.

BACKGROUND: Dietary restriction (DR), defined as reduced nutrient intake without malnutrition, is associated with longevity extension, improved glucose metabolism, and increased stress resistance, but also poor wound healing. Short-term preoperative DR followed by a return to normal feeding after surgery results in improved surgical outcomes in preclinical models. However, the effect of preoperative DR on wound healing and perioperative glucose homeostasis is currently unknown. Here, we tested the effects of two different preoperative DR regimens-protein restriction (PR) and methionine restriction (MR)-on wound healing and perioperative glucose homeostasis using an established murine model of wound healing in both nondiabetic and diabetic mice. MATERIALS AND METHODS: Surgical outcomes were tested using the McFarlane flap in nondiabetic and streptozotocin-induced diabetic mice. Short-term dietary preconditioning included 1 wk of PR or MR diet (1-2 wk) versus an isocaloric complete diet before surgery; all mice were returned to a complete diet postoperatively. Outcome measures of flap wound recovery included skin viability and laser Doppler imaging of flap perfusion and assessment of CD45+ cell infiltration. Glucose homeostasis was assessed by glucose tolerance testing and by perioperative glucose levels in the diabetic cohort. RESULTS: No significant differences were observed in percentage of viable skin, perfusion, or immune cell infiltration at 7-10 d after surgery in PR or MR mice compared with controls in healthy or diabetic mice. Preoperative glucose tolerance and postoperative glucose levels were however significantly improved by both PR and MR in diabetic mice. CONCLUSIONS: Short-term dietary preconditioning with PR or MR did not impair wound healing in nondiabetic or diabetic mice. However, both regimens reduced preoperative hyperglycemia in diabetic mice. Thus, brief preoperative dietary manipulations stand as strategies to potentially improve perioperative hyperglycemia with no deleterious effects on wound healing in mice.

Myxoid Liposarcoma: Treatment Outcomes from Chemotherapy and Radiation Therapy.

INTRODUCTION: Myxoid liposarcoma (MLS) is a subtype of liposarcoma characterized morphologically by lipomatous differentiation with a myxoid stroma. The purpose of this study was to review clinical and pathological information for patients treated for MLS at our institution to better understand neoadjuvant and adjuvant therapy. MATERIALS AND METHODS: An institutional database of sarcomas was queried for patients who were treated for MLS at our institution between 1992 and 2013. Survival curves were constructed using Kaplan-Meier analysis, and univariate and multivariate statistics were performed using the Cox-proportional hazards model and using linear regression. RESULTS: A total of 85 patients with myxoid liposarcoma were identified. The mean and median histologic response rate to treatment for patients who received preoperative radiation therapy was 77.6%. Five-year disease-free survival, distant metastasis-free survival, local recurrence-free survival, and overall survival were 78.6% (95% CI: 67.8-86.1), 84.7% (95% CI: 74.5-91.0), 95.6% (95% CI: 86.9-98.6), and 87.5% (95% CI: 77.2-93.3) respectively. On univariate analysis, there was a trend towards higher necrosis or treatment response rates in patients who received concurrent chemotherapy, 84.7% (95% CI: 75.9-93.4) and 69.5% (95% CI: 55.1-83.8), p=0.061. Tumor size was associated with inferior disease-free and overall survival. Hazard ratio for disease-free survival is 1.08 (per cm) (95% CI: 1.01-1.16), p=0.019. CONCLUSIONS: Myxoid liposarcoma exhibits histological response to chemotherapy and radiation therapy. Tumor size appears to be greatest predictor of long-term disease control and overall survival. We were not able to show that chemotherapy provides a clinical benefit with regard to local control, disease-free survival, or overall survival. However, it is important to note that the selected usage of chemotherapy in the highest risk patients confounds this analysis. Further investigation is needed to help better determine the optimal use of chemotherapy in this group of patients.

Can Machine-learning Techniques Be Used for 5-year Survival Prediction of Patients With Chondrosarcoma?

BACKGROUND: Several studies have identified prognostic factors for patients with chondrosarcoma, but there are few studies investigating the accuracy of computationally intensive methods such as machine learning. Machine learning is a type of artificial intelligence that enables computers to learn from data. Studies using machine learning are potentially appealing, because of its possibility to explore complex patterns in data and to improve its models over time. QUESTIONS/PURPOSES: The purposes of this study were (1) to develop machine-learning algorithms for the prediction of 5-year survival in patients with chondrosarcoma; and (2) to deploy the best algorithm as an accessible web-based app for clinical use. METHODS: All patients with a microscopically confirmed diagnosis of conventional or dedifferentiated chondrosarcoma were extracted from the Surveillance, Epidemiology, and End Results (SEER) Registry from 2000 to 2010. SEER covers approximately 30% of the US population and consists of demographic, tumor characteristic, treatment, and outcome data. In total, 1554 patients met the inclusion criteria. Mean age at diagnosis was 52 years (SD 17), ranging from 7 to 102 years; 813 of the 1554 patients were men (55%); and mean tumor size was 8 cm (SD 6), ranging from 0.1 cm to 50 cm. Exact size was missing in 340 of 1544 patients (22%), grade in 88 of 1544 (6%), tumor extension in 41 of 1544 (3%), and race in 16 of 1544 (1%). Data for 1-, 3-, 5-, and 10-year overall survival were available for 1533 (99%), 1512 (98%), 1487 (96%), and 977 (63%) patients, respectively. One-year survival was 92%, 3-year survival was 82%, 5-year survival was 76%, and 10-year survival was 54%. Missing data were imputed using the nonparametric missForest method. Boosted decision tree, support vector machine, Bayes point machine, and neural network models were developed for 5-year survival. These models were chosen as a result of their capability of predicting two outcomes based on prior work on machine-learning models for binary classification. The models were assessed by discrimination, calibration, and overall performance. The c-statistic is a measure of discrimination. It ranges from 0.5 to 1.0 with 1.0 being perfect discrimination and 0.5 that the model is no better than chance at making a prediction. The Brier score measures the squared difference between the predicted probability and the actual outcome. A Brier score of 0 indicates perfect prediction, whereas a Brier score of 1 indicates the poorest prediction. The Brier scores of the models are compared with the null model, which is calculated by assigning each patient a probability equal to the prevalence of the outcome. RESULTS: Four models for 5-year survival were developed with c-statistics ranging from 0.846 to 0.868 and Brier scores ranging from 0.117 to 0.135 with a null model Brier score of 0.182. The Bayes point machine was incorporated into a freely available web-based application. This application can be accessed through https://sorg-apps.shinyapps.io/chondrosarcoma/. CONCLUSIONS: Although caution is warranted, because the prediction model has not been validated yet, healthcare providers could use the online prediction tool in daily practice when survival prediction of patients with chondrosarcoma is desired. Future studies should seek to validate the developed prediction model. LEVEL OF EVIDENCE: Level III, prognostic study.

Optimization of combined proton-photon treatments.

PURPOSE: Proton treatment slots are a limited resource. Therefore, we consider combined proton-photon treatments in which most fractions are delivered with photons and only a few with protons. We demonstrate how both modalities can be combined to optimally capitalize on the proton's ability to reduce normal tissue dose. METHODS: An optimal combined treatment must account for fractionation effects. We therefore perform simultaneous optimization of intensity-modulated proton (IMPT) and photon (IMRT) plans based on their cumulative biologically effective dose (BED). We demonstrate the method for a sacral chordoma patient, in whom the gross tumor volume (GTV) abuts bowel and rectum. RESULTS: In an optimal combination, proton and photon fractions deliver similar doses to bowel and rectum to protect these dose-limiting normal tissues through fractionation. However, proton fractions deliver, on average, higher doses to the GTV. Thereby, the photon dose bath is reduced. An optimized 30-fraction treatment with 10 IMPT fractions achieved more than 50% of the integral dose reduction in the gastrointestinal tract that is possible with 30 IMPT fractions (compared to 33% for a simple proton-photon combination in which both modalities deliver the same target dose). CONCLUSIONS: A limited number of proton fractions can best be used if protons hypofractionate parts of the GTV while maintaining near-uniform fractionation in dose-limiting normal tissues.

Body composition predictors of therapy response in patients with primary extremity soft tissue sarcomas.

Background Recent studies have suggested that the quantity and quality of adipose tissue and muscle, assessed on non-contrast computed tomography (CT), may serve as imaging biomarkers of survival in patients with and without neoplasms. Purpose To assess body composition measures that could serve as predictors of therapy response in patients with extremity soft tissue sarcomas treated with radiation therapy and surgery. Material and Methods The study was IRB-approved. Sixty patients had a history of extremity soft tissue sarcoma and underwent FDG-PET/CT prior to radiation therapy and surgical resection. Cross-sectional areas and CT attenuation (HU) of abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and psoas muscle were assessed on non-contrast CT. Clinical information on predictors of tumor recurrence and post-surgical wound infections were recorded. Cox proportional hazard models were used to determine longitudinal associations between body composition and tumor recurrence/wound infections. Results Twenty-three tumor recurrences occurred over a follow-up period of 43 ± 35 months. Higher SAT and lower psoas attenuation were associated with tumor recurrence which remained significant after adjustment for covariates ( P ≤ 0.01). There were 13 post-surgical wound infections. Higher VAT and SAT attenuation were associated with post-surgical wound infections ( P < 0.04); however, VAT attenuation lost significance after adjustment for covariates. Conclusion Abdominal adipose tissue and psoas muscle attenuation assessed on non-contrast CT may predict tumor recurrence and post-surgical infections in patients with extremity soft tissue sarcomas.

Phase 1 trial of preoperative image guided intensity modulated proton radiation therapy with simultaneously integrated boost to the high risk margin for retroperitoneal sarcomas.

PURPOSE: To conduct phase 1 and 2 trials with photon intensity modulated radiation therapy and intensity modulated proton therapy (IMPT) arms to selectively escalate the retroperitoneal sarcoma preoperative radiation dose to tumor volume (clinical target volume [CTV] 2) that is judged to be at a high risk for positive margins and aim to reduce local recurrence. We report on the IMPT study arm in phase 1. METHODS AND MATERIALS: Patients aged ≥18 years with primary or locally recurrent retroperitoneal sarcoma were treated with preoperative IMPT, 50.4 GyRBE in 28 fractions, to CTV1 (gross tumor volume and adjacent tissues at risk of subclinical disease) with a simultaneous integrated boost to CTV2 to doses of 60.2, 61.6, and 63.0 GyRBE in 28 fractions of 2.15, 2.20, and 2.25 GyRBE, respectively. The primary objective of the phase 1 study was to determine the maximum tolerated dose to CTV2, which will be further tested in the phase 2 study. RESULTS: Eleven patients showed increasing IMPT dose levels without acute dose limiting toxicities that prevented dose escalation to maximum tolerated dose. Acute toxicity was generally mild with no radiation interruptions. No unexpected perioperative morbidity was noted. Eight months postoperatively, one patient developed hydronephrosis that was treated by stent with ureter dissected off tumor and received 57.5 GyRBE. Retained ureter(s) was (were) subsequently constrained to 50.4 GyRBE without further problem. With an 18-month median follow-up, there were no local recurrences. CONCLUSIONS: IMPT dose escalation to CTV2 to 63 GyRBE was achieved without acute dose limiting toxicities. The phase 2 study of IMPT will accrue patients to that dose. Parallel intensity modulated radiation therapy phase 1 arm is currently accruing at the initial dose level. Ureters that undergo a high dose radiation and/or surgery are at risk for late hydro-ureter. Future studies will constrain retained ureters to 50.4 GyRBE to avoid ureteral stricture.

Targeting ABCB1 (MDR1) in multi-drug resistant osteosarcoma cells using the CRISPR-Cas9 system to reverse drug resistance.

BACKGROUND: Multi-drug resistance (MDR) remains a significant obstacle to successful chemotherapy treatment for osteosarcoma patients. One of the central causes of MDR is the overexpression of the membrane bound drug transporter protein P-glycoprotein (P-gp), which is the protein product of the MDR gene ABCB1. Though several methods have been reported to reverse MDR in vitro and in vivo when combined with anticancer drugs, they have yet to be proven useful in the clinical setting. RESULTS: The meta-analysis demonstrated that a high level of P-gp may predict poor survival in patients with osteosarcoma. The expression of P-gp can be efficiently blocked by the clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas9 system (CRISPR-Cas9). Inhibition of ABCB1 was associated with reversing drug resistance in osteosarcoma MDR cell lines (KHOSR2 and U-2OSR2) to doxorubicin. MATERIALS AND METHODS: We performed a meta-analysis to investigate the relationship between P-gp expression and survival in patients with osteosarcoma. Then we adopted the CRISPR-Cas9, a robust and highly efficient novel genome editing tool, to determine its effect on reversing drug resistance by targeting endogenous ABCB1 gene at the DNA level in osteosarcoma MDR cell lines. CONCLUSION: These results suggest that the CRISPR-Cas9 system is a useful tool for the modification of ABCB1 gene, and may be useful in extending the long-term efficacy of chemotherapy by overcoming P-gp-mediated MDR in the clinical setting.

Clinical outcomes for patients after surgery and radiation therapy for mesenchymal chondrosarcomas.

INTRODUCTION: We report the outcome of 23 patients with mesenchymal chondrosarcomas treated with surgery and radiation therapy +/- chemotherapy. The intent of the project was to review the impact of patient and treatment variables on treatment outcome, in particular with regard to extent of surgery and radiation dose. PATIENTS AND METHODS: Twenty-three patients with mesenchymal chondrosarcomas were treated with surgery and radiation therapy (min. dose 44 Gy; max. dose 78 Gy; median dose 60 Gy; mean dose 61 Gy). RESULTS: The median survival for the entire cohort of patients was 21.65 years (95% confidence interval ± 4.25). The 5- and 10-year OS was 78.6%. Median disease-free survival for the 23 patients was 7.2 years. Disease-free survival (DFS) at 3 and 5 years was 70.7% and 57.8%, respectively. The local control rate at 5 and 10 years was 89.5% (95%CI 64.1-97.3%). Only three patients experienced local failure, three patients had regional failure, and eight developed distant metastases. CONCLUSIONS: In this cohort of patients local tumor control was high when using a combination of surgery and radiation. There was not a clear relationship between radiation dose and local tumor control. J. Surg. Oncol. 2016;114:982-986. © 2016 Wiley Periodicals, Inc.

Chordomas and chondrosarcomas-The role of radiation therapy.

Achieving negative surgical margins can be challenging for skull base and spinal/paraspinal sarcomas. Data shows that pre- or post-operative radiation therapy improves local control. Delivery of sufficient dose of radiation can be difficult because of the proximity to normal organs/tissues that are sensitive to radiation therapy and therefore dose-limiting. A comprehensive literature search was conducted using PubMed search engine. The scarcity of prospective, randomized data limits the ability to generate definitive treatment recommendations. J. Surg. Oncol. 2016;114:564-569. © 2016 Wiley Periodicals, Inc.

Preoperative radiation therapy combined with radical surgical resection is associated with a lower rate of local recurrence when treating unifocal, primary retroperitoneal liposarcoma.

BACKGROUND AND OBJECTIVES: Local recurrence (LR) is the primary cause of death in patients with retroperitoneal liposarcoma (RP-LPS). The purpose of this study was to evaluate if the addition of preoperative radiation therapy (XRT) to radical resection for RP-LPS at a single institution was associated with improved LR. METHODS: This retrospective analysis included patients with unifocal, primary RP-LPS who underwent complete R0/R1 resection at a single institution between 1991 and 2013. Multiple patient, tumor, and surgeon characteristics were tested to evaluate their association to LR (recurrence in the retroperitoneal space). We used competing risk hazards regression to evaluate the effect of preoperative XRT on the probability of LR. RESULTS: There were 41 patients with liposarcoma histology whose tumors included entirely well-differentiated (N = 13), de-differentiated components (n = 26), myxoid (n = 1), and NOS (n = 1). Preoperative XRT was significantly associated with a lower probability of LR (HR 0.11, 95%CI 0.01-0.91, P = 0.04) and a higher 5-year local recurrence-free survival (95.6%, 95%CI 72.4-99.4%, vs. 75.0%, 95%CI 40.8-91.2%; P = 0.0213), but not with 5-year distant recurrence-free survival or disease-specific survival. CONCLUSIONS: Preoperative XRT combined with complete R0/R1 resection for unifocal, primary RP-LPS was associated with improved LR and it should be considered in the multimodality treatment of RP-LPS. J. Surg. Oncol. 2016;114:814-820. © 2016 2016 Wiley Periodicals, Inc.

Adipose tissue and muscle attenuation as novel biomarkers predicting mortality in patients with extremity sarcomas.

OBJECTIVES: To assess CT-attenuation of abdominal adipose tissue and psoas muscle as predictors of mortality in patients with sarcomas of the extremities. METHODS: Our study was IRB approved and HIPAA compliant. The study group comprised 135 patients with history of extremity sarcoma (mean age: 53 ± 17 years) who underwent whole body PET/CT. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and psoas muscle attenuation (HU) was assessed on non-contrast, attenuation-correction CT. Clinical information including survival, tumour stage, sarcoma type, therapy and pre-existing comorbidities were recorded. Cox proportional hazard models were used to determine longitudinal associations between adipose tissue and muscle attenuation and mortality. RESULTS: There were 47 deaths over a mean follow-up period of 20 ± 17 months. Higher SAT and lower psoas attenuation were associated with increased mortality (p = 0.03 and p = 0.005, respectively), which remained significant after adjustment for age, BMI, sex, tumor stage, therapy, and comorbidities (p = 0.002 and p = 0.02, respectively). VAT attenuation was not associated with mortality. CONCLUSION: Attenuation of SAT and psoas muscle, assessed on non-contrast CT, are predictors of mortality in patients with extremity sarcomas, independent of other established prognostic factors, suggesting that adipose tissue and muscle attenuation could serve as novel biomarkers for mortality in patients with sarcomas. KEY POINTS: • CT-attenuation of adipose tissue and muscle predict mortality in sarcoma patients • CT-attenuation predicts mortality independent of established prognostic factors • Patients with sarcomas often undergo CT for staging or surveillance • Adipose tissue and muscle attenuation could serve as biomarkers for mortality.

Thoracolumbar spinal cord tolerance to high dose conformal proton-photon radiation therapy.

PURPOSE: To evaluate and understand the tolerance of the thoracolumbar spinal cord using equivalent uniform dose (EUD) and dose volume histogram (DVH) analysis after combined high dose photon-proton radiotherapy. MATERIALS AND METHODS: A total of 68 patients were identified as having high dose radiotherapy, ⩾5900cGy (RBE) in the region of the thoracolumbar spinal cord, defined as extending inferiorly to L2. Pathological diagnosis for patients in this review included chordoma (50 patients, 53.1%), chondrosarcoma (28 patients, 29.8%), osteosarcoma (3 patients, 3.2%), other sarcoma (11 patients, 11.7%), and other (2 patients, 2.1%). Patient data were reviewed retrospectively, detailed dose volume histogram data (DVH) were available for 23 patients. Composite plans and DVH were constructed for both pre-operative and post-operative radiation therapy courses in MIM-Vista software, as available. Dose constraints to the center and surface of the cord were 5400cGy (RBE), and 6300cGy (RBE) respectively, and patients receiving concurrent chemotherapy received an eight percent dose reduction. Spinal cord toxicity was recorded using the RTOG/EORTC late effects scoring system. RESULTS: Clinical and dosimetric data for each patient were analyzed. Median prescription dose was 7020cGy (RBE), range (5940-7820cGy (RBE)). Median follow-up was 12.9months. Five-year overall survival for all patients in this group was 88.7%, 95%CI (74.7-95.2). One patient suffered from transient paralysis following stem cell transplant for treatment of myelodysplastic syndrome. Other reasons for spinal cord injury following treatment included: local disease progression, noted in 7 patients (10.3%), and direct result of surgery, noted in 8 patients (11.8%). Freedom from neurological injury (RTOG Grade 2 or higher) at 5years was 92.9%(95%CI: 74.6-98.2), at 6years was 80.9%(95%CI: 55.3-92.7), and at 8years 80.9%(95%CI: 55.3-92.7). CONCLUSION: Our clinical and dosimetric data suggest that the noted dose constraints are safe and acceptable with regard to spinal cord complications. Pre-existing disease characteristics, surgical complications, as well as tumor progression, appear to be more important factors when it comes to spinal cord toxicity.

Role of radiation therapy for non-extremity soft tissue sarcomas.

BACKGROUND: Negative surgical margins are uncommon for non-extremity soft tissue sarcomas. Radiation therapy is usually recommended to improve local control; however, appropriate RT dosing is challenging due to nearby dose-limiting normal structures. MATERIAL AND METHODS: Comprehensive literature search using PubMed (March 2014). RESULTS: Data suggest radiation therapy is an important modality in maximizing local tumor control in non-extremity sarcomas. CONCLUSION: The literature supports the use of RT to improve local control for non-extremity soft tissue sarcomas.

Early clinical outcomes using proton radiation for children with central nervous system atypical teratoid rhabdoid tumors.

PURPOSE: Atypical teratoid/rhabdoid tumor (AT/RT) is an uncommon and aggressive tumor that often affects infants. Irradiation improves survival but has traditionally been avoided in patients under the age of 3 due to the increasing risk of neurocognitive side effects. We report the first cohort of AT/RT patients treated with proton therapy. METHODS AND MATERIALS: All patients with AT/RT treated at Massachusetts General Hospital (MGH) Frances H. Burr Proton Beam Therapy Benter between July 2004 and November 2011 were included in this study. All patients were treated with 3-dimensional conformal proton therapy (3D-CPT). RESULTS: Ten consecutive patients of a median 2.3 years of age and with a median follow-up of 27.3 months (range, 11.3-99.4 months) were identified. Two patients suffered distant relapse; 1 patient was successfully treated with involved field irradiation and chemotherapy, while the second patient died of disease. At last follow-up, 9 patients were alive without evidence of disease. Proton radiation demonstrated increasing sparing of the cerebrum, temporal lobe, cochlea, and hypothalamus. CONCLUSIONS: Initial clinical outcomes with proton therapy are favorable. The advantages of proton therapy are particularly suited to the treatment of AT/RT, a tumor that often requires irradiation treatment at an age when avoiding irradiation to healthy tissues is most desirable.

Results of the 2005 to 2008 Association of Residents in Radiation Oncology surveys of chief residents in the United States: didactics and research experience.

OBJECTIVES: To analyze the didactics and research experience reported by chief residents during their residency training. METHODS: During the academic years 2005 to 2006, 2006 to 2007, and 2007 to 2008, the Association of Residents in Radiation Oncology (ARRO) conducted a nationwide survey of all radiation oncology chief residents in the United States. Chi-square statistic was used to assess for changes in didactics and research experience over time. RESULTS: During the years surveyed, an increasing percentage of programs offered curriculum-based didactics in clinical oncology (P=0.042), with a similar trend of borderline significance observed in biostatistics (P = 0.056). Each year, the majority of programs offered >40 hours of curriculum-based training in clinical oncology and physics, >20 hours in radiobiology, and 10 hours or fewer in biostatistics. 11% to 13% of residents reported having no full-time equivalent radiation biologists affiliated with their training program. Less than 64% of programs incorporated mock oral boards into their training. An increasing percentage of programs evaluated residents in a "360 degree" manner, with a trend to significance (P=0.073). Over 80% of programs required resident participation in research activities and allocated dedicated elective research time, typically 4 months or longer. Though the vast majority of programs make clinical research activities available to interested residents, borderline significance (P = 0.051) was observed for a decreasing percentage of such programs during the years analyzed. CONCLUSIONS: Trends in didactics and research experience over three years are documented to allow residents and program directors to assess their residency training.

Results of the 2005-2008 Association of Residents in Radiation Oncology survey of chief residents in the United States: clinical training and resident working conditions.

PURPOSE: To document clinical training and resident working conditions reported by chief residents during their residency. METHODS AND MATERIALS: During the academic years 2005 to 2006, 2006 to 2007, and 2007 to 2008, the Association of Residents in Radiation Oncology conducted a nationwide survey of all radiation oncology chief residents in the United States. Chi-square statistics were used to assess changes in clinical training and resident working conditions over time. RESULTS: Surveys were completed by representatives from 55 programs (response rate, 71.4%) in 2005 to 2006, 60 programs (75.9%) in 2006 to 2007, and 74 programs (93.7%) in 2007 to 2008. Nearly all chief residents reported receiving adequate clinical experience in commonly treated disease sites, such as breast and genitourinary malignancies; and commonly performed procedures, such as three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. Clinical experience in extracranial stereotactic radiotherapy increased over time (p < 0.001), whereas clinical experience in endovascular brachytherapy (p <0.001) decreased over time. The distribution of gynecologic and prostate brachytherapy cases remained stable, while clinical case load in breast brachytherapy increased (p = 0.006). A small but significant percentage of residents reported receiving inadequate clinical experience in pediatrics, seeing 10 or fewer pediatric cases during the course of residency. Procedures involving higher capital costs, such as particle beam therapy and intraoperative radiotherapy, and infrequent clinical use, such as head and neck brachytherapy, were limited to a minority of institutions. Most residency programs associated with at least one satellite facility have incorporated resident rotations into their clinical training, and the majority of residents at these programs find them valuable experiences. The majority of residents reported working 60 or fewer hours per week on required clinical duties. CONCLUSIONS: Trends in clinical training and resident working conditions over 3 years are documented to allow residents and program directors to assess their residency training.