Outcomes After Salvage Radiation Therapy for Recurrent Endometrial Cancer in Patients With No Prior Adjuvant Therapy: An Institutional Review.

PURPOSE: After definitive surgery, women with early-stage, low-risk endometrial cancer are observed. However, some will require salvage radiation therapy for recurrence. The purpose of this study was to evaluate our experience using salvage radiation for recurrent endometrial cancer in patients who did not receive upfront adjuvant therapy. METHODS AND MATERIALS: Twenty-eight women with endometrial cancer who had undergone initial definitive hysterectomy without adjuvant therapy developed isolated local or regional recurrence and were treated with salvage radiation in our department from 2004 to 2018. Salvage radiation included whole pelvic radiation, vaginal brachytherapy, or both. Patient and tumor characteristics, treatment details, and toxicities were recorded and analyzed. RESULTS: The median time to first recurrence was 1.7 years. First recurrences consisted of local recurrence in 23 patients, regional recurrence in 4, and both in 1. The median times from hysterectomy to first recurrence, local and regional, were 1.2 and 4.0 years, respectively. All patients underwent salvage radiation for management of their first recurrence. The median total equivalent dose in 2 Gy fractions for this treatment was 67.6 Gy (37.5-81.8 Gy). Two second recurrences occurred following salvage treatment, both local recurrence, at 6.5 and 13.5 months after radiation. The 2-year rates of local control, disease-free survival, and overall survival were 93%, 80%, and 88%, respectively. Treatment was well-tolerated, with low rates of gastrointestinal and genitourinary toxicity. CONCLUSIONS: In this group of patients, salvage radiation therapy for local or regional recurrence of endometrial cancer resulted in excellent control with low rates of acute and chronic toxicities.

Deep convolutional neural networks for automatic segmentation of thoracic organs-at-risk in radiation oncology - use of non-domain transfer learning.

PURPOSE: Segmentation of organs-at-risk (OARs) is an essential component of the radiation oncology workflow. Commonly segmented thoracic OARs include the heart, esophagus, spinal cord, and lungs. This study evaluated a convolutional neural network (CNN) for automatic segmentation of these OARs. METHODS: The dataset was created retrospectively from consecutive radiotherapy plans containing all five OARs of interest, including 22,411 CT slices from 168 patients. Patients were divided into training, validation, and test datasets according to a 66%/17%/17% split. We trained a modified U-Net, applying transfer learning from a VGG16 image classification model trained on ImageNet. The Dice coefficient and 95% Hausdorff distance on the test set for each organ was compared to a commercial atlas-based segmentation model using the Wilcoxon signed-rank test. RESULTS: On the test dataset, the median Dice coefficients for the CNN model vs. the multi-atlas model were 71% vs. 67% for the spinal cord, 96% vs. 94% for the right lung, 96%vs. 94% for the left lung, 91% vs. 85% for the heart, and 63% vs. 37% for the esophagus. The median 95% Hausdorff distances were 9.5  mm vs. 25.3 mm, 5.1  mm vs. 8.1 mm, 4.0  mm vs. 8.0 mm, 9.8  mm vs. 15.8 mm, and 9.2 mm vs. 20.0 mm for the respective organs. The results all favored the CNN model (P < 0.05). CONCLUSIONS: A 2D CNN can achieve superior results to commercial atlas-based software for OAR segmentation utilizing non-domain transfer learning, which has potential utility for quality assurance and expediting patient care.

Role of T0 status in overall survival for unresectable stage III non-small cell lung cancer: A NCDB analysis.

OBJECTIVES: Occult primary non-small cell lung cancer (NSCLC) with mediastinal involvement is a known but rare clinical condition. Very limited retrospective data are available in the literature. Its prognosis and response to systemic chemotherapy have not been investigated with large scale data. MATERIALS AND METHODS: Using National Cancer Database (NCDB), cases that had undergone radiation therapy without surgery for N2-3M0 NSCLC were selected. Demographics and survival data were compared between T0 and T1-4 groups. Survival analyses were conducted with Kaplan-Meier and log-rank tests. Cox proportional hazard models were used for univariate and multivariate analyses. RESULTS: Between 2004 and 2016, 84,263 and 458 cases met criteria for unresectable stage III NSCLC with T1-4 and T0 stage, respectively. T0 status was associated with younger age, recent diagnosis (year 2010-2016), adenocarcinoma histology, N3 stage, and use of chemotherapy. Survival analysis demonstrated that those with T0 status had prolonged overall survival as compared to T1-4 counterparts in both overall and chemotherapy groups (p < 0.0001 for each). Five-year overall survival rates for T0 and T1-4 groups were 30.5% and 12.7% in all groups, and 33.6% and 14.6% in chemotherapy groups, respectively. Propensity score matching also demonstrated a statistically significant difference in overall survival (p < 0.0001). These findings are confirmed by independent analysis using Surveillance, Epidemiology, and End Results Program (SEER). CONCLUSION: This large hospital-based study demonstrates the favorable prognosis for T0 status in the setting of unresectable stage III NSCLC. Researchers may consider it as distinct stage (e.g., stage IIC) for future studies.

The Cost-Effectiveness and Value Proposition of Brachytherapy.

Brachytherapy is an effective treatment modality for a wide range of malignancies. However, brachytherapy utilization for both prostate and gynecologic malignancies has significantly declined over the last 20 years in favor of external beam radiation techniques. The cause of this decline is multifactorial, with logistical challenges, lower reimbursement, and inadequate training contributing to the preference of many radiation oncologists to more frequently recommend external beam radiation therapy. While the authors recognize the application of brachytherapy to a wider range of disease presentations among which include breast, skin, head and neck, and connective tissue cancers, in this review, we will review the analyses supporting brachytherapy as a cost-effective component of the management in patients with prostate, cervix, and endometrial cancer.

Cost-effectiveness of prostate boost with high-dose-rate brachytherapy versus intensity-modulated radiation therapy in the treatment of intermediate-high risk prostate cancer.

PURPOSE: The recently published ASCENDE-RT randomized clinical trial demonstrated improved biochemical control, albeit with increased toxicity, for a prostate boost with brachytherapy versus external beam radiation therapy alone in patients with intermediate-high risk prostate cancer. In this study, we investigated the cost-effectiveness of these two modalities in the treatment of intermediate-high risk prostate cancer. METHODS AND MATERIALS: A multistate Markov model was created to model a patient with intermediate-high risk prostate cancer. The two treatment options modeled were (1) 23 fractions of intensity-modulated radiation therapy (IMRT) and two fractions of high-dose-rate prostate brachytherapy (brachytherapy boost) and (2) 44 fractions of IMRT (IMRT alone). Each patient received 1 year of hormone therapy, per the ASCENDE-RT protocol. Model assumptions, including clinical outcomes, toxicity, and utilities were derived from the medical literature. Costs of radiation therapy were estimated using Medicare reimbursement data. RESULTS: The estimated expected lifetime cost of brachytherapy boost was $68,696, compared to $114,944 for IMRT alone. Brachytherapy boost significantly lowered expected lifetime treatment costs because it decreased the incidence of metastatic castration-resistant prostate cancer, cutting the use of expensive targeted therapy for metastatic castration-resistant prostate cancer. Brachytherapy boost had an expected quality-adjusted life years of 10.8 years, compared to 9.3 years for IMRT alone. One-way sensitivity analyses of our results found brachytherapy boost to be cost-effective over a wide range of cost, utility, and cancer progression rate assumptions. CONCLUSIONS: IMRT with high-dose-rate brachytherapy boost is a cost-effective treatment for intermediate-high risk prostate cancer compared to IMRT alone.

Trends in Medicare Reimbursement and Work Relative Value Unit Production in Radiation Oncology.

PURPOSE: Medicare payments to individual physicians are released annually by the CMS. The purpose of this study is to analyze trends in Medicare reimbursement and work relative value unit (wRVU) production to radiation oncologists. MATERIALS AND METHODS: The Medicare Physician Supplier and Other Provider Public Use File and the CMS Physician Fee Schedule Relative Value Files (to calculate wRVUs) for the calendar years 2012 to 2015 were used in this analysis. Medicare reimbursement was aggregated for each calendar year. Using the CMS Physician Fee Schedule Relative Value Files, the number of Medicare wRVUs was calculated for each radiation oncologist. RESULTS: In 2015, 4,323 radiation oncologists produced 12,895,298 wRVUs compared with 11,352,286 wRVUs produced in 2012. These datasets include only Medicare reimbursements and do not include wRVUs from private insurance or other payers. In 2015, radiation oncologists produced a median of 2,486 wRVUs from Medicare (range 3 to 24,349). Billing to Healthcare Common Procedure Coding System Code 77427 (radiation treatment management, five treatments), a proxy for total radiation treatments, fell from 1,111,670 in 2012 to 1,039,403 in 2015, a decline of 7%. CONCLUSION: The total number of wRVUs produced by radiation oncologists has risen by 14% from 2012 to 2015. However, the number of external beam radiation fractions has declined by approximately 7% over this same period, likely due to a trend toward hypofractionated courses of treatment and use of special treatment modalities such as proton beam therapy or stereotactic body radiation therapy.

How many lymph nodes are enough?-defining the extent of lymph node dissection in stage I-III gastric cancer using the National Cancer Database.

BACKGROUND: Surgical resection with lymph node dissection is the primary therapeutic modality for gastric cancer. National Cancer Database (NCDB) was used to determine the extent of lymph nodes (LNs) dissection for gastric cancer. METHODS: The NCDB was queried from 2004-2013 for patients with margin-negative, invasive resected gastric cancer. The optimal number of LNs dissected was determined using a univariate χ2 cut-point analysis. Multiple sensitivity analyses were utilized to decrease bias. RESULTS: A total of 17,851 patients were included. For all patients, the optimal number of LNs needed to be examined was 20+ nodes. When correcting for stage migration (<7 LNs removed), the optimal cut-off value was 20+ LNs. When stratifying by pathologic nodal stage, the cut-off point was 10+ LNs for pN1 and pN2. The 5-year survival was 30.6%±1.6% for 0-9 removed LNs compared to 48.2%±1.2% for 10+ removed LNs (P<0.001) in pN1 disease and 18.3%±1.7% for 0-9 removed LNs compared to 32.6%±1.2% for 10+ removed LNs (P<0.001) in pN2 disease. For pN3 disease, the optimal cut-off point was 20+ LNs; the 5-year survival was 17.2%±1.3% for 0-19 removed LNs compared to 28.5%±1.7% for 20+ removed LNs (P<0.001). Moreover, the outcome was inferior among patients who had >10% positive dissected LNs (P<0.05). CONCLUSIONS: The extent of dissected lymph nodes of 20 or greater lymph nodes was associated with superior survival. Extended LN dissection is to be considered especially in patients with clinical lymphadenopathy.

Improved Survival With Increased Time-To-Radiation and Sequential Chemotherapy After Surgery for pN2 Non-Small-cell Lung Cancer.

BACKGROUND: Currently, the ideal timing for postoperative radiotherapy (PORT) and chemotherapy is unknown. The present study evaluated their relative timing on overall survival (OS) using the National Cancer Database (NCDB). MATERIALS AND METHODS: The NCDB was queried for patients from 2004 to 2012 with resected non-small-cell lung cancer (NSCLC), pathologically involved N2 (pN2) nodes, and negative margins. All patients underwent adjuvant chemotherapy and external beam radiotherapy. The time to radiation (TTR) was determined from the date of surgery to the start of PORT, with the exclusion of those receiving PORT < 4 weeks or > 24 weeks postoperatively. Early and late TTR was dichotomized at 8 weeks after receiver operating characteristic analysis. Multivariate Cox regression analysis was conducted to predict the variables significantly associated with survival. RESULTS: A total of 1629 patients were eligible for analysis. Of the 1629 patients, 703 had received PORT < 8 weeks and 926 had received PORT ≥ 8 weeks postoperatively. The receipt of PORT after 8 weeks was associated with better OS (P = .0044). No significant differences were found in survival in the concurrent group comparing early and later TTR (P = .9119). However, a significant OS benefit was found for sequential chemotherapy with an increased TTR (P = .0045). Older age, male sex, shorter distance traveled, increased nodal positivity, larger tumor size, higher Charlson/Deyo comorbidity score, and early TTR were associated with inferior survival on multivariate analysis. CONCLUSION: A TTR of ≥ 8 weeks with sequential chemotherapy in the setting of PORT was associated with improved survival in patients with NSCLC with pN2 nodes.

Variations in Medicare Reimbursement in Radiation Oncology: An Analysis of the Medicare Provider Utilization and Payment Data Set.

PURPOSE: The purposes of this study were to summarize recently published data on Medicare reimbursement to individual radiation oncologists and to identify the causes of variation in Medicare reimbursement in radiation oncology. METHODS AND MATERIALS: The Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File (POSPUF), which details nearly all services provided by radiation oncologists in 2012, was used for this study. The data were filtered and analyzed by physician and by billing code. Statistical analysis was performed to identify differences in reimbursements based on sex, rurality, billing of technical services, or location in a certificate of need (CON) state. RESULTS: There were 4135 radiation oncologists who received a total of $1,499,625,803 in payments from Medicare in 2012. Seventy-five percent of radiation oncologists were male. The median reimbursement was $146,453. The code with the highest total reimbursement was 77418 (radiation treatment delivery intensity modulated radiation therapy [IMRT]). The most commonly billed evaluation and management (E/M) code for new visits was 99205 (49%). The most commonly billed E/M code for established visits was 99213 (54%). Forty percent of providers billed none of their new office visits using 99205 (the highest E/M billing code), whereas 34% of providers billed all of their new office visits using 99205. For the 1510 radiation oncologists (37%) who billed technical services, median Medicare reimbursement was $606,008, compared with $93,921 for all other radiation oncologists (P<.001). On multivariate analysis, technical services billing (P<.001), male sex (P<.001), and rural location (P=.007) were predictive of higher Medicare reimbursement. CONCLUSIONS: The billing of technical services, with their high capital and labor overhead requirements, limits any comparison in reimbursement between individual radiation oncologists or between radiation oncologists and other specialists. Male sex and rural practice location are independent predictors of higher total Medicare reimbursements.

Extraskeletal Osteosarcoma: An International Rare Cancer Network Study.

OBJECTIVES: To report characteristics, treatment, and outcomes for an international cohort of patients with extraskeletal osteosarcoma (ESOS). MATERIALS AND METHODS: Through the Rare Cancer Network, retrospective data on patients with ESOS were collected. Patient characteristics, multimodality treatment information, and survival status were analyzed. RESULTS: Thirty-seven patients in 4 health care institutions were identified. Thirty-one (86%) patients had grade 3 or 4 tumors. Most patients (27 [73%]) had stage III disease. Fourteen (38%) received neoadjuvant chemotherapy or chemoradiation. Of 28 (85%) who underwent surgery, 21 (75%) had free margins achieved and 15 (41%) subsequently received adjuvant chemotherapy. At median follow-up of 45 months, 20 (55%) patients were alive, 13 (43%) of whom were disease free. Univariate analysis showed that poor overall survival was related to stage IV (P<0.001), no surgery (P<0.001), primary size >10 cm (P=0.002), and age (P=0.002). In multivariate analysis, primary size >10 cm (P=0.005) was prognostic for overall survival. For patients without metastases, univariate analysis showed disease-free survival (DFS) related to primary size >10 cm (P=0.003), surgery (P=0.004), local recurrence (P=0.003), and age (P<0.001). In multivariate analysis for DFS, primary size >10 cm (P=0.01) and older age (P<0.001) were significant for worse outcome. CONCLUSIONS: Multimodality treatment remains standard for localized ESOS, with indications for neoadjuvant therapy less clear. Larger tumor size and older age were prognostic of poorer DFS.

Stereotactic body radiation therapy for stage I non-small cell lung cancer: a small academic hospital experience.

PURPOSE/OBJECTIVE(S): Stereotactic body radiation therapy (SBRT) has been shown to have increased local control and overall survival relative to conventional external beam radiation therapy in patients with medically inoperable stage I non-small cell lung cancer (NSCLC). Excellent rates of local control have been demonstrated both in clinical trials and in single-center studies at large academic institutions. However, there is limited data on the experiences of small academic hospitals with SBRT for stage I NSCLC. The purpose of this study is to report the local control and overall survival rates in patients treated with SBRT for stage I NSCLC at Winthrop-University Hospital (WUH), a small academic hospital. MATERIALS/METHODS: This is a retrospective review of 78 stage I central and peripheral NSCLC tumors treated between December 2006 and July 2012 with SBRT at WUH. Treatment was given utilizing fiducials and a respiratory tracking system. If the fiducials were not trackable, a spine tracking system was used for tumor localization. CT-based planning was performed using the ray trace algorithm. Treatment was delivered over consecutive days to a median dose of 4800 cGy delivered in four fractions. The Kaplan-Meier method was used to calculate local control and overall survival. RESULTS: The median age was 78.5 years. Fifty-four percent of the patient population was female. Sixty seven percent of the tumors were stage IA, and 33% of the tumors were stage IB. Fifty-three percent of the tumors were adenocarcinomas and 29% were squamous cell carcinomas, with the remainder being of unknown histology or NSCLC, not otherwise specified The 2-year local control rate was 87%, and the 2-year overall survival was 68%. CONCLUSION: Our findings support that local control and overall survival at a small academic hospital are comparable to that of larger academic institutions' published experiences with SBRT for stage I NSCLC.

Prostate-specific antigen bounce following stereotactic body radiation therapy for prostate cancer.

INTRODUCTION: Prostate-specific antigen (PSA) bounce after brachytherapy has been well-documented. This phenomenon has also been identified in patients undergoing stereotactic body radiation therapy (SBRT). While the parameters that predict PSA bounce have been extensively studied in prostate brachytherapy patients, this study is the first to analyze the clinical and pathologic predictors of PSA bounce in prostate SBRT patients. MATERIALS AND METHODS: Our institution has maintained a prospective database of patients undergoing SBRT for prostate cancer since 2006. Our study population includes patients between May 2006 and November 2011 who have at least 18 months of follow-up. All patients were treated using the CyberKnife treatment system. The prescription dose was 35-36.25 Gy in five fractions. RESULTS: One hundred twenty patients were included in our study. Median PSA follow-up was 24 months (range 18-78 months). Thirty-four (28%) patients had a PSA bounce. The median time to PSA bounce was 9 months, and the median bounce size was 0.50 ng/mL. On univariate analysis, only younger age (p = 0.011) was shown to be associated with an increased incidence of PSA bounce. Other patient factors, including race, prostate size, prior treatment by hormones, and family history of prostate cancer, did not predict PSA bounces. None of the tumor characteristics studied, including Gleason score, pre-treatment PSA, T-stage, or risk classification by NCCN guidelines, were associated with increased incidence of PSA bounces. Younger age was the only statistically significant predictor of PSA bounce on multivariate analysis (OR = 0.937, p = 0.009). CONCLUSION: PSA bounce, which has been reported after prostate brachytherapy, is also seen in a significant percentage of patients after CyberKnife SBRT. Close observation rather than biopsy can be considered for these patients. Younger age was the only factor that predicted PSA bounce.

Prognostic value of metabolic tumor volume and total lesion glycolysis from ¹8F-FDG PET/CT in patients undergoing stereotactic body radiation therapy for stage I non-small-cell lung cancer.

OBJECTIVES: The aim of this study was to evaluate the prognostic value of pretreatment F-fluorodeoxyglucose PET/computed tomography (CT), particularly in the assessment of metabolic tumor burden markers such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), with respect to clinical outcomes in stage I non-small-cell lung cancer (NSCLC) patients undergoing stereotactic body radiation therapy (SBRT). METHODS: This retrospective study evaluated 50 patients who underwent SBRT for stage I NSCLC from May 2007 to December 2012. The maximum standardized uptake value (SUVmax), average SUV (SUVavg), MTV, and TLG were measured from the PET/CT scan. The study population was dichotomized at the median into high and low groups. Kaplan-Meier log-rank tests were then used to compare high with low PET/CT parameter groups, and univariate Cox proportional hazards regression analysis was carried out to identify predictors of overall survival. RESULTS: The 2-year local control rate was 93.7%. After a median follow-up of 25.1 months, the 2-year overall survival was 79.3%. Eight patients (16%) had disease recurrence. There were three local failures (6%), three mediastinal failures (6%), and six cases of distant metastases (12%). Both Kaplan-Meier actuarial analysis and Cox proportional hazards regression found no correlation between SUVmax, SUVavg, MTV, and TLG and overall survival. CONCLUSION: Standard PET/CT measures, such as SUVmax, as well as newer measures of metabolic tumor burden, such as MTV and TLG, were not correlated with overall survival in our study population of stage I NSCLC patients undergoing SBRT. Larger studies with longer follow-up periods are needed to confirm these results.