Trimodality therapy for patients with stage III non-small-cell lung cancer: A comprehensive surveillance, epidemiology, and end results analysis.

PURPOSE: Debate exists regarding the optimal management for patients with stage III non-small-cell lung cancer (NSCLC). Recent inclusion of chemotherapeutic data in the Surveillance, Epidemiology, and End Results (SEER) database has made it possible to identify patients with NSCLC who received chemotherapy. We hypothesized that patients with stage III NSCLC experience improved overall survival from trimodality therapy (TMT) versus definitive chemoradiation therapy (CRT) alone. MATERIALS AND METHODS: We analyzed the overall survival of stage III NSCLC patients based on the receipt of TMT versus CRT alone. This included crude and adjusted univariate models as well as crude and doubly robust adjusted multivariable analyses, both utilizing propensity score matching and inverse probability of treatment weighting. Factors included in the multivariable analyses included: age, sex, marital status, income, date of diagnosis, primary site, histology, grade, T stage, N stage, and intended treatment. Planned subset analyses were performed for stage III(N2) patients. RESULTS: Adult patients with stage III NSCLC (N = 9008) from the SEER database were included in our analyses. In our univariate analyses, an overall survival benefit was observed for TMT versus CRT (CrudeHR = 0.58, 95% CI = 0.55-0.61, p < 0.001; AdjHR = 0.58, 95% CI = 0.54-0.61, p < 0.001). This persisted in both crude and doubly robust multivariable analyses (CrudeHR = 0.57, 95% CI = 0.53-0.61, p < 0.001; AdjHR = 0.56, 95% CI = 0.53-0.59, p < 0.001). Patients with stage III(N2) disease also demonstrated a significant benefit to OS with TMT versus CRT alone. CONCLUSION: The significant difference in overall survival seen with TMT suggests this may be an effective treatment approach for select patients.

Synthetic pulmonary perfusion images from 4DCT for functional avoidance using deep learning.

Purpose.To develop and evaluate the performance of a deep learning model to generate synthetic pulmonary perfusion images from clinical 4DCT images for patients undergoing radiotherapy for lung cancer.Methods. A clinical data set of 58 pre- and post-radiotherapy99mTc-labeled MAA-SPECT perfusion studies (32 patients) each with contemporaneous 4DCT studies was collected. Using the inhale and exhale phases of the 4DCT, a 3D-residual network was trained to create synthetic perfusion images utilizing the MAA-SPECT as ground truth. The training process was repeated for a 50-imaging study, five-fold validation with twenty model instances trained per fold. The highest performing model instance from each fold was selected for inference upon the eight-study test set. A manual lung segmentation was used to compute correlation metrics constrained to the voxels within the lungs. From the pre-treatment test cases (N = 5), 50th percentile contours of well-perfused lung were generated from both the clinical and synthetic perfusion images and the agreement was quantified.Results. Across the hold-out test set, our deep learning model predicted perfusion with a Spearman correlation coefficient of 0.70 (IQR: 0.61-0.76) and a Pearson correlation coefficient of 0.66 (IQR: 0.49-0.73). The agreement of the functional avoidance contour pairs was Dice of 0.803 (IQR: 0.750-0.810) and average surface distance of 5.92 mm (IQR: 5.68-7.55).Conclusion. We demonstrate that from 4DCT alone, a deep learning model can generate synthetic perfusion images with potential application in functional avoidance treatment planning.

Higher biologically effective dose is associated with improved survival in patients with squamous cell carcinoma of the lung treated with stereotactic body radiation therapy.

BACKGROUND: Multiple studies have suggested that patients with early-stage SCC of the lung treated with SBRT are more susceptible to local failure compared to other NSCLC histologies. It is unknown if higher BED leads to improved outcomes in this patient population. We evaluated the effect of "high" BED versus "low" BED SBRT on overall survival (OS) in SCC and non-SCC NSCLC patients. METHODS: The National Cancer Database was used to identify patients with cT1-2N0M0 NSCLC diagnosed between 2006-2016 treated with 3-5 fraction SBRT. Patients were grouped by BEDhigh (>150 Gy) and BEDlow (≤132 Gy). Univariate and multivariable analysis using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment (IPTW) weighting was used to account for selection bias. RESULTS: We identified 4,717 eligible SCC patients and 8,807 eligible non-SCC NSCLC patients. In SCC patients, BEDhigh was associated with improved OS in both univariate and multivariate analysis (MVA HR 0.84 95% CI 0.76-0.92, p < 0.001), with estimated IPTW-adjusted 3-year OS of 49% compared to 41% for the BEDlow group. In contrast, BEDhigh was not associated with improved OS compared to BEDlow for non-SCC NSCLC patients (MVA HR 0.94 95% CI 0.86-1.04, p = 0.23), with estimated IPTW-adjusted 3-year OS of 54% and 53%, respectively. CONCLUSIONS: Our analysis suggests that in patients with early-stage NSCLC, SBRT regimens with BED > 150 Gy may confer a survival benefit in patients with SCC histology. Histology-based dose modification should be considered, and prospective validation may be warranted.

The Role of Postoperative Radiation Therapy for pN2 Non-small-cell Lung Cancer.

BACKGROUND: The role for postoperative radiation therapy (PORT) for patients with non-small-cell lung cancer (NSCLC) with mediastinal lymph node (LN) involvement (pN2 disease) is controversial. We compared surgery alone with PORT among patients with pN2 NSCLC. We then performed subset analyses to better delineate patients that might benefit from PORT. PATIENTS AND METHODS: We conducted a propensity score (PS)-matched, inverse probability of treatment weighting (IPTW) Surveillance, Epidemiology, and End Results (SEER) analysis of patients with pN2 disease from 1989 to 2016 with surgery alone or PORT. Multiple imputation with chained equations was used for missing LN data. RESULTS: A total of 8631 patients were included in this analysis; 4579 underwent surgery alone, and 4052 underwent PORT. Following PS matching and IPTW, there was no difference in overall survival (OS) (hazard ratio [HR], 0.99; P = .76). However, PORT improved OS among a subset of patients with a LN positive to sampled ratio ≥ 50% (HR, 0.90; P = .01). Moreover, there was a trend towards improved OS among this subset, even with chemotherapy (HR, 0.91; P = .09). CONCLUSION: PORT is not associated with an improvement or detriment in OS for all patients with pN2 NSCLC. However, patients with a positive to sampled LN ratio ≥ 50% may benefit, regardless of chemotherapy status. Nevertheless, PORT will remain the standard of care as we await the results of the ongoing LUNG ART trial.

Predictors of radiation necrosis in long-term survivors after Gamma Knife stereotactic radiosurgery for brain metastases.

BACKGROUND: The long-term risk of necrosis after radiosurgery for brain metastases is uncertain. We aimed to investigate incidence and predictors of radiation necrosis for individuals with more than 1 year of survival after radiosurgery for brain metastases. METHODS: Patients who had a diagnosis of brain metastases treated between December 2006 and December 2014, who had at least 1 year of survival after first radiosurgery were retrospectively reviewed. Survival was analyzed using the Kaplan-Meier estimator, and the incidence of radiation necrosis was estimated with death or surgical resection as competing risks. Patient and treatment factors associated with radiation necrosis were also analyzed. RESULTS: A total of 198 patients with 732 lesions were analyzed. Thirty-four lesions required salvage radiosurgery and 10 required salvage surgical resection. Median follow-up was 24 months. The estimated median survival for this population was 25.4 months. The estimated per-lesion incidence of radiation necrosis at 4 years was 6.8%. Medical or surgical therapy was required for 60% of necrosis events. Tumor volume and male sex were significant factors associated with radiation necrosis. The per-lesions incidence of necrosis for patients undergoing repeat radiosurgery was 33.3% at 4 years. CONCLUSIONS: In this large series of patients undergoing radiosurgery for brain metastases, patients continued to be at risk for radiation necrosis throughout their first 4 years of survival. Repeat radiosurgery of recurrent lesions greatly exacerbates the risk of radiation necrosis, whereas treatment of larger target volumes increases the risk modestly.

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.

Addition of radiotherapy to surgery and chemotherapy improves survival in localized malignant pleural mesothelioma: A Surveillance, Epidemiology, and End Results (SEER) study.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a devastating disease with poor survival outcomes for most patients. Optimizing therapeutic approaches is thus vital, but has been hampered by a dearth of randomized trials to guide decision making. We used a population-level database to evaluate the impact of radiotherapy as a component of trimodality therapy on overall survival (OS) in MPM. METHODS: We retrospectively reviewed the SEER Radiation/Chemotherapy database for patients with MPM who received surgery and chemotherapy, with or without radiotherapy. A propensity score-matched analysis with inverse probability of treatment weighting (IPTW) was performed. Weight-adjusted univariate KM analysis was performed and doubly robust, IPTW-adjusted multivariable cox proportional hazards regression modeling was also performed to quantify the effect of radiotherapy on OS in trimodality therapy for MPM. RESULTS: 1015 patients were identified. 678 patients received surgery and chemotherapy, and 337 patients received trimodality therapy. For patients with localized disease, OS was significantly improved with trimodality therapy (HR 0.56, CI 0.4 - 0.8, p = 0.001), which persisted with IPTW adjustment (HR 0.65, CI 0.49 - 0.95, p = 0.0248). No significant benefit was seen for patients with regional or distant disease. On multivariate analysis, positive predictors of survival after IPTW adjustment were female sex, diagnosis after 2005, and left-sided disease. CONCLUSIONS: These findings support a significant benefit to OS by incorporating radiotherapy as a component of trimodality therapy for patients with localized MPM compared to only surgery and chemotherapy. It does not provide a significant overall survival benefit for patients with regional or metastatic disease.

Evaluation of First-line Radiosurgery vs Whole-Brain Radiotherapy for Small Cell Lung Cancer Brain Metastases: The FIRE-SCLC Cohort Study.

Importance: Although stereotactic radiosurgery (SRS) is preferred for limited brain metastases from most histologies, whole-brain radiotherapy (WBRT) has remained the standard of care for patients with small cell lung cancer. Data on SRS are limited. Objective: To characterize and compare first-line SRS outcomes (without prior WBRT or prophylactic cranial irradiation) with those of first-line WBRT. Design, Setting, and Participants: FIRE-SCLC (First-line Radiosurgery for Small-Cell Lung Cancer) was a multicenter cohort study that analyzed SRS outcomes from 28 centers and a single-arm trial and compared these data with outcomes from a first-line WBRT cohort. Data were collected from October 26, 2017, to August 15, 2019, and analyzed from August 16, 2019, to November 6, 2019. Interventions: SRS and WBRT for small cell lung cancer brain metastases. Main Outcomes and Measures: Overall survival, time to central nervous system progression (TTCP), and central nervous system (CNS) progression-free survival (PFS) after SRS were evaluated and compared with WBRT outcomes, with adjustment for performance status, number of brain metastases, synchronicity, age, sex, and treatment year in multivariable and propensity score-matched analyses. Results: In total, 710 patients (median [interquartile range] age, 68.5 [62-74] years; 531 men [74.8%]) who received SRS between 1994 and 2018 were analyzed. The median overall survival was 8.5 months, the median TTCP was 8.1 months, and the median CNS PFS was 5.0 months. When stratified by the number of brain metastases treated, the median overall survival was 11.0 months (95% CI, 8.9-13.4) for 1 lesion, 8.7 months (95% CI, 7.7-10.4) for 2 to 4 lesions, 8.0 months (95% CI, 6.4-9.6) for 5 to 10 lesions, and 5.5 months (95% CI, 4.3-7.6) for 11 or more lesions. Competing risk estimates were 7.0% (95% CI, 4.9%-9.2%) for local failures at 12 months and 41.6% (95% CI, 37.6%-45.7%) for distant CNS failures at 12 months. Leptomeningeal progression (46 of 425 patients [10.8%] with available data) and neurological mortality (80 of 647 patients [12.4%] with available data) were uncommon. On propensity score-matched analyses comparing SRS with WBRT, WBRT was associated with improved TTCP (hazard ratio, 0.38; 95% CI, 0.26-0.55; P < .001), without an improvement in overall survival (median, 6.5 months [95% CI, 5.5-8.0] for SRS vs 5.2 months [95% CI, 4.4-6.7] for WBRT; P = .003) or CNS PFS (median, 4.0 months for SRS vs 3.8 months for WBRT; P = .79). Multivariable analyses comparing SRS and WBRT, including subset analyses controlling for extracranial metastases and extracranial disease control status, demonstrated similar results. Conclusions and Relevance: Results of this study suggest that the primary trade-offs associated with SRS without WBRT, including a shorter TTCP without a decrease in overall survival, are similar to those observed in settings in which SRS is already established.

Post-mastectomy radiotherapy is associated with improved overall survival in T3N0 patients who do not receive chemotherapy.

BACKGROUND AND PURPOSE: There is limited retrospective evidence addressing the utility of post-mastectomy radiotherapy (PMRT) in patients with T3N0 breast cancer. We performed a retrospective analysis of the National Cancer Database (NCDB) comparing overall survival (OS) in T3N0 patients treated with mastectomy alone (MTX) or with PMRT. MATERIALS AND METHODS: We performed a matched-cohort analysis of NCDB breast cancer patients with pT3N0 disease who did not receive NAC, or cT3N0 patients who received NAC treated between 2006 and 2014. Patients were matched for all available baseline characteristics using propensity scores with inverse probability of treatment weighting (IPTW) with stabilized weights. RESULTS: We identified 13,901 eligible patients. In the pT3N0 cohort, median follow-up was 47 months for the MTX group and 50 months for the PMRT group. In the cT3N0 cohort, median follow-up was 44 months for the MTX group and 46 months for the PMRT group. OS was higher in pT3N0 patients treated with PMRT compared to MTX: 7-year OS of 74% vs. 65% (P < 0.001). Doubly robust multivariable analysis showed an association between PMRT and improved OS (HR 0.78, 95% CI 0.68-0.89, P < 0.001). There was no benefit to PMRT in patients who received adjuvant chemotherapy (AC). In the NAC cohort, PMRT did not change OS, with 7-year OS of 78% with MTX and 79% with PMRT. There was a trend of improved OS with PMRT in patients with residual disease in the breast and lymph nodes (HR 0.70, 95% CI 0.46-1.07). CONCLUSION: PMRT improves OS in patients with pT3N0 disease, but the benefit appears limited to those who do not receive AC. PMRT does not improve OS in patients with cT3N0 disease who receive NAC, but there might be a benefit in patients with a poor response to chemotherapy. However, longer follow-up may be needed to make a definitive conclusion about the benefit of PMRT in patients who receive chemotherapy.

Stereotactic radiosurgery for pediatric brain arteriovenous malformations: long-term outcomes.

OBJECTIVE: Contrary to the better described obliteration- and hemorrhage-related data after stereotactic radiosurgery (SRS) of brain arteriovenous malformations (AVMs) in pediatric patients, estimates of the rarer complications, including cyst and tumor formation, are limited in the literature. The aim of the present study was to assess the long-term outcomes and risks of SRS for AVMs in pediatric patients (age < 18 years). METHODS: The authors retrospectively analyzed the International Radiosurgery Research Foundation pediatric AVM database for the years 1987 to 2018. AVM obliteration, post-SRS hemorrhage, cyst formation, and tumor formation were assessed. Cumulative probabilities, adjusted for the competing risk of death, were calculated. RESULTS: The study cohort comprised 539 pediatric AVM patients (mean follow-up 85.8 months). AVM obliteration was observed in 64.3% of patients, with cumulative probabilities of 63.6% (95% CI 58.8%-68.0%), 77.1% (95% CI 72.1%-81.3%), and 88.1% (95% CI 82.5%-92.0%) over 5, 10, and 15 years, respectively. Post-SRS hemorrhage was observed in 8.4% of patients, with cumulative probabilities of 4.9% (95% CI 3.1%-7.2%), 9.7% (95% CI 6.4%-13.7%), and 14.5% (95% CI 9.5%-20.5%) over 5, 10, and 15 years, respectively. Cyst formation was observed in 2.1% of patients, with cumulative probabilities of 5.5% (95% CI 2.3%-10.7%) and 6.9% (95% CI 3.1%-12.9%) over 10 and 15 years, respectively. Meningiomas were observed in 2 patients (0.4%) at 10 and 12 years after SRS, with a cumulative probability of 3.1% (95% CI 0.6%-9.7%) over 15 years. CONCLUSIONS: AVM obliteration can be expected after SRS in the majority of the pediatric population, with a relatively low risk of hemorrhage during the latency period. Cyst and benign tumor formation after SRS can be observed in 7% and 3% of patients over 15 years, respectively. Longitudinal surveillance for delayed neoplasia is prudent despite its low incidence.

Radiosurgery for Unruptured Intervention-Naïve Pediatric Brain Arteriovenous Malformations.

BACKGROUND: Long-term data regarding stereotactic radiosurgery (SRS) as a standalone therapy for unruptured pediatric brain arteriovenous malformations (AVMs) are incompletely defined. OBJECTIVE: To evaluate, in a multicenter, retrospective cohort study, the outcomes after SRS for unruptured, intervention-naïve pediatric AVMs. METHODS: To retrospectively analyze the International Radiosurgery Research Foundation pediatric AVM database from 1987 to 2018. Pediatric patients with unruptured, previously untreated AVMs who underwent SRS were included. The primary endpoint was a composite of hemorrhagic stroke, death, or permanently symptomatic radiation-induced changes. RESULTS: The study cohort comprised 101 patients (mean follow-up 80.8 mo). The primary endpoint occurred in 14%, comprising hemorrhagic stroke, death, and permanent radiation-induced changes in 6%, 3%, and 8%, respectively. Estimated probabilities of the primary endpoint were 5.2%, 10.8%, and 23.0% at 2, 5, and 10 yr, respectively. Estimated probabilities of AVM obliteration at 5 and 10 yr were 64% and 82%, respectively. Single SRS treatment (P = .007) and higher margin dose (P = .005) were predictors of obliteration. Subgroup analysis of Spetzler-Martin grade I-III AVMs estimated primary endpoint probabilities of 3.7%, 8.4%, and 18.7% at 2, 5, and 10 yr, respectively. CONCLUSION: Treatment of unruptured, intervention-naïve AVMs in the pediatric population with SRS carries an approximately 2% annual risk of morbidity and mortality, which appears to plateau after 10 yr. The poorly described natural history of pediatric AVMs renders any comparison of SRS vs conservative management imperfect.

Role of Gamma Knife Radiosurgery in Small Cell Lung Cancer: A Multi-Institutional Retrospective Study of the International Radiosurgery Research Foundation (IRRF).

BACKGROUND: Despite a high incidence of brain metastases in patients with small-cell lung cancer (SCLC), limited data exist on the use of stereotactic radiosurgery (SRS), specifically Gamma Knife™ radiosurgery (Elekta AB), for SCLC brain metastases. OBJECTIVE: To provide a detailed analysis of SCLC patients treated with SRS, focusing on local failure, distant brain failure, and overall survival (OS). METHODS: A multi-institutional retrospective review was performed on 293 patients undergoing SRS for SCLC brain metastases at 10 medical centers from 1991 to 2017. Data collection was performed according to individual institutional review boards, and analyses were performed using binary logistic regression, Cox-proportional hazard models, Kaplan-Meier survival analysis, and competing risks analysis. RESULTS: Two hundred thirty-two (79%) patients received SRS as salvage following prior whole-brain irradiation (WBRT) or prophylactic cranial irradiation, with a median marginal dose of 18 Gy. At median follow-up after SRS of 6.4 and 18.0 mo for surviving patients, the 1-yr local failure, distant brain failure, and OS were 31%, 49%, and 28%. The interval between WBRT and SRS was predictive of improved OS for patients receiving SRS more than 1 yr after initial treatment (21%, <1 yr vs 36%, >1 yr, P = .01). On multivariate analysis, older age was the only significant predictor for OS (hazard ratio 1.63, 95% CI 1.16-2.29, P = .005). CONCLUSION: SRS plays an important role in the management of brain metastases from SCLC, especially in salvage therapy following WBRT. Ongoing prospective trials will better assess the value of radiosurgery in the primary management of SCLC brain metastases and potentially challenge the standard application of WBRT in SCLC patients.

Trimodality therapy for atypical teratoid/rhabdoid tumor is associated with improved overall survival: A surveillance, epidemiology, and end results analysis.

BACKGROUND: Atypical teratoid/rhabdoid tumors (AT/RTs) are rare aggressive central nervous system tumors. The use of radiation therapy (RT) remains controversial, especially for patients younger than three years of age. The purpose of the current investigation is to robustly analyze the impact of RT among pediatric AT/RT patients using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: SEER 18 Custom Data registries were queried for AT/RT (ICD-0-3 9508/3). A total of 190 pediatric AT/RT patients were identified, of whom 102 underwent surgery + chemotherapy and 88 underwent trimodality therapy. Univariate and multivariable analyses using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment weighting was performed to account for indication bias. The landmark method was used to account for immortal time bias. RESULTS: The majority of patients were <3 years old (75.8%). Patients <3 were more likely to be treated without RT as compared with older patients (62% vs 38%). Doubly robust MVA identified distant disease as a negative prognostic factor (HR 2.1, P = 0.003), whereas trimodality therapy was strongly protective (HR 0.39, P < 0.001). Infants (<1), toddlers (1-2), and older children (3+) all benefited from trimodality therapy, with largest benefit for infants (HR 0.34, P = 0.02) and toddlers (HR 0.31, P < 0.001). CONCLUSION: The current study provides further evidence that trimodality therapy improves clinical outcomes among patients with AT/RT. This finding was most pronounced for younger patients; therefore, further studies are needed to confirm this finding in this vulnerable population.

Five-Year Outcomes of a Single-Institution Prospective Trial of 19-Gy Single-Fraction High-Dose-Rate Brachytherapy for Low- and Intermediate-Risk Prostate Cancer.

PURPOSE: To update outcome and toxicity results of a prospective trial of 19-Gy single-fraction high-dose-rate (HDR) brachytherapy for men with low- and intermediate-risk prostate cancer. METHODS AND MATERIALS: Patients were treated on a prospective study of single-fraction HDR brachytherapy. All patients had low- or intermediate-risk prostate cancer. Patients with prostate volumes >50 cm3, taking alpha-blockers for urinary symptoms, or with baseline American Urologic Association symptom scores >12 were ineligible. Patients underwent transrectal ultrasound-guided interstitial implant of the prostate followed by single-fraction HDR brachytherapy to a prescription dose of 19 Gy. RESULTS: Sixty-eight patients were enrolled with a median follow-up of 3.9 years. Median age was 62 years. Median gland volume at the time of treatment was 35 cm3, 92.6% of patients had T1 disease, 63.2% had a Gleason score of 6, and median pretreatment prostate-specific antigen was 5.0 ng/mL. Chronic grade 2 genitourinary toxicity was 14.7%. No grade 3 urinary toxicity occurred. A single patient experienced grade 2+ rectal toxicity (grade 3 diarrhea) that was transient and resolved with medical management. The 5-year estimated disease-free survival was 77.2% with no significant difference between low- and intermediate-risk patients. A single patient developed distant metastases during the follow-up period. Biopsy-proven local failure at 5 years was 18.8%, occurring at a median interval of 4.0 years posttreatment. No deaths occurred during follow-up. CONCLUSIONS: With extended follow-up, toxicity rates after single-fraction 19-Gy HDR brachytherapy remain low. Higher-than-expected rates of biochemical and local failure, however, raise concerns regarding the adequacy of this dose. Additional investigation to define the optimal single-fraction HDR brachytherapy dose is warranted, and single-fraction treatment currently should not be offered outside the context of a clinical trial.

Adjuvant androgen deprivation therapy for prostate cancer treated with radiation therapy.

Radiation therapy is a commonly used curative modality for prostate cancer. The addition of androgen deprivation therapy (ADT) increases the curative potential of prostate radiotherapy (RT) in multiple subsets of patients. In addition to having an independent cytotoxic effect, current evidence suggests that androgen deprivation synergistically works with radiation therapy by preventing DNA repair. Given the wide-ranging toxicities of this therapy, clinicians must judiciously choose which patients may benefit from ADT and also consider the appropriate length of treatment. With recent advances in RT delivery, higher doses of radiation are currently used when compared with the dose used in historic trials, leading to the unanswered question of how RT dose interacts with ADT. Current and future clinical studies are attempting to further define the appropriate indications and patient populations for which ADT represents a clinically appropriate addition to prostate RT.

Early versus late Gamma Knife radiosurgery following transsphenoidal surgery for nonfunctioning pituitary macroadenomas: a multicenter matched-cohort study.

OBJECTIVE Gamma Knife radiosurgery (GKRS) is frequently used to treat residual or recurrent nonfunctioning pituitary macroadenomas. There is no consensus as to whether GKRS should be used early after surgery or if radiosurgery should be withheld until there is evidence of imaging-defined progression of tumor. Given the high incidence of adenoma progression after subtotal resection over time, the present study intended to evaluate the effect of timing of radiosurgery on outcome. METHODS This is a multicenter retrospective review of patients with nonfunctioning pituitary macroadenomas who underwent transsphenoidal surgery followed by GKRS from 1987 to 2015 at 9 institutions affiliated with the International Gamma Knife Research Foundation. Patients were matched by adenoma and radiosurgical parameters and stratified based on the interval between last resection and radiosurgery. Operative results, imaging data, and clinical outcomes were compared across groups following early (≤ 6 months after resection) or late (> 6 months after resection) radiosurgery. RESULTS After matching, 222 patients met the authors' study criteria (from an initial collection of 496 patients) and were grouped based on early (n = 111) or late (n = 111) GKRS following transsphenoidal surgery. There was a greater risk of tumor progression after GKRS (p = 0.013) and residual tumor (p = 0.038) in the late radiosurgical group over a median imaging follow-up period of 68.5 months. No significant difference in the occurrence of post-GKRS endocrinopathy was observed (p = 0.68). Thirty percent of patients without endocrinopathy in the early cohort developed new endocrinopathies during the follow-up period versus 27% in the late cohort (p = 0.84). Fourteen percent of the patients in the early group and 25% of the patients in the late group experienced the resolution of endocrine dysfunction after original presentation (p = 0.32). CONCLUSIONS In this study, early GKRS was associated with a lower risk of radiological progression of subtotally resected nonfunctioning pituitary macroadenomas compared with expectant management followed by late radiosurgery. Delaying radiosurgery may increase patient risk for long-term adenoma progression. The timing of radiosurgery does not appear to significantly affect the rate of delayed endocrinopathy.

Stereotactic Radiation for Palliation of Skull Base Recurrences of Salivary Gland Carcinomas: Implications for Tumor Targeting.

Background Approximately 3 to 13% of salivary carcinomas recur at the skull base. We report our experience treating these recurrences with stereotactic radiation. Methods In total, 14 patients with skull base recurrence of salivary gland carcinoma were identified. Patient characteristics, treatment parameters, response to treatment, local recurrence-free/overall survival, and patterns of failure were studied. Results All 12 symptomatic patients experienced palliation of symptoms. Two grade 3 toxicities were observed. Local recurrence-free survival after skull base treatment was 28 months (74 months after allowing for additional course of salvage radiotherapy). Overall survival was 153 months from primary diagnosis and 67 months from first skull base failure. Of 13 treatment failures, 8 occurred at margins; the rest were infield. All intracranial failures occurred along meningeal surfaces. Conclusions Stereotactic radiation provides well-tolerated palliation for the majority of patients, but with a high rate of local failure. Due to the propensity for meningeal failures, we suggest increasing margins along the meningeal surfaces when treating these patients.

The role of vaginal cuff brachytherapy in endometrial cancer.

OBJECTIVE: The purpose of this article is to review the data, rationale, and recommendations of vaginal brachytherapy (VBT) in the post-operative treatment of endometrial cancer patients. METHODS: The authors performed a thorough review of the medical literature regarding the use of adjuvant VBT in the treatment of endometrial cancer. Relevant data are presented in this review. Additionally, personal and institutional practices from the authors are incorporated where relevant. RESULTS: VBT for the adjuvant treatment of early stage endometrial cancer patients results in a low rate of recurrence (0-3.1%) with very low rates of toxicity. PORTEC-2 supports the use of adjuvant VBT versus external beam radiotherapy specifically for high-intermediate risk endometrial cancer patients. VBT has low rates of acute and chronic gastrointestinal and genitourinary toxicity and very low rates of second primary malignancy. The primary toxicity of VBT is vaginal atrophy and stenosis with controversy regarding the use of vaginal dilators for prevention. Data support that patients prefer to be involved in the decision making process for their adjuvant therapy, and patients have a lower minimal desired benefit of adjuvant VBT than do physicians. Guidelines exist from the American Brachytherapy Society and American Society of Radiation Oncology with support from the Society for Gynecologic Oncologists regarding the use of adjuvant VBT. CONCLUSIONS: VBT decreases the risk of recurrence with minimal toxicity in the adjuvant treatment of endometrial cancer. Adjuvant therapy should be discussed in a multi-disciplinary setting with detailed counseling of the risks and benefits with the patient so that she ultimately makes an informed decision regarding her adjuvant therapy.