Analysis of Retrospective Versus Prospective Peer Review in a Multisite Academic Radiation Department.

Purpose: Our multisite academic radiation department reviewed our experience with transitioning from weekly primarily retrospective to daily primarily prospective peer review to improve plan quality and decrease the rate of plan revisions after treatment start. Methods and Materials: This study was an institutional review board-approved prospective comparison of radiation treatment plan review outcomes of plans reviewed weekly (majority within 1 week after treatment start) versus plans reviewed daily (majority before treatment start, except brachytherapy, frame-based radiosurgery, and some emergent plans). Deviations were based on peer comments and considered major if plan revisions were recommended before the next fraction and minor if modifications were suggested but not required. Categorical variables were compared using χ2 distribution tests of independence; means were compared using independent t tests. Results: In all, 798 patients with 1124 plans were reviewed: 611 plans weekly and 513 plans daily. Overall, 76 deviations (6.8%) were noted. Rates of any deviation were increased in the daily era (8.6% vs 5.2%; P = .026), with higher rates of major deviations in the daily era (4.1% vs 1.6%; P = .012). Median working days between initial simulation and treatment was the same across eras (8 days). Deviations led to a plan revision at a higher rate in the daily era (84.1% vs 31.3%; P < .001). Conclusions: Daily prospective peer review is feasible in a multisite academic setting. Daily peer review with emphasis on prospective plan evaluation increased constructive plan feedback, plan revisions, and plan revisions being implemented before treatment start.

Concurrent chemotherapy with partial breast irradiation in triple negative breast cancer patients may improve disease control compared with sequential therapy.

Purpose: To report outcomes on a subset of patients with triple negative breast cancer (TNBC) treated on prospective trials with post-lumpectomy partial breast irradiation and concurrent chemotherapy (PBICC) and compare them to a retrospectively assessed similar cohort treated with whole breast irradiation after adjuvant chemotherapy (WBIaC). Methods and materials: Women with T1-2, N0-1 invasive breast cancer with ≥ 2mm lumpectomy margins were offered therapy on one of two PBICC trials. PBI consisted of 40.5 Gy in 15 daily 2.7 Gy fractions delivered concurrently with the first 2 cycles of adjuvant chemotherapy. The comparison cohort received WBI to a median dose of 60.7 Gy, (including boost, range 42.5 - 66 Gy), after completion of non-concurrent, adjuvant chemotherapy. We evaluated disease-free survival (DFS), and local/loco-regional/distant recurrence-free survival (RFS). We compared survival rates using Kaplan-Meier curves and log-rank test of statistical significance. Results: Nineteen patients with TNBC were treated with PBICC on prospective protocol, and 49 received WBIaC. At a median follow-up of 35.5 months (range 4.8-71.9), we observed no deaths in the PBICC cohort and 2 deaths in the WBIaC cohort (one from disease recurrence). With a median time of 23.4 (range 4.8 to 47) months, there were 7 recurrences (1 nodal, 4 local, 4 distant), all in the WBIaC group. At 5 years, there was a trend towards increased local RFS (100% vs. 85.4%, p=0.17) and loco-regional RFS (100% vs. 83.5, p=0.13) favoring the PBICC cohort. There was no significant difference in distant RFS between the two groups (100% vs. 94.4%, p=0.36). Five-year DFS was 100% with PBICC vs.78.9% (95% CI: 63.2 to 94.6%, p=0.08) with WBIaC. Conclusion: This study suggests that PBICC may offer similar and possibly better outcomes in patients with TNBC compared to a retrospective cohort treated with WBIaC. This observation is hypothesis-generating for prospective trials.

Patient characteristics and clinical factors affecting lumpectomy cavity volume: implications for partial breast irradiation.

Introduction: Partial breast irradiation (PBI) has increased in utilization, with the postoperative lumpectomy cavity and clips used to guide target volumes. The ideal timing to perform computed tomography (CT)-based treatment planning for this technique is unclear. Prior studies have examined change in volume over time from surgery but not the effect of patient characteristics on lumpectomy cavity volume. We sought to investigate patient and clinical factors that may contribute to larger postsurgical lumpectomy cavities and therefore predict for larger PBI volumes. Methods: A total of 351 consecutive women with invasive or in situ breast cancer underwent planning CT after breast-conserving surgery at a single institution during 2019 and 2020. Lumpectomy cavities were contoured, and volume was retrospectively computed using the treatment planning system. Univariate and multivariate analyses were performed to evaluate the associations between lumpectomy cavity volume and patient and clinical factors. Results: Median age was 61.0 years (range, 30-91), 23.9% of patients were Black people, 52.1% had hypertension, the median body mass index (BMI) was 30.4 kg/m², 11.4% received neoadjuvant chemotherapy, 32.5% were treated prone, mean interval from surgery to CT simulation was 54.1 days ± 45.9, and mean lumpectomy cavity volume was 42.2 cm3 ± 52.0. Longer interval from surgery was significantly associated with smaller lumpectomy cavity volume on univariate analysis, p = 0.048. Race, hypertension, BMI, the receipt of neoadjuvant chemotherapy, and prone position remained significant on multivariate analysis (p < 0.05 for all). Prone position vs. supine, higher BMI, the receipt of neoadjuvant chemotherapy, the presence of hypertension, and race (Black people vs. White people) were associated with larger mean lumpectomy cavity volume. Discussion: These data may be used to select patients for which longer time to simulation may result in smaller lumpectomy cavity volumes and therefore smaller PBI target volumes. Racial disparity in cavity size is not explained by known confounders and may reflect unmeasured systemic determinants of health. Larger datasets and prospective evaluation would be ideal to confirm these hypotheses.

Discovery of increased number or interval growth of brain metastases on same-day GammaKnife™ planning MRI: Predicting factors and patient outcomes.

Purpose: To determine factors associated with increased risk of finding new and/or enlarged brain metastases (BM) on GammaKnife™ (GK) MRI and their impact on patient outcomes. Results: 43.9% of patients showed BM growth, 32.9% had additional brain metastases (aBM), and 18.1 % had both. Initial brain metastasis velocity (iBMV) was associated with finding aBM. Time between diagnostic MRI (dMRI) and GK MRI was associated with interval growth and each day increased this risk by 2%. Prior brain metastasectomy and greater time between either dMRI or latest extracranial RT and GK MRI predicted both aBM and BM growth. aBM and/or BM growth led to management change in 1.8% of cases and were not associated with OS or incidence of distant intracranial failure. Conclusions: Number of metastases seen on dMRI and iBMV predicted both aBM and/or BM growth, however, these factors did not significantly affect survival or incidence of distant intracranial failure.

Clinical and Preclinical Outcomes of Combining Targeted Therapy With Radiotherapy.

In the era of precision medicine, radiation medicine is currently focused on the precise delivery of highly conformal radiation treatments. However, the tremendous developments in targeted therapy are yet to fulfill their full promise and arguably have the potential to dramatically enhance the radiation therapeutic ratio. The increased ability to molecularly profile tumors both at diagnosis and at relapse and the co-incident progress in the field of radiogenomics could potentially pave the way for a more personalized approach to radiation treatment in contrast to the current ''one size fits all'' paradigm. Few clinical trials to date have shown an improved clinical outcome when combining targeted agents with radiation therapy, however, most have failed to show benefit, which is arguably due to limited preclinical data. Several key molecular pathways could theoretically enhance therapeutic effect of radiation when rationally targeted either by directly enhancing tumor cell kill or indirectly through the abscopal effect of radiation when combined with novel immunotherapies. The timing of combining molecular targeted therapy with radiation is also important to determine and could greatly affect the outcome depending on which pathway is being inhibited.

Analysis of Virtual Versus In-Person Prospective Peer Review Workflow in a Multisite Academic Radiation Oncology Department.

PURPOSE: In radiation oncology, peer review is a process where subjective treatment planning decisions are assessed by those independent of the prescribing physician. Before March 2020, all peer review sessions occurred in person; however due to the COVID-19 pandemic, the peer-review workflow was transitioned from in-person to virtual. We sought to assess any differences between virtual versus in-person prospective peer review. METHODS AND MATERIALS: Patients scheduled to receive nonemergent nonprocedural radiation therapy (RT) were presented daily at prospective peer-review before the start of RT administration. Planning software was used, with critical evaluation of several variables including treatment intent, contour definition, treatment target coverage, and risk to critical structures. A deviation was defined as any suggested plan revision. RESULTS: In the study, 274 treatment plans evaluated in-person in 2017 to 2018 were compared with 195 plans evaluated virtually in 2021. There were significant differences in palliative intent (36% vs 22%; P = .002), but not in total time between simulation and the start of treatment (9.2 vs 10.0 days; P = .10). Overall deviations (8.0% in-person vs 2.6% virtual; P = .015) were significantly reduced in virtual peer review. CONCLUSIONS: Prospective daily peer review of radiation oncology treatment plans can be performed virtually with similar timeliness of patient care compared with in-person peer review. A decrease in deviation rate in the virtual peer review setting will need to be further investigated to determine whether virtual workflow can be considered a standard of care.

Predictors of Whole Breast Radiation Therapy Completion in Early Stage Breast Cancer Following Lumpectomy.

BACKGROUND: Whole breast radiation therapy (RT) has become standard of care in early stage breast cancer treatment following lumpectomy. Predictors of RT completion have been sparsely studied, with no previous nationwide examination of the impact of fractionation regimen on completion rate. PATIENTS AND METHODS: The National Cancer Database identified patients with early stage breast cancer having undergone lumpectomy and RT from 2004 through 2015. Fraction size of 1.8-2.0 Gray (Gy) was defined as standard fractionation (SFRT); 2.66-2.70 Gy/fraction as hypofractionation (HFRT). RT completion was defined as receipt of at least 46 Gy for SFRT and 40 Gy for HFRT. A multivariable logistic regression model characterized RT completion predictors. RESULTS: A total of 100,734 patients were identified where fraction size could be reliably characterized as above; more than 87% completed RT. Of these, 66.8% received SFRT, yet HFRT use significantly increased over time (5.2% increase/year; P < .0001). RT completion rates were significantly greater following HFRT (99.3%) versus SFRT (79.7%); patients receiving SFRT had higher odds of not completing RT (odds ratio, 41.5; 95% confidence interval, 36.6-47.1; P < .0001). Multivariable analysis revealed that African-American and Caucasian patients treated with SFRT versus HFRT had 22 and 43 times the odds of not completing RT, respectively (P < .0001). CONCLUSIONS: SFRT remained the majority of RT fractionation in the studied time period, although HFRT use has increased over time. Patients residing > 10 miles from a treatment facility or of African-American race had lower odds of completing RT, as were patients treated with SFRT versus HFRT. These findings suggest compliance advantages of HFRT for patients with early stage breast cancer having undergone lumpectomy.

Radiosurgery dose reduction for brain metastases on immunotherapy (RADREMI): A prospective phase I study protocol.

INTRODUCTION: Up to 20% of patients with brain metastases treated with immune checkpoint inhibitor (ICI) therapy and concomitant stereotactic radiosurgery (SRS) suffer from symptomatic radiation necrosis. The goal of this study is to evaluate Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI) on six-month symptomatic radiation necrosis rates. METHODS: This study is a prospective single arm Phase I pilot study which will recruit patients with brain metastases receiving ICI delivered within 30 days before SRS. All patients will be treated with RADREMI dosing, which involves SRS doses of 18 Gy for 0-2 cm lesions, 14 Gy for 2.1-3 cm lesions, and 12 Gy for 3.1-4 cm lesions. All patients will be monitored for six-month symptomatic radiation necrosis (defined as a six-month rate of clinical symptomatology requiring steroid administration and/or operative intervention concomitant with imaging findings consistent with radiation necrosis) and six-month local control. We expect that RADREMI dosing will significantly reduce the symptomatic radiation necrosis rate of concomitant SRS + ICI without significantly sacrificing the local control obtained by the present RTOG 90-05 SRS dosing schema. Local control will be defined according to the Response Assessment in Neuro-Oncology (RANO) criteria. DISCUSSION: This study is the first prospective trial to investigate the safety of dose-reduced SRS in treatment of brain metastases with concomitant ICI. The findings should provide fertile soil for future multi-institutional collaborative efficacy trials of RADREMI dosing for this patient population. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04047602 (registration date: July 25, 2019).

Exploiting tumor position differences between deep inspiration and expiration in lung stereotactic body radiation therapy planning.

PURPOSE: We demonstrate proof of principle that normal tissue doses can be greatly reduced in lung stereotactic body radiation therapy (SBRT) for mobile tumors, if the delivered dose is split between opposite respiratory states. METHODS: Patients that underwent 5 fraction lung SBRT at our institution and had deep inspiration breath hold (DIBH) and free breathing 4D computed tomography scans were included. Volumetric modulated arc therapy plans were generated on both respiratory phases and a third composite plan was generated delivering half the dose using the DIBH plan and the other half using the expiratory phase plan for each fraction. Computed tomography scans for the composite plan were fused based on ribs adjacent to the tumor to evaluate the dose volume histogram of critical structures. RESULTS: Four patients with 4 total tumors had requisite planning scans available. Tumor size was between 0.7 to 2.9 cm and tumor movement 1.4 to 2.9 cm. Median reduction in the chest wall (CW) V30Gy for the composite plan was 74.6% (range 33.7 to 100%), 76.9% (range 32.9 to 100%), and 89.3% (range 69.5 to 100%) compared to the DIBH, expiration phase, and free breathing plans, respectively. Median reduction in CW maximum dose for the composite plan was 23.3% (range 0.27% to 46.4%), 23.5% (range 3.2 to 48.2%), and 23.4% (range 0.27% to 48.4%) compared to the DIBH, expiration phase, and free breathing plans, respectively. Greater reduction in CW maximum dose was observed when patients had no overlap in planning target volumes between DIBH and expiration phases (median reduction 43.9% for no overlap vs 2.7% with overlap). Between all plans, lung V20Gy absolute differences were within 1.3%. For 2 of 4 patients, the composite plan met constraints for 3 fraction SBRT, while standard plans did not. CONCLUSIONS: We conclude that composite DIBH-expiration SBRT planning has the potential to improve organ at risk sparing.

Stage-matched survival differences by ethnicity among gastric cancer patients of Asian ancestry treated in the United States.

BACKGROUND: Differences have been noted in overall survival (OS) in gastric cancer (GC) between trials conducted in Western vs Asian countries. The National Cancer Database (NCDB) reports outcomes and patient/disease variables relevant to OS. METHODS: Using NCDB, we identified 89 558 adult patients with GC diagnosed (2004-2012), where self-reported race/ethnicity was available. Cox proportional hazard model was used to calculate multivariable hazard ratio (HR) of death, adjusting for race/ethnicity, age, gender, insurance, histology, grade, location, stage, and treatment type. RESULTS: After adjustment, Asian patients had improved OS (HR = 0.74, 95% confidence intervals [CI] = 0.71-0.77). There were differences in OS between Asian ethnicities compared with white patients (n = 69 945), notably with Korean (n = 1249, HR = 0.70, 95% CI = 0.64-0.75), Chinese (n = 1271, HR = 0.69, 95% CI = 0.64-0.75), and Indian/Pakistani patients (n = 492, HR = 0.68, 95% CI = 0.61-0.76). Japanese (n = 829, HR = 0.84, 95% CI = 0.77-0.91) and Vietnamese (n = 560, HR = 0.79, 95% CI = 0.71-0.88) OS was also improved (P < 0.0001), while Filipino patients showed no difference (n = 415, HR = 1.00). Black patients had slightly improved OS (n = 13 500, HR = 0.98, 95% CI = 0.95-1.00, P = 0.035). CONCLUSIONS: This analysis supports improved OS in Asian patients independent of stage, treatment, and known patient or disease characteristics in this large US cohort, and is the largest to define OS differences between Asian ethnicities.

Prostate-specific antigen doubling time is a significant predictor of overall and disease-free survival in patients with prostate adenocarcinoma treated with brachytherapy.

PURPOSE: Recently, new approaches have been implemented in treating patients with newly diagnosed metastatic prostate cancer (PCa). An interesting area of study is to determine which risk factors may be used as predictors of more aggressive PCa behavior in patients with biochemical failure. The aim of this study was to determine prognostic factors in patients with prostate-specific antigen (PSA) failure after undergoing brachytherapy. METHODS AND MATERIALS: Between 1990 and 2015, 2771 patients with localized PCa underwent treatment at our institution treated by a single radiation oncologist with low-dose-rate brachytherapy as a component of definitive radiation therapy. Disease-specific survival (DSS), distant metastases (DM), and overall survival were calculated by the Kaplan-Meier method. Multivariable Cox regression analysis was also performed. RESULTS: In this group, 2126 patients (89%) had no evidence of PSA failure. Of the 251 of patients that did have biochemical failure, 115 (45.8%), 58 (23.1%), 78 (31.1%) had a PSA doubling time (PSADT) of <6 months, 6-12 months, and >12 months, respectively. Doubling time was associated with a statistically significant impact on DSS and DM but not overall survival, which appears to be dominated by initial age at diagnosis as well as stage. CONCLUSIONS: We have shown here that PSADT predicts for DSS and freedom from DM in our large prospectively followed cohort. Given the variable trajectory of metastatic and recurrent PCa, strong prognostic factors such as PSADT may be able to select a group of patients who benefit from earlier or escalated systemic therapies such as androgen deprivation or cytotoxic chemotherapy.

Gastric adenocarcinoma in young adult patients: patterns of care and survival in the United States.

BACKGROUND: Evidence regarding gastric cancer patients < 40 years old is limited. This study examines young adults with gastric adenocarcinoma in the National Cancer Database to describe demographics and treatment practices, and to develop a nomogram to predict survival. METHODS: The database was queried for adult patients diagnosed with gastric adenocarcinoma from 2004 to 2013. Patients were stratified into two age groups: <40 and ≥ 40 years. The database was analyzed to compare demographics, clinical characteristics, and treatments used for each group. Differences in survival were assessed using Kaplan-Meier curves and log-rank test. For adults < 40 years old, an accelerated failure time survival model was fitted for overall survival and a descriptive nomogram was constructed. RESULTS: Of 70,084 patients included, 2615 (4%) were < 40 years old and 67,469 (96%) were ≥ 40 years. Compared to older patients, adults < 40 years old were more likely to be female (46 vs. 35%), non-white (31 vs. 23%), Hispanic (32 vs. 11%), from the northeast (36 vs. 23%), and to present with stage IV disease (59 vs. 42%) and bone metastases (36 vs. 21%; p < 0.001 for all). The nomogram showed clinical stage as the strongest predictor of overall survival, followed by treatment, grade, race, Charlson-Deyo comorbidity score, and sex. CONCLUSIONS: Young adults with gastric adenocarcinoma are more likely to be Hispanic, female, from the northeast, and to present with metastases. Despite these differences, clinical stage, treatment, and tumor grade are most predictive of overall survival for young adult patients.

Postmastectomy Radiation in Breast Cancer Patients With Pathologically Positive Lymph Nodes After Neoadjuvant Chemotherapy: Usage Rates and Survival Trends.

PURPOSE: To analyze postmastectomy radiation therapy (PMRT) usage and its association with overall survival (OS) in breast cancer patients with pathologically positive lymph nodes after neoadjuvant chemotherapy (NAC). METHODS AND MATERIALS: Using the National Cancer Database, we identified women with nonmetastatic breast cancer diagnosed from 2004 to 2013 who had received NAC and undergone mastectomy with macroscopic pathologically positive lymph nodes. Joinpoint regression models were used to assess temporal trends in annual PMRT usage. Multivariable regression models were used to identify factors associated with PMRT use. A time-dependent Cox model was used to evaluate the predictors of mortality. RESULTS: The study included 29,270 patients, of whom 62.5% received PMRT. PMRT was markedly underused among all nodal subgroups, in particular, among ypN2 (68.4%) and ypN3 (67.0%) patients. Hispanic patients and those with Medicaid or Medicare insurance were less likely to receive PMRT than were non-Hispanics and patients with other insurance carriers. The adjusted 5-year OS rates were similar in ypN1 and ypN2 patients with or without PMRT but were significantly greater in ypN3 patients receiving PMRT (66% vs 63%; P=.042). On multivariable analysis, PMRT was associated with improved survival only among ypN3 patients after adjusting for patient, facility, and tumor variables (multivariable hazard ratio 0.85; 95% confidence interval 0.74-0.97). CONCLUSIONS: A considerable portion of breast cancer patients with advanced residual nodal disease after NAC did not receive appropriate adjuvant radiation. We also found socioeconomic disparities in national PMRT practice patterns. Patients with ypN3 disease might derive a survival benefit from PMRT.

Prognostic significance of Kadish staging in esthesioneuroblastoma: An analysis of the National Cancer Database.

BACKGROUND: Given the rarity of esthesioneuroblastoma, it is difficult to validate a staging system. The purpose of this study was to investigate the utility of the Kadish staging system in esthesioneuroblastoma using the National Cancer Database (NCDB). METHODS: One thousand one hundred sixty-seven patients with esthesioneuroblastoma were identified from the NCDB. RESULTS: Five-year survival was 80.0% for Kadish A, 87.7% for Kadish B, 77.0% for Kadish C, and 49.5% for Kadish D. Kadish B had higher survival than Kadish A. More Kadish B patients received surgery with adjuvant therapy than Kadish A patients (41.6% vs 32.5%; P = .0038) and also had more positive margins (21.6% vs 11.3%; P = .03). There was no difference in age distribution, sex, race, or neck dissection status between the 2 groups. CONCLUSION: Kadish B had greater survival than Kadish A, but the treatment characteristics could not account for this difference. The utility of early-stage Kadish staging is uncertain and requires further study.

Adjuvant radiation for salivary gland malignancies is associated with improved survival: A National Cancer Database analysis.

OBJECTIVE: There are no randomized data to support the use of postoperative radiation for salivary gland malignancies. This study uses the National Cancer Database (NCDB) to describe the epidemiology of salivary gland cancer patients and to investigate whether treatment with adjuvant radiation improves overall survival. METHODS AND MATERIALS: A total of 8243 patients diagnosed with a major salivary gland cancer were identified from the NCDB. All patients received primary surgical resection of their malignancy. Patients were risk-stratified by adverse features, and overall survival rates were determined. Patients were considered high risk if they had extracapsular extension and/or positive margin after resection. Patients were considered intermediate risk if they did not meet the criteria for high risk but had pT3-T4 disease, pN+ disease, lymphovascular space invasion, adenoid cystic histology, or grade 2-3 disease. Patients who did not meet criteria for high or intermediate risk were considered low risk. Overall patient demographics, disease characteristics, treatment factors, and outcomes were summarized with descriptive statistics and analyzed with STATA. RESULTS: Median follow-up in this cohort was 42.4 months, with the median age of 58 years. Patients in the high-risk group had greater survival (hazard ratio [HR], 0.76; P = .002; 95% confidence interval [CI], 0.64-0.91) if they received adjuvant radiation therapy. In contrast, patients in the intermediate- (HR, 1.01; P = .904; 95% CI, 0.85-1.20) and low-risk groups (HR, 0.85; P = .427; 95% CI, 0.57-1.26) did not experience a survival benefit with adjuvant radiation therapy. CONCLUSIONS: This large analysis compared survival outcomes between observation and adjuvant radiation alone in risk-stratified patients after resection of major salivary glands using a national database. The use of adjuvant radiation for high-risk major salivary gland cancers appears to offer a survival benefit. Although an overall survival benefit was not seen in low- and intermediate-risk salivary gland cancers, this study could not address impact on local control because of the limitations of the NCDB.

Predictors of Positive Margins After Definitive Resection for Gastric Adenocarcinoma and Impact of Adjuvant Therapies.

PURPOSE: Positive margins after definitive resection in gastric adenocarcinoma are associated with inferior outcomes. There are few randomized data to guide optimal adjuvant therapy after positive margins. METHODS: Using the National Cancer Database, we identified 24,619 nonmetastatic gastric adenocarcinoma patients who received diagnoses from 2004 to 2013 and underwent definitive resection to analyze for predictors of positive surgical margins. Of these patients, 2754 had positive margins (11.2%). Multivariate prevalence ratios were used to determine predictors. Survival analyses were performed with a Cox proportional hazards model by use of several methods of propensity score analysis. RESULTS: Increasing T and/or N category, high grade, and lymphovascular invasion predicted higher rates of positive margins. Asian race, treatment at an academic center, and robotic surgery predicted lower rates of positive margins. Among positive-margin patients with adjuvant treatment (n=1021), with a median follow-up period of 55 months, age, comorbidity score, nodal disease, and T4 disease predicted for worse overall survival (OS). Treatment at an academic center was associated with improved OS. Use of adjuvant concurrent chemoradiation therapy (CCRT) was associated with higher OS compared with chemotherapy alone after positive margins (hazard ratio, 0.72; 95% confidence interval, 0.58-0.91; P=.005) after propensity matching adjusting for predictors of OS. The 2-year and 3-year OS for positive-margin patients with chemotherapy alone was 43% and 29%, respectively, compared with 53% and 38%, respectively, with adjuvant CCRT. The log-rank P value for survival was .0015. CONCLUSIONS: Stage, race, treatment center, and surgery approach predict for margin status after resection. Adjuvant CCRT after positive margins is associated with improved OS after accounting for available clinical variables.

Long-term outcomes of acromegaly treated with fractionated stereotactic radiation: case series and literature review.

BACKGROUND: Growth hormone (GH)-secreting pituitary adenomas represent an uncommon subset of pituitary neoplasms. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) have been used as primary or adjuvant treatment. The purpose of this study is to report the long-term tumor control and toxicity from our institution and to perform a systematic literature review of acromegaly patients treated with FSRT. METHODS: We retrospectively reviewed all patients treated with FSRT (median dose 50.4 Gray [Gy], range 50.4-54 Gy) between 2005 and 2012 who had: 1) GH-secreting adenoma with persistently elevated insulin growth factor-1 (IGF-1) despite medical therapy and 2) clinical follow up >3 years after FSRT. Patients were treated with modern FSRT planning techniques. Biochemical control was defined as IGF-1 normalization. Systematic review of the literature was performed for FSRT in acromegaly. RESULTS: With a median follow-up of 80 months, radiographic control was achieved in all 11 patients and overall survival was 100%. Long-term biochemical control was achieved in 10 patients (90.9%) with either FSRT alone (36.4%) or FSRT with continued medical management (45.5%). No patient experienced new hypopituitarism, cranial nerve dysfunctions, or visual deficits. Our systematic review found published rates of biochemical control and hypopituitarism vary, with uniformly good radiographic control and low incidence of visual changes. CONCLUSIONS: Adjuvant FSRT offered effective long-term biochemical control and radiographic control, and there was a lower rate of complications in this current series. Review of the literature shows variations in published rates of biochemical control after FSRT for acromegaly, but low incidence of serious toxicities.

Adjuvant Proton Beam Therapy in the Management of Thymoma: A Dosimetric Comparison and Acute Toxicities.

BACKGROUND: We evaluated the dosimetric differences between proton beam therapy (PBT) and intensity modulated radiation therapy (IMRT) for resected thymoma. We simultaneously report our early clinical experience with PBT in this cohort. PATIENTS AND METHODS: We identified 4 patients with thymoma or thymic carcinoma treated at our center from 2012 to 2014 who completed adjuvant PBT to a median dose of 57.0 cobalt Gy equivalents (CGE; range, 50.4-66.6 CGE) after definitive resection. Adjuvant radiation was indicated for positive (n = 3) or close margin (n = 1). Median age was 45 (range, 32-70) years. Stages included II (n = 2), III (n = 1), and IVA (n = 1). Analogous IMRT plans were generated for each patient for comparison, and preset dosimetric endpoints were evaluated. Early toxicities were assessed according to retrospective chart review. RESULTS: Compared with IMRT, PBT was associated with lower mean doses to the lung (4.6 vs. 8.1 Gy; P = .02), esophagus (5.4 vs. 20.6 Gy; P = .003), and heart (6.0 vs. 10.4 Gy; P = .007). Percentages of lung, esophagus, and heart receiving radiation were consistently lower in the PBT plans over a wide range of radiation doses. There was no difference in mean breast dose (2.68 vs. 3.01 Gy; P = .37). Of the 4 patients treated with PBT, 3 patients experienced Grade 1 radiation dermatitis, and 1 patient experienced Grade 2 dermatitis, which resolved after treatment. With a median follow-up of 5.5 months, there were no additional Grade ≥ 2 acute or subacute toxicities, including radiation pneumonitis. CONCLUSION: PBT is clinically well tolerated after surgical resection of thymoma, and is associated with a significant reduction in dose to critical structures without compromising coverage of the target volume. Prospective evaluation and longer follow-up is needed to assess clinical outcomes and late toxicities.