Omission of Axillary Lymph Node Dissection is Associated with Inferior Survival in Breast Cancer Patients with Residual N1 Nodal Disease Following Neoadjuvant Chemotherapy.

BACKGROUND: The appropriateness of substituting sentinel lymph node dissection (SLND) and regional nodal irradiation (RNI) for axillary lymph node dissection (ALND) in patients with residual lymph node (LN) disease following neoadjuvant chemotherapy (NAC) is unknown. We used the National Cancer Database (NCDB) to compare survival following SLND and ALND in breast cancer patients with residual LN disease. METHODS: We analyzed NCDB patients, treated between 2006 and 2014, with cT1-3, cN1, cM0 breast cancer and residual disease in 1-3 axillary LNs (ypN1) following NAC. Patients were grouped into those who received SLND (defined as removal of ≤ 4 LNs) and RNI, or ALND and RNI. Patients were matched for all patient, tumor, and treatment characteristics. RESULTS: We identified 1313 eligible patients in the ALND group and 304 patients in the SLND group. For the matched cohorts, SLND was associated with significantly lower survival in both univariate and doubly robust multivariable analyses (MVA) (HR 1.7, 95% CI 1.3-2.2, P < 0.001 for MVA), with estimated 5-year OS of 71%, compared with 77% in the ALND group (P = 0.01). Exploratory subgroup analyses showed that SLND was comparable with ALND in patients with luminal A or B tumors with a single metastatic LN (HR 1.03, 95% CI 0.59-1.8, (P = 0.91). CONCLUSIONS: Our analysis suggests that, while an ALND may not be needed for patients with limited residual nodal burden and biologically favorable tumors, SLND should not be routinely substituted for ALND in patients with ypN1 disease following NAC until its efficacy is confirmed by prospective trials.

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.

Newly Diagnosed Mental Health Disorders in Patients With Breast Cancer Receiving Radiation Therapy.

PURPOSE: Patients with a mental health disorder (MHD) have higher age-adjusted mortality compared with the general population. Few reports investigate factors contributing to MHD among patients with breast cancer receiving radiation therapy. We report the incidence of acquired MHD after the diagnosis of breast cancer and treatment with radiation therapy. METHODS AND MATERIALS: Using a single institution, prospectively maintained database, we analyzed patients with breast cancer treated with radiation therapy between 2012 and 2017. We cross-referenced these patients with newly acquired International Classification of Diseases, Tenth Revision (ICD-10) MHD codes (F01-F99) within 3 years postbreast cancer diagnosis. The study included baseline National Comprehensive Cancer Network® (NCCN) distress tool scores and area deprivation index (ADI). Univariate and multivariable (MVA) Cox regression analyses were conducted to evaluate factors affecting new MHD onset. RESULTS: Of the 967 included patients, 318 (33%) developed an MHD after their breast cancer diagnosis, which was predominately anxiety (45.1%) and depression (20.1%) related, with a median (IQR) time to diagnosis of 30 (24-33) months. Univariate analysis showed lymph node-positive disease, receipt of chemotherapy, receipt of a mastectomy, high comorbidity index, divorced status, retired status, and fourth-quartile ADI as significant predictors. On MVA, only receipt of chemotherapy (hazard ratio [HR], 1.70; P = .014) and divorced status (HR, 2.04; P = .009) remained significant. Fourth-quartile ADI, retired status, and high comorbidity index showed trends toward significance (HR, 1.78, P = .065; HR, 1.46, P = .094; HR, 1.41, P = .059, respectively). On MVA examining the effects of the radiation therapy type on MHD, whole breast with regional nodal irradiation (HR, 2.31, P = .015) and postmastectomy radiation therapy (HR, 1.88, P = .024) were both strong predictors of MHD development. Additionally, an NCCN distress tool score of >3 was also predictive of MHD onset. CONCLUSIONS: In this cohort, 1 in 3 patients with localized breast cancer developed a new MHD, predominantly related to anxiety and depression. MHD risk was higher among divorced patients, those receiving chemotherapy, and patients receiving postmastectomy radiation therapy or whole breast with regional nodal irradiation. These findings highlight the importance of future studies and targeted interventions to support this vulnerable population.

Near-Surface Dose Correlates With Moist Desquamation and Unplanned Reconstructive Surgery in Patients With Implant-Based Reconstruction Receiving Postmastectomy Radiation Therapy.

Purpose: Postmastectomy radiation therapy (PMRT) reduces disease recurrence in appropriately selected patients but may compromise implant-based reconstruction. We investigated whether near-surface dose correlates with radiation-related toxic effects in these patients. Methods and Materials: Patients receiving PMRT at a single institution from 2016 to 2019 were retrospectively reviewed. Patient demographics and treatment information were collected. Three near-surface structures were retrospectively generated, bound by the chest wall tangent beam as well as the skin surface and the skin-3 mm contour (SR3), skin surface and skin-5 mm contour (SR5), or skin-5 and skin-10 mm contours. Dosimetric analysis of these near-surface contours was performed in 2 Gy intervals. Univariate and multivariate analyses were used to identify predictors of moist desquamation, grade 2+ chest wall pain, use of opiate pain medication, unplanned reconstructive surgery, and implant failure. Logistic regression for each outcome and near-surface contour was performed for receiver-operator area under the curve (AUC) analysis and the Youden J Statistic was used to determine the optimal threshold for each dosimetric parameter. Results: Of 126 patients reviewed, 109 met the study's eligibility criteria. Median follow-up was 2.3 years. Twenty-five patients (23%) underwent unplanned reconstructive surgery, and 10 (9.2%) experienced implant failure. Among clinical variables, low body mass index and history of smoking predicted unplanned surgery on univariate and multivariate analyses, and moist desquamation predicted grade 2+ chest wall pain. The top dosimetric parameters by AUC for moist desquamation, grade 2+ chest wall pain, use of opiates, unplanned reconstructive surgery, and implant failure were SR5 D10 cc (AUC = 0.701, optimal threshold 57.8 Gy, P < .001), SR3 D10 cc (AUC = 0.600, optimal threshold 56.8 Gy, P = .079), SR5 D10 cc (AUC = 0.642, optimal threshold 57.3 Gy, P = .041), SR3 V44 Gy (AUC = 0.711, optimal threshold 81%, P = .001), and SR3 V44 Gy (AUC = 0.688, optimal threshold 82%, P = .052), respectively. Conclusions: Near-surface dose correlates with moist desquamation and unplanned reconstructive surgery after PMRT. Further evaluation of prospective optimization of dosimetric parameters related to SR3 and SR5 should be considered.

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.

Dose to the Left Anterior Descending Artery Correlates With Cardiac Events After Irradiation for Breast Cancer.

PURPOSE: Although global heart dose has been associated with late cardiac toxic effects in patients who received radiation therapy for breast cancer, data detailing the clinical significance of cardiac substructure dosimetry are limited. We investigated whether dose to the left anterior descending artery (LAD) correlates with adverse cardiac events. METHODS AND MATERIALS: We identified 375 consecutively treated female patients from 2012 to 2018 who received left-sided breast or chest wall irradiation (with or without regional nodal irradiation). Medical records were queried to identify cardiac events after radiation therapy. Mean and maximum LAD and heart doses (LAD Dmean, LAD Dmax, heart Dmean, and heart Dmax) were calculated and converted to 2-Gy equivalent doses (EQD2). Univariate and multivariable Cox regression analyses were performed to determine association with cardiac toxic effects. Potential dose thresholds for each of the 4 dose parameters were identified by receiver operating characteristic (ROC) curve analysis, after which Kaplan-Meier analysis was performed to compare cardiac event-free survival based on these constraints. RESULTS: Median follow-up time was 48 months. Thirty-six patients experienced a cardiac event, and 23 patients experienced a major cardiac event. On univariate and multivariable analyses, increased LAD Dmean, LAD Dmax, and heart Dmean were associated with increased risk of any cardiac event and a major cardiac event. ROC curve analysis identified a threshold LAD Dmean EQD2 of 2.8 Gy (area under the ROC curve, 0.69), above which the risk for any cardiac event was higher (P = .001). Similar results were seen when stratifying by LAD Dmax EQD2 of 6.7 Gy (P = .005) and heart Dmean EQD2 of 0.8 Gy (P = .01). CONCLUSIONS: Dose to the LAD correlated with adverse cardiac events in this cohort. Contouring and minimizing dose to the LAD should be considered for patients receiving radiation therapy for left-sided breast cancer.

Clinical Outcomes of Hypofractionated Whole Breast Irradiation in Early Stage, Biologically High-Risk Breast Cancer.

PURPOSE: Adoption of hypofractionated whole breast irradiation (HWBI) for patients with early-stage, biologically high-risk breast cancer remains relatively low. We compared clinical outcomes of conventionally fractionated whole breast irradiation (CWBI) versus moderate HWBI in this patient population. METHODS AND MATERIALS: We queried a prospectively maintained database for patients with early-stage (T1-2, N0, M0) breast cancer who received whole breast irradiation with either CWBI or moderate HWBI at a single institution. We included only patients with biologically high-risk tumors (defined as either estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 negative, human epidermal growth factor receptor 2 amplified, and/or patients with a high-risk multigene assay) who received systemic chemotherapy. Inverse probability of treatment weighting was used to compare treatment cohorts and to estimate 5-year time to event endpoints. Hazard ratios (HR) and 95% confidence interval (CI) were determined based on Cox proportional hazards model. RESULTS: We identified 300 patients, of whom 171 received CWBI and 129 received HWBI. There was a statistically significant difference in median age at diagnosis, 59 years for CWBI versus 63 years for HWBI (P = .004), and in median follow-up time, 97 months for CWBI versus 55 months for HWBI (P < .001). After accounting for differences in patient and tumor characteristics with inverse probability of treatment weighting, we found similar 5-year freedom from local recurrence (HR, 0.76; 95% CI, 0.14-4.1), freedom from regional recurrence (HR, 3.395% CI 0.15-69), freedom from distant metastasis (HR 3.9, 95% CI 0.86-17), and disease-free survival (HR 0.84; 95% CI, 0.3-2.4), between those treated with CWBI and those treated with HWBI. Results were similar among each of the 3 high-risk subtypes. CONCLUSIONS: Our data support the use of moderate HWBI in patients with early-stage, biologically high-risk breast cancer.

Inhibition of Colony-Stimulating Factor-1 Receptor Enhances the Efficacy of Radiotherapy and Reduces Immune Suppression in Glioblastoma.

AIM: To use inhibition of colony-stimulating factor-1 receptor (CSF-1R) to target tumor-associated macrophages (TAMs) and improve the efficacy of radiotherapy in glioblastoma (GBM). MATERIALS AND METHODS: The CSF-1R inhibitor BLZ-945 was used to examine the impact of CSF-1R inhibition on M2 polarization in vitro. Using an orthotopic, immunocompetent GBM model, mice were treated with vehicle, RT, BLZ-945, or RT plus BLZ-945. RESULTS: BLZ-945 reduced M2 polarization in vitro. BLZ-945 alone did not improve median overall survival (mOS=29 days) compared to control mice (mOS=27 days). RT improved survival (mOS=45 days; p=0.02), while RT plus BLZ-945 led to the longest survival (mOS=not reached; p=0.005). Resected tumors had a relatively large population of M2 TAMs in GBM at baseline, which was increased in response to RT. BLZ-945 reduced RT-induced M2 infiltration. CONCLUSION: Inhibition of CSF-1R improved response to RT in the treatment of GBM and may represent a promising strategy to improve RT-induced antitumor immune responses.

Investigation of the Prognostic Significance of Neuroendocrine Differentiation in Gleason Score 7 to 10 Prostate Adenocarcinoma in Patients With Distant Metastasis After Definitive Radiotherapy.

OBJECTIVES: We investigated the prognostic implications of neuroendocrine differentiation (NED) in prostate adenocarcinoma detected by chromogranin A (CgA) in patients who developed distant metastasis (DM) after radiotherapy. METHODS: Patients with Gleason score 7 to 10 conventional acinar prostate adenocarcinoma treated with definitive radiotherapy and with core biopsy CgA staining completed were reviewed. Patients who developed DM, defined as disease beyond the primary tumor or pelvic lymph nodes, underwent detailed chart review. Statistical analysis included Kaplan-Meier estimates and descriptive statistics to compare based on quantification of CgA staining. RESULTS: Thirty-five patients had confirmed DM. Twenty-five patients had less than 1% of cells staining positive for CgA, and 10 patients had more than 1%. Median overall survival (OS) time was 3.26 and 1.04 years, respectively (P = .52). Median cause-specific survival (CSS) was 6.15 and 1.04 years, respectively (P = .21). Fifty-six percent of patients with CgA less than 1% died of prostate cancer compared with 90% of those with CgA more than 1% (P = .059). There were no significant differences in sites of metastatic disease or administration of systemic therapies. CONCLUSIONS: No significant differences in OS and CSS were observed based on NED detected by CgA. Reduced median survival time and increased cancer-related death in cases with focal NED generates the hypothesis of inferior outcomes among patients with documented DM.

Usefulness of Coronary Computed Tomographic Angiography to Evaluate Coronary Artery Disease in Radiotherapy-Treated Breast Cancer Survivors.

Breast cancer is the most commonly diagnosed cancer in women and radiotherapy is a widely used treatment approach. However, there is an increased risk of coronary artery disease and cardiac death in women treated with radiotherapy. The present study was undertaken to clarify the relation between radiotherapy and coronary disease in women with previous breast irradiation using coronary computed tomographic angiography (CCTA). We conducted a retrospective analysis of women with a history of right or left-sided breast cancer (RBC; LBC) treated with radiotherapy who subsequently underwent CCTA. RBC patients who had reduced radiation doses to the myocardium served as controls. Patients (n = 6,593) with a history of nonmetastatic breast cancer treated with radiotherapy were screened for completion of CCTA; 49 LBC and 45 RBC women were identified. Age and risk factor matched patients with LBC had higher rates of coronary disease compared with RBC patients; left anterior descending (LAD) coronary artery (76% vs 31% [p < 0.001]), left circumflex (33% vs. 6.7% [p = 0.004]), and right coronary artery (37% vs 13% [p = 0.018]). Mean LAD radiation dose and mean heart dose strongly correlated with coronary disease, with a 21% higher incidence of disease in the LAD per Gy for mean LAD dose and a 95% higher incidence of disease in the LAD per Gy for mean heart dose. In conclusion, LBC patients treated with radiotherapy have a significantly higher incidence of coronary disease when compared with a matched group of patients treated for RBC. Radiation doses correlated with the incidence of coronary disease.

A population-based analysis of chemoradiation versus radiation alone in the definitive treatment of patients with stage I-II squamous cell carcinoma of the anus.

BACKGROUND: The optimal management of patients with stage I-II squamous cell carcinoma (SCC) of the anus is controversial. The current study evaluates the efficacy of combined chemotherapy and radiation therapy (CRT) versus radiation therapy (RT) alone in the treatment of these patients using the Surveillance, Epidemiology, and End Results (SEER) registries. METHODS: SEER 18 Custom Data registries were queried for patients with stage I-II SCC of the anus. Univariate analysis (UVA) and multivariable analysis (MVA) using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment weighting (IPTW) was used to account for indication bias. RESULTS: A total of 4,288 patients with stage I-II disease were identified, of whom 3,982 (93%) underwent CRT and 306 (7%) underwent RT. Median follow-up was 42 months. Approximately 30.8% had T1 disease and 69.2% had T2-T3 disease. The IPTW-adjusted 5-year overall survival (OS) was 76.7%, with no significant differences between the CRT and RT groups (77% vs. 73.5%, P=0.33). On multivariate IPTW-adjusted analysis, the lack of association between CRT use and OS was upheld (HR, 0.84, 95% CI, 0.65-1.08, P=0.2). On subgroup analyses, 5-year OS was 86% with CRT (n=1,216) and 84.2% with RT (n=103) (P=0.74) in stage I (T1N0) patients, while 5-year OS was 72.8% with CRT (n=2,766) and 66.4% with RT (n=203) (P=0.13) in stage II (T2-3N0) patients. CRT was associated with improved median OS in stage II patients (119 months vs. not reached, P=0.04). CONCLUSIONS: The current study suggests that omission of concurrent chemotherapy is not associated with inferior OS in patients with stage I SCC of the anus. However, combined chemoradiation was superior to radiation alone in patients with stage II disease. Prospective evidence is needed to optimize clinical decision-making in this patient population.

Non-small cell lung cancer stage migration as a function of wait times from diagnostic imaging: A pooled analysis from five international centres.

INTRODUCTION: Patients with non-small cell lung cancer (NSCLC) can experience rapid disease progression between initial staging FDG-PET scans and commencement of curative-intent radiotherapy (RT). Previous studies that estimated stage migration rates by comparing staging PET/CT and treatment-planning PET/CT images were limited by small sample sizes. METHODS: This multicenter, international study combined prospective data from five institutions for PET-staged patients with NSCLC who were intended to receive curative-intent RT. TNM status was compared for staging and RT planning scans and the probability of TNM status and overall stage migration was analyzed as a function of the interval between PET/CT scans. The impacts of N classification, overall stage, and pathology were also studied. RESULTS: Pooled data from 181 patients were analyzed. The median interval between PET/CT scans was 42 days (range, 2-208). Upstaging occurred in 32 % of patients. The overall rate of stage migration was higher for patients presenting with initial stage IIIB/IIIC disease (p = 0.006) and patients with N2-3 nodal disease (p = 0.019). Upstaging to M1 disease was significantly associated with initial stage IIIB/IIIC disease (HR = 15.2) and adenocarcinoma (HR = 10) histology. CONCLUSION: Longer intervals between imaging and treatment in patients with NSCLC were associated with high rates disease progression with consequent risks of geographic miss in RT planning and futile treatment in patients with M1 disease. Patients with more extensive initial nodal involvement and those with adenocarcinoma had the highest rates of stage migration. Dedicated RT planning PET/CT imaging is recommended, especially if >3 weeks have elapsed after initial staging.

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.

Toxicity and Efficacy After Adjuvant Vaginal Brachytherapy Using 30 Gy in 6 Fractions for Stages I and II Endometrial Cancer.

PURPOSE: This study aimed to evaluate outcomes and toxicity in patients with endometrial cancer per our institutional adjuvant vaginal cuff brachytherapy (VBT) fractionation scheme. METHODS AND MATERIALS: We identified women with International Federation of Gynecology and Oncology stages I and II endometrial cancer who underwent surgical staging and adjuvant high-dose-rate VBT without external beam radiation. All patients received 30 Gy in 6 fractions to the upper one-third of the vagina, prescribed to a depth of 5 mm and delivered twice weekly. Toxicities were prospectively elicited at each follow up, and rates of recurrence and survival were retrospectively assessed. RESULTS: We identified 247 eligible patients treated between 1992 and 2018 with a median follow up of 5.8 years (range, 0.1-24.7 years). Most patients had stage I disease (52% stage IA; 37% stage IB), and 11% of patients were stage II. Deep myometrial invasion was predictive of local recurrence (P = .002). The 5-year rates of local recurrence, regional recurrence, and distant metastases were 5%, 5%, and 7%, respectively. Five-year overall and disease-free survival were 91% and 83%, respectively. The most common grade 1 toxicities were acute fatigue (11% crude rate), urinary frequency (11%), chronic (>6 months) urinary frequency (13%), urinary incontinence (13%), and vaginal stenosis (21%). There were few grade 2 toxicities (all <5%) and no grade 3 to 5 toxicities. CONCLUSIONS: The adjuvant VBT fractionation scheme of 30 Gy in 6 fractions results in low rates of toxicity, with no grade ≥3 adverse events, and local control rates comparable with those from other published series using different fractionation schemes.

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.

Pulsed radiation therapy for the treatment of newly diagnosed glioblastoma.

BACKGROUND: Pulsed radiation therapy (PRT) has shown effective tumor control and superior normal-tissue sparing ability compared with standard radiotherapy (SRT) in preclinical models and retrospective clinical series. This is the first prospective trial to investigate PRT in the treatment of patients with newly diagnosed glioblastoma (GBM). METHODS: This is a single-arm, prospective study. Patients with newly diagnosed GBM underwent surgery, followed by 60 Gy of PRT with concurrent temozolomide (TMZ). Each day, a 2-Gy fraction was divided into ten 0.2-Gy pulses, separated by 3-minute intervals. Patients received maintenance TMZ. Neurocognitive function (NCF) and quality of life (QoL) were monitored for 2 years using the Hopkins Verbal Learning Test‒Revised and the European Organisation for Research and Treatment of Cancer QLQ-C30 QoL questionnaire. Change in NCF was evaluated based on a minimal clinically important difference (MCID) threshold of 0.5 standard deviation. RESULTS: Twenty patients were enrolled with a median follow-up of 21 months. Median age was 60 years. Forty percent underwent subtotal resection, and 60% underwent gross total resection. One patient had an isocitrate dehydrogenase (IDH)-mutated tumor. Median progression-free survival (PFS) and overall survival (OS) were 10.7 and 20.9 months, respectively. In a post-hoc comparison, median OS for the prospective cohort was longer, compared with a matched cohort receiving SRT (20.9 vs 14 mo, P = 0.042). There was no decline in QoL, and changes in NCF scores did not meet the threshold of an MCID. CONCLUSIONS: Treatment of newly diagnosed GBM with PRT is feasible and produces promising effectiveness while maintaining neurocognitive function and QoL. Validation of our results in a larger prospective trial warrants consideration.

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.

Breast conserving therapy is associated with improved overall survival compared to mastectomy in early-stage, lymph node-negative breast cancer.

BACKGROUND AND PURPOSE: Recent retrospective studies suggest improved overall survival (OS) with breast conserving therapy (BCT), including breast conserving surgery and adjuvant whole breast radiotherapy, compared to mastectomy in the modern era. The patient subset most likely to benefit from BCT remains unclear, and the role of Oncotype DX Recurrence Score (RS) in this context is unknown. We compared BCT to mastectomy in early-stage, node-negative breast cancer. We further explored outcomes after stratification by RS and age. MATERIALS AND METHODS: We performed a matched-cohort analysis of National Cancer Database (NCDB) patients with pT1-2, pN0, cM0 breast cancer treated between 2006 and 2014 with BCT or mastectomy. Patients were matched for all available baseline characteristics using propensity scores with inverse probability of treatment weighting (IPTW) with stabilized weights. RESULTS: We identified 144,263 eligible patients treated with BCT and 87,379 patients treated with mastectomy. After IPTW-matching, OS was higher with BCT compared to mastectomy: 5-year OS of 94.4% vs. 91.8% (P < 0.001) and 7-year OS of 90% vs. 85.2% (P < 0.001). Doubly robust multivariable analysis showed an association between BCT and improved OS (HR 0.66, 95% CI, 0.64-0.69, P < 0.001). In a subset analysis, BCT was associated with improved OS in patients with RS >25, but not patients with RS ≤25. When stratified by age, only patients >50 years had improved OS with BCT. CONCLUSION: BCT is associated with improved OS compared to mastectomy in women with early-stage, node-negative breast cancer. The improvement in OS with BCT appears to be most pronounced in patients with high RS and >50 years of age. Prospective validation of these findings is required.

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.