5-year outcomes after stereotactic ablative body radiotherapy for primary renal cell carcinoma: an individual patient data meta-analysis from IROCK (the International Radiosurgery Consortium of the Kidney).

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a non-invasive treatment option for primary renal cell carcinoma, for which long-term data are awaited. The primary aim of this study was to report on long-term efficacy and safety of SABR for localised renal cell carcinoma. METHODS: This study was an individual patient data meta-analysis, for which patients undergoing SABR for primary renal cell carcinoma across 12 institutions in five countries (Australia, Canada, Germany, Japan, and the USA) were eligible. Eligible patients had at least 2 years of follow-up, were aged 18 years or older, had any performance status, and had no previous local therapy. Patients with metastatic renal cell carcinoma or upper-tract urothelial carcinoma were excluded. SABR was delivered as a single or multiple fractions of greater than 5 Gy. The primary endpoint was investigator-assessed local failure per the Response Evaluation Criteria in Solid Tumours version 1.1, and was evaluated using cumulative incidence functions. FINDINGS: 190 patients received SABR between March 23, 2007, and Sept 20, 2018. Single-fraction SABR was delivered in 81 (43%) patients and multifraction SABR was delivered in 109 (57%) patients. Median follow-up was 5·0 years (IQR 3·4-6·8). 139 (73%) patients were men, and 51 (27%) were women. Median age was 73·6 years (IQR 66·2-82·0). Median tumour diameter was 4·0 cm (IQR 2·8-4·9). 96 (75%) of 128 patients with available operability details were deemed inoperable by the referring urologist. 56 (29%) of 190 patients had a solitary kidney. Median baseline estimated glomerular filtration rate (eGFR) was 60·0 mL/min per 1·73 m2 (IQR 42·0-76·0) and decreased by 14·2 mL/min per 1·73 m2 (IQR 5·4-22·5) by 5 years post-SABR. Seven (4%) patients required dialysis post-SABR. The cumulative incidence of local failure at 5 years was 5·5% (95% CI 2·8-9·5) overall, with single-fraction SABR yielding fewer local failures than multifraction (Gray's p=0·020). There were no grade 3 toxic effects or treatment-related deaths. One (1%) patient developed an acute grade 4 duodenal ulcer and late grade 4 gastritis. INTERPRETATION: SABR is effective and safe in the long term for patients with primary renal cell carcinoma. Single-fraction SABR might yield less local failure than multifraction, but further evidence from randomised trials is needed to elucidate optimal treatment schedules. These mature data lend further support for renal SABR as a treatment option for patients unwilling or unfit to undergo surgery. FUNDING: None.

Prognostic and predictive impact of MGMT promoter methylation status in high risk grade II glioma.

BACKGROUND: MGMT promoter methylation has been associated with favorable prognosis and survival outcomes in patients with glioblastoma and WHO grade III glioma. However, the effects of promoter methylation of MGMT in patients with WHO grade II gliomas have not been established. The purpose of the current study is to evaluate the prognostic impact and predictive values of MGMT methylation in patients with grade II glioma. METHODS: The National Cancer Database (NCDB) was queried (2004-2016) for patients with newly diagnosed grade II glioma. Demographics and clinical characteristics of these patients were examined. Statistics included Kaplan-Meier overall survival (OS) analysis alongside Cox proportional hazards modeling. RESULTS: A total of 11,223 patients met the selection criteria; 1252 patients (11%) had MGMT testing. Of the patients who had MGMT testing, 58.5% were MGMT methylated (mMGMT), and 43.5% were MGMT unmethylated (uMGMT). mMGMT patients had greater median overall survival (77.3 months) than both uMGMT patients (42.6 months) and patients with no MGMT status reported (61.9 months (p < 0.001 for both). mMGMT was also associated with improved OS, when compared to patients with uMGMT, for patients receiving adjuvant chemoradiation or adjuvant radiation therapy. CONCLUSIONS: This is the largest study to date demonstrating both the prognostic and predictive impact of MGMT methylation on patients with grade II glioma. The current results show that mMGMT is a prognostic factor and possibly a predictive biomarker for grade II glioma patients. MGMT methylation status can be used to determine and stratify patients by risk levels, and thus select patients for treatment intensification. IMPORTANCE OF STUDY: The present study is the largest to date examining the prognostic and predictive significance of MGMT methylation (mMGMT) in patients with WHO grade II glioma. The results suggest that mMGMT is prognostic with increasing overall survival rates for patients with mMGMT compared to uMGMT patients. The results also suggest that mMGMT is predictive as shown by improved overall survival in patients receiving gross total resection, adjuvant chemoradiation or adjuvant radiation therapy, but no difference was observed in patients receiving adjuvant chemotherapy or no adjuvant treatment.

Quantifying the rate and predictors of occult lymph node involvement in patients with clinically node-negative non-small cell lung cancer.

PURPOSE: It is essential to evaluate the risk of occult lymph node (LN) disease in early-stage non-small cell lung cancer (NSCLC), especially because delivering stereotactic ablative radiotherapy (SABR) assumes no occult spread. This study was designed to assist clinicians in roughly quantifying this risk for cN0 NSCLC. METHODS: The National Cancer Data Base was queried for cN0 cM0 lung squamous cell or adenocarcinoma who underwent surgery and LN dissection without neoadjuvant therapy. Statistics included multivariable logistic regression to evaluate factors associated with pN + disease. RESULTS: 109,964 patients were included. For tumors with size ≤1.0, 1.1-2.0, 2.1-3.0, 3.1-4.0, 4.1-5.0, 5.1-6.0, 6.1-7.0, and >7.0 cm, the pN + rate was 4.4, 7.7, 12.9, 18.0, 20.2, 22.5, 24.4, and 26.4%, respectively. When examining patients with more complete LN dissections (defined as removal of at least 10 LNs), the respective values were 6.6, 11.5, 17.6, 25.3, 26.8, 29.7, 30.7, and 31.6%. Moderately-poorly differentiated disease and adenocarcinomas were associated with a higher rate of pN + disease (p < .001 for both). For every cm increase in tumor size, the relative occult nodal risk increased by 10-14% (p < .001). For every elapsed day from initial diagnosis, the relative risk increased by ∼1% (p < .001). Graphs with best-fit lines were created based on tumor size, histology, and differentiation to aid physicians in estimating the pN + risk. CONCLUSIONS: This nationwide study can allow clinicians to roughly estimate the rate of occult LN disease in cN0 NSCLC. These data can also assist in guiding enrollment on randomized trials of SABR ± immunotherapy, individualizing follow-up imaging surveillance, and patient counseling to avoid post-diagnosis delays.

A phase II clinical trial of neoadjuvant sasanlimab and stereotactic body radiation therapy as an in situ vaccine for cisplatin-ineligible MIBC: the RAD VACCINE MIBC trial.

The utilization of neoadjuvant immune checkpoint inhibitor therapy, specifically anti-PD-1/L1 agents, prior to radical cystectomy is an emerging paradigm in muscle-invasive bladder cancer (MIBC). In situ vaccination represents a strategy to manipulate the tumor in order to augment the immune response toward improved local and distant cancer control. The authors describe the study rationale, design and objectives for RAD VACCINE MIBC, a single-arm, single-institution, phase II trial evaluating the efficacy and safety of combination neoadjuvant sasanlimab (humanized IgG monoclonal antibody that targets PD-1) with stereotactic body radiotherapy as an in situ vaccine in cisplatin-ineligible patients with MIBC. The results from this trial will establish the safety profile of this combination strategy and evaluate pathologic complete response rates.

RAD VACCINE MIBC is a phase II clinical trial that aims to determine the safety and effectiveness of a study drug called sasanlimab (an immune checkpoint inhibitor), combined with radiation therapy (stereotactic body radiation therapy) prior to surgery to remove the bladder (known as radical cystectomy [RC]) in muscle-invasive bladder cancer patients. For this type of cancer, patients typically receive chemotherapy followed by RC as the standard of care. However, many patients who have pre-existing medical conditions such as poor kidney function are unable to receive chemotherapy. These patients undergo RC alone at the risk of less optimal cancer control. Bladder cancer is known to inhibit the immune cells (T cells) from attacking it, which is an important way in which the body controls cancer cells. Sasanlimab allows T cells that are specific to the cancer to potentially reactivate. Ongoing studies have shown that drugs similar to sasanlimab can be used to achieve improvement in cancer control in the bladder (as measured by shrinking the cancer or eradicating it) before surgery. The authors are studying the use of the study drug with the addition of stereotactic body radiotherapy (SBRT) as a combined therapy. The role of SBRT as a combined therapy to immune checkpoint inhibition has been well studied to help improve the process of how immune cells recognize cancer cells. By giving both the study drug and SBRT together before RC, the authors aim to demonstrate the safety of this technique and its effectiveness in eradicating all cancer in the bladder. Clinical Trial Registration: NCT05241340 (ClinicalTrials.gov).

Neurodevelopmental outcome at 2 years of corrected age in fetuses with increased nuchal translucency thickness and normal karyotype compared with matched controls.

OBJECTIVES: Increased nuchal translucency (NT) thickness is an antenatal marker of aneuploidy or malformation that can lead to termination of pregnancy. This study assessed the long-term neurodevelopmental prognosis of infants who had isolated increased NT in utero. METHODS: This was a prospective cohort study of infants with a NT thickness > 95th percentile in the first trimester, but with a normal karyotype and no major anomalies, and controls with normal NT matched for birth weight, Apgar score, place of birth, parity and gestational age at birth. At 2 years of corrected age, all infants underwent the psychometric Brunet-Lézine test to evaluate their developmental quotient (DQ), overall (global) and specifically for the areas of posture, language, coordination and sociability. RESULTS: A total of 203 chromosomally normal infants were included in the increased-NT group and 208 in the control group. The mean global DQ was significantly lower in the increased-NT group than in the control group (108.6 ± 9.7 vs 112.8 ± 8.3; P < 0.0001), but it was within the normal range expected for that age in both groups. Similarly, the mean DQs for coordination, sociability and language, but not for posture, were significantly lower in infants with increased NT than in controls. Only one case with increased NT had a DQ < 70 (defined as severe neurodevelopmental impairment), compared with none in the control group. The difference between the two groups remained significant for a NT threshold ≥ 99th percentile and when the data were adjusted for NT thickness, the infant's sex and the mother's educational level. In the increased-NT group, NT thickness was < 3.5 mm in over half (56%) of the infants, between 3.5 mm and 5 mm in 33% and > 5 mm in 11%, with a mean global DQ of 108.4, 110.1 and 109.7, respectively. CONCLUSIONS: Infants who had isolated increased fetal NT in the first trimester had a significantly lower, but normal, DQ at a corrected age of 2 years, when compared with controls. The findings were independent of the infant's sex, fetal NT thickness and the mother's educational level. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Comparison of Survival Outcomes With/Without Adjuvant Radiation Therapy in Desmoplastic Melanoma.

BACKGROUND: Desmoplastic melanoma (DM) is a rare variant of cutaneous melanoma with a high rate of local recurrence. Recent studies have indicated a potential benefit in local control with the addition of adjuvant radiotherapy (RT). OBJECTIVE: This study sought to evaluate the outcomes of adjuvant RT for patients with DM. MATERIALS AND METHODS: The National Cancer Database was queried (2004-2015) for patients with newly diagnosed, nonmetastatic DM. Patients were divided into 2 groups based on the adjuvant therapy they received: RT or observation. Statistics included multivariable logistic regression to determine factors predictive of receiving adjuvant RT, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS. RESULTS: There was no difference in median OS between patients treated with RT when compared with patients observed (111.4 months vs 133.9 months, p = .1312). On multivariable analysis, older age, T stage ≥2, N stage ≥1, and no receipt of immunotherapy were associated with worse OS. CONCLUSION: In this large study evaluating efficacy of adjuvant RT in DM, no overall survival benefit was observed among patients receiving adjuvant RT.

Outcomes following stereotactic radiosurgery or whole brain radiation therapy by molecular subtype of metastatic breast cancer.

BACKGROUND: This study quantified clinical outcomes by molecular subtype of metastatic breast cancer (BC) following whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS). Doing so is important for patient counseling and to assess the potential benefit of combining targeted therapy and brain radiotherapy for certain molecular subtypes in ongoing trials. MATERIALS AND METHODS: The National Cancer Database was queried for BC (invasive ductal carcinoma) cases receiving brain radiotherapy (divided into WBRT and SRS ). Statistics included multivariable logistic regression to determine factors associated with SRS delivery, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling. RESULTS: Of 1,112 patients, 186 (16.7%) received SRS and 926 (83.3%) underwent WBRT. Altogether, 410 (36.9%), 195 (17.5%), 162 (14.6%), and 345 (31.0%) were ER+/HER2-, ER+/HER2+, ER-/HER2+, and ER-/HER2-, respectively. In the respective molecular subtypes, the proportion of subjects who underwent SRS was 13.4%, 19.4%, 24.1%, and 15.7%. Respective OS for WBRT patients were 12.9, 22.8, 10.6, and 5.8 months; corresponding figures for the SRS cohort were 28.3, 40.7, 15.0, and 12.9 months (p < 0.05 for both). When comparing OS between treatment different histologic subtypes, patients with ER-/HER2+ and ER-/HER2- disease had worse OS than patients with ER+/HER2- disease, for both patients treated with SRS and for patients treated with WBRT. CONCLUSIONS: Molecular subtype may be a useful prognostic marker to quantify survival following SRS/WBRT for metastatic BC. Patients with HER 2-enriched and triple-negative disease had the poorest survival following brain irradiation, lending credence to ongoing studies testing the addition of targeted therapies for these subtypes.

The impact of HER2-directed targeted therapy on HER2-positive DCIS of the breast.

BACKGROUND: In invasive breast cancer, HER2 is a well-established negative prognostic factor. However, its significance on the prognosis of ductal carcinoma in situ (DCIS) of the breast is unclear. As a result, the impact of HER2-directed therapy on HER2-positive DCIS is unknown and is currently the subject of ongoing clinical trials. In this study, we aim to determine the possible impact of HER 2-directed targeted therapy on survival outcomes for HER2-positive DCIS patients. MATERIALS AND METHODS: The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven DCIS diagnosed from 2004-2015. Patients were divided into two groups based on the adjuvant therapy they received: systemic HER2-directed targeted therapy or no systemic therapy. Statistics included multivariable logistic regression to determine factors predictive of receiving systemic therapy, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS. RESULTS: Altogether, 1927 patients met inclusion criteria; 430 (22.3%) received HER2-directed targeted therapy; 1497 (77.7%) did not. Patients who received HER2-directed targeted therapy had a higher 5-year OS compared to patients that did not (97.7% vs. 95.8%, p = 0.043). This survival benefit remained on multivariable analysis. Factors associated with worse OS on multivariable analysis included Charlson-Deyo Comorbidity Score ≥ 2 and no receipt of hormonal therapy. CONCLUSION: In this large study evaluating HER2-positive DCIS patients, the receipt of HER2-directed targeted therapy was associated with an improvement in OS. The results of currently ongoing clinical trials are needed to confirm this finding.

Pulmonary embolism: clinical presentation and diagnosis in the oldest old.

The incidence of pulmonary embolism (PE) in the oldest old (persons aged ≥85) is increasing, but there are limited data on its clinical features and diagnosis. We performed a retrospective cohort study of 302 consecutive patients with confirmed PE and compared the oldest old to the young (aged <65) and the younger old (aged 65-84). The most common symptoms in the oldest old were dyspnoea (74.3%) and tachypnoea (71.4%), but the prevalence of chest pain decreased with advancing age. Delayed diagnosis was most common in the oldest old and was associated with increasing age, absence of dyspnoea, presence of cardiorespiratory disease and a higher Charlson Comorbidity index. Better age-specific diagnostic pathways are required in this population.

Clinical presentation, national practice patterns, and outcomes of breast adenomyoepithelioma.

Breast adenomyoepithelioma (AME) is a rare tumor with the published literature mainly in the form of case reports. Thus, there is currently only limited published data to guide evidence-based management. We sought to use a large, contemporary US database to evaluate how these patients are managed and describe expected outcomes. The National Cancer Database was queried (2004-2013) for women with AME. Statistics included multivariable logistic regression, Kaplan-Meier analysis to evaluate overall survival (OS) and Cox proportional hazards modeling. Overall, 110 patients were analyzed. At diagnosis, the median age was 67 years and the median tumor size was 2.0 cm. All but four patients had node-negative disease. A majority (55%) of tumors were estrogen receptor negative, and only one was positive for HER2/neu. The most common surgical procedure was lumpectomy (60%); a minority (10.9%) of subjects underwent complete axillary nodal dissection, with one-quarter not undergoing pathologic nodal sampling. Chemotherapy, hormonal therapy, and radiotherapy were utilized in a minority of patients (26%, 8%, and 36%, respectively), and none were associated with OS. At median follow-up of 52 months, the 5-year OS for the entire population was 74.4%. Disease-related characteristics and practice patterns are described for AME, the largest study of this rare tumor to date. Resection is the most important aspect of management, and based on this dataset the low rate of nodal involvement suggests that in some cases nodal sampling could be safely omitted. Adjuvant therapy may be considered on a case-by-case basis. Taken together, these data provide valuable insight into a rare neoplasm that may better inform management of these patients.

Knockdown of α2,3-Sialyltransferases Impairs Pancreatic Cancer Cell Migration, Invasion and E-selectin-Dependent Adhesion.

Aberrant sialylation is frequently found in pancreatic ductal adenocarcinoma (PDA). α2,3-Sialyltransferases (α2,3-STs) ST3GAL3 and ST3GAL4 are overexpressed in PDA tissues and are responsible for increased biosynthesis of sialyl-Lewis (sLe) antigens, which play an important role in metastasis. This study addresses the effect of α2,3-STs knockdown on the migratory and invasive phenotype of PDA cells, and on E-selectin-dependent adhesion. Characterization of the cell sialome, the α2,3-STs and fucosyltransferases involved in the biosynthesis of sLe antigens, using a panel of human PDA cells showed differences in the levels of sialylated determinants and α2,3-STs expression, reflecting their phenotypic heterogeneity. Knockdown of ST3GAL3 and ST3GAL4 in BxPC-3 and Capan-1 cells, which expressed moderate to high levels of sLe antigens and α2,3-STs, led to a significant reduction in sLex and in most cases in sLea, with slight increases in the α2,6-sialic acid content. Moreover, ST3GAL3 and ST3GAL4 downregulation resulted in a significant decrease in cell migration and invasion. Binding and rolling to E-selectin, which represent key steps in metastasis, were also markedly impaired in the α2,3-STs knockdown cells. Our results indicate that inhibition of ST3GAL3 and ST3GAL4 may be a novel strategy to block PDA metastasis, which is one of the reasons for its dismal prognosis.

Approach to radiation therapy in the Jehovah's Witness patient: An overview.

Jehovah's Witnesses are well-known in the medical community for their inability to accept blood products. Novel methods of treatment are often needed to avoid anemia and hematologic toxicity as inability to receive blood products may increase the risk of treatment related complications. We provide an overview of radiation treatment for Jehovah's Witness patients with an emphasis on bone marrow sparing strategies with intensity modulated radiation therapy (IMRT) to minimize hematologic toxicity.

Stereotactic Radiotherapy as a Treatment Option for Renal Tumors in the Solitary Kidney: A Multicenter Analysis from the IROCK.

PURPOSE: Stereotactic ablative radiotherapy is an emerging treatment for renal cell carcinoma. Our study objective was to evaluate this therapy in patients with a solitary kidney, focusing on oncologic and renal function outcomes. MATERIALS AND METHODS: We pooled individual patient data from 9 IROCK (International Radiosurgery Oncology Consortium for Kidney) institutions in Germany, Australia, the United States of America, Canada and Japan. Median followup was 2.6 years. Baseline characteristics and outcomes were compared between the solitary and bilateral kidney cohorts. Predictors of renal function after stereotactic ablative radiotherapy were assessed by logistic regression modeling. RESULTS: A total of 81 patients with a solitary kidney underwent stereotactic ablative radiotherapy. Mean age was 67.3 years and 97.5% of patients had good performance status, including ECOG (Eastern Cooperative Oncology Group) 0-1 or KPS (Karnofsky Performance Status) 70% or greater. Median tumor diameter was 3.7 cm (IQR 2.5-4.3) and 37% of tumors were 4 cm or greater. The 138 patients in the bilateral cohort harbored larger tumors and were older (p <0.001) with a lower baseline estimated glomerular filtration rate (p = 0.024). After stereotactic ablative radiotherapy in the solitary kidney cohort the mean ± SD estimated glomerular filtration rate decrease was -5.8 ± 10.8 ml per minute (-9%). No patient with a solitary kidney required dialysis. After stereotactic ablative radiotherapy a tumor size of 4 cm or greater was associated with an estimated glomerular filtration rate decrease of 15 ml per minute or greater (OR 4.2, p = 0.029). At 2 years the rates of local control, and progression-free, cancer specific and overall survival in the solitary cohort were 98.0%, 77.5%, 98.2% and 81.5%, respectively. There was no significant difference in renal function or oncologic outcomes between the cohorts (p >0.05). CONCLUSIONS: In this analysis of the IROCK database stereotactic ablative radiotherapy in patients with a solitary kidney had an acceptable impact on renal function and achieved excellent oncologic outcomes, similar to those in patients with bilateral kidneys. Thus, stereotactic ablative radiotherapy represents a viable treatment option in patients with renal cell carcinoma in a solitary kidney.

Survival Outcomes and Patterns of Management for Anal Adenocarcinoma.

BACKGROUND: Anal adenocarcinoma (AA) is a rare histologic subtype of anal cancer believed to have worse outcomes than anal squamous cell carcinoma (AS). This study aimed to examine practice patterns and treatment outcomes for this rare subtype using the National Cancer Data Base (NCDB). METHODS: Patients who had new diagnoses of anal cancer treated with chemoradiation were selected from the NCDB from 2004 to 2015. The patients were divided into two histologic groups (AA or AS). Statistics included the Chi square test to analyze categorical proportions in demographic information, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS. RESULTS: The study analyzed 24,461 patients. Compared with AS patients, AA patients were more likely to be male, to present with a higher cancer stage, to be older (> 65 years), and to undergo surgery with an abdominoperineal resection (APR). The median OS was 72.5 months for the AA patients and 143.8 months for the AS patients (P < 0.001). Survival was longer for the AA patients undergoing APR within 6 months after chemoradiation (CRT) than for the AA patients who had an APR 6 months after CRT (88.3 vs. 58.1 months; P < 0.001). In the multivariable analysis, the factors associated with worse survival included adenocarcinoma subtype, age of 55 years or older, male gender, T stage of 3 or higher, comorbidity score of 1 or higher, lower income, and treatment at a nonacademic institution. CONCLUSIONS: In this largest study of anal adenocarcinoma to date, trimodality therapy was associated with better survival than chemoradiation alone.

The Role of Adjuvant Radiotherapy in the Treatment of Pleural Mesothelioma.

BACKGROUND: Pleural mesothelioma is a rare but aggressive form of cancer. Local recurrence represents the majority of treatment failures and overall survival (OS) outcomes remain dismal. Adding locoregional treatment with radiotherapy after surgical resection has been considered but its role remains uncertain. OBJECTIVE: The purpose of this study was to evaluate the outcomes of adjuvant radiation therapy (RT) for patients with malignant pleural mesothelioma. METHODS: The National Cancer Data Base (NCDB) was queried (2004-2013) for patients with malignant mesothelioma. Patients were divided into three groups: observation, surgery alone, and surgery followed by adjuvant RT. Statistics included Fisher's exact or Chi square tests to analyze categorical proportions between groups, Kaplan-Meier analysis to evaluate OS, and Cox proportional hazards modeling to determine variables associated with OS. Propensity matching was performed to make comparisons between homogenous groups. RESULTS: Overall, the surgery plus radiotherapy group had a higher median survival (21.4 months) compared with surgery alone (16.59 months) [p < 0.001]. RT was more likely to be delivered after extrapleural pneumonectomy than with lung-sparing surgical approaches. On multivariable analysis, receipt of surgery plus radiotherapy, chemotherapy administration, and higher socioeconomic status were associated with improved OS (p < 0.0001). After propensity matching, receipt of surgery plus radiotherapy and chemotherapy administration were still associated with improved OS (p < 0.05). CONCLUSIONS: In the treatment of malignant pleural mesothelioma, adjuvant radiotherapy after surgical intervention was associated with improved OS. This study is the largest study of adjuvant radiotherapy to date, and our findings highlight the need for additional prospective data.

Socioeconomic Factors Associated with Lack of Treatment in Early Stage Non-Small Cell Lung Cancer.

With modern radiotherapy, stage I non-small cell lung cancer (S1NSCLC) cure is extended to nonsurgical candidates. Despite this, some S1NSCLC remains untreated. We aim to identify factors associated with no treatment. 62,213 S1NSCLC cases were identified (SEER: 2004-2012). Demographics were compared using Chi-squared. Multivariate analysis was performed using COX proportional HR. 11.9% of the 7373 patients lacked treatment. No insurance, Medicaid-dependence, unmarried status, advancing age, lower income, African American and Asian/Pacific Islander race, and male sex are associated with no treatment (p < .0001). No treatment portends a worse cancer-specific survival (21% vs 66% at 5Y, p < .0001) and OS (10% vs 50% at 5Y, p < .0001).

Stereotactic radiosurgery for brain metastases from newly diagnosed small cell lung cancer: practice patterns and outcomes.

BACKGROUND: Up-front stereotactic radiosurgery (SRS) has been historically thought of as inadequate for brain metastases (BM) from newly diagnosed small cell lung cancer (SCLC). This study evaluates national practice patterns and clinical outcomes for BM from SCLC. MATERIAL AND METHODS: The National Cancer Database was queried (2004-2013) for patients with newly diagnosed metastatic SCLC receiving intracranial radiotherapy. Patients were grouped into three categories: upfront SRS, whole-brain radiotherapy (WBRT) alone, or WBRT with boost (SRS or fractionated radiotherapy). Statistics included temporal trend assessment by annual percent change (APC), logistic regression, exploratory Kaplan-Meier overall survival (OS) analysis without and with propensity matching, and Cox proportional hazards modeling. RESULTS: A total of 14,722 patients met selection criteria, of whom 487 (3.3%), 13,657 (92.8%), and 578 (3.9%) received upfront SRS, WBRT and WBRT with boost, respectively. Utilization of SRS showed a slight increasing trend from 2004 to 2013 (2.7-4.3%). In addition to socioeconomic factors, other variables associated with SRS use included diagnosis after 2010, treatment at academic centers, and residing in higher-educated regions. SRS was less often delivered to patients with node-positive disease (p < .05). On exploratory analysis, SRS cohort was observed to have a higher overall survival (OS) than WBRT-based groups (p < .001), namely in patients without extracranial metastases. CONCLUSIONS: Utilization of up-front SRS for SCLC BM has been increasing over time but is driven by socioeconomic disparities. Although there are likely numerous biases associated with the OS findings herein, further research is needed to validate this finding as well as the role of SRS on patients with brain metastases due to SCLC.

Neoadjuvant stereotactic body radiation therapy for nonmetastatic pancreatic adenocarcinoma.

Background: Neoadjuvant therapy is a strategy for resectable and borderline resectable pancreatic cancer, but a consensus approach regarding optimal management is undetermined. Neoadjuvant options include chemotherapy with/without radiotherapy. Stereotactic body radiation therapy (SBRT) is a novel radiation technique that may provide benefit over conventionally fractionated radiation therapy (CFRT) in the neoadjuvant setting. The purpose of the present study is to determine neoadjuvant treatment with SBRT to other neoadjuvant treatment options for patients with resectable pancreatic cancer. Material and methods: The National Cancer Database was queried (2004-2015) for patients with nonmetastatic pancreatic adenocarcinoma receiving neoadjuvant therapy followed by pancreatectomy. Patients were categorized based on the type of neoadjuvant treatment administered. Statistics included temporal trend assessment by annual percent change (APC), predictors for SBRT by multivariable logistic regression, Kaplan-Meier overall survival (OS) analysis without and with propensity matching, and Cox proportional hazards modeling for univariable OS analysis. Results: Of 5828 patients, 332 (5.7%), 3234 (55.5%) and 2262 (38.8%) received neoadjuvant chemo-SBRT, chemotherapy, and chemo-CFRT, respectively. SBRT utilization increased from 0% in 2004 to 9.5% in 2015, with a greater APC after 2010 (p < .001). SBRT was more likely to be utilized in patients with T3-4 and node-positive disease (p < .05 for all). The chemo-SBRT cohort was associated with a higher OS rate before and after propensity matching (p < .05 for both). The rate of R0 resection was higher in radiotherapy groups than the chemotherapy cohort (p < .001). Conclusions: Utilization of neoadjuvant SBRT for pancreatic cancer is increasing. In the neoadjuvant setting, chemo-SBRT may improve R0 resection and OS over chemotherapy and chemo-CFRT, although confirmatory prospective studies are needed for confirmation.

The impact of molecular status on survival outcomes for invasive micropapillary carcinoma of the breast.

Invasive micropapillary carcinoma (IMPC) is an uncommon variant of breast cancer. Previous studies demonstrated this subtype is often hormone receptor (HR)-positive, resulting in survival outcomes similar to invasive ductal carcinoma. However, many of these studies were conducted prior to HER2 testing availability. We aim to determine the impact of molecular marker status (including HER2 status) on IMPC survival outcomes. The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven IMPC from 2007 to 2012. Only patients with known HR and HER2 status were included. Cox multivariate regression was used to determine prognostic factors. In total, 865 patients were included; median follow-up was 2.5 years. Overall, 651 patients (75.3%) had HR + HER2- disease, 128 (14.8%) had HR + HER2+ disease, 41 (4.7%) had HR-HER2 + disease, and 45 (5.2%) had triple negative disease. Patients with triple negative disease were more likely to have poorly differentiated histology (66.7%), lymphovascular invasion (73.3%), stage 3 disease (37.8%), undergone mastectomy (68.9%), and positive surgical margins (15.6%). On Cox multivariate regression, those with triple negative disease had worse overall survival (hazard ratio [HR] 7.28, P < 0.001). Other adverse prognostic factors included African-American descent (HR 2.24, P = 0.018), comorbidity score of 1 (HR 2.50, P = 0.011), comorbidity score ≥2 (HR 3.27, P = 0.06), and ≥3 positive lymph nodes (HR 3.23, P = 0.007). Similar to invasive ductal carcinoma, triple negative disease in IMPC results in worse survival outcomes. This is the largest and first study to characterize molecular status (including HER2 status) in patients with IMPC and its impact on survival outcomes.

Omission of radiation therapy following breast conservation in older (≥70 years) women with T1-2N0 triple-negative breast cancer.

BACKGROUND: Although randomized data support omitting adjuvant radiotherapy (RT) following breast conservation for T1-2N0 estrogen receptor positive breast cancer in ≥70-year-old women, there remains a knowledge gap regarding its omission for triple-negative BC (TNBC). METHODS AND MATERIALS: The National Cancer Database (NCDB) was queried for ≥70-year-old females with newly diagnosed T1-2N0M0 TNBC treated with breast conservation. Multivariable logistic regression ascertained factors associated with adjuvant RT administration. Overall survival (OS) between patients treated with or without adjuvant RT was estimated using the Kaplan-Meier method. Cox proportional hazards modeling determined variables associated with OS. RESULTS: Of 8526 patients, 6283 (74%) patients received adjuvant RT, and 2243 (26%) did not. RT was more frequently withheld in older patients, those with higher comorbidities, lower income, pT2 disease, following margin-positive resection, receipt of chemotherapy, and at academic centers (P < 0.05 for all). Median follow-up was 38.0 months. Five-year OS was greater in the adjuvant RT group (77.2% vs 55.3%, P < 0.001); these differences persisted when stratifying for age, T stage, and chemotherapy utilization (P < 0.001 for all). Omission of RT was also independently associated with poorer OS on multivariate analysis (P < 0.001). CONCLUSIONS: This investigation, the largest known such study to date, observed that omission of adjuvant RT for elderly women with T1-2N0 TNBC was associated with poorer OS; this was observed across a range of age groups, as well as following stratification by T stage and chemotherapy usage. Although these results do not imply causation, caution must be exercised when considering omission of adjuvant RT in node-negative TNBC patients.