Faculty Bibliography

It is unclear whether there is a survival benefit with postoperative radiation for low-grade gliomas deemed to be high-risk. We sought to analyze patterns of care and outcomes of radiation use. We accessed the National Cancer Database to identify patients with WHO grade II oligodendroglioma or astrocytoma between 2010 and 2012. Multivariable logistic regression was used to identify predictors of radiation use and multivariable Cox regression was used to identify covariables associated with differences in survival. There were 1952 patients included in this study, of which 518 (26.5%) received postoperative radiation. The majority had oligodendroglioma histology (n = 1121, 57.4%) compared to astrocytoma (n = 831, 42.6%). There were 1626 patients who were either ≥40 years old or underwent a subtotal resection ("high-risk"), and from these 495 (30.4%) received postoperative radiation. On multivariable logistic regression treatment at an academic facility (OR 0.72) was associated with a lower likelihood of receiving postoperative radiation. Astrocytoma histology (OR 2.08), age ≥40 years (OR 2.23), tumor size ≥6 cm (OR 1.64), subtotal resection (OR 1.55), and chemotherapy use (OR 3.93) were associated with an increased likelihood of postoperative radiation. On multivariable analysis, astrocytoma histology (HR 3.49, p < 0.001) and receipt of radiation (HR 2.06, p < 0.001) were associated with worse overall survival. GTR (HR 0.51, p = 0.001) was associated with improved overall survival. Patients treated in United States hospitals are not routinely referred for postoperative radiation for high-risk, low-grade gliomas. Patients who received radiation did not do better than those who did not receive radiation.

PURPOSE/OBJECTIVES/OBJECTIVE:While treatment with tumor resection followed by chemoradiation is generally the accepted standard of care for glioblastoma (GBM), the treatment for patients with poor performance status remains uncertain. Therefore we sought to examine patterns of care and survival outcomes among patients with poor performance status utilizing a large hospital database. METHODS/MATERIALS/METHODS:We queried the National Cancer Database (NCDB) for patients with GBM and Karnofsky performance status (KPS) <60 between 2010 and 2013. Data was collected regarding surgery, radiation therapy and chemotherapy. Logistic regression was used to analyze predictors for utilization of chemoradiation. The Kaplan-Meier method was used to compare survival between those who received chemoradiation to radiation alone and Cox regression was performed to assess covariates associated with survival. RESULTS:There were 488 patients included in the analysis of which 51.2% received chemoradiation and 46.1% underwent subtotal or gross total resection. None of the factors analyzed were significantly associated with increased likelihood of receiving chemoradiation over radiation alone. Survival data was available for 236 patients that received radiation therapy with and without combination chemotherapy. The median overall survival for those receiving radiation alone was 3.6 months and 8.7 months in those who received chemoradiation (p < 0.001). On multivariable Cox regression, older age (HR 1.80-2.10, p = 0.001) was associated with worse survival and subtotal/gross total resection compared to no surgery (HR 0.60, p = 0.003) was associated with improved survival. CONCLUSION/CONCLUSIONS:Even patients with poor performance status had better survival outcomes when they received treatment with chemoradiation over radiation alone.

BACKGROUND:Tumor testing for mutations in the epidermal growth factor receptor (EGFR) gene is indicated for all newly diagnosed, metastatic lung cancer patients, who may be candidates for first-line treatment with an EGFR tyrosine kinase inhibitor. Few studies have analyzed population-level testing. METHODS:We identified clinical, demographic, and regional predictors of EGFR & KRAS testing among Medicare beneficiaries with a new diagnosis of lung cancer in 2011-2013 claims. The outcome variable was whether the patient underwent molecular, EGFR and KRAS testing. Independent variables included: patient demographics, Medicaid status, clinical characteristics, and region where the patient lived. We performed multivariate logistic regression to identify factors that predicted testing. RESULTS:From 2011 to 2013, there was a 19.7% increase in the rate of EGFR testing. Patient zip code had the greatest impact on odds to undergo testing; for example, patients who lived in the Boston, Massachusetts hospital referral region were the most likely to be tested (odds ratio (OR) of 4.94, with a 95% confidence interval (CI) of 1.67-14.62). Patient demographics also impacted odds to be tested. Asian/Pacific Islanders were most likely to be tested (OR 1.63, CI 1.53-1.79). Minorities and Medicaid patients were less likely to be tested. Medicaid recipients had an OR of 0.74 (CI 0.72-0.77). Hispanics and Blacks were also less likely to be tested (OR 0.97, CI 0.78-0.99 and 0.95, CI 0.92-0.99), respectively. Clinical procedures were also correlated with testing. Patients who underwent transcatheter biopsies were 2.54 times more likely to be tested (CI 2.49-2.60) than those who did not undergo this type of biopsy. CONCLUSIONS:Despite an overall increase in EGFR testing, there is widespread underutilization of guideline-recommended testing. We observed racial, income, and regional disparities in testing. Precision medicine has increased the complexity of cancer diagnosis and treatment. Targeted interventions and clinical decision support tools are needed to ensure that all patients are benefitting from advances in precision medicine. Without such interventions, precision medicine may exacerbate racial disparities in cancer care and health outcomes.

BACKGROUND:Although outcomes for patients with squamous cell carcinoma of the anus (SCCA) have improved, the gains in benefit may not be shared uniformly among patients of disparate socioeconomic status. In the current study, the authors investigated whether area-based median household income (MHI) is predictive of survival among patients with SCCA. METHODS:Patients diagnosed with SCCA from 2004 through 2013 in the Surveillance, Epidemiology, and End Results registry were included. Socioeconomic status was defined by census-tract MHI level and divided into quintiles. Multivariable Cox proportional hazards models and logistic regression were used to study predictors of survival and radiotherapy receipt. RESULTS:A total of 9550 cases of SCCA were included. The median age of the patients was 58 years, 63% were female, 85% were white, and 38% were married. In multivariable analyses, patients living in areas with lower MHI were found to have worse overall survival and cancer-specific survival (CSS) compared with those in the highest income areas. Mortality hazard ratios for lowest to highest income were 1.32 (95% confidence interval [95% CI], 1.18-1.49), 1.31 (95% CI, 1.16-1.48), 1.19 (95% CI, 1.06-1.34), and 1.16 (95% CI, 1.03-1.30). The hazard ratios for CSS similarly ranged from 1.34 to 1.22 for lowest to highest income. Older age, black race, male sex, unmarried marital status, an earlier year of diagnosis, higher tumor grade, and later American Joint Committee on Cancer stage of disease also were associated with worse CSS. Income was not found to be associated with the odds of initiating radiotherapy in multivariable analysis (odds ratio of 0.87 for lowest to highest income level; 95% CI, 0.63-1.20). CONCLUSIONS:MHI appears to independently predict CSS and overall survival in patients with SCCA. Black race was found to remain a predictor of SCCA survival despite controlling for income. Further study is needed to understand the mechanisms by which socioeconomic inequalities affect cancer care and outcomes. Cancer 2018. © 2018 American Cancer Society.

Multiple studies have identified O⁶-methylguanine-DNA methyltransferase (MGMT) promoter methylation status to be an important prognostic factor in glioblastoma (GBM). We used the National Cancer Data Base (NCDB) to analyze completeness of coding for MGMT as well as to compare outcomes of GBM patients treated with adjuvant chemoradiation based on MGMT promoter methylation status (positive, negative, unknown). Patients diagnosed with GBM from 2010 to 2012 who received adjuvant chemoradiation were identified. MGMT promoter methylation status was obtained. The Kaplan-Meier method was used to assess overall survival (OS) by coding status of MGMT promoter methylation (positive, negative, unknown) and Cox regression analysis was used to assess impact of covariables on OS. There were 12,725 patients who met the study criteria, of which 626 (4.9%) were MGMT+, 1,037 (8.1%) were MGMT- and 11.062 (86.9%) were coded as unknown/not coded. Treatment at academic centers was strongly associated with MGMT promoter status testing (OR 2.23, p < 0.001), as well as hospital facility within the Northeast (OR 1.55, p < 0.001). The median and 2-year OS was 20 months and 40.2% for MGMT+ compared to 15 months and 24.1% for MGMT-, respectively (p < 0.001). For those coded as MGMT unknown, median and 2-year OS was 14.6 months and 27.5%, which was significantly worse compared to MGMT+ (p < 0.001) but not compared to MGMT- (p = 0.78). On multivariable analysis, MGMT+ was strongly associated with improved OS (HR 0.74, p < 0.001). Despite convincing evidence that MGMT promoter methylation status has a strong influence on prognosis; it appears to be a highly underutilized test in United States hospitals.

OBJECTIVES: Despite previous retrospective reports that the number of lymph nodes resected at curative intent surgery for lung cancer correlates with overall survival (OS), no consensus exists regarding the minimal nor optimal number of lymph nodes to resect at curative lung cancer surgery. METHODS: We studied subjects in the Surveillance Epidemiology and End Results Database (SEER) diagnosed with non-small cell lung cancer between 2000 and 2011 who underwent either lobectomy or pneumonectomy and had pathologic negative nodal evaluation. We excluded patients with sublobar resection and/or no lymph node evaluation. We examined associations between number of lymph nodes evaluated and OS/lung cancer-specific survival by multivariable Cox regression; and predictors of evaluation of more lymph nodes. RESULTS: Among the 33,463 patients in our sample, a median of 7 lymph nodes were evaluated. We found that lung cancer-specific survival and OS improved with increasing lymph node evaluation up to 16 to 18 lymph nodes (hazard ratio, 0.77 [95% confidence interval, 0.70-0.85] and 0.78 [95% confidence interval, 0.72-0.86], respectively). There was little additional improvement in outcomes with evaluation of >16 to 18 lymph nodes. Blacks, Hispanics, females, and patients from distinct geographical regions were less likely to have 16 or more lymph nodes evaluated. CONCLUSIONS: There was a consistently increasing survival benefit associated with a more extensive lymph node evaluation at lung cancer resection, up to 16 to 18 lymph nodes removed. The median number of nodes evaluated was, however, only 7, suggesting that setting a goal of >/=16 examined lymph nodes may lead to improved survival outcomes, and reduce disparities in care.

Background Metformin has been shown to have anti-neoplastic activity in non-small cell lung cancer (NSCLC) in both preclinical and observational studies, however this has never been prospectively evaluated. This single-arm phase II trial, while not fully accrued, is the first known prospective study evaluating the use of metformin with chemotherapy in advanced NSCLC. Methods Patients received carboplatin AUC 5 + pemetrexed 500 mg/m2 IV every 21 days for 4 cycles. For patients who achieved at least stable disease, maintenance pemetrexed was administered until progression or toxicity. Metformin was initiated at 1000 mg/day for week 1, 1500 mg/day for week 2, then 2000 mg/day thereafter, in divided doses. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and adverse events (AE). Tumor tissue was tested for LKB1/STK11 mutations, and non-fasting serum insulin levels were longitudinally assessed. Results Of a planned 50 patients, 14 were enrolled. ORR was 23% and median PFS was 3.9 months. Median OS was 11.7 months. No LKB1/STK11 mutations were identified. The most common AE were fatigue (42.9%), anemia, and nausea (28.6% each). The most common grade III AE was nausea (14.3%). No grade IV AE occurred. Mean duration of metformin treatment was 5.6 months. Conclusion Adding metformin to chemotherapy for advanced NSCLC was safe but did not significantly improve clinical outcomes compared to historical phase III controls. These results are limited by the small sample size; larger trials are needed.

Recently, a firmer understanding of tumor immunology and tumor escape mechanisms has led to the development of immune checkpoint inhibitors, antibodies against programmed death-1 (PD-1) and its ligand (PD-L1). Nivolumab, pembrolizumab, and atezolizumab have dramatically altered the treatment paradigm in non-small cell lung cancer (NSCLC) and have each demonstrated improvements in outcomes and quality of life when compared to chemotherapy. Enrichment strategies to better select those patients more likely to respond have identified PD-L1 staining by immunohistochemistry (IHC) to be a predictive biomarker in both treatment naive and refractory patients. Unfortunately, many challenges exist with this strategy and underscore the need for further exploration for more reliable biomarkers. Multiple tissue and plasma-based enrichment strategies have been identified in the hope of identifying patients more likely to benefit from checkpoint inhibitors. These include tumor mutational load; the "inflamed phenotype" including tumor infiltrating lymphocytes (TILS) and immunoscore; T-cell receptor clonality; gene signatures, and several plasma biomarkers. Several studies have revealed many of these biomarkers to be reliable predictors of response to immune checkpoint inhibitors across multiple tumor types. Given the small nature of these studies, additional prospective studies are warranted to formalize and validate each of these enrichment strategies.