BACKGROUND: Better cancer-related outcomes are associated with physicians and hospitals with higher case volume. This serves as an incentive to refer patients requiring complex cancer operations to large referral centers, which may require increased travel for patients. However, barriers exist for patients to travel for cancer care, some of which may be aggravated or alleviated by factors relating to the health of the national economy. This impact may be reflected in variability of travel distances for cancer operations over time particularly for complex operation such as pancreatectomy and esophagectomy compared with less complex resections such as those for breast cancer or melanoma. METHODS: We obtained the estimated travel distance for patients undergoing operations for cancer of the pancreas, esophagus, skin (melanoma), and breast from the National Cancer Database from 2004 to 2017 and correlated them with economic factors obtained from public sources. We then examined the impact of unemployment rates, gas prices, and inflation on travel distances regarding disadvantaged groups. Correlations were measured by the (rank-based, nonparametric) Spearman's correlation coefficient, and the corresponding P value is obtained by the asymptotic distribution of the coefficient. A P value of 0.05 equates to an absolute correlation value of 0.532. To adjust for multiple tests, a more restrictive P value of 0.01 was also assessed, which equates to correlation coefficients of absolute value greater than 0.661. RESULTS: There were 4,222,380 cases in the dataset, of which 1,781,056 remained after exclusion. The economic factors that were associated most strongly with the distance patients traveled for all cancer operation types were the labor force participation rate, personal savings, consumer price index, and changes in gasoline prices. Inflation and rising gasoline prices were often inversely related with travel distance in lower-income and less well-educated regions and African American patients. CONCLUSIONS: Several macroeconomic factors correlate with the travel distance for operations, suggesting that the economic health of the nation may aggravate or alleviate the financial barriers to travel for cancer operations. Financially disadvantaged groups may be particularly vulnerable to changes in gasoline prices and inflation. Organizations serving these populations may need to increase patient support services during times of economic hardship to avoid the exacerbation of health care disparities.

Background: Two large randomized trials, CALGB 9343 and PRIME II, support omission of radiotherapy after breast conserving surgery (BCS) in elderly women with favorable-risk early stage breast cancer intending to take endocrine therapy. However, patients with grade 3 histology were underrepresented on these trials. We hypothesized that high-grade disease may be unsuitable for treatment de-escalation and report the oncologic outcomes for elderly women with favorable early stage breast cancer treated with BCS with or without radiotherapy. Materials and Methods: The Surveillance, Epidemiology, and End Results database was queried for women between 70 and 79 years of age with invasive ductal carcinoma diagnosed between 1998 and 2007. This cohort was narrowed to women with T1mic-T1c, N0, estrogen receptor-positive, invasive ductal carcinoma treated with BCS with or without external beam radiation (EBRT). The primary endpoints were 5- and 10-year cause-specific survival (CSS). Univariate and multivariate analyses were performed. Propensity-score matching of T-stage, year of diagnosis, and age was utilized to reduce selection bias while comparing treatment arms within the grade 3 subgroup. Results: A total of 12,036 women met inclusion criteria, and the median follow-up was 9.4 years. EBRT was omitted in 22% of patients, including 21% with grade 3 disease. Patients in the EBRT cohort were slightly younger (median, 74 vs. 75 years; P < .01) and had fewer T1a tumors (11% vs. 13%; P = .02). Histologic grades 1, 2, and 3 comprised 36%, 50%, and 14% of the cohort, respectively, and there were no differences in EBRT utilization by grade. Utilization of EBRT decreased following the publication of the CALGB trial in 2004 decreasing from 82% to 85% in 1998 to 2000 to 73% to 75% in 2005 to 2007 (P < .01). Unadjusted outcomes showed that in grade 1 disease, there were no differences in CSS with or without EBRT at 5 (99%) and 10 years (95%-96%). EBRT was associated with an improvement in CSS in grade 2 histology at 5 years (97% vs. 98%) and 10 years (92% vs. 95%) (P = .004). The benefit was more pronounced in grade 3 disease with CSS increasing from 93% to 96% at 5 years and from 87% to 92% at 10 years (P = .02) with EBRT. In the grade 3 subgroup, propensity-score matching confirmed EBRT was associated with superior CSS compared with surgery alone (hazard ratio, 0.58; 95% confidence interval, 0.34-0.98; P = .043). Conclusion: In this database analysis, omission of radiotherapy after BCS in elderly women with favorable-risk, early stage, grade 3 breast cancer was associated with inferior CSS. Further prospective data in this patient population are needed to confirm our findings and conclusions. Grade 3 disease was not well-represented in clinical trials investigating the omission of radiotherapy following breast conserving surgery in elderly women with early stage breast cancer. This Surveillance, Epidemiology, and End Results analysis of 12,036 women aged 70 to 79 years with T1N0, estrogen receptor-positive, invasive ductal carcinoma found that women with grade 3 disease had both an overall survival and breast cancer-specific mortality benefit with radiotherapy.

Oncogenic RAS mutations drive aggressive cancers that are difficult to treat in the clinic, and while direct inhibition of the most common KRAS variant in lung adenocarcinoma (G12C) is undergoing clinical evaluation, a wide spectrum of oncogenic RAS variants together make up a large percentage of untargetable lung and GI cancers. Here we report that loss-of-function alterations (mutations and deep deletions) in the gene that encodes HD-PTP ( PTPN23 ) occur in up to 14% of lung cancers in the ORIEN Avatar lung cancer cohort, associate with adenosquamous histology, and occur alongside an altered spectrum of KRAS alleles. Furthermore, we show that in publicly available early-stage NSCLC studies loss of HD-PTP is mutually exclusive with loss of LKB1, which suggests they restrict a common oncogenic pathway in early lung tumorigenesis. In support of this, knockdown of HD-PTP in RAS-transformed lung cancer cells is sufficient to promote FAK-dependent invasion. Lastly, knockdown of the Drosophila homolog of HD-PTP (dHD-PTP/Myopic) synergizes to promote RAS-dependent neoplastic progression. Our findings highlight a novel tumor suppressor that can restrict RAS-driven lung cancer oncogenesis and identify a targetable pathway for personalized therapeutic approaches for adenosquamous lung cancer.

Background: Receptor status in breast cancer is known to be related to survival. However, the relationship between breast cancer subtype, preferential sites of metastasis, and overall survival is not clear. Methods: A total of 414,528 patients from the National Cancer Database (2010-2013) were examined. All patients received surgery and systemic treatments. Breast cancer was subtyped based on hormonal receptor (HR) and HER2 status. Results: HR-/HER2+ breast cancer patients had the highest overall rate of metastasis while HR+/HER2- had the lowest. HR+/HER2+ cancer had the most frequent metastasis to the bone, and HR-/HER2+ to brain, liver, lung and multiple sites. Generally, patients with brain or multiple metastasis had the worst overall survival (OS) across different subtypes. Patients with bone oligometastasis tend to have better OS than patients with metastasis to other site but significantly worse OS than patients without any metastasis. Conclusions: This large study exhibits how breast cancer subtype plays a role in the rate and site of metastasis as well as in overall survival. Surveillance and treatment strategies should be tailored on the risk and potential site of metastases based upon receptor subtype.

Background: Retrospective studies have shown some improvement in survival for patients receiving surgical management of the intact primary tumor in patients with presenting with Stage IV disease, while prospective studies have revealed mixed results. Methods: An examination of the NCDB from 2004–2013 was undertaken to examine factors related to the utilization of surgery and overall survival in patients with de novo Stage IV disease. Univariate and multivariable analyses were conducted to determine factors related to survival. Propensity score matching method was implemented to balance patients’ baseline characteristics. Results: A total of 11,694 patients with Stage IV breast cancer at diagnosis met inclusion criteria. Surgical intervention occurred in 5,202 patients (44.5%), with the use of surgery decreasing throughout the study period (53.6% surgery 2004–2006; 31.8% surgery 2011–2013). Selection for surgical intervention was associated with small tumors (T1) and a higher nodal burden (N2/3). Uninsured patients, those treated at academic centers, those treated in the Northeast, and those with hormone receptor positive tumors were less likely to undergo surgery. Surgery was independently associated with a better overall survival. Propensity score matching revealed a persistent survival advantage for surgical patients receiving surgery, regardless of the receipt of systemic therapy. Conclusions: Surgery on the intact primary tumor for patients presenting with de novo Stage IV breast cancer is associated with improved overall survival. Surgical resection in patients with Stage IV breast cancer should be considered for well-selected patients as a part of multimodality therapy.

Background: Recurrence score (RS) testing in early-stage, ER-positive breast cancer is used to predict the benefit of adjuvant chemotherapy for disease recurrence and overall survival. TAILORx results decreased the ambiguity of “intermediate risk” RS by creating a binary classification system. We aimed to determine how women ≥ 70 years with intermediate RS were redistributed post-TAILORx and to identify predictors of low RS. Methods: Patients ≥ 70 years with early-stage, node-negative, ER-positive breast cancers in the National Cancer Database(2006–2014) were included. “Pre-TAILORx” RS were classified as low (0–17), intermediate (18–30), and high (> 30). “Post-TAILORx” RS were classified as low (0–25) and high (> 25). Results: In total, 14,925 women were included. Average age was 74 years. 60% (n = 9009) had low pre-TAILORx RS, 31% (n = 4635) intermediate, and 9% (n = 1281) high. Of 4635 patients with intermediate RS, 72% (n = 3660) were reclassified to low RS. Only 12% (n = 1783) of patients received chemotherapy. Of patients with pre-TAILORx intermediate RS who received chemotherapy, 55% (n = 417) would have been spared chemotherapy by being reclassified with low RS post-TAILORx. The strongest predictor of post-TAILORx low RS was tumor grade; 95% of well-differentiated had low RS, compared with 56% of poorly/undifferentiated tumors (p < 0.001). Smaller tumor size also was associated with low RS. Age was not associated with RS. Conclusions: With post-TAILORx RS criteria, the vast majority of patients ≥ 70 years can be classified as low-risk and unlikely to benefit from chemotherapy. Given that the elderly have greater rates of chemotherapy-associated complications, reconsideration of routine RS testing in patients ≥ 70 years is warranted. Tumor grade and size also may inform the decision to omit RS testing.

Background: Primary hyperaparathyroidism (pHPT) is often accompanied by underlying thyroid pathology that can confound preoperative parathyroid localization studies and com-plicate intra-operative decision making. The aim of this study was to examine the utility of preoperative thyroid ultrasonography (US) in patients prior to undergoing parathyroidec-tomy for pHPT. Methods: An Institutional Review Board approved prospective study was undertaken from January 2005 through July 2008. All patients with pHPT meeting inclusion criteria (n=94) underwent preoperative thyroid ultrasound in addition to standard 99mTc-sestamibi scintig-raphy for parathyroid localization. Demographics, operative management and final pathology were examined in all cases. Results: Fifty-four of the 94 patients (57%) were noted to have a thyroid nodule on pre-operative US, of which 30 (56%) underwent further examination with fine needle aspiration biopsy. Alteration of the operative plan attributable to underlying thyroid pathology occurred in 16 patients (17%), with patients undergoing either total thyroidectomy (n=9) or thyroid lobectomy (n=7). Thyroid cancer was noted in 33% of patients undergoing thyroid resection, and 6% of all patients with HPT. Conclusions: The routine utilization of preoperative thyroid ultrasound in patients prior to undergoing parathyroid surgery for pHPT is indicated. The added information from this non-invasive modality facilitates timely management of co-incidental, and sometimes malig-nant, thyroid pathology.