Identification of Populations at Risk for "Choosing Un-Wisely": A SEER Population-Based Study.

BACKGROUND: Since 2016, the Choosing Wisely campaign has recommended against routine axillary surgery in elderly patients with early stage, hormone receptor positive (ER+) breast cancer. The objective was to evaluate factors associated with axillary surgery in breast cancer patients meeting criteria for sentinel lymph node biopsy (SLNB) omission and identify potential disparities. METHODS: Female patients age ≥70 years with cT1-2N0M0, ER+, HER2-negative breast cancer diagnosed after publication of the Choosing Wisely recommendations, between 2016 and 2019, were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patient demographics and tumor characteristics associated with axillary surgery were analyzed. RESULTS: Of the 31 756 patients meeting omission criteria, 25 771 (81.2%) underwent axillary surgery. Hispanic ethnicity, median household income between $35,000 and $70,000, treatment in rural areas, poor differentiation, lobular and mixed lobular with ductal histology, T2 tumors, radiation therapy, and systemic therapy were factors associated with receiving axillary surgery on multivariable analysis. In the axillary surgery cohort, a median of 2 (IQR = 2) nodes were examined and 529 (2.1%) patients were found to have 1 or more positive lymph nodes. DISCUSSION: Among elderly patients meeting Choosing Wisely criteria for SLNB omission, particular racial, ethnic, socioeconomic, and geographic populations may be at increased risk for potential over treatment. Identification of these factors provides specific opportunities for education and implementation of de-escalation of unnecessary procedures.

A phase II trial of gemcitabine and erlotinib followed by ChemoProton therapy plus capecitabine and oxaliplatin for locally advanced pancreatic cancer.

Background: Epidermal growth factor receptor (EGFR) is overexpressed in pancreatic cancer. EGFR expression plays a potentially important role in modulation of tumor sensitivity to either chemotherapy or radiotherapy. Erlotinib is a receptor tyrosine kinase inhibitor with specificity for EGFR/HER1. A phase II trial was conducted to explore the efficacy of a regimen utilizing erlotinib and proton therapy. Methods: Patients with unresectable or borderline resectable non-metastatic adenocarcinoma of the pancreas were included. Patients received 8-week systemic treatment with gemcitabine 1,000 mg/m2 and erlotinib 100 mg (GE). If there was no evidence of metastatic disease after GE, then patients preceded with proton therapy to 50.4 Gy in 28 fractions with concurrent capecitabine 825 mg/m2 (CPT). This was followed with oxaliplatin 130 mg/m2 and capecitabine 1,000 mg/m2 (CapOx) for 4 cycles. The primary study objective was 1-year overall survival (OS). The benchmark was 43% 1-year survival as demonstrated in RTOG/NRG 98-12. The Kaplan-Meier method was used to estimate the one-year OS and the median OS and progression-free survival (PFS). Results: The study enrolled 9 patients ages 47-81 years old (median 62) between January 2013 and March 2016, when the trial was closed due to low patient accrual. The 1-year OS rate was 55.6% (95% CI: 31% to 99%). The median OS was 14.1 months (95% CI: 11.4-NE) and the median PFS was 10.8 months (95% CI: 7.44-NE). A majority of patients completed CPT and GE, but only 33.3% completed the four cycles of CapOx. A third of patients experienced grade 3 toxicities, which were all hepatic along with one patient who also had grade 3 diarrhea. There were no grade 4 or 5 toxicities. Four patients were enrolled with borderline resectable disease, three of which were eligible for pancreaticoduodenectomy after GE and CPT treatment. One of two patients who underwent resection had a negative margin. Conclusions: This regimen for locally advanced pancreatic cancer (LAPC) exceeded the pre-specified benchmark and was safe and well tolerated. Additional investigations utilizing more current systemic treatment regimens with proton therapy are warranted. Trial Registration: ClinicalTrials.gov identifier (NCTNCT01683422).

Redistribution of Outpatient Oncologic Surgical Specialty Referrals During COVID-19.

BACKGROUND: Initial reports of significantly worse outcomes for cancer patients with COVID-19 led to guidelines for triaging surgical cancer treatment. We sought to evaluate the effects of the COVID-19 pandemic on oncologic surgical specialty referrals. METHODS: We compared referrals to oncologic surgical specialty clinics at an academic tertiary care institution following implementation of stay-at-home orders in California (3/19/20-7/31/20, "COVID") to the same time period the year prior (3/19/19-7/31/19, "Pre-COVID"). The number of appointments, consulted surgical services, insurance types, acuity of diagnoses, and times from referral to first appointment (TRFA) were assessed. RESULTS: The overall number of patients seen in matched time periods decreased by 21.6% from 900 (pre-COVID) to 705 (COVID). Proportions of patients with malignant and suspicious diagnoses, surgical and thoracic oncology visits, and Medicaid insurance differed from comparison groups during the COVID period (P < .05). Overall median (interquartile range) TRFA decreased from 14 (20) to 12 (19) days (P = .001) during COVID. CONCLUSION: After implementation of stay-at-home orders, higher acuity and vulnerable patients were appropriately seen in oncologic surgical specialty clinics. While the long-term effects of decreased clinic visits during COVID remain uncertain, further examination of scheduling practices that led to shorter referral times may identify methods to improve timeliness of care and surgical oncologic outcomes in non-pandemic settings.

The Impact of Primary Tumor Surgery on Survival in HER2 Positive Stage IV Breast Cancer Patients in the Current Era of Targeted Therapy.

OBJECTIVE: We sought to examine the impact of primary tumor resection on survival in HER2+ stage IV breast cancer patients in the era of HER2 targeted therapy. METHODS: We conducted a retrospective cohort study of women with HER2+ stage IV breast cancer in the National Cancer Database from 2010 to 2012 comparing those who did and did not undergo definitive breast surgery. RESULTS: Of 3231 patients, treatment included primary site surgery in 35.0%; chemo/targeted therapy in 89.4%; endocrine therapy in 37.7%; and radiation in 31.8%. Surgery was associated with Medicare/other government (OR 1.36, 95% CI 1.03-1.81) or private insurance (OR 1.93, 95% CI 1.53-2.42) versus none/Medicaid, radiation (OR 2.10, 95% CI 1.76-2.51), chemo/targeted therapy (OR 1.99, 95% CI 1.47-2.70), and endocrine therapy (OR 1.73, 95% CI 1.40-2.14). Non-Hispanic Black versus White patients (OR 0.68, 95% CI 0.53-0.87) were less likely to have surgery. Overall mortality was associated with insurance (Medicare/other government versus none/Medicaid, HR 0.36, p < 0.0001), receipt of chemo/targeted therapy (HR 0.76, p = 0.008), endocrine therapy (HR 0.70, p = 0.0006), and radiation therapy (HR 1.33, p = 0.0009), NH Black versus White race/ethnicity (HR 1.39, p = 0.002), visceral versus bone-only metastases (HR 1.44, p = 0.0003), and lowest versus highest income quartile (HR 1.36, p = 0.01). Propensity score analysis showed surgery was associated with improved survival versus no surgery (HR 0.56, 95% CI 0.40-0.77). CONCLUSIONS: Surgery of the primary site for metastatic HER2+ breast cancer is associated with improved overall survival in selected patients.

Gastric Cancer Peritoneal Carcinomatosis Risk Score.

BACKGROUND: Gastric cancer (GC) peritoneal carcinomatosis (PC) is associated with a poor prognosis. Although grade, histology, and stage are associated with PC, the cumulative risk of PC when multiple risk factors are present is unknown. This study aimed to develop a cumulative GCPC risk score based on individual demographic/tumor characteristics. METHODS: Patient-level data (2004-2014) from the California Cancer Registry were reviewed by creating a keyword search algorithm to identify patients with gastric PC. Multivariable logistic regression was used to assess demographic/tumor characteristics associated with PC in a randomly selected testing cohort. Scores were assigned to risk factors based on beta coefficients from the logistic regression result, and these scores were applied to the remainder of the subjects (validation cohort). The summed scores of each risk factor formed the total risk score. These were grouped, showing the percentages of patients with PC. RESULTS: The study identified 4285 patients with gastric adenocarcinoma (2757 males, 64.3%). The median age of the patients was 67 years (interquartile range [IQR], 20 years). Most of the patients were non-Hispanic white (n = 1748, 40.8%), with proximal (n = 1675, 39.1%) and poorly differentiated (n = 2908, 67.9%) tumors. The characteristics most highly associated with PC were T4 (odds ratio [OR], 3.12; 95% confidence interval [CI], 2.19-4.44), overlapping location (OR 2.27; 95% CI 1.52-3.39), age of 20-40 years (OR 3.42; 95% CI 2.24-5.21), and Hispanic ethnicity (OR 1.86; 95% CI 1.36-2.54). The demographic/tumor characteristics used in the risk score included age, race/ethnicity, T stage, histology, tumor grade, and location. Increasing GCPC score was associated with increasing percentage of patients with PC. CONCLUSION: Based on demographic/tumor characteristics in GC, it is possible to distinguish groups with varying odds for PC. Understanding the risk for PC based on the cumulative effect of high-risk features can help clinicians to customize surveillance strategies and can aid in early identification of PC.

Improved Survival with Immunotherapy but Lack of Synergistic Effect with Radiation for Stage IV Melanoma of the Head and Neck.

Prospective randomized studies have demonstrated a survival benefit of immunotherapy in stage IV cutaneous melanoma. Some retrospective studies have hypothesized a synergistic effect of radiation and immunotherapy. Our objective was to identify whether there is a survival benefit for patients treated with radiation and immunotherapy in stage IV cutaneous melanoma of the head and neck (CMHN). The National Cancer Database was used to identify patients with stage IV CMHN between 2012 and 2014. These patients were stratified based on receipt of radiation and immunotherapy. Adjusted Cox regression was used to analyze overall survival. A total of 542 patients were identified with stage IV CMHN, of whom 153 (28%) patients received immunotherapy. Receipt of immunotherapy (hazard ratio [HR] 0.69, P = 0.02) and negative LNs (HR 0.50, P = 0.002) were independently associated with improved survival, whereas radiation conferred no survival benefit (HR 1.17, P = 0.26). Patients who received immunotherapy without radiation were associated with significantly improved survival compared with those who received immunotherapy with radiation (P < 0.0001). However, of patients who received radiation, the addition of immunotherapy did not seem to improve survival (P = 0.979). In stage IV CMHN, immunotherapy confers a 32 per cent survival benefit. The use of immunotherapy in patients who require radiation, however, is not associated with improved survival.

Response to Neoadjuvant Treatment Is Influenced by Grade in Gastric Cancer.

Neoadjuvant therapy is commonly used in the management of gastric cancer. Primary tumor response to treatment correlates with prognosis. Published studies have compared efficacy of neoadjuvant therapy based on stage but not grade. The objective of this study was to determine the change in staging of gastric cancer after neoadjuvant therapy and resection based on grade. A retrospective analysis of gastric cancer patients treated at our institution between 2005 and 2017 was performed. Patient demographics, tumor characteristics, clinical and pathological stage, and microscopic treatment response were analyzed based on grade. Of the 269 patients identified during this period, 82 patients underwent definitive surgical resection, of which 38 patients received neoadjuvant therapy (low grade (grades 1 and 2), n = 17; high grade (grade 3), n = 18; and unknown grade, n = 3). Pathologic downstaging was observed in 52.9 per cent (9/17) of low-grade tumors compared with 22.2 per cent (4/18) of high-grade tumors. Majority of high-grade tumors (77.8%, 14/18) had either upstaging or unchanged stage. High-grade gastric cancers often lack response to neoadjuvant therapy. Novel targeted therapies based on biologic behavior should be evaluated and incorporated into neoadjuvant treatment. Neoadjuvant studies should stratify patients based on grade and report response by grade.

From Evidence to Practice: Are Low-Risk Breast Cancer Patients still Enduring Unnecessary Costs of Radiation?

Radiation is routinely recommended after conservative surgery for breast cancer, despite long-standing Level I evidence showing no survival benefit for elderly patients with favorable disease using endocrine therapy. We sought to evaluate radiation use and costs in patients eligible for omission of radiation. A retrospective single-institution review from 2005 to 2017 was performed of women aged ≥70 years, with cT1N0M0, who were ER/PR positive and HER-2 negative, and receiving breast-conserving surgery. Patient, tumor, and treatment characteristics were compared by use of radiation. Cost estimates used Medicare's 2019 fee schedule. Of 84 patients meeting the study criteria, 72.6 per cent received radiation and 56 per cent received endocrine therapy, with four recurrences (4.9% radiated and 4.4% not radiated, P = 0.9). Early and late grade I radiation toxicities occurred in 67.2 per cent and 26.2 per cent of radiated patients, respectively. Younger age (P = 0.01), receipt of endocrine therapy (P < 0.0001), and axillary surgery (P < 0.0001) were significantly associated with radiation use. There were no significant differences in radiation use based on race/ethnicity, language, comorbidities, BMI, or pathologic tumor size. Estimated total radiation cost was $646,426. Radiation remains overused and endocrine therapy, underused in breast cancer patients eligible to avoid radiation. As gatekeepers for radiation oncology referrals, surgeons can diminish both physical and financial costs of radiation in eligible patients.

Costs and Complications: Delayed Gastric Emptying after Pancreaticoduodenectomy.

Postoperative delayed gastric emptying (DGE) is a very common complication after a pancreaticoduodenectomy (PD). This along with other complications can lead to increased health-care costs. This study investigates the costs and length of stay (LOS) associated with these. A retrospective study of 131 patients undergoing PD between 2000 and 2016 at Loma Linda University Health was performed. Chi-squared test was used to determine statistically significant differences between patients with and without DGE (according to the definition of the International Study Group of Pancreatic Surgery). Multiple logistic and linear regression analyses were performed to obtain adjusted odds ratios for variables of interest in association with DGE and relationship to LOS. Of 150 patients undergoing PD, 131 patients with tumors were analyzed. The overall incidence of DGE was 56 per cent. No pre- or postoperative factors were associated with increased risk of DGE. The median LOS for patients with DGE was 15 days versus 9 days for patients without DGE. Patients with DGE added $21,198 to the overall cost of hospitalization. Fourteen patients (10.7%) were readmitted, of whom 11 were because of DGE. Further studies assessing the utility of intraoperative G-tube placement in decreasing hospital costs and readmissions are needed.

Improved long-term patient-reported health and well-being outcomes of early-stage breast cancer treated with partial breast proton therapy.

BACKGROUND: Because early-stage breast cancer can be treated successfully by a variety of breast-conservation approaches, long-term quality of life (QoL) is an important consideration in assessing treatment outcomes for these patients. This study compares patient-reported QoL outcomes among women with stage 0-2 disease treated via lumpectomy followed by whole breast irradiation (WBI) or partial breast proton irradiation (PBPT). METHODS: In this cross-sectional study, 129 participants evaluated QoL several years post-treatment by responding to subjective instruments, including established scalar questionnaires and self-report measures. Responses were averaged between the two groups. RESULTS: At 6.5 years (median) postdiagnosis, participants' demographic, and clinical characteristics were similar. Patient-reported outcomes were reported as mean scale scores for the two groups, all displaying significant differences favoring PBPT, including: cosmetic breast cancer treatment outcome scale (BCTOS) (PBPT mean 1.45, WBI mean 1.88, P < 0.001); breast pain (PBPT mean 1.30, WBI mean 1.67, P < 0.05); breast texture (BPT mean 1.44, WBI mean 1.91, P < 0.001); clothing fit (PBPT mean 1.06, WBI 1.46, P < 0.001); fatigue (PBPT mean 2.24, WBI mean 3.77, P < 0.002); impact of daily life fatigue on personal relations (OBPT mean 0.83, WBI mean 2.15, P < 0.001); and self-consciousness (appearance dissatisfaction) (PBPT mean 1.38, WBI mean 1.77, P < 0.004). CONCLUSION: Patients' responses suggest that PBPT is associated with improved overall QoL compared to standard whole breast treatment. These self-perceptions are reported by patients who are 5-10 years post-treatment, and that PBPT may enhance QoL in a multitude of interrelated ways.

Sexual and urinary outcomes in robotic rectal surgery: review of the literature and technical considerations.

Several studies have reported high rates of urogenital dysfunction after open and laparoscopic surgery for rectal cancer. Robotic surgery has several features that could facilitate identification and preservation of autonomic nerves. This manuscript aims to summarize the literature regarding urogenital function after robotic rectal cancer surgery and focus on technical aspects of nerve-sparing total mesorectal excision. Comprehensive searches were conducted through online databases. Selection criteria included: original articles assessing urinary and sexual function after robotic surgery of males and/or females with standardized questionnaires. A total of 16 articles were included in the review. Seven of the nine cohort studies evaluating male sexual function showed earlier recovery or better outcomes in patients operated with robotic techniques. Two studies did not find any statistically significant difference. Three out of four case series found no difference in sexual function scores measured preoperatively and after 1 year. Female sexual function was assessed in seven studies: two case series show no deterioration of at 1 year. Three comparative studies showed no difference between robotic and laparoscopic groups. Two randomized control trials showed different results in terms of male and female sexual functions with better preservation at 1 year in the robotic group in one and no difference in another. Urinary functions assessed in males and/or females in the 16 studies showed no statistically significant differences at long-term follow-up. At present, there is no evidence of superiority of robotic surgery for performing nerve-sparing rectal cancer surgery.

Role of lymph node ratio in selection of adjuvant treatment (chemotherapy vs. chemoradiation) in patients with resected gastric cancer.

BACKGROUND: Recent randomized controlled trials have failed to show a survival difference between adjuvant chemotherapy (CT) and adjuvant chemoradiotherapy (CRT) in patients with resected gastric cancer (GC). However, a subset of patients with lymph node (LN) positive disease may still benefit from CRT. Additional evidence is needed to help guide physicians in identifying patients in whom CRT should be considered. Our objective was then to compare survival outcomes based on lymph node ratio (LNR) (ratio of metastatic to harvested LNs) for patients with gastric and gastroesophageal junction (GEJ) adenocarcinoma treated with surgery and either CT or CRT. METHODS: This retrospective population-based study used California Cancer Registry (CCR) data from 2004 to 2013. It included 1,493 patients diagnosed with stage IB-III gastric/GEJ adenocarcinoma and treated with CT or CRT following total or partial gastrectomy. Overall survival (OS) was the primary outcome and GC-specific survival was secondary. Mortality hazards ratios (HR) for these outcomes were computed using propensity score weighted Cox regression models, stratified by LNR strata categories as 0%, 1-9%, 10-25% and >25%. RESULTS: Out of 1,493 patients that met inclusion criteria, 462 were treated with CT while 1,031 received CRT. Median follow-up for all subjects was 76 months and median survival was 54 months for CRT and 35 for the CT cohort, P<0.001. Compared to CT, CRT was associated with improved survival among patients with LNR of 10-25% [HR =0.62 (95% CI, 0.46-0.83)] and >25% [HR =0.67 (95% CI, 0.56-0.80)]. Similar findings were observed for GC-specific survival and for analyses limited to patients that had at least 15 LNs evaluated. CONCLUSIONS: LNR appears to be a simple and readily available measure that could be used in treatment planning for resected GC. CRT offers significant survival advantage over CT among patients with high LN disease burden (LNR of ≥10%).

High-Risk Stage II Colon Cancer: Not All Risks Are Created Equal.

INTRODUCTION: Adjuvant chemotherapy is recommended in patients with stage II colon cancer with high-risk features (HRF). However, there is no quantification of the amount of risk conferred by each HRF or the overall survival (OS) benefit gained by chemotherapy based on the risk factor. OBJECTIVE: To assess survival benefits associated with adjuvant chemotherapy among stage II colon cancer patients having one or more HRF [T4 tumors, less than 12 lymph nodes examined (< 12LN), positive margins, high-grade tumor, perineural invasion (PNI), and lymphovascular invasion (LVI)]. METHODS: Patients diagnosed with stage II colon cancer between 2010 and 2013 were identified from California Cancer Registry. Propensity score weighted all-cause mortality hazard ratios (HR) were calculated for combinations of HRF. RESULTS: A total of 5160 stage II colon cancer patients were identified, of which 2398 had at least one HRF and 510 of 2398 (21%) received adjuvant chemotherapy. Compared with patients with a single HRF, presence of any 2 or ≥ 3 HRF showed increasingly poorer survival [HR 1.42, 95% confidence interval (CI) 1.16-1.73 and HR 2.50, 95% CI 1.96-3.20, respectively]. Chemotherapy was associated with improved overall survival only among patients with T4 as the single HRF (HR 0.51, 95% CI 0.34-0.78) or combinations involving T4 as T4/< 12 LN (HR 0.31, 95% CI 0.11-0.90), T4/high grade (HR 0.26, 95% CI 0.11-0.61), and T4/LVI (HR 0.16, 95% CI 0.04-0.61). CONCLUSIONS: Not all high-risk features have similar adverse effects on OS. T4 tumors and their combination with other HRF achieve the most survival benefit with adjuvant therapy. Type and number of high-risk features should be taken into consideration when recommending adjuvant chemotherapy in stage II colon cancer.

Comparison of perioperative chemotherapy with adjuvant chemoradiotherapy for resectable gastric cancer: findings from a population-based study.

BACKGROUND: Both perioperative chemotherapy (PC) and adjuvant chemoradiotherapy (CRT) improve survival in resectable gastric cancer; however, these treatments have never been formally compared. Our objective was to evaluate treatment trends and compare survival outcomes for gastric cancer patients treated with surgery and either PC or CRT. METHODS: We performed a retrospective population-based cohort study between 2007 through 2013 using California Cancer Registry data. Patients diagnosed with stage IB-III gastric adenocarcinoma and treated with total or partial gastrectomy were eligible for this study. Based on the type of treatment received, patients were grouped into surgery-only, PC, or CRT. Primary and secondary outcomes were overall survival (OS) and gastric cancer-specific survival (GCCS) respectively. Mortality hazards ratios (HRs) for each of these outcomes were computed using propensity score weighted and covariate-adjusted Cox regression models, stratified by clinical node status. RESULTS: Of 2,146 patients who underwent surgical resection, 1,067 had surgery-only, while 771 and 308 received PC or CRT, respectively. Median OS was 25, 33, and 52 months for surgery-only, PC, and CRT, respectively; P<0.001. Overall, patients treated with PC had significantly poorer survival compared to CRT (HR =1.45; 95% CI: 1.22-1.73). PC was also associated with higher mortality in patients with signet ring histology (HR =1.66; 95% CI: 1.21-2.28) and clinical node negative cancer (HR =1.85; 95% CI: 1.32-2.60). Survival was not different between PC vs. CRT in clinical node positive patients (HR =1.29; 95% CI: 0.84-2.08). Of note, the percentage of patients receiving PC increased from 17.5% in 2007-2008, to 41.5% in 2013-2014; P<0.001. CONCLUSIONS: Despite the rapid adoption of PC, overall, CRT is associated with better survival than PC. Specifically, clinical node negative and signet ring histology patients had better survival when treated with CRT compared to PC. Based on these findings, we recommend against indiscriminate adoption of PC and consideration for CRT over PC in clinical node negative patients.

Stratifying SLN incidence in intermediate thickness melanoma patients.

BACKGROUND: Guidelines for melanoma recommend sentinel lymph node biopsy (SLNB) in patients with melanomas ≥1 mm thickness. Recent single institution studies have found tumors <1.5 mm a low-risk group for positive SLNB. METHODS: A retrospective review of the Sentinel Lymph Node Working Group multicenter database identified patients with intermediate thickness melanoma (1.01-4.00 mm) who had SLNB, and assessed predictors for positive SLNB. RESULTS: 3460 patients were analyzed, 584 (17%) had a positive SLNB. Univariate factors associated with a positive SLNB included age <60 (p < .001), tumor on the trunk/lower extremity (p < .001), Breslow depth ≥2 mm (p < .001), ulceration (p < .001), mitotic rate ≥1/mm2 (p = .01), and microsatellitosis (p < .001). Multivariate analysis revealed age, location, and Breslow depth as significant predictors. Patients ≥75 with lesions 1.01-1.49 mm on the head/neck/upper extremity and 1.5-1.99 mm without high-risk features had <5% risk of SLN positivity. CONCLUSIONS: Intermediate thickness melanoma has significant heterogeneity of SLNB positivity. Low-risk subgroups can be found among older patients in the absence of high-risk features.

Benefit of Surgical Resection of the Primary Tumor in Patients Undergoing Chemotherapy for Stage IV Colorectal Cancer with Unresected Metastasis.

PURPOSE: Resection of the primary tumor in patients with unresected metastatic colorectal cancer is controversial, and often performed only for palliation of symptoms. Our goal was to determine if resection of the primary tumor in this patient population is associated with improved survival. METHODS: This is a retrospective cohort study of the National Cancer Data Base from 2004 to 2012. The study population included all patients with synchronous metastatic colorectal adenocarcinoma who were treated with systemic chemotherapy. The study groups were patients who underwent definitive surgery for the primary tumor and those who did not. Patients were excluded if they had surgical intervention on the sites of metastasis or pathology other than adenocarcinoma. Primary outcome was overall survival. RESULTS: Of the 65,543 patients with unresected stage IV colorectal adenocarcinoma undergoing chemotherapy, 55% underwent surgical resection of the primary site. Patients who underwent surgical resection of the primary tumor had improved median survival compared to patients treated with chemotherapy alone (22 vs 13 months, p < .0001). The surgical survival benefit was present for patients who were treated with either multi-agent or single-agent chemotherapy (23 vs 14 months, p < 0.001; 19 vs 9 months, p < 0.001). Surgical resection of the primary tumor was also associated with improved survival when using multivariate analysis with propensity score matching (OR = 0.863; 95% CI [0.805-.924]; HR = 0.914; 95% CI [0.888-0.942]). CONCLUSIONS: Our results show that in patients with synchronous unresected stage IV colorectal adenocarcinoma undergoing single- or multi-agent chemotherapy, after adjusting for confounding variables, definitive resection of the primary site was associated with improved overall survival. Large randomized controlled trials are needed to determine if there is a causal relationship between surgery and increased overall survival in this patient population.

Association of Primary Tumor Site With Mortality in Patients Receiving Bevacizumab and Cetuximab for Metastatic Colorectal Cancer.

Importance: Biologic therapy (BT) (eg, bevacizumab or cetuximab) is increasingly used to treat metastatic colorectal cancer (mCRC). Recent investigations have suggested that right- or left-sided primary tumor origin affects survival and response to BT. Objective: To evaluate the association of tumor origin with mortality in a diverse population-based data set of patients receiving systemic chemotherapy (SC) and bevacizumab or cetuximab for mCRC. Design, Setting, and Participants: This population-based nonconcurrent cohort study of statewide California Cancer Registry data included all patients aged 40 to 85 years diagnosed with mCRC and treated with SC only or SC plus bevacizumab or cetuximab from January 1, 2004, through December 31, 2014. Patients were stratified by tumor origin in the left vs right sides. Interventions: Treatment with SC or SC plus bevacizumab or cetuximab. Main Outcomes and Measures: Mortality hazards by tumor origin (right vs left sides) were assessed for patients receiving SC alone or SC plus bevacizumab or cetuximab. Subgroup analysis for patients with wild-type KRAS tumors was also performed. Results: A total of 11 905 patients with mCRC (6713 men [56.4%] and 5192 women [43.6%]; mean [SD] age, 60.0 [10.9] years) were eligible for the study. Among these, 4632 patients received SC and BT. Compared with SC alone, SC plus bevacizumab reduced mortality among patients with right- and left-sided mCRC, whereas SC plus cetuximab reduced mortality only among patients with left-sided tumors and was associated with significantly higher mortality for right-sided tumors (hazard ratio [HR], 1.31; 95% CI, 1.14-1.51; P < .001). Among patients treated with SC plus BT, right-sided tumor origin was associated with higher mortality among patients receiving bevacizumab (HR, 1.31; 95% CI, 1.25-1.36; P < .001) and cetuximab (HR, 1.88; 95% CI, 1.68-2.12; P < .001) BT, compared with left-sided tumor origin. In patients with wild-type KRAS tumors (n = 668), cetuximab was associated with reduced mortality among only patients with left-sided mCRC compared with bevacizumab (HR, 0.75; 95% CI, 0.63-0.90; P = .002), whereas patients with right-sided mCRC had more than double the mortality compared with those with left-sided mCRC (HR, 2.44; 95% CI, 1.83-3.25, P < .001). Conclusions and Relevance: Primary tumor site is associated with response to BT in mCRC. Right-sided primary tumor location is associated with higher mortality regardless of BT type. In patients with wild-type KRAS tumors, treatment with cetuximab benefited only those with left-sided mCRC and was associated with significantly poorer survival among those with right-sided mCRC. Our results underscore the importance of stratification by tumor site for current treatment guidelines and future clinical trials.

Factors Predictive of Outcomes after Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy for Colon and Appendiceal Carcinomatosis: A Single-Institution Experience.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), although considered an acceptable treatment option in the management of selected patients with colon and appendiceal peritoneal carcinomatosis (PC), concerns about morbidity have limited its acceptance. Our objective was to evaluate the short- and long-term outcomes of CRS/HIPEC for appendix and colon PC performed at our institution and to elucidate factors predictive of patient outcomes. All patients who underwent CRS/HIPEC for appendix or colon PC from 2011 to 2017 were identified from our institution's prospective database. Postoperative outcomes, overall survival, and recurrence-free survival were assessed. Of 125 patients who underwent CRS/HIPEC during the study period, 45 patients were eligible (appendix n = 26; colon n = 19). The median postoperative length of stay was nine days (5-28 days). Grade III/IV complications occurred in 4/45 (8.8%) patients. There were no postoperative mortalities. Median DFS and overall survival have not yet been reached, in both the colon and appendix groups. As of the study conclusion date, 37/45 (82.2%) patients were alive with or without disease. Lymph node status was predictive of recurrence in appendix PC. In our experience, CRS/HIPEC can be safely performed with acceptable short- and long-term outcomes. Lymph node status is an important predictor of recurrence.

Attending Surgeon Variation in Operative Case Length: An Opportunity for Quality Improvement.

Balancing resident education with operating room (OR) efficiency, while accommodating different styles of surgical educators and learners, is a challenging task. We sought to evaluate variability in operative time for breast surgery cases. Accreditation Council for Graduate Medical Education case logs of breast operations from 2011 to 2017 for current surgical residents at Loma Linda University were correlated with patient records. The main outcome measure was operative time. Breast cases were assessed as these operations are performed during all postgraduate years (PGY). Breast procedures were grouped according to similarity. Variables analyzed included attending surgeon, PGY level, procedure type, month of operation, and American Society of Anesthesiologists class. Of 606 breast cases reviewed, median overall operative time was 150 minutes (interquartile range 187-927). One-way analysis of covariance demonstrated statistically significant variation in operative time by attending surgeon controlling for covariates (PGY level, procedure, American Society of Anesthesiologists class, and month) (P = 0.04). With institutional OR costs of $30 per minute, the average difference between slowest and fastest surgeon was $2400 per case [(218-138) minutes × $30/min]. Minimizing variability for common procedures performed by surgical educators may enhance OR efficiency. However, the impact of case length on surgical resident training requires careful consideration.