Germline Genetic Testing Among Women ≤ 45 Years of Age with Ductal Carcinoma In Situ Versus Invasive Breast Cancer in a Large Integrated Health Care System.

BACKGROUND: We compared the results of hereditary cancer multigene panel testing among patients ≤ 45 years of age diagnosed with ductal carcinoma in situ (DCIS) versus invasive breast cancer (IBC) in a large integrated health care system. METHODS: A retrospective cohort study of hereditary cancer gene testing among women ≤ 45 years of age diagnosed with DCIS or IBC at Kaiser Permanente Northern California between September 2019 and August 2020 was performed. During the study period, institutional guidelines recommended the above population be referred to genetic counselors for pretesting counseling and testing. RESULTS: A total of 61 DCIS and 485 IBC patients were identified. Genetic counselors met with 95% of both groups, and 86.4% of DCIS patients and 93.9% of IBC patients (p = 0.0339) underwent gene testing. Testing differed by race/ethnicity (p = 0.0372). Among those tested, 11.76% (n = 6) of DCIS patients and 16.71% (n = 72) of IBC patients had a pathogenic variant (PV) or likely pathogenic variant (LPV) based on the 36-gene panel (p = 0.3650). Similar trends were seen in 13 breast cancer (BC)-related genes (p = 0.0553). Family history of cancer was significantly associated with both BC-related and non-BC-related PVs in IBC, but not DCIS. CONCLUSION: In our study, 95% of patients were seen by a genetic counselor when age was used as an eligibility criterion for referral. While larger studies are needed to further compare the prevalence of PVs/LPVs among DCIS and IBC patients, our data suggest that even in younger patients, the prevalence of PVs/LPVs in BC-related genes is lower in DCIS patients.

Survival of Elderly Patients Undergoing Pancreatoduodenectomy in an Integrated Health System.

INTRODUCTION: The purpose of this study is to examine pancreatoduodenectomy (PD) perioperative outcomes and consider how age may be related to overall survival in an integrated health system. MATERIALS AND METHODS: A retrospective review was performed of 309 patients who underwent PD between December 2008 and December 2019. Patients were divided into two groups: aged 75 y or less and more than 75 y, defined as senior surgical patients. Univariate and multivariable analyses of predictive clinicopathologic factors associated with overall survival at 5 y were performed. RESULTS: In both groups, the majority underwent PD for malignant disease. The proportion of senior surgical patients alive at 5 y was 33.3% compared to 53.6% of younger patients (P = 0.003). There were also statistically significant differences between the two groups with respect to body mass index, cancer antigen 19-9, Eastern Cooperative Oncology Group performance status, and Charlson comorbidity index. On multivariable analysis, disease type, cancer antigen 19-9, hemoglobin A1c, length of surgery, length of stay, Charlson comorbidity index, and Eastern Cooperative Oncology Group performance status were found to be statistically significant factors for overall survival. Age was not significantly related to overall survival on multivariable logistic regression and when the analysis was limited to pancreatic cancer patients. CONCLUSIONS: Although the difference in overall survival between patients aged less than and more than 75 years was significant, age was not an independent risk factor for overall survival on multivariable analysis. Rather than a patient's chronological age, his/her physiologic age including medical comorbidities and functional status may be more correlated to overall survival.

Utilization and Outcomes of Observation for Spontaneous Pneumothorax at an Integrated Health System.

INTRODUCTION: Though limited, recent evidence supports observation rather than intervention for spontaneous pneumothorax management. We sought to compare the utilization and outcomes between observation and intervention for patients with primary and secondary spontaneous pneumothoraces. METHODS: A retrospective cohort study of all adults presenting to Kaiser Permanente Northern California emergency rooms with spontaneous pneumothorax from 2016 to 2020 was performed. Those with prior pneumothoraces, tension physiology, bilateral pneumothoraces, effusions, and prior thoracic procedures or surgery on the affected side were excluded. Groups included observation versus intervention. Baseline clinicodemographic variables and outcomes were compared. Treatment was considered successful if further interventions were not required for pneumothorax resolution. Wilcoxon rank-sum tests, chi-square tests, Fischer exact tests, and multivariable logistic regression models were performed. RESULTS: Of the 386 patients with primary spontaneous pneumothorax, age, race/ethnicity, body mass index, smoking status, and the Charlson comorbidity index were not different between treatment groups. Of 86 patients with secondary spontaneous pneumothorax, age, gender, and smoking status were not different between treatment groups. Among patients with primary pneumothoraces, 83 underwent observation while 303 underwent intervention. The success rate was 92.8% for observation and 60.4% for intervention (P < 0.0001). Among patients with secondary pneumothoraces, 15 underwent observation while 71 underwent intervention, with a successful rate of 73.3% for observation and 32.4% for intervention (P = 0.003). CONCLUSIONS: Given the high success rates for observation of both small and moderate primary and secondary pneumothoraces, observation should be considered for clinically stable patients. Observation may be the superior choice for decreasing morbidity and healthcare costs.

Association of Surgical Timing with Outcomes in Early Stage Lung Cancer.

BACKGROUND: Optimal time to surgery for lung cancer is not well established. We aimed to assess whether time to surgery correlates with outcomes. METHODS: We assessed patients 18-84 years old who were diagnosed with stage I/II lung cancer at our integrated healthcare system from 2009 to 2019. Time to surgery was defined to start with disease confirmation (imaging or biopsy) prior to the surgery scheduling date. Outcomes of unplanned return to care within 30 days of lung cancer surgery, all-cause mortality, and disease recurrence were compared based on time to surgery before and after 2, 4, and 12 weeks. RESULTS: Of 2861 included patients, 70% were over 65 years old and 61% were female. Time to surgery occurred in 1-2 weeks for 6%, 3-4 weeks for 31%, 5-12 weeks for 58%, and 13-26 weeks for 5% of patients. Patients with time to surgery > 4 (vs. ≤ 4) weeks had greater risk of both death (hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.00-1.39) and recurrence (HR 1.33, 95% CI 1.10-1.62). Associations were not statistically significant when dichotomizing time to surgery at 2 or 12 weeks for death (2 week HR 1.23, 95% CI 0.93-1.64; 12 week HR 1.35, 95% CI 0.97-1.88) and recurrence (2 week HR 1.54, 95% CI 0.85-2.80; 12 week HR 2.28, 95% CI 0.80-6.46). CONCLUSIONS: Early stage lung cancer patients with time to surgery within 4 weeks experienced lower rates of recurrence. Optimal time to surgical resection may be shorter than previously reported.

Pancreatic Adenosquamous Carcinoma: Experience Within an Integrated Health Care System.

Introduction Adenosquamous carcinoma (ASC) of the pancreas is a rare form of pancreatic cancer with a worse prognosis than pancreatic ductal adenocarcinoma. The authors report on a retrospective study of 13 patients diagnosed with ASC in an integrated health care system. Methods A retrospective review was performed of all patients with pancreatic cancer identified between February 2010 and December 2018. Twenty-three patients were diagnosed with pancreatic ASC. Patient demographics, tumor characteristics, treatment modalities, and median survival were evaluated. Results Median overall survival was 8 months (standard devision [SD] = 18.6). Eight out of 13 patients who received surgery upfront had a positive surgical margin (62%). Eleven patients received adjuvant therapy. Median survival for patients who received multimodal treatment was 57 months (SD = 5.7) compared with 2.5 months for patients who received only surgery. Median survival for patients with negative pathologic margins was 17 months (SD = 23.6). One patient was receiving neoadjuvant chemotherapy (6 months into treatment without any evidence of metastatic disease). Discussion The high proportion of positive surgical margins and large tumor size upon presentation suggest that primary tumor downstaging should be considered. The positive results from recent prospective trials on neoadjuvant chemoradiation for pancreatic ductal adenocarcinoma could be a promising foundation of information for the treatment of ASC. Conclusion ASC of the pancreas is an extremely aggressive malignancy with poor prognosis. Further work is needed to determine the optimal multimodal treatment regimen.

Sociodemographic and clinical characteristics associated with never-smoking status in patients with lung cancer: findings from a large integrated health system.

Background: Evidence is limited characterizing sociodemographically diverse patient populations with lung cancer in relation to smoking status. Methods: In a cross-sectional analysis of adults diagnosed with lung cancer at ages ≥30 years from 2007-2018 within an integrated healthcare system, overall and sex-specific prevalence of never smoking were estimated according to sociodemographic and clinical characteristics. Adjusted prevalence ratio (aPR) and 95% confidence interval (CI) were also estimated using modified Poisson regression to identify patient characteristics associated with never smoking, overall and by sex. Similar analyses were conducted to explore whether prevalence and association patterns differed between non-Hispanic White and Asian/Pacific Islander patients. Results: Among 17,939 patients with lung cancer, 2,780 (15.5%) never smoked and 8,698 (48.5%) had adenocarcinoma. Overall prevalence of never smoking was higher among females than males (21.2% vs. 9.2%, aPR 2.13, 95% CI: 1.98-2.29); Asian/Pacific Islander (aPR 2.85, 95% CI: 2.65-3.07) and Hispanic (aPR 1.72, 95% CI: 1.51-1.95) than non-Hispanic White patients; patients who primarily spoke Spanish (aPR 1.60, 95% CI: 1.32-1.94), any Asian language (aPR 1.20, 95% CI: 1.10-1.30), or other languages (aPR 1.84, 95% CI: 1.27-2.65) than English; patients living in the least vs. most deprived neighborhoods (aPR 1.36, 95% CI: 1.24-1.50); and patients with adenocarcinoma (aPR 2.57, 95% CI: 2.18-3.03), other non-small cell lung cancer (NSCLC) (aPR 2.00, 95% CI: 1.63-2.45), or carcinoid (aPR 3.60, 95% CI: 2.96-4.37) than squamous cell carcinoma tumors. Patterns of never smoking associated with sociodemographic, but not clinical factors, differed by sex. The higher prevalence of never smoking associated with Asian/Pacific Islander race/ethnicity was more evident among females (aPR 3.30, 95% CI: 2.95-3.47) than males (aPR 2.25, 95% CI: 1.92-2.63), whereas the higher prevalence of never smoking associated with living in the least deprived neighborhoods was more evident among males (aPR 1.93, 95% CI: 1.56-2.38) than females (aPR 1.18, 95% CI: 1.06-1.31). Associations between primary language and never-smoking status were found only among females. Overall and sex-specific prevalence and association patterns differed between Asian/Pacific Islander and non-Hispanic white patients. Conclusions: Our findings suggest that patterns of never-smoking status associated with sociodemographic and clinical characteristics are different across sex and race/ethnicity among patients with lung cancer. Such data are critical to increasing awareness and expediting diagnosis of this disease.

Comparison of Survival by Multimodal Treatment Regimen Among Malignant Pleural Mesothelioma Patients in an Integrated Health System.

BACKGROUND: Optimal therapy for malignant pleural mesothelioma (MPM) remains unclear. We compared overall survival in patients with MPM after various multimodal treatment regimens including combinations of immunotherapy, chemotherapy, and surgery. PATIENTS AND METHODS: We examined MPM patients treated within our integrated health system from January 1, 2009 to December 31, 2020. Patients were grouped based on treatment regimen: chemotherapy alone (CT), immunotherapy with or without chemotherapy (iCT), surgery with chemotherapy (sCT), and surgery with immunotherapy and chemotherapy (siCT). We analyzed baseline characteristics and overall patient survival among these groups and several subgroups. RESULTS: One hundred seventy-nine patients were included. Among the study groups, there was no difference in age, sex, race/ethnicity, Charlson Comorbidity Index, or Eastern Cooperative Oncology Group performance status. Patients treated with CT (N = 109), iCT (N = 35), sCT (N = 26), and siCT (N = 9) had median (95% confidence interval) survivals of 11.7 (9.9-16.3), 18.2 (14.5-29.8), 20.7 (11.6-37.2), and 22.6 (19.7-37.8) months, respectively (P < .001). Median survival among patients with and without immunotherapy was 19.7 (17.4-29.8) and 12.3 (10.6-17.3) months, respectively (P = .023). Median survival among patients with and without surgery was 21.7 (17.6-34.8) and 13.6 (11.5-17.3) months, respectively (P = .007). Patients with biphasic/sarcomatoid subtypes who received immunotherapy experienced 76.2% (55.8%-100.0%) 12 month survival vs. 13.6% (4.8%-39.0%) among those who did not (P < .001). CONCLUSION: MPM patients receiving surgery and immunotherapy as part of multimodal treatment regimens experienced the longest survival. Surgery and immunotherapy are each associated with survival. Further investigations are warranted to assess the benefit of immunotherapy within multimodal treatment regimens for MPM.

Predicting early discharge and readmission following pancreaticoduodenectomy [S079].

INTRODUCTION: Implementing enhanced recovery after surgery (ERAS) protocols for major abdominal surgery has been shown to decrease length of stay (LOS) and postoperative complications, including mortality and readmission. Little is known to guide which patients undergoing pancreaticoduodenectomy (PD) should be eligible for ERAS protocols. METHODS AND PROCEDURES: A retrospective chart review of all PD performed from 2010 to 2018 within an integrated healthcare system was conducted. A predictive score that ranges from 0 to 4 was developed, with one point assigned to each of the following: obesity (BMI > 30), operating time > 400 min, estimated blood loss (EBL) > 400 mL, low- or high-risk pancreatic remnant (based on the presence of soft gland or small duct). Chi-squared tests and ANOVA were used to assess the relationship between this score and LOS, discharge before postoperative day 7, readmission, mortality, delayed gastric emptying (DGE), and pancreatic leak/fistula. RESULTS: 291 patients were identified. Mean length of stay was 8.5 days in those patients who scored 0 compared to 16.2 days for those who scored 4 (p = 0.001). 30% of patients who scored 0 were discharged before postoperative day 7 compared to 0% of those who scored 4 (p = 0.019). Readmission rates for patients who scored 0 and 4 were 12% and 33%, respectively (p = 0.017). Similarly, postoperative pancreatic fistula occurred in 2% versus 25% in these groups (p = 0.007). CONCLUSION: A simple scoring system using BMI, operating time, EBL, and pancreatic remnant quality can help risk-stratify postoperative PD patients. Those with lower scores could potentially be managed via an ERAS protocol. Patients with higher scores required longer hospitalizations, and adjunctive therapy such as medication and surgical technique to decrease risk of delayed gastric emptying and pancreatic fistula could be considered.

Pancreatic Neuroendocrine Tumor: Rationale for Centralization in an Integrated Health Care System.

OBJECTIVES: Given the complex surgical management and infrequency of pancreatic neuroendocrine tumor, we hypothesized that treatment at a center of excellence improves survival. METHODS: Retrospective review identified 354 patients with pancreatic neuroendocrine tumor treated between 2010 and 2018. Four hepatopancreatobiliary centers of excellence were created from 21 hospitals throughout Northern California. Univariate and multivariate analyses were performed. The χ2 test of clinicopathologic factors determined which were predictive for overall survival (OS). RESULTS: Localized disease was seen in 51% of patients, and metastatic disease was seen in 32% of patients with mean OS of 93 and 37 months, respectively (P < 0.001). On multivariate survival analysis, stage, tumor location, and surgical resection were significant for OS (P < 0.001). All stage OS for patients treated at designated centers was 80 and 60 months for noncenters (P < 0.001). Surgery was more common across stages at the centers of excellence versus noncenters at 70% and 40%, respectively (P < 0.001). CONCLUSIONS: Pancreatic neuroendocrine tumors are indolent but have malignant potential at any size with management often requiring complex surgeries. We showed survival was improved for patients treated at a center of excellence, where surgery was more frequently utilized.

Centralization of pancreatic cancer treatment within an integrated healthcare system improves overall survival.

BACKGROUND: Higher-volume centers for pancreatic cancer surgeries have been shown to have improved outcomes such as length of stay. We examined how centralization of pancreatic cancer care within a regional integrated healthcare system improves overall survival. METHODS: We conducted a retrospective study of 1621 patients treated for pancreatic cancer from February 2010 to December 2018. Care was consolidated into 4 Centers of Excellence (COE) in surgery, medical oncology, and other specialties. Descriptive statistics, bivariate analysis, Chi-square tests, and Kaplan-Meier analysis were performed. RESULTS: Neoadjuvant chemotherapy use rose from 10% to 31% (p < .001). The median overall survival (OS) improved by 3 months after centralization (p < .001), but this did not reach significance on multivariate analysis. CONCLUSIONS: Our results suggest that in a large integrated healthcare system, centralization improves overall survival and neoadjuvant therapy utilization for pancreatic cancer patients.