Why the Treatment Sequence Matters: Interplay Between Chemotherapy Cycles Received, Cumulative Dose Intensity, and Survival in Resected Early-stage Pancreas Cancer.

OBJECTIVE: To define the optimal threshold of perioperative chemotherapy completion and relative dose intensity (RDI) for patients with resected pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Many patients who undergo pancreatectomy for PDAC fail to initiate or complete recommended perioperative chemotherapy. The association between the amount of perioperative chemotherapy received and overall survival (OS) is not well-defined. METHODS: Single-institution analysis of 225 patients who underwent pancreatectomy for stage I/II PDAC (2010-2021). Associations between OS, chemotherapy cycles completed, and RDI were analyzed. RESULTS: Regardless of treatment sequence, completion of ≥67% of recommended cycles was associated with improved OS compared with no chemotherapy [median OS: 34.5 vs 18.1 months; hazard ratio (HR): 0.43; 95% CI: 0.25-0.74] and <67% of cycles (median OS: 17.9 months; HR: 0.39; 95% CI: 0.24-0.64). A near-linear relationship existed between cycles completed and the RDI received (ß = 0.82). A median RDI of 56% corresponded to the completion of 67% of cycles. Receipt of ≥56% RDI was associated with improved OS compared with no chemotherapy (median OS: 35.5 vs 18.1 months; HR: 0.44; 95% CI: 0.23-0.84) and <56% RDI (median OS: 27.2 months; HR: 0.44; 95% CI: 0.20-0.96). Neoadjuvant chemotherapy is associated with increased odds of receiving ≥67% of recommended cycles (odds ratio: 2.94; 95% CI: 1.45-6.26) and ≥56% RDI (odds ratio: 4.47; 95% CI: 1.72-12.50). CONCLUSIONS: Patients with PDAC who received ≥67% of recommended chemotherapy cycles or ≥56% cumulative RDI had improved OS. Neoadjuvant therapy was associated with increased odds of receiving ≥67% of cycles and ≥56% cumulative RDI and should be considered in all patients with resectable PDAC.

Survival in elderly patients with breast cancer with and without autoimmune disease.

BACKGROUND: Patients with certain autoimmune conditions are at a reduced risk of developing breast cancer compared to the general population. Despite this, little is known about outcomes in patients with breast cancer who have a concurrent autoimmune diagnosis. METHODS: This study compared differences in outcomes between women with breast cancer who had or did not have an autoimmune diagnosis. The SEER-Medicare databases (2007-2014) were used to identify patients with breast cancer and diagnosis codes were used to identify those with an autoimmune disorder. RESULTS: The studied autoimmune diseases had a prevalence of 27% among the 137,324 patients with breast cancer. Autoimmune disease was associated with significantly longer overall survival (OS) and significantly lower cancer-specific mortality (CSM) among stage IV breast cancer patients (p < 0.0001). After controlling for the effects of age, race, chronic kideny disease, chemotherapy, and radiation therapy autoimmune disease was still predictive of improved OS (HR: 1.45, 95% CI: 1.35-1.55, p < 0.0001) and CSM (HR: 1.40, 95% CI: 1.29-1.5, p < 0.0001). By contrast, in patients with stage I-III breast cancer, the presence of an autoimmune diagnosis was associated with a lower OS (p < 0.0001, p < 0.0001, and p = 0.026, respectively), compared to patients without autoimmune disease. CONCLUSIONS: We found a higher prevalence of rheumatoid arthritis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus in patients with breast cancer compared to age matched cohorts in the general population. The presence of an autoimmune diagnosis was associated with a lower OS in stages I-III breast cancer and improved OS and CSM in patients with stage IV disease. These results suggest that anti-tumor immunity plays an important role in late stage breast cancer and could potentially be exploited to improve the effectiveness of immunotherapy.

Discordance Between Conventional and Detailed Lymph Node Analysis in Resected, Node-negative Pancreatic or Ampullary Adenocarcinomas and Association With Adverse Survival Outcomes: A Single-institution Analysis.

OBJECTIVE: To assess the frequency of occult metastases (OM) in patients with resected pancreatic ductal adenocarcinoma (PDAC) or ampullary adenocarcinoma (AA) discovered on detailed pathologic examination on lymph nodes (LNs) previously considered negative by conventional analysis and to examine the association between OM and overall survival (OS). BACKGROUND: Poor prognosis of patients with no pathologic evidence of LN metastases may be due to OM that is not detected on conventional LN analysis. METHODS: Patients with LN-negative resected PDAC or AA (2010-2020) were identified from our institutional database. Original hematoxylin and eosin ( H and E ) slides were reanalyzed. In addition, selected LN were analyzed by H and E (3 sections/LN) and pan-cytokeratin (AE1-AE3/PCK26) immunohistochemistry. RESULTS: A total of 598 LNs from 74 LN-negative patients were reexamined. Nineteen patients (25.7%) had OM; 9 (47.4%) were found with immunohistochemistry but not on H and E . The number of positive LNs ranged from 1 to 3. No clinicodemographic, pathologic, or treatment-related factors were associated with OM. On conventional LN analysis, 3/19 patients (15.8%) had stage IA, 9/34 (26.5%) had stage IB, and 7/19 (36.8%) had stage IIA. On detailed LN analysis, 11/19 patients (57.9%) were upstaged to IIB, whereas 8/19 (42.1%) had isolated tumor cells only (N0i+). OM was associated with shorter OS (median OS: 22.3 vs 50.5 months; hazard ratio=3.95, 95% CI: 1.58-9.86). CONCLUSIONS: There is a 26% discordance rate between conventional and detailed LN pathologic analysis in resected PDAC and AA. The presence of OM is associated with shorter OS.

An Analysis of Cancer Center-Provided Rideshare Utilization for Radiation Therapy.

OBJECTIVES: The potential of rideshare services to facilitate timely radiation therapy (RT), especially for resource-limited patients, is understudied. METHODS: Patients (n = 63) who received 73 courses of RT (1,513 fractions) and utilized free hospital-provided rideshare service (537 rides) were included in this retrospective study. A multidimensional analysis was conducted including a comparison of demographic, disease characteristics, and treatment completion data; a revenue analysis to evaluate the financial impact of rideshare services; and a geospatial analysis to evaluate community-level characteristics of patients. RESULTS: Median age was 59; most were female (56%) and self-identified as Black or African American (56%), not working (91%), not partnered (83%), high school educated or less (78%), and insured with Medicaid (51%). Geospatial analysis revealed that patients lived in communities with significantly higher rates of resource deprivation. Median rideshare distance was 6.4 miles (interquartile range 3.4-11.2) with a median cost of $13.04 per rideshare (interquartile range 9-19). Of the rideshare-facilitated treatments, 100% were completed, with an overall course completion rate of 97.3% compared with 85.4% for those who did not use rideshare (P = .001); two patients discontinued RT for reasons unrelated to transportation. High rideshare utilization (n = 32), defined as utilization ≥ 45% of the treatment course, was associated with significantly shorter treatment courses and lower radiation doses compared with low rideshare utilization (P = .04). Total rideshare cost for high utilizers and whole cohort was $11,589 and $16,895, facilitating an estimated revenue of $401,952 and $1,175,119, respectively. CONCLUSIONS: Free hospital-provided rideshare service is economically feasible and associated with high RT completion rates. It may help enhance quality radiation care for those who come from resource-limited communities.

Comparing Survival in Patients With Lung Cancer With and Without a History of Common Autoimmune Disease.

Introduction: Autoimmune disease has both a predisposing and a protective effect toward malignancy. Though studies have investigated the risk of malignancy in patients with autoimmune disease, there is limited research on how autoimmunity affects survival. Methods: This study compared survival in patients with lung cancer with and without autoimmune disease. Patients with lung cancer were culled from the Surveillance, Epidemiology, and End Results Medicare databases (2007-2014), and autoimmune diseases were identified using diagnosis codes. Results: The overall prevalence of investigated autoimmune diseases among the 112,445 patients was 22.7%. Overall survival (OS) (p < 0.0001) was longer and cancer-specific mortality (CSM) (p < 0.0001) reduced among patients with autoimmune disease. Median OS was 5 months higher. Improved OS and CSM were also apparent in disease stages 1, 3, and 4 in the NSCLC and SCLC subgroups (p < 0.0001) and across most specific autoimmune diseases. After adjusting for the effects of age, sex, race, disease stage, and chronic kidney disease, autoimmune disease was still predictive of higher OS (hazard ratio = 1.23, 95% confidence interval: 1.21-1.25, p < 0.0001) and reduced CSM (hazard ratio = 1.16, 95% confidence interval: 1.14-1.18, p < 0.0001). Conclusions: The prevalence of rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematous was highly enriched compared with the general population. The improvement in OS and CSM was larger in NSCLC than in SCLC, suggesting a larger role for the immune system in NSCLC. Alternate explanations for the improved survival include lead time bias, better access to health care, and a survival or autoimmunity-inducing genetic factor.

Prodromal depression and anxiety are associated with worse treatment compliance and survival among patients with pancreatic cancer.

OBJECTIVE: To determine the frequency of depression or anxiety preceding a diagnosis of pancreatic cancer (PC). Further, to examine the association of PC-associated depression or anxiety with treatment compliance and survival. METHODS: 856 patients with PC from a single institution were identified using International Classification of Diseases (ICD) codes. For each case, two non-cancer age- and sex-matched controls were included. Dates of depression or anxiety diagnosis identified using ICD codes were compared to the date of PC diagnosis. The medical record was queried to further explore psychiatric symptoms. Multivariable analyses were performed to examine if prediagnosis depression or anxiety was associated with receipt of treatment or survival. RESULTS: A greater proportion of patients with PC experienced depression or anxiety in the year preceding diagnosis than the overall frequency in controls (4.6% vs. 2.6%, p = 0.005) based on ICD codes. Patients with PC exhibited signs of prodromal depression or anxiety based on ICD codes, clinical documentation of psychiatric symptoms, or initiation of new psychiatric medications more often than controls (20.7% vs. 6.7%, p < 0.001). Prediagnosis depression or anxiety was associated with a reduced likelihood of receiving chemotherapy (OR = 0.58, p = 0.04). There was an associated decrease in overall survival among patients with metastatic disease who experienced depression or anxiety before PC diagnosis (HR = 1.32, p = 0.04). CONCLUSIONS: The frequency of depression or anxiety among patients with PC was higher than the general population. Prediagnosis psychiatric symptoms were associated with reduced chemotherapy utilization and worse overall survival. Thus, timely identification and treatment of these symptoms may improve outcomes.

Weight Tracking as a Novel Prognostic Marker After Pancreatectomy.

BACKGROUND: Objective measures of post-pancreatectomy weight change for pancreatic ductal adenocarcinoma (PDAC) have not been extensively studied for long-term outcomes. We used weight measurements in our institutional medical record to analyze trends in post-pancreatectomy weight and determine the association with disease status. METHODS: Pancreatectomies for PDAC (n = 315) and benign indications (n = 111) were identified. Preoperative baseline, minimum postoperative (Min #1), and subsequent postoperative maximum (Max) weights were abstracted. Multivariable Cox hazards regression was conducted to analyze the association between weight change and survival. RESULTS: Median weight loss postoperatively in each group was > 20 lbs. PDAC patients gained 10 lbs after Min #1 compared to 15 lbs in the benign cohort (p < 0.001). Few patients returned to their preoperative weight (29.8% PDAC vs. 40.5% benign, p = 0.04). Patients with early PDAC recurrence (< 13 months) lost more weight (18.0% vs. 13.3% vs. 10.9%, p < 0.001) and gained less weight (2.1% vs. 12.0% vs. 7.9%, p < 0.001) compared with those with late cancer recurrence (≥ 13 months) or no evidence of active disease, respectively. PDAC patients lost 11.2 lbs in the year preceding recurrence diagnosis. Weight loss was not associated with survival; however, weight gain was associated with improved survival. CONCLUSIONS: Resections for PDAC are complicated by a similar degree of weight loss as patients with benign disease, and there is no association with survival. However, failure to gain weight is especially ominous. Weight loss after weight recovery foreshadows disease recurrence. These data suggest that rigorous weight tracking is an untapped surveillance strategy in patients with PDAC.

Weight loss during neoadjuvant therapy for pancreatic cancer does not predict poor outcomes.

BACKGROUND: Weight changes during neoadjuvant chemotherapy (NAC) for pancreatic cancer (PDAC) are not well studied. We hypothesized that weight loss may predict poor outcomes. METHODS: Weight change from NAC initiation to pancreatectomy was grouped: gain (≥5%), stable, and loss (≥5%). Pathologic, postoperative, and survival outcomes were compared. RESULTS: 95 patients were included: 31.6% lost weight, 58.9% maintained weight, and 9.5% gained weight. There were no differences in chemotherapeutic regimens. Median recurrence-free survival (RFS) and overall survival (OS) were similar between patients with stable weight and those who lost weight (RFS: 9.6vs14.0months; OS: 25.8vs26.7months). Among those who gained weight, RFS (29.5months) and OS (38.4months) were greater relative to the other weight categories. On multivariable regression, weight gain was associated with improved RFS compared to loss (HR = 0.16). CONCLUSION: Most patients maintain or lose weight during NAC, and weight loss does not predict poor outcomes. Weight gain may predict improved RFS.

The Negative Impact of the COVID-19 Pandemic on Oncology Care at an Academic Cancer Referral Center.

Objectives: COVID-19 created unexpected delays in oncologic treatment. This study sought to assess the volume of missed cancer-related services due to the pandemic. Methods: This case-controlled trial evaluated more than 345,000 oncologic clinic, lab, and radiation appointments from January 1, 2019, through December 31, 2020, and surgery appointments from January 1, 2019, through October 31, 2020. All patients at the Seidman Cancer Center with a cancer diagnosis based on a comprehensive list of 2178 International Classification of Diseases, Ninth Edition (ICD-9) and ICD-10 codes were included in the analysis. Subgroup analyses based on age, race, and sex were also performed. Results: Clinic, lab, and surgical visit cancellations increased by 4.20% (P <.001), 4.84% (P <.001), and 5.22% (P <.001), respectively. In the first 10 months of 2020, there were 703 (9.2%) fewer surgeries compared with the same time period in 2019. The following cancellation rates peaked in March 2020: clinic visits (26.53%), labs (43.66%), surgery (34.00%). Radiation oncology (12.53%) cancellations peaked in April 2020. Prior to the emergence of COVID-19, the group aged 0 to 39 years had the highest clinic cancellation rate (17.85%) compared with patients aged 40 to 64 years (15.95%) and 65 years and older (14.52%; P <.001). Men cancelled (15.63%) significantly more often than women (14.93%; P <.001) in 2019. This reversed during the pandemic: Women (19.56%) cancelled more frequently than men (19.20%; P <.036). Conclusions: There was a large increase in cancelled oncologic care in 2020, which has implications for delayed diagnosis and treatment. This was especially true for patients older than 65 years and for women. These delays could result in patients presenting with more advanced disease, complicating morbidities, and ultimately worse long-term outcomes.

Weight Loss as an Untapped Early Detection Marker in Pancreatic and Periampullary Cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has the worst survival of common cancers, partly because there are no reliable early detection tests. Unintentional weight loss (≥ 5% decrease from baseline) has been linked to PDAC, but the frequency and severity of weight loss using objective measures, and its relationship to prognosis, have not been well characterized. METHODS: We identified 390 patients with PDAC (all stages) and two or more prediagnosis weights in the electronic medical record. Percentage weight loss in the 365 and 180 days preceding diagnosis was calculated. Results were compared with raw weights of age- and sex-matched non-cancer controls (n = 780). Odds ratios for PDAC were calculated using conditional logistic regression. Cox proportional hazards models were used for survival. RESULTS: Within 1 year of diagnosis, more PDAC patients lost ≥ 5% weight relative to controls (74.9% vs. 11.2%; p < 0.001), with a median weight loss of 14.2 versus 2.9 lbs. The odds ratio for PDAC comparing weight loss within 1 year of 5 to < 10% was 10.30 (p < 0.001) and 77.82 for ≥ 10% (p < 0.001), compared with stable weight. Weight loss prior to diagnosis was also associated with early-stage PDAC. PDAC cases with ≥ 10% prediagnosis weight loss had worse survival compared with stable weights (hazard ratio [HR] 1.60; p = 0.01). Greater prediagnosis weight loss was associated with poor survival after pancreatectomy (5 to < 10% vs. < 5%, HR 2.40, p = 0.03; ≥ 10% vs. < 5%, HR 2.59, p = 0.03). CONCLUSIONS: Diagnosis of PDAC is preceded by unintentional weight loss in the majority of patients, even at an early stage. Greater prediagnosis weight loss severity is also associated with poor postoperative survival.