INTRODUCTION: Pancreatic cancer (PC) surgery has been associated with improved outcomes and value when performed at high-volume centers (HVC; ≥20 surgeries annually) compared to low-volume centers (LVC). Some have used these differences to suggest that regionalization of PC surgery would optimize patient outcomes and expenditures. METHODS: A Markov model was created to evaluate 30-day mortality, 30-day complications, and 30-day costs. The differences in these outcome measures between the current and future states were measured to assess the population-level benefits of regionalization. A sensitivity analysis was performed to evaluate the impact of variations of input variables in the model. RESULTS: Among 5958 new cases of pancreatic cancer in California in 2021, a total of 2443 cases (41 %) would be resectable; among patients with resectable PC, a total of 977 (40 %) patients would undergo surgery. In aggregate, HVC and LVC 30-day postoperative complications occurred in 364 patients, 30-day mortality in 35 patients, and healthcare costs expended managing complications were $6,120,660. In the predictive model of complete regionalization to only HVC in California, an estimated 29 fewer complications, 17 fewer deaths, and a cost savings of $487,635 per year would occur. CONCLUSIONS AND RELEVANCE: Pancreatic cancer (PC) surgery has been associated with improved outcomes and value when performed at high-volume centers (HVC; ≥20 surgeries annually) compared to low-volume centers (LVC). Complete regionalization of pancreatic cancer surgery predicted benefits in mortality, complications and cost, though implementing this strategy at a population-level may require investment of resources and redesigning care delivery models.

Background

Volume of operative cases may be an important factor associated with improved survival for early-stage pancreatic cancer. Most high-volume pancreatic centers are also academic institutions, which have been associated with additional healthcare costs. We hypothesized that at high-volume centers, the value of the extra survival outweighs the extra cost.

Study design

This retrospective cohort study used data from the California Cancer Registry linked to the Office of Statewide Health Planning and Development database from January 1, 2004 through December 31, 2012. Stage I-II pancreatic cancer patients who underwent resection were included. Multivariable analyses estimated overall survival and 30-day costs at low- vs high-volume pancreatic surgery centers. The incremental cost-effectiveness ratio (ICER) and incremental net benefit (INB) were estimated, and statistical uncertainty was characterized using net benefit regression.

Results

Of 2,786 patients, 46.5% were treated at high-volume centers and 53.5% at low-volume centers. There was a 0.45-year (5.4 months) survival benefit (95% CI 0.21-0.69) and a $7,884 extra cost associated with receiving surgery at high-volume centers (95% CI $4,074-$11,694). The ICER was $17,529 for an additional year of survival (95% CI $7,997-$40,616). For decision-makers willing to pay more than $20,000 for an additional year of life, high-volume centers appear cost-effective.

Conclusions

Although healthcare costs were greater at high-volume centers, patients undergoing pancreatic surgery at high-volume centers experienced a survival benefit (5.4 months). The extra cost of $17,529 per additional year is quite modest for improved survival and is economically attractive by many oncology standards.

Objectives

Comorbid psychiatric illness has been associated with worse outcomes after some major surgical procedures. We hypothesized that patients with preexisting mood disorders would have worse postoperative and oncologic outcomes after pancreatic cancer resection.

Methods

This retrospective cohort study analyzed Surveillance, Epidemiology, and End Results patients with resectable pancreatic adenocarcinoma. A preexisting mood disorder was classified if a patient was diagnosed and/or treated with medication approved for depression/anxiety within 6 months before surgery.

Results

Of 1305 patients, 16% had a preexisting mood disorder. Mood disorders had no impact on hospital length of stay (12.9 vs 13.2 days, P = 0.75), 30-day complications (26% vs 22%, P = 0.31), 30-day readmissions (26% vs 21%, P = 0.1), or mortality (30 days: 3% vs 4%, P = 0.35); only an increased 90-day readmissions rate (42% vs 31%, P = 0.001) was observed. No effect on adjuvant chemotherapy receipt (62.5% vs 69.2%, P = 0.06) or survival (24 months, 43% vs 39%, P = 0.44) was observed.

Conclusions

Preexisting mood disorders influenced 90-day readmissions after pancreatic resection, but not other postoperative or oncologic outcomes. These findings suggest that affected patients should be expected to have outcomes similar to patients without mood disorders.

Purpose

Breast cancer (BC) is the most common secondary cancer and has poorer survival than primary BC (pBC) after any prior malignancy. For BC survivors, developing a contralateral secondary BC (CSBC) is the most frequent second-cancer event and is currently treated similarly to pBC. Identifying survival differences between pBC and CSBC could influence future counseling and treatments for patients with CSBC.

Methods

Women (≥15 years) diagnosed with pBC from 1991 to 2015 in the California Cancer Registry (n = 377,176) were compared with those with CSBC (n = 15,586) by age group (15-39 years, n = 406; 40-64 years, n = 6814; ≥ 65 years, n = 8366). Multivariable logistic regression models assessed factors associated with CSBC. Multivariable Cox proportional hazards regression models assessed BC-specific survival (BCSS), while accounting for the competing risk of death.

Results

Across all ages, CSBC patients were more likely to have smaller tumors (T2 vs. T1a; 15-39 yeras: OR 0.25, CI 0.16-0.38; 40-64 years: OR 0.41, CI 0.37-0.45; ≥ 65 years: OR 0.46, CI 0.42-0.51) and lymph node-negative disease (positive vs. negative; 15-39 years: OR 0.86, CI 0.69-1.08; 40-64 years: OR 0.88, CI 0.83-0.93; ≥ 65 years: OR 0.89, CI 0.84-0.94). Additionally, CSBC was associated with worse survival compared with pBC across all ages (15-39 years: HR 2.73, CI 2.30-3.25; 40-64 years: HR 2.13, CI 2.01-2.26; ≥ 65 years: HR 1.52, CI 1.43-1.61).

Conclusion

BCSS is worse among all women diagnosed with CSBC compared with pBC, with the strongest impact seen in adolescent and young adult women. Worse survival after CSBC, despite associations with smaller tumors and lymph node negativity, suggests that CSBC may need eventual treatment reconsideration.

Purpose

Current treatment guidelines for male breast cancer are guided by female-only trials despite data suggesting distinct clinicopathologic differences between sexes. We sought to evaluate whether radiation therapy (RT) after lumpectomy was associated with equivalent survival among men > 70 years of age with stage I, estrogen receptor (ER) positive tumors, as seen in women from the Cancer and Leukemia Group B (CALGB) 9343 trial.

Methods

We performed a retrospective analysis of 752 stage I, ER-positive male breast cancer patients ≥ 70 years who were treated with hormone therapy and surgery, with or without RT, from the National Cancer Database between 2004 and 2014. Patients were categorized based on surgery and RT (lumpectomy alone, lumpectomy with RT, and mastectomy alone). Multivariable Cox proportional hazards regression analysis was used to compare overall survival between treatment groups.

Results

Most patients underwent total mastectomy, with only 32.6% treated with lumpectomy. Of those who underwent lumpectomy, 72.7% received adjuvant RT. In multivariate analysis, there was no statistical difference in overall survival when comparing lumpectomy alone and lumpectomy with RT (aHR 0.72 [95% CI 0.38-1.37], p = 0.31) or when comparing lumpectomy (alone or with RT) and mastectomy (aHR 1.28 [95% CI 0.88-1.87], p = 0.20).

Conclusions

In this national sample of elderly men with ER-positive early-stage disease treated with endocrine therapy, there were no significant differences in overall survival when comparing lumpectomy alone and lumpectomy with RT, or lumpectomy (alone or with RT) and mastectomy. These results suggest that less aggressive treatment may be appropriate for a subset of male breast cancer patients.

The microbiome has clearly been established as a cutting-edge field in tumor immunology and immunotherapy. Growing evidence supports the role of the microbiome in immune surveillance, self-tolerance, and response to immune checkpoint inhibitors such as anti PD-L1 and CTLA-4 blockade (1-6). Moreover, recent studies including those using fecal microbial transplantation (FMT) have demonstrated that response to checkpoint immunotherapies may be conferred or eliminated through gut microbiome modulation (7, 8). Consequently, studies evaluating microbiota-host immune and metabolic interactions remain an area of high impact research. While observations in murine models have highlighted the importance of the microbiome in response to therapy, we lack sufficient understanding of the exact mechanisms underlying these interactions. Furthermore, mouse and human gut microbiome composition may be too dissimilar for discovery of all relevant gut microbial biomarkers. Multiple cancers in dogs, including lymphoma, high grade gliomas, melanomas and osteosarcoma (OSA) closely resemble their human analogues, particularly in regard to metastasis, disease recurrence and response to treatment. Importantly, dogs with these spontaneous cancers also have intact immune systems, suggesting that microbiome analyses in these subjects may provide high yield information, especially in the setting of novel immunotherapy regimens which are currently expanding rapidly in canine comparative oncology (9, 10). Additionally, as onco-microbiotic therapies are developed to modify gut microbiomes for maximal responsiveness, large animal models with intact immune systems will be useful for trialing interventions and monitoring adverse events. Together, pre-clinical mechanistic studies and large animal trials can help fully unlock the potential of the microbiome as a diagnostic and therapeutic target in cancer.

Background

Groundbreaking studies have linked the gut microbiome with immune homeostasis and antitumor immune responses. Mounting evidence has also demonstrated an intratumoral microbiome, including in soft tissue sarcomas (STS), although detailed characterization of the STS intratumoral microbiome is limited. We sought to characterize the intratumoral microbiome in patients with STS undergoing preoperative radiotherapy and surgery, hypothesizing the presence of a distinct intratumoral microbiome with potentially clinically significant microbial signatures.

Methods

We prospectively obtained tumor and stool samples from adult patients with non-metastatic STS using a strict sterile collection protocol to minimize contamination. Metagenomic classification was used to estimate abundance using genus and species taxonomic levels across all classified organisms, and data were analyzed with respect to clinicopathologic factors.

Results

Fifteen patients were enrolled. Most tumors were located at an extremity (67%) and were histologic grade 3 (87%). 40% were well-differentiated/dedifferentiated liposarcoma histology. With a median follow-up of 24 months, 4 (27%) patients developed metastases, and 3 (20%) died. Despite overwhelming human DNA (>99%) intratumorally, we detected a small but consistent proportion of bacterial DNA (0.02-0.03%) in all tumors, including Proteobacteria, Bacteroidetes, and Firmicutes, as well as viral species. In the tumor microenvironment, we observed a strong positive correlation between viral relative abundance and natural killer (NK) infiltration, and higher NK infiltration was associated with superior metastasis-free and overall survival by immunohistochemical, flow cytometry, and multiplex immunofluorescence analyses.

Conclusions

We prospectively demonstrate the presence of a distinct and measurable intratumoral microbiome in patients with STS at multiple time points. Our data suggest that the STS tumor microbiome has prognostic significance with viral relative abundance associated with NK infiltration and oncologic outcome. Additional studies are warranted to further assess the clinical impact of these findings.