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Our objective was to investigate the potential cost savings of immunization information systems (IIS) in performing some administrative tasks associated with the federal Vaccines for Children (VFC) program at the state and practice levels. VFC is an entitlement program providing free vaccine to eligible children. We timed the staff of the Utah Department of Health (UDOH) and 72 private VFC practices for administrative VFC-related tasks from September 2003 through March 2004. Time measurements included time for practices to produce VFC reports and for UDOH staff to assess practice coverage levels and process VFC reports manually or via the Utah Statewide Immunization Information System (USIIS). Median cost savings to the state health department could be as much as $11 740 annually. Utah VFC practices could save up to a maximum of $446 annually per practice by using USIIS for VFC tasks. If applied to the 218 enrolled private practices statewide, this would result in a median total cost savings of $17,615 ($15,519 for reports and $2,096 for pulling medical charts). [ABSTRACT FROM AUTHOR]

Provides information on the data from U.S. Centers for Disease Control and Prevention's 2002 Immunization Registry Annual Report, a survey of registry activity among immunization programs for children in the 50 states and the District of Columbia that receive grant funding under section 317b of the Public Health Service Act. Key tools to increase and sustain high vaccination coverage; Percentage of states which are reported operating registries that target only regions or counties within their geographical areas; Four states that implemented all elements of the 12 functional standards.

Background : Preclinical and clinical data indicate that chemoradiotherapy (CRT) in combination with checkpoint inhibitors may prime an anti-tumor immunological response in esophageal cancer. However, responses to neoadjuvant therapy can vary widely and the key biomarkers to determine response remain poorly understood. The fecal microbiome is a novel and potentially modifiable biomarker of immunotherapy response, and both fecal and tumor microbes have been found to associate with outcomes in esophageal cancer. Methods : Fecal and tumor samples were collected from patients with stage II-III resectable esophageal or gastroesophageal junction carcinoma treated with neoadjuvant immune checkpoint inhibitors (ICIs) plus CRT prior to surgical resection. Microbiome profiles were analyzed by 16S rRNA amplicon sequencing and taxonomic data were integrated with fecal metabolite analysis to assess microbial function. Results : The fecal microbiome of patients with pathological complete response (PCR) grouped in distinct clusters compared to patients with residual viable tumor (RVT) by Bray-Curtis diversity metric. Integrated taxonomic and metabolomic analysis of fecal samples identified a sphingolipid and primary bile acid as enriched in the PCR, the levels of which correlated with several bacterial species: Roseburis inulinivorans, Ruminococcus callidus, and Fusicantenibacter saccharivorans. Analysis of the tumor microbiome profiles identified several bacterial genera previously associated with esophageal tumors, including Streptococcus and Veillonella . Conclusions : These results further characterize the fecal and tumor microbiome of patients with operable esophageal cancer and identify specific microbes and metabolites that may help elucidate how microbes contribute to tumor response with neoadjuvant CRT combined with ICI.

Background: Peritoneal metastases due to gastric adenocarcinoma (GCPM) carry a dismal prognosis. A promising treatment strategy is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), but clear eligibility criteria for GCPM are lacking. We sought to identify factors associated with overall survival (OS) following CRS-HIPEC for GCPM to help optimize patient selection and clinical outcomes., Patients and Methods: In this single-center retrospective cohort study, we examined CRS-HIPEC outcomes for patients with GCPM between 2001 and 2021. After analyzing patient demographic, clinicopathologic, and perioperative variables, we applied multivariable Cox hazard models to assess factors associated with OS. We then assessed associations between baseline predictors and prognostically important variables using multivariable logistic regression., Results: We analyzed 55 patients with GCPM who underwent CRS-HIPEC. Median age was 54 years and 42% were female. Median peritoneal carcinomatosis index (PCI) was 8, and 75% of patients achieved a cytoreduction completeness score (CC score) of 0. Median progression-free survival (PFS) was 6.9 months, and median OS was 14.1 months. On adjusted analysis, a CC score > 0 (HR 2.3, p = 0.02) was significantly associated with worse OS. A peritoneal carcinomatosis index greater than 13 (OR 52.6, p = 0.001) and fewer lymph nodes (especially < 18) resected with the primary tumor (OR 0.86, p = 0.042) in the metachronous setting were significantly associated with incomplete macroscopic cytoreduction (CC score > 0)., Conclusions: We demonstrated that PCI > 13 and primary lymph nodes harvested < 18 in metachronous tumors are associated with CC score > 0, which in turn portends a worse OS. Although these results warrant prospective validation, they provide insight into improved selection of patients with GCPM for CRS-HIPEC., (© 2024. Society of Surgical Oncology.)

Background and Objectives: We evaluated the long-term quality of life (QOL) and priorities of an international cohort of cancer surgery survivors., Methods: Patients were surveyed through online support groups. We utilized the Short Form-12 questionnaire to evaluate QOL and a novel survey to assess the relative importance of longevity, experience, and costs., Results: A total of 592 patients from six continents responded. They were 58 ± 12 years old, 70% female, and 92% White. Patients averaged 37 months from their initial cancer diagnosis, with a maximum survivorship of 46 years. Across 17 disease sites, respondents generally ranked longevity, functional independence, and emotional well-being most important, while treatment experience and costs were ranked least important (W = 33.6%, p < 0.001). However, a subset of respondents ranked costs as significantly important. There were no differences in QOL based on demographics, except patients with higher education and income reported better QOL scores. Despite improvements in QOL throughout survivorship, both physical-QOL (41.1 ± 11.1 at 1 year vs. 42.3 ± 12.6 at 5 years, p = 0.511) and mental-QOL (41.3 ± 13.4 at 1 year vs. 44.6 ± 13.9 at 5 years, p = 0.039) remained below that of the general population (50 ± 10; both p < 0.001)., Conclusions: Cancer survivors experience enduring physical and mental impairment throughout survivorship. Future efforts should aim to provide sustained support across varied socioeconomic groups, ensuring equitable care and enhancement of QOL postcancer treatment., (© 2024 Wiley Periodicals LLC.)

Background: Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is a multimodal therapeutic option for the management of peritoneal metastases (PM). Treatment outcomes for patients with colorectal cancer (CRC) PM undergoing CRS+HIPEC with microsatellite instability (MSI) remain unknown. We examined the patient characteristics and outcomes in patients with MSI CRC after CRS+HIPEC., Methods: This was a retrospective cohort study of a prospectively maintained database of all patients with CRC PM undergoing CRS+HIPEC (2010-2020). Categorical and continuous variables were analyzed using the chi-square test and independent samples t test, respectively. Survival was evaluated with the Kaplan-Meier analysis., Results: There were 324 patients diagnosed as having CRC PM undergoing CRS+HIPEC (MSI, n = 23; microsatellite stable [MSS], n = 301). There was no statistically significant difference in patient demographics, tumor characteristics, or perioperative factors between the 2 groups. There was a trend toward improved survival in the MSI group with a median overall survival (OS) of 96.7 month compared with patients with MSS disease (median OS, 51.4 months; P = .10). Patients with MSI demonstrated median progression-free survival (PFS) 8.5 months compared with 11.4 months in the MSS cohort (P = .28)., Conclusion: Patients with CRC PM, regardless of MSI or MSS status, demonstrate similar OS and PFS after CRS+HIPEC. MSI status should not change a patient's candidacy for CRS+HIPEC., (Copyright © 2024. Published by Elsevier Inc.)

Background and Objectives: Primary adrenal sarcoma (PAS) is an exceedingly rare malignancy with limited data available on its epidemiology, management, and outcomes. This study aimed to characterize the national incidence, treatment patterns, and survival of PAS utilizing a National Cancer Database., Methods: The National Cancer Database was queried for patients diagnosed with primary adrenal tumors from 2004 to 2019. Cases with sarcoma histology were identified as PAS. Annual incidence trends, histological distribution, treatment modalities (surgery, chemotherapy, radiation therapy), perioperative outcomes, and overall survival (OS) were analyzed., Results: Of 7213 primary adrenal tumor cases, 332 (4.6%) were PAS. The most common histological subtypes were leiomyosarcoma (37.3%), hemangiosarcoma (27.1%), and sarcoma not otherwise specified (6.0%). Most cases (71.7%) presented as locoregional disease. Treatment included surgery alone (47.8%), surgery plus chemotherapy and/or radiation (27.1%), chemotherapy/radiation alone (13.3%), or no treatment (13.9%). For surgical cases, the median length of stay was 5 days, the 30-day readmission rate was 3.36%, and the 30/90-day mortality rates were 3.65% and 9.90%, respectively. The 5-year OS rate for surgery alone was 43%, with a median OS of 34.6 months. For surgery with radiation/chemotherapy, the 5-year OS rate was 37.3%, with a median OS of 35.4 months., Conclusions: This largest analysis of PAS to date demonstrates that most cases present as locoregional disease amenable to surgical resection, with favorable outcomes. The role of adjuvant therapy remains unclear, as no significant survival difference was observed between surgery alone and multimodal treatment., (© 2024 Wiley Periodicals LLC.)

Background: Many cancers metastasize to the pleura, resulting in effusions that cause dyspnea and discomfort. Regardless of the tissue of origin, pleural malignancies are aggressive and uniformly fatal, with no treatment shown to prolong life. The pleural mesothelial monolayer is joined by tight junctions forming a contained bioreactor-like space, concentrating cytokines and chemokines secreted by the mesothelium, tumor, and infiltrating immune cells. This space represents a unique environment that profoundly influences tumor and immune cell behavior. Defining the pleural secretome is an important step in the rational development localized intrapleural immunotherapy., Method: We measured cytokine/chemokine content of 252 malignant pleural effusion (MPE) samples across multiple cancers using a 40-analyte panel and Luminex multiplexing technology., Results: Eleven analytes were consistently present in concentrations ≥ 10.0 pM: CXCL10/IP10 (geometric mean = 672.3 pM), CCL2/MCP1 (562.9 pM), sIL-6Rα (403.1 pM), IL-6 (137.6 pM), CXCL1/GRO (80.3 pM), TGFβ1 (76.8 pM), CCL22/MDC (54.8 pM), CXCL8/IL-8 (29.2 pM), CCL11/Eotaxin (12.6 pM), IL-10 (11.3 pM), and G-CSF (11.0 pM). All are capable of mediating chemotaxis, promotion of epithelial to mesenchymal transition, or immunosuppression, and many of are reportedly downstream of a pro-inflammatory cytokine cascade mediated by cytokine IL-6 and its soluble receptor., Conclusion: The data indicate high concentrations of several cytokines and chemokines across epithelial cancers metastatic to the pleura and support the contention that the pleural environment is the major factor responsible for the clinical course of MPE across cancer types. A sIL-6Rα to IL-6 molar ratio of 2.7 ensures that virtually all epithelial, immune and vascular endothelial cells in the pleural environment are affected by IL-6 signaling. The central role likely played by IL-6 in the pathogenesis of MPE argues in favor of a therapeutic approach targeting the IL-6/IL-6R axis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Donnenberg, Luketich, Popov, Bartlett and Donnenberg.)

Background: For patients with peritoneal carcinomatosis, extent of disease and completeness of cytoreductive surgery (CRS) are major prognostic factors for long-term survival. Assessment of these factors could be improved using imaging agents. Pegsitacianine is a pH-sensitive polymeric micelle conjugated to the fluorophore indocyanine green. The micelle disassembles in acidic microenvironments, such as tumors, resulting in localized fluorescence unmasking. We assessed the utility of pegsitacianine in detecting residual disease following CRS., Patients and Methods: NCT04950166 was a phase II, non-randomized, open-label, multicenter US study. Patients eligible for CRS were administered an intravenous dose of pegsitacianine at 1 mg/kg 24-72 h before surgery. Following CRS, the peritoneal cavity was reexamined under near-infrared (NIR) illumination to evaluate for fluorescent tissue. Fluorescent tissue identified was excised and evaluated by histopathology. The primary outcome was the rate of clinically significant events (CSE), defined as detection of histologically confirmed residual disease excised with pegsitacianine or a revision in the assessment of completeness of CRS. Secondary outcomes included acceptable safety and pegsitacianine performance., Results: A total of 53 patients were screened, 50 enrolled, and 40 were evaluable for CSE across six primary tumor types. Residual disease was detected with pegsitacianine in 20 of 40 (50%) patients. Pegsitacianine showed high sensitivity and was well tolerated with no serious adverse events (SAEs). Transient treatment-related, non-anaphylactic infusion reactions occurred in 28% of patients., Conclusions: Pegsitacianine was well tolerated and facilitated the recognition of occult residual disease following CRS. The high rate of residual disease detected suggests that the use of pegsitacianine augmented surgeon assessment and performance during CRS., (© 2024. Society of Surgical Oncology.)

Background: This study assessed the long-term quality of life (QOL) and priorities of pancreaticoduodenectomy (PD) survivors., Methods: Survivors were surveyed via internet-based support groups. The relative importance of longevity, experience, costs, and QOL were assessed., Results: The PD cohort (n = 247, 35%) was 60 ± 12 years, 71% female, and 93% white. With moderate agreement, patients ranked survival most important, followed by functional and emotional well-being; costs and experience were least important (W = 35.7%, p < 0.001). Well-being improved throughout survivorship (P-QOL: 39 ± 12 at ≤3 mo vs 43 ± 12 at >10 y, p = 0.170; M-QOL: 38 ± 13 at ≤3 mo vs 44 ± 16 at >10 y; p = 0.015) but remained below the general population (p < 0.001). PD patients with benign diagnoses ranked functional independence as most important (2.00 ± 1.13 vs 2.63 ± 1.19, p < 0.001, W = 41.1%); PD patients with malignant diagnoses regarded overall survival most important (2.10 ± 1.20 vs 1.82 ± 1.22, p < 0.16, W = 35.1%). The mean rank order of priorities remained concordant between short-term (<1 year) and long-term (>5 years) survivors., Conclusion: PD survivors experience long-term mental and physical health impairments, underscoring the importance of functional and emotional support. Survivors place paramount importance on overall survival, functional independence, and emotional well-being. Cancer survivors prioritize longevity, while survivors of chronic benign conditions prioritize functional independence., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Normal carcinoembryonic antigen (CEA) levels (≤ 2.5 ng/ml) after resection of localized colorectal cancer or liver metastases are associated with improved survival, however, these trends are understudied for colorectal peritoneal metastases (CRPM)., Patients and Methods: We conducted a retrospective single-institution study of patients with CRPM undergoing cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) with and without neoadjuvant chemotherapy (NACT). CEA was measured before and after NACT and within 3 months after CRS/HIPEC., Results: A total of 253 patients (mean age 55.3 years) with CRPM undergoing CRS/HIPEC had complete CEA data and 191 also underwent NACT with complete data. The median peritoneal carcinomatosis index score (PCI) of the overall cohort was 12 and 82.7% of patients had complete cytoreduction (CC0). In total, 64 (33.5%) patients had normal CEA levels after NACT with a median overall survival (OS) of 45.2 months compared with those with an elevated CEA (26.4 months, p = 0.004). Patients with normal CEA after NACT had a lower PCI found at the time of surgery than those with elevated CEA (10 versus 14, p < 0.001), 68 (26.9%) patients with an elevated preoperative CEA level experienced normalization after CRS/HIPEC, and 118 (46.6%) patients had elevated CEA after CRS/HIPEC. Patients who experienced normalization demonstrated similar OS to patients that had normal CEA levels pre- and post-surgery and improved OS compared with those with elevated postop CEA (median 41.9 versus 47 months versus 17.1 months, respectively, p < 0.001)., Conclusions: Normal CEA levels after NACT and/or CRS/HIPEC are associated with improved survival for patients with CRPM. Patients that normalize CEA levels after surgery have similar survival to those with normal preoperative levels., (© 2024. Society of Surgical Oncology.)

Background or Purpose: Carcinomatosis, a distinct pattern of metastatic cancer in the peritoneal cavity, poses challenges for treatment and has limited therapeutic options. Understanding the immune environment of peritoneal surface malignancies is crucial for developing effective immunotherapeutic approaches. This study characterizes soluble immune mediators in the peritoneal fluid of patients with and without carcinomatosis to identify targets for novel treatment strategies., Patients and Methods: Serum and peritoneal fluid samples were collected from surgical patients, and a multianalyte analysis was performed using the Luminex platform. Patient characteristics, tumor sites, and sample collection details were recorded. Soluble immune mediator levels were measured and compared between peritoneal fluid and serum samples and among clinical subgroups. Statistical analysis was conducted to assess differences in analyte concentrations and correlations between samples., Results: There were 39 patients included in the study, with varying surgical indications. Significant differences were observed in soluble immune mediator levels between peritoneal fluid and serum, with peritoneal fluid exhibiting lower concentrations. Carcinomatosis was associated with elevated levels of proinflammatory mediators, including IL-6 and IL-8, while adaptive immune response markers were low in peritoneal fluid., Conclusions: The peritoneal immune microenvironment in carcinomatosis favors innate immunity, presenting a challenging environment for effective antitumor response. High levels of proinflammatory mediators suggest potential targets for intervention, such as the IL-6 axis, FGF2, IL-8, and CCL2; these could be explored as potential mitigators of malignant ascites and enhance anti-tumor immune responses. These findings provide valuable insights for developing immunotherapy strategies and improving outcomes in patients with peritoneal carcinomatosis., (© 2023. Society of Surgical Oncology.)

The success of cancer immunotherapy is largely associated with immunologically hot tumors. Approaches that promote the infiltration of immune cells into tumor beds are urgently needed to transform cold tumors into hot tumors. Oncolytic viruses can transform the tumor microenvironment (TME), resulting in immunologically hot tumors. Cytokines are good candidates for arming oncolytic viruses to enhance their function in this transformation. Here, we used the oncolytic vaccinia virus (oVV) to deliver interleukin-9 (IL-9) into the tumor bed and explored its antitumor effects in colon and lung tumor models. Our data show that IL-9 prolongs viral persistence, which is probably mediated by the up-regulation of IL-10. The vvDD-IL-9 treatment elevated the expression of Th1 chemokines and antitumor factors such as IFN-γ, granzyme B, and perforin. IL-9 expression increased the percentages of CD4 + and CD8 + T cells in the TME and decreased the percentage of oVV-induced immune suppressive myeloid-derived suppressor cells (MDSC), leading to potent antitumor effects compared with parental virus treatment. The vvDD-IL-9 treatment also increased the percentage of regulatory T cells (Tregs) in the TME and elevated the expression of immune checkpoint molecules such as PD-1, PD-L1, and CTLA-4, but not GITR. The combination therapy of vvDD-IL-9 and the anti-CTLA-4 antibody, but not the anti-GITR antibody, induced systemic tumor-specific antitumor immunity and significantly extended the overall survival of mice, indicating a potential translation of the IL-9-expressing oncolytic virus into a clinical trial to enhance the antitumor effects elicited by an immune checkpoint blockade for cancer immunotherapy.

Advancing cancer treatment relies on the rapid translation of new scientific discoveries to patient care. To facilitate this, an oncology biobank and data repository program, also referred to as the "Moonshot" program, was launched in 2021 within the Integrated Network Cancer Program of the Allegheny Health Network. A clinical data program (CDP) and biospecimen repository were established, and patient data and blood and tissue samples have been collected prospectively. To date, the study has accrued 2920 patients, predominantly female (61%) and Caucasian (90%), with a mean age of 64 ± 13 years. The most common cancer sites were the endometrium/uterus (12%), lung/bronchus (12%), breast (11%), and colon/rectum (11%). Of patients diagnosed with cancer, 34% were diagnosed at stage I, 25% at stage II, 26% at stage III, and 15% at stage IV. The CDP is designed to support our initiative in advancing personalized cancer research by providing a comprehensive array of patient data, encompassing demographic characteristics, diagnostic details, and treatment responses. The "Moonshot" initiative aims to predict therapy responses and clinical outcomes through cancer-related biomarkers. The CDP facilitates this initiative by fostering data sharing, enabling comparative analyses, and informing the development of novel diagnostic and therapeutic methods.

Purpose: Although immunotherapy is the mainstay of therapy for advanced non-small cell lung cancer (NSCLC), robust biomarkers of clinical response are lacking. The heterogeneity of clinical responses together with the limited value of radiographic response assessments to timely and accurately predict therapeutic effect-especially in the setting of stable disease-calls for the development of molecularly informed real-time minimally invasive approaches. In addition to capturing tumor regression, liquid biopsies may be informative in capturing immune-related adverse events (irAE)., Experimental Design: We investigated longitudinal changes in circulating tumor DNA (ctDNA) in patients with metastatic NSCLC who received immunotherapy-based regimens. Using ctDNA targeted error-correction sequencing together with matched sequencing of white blood cells and tumor tissue, we tracked serial changes in cell-free tumor load (cfTL) and determined molecular response. Peripheral T-cell repertoire dynamics were serially assessed and evaluated together with plasma protein expression profiles., Results: Molecular response, defined as complete clearance of cfTL, was significantly associated with progression-free (log-rank P = 0.0003) and overall survival (log-rank P = 0.01) and was particularly informative in capturing differential survival outcomes among patients with radiographically stable disease. For patients who developed irAEs, on-treatment peripheral blood T-cell repertoire reshaping, assessed by significant T-cell receptor (TCR) clonotypic expansions and regressions, was identified on average 5 months prior to clinical diagnosis of an irAE., Conclusions: Molecular responses assist with the interpretation of heterogeneous clinical responses, especially for patients with stable disease. Our complementary assessment of the peripheral tumor and immune compartments provides an approach for monitoring of clinical benefits and irAEs during immunotherapy., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Complex, minimally invasive hepatopancreatobiliary surgery (MIS HPB) is safe at high-volume centers, yet outcomes during early implementation are unknown. We describe our experience during period of rapid growth in an MIS HPB program at a large regional health system., Methods: During an increase in MIS HPB (60% greater from preceding year), hospital records of patients who underwent HPB surgery between 1/1/2019 and 12/31/2020 were reviewed. Operative time, estimated blood loss (EBL), conversion rates, length of stay (LOS), and perioperative outcomes were assessed., Results: 267 patients' cases were reviewed. The population was 62 ± 13 years, 50% female, 90% white. MIS was more frequently performed for hepatic than pancreatic resections (59% vs 21%, P < .001). Open cases were more frequently performed for invasive malignancy in both pancreatic (70% vs 40%, P < .018) and hepatic (87% vs 70%, P = .046) resections. There was no difference in operative time between MIS and open surgery (293[218-355]min vs 296[199-399]min, P = .893). When compared to open, there was a shorter LOS (4[2-6]d vs 7[6-10]d, P < .001) and lower readmission rate (21% vs 37%, P = .005) following MIS. Estimated blood loss was lower in MIS liver resections, particularly when performed for benign disease (200[63-500]mL vs 600[200-1200]mL, P = .041). Overall 30-day mortality was similar between MIS and open surgery (1.0% vs 1.8%, P = 1.000)., Discussion: During a surgical expansion phase within our regional health system, MIS HPB offered improved perioperative outcomes when compared to open surgery. These data support the safety of implementation even during intervals of rapid programmatic growth., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Despite advances in cancer treatment, the quality of life (QOL) of survivors varies significantly. We assessed the correlation between socioeconomic factors and long-term QOL in a global cohort of cancer survivors., Materials and Methods: Patients were offered surveys via online support groups. Using the Short Form-12 validated questionnaire, physical QOL (PQOL) and mental QOL (MQOL) well-being were compared to the general population. Socioeconomic factors were assessed with regression analysis for impact on QOL., Results: Seven hundred eighty two survivors from six continents responded. They were 57 ± 13 y and 68% female, 90.8% White, with 43 distinct cancer diagnoses. All survivors had PQOL and MQOL scores lower than the general population. Lower education level, household income, and non-White race all correlated with reduced PQOL and/or MQOL. Age was negatively correlated with PQOL (r = -0.08, P = 0.03) and positively correlated with MQOL (r = 0.142, P < 0.001). Care at large regional/academic centers was associated with higher MQOL (42 ± 14 versus 38 ± 11, P = 0.005). Age (β = -0.1, P = 0.04), education (β = 1.1, P = 0.005), and income (β = 2.0, P < 0.001) were predictors of PQOL, while age (β = 0.2, P < 0.001), income (β = 1.7, P = 0.002), and community hospital care (β = -3.6, P = 0.013) were predictors of MQOL., Conclusions: In a large international survey of cancer survivors, we identified socioeconomic factors and their associations with QOL. Further work should be directed to provide durable support across all socioeconomic classes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: We used a framework to assess the value implications of thoracic surgeon operative volume within an 8-hospital health system., Methods: Surgical cases for non-small cell lung cancer were assessed from March 2015 to March 2021. High-volume (HV) surgeons performed >25 pulmonary resections annually. Metrics include length of stay, infection rates, 30-day readmission, in-hospital mortality, median 30-day charges and direct costs, and 3-year recurrence-free and overall survival. Multivariate regression-based propensity scores matched patients between groups. Metrics were graphed on radar charts to conceptualize total value., Results: All 638 lung resections were performed by 12 surgeons across 6 hospitals. Two HV surgeons performed 51% (n = 324) of operations, and 10 low-volume surgeons performed 49% (n = 314). Median follow-up was 28.8 months (14.0-42.3 months). Lobectomy was performed in 71% (n = 450) of cases. HV surgeons performed more segmentectomies (33% [n = 107] vs 3% [n = 8]; P  < .001). Patients of HV surgeons had a lower length of stay (3 [2-4] vs 5 [3-7]; P  < .001) and infection rates (0.6% [n = 1] vs 4% [n = 7]; P  = .03). Low-volume and HV surgeons had similar 30-day readmission rates (14% [n = 23] vs 7% [n = 12]; P  = .12), in-hospital mortality (0% [n = 0] vs 0.6% [n = 1]; P  = .33), and oncologic outcomes; 3-year recurrence-free survival was 95% versus 91%; P  = .44, and 3-year overall survival was 94% versus 90%; P  = 0. Charges were reduced by 28%, and direct costs were reduced by 23% (both P  < .001) in the HV cohort., Conclusions: HV surgeons provide comprehensive value across a health system. This multidomain framework can be used to help drive oncologic care decisions within a health system., Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2023 The Author(s).)

Background: Appendiceal mucinous neoplasms (AMNs) with disseminated disease (pseudomyxoma peritonei) are heterogeneous tumors with variable clinicopathologic behavior. Despite the development of prognostic systems, objective biomarkers are needed to stratify patients. With the advent of next-generation sequencing (NGS), it remains unclear if molecular testing can improve the evaluation of disseminated AMN patients., Methods: Targeted NGS was performed for 183 patients and correlated with clinicopathologic features to include American Joint Committee on Cancer/World Health Organization (AJCC/WHO) histologic grade, peritoneal cancer index (PCI), completeness of cytoreduction (CC) score, and overall survival (OS)., Results: Genomic alterations were identified for 179 (98%) disseminated AMNs. Excluding mitogen-activated protein kinase genes and GNAS due to their ubiquitous nature, collective genomic alterations in TP53, SMAD4, CDKN2A, and the mTOR genes were associated with older mean age, higher AJCC/WHO histologic grade, lymphovascular invasion, perineural invasion, regional lymph node metastasis, and lower mean PCI (p < 0.040). Patients harboring TP53, SMAD4, ATM, CDKN2A, and/or mTOR gene alterations were found to have lower OS rates of 55% at 5 years and 14% at 10 years, compared with 88% at 5 years and 88% at 10 years for patients without the aforementioned alterations (p < 0.001). Based on univariate and multivariate analyses, genomic alterations in TP53, SMAD4, ATM, CDKN2A, and/or the mTOR genes in disseminated AMNs were a negative prognostic factor for OS and independent of AJCC/WHO histologic grade, PCI, CC score, and hyperthermic intraperitoneal chemotherapy treatment (p = 0.006)., Conclusions: Targeted NGS improves the prognostic assessment of patients with disseminated AMNs and identifies patients who may require increased surveillance and/or aggressive management., (© 2023. Society of Surgical Oncology.)

Background: Advances in treatment of peritoneal surface malignancies including cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS±HIPEC) have led to long-term survivorship, yet the subsequent quality of life (QOL) and values of these patients are unknown., Patients and Methods: Survivors were offered surveys via online support groups. Novel items assessed how patients prioritized experience, costs, longevity, and wellbeing., Results: Of the 453 gastrointestinal/hepatobiliary (GI/HPB) surgical patients that responded, 74 underwent CRS±HIPEC and were 54±12 years old, 87% female, and 93% white. Respondents averaged 29 months from diagnosis, with a maximum survival of 20 years. With a moderate level of agreement (W = 39%), rankings of value metrics among respondents were predictable (p < 0.001). Longevity and functional independence were ranked highest; treatment experience and cost of treatment were ranked lowest (p < 0.001). Those who underwent CRS±HIPEC or other GI/HPB surgeries reported the same rank order. QOL in CRS±HIPEC survivors, both mental (M-QOL) (44±13) and physical (P-QOL) (41±11) were lower than in the general population (50±10); p < 0.001. Impairments persisted throughout survivorship, but M-QOL improved over time (p < 0.05). When comparing CRS±HIPEC with other GI/HPB cancer surgery survivors, M-QOL (43±13 versus 43±14, p = 0.85) and P-QOL (40±11 versus 42±12, p = 0.41) were similar., Conclusions: Although CRS±HIPEC survivors experience long-term mental and physical health impairments, they were similar to those experienced by survivors of other GI/HPB cancer surgeries, and their QOL improved significantly throughout survivorship. As CRS±HIPEC survivors prioritize longevity above all other metrics, survival benefit may outweigh a temporary reduction in QOL., (© 2023. Society of Surgical Oncology.)

Peritoneal carcinomatosis originating from gastric/gastroesophageal junction cancer (GC-PC) occurs in a defined subset of gastric cancer patients with unique clinical, pathologic, molecular and immunologic characteristics that create significant obstacles to effective treatment with modern therapy. Although systemic chemo- and immuno- therapy have yielded disappointing results in GC-PC, recent advances in the characterization of GC-PC and peritoneal immune biology present new opportunities for targeted therapeutics. In this review article, we discuss the distinct properties of GC-PC and the peritoneal immune environment as they pertain to current and investigative treatment strategies. We discuss pre-clinical studies and clinical trials relevant to the modulation of the peritoneal environment as a therapeutic intervention in GC-PC. Finally, we present a road map for future combinatorial strategies based on the conception of the peritoneal cavity as a bioreactor. Within this isolated compartment, prevailing immunosuppressive conditions can be altered through regional interventions toward an adaptive phenotype that would support the effectiveness of regionally delivered cellular therapy products. It is hoped that novel combination strategies would promote efficacy not only in the sequestered peritoneal environment, but also via migration into the circulation of tumor-reactive lymphocytes to produce durable systemic disease control, thereby improving oncologic outcome and quality of life in patients with GC-PC.

Background: CRS-HIPEC provides oncologic benefit in well-selected patients with peritoneal carcinomatosis; however, it is a morbid procedure. Decision tools for preoperative patient selection are limited. We developed a risk score to predict severity of 90 day complications for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC)., Patients and Methods: Adults who underwent CRS-HIPEC at the University of Pittsburgh Medical Center (March 2001-April 2020) were analyzed as part of this study. Primary endpoint was severe complications within 90 days following CRS-HIPEC, defined using Comprehensive Complication Index (CCI) scores as a dichotomous (determined using restricted cubic splines) and continuous variable. Data were divided into training and test sets. Several machine learning and traditional algorithms were considered., Results: For the 1959 CRS-HIPEC procedures included, CCI ranged from 0 to 100 (median 32.0). Adjusted restricted cubic splines model defined severe complications as CCI > 61. A minimum of 20 variables achieved optimal performance of any of the models. Linear regression achieved the highest area under the receiving operator characteristic curve (AUC, 0.74) and outperformed the NSQIP Surgical Risk calculator (AUC 0.80 vs. 0.66). Factors most positively associated with severe complications included peritoneal carcinomatosis index score, symptomatic status, and undergoing pancreatectomy, while American Society of Anesthesiologists 2 class, appendiceal diagnosis, and preoperative albumin were most negatively associated with severe complications., Conclusions: This study refines our ability to predict severe complications within 90 days of discharge from a hospitalization in which CRS-HIPEC was performed. This advancement is timely and relevant given the growing interest in this procedure and may have implications for patient selection, patient and referring provider comfort, and survival., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: There is an increasing usage of noninvasive screening modalities for colorectal cancer (CRC), primarily the fecal immunochemical test (FIT) and multi-target stool DNA test (Cologuard [CG]). The aim of this study was to determine the comprehensive, long-term cost implications of these noninvasive screening modalities., Study Design: Using a national insurer-based administrative dataset, patients screened for CRC from January 1, 2019 to December 31, 2019 were analyzed. A hierarchical logic system was used to determine the primary screening modality for each patient. The total annual costs in US dollars ($) were extrapolated using number of patients screened, costs per test, screening intervals, and costs incurred from false results. Patients within our tumor registry diagnosed with CRC were matched to their claims data, and cancer stage distribution was compared., Results: Of 119,334 members who underwent noninvasive screening, 38.1% underwent screening with FIT and 40.0% with CG. The combined annual cost for these 2 screening modalities was $13.7 million. By transitioning to FIT alone for all noninvasive screening, the total annual cost would decrease to $7.9 million, resulting in a savings of approximately $5.8 million per year. Additionally, by combining data from the network cancer registry and insurer-based claims dataset, we were able to match 533 individuals who underwent screening and were later diagnosed with CRC. The rate of early-stage (stage 0 to II) disease was found to be similar between those screened with FIT and CG (59.5% FIT vs 63.2% CG; p = 0.77)., Conclusions: The adoption of FIT as the primary noninvasive CRC screening method has the potential to generate significant cost savings, and therefore, carries significant value implications for a large population health system., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Colorectal cancer leads to peritoneal metastases (CRPM) in 10% of cases. Cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC) improves survival. Primary tumor location and abnormalities in RAS, BRAF, and mismatch repair/microsatellite stability (MMR/MSI) may affect post-CRS-HIPEC survival, but studies have not been consistent. We estimated the effects of primary tumor site and genomic alterations on post-CRS-HIPEC survival., Methods: This retrospective cohort study included CRS-HIPEC cases for CRPM at a high-volume center from 2001 to 2020. Next-generation sequencing and microsatellite testing defined the RAS, BRAF, and MMR/MSI genotypes. Adjusted effects of tumor sidedness and genomics on survival were evaluated using a multivariable Cox proportional hazards model. We analyzed these variables' effects on progression-free survival and the effects of immune checkpoint-inhibitors., Results: A total of 250 patients underwent CRS-HIPEC with testing for RAS, BRAF, and MMR/MSI; 50.8% of patients were RAS-mutated, 12.4% were BRAF-mutated, and 6.8% were deficient-MMR/MSI-high (dMMR/MSI-H). Genomic alterations predominated in right-sided cancers. After adjustment for comorbidities and oncological and perioperative variables, rectal origin [hazard ratio (HR) 1.9, p = 0.01], RAS mutation (HR 1.6, p = 0.01), and BRAF mutation (HR 1.7, p = 0.05) were associated with worse survival. RAS mutation was also associated with shorter progression-free survival (HR 1.6, p = 0.01 at 6 months post-operatively), and dMMR/MSI-H status was associated with superior survival (HR 0.3, p = 0.01 at 2 years). dMMR/MSI-H patients receiving immune checkpoint-inhibitors trended toward superior survival., Conclusions: Rectal origin, RAS mutations, and BRAF mutations are each associated with poorer survival after CRS-HIPEC for CRPM. Patients with CRPM and dMMR/MSI-H status have superior survival. Further research should evaluate benefits of immune checkpoint-inhibitors in this subgroup., (© 2023. Society of Surgical Oncology.)

Introduction: Treatment options for patients with malignant pleural effusions (MPE) are limited due, at least in part, to the unique environment of the pleural space, which drives an aggressive tumor state and governs the behavior of infiltrating immune cells. Modulation of the pleural environment may be a necessary step toward the development of effective treatments. We examine immune checkpoint molecule (ICM) expression on pleural T cells, the secretomes of pleural fluid, pleural infiltrating T cells (PIT), and ability to activate PIT ex vivo., Methods: ICM expression was determined on freshly drained and in vitro activated PIT from breast, lung and renal cell cancer. Secretomics (63 analytes) of activated PIT, primary tumor cultures and MPE fluid was determined using Luminex technology. Complementary digital spatial proteomic profiling (42 analytes) of CD45+ MPE cells was done using the Nanostring GeoMx platform. Cytolytic activity was measured against autologous tumor targets., Results: ICM expression was low on freshy isolated PIT; regulatory T cells (T-reg) were not detectable by GeoMx. In vitro activated PIT coexpressed PD-1, LAG-3 and TIGIT but were highly cytotoxic against autologous tumor and uniquely secreted cytokines and chemokines in the > 100 pM range. These included CCL4, CCL3, granzyme B, IL-13, TNFα, IL-2 IFNγ, GM-CSF, and perforin. Activated PIT also secreted high levels of IL-6, IL-8 and sIL-6Rα, which contribute to polarization of the pleural environment toward wound healing and the epithelial to mesenchymal transition. Addition of IL-6Rα antagonist to cultures reversed tumor EMT but did not alter PIT activation, cytokine secretion or cytotoxicity., Discussion: Despite the negative environment, immune effector cells are plentiful, persist in MPE in a quiescent state, and are easily activated and expanded in culture. Low expression of ICM on native PIT may explain reported lack of responsiveness to immune checkpoint blockade. The potent cytotoxic activity of activated PIT and a proof-of-concept clinical scale GMP-expansion experiment support their promise as a cellular therapeutic. We expect that a successful approach will require combining cellular therapy with pleural conditioning using immune checkpoint blockers together with inhibitors of upstream master cytokines such as the IL-6/IL-6R axis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Donnenberg, Luketich, Sultan, Lister, Bartlett, Ghosh and Donnenberg.)

Background: People who have or had the potential to menstruate (PPM) with inherited bleeding disorders (BD) face particular challenges receiving appropriate diagnosis and care and participating in research. As part of an initiative to create a National Research Blueprint for future decades of research, the National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive all-stakeholder consultations to identify the priorities of PPM with inherited BDs and those who care for them., Research Design and Methods: Working group (WG) 4 of the NHF State of the Science Research Summit distilled community-identified priorities for PPM with inherited BDs into concrete research questions and scored their feasibility, impact, and risk., Results: WG4 identified important gaps in the foundational knowledge upon which to base optimal diagnosis and care for PPM with inherited BDs. They defined 44 top-priority research questions concerning lifespan sex biology, pregnancy and the post-partum context, uterine physiology and bleeding, bone and joint health, health care delivery, and patient-reported outcomes and quality-of-life., Conclusions: The needs of PPM will best be advanced with research designed across the spectrum of sex and gender biology, with methodologies and outcome measures tailored to this population, involving them throughout.

Background: Sedentary behavior (SB) is prevalent after abdominal cancer surgery, and interventions targeting perioperative SB could improve postoperative recovery and outcomes. We conducted a pilot study to evaluate the feasibility and preliminary effects of a real-time mobile intervention that detects and disrupts prolonged SB before and after cancer surgery, relative to a monitoring-only control condition., Objective: Our aim was to evaluate the feasibility and preliminary effects of a perioperative SB intervention on objective activity behavior, patient-reported quality of life and symptoms, and 30-day readmissions., Methods: Patients scheduled for surgery for metastatic gastrointestinal cancer (n=26) were enrolled and randomized to receive either the SB intervention or activity monitoring only. Both groups used a Fitbit smartwatch and companion smartphone app to rate daily symptoms and collect continuous objective activity behavior data starting from at least 10 days before surgery through 30 days post discharge. Participants in the intervention group also received prompts to walk after any SB bout that exceeded a prespecified threshold, with less frequent prompts on days that patients reported more severe symptoms. Participants completed end-of-study ratings of acceptability, and we also examined adherence to assessments and to walking prompts. In addition, we examined effects of the intervention on objective SB and step counts, patient-reported quality of life and depressive and physical symptoms, as well as readmissions., Results: Accrual (74%), retention (88%), and acceptability ratings (mean overall satisfaction 88.5/100, SD 9.1) were relatively high. However, adherence to assessments and engagement with the SB intervention decreased significantly after surgery and did not recover to preoperative levels after postoperative discharge. All participants exhibited significant increases in SB and symptoms and decreases in steps and quality of life after surgery, and participants randomized to the SB intervention unexpectedly had longer maximum SB bouts relative to the control group. No significant benefits of the intervention with regard to activity, quality of life, symptoms, or readmission were observed., Conclusions: Perioperative patients with metastatic gastrointestinal cancer were interested in a real-time SB intervention and rated the intervention as highly acceptable, but engagement with the intervention and with daily symptom and activity monitoring decreased significantly after surgery. There were no significant effects of the intervention on step counts, patient-reported quality of life or symptoms, and postoperative readmissions, and there was an apparent adverse effect on maximum SB. Results highlight the need for additional work to modify the intervention to make reducing SB and engaging with mobile health technology after abdominal cancer surgery more feasible and beneficial., Trial Registration: ClinicalTrials.gov NCT03211806; https://tinyurl.com/3napwkkt., (©Carissa A Low, Michaela Danko, Krina C Durica, Julio Vega, Meng Li, Abhineeth Reddy Kunta, Raghu Mulukutla, Yiyi Ren, Susan M Sereika, David L Bartlett, Dana H Bovbjerg, Anind K Dey, John M Jakicic. Originally published in JMIR Perioperative Medicine (http://periop.jmir.org), 12.01.2023.)