Insight into Predictors of Cytoreduction Score Following Cytoreductive Surgery-Hyperthermic Intraperitoneal Chemotherapy for Gastric Peritoneal Carcinomatosis Improves Patient Selection and Prognostic Outcomes.

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.

Management of distal cholangiocarcinoma with arterial involvement: Systematic review and case series on the role of neoadjuvant therapy.

BACKGROUND: The use of neoadjuvant therapy (NAT) in distal cholangiocarcinoma (dCCA) with regional arterial or extensive venous involvement, is not widely accepted and evidence is sparse. AIM: To synthesise evidence on NAT for dCCA and present the experience of a high-volume tertiary-centre managing dCCA with arterial involvement. METHODS: A systematic review was performed according to PRISMA guidance to identify all studies reporting outcomes of patients with dCCA who received NAT. All patients from 2017 to 2022 who were referred for NAT for dCCA at our centre were retrospectively collected from a prospectively maintained database. Baseline characteristics, NAT type, progression to surgery and oncological outcomes were collected. RESULTS: Twelve studies were included. The definition of "unresectable" locally advanced dCCA was heterogenous. Four studies reported outcomes for 9 patients who received NAT for dCCA with extensive vascular involvement. R0 resection rate ranged between 0 and 100% but without survival benefit in most cases. Remaining studies considered either NAT in resectable dCCA or inclusive with extrahepatic CCA. The presented case series includes 9 patients (median age 67, IQR 56-74 years, male:female 5:4) referred for NAT for borderline resectable or locally advanced disease. Three patients progressed to surgery and 2 were resected. One patient died at 14 months with evidence of recurrence at 6 months and the other died at 51 months following recurrence 6 months post-operatively. CONCLUSION: Evidence for benefit of NAT is limited. Consensus on criteria for uniform definition of resectability for dCCA is required. We propose using the established National-Comprehensive-Cancer-Network® criteria for pancreatic ductal adenocarcinoma.

SIMAP500: A novel risk score to identify recipients at higher risk of hepatocellular carcinoma recurrence following liver transplantation.

BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) has a devastating influence on recipients' survival; however, the risk of recurrence is not routinely stratified. Risk stratification is vital with a long LT waiting time, as that could influence the recurrence despite strict listing criteria. AIM: This study aims to identify predictors of recurrence and develop a novel risk prediction score to forecast HCC recurrence following LT. METHODS: A retrospective review of LT for HCC recipients at University Hospitals Birmingham between July 2011 and February 2020. Univariate and multivariate analyses were performed to identify recurrence predictors, based on which the novel SIMAP500 (satellite nodules, increase in size, microvascular invasion, AFP > 500, poor differentiation) risk score was proposed. RESULTS: 234 LTs for HCC were performed with a median follow-up of 5.3 years. Recurrence developed in 25 patients (10.7%). On univariate analyses, RETREAT score > 3, α-fetoprotein (AFP) at listing 100-500 and > 500, bridging, increased tumour size between imaging at the listing time and explant histology, increase in the size of viable tumour between listing and explant, presence of satellite nodules, micro- and macrovascular invasion on explant and poor differentiation of tumours were significantly associated with recurrence, based on which, the SIMAP500 risk score is proposed. The SIMAP500 demonstrated an excellent predictive ability (c-index = 0.803) and outperformed the RETREAT score (c-index = 0.73). SIMAP500 is indicative of the time to disease recurrence. CONCLUSION: SIMAP500 risk score identifies the LT recipients at risk of HCC recurrence. Risk stratification allows patient-centric post-transplant surveillance programs. Further validation of the score is recommended.

A common secretomic signature across epithelial cancers metastatic to the pleura supports IL-6 axis therapeutic targeting.

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), TGFß1 (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.

Long-term patient-reported values following cancer surgery: A global survey study.

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.

Primary adrenal sarcomas: A national analysis of epidemiological trends, treatment patterns, and outcomes.

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.

Gastrointestinal Permeability After Bariatric Surgery: A Systematic Review.

Gastrointestinal permeability refers to the movement of substances across the gut wall. This is mediated by endotoxemia (bacterial products entering the systemic circulation), and is associated with metabolic disease. The effect of bariatric surgery on permeability remains uncertain; the associated dietary, metabolic and weight changes are suggested to influence, or trigger, altered permeability. The primary aim of this study is to synthesize evidence and analyze the effect of bariatric surgery on permeability. A systematic review was performed, searching MEDLINE, EMBASE, and Scopus until February 2023, using MESH terms "intestinal permeability", "bariatric", for studies reporting in vivo assessment of permeability. Three cohort studies and two case series were identified (n=96). Data was heterogeneous; methodology and controls preclude meta-analysis. Gastroduodenal permeability reduced post-sleeve gastrectomy (SG). Two studies showed an increase in small intestinal permeability after biliopancreatic diversion. Two studies revealed a decrease in post-Roux-en-Y gastric bypass. One study identified increased colonic permeability six months post-SG. Evidence regarding permeability change after bariatric surgery is conflicting, notably for the small intestine. Impaired colonic permeability post-SG raises concerns regarding colonic protein fermentation and harmful dietary sequelae. There are multiple interacting variables confounding gastrointestinal permeability change; procedure type, altered microbiota and metabolic response to surgery. Further understanding of this important aspect of obesity is required, both before and after bariatric surgery.

Meta-analysis of survival after pulmonary resection for isolated metachronous pancreatic cancer metastasis: a promising, albeit infrequent, approach.

BACKGROUND: To evaluate survival outcomes of pulmonary resection for isolated metachronous pancreatic cancer metastasis. METHODS: A systematic search of electronic data sources and reference lists were conducted. Proportion meta-analysis model was constructed to quantify 1- to 5-year survival after pulmonary resection for isolated metachronous pancreatic cancer metastasis. Random-effects modelling was applied to calculate pooled outcome data. RESULTS: Twenty-four retrospective studies were included reporting a total of 168 patients who underwent pulmonary resection for isolated pancreatic cancer metastasis. The nature of the index pancreatic surgery included 65% pancreaticoduodenectomies, 17.5% distal pancreatectomies, 0.5% total pancreatectomy, and 17% unspecified. Adjuvant chemotherapy was given to 88% of the patients. The median disease-free interval was 35 (8-96) months. The type of pulmonary resection included 54% wedge resections, 26% lobectomies, 4% segmentectomies, 1% pneumonectomies, and 15% unspecified. Pulmonary resection was associated with 1-year survival of 91.1% (95% CI 86.6%-95.5%), 2-year survival of 77.5% (95% CI 68.9%-86.0%), 3-year survival of 65.0% (95% CI 50.7%-79.3%), 4-year survival of 52.0% (95% CI 37.2%-66.9%), and 5-year survival of 37.0% (95% CI 25.0%-49.1%). CONCLUSION: Pulmonary resection for isolated pancreatic cancer metastasis is associated with acceptable overall patient survival. We recommend selective pulmonary resection for isolated pulmonary metastasis from pancreatic cancer. Our findings may encourage conduction of better-quality studies in this context to help establishment of definitive treatment strategies.

Microsatellite instability should not determine candidacy for cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion in patients with peritoneal metastases from colorectal cancer.

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.

A machine learning approach for predicting textbook outcome after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

INTRODUCTION: Peritoneal carcinomatosis is considered a late-stage manifestation of neoplastic diseases. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) can be an effective treatment for these patients. However, the procedure is associated with significant morbidity. Our aim was to develop a machine learning model to predict the probability of achieving textbook outcome (TO) after CRS-HIPEC using only preoperatively known variables. METHODS: Adult patients with peritoneal carcinomatosis and who underwent CRS-HIPEC were included from a large, single-center, prospectively maintained dataset (2001-2020). TO was defined as a hospital length of stay ≤14 days and no postoperative adverse events including any complications, reoperation, readmission, and mortality within 90 days. Four models (logistic regression, neural network, random forest, and XGBoost) were trained, validated, and a user-friendly risk calculator was then developed. RESULTS: A total of 1954 CRS-HIPEC procedures for peritoneal carcinomatosis were included. Overall, 13% (n = 258) achieved TO following CRS-HIPEC procedure. XGBoost and logistic regression had the highest area under the curve (AUC) (0.76) after model optimization, followed by random forest (AUC 0.75) and neural network (AUC 0.74). The top preoperative variables associated with achieving a TO were lower peritoneal cancer index scores, not undergoing proctectomy, splenectomy, or partial colectomy and being asymptomatic from peritoneal metastases prior to surgery. CONCLUSION: This is a data-driven study to predict the probability of achieving TO after CRS-HIPEC. The proposed pipeline has the potential to not only identify patients for whom surgery is not associated with prohibitive risk, but also aid surgeons in communicating this risk to patients.

Detection of Residual Peritoneal Metastases Following Cytoreductive Surgery Using Pegsitacianine, a pH-Sensitive Imaging Agent: Final Results from a Phase II Study.

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.

Targeting interleukin-6 as a treatment approach for peritoneal carcinomatosis.

Peritoneal carcinomatosis (PC) is a complex manifestation of abdominal cancers, with a poor prognosis and limited treatment options. Recent work identifying high concentrations of the cytokine interleukin-6 (IL-6) and its soluble receptor (sIL-6-Rα) in the peritoneal cavity of patients with PC has highlighted this pathway as an emerging potential therapeutic target. This review article provides a comprehensive overview of the current understanding of the potential role of IL-6 in the development and progression of PC. We discuss mechansims by which the IL-6 pathway may contribute to peritoneal tumor dissemination, mesothelial adhesion and invasion, stromal invasion and proliferation, and immune response modulation. Finally, we review the prospects for targeting the IL-6 pathway in the treatment of PC, focusing on common sites of origin, including ovarian, gastric, pancreatic, colorectal and appendiceal cancer, and mesothelioma.

Marker selection strategies for circulating tumor DNA guided by phylogenetic inference.

Motivation: Blood-based profiling of tumor DNA ("liquid biopsy") has offered great prospects for non-invasive early cancer diagnosis, treatment monitoring, and clinical guidance, but require further advances in computational methods to become a robust quantitative assay of tumor clonal evolution. We propose new methods to better characterize tumor clonal dynamics from circulating tumor DNA (ctDNA), through application to two specific questions: 1) How to apply longitudinal ctDNA data to refine phylogeny models of clonal evolution, and 2) how to quantify changes in clonal frequencies that may be indicative of treatment response or tumor progression. We pose these questions through a probabilistic framework for optimally identifying maximum likelihood markers and applying them to characterizing clonal evolution. Results: We first estimate a distribution over plausible clonal lineage models, using bootstrap samples over pre-treatment tissue-based sequence data. We then refine these lineage models and the clonal frequencies they imply over successive longitudinal samples. We use the resulting framework for modeling and refining tree distributions to pose a set of optimization problems to select ctDNA markers to maximize measures of utility capturing ability to solve the two questions of reducing uncertain in phylogeny models or quantifying clonal frequencies given the models. We tested our methods on synthetic data and showed them to be effective at refining distributions of tree models and clonal frequencies so as to minimize measures of tree distance relative to the ground truth. Application of the tree refinement methods to real tumor data further demonstrated their effectiveness in refining a clonal lineage model and assessing its clonal frequencies. The work shows the power of computational methods to improve marker selection, clonal lineage reconstruction, and clonal dynamics profiling for more precise and quantitative assays of tumor progression. Availability: https://github.com/CMUSchwartzLab/Mase-phi.git. Contact: russells@andrew.cmu.edu.

Modeling the Effect of Spatial Structure on Solid Tumor Evolution and Circulating Tumor DNA Composition.

Circulating tumor DNA (ctDNA) monitoring, while sufficiently advanced to reflect tumor evolution in real time and inform cancer diagnosis, treatment, and prognosis, mainly relies on DNA that originates from cell death via apoptosis or necrosis. In solid tumors, chemotherapy and immune infiltration can induce spatially variable rates of cell death, with the potential to bias and distort the clonal composition of ctDNA. Using a stochastic evolutionary model of boundary-driven growth, we study how elevated cell death on the edge of a tumor can simultaneously impact driver mutation accumulation and the representation of tumor clones and mutation detectability in ctDNA. We describe conditions in which invasive clones are over-represented in ctDNA, clonal diversity can appear elevated in the blood, and spatial bias in shedding can inflate subclonal variant allele frequencies (VAFs). Additionally, we find that tumors that are mostly quiescent can display similar biases but are far less detectable, and the extent of perceptible spatial bias strongly depends on sequence detection limits. Overall, we show that spatially structured shedding might cause liquid biopsies to provide highly biased profiles of tumor state. While this may enable more sensitive detection of expanding clones, it could also increase the risk of targeting a subclonal variant for treatment. Our results indicate that the effects and clinical consequences of spatially variable cell death on ctDNA composition present an important area for future work.

Intratumoral Delivery of Interleukin 9 via Oncolytic Vaccinia Virus Elicits Potent Antitumor Effects in Tumor Models.

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.

Assessing the long-term priorities of pancreaticoduodenectomy survivors.

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.