Multi-Institutional Study Evaluating the Role of Circulating Tumor DNA in the Management of Appendiceal Cancers.

PURPOSE: Conventional surveillance methods are poorly sensitive for monitoring appendiceal cancers (AC). This study investigated the utility of circulating tumor DNA (ctDNA) in evaluating systemic therapy response and recurrence after surgery for AC. METHODS: Patients from two specialized centers who underwent tumor-informed ctDNA testing (Signatera) were evaluated to determine the association between systemic therapy and ctDNA detection. In addition, the accuracy of ctDNA detection during surveillance for the diagnosis of recurrence after complete cytoreductive surgery (CRS) for grade 2-3 ACs with peritoneal metastases (PM) was investigated. RESULTS: In this cohort of 94 patients with AC, most had grade 2-3 tumors (84.0%) and PM (84.0%). Fifty patients completed the assay in the presence of identifiable disease, among which ctDNA was detected in 4 of 7 (57.1%), 10 of 16 (62.5%), and 19 of 27 (70.4%) patients with grade 1, 2, and 3 diseases, respectively. Patients who had recently received systemic chemotherapy had ctDNA detected less frequently (7 of 16 [43.8%] v 26 of 34 [76.5%]; odds ratio, 0.22 [95% CI, 0.06 to 0.82]; P = .02). Among 36 patients with complete CRS for grade 2-3 AC-PM, 16 (44.4%) developed recurrence (median follow-up, 19.6 months). ctDNA detection was associated with shorter recurrence-free survival (median 11.3 months v not reached; hazard ratio, 14.1 [95% CI, 1.7 to 113.8]; P = .01) and showed high accuracy for the detection of recurrence (sensitivity 93.8%, specificity 85.0%). ctDNA was more sensitive than carcinoembryonic antigen (62.5%), CA19-9 (25.0%), and CA125 (18.8%) and was the only elevated biomarker in four (25%) patients with recurrence. CONCLUSION: This study revealed a reduced ctDNA detection frequency after systemic therapy and accurate recurrence assessment after CRS. These findings underscore the role of ctDNA as a predictive and prognostic biomarker for grade 2-3 AC-PM management.

Outcomes of parenteral nutrition in patients with advanced cancer and malignant bowel obstruction.

BACKGROUND: Malignant bowel obstruction (MBO) affects 3% to 15% of all cancer patients. In patients with advanced cancer and inoperable MBO, the average survival varies between four to nine weeks. Parenteral nutrition (PN) may improve survival in specific patient populations with malignant bowel obstruction. AIMS: This retrospective, single-center cohort study aimed to review individual patient outcomes on PN in the setting of advanced cancer with a diagnosis of MBO and identify clinical and laboratory markers predictive of short- and long-term survival to further highlight patients that would benefit from PN in the setting of an inoperable MBO. RESULTS: In a retrospective analysis of 68 patients receiving PN for inoperable MBO, the median survival was 142 (IQR: 63.3-239.5) days. Patients experienced a median number of two hospital readmissions (range: 0-10) and spent a median of 29 days (range: 0-105) in the hospital after starting PN. Eighteen (26.5%) patients developed a catheter-related bloodstream infection (CRBSI). A diagnosis of appendiceal cancer was identified as a predictive marker of improved survival (HR: 0.53, 95% CI: 0.29-0.92, p = 0.023). CONCLUSIONS: The use of PN in the context of end-of-life cancer care is a practice that necessitates improvement. Recognizing the outcomes and patient experiences of PN utilization is essential to physicians and patients.

Implementation of a high-resolution, high-contrast magnetic resonance imaging protocol with extended delayed phases for peritoneal mesothelioma.

Background: Imaging of peritoneal malignancies using conventional cross-sectional imaging is challenging, but accurate assessment of peritoneal disease burden could guide better selection for definitive surgery. Here we demonstrate feasibility of high-resolution, high-contrast magnetic resonance imaging (MRI) of peritoneal mesothelioma and explore optimal timing for delayed post-contrast imaging. Methods: Prospective data from inpatients with malignant peritoneal mesothelioma (MPM), imaged with a novel MRI protocol, were analyzed. The new sequences augmenting the clinical protocol were (I) pre-contrast coronal high-resolution T2-weighted single-shot fast spin echo (COR hr T2w SSH FSE) of abdomen and pelvis; and (II) post-contrast coronal high-resolution three-dimensional (3D) T1-weighted modified Dixon (COR hr T1w mDIXON) of abdomen, acquired at five delay times, up to 20 min after administration of a double dose of contrast agent. Quantitative analysis of contrast enhancement was performed using linear regression applied to normalized signal in lesion regions of interest (ROIs). Qualitative analysis was performed by three blinded radiologists. Results: MRI exams from 14 participants (age: mean ± standard deviation, 60±12 years; 71% male) were analyzed. The rate of lesion contrast enhancement was strongly correlated with tumor grade (cumulative nuclear score) (r=-0.65, P<0.02), with 'early' delayed phase (12 min post-contrast) and 'late' delayed phase (19 min post-contrast) performing better for higher grade and lower grade tumors, respectively, in agreement with qualitative scoring of image contrast. Conclusions: High-resolution, high-contrast MRI with extended post-contrast imaging is a viable modality for imaging peritoneal mesothelioma. Multiple, extended (up to 20 min post-contrast) delayed phases are necessary for optimal imaging of peritoneal mesothelioma, depending on the grade of disease.

Venous Thromboembolism in Peritoneal Mesothelioma: Uncovering the Hidden Risk.

INTRODUCTION: Venous thromboembolism (VTE) is a common complication in patients with abdominal malignancies. Despite known associations between pleural mesothelioma and increased VTE risk, the characteristics of VTE in patients with peritoneal mesothelioma (PeM) remain undescribed. METHODS: Patients treated for PeM were retrospectively identified from our institutional database. The frequency of VTE was assessed and logistic regression modeling was employed to assess VTE risk factors. The association between VTE and overall survival was also ascertained. Recommended thromboprophylaxis for patients who underwent surgery at our institution comprised a single preoperative dose of prophylactic anticoagulation, followed by daily dosing for four weeks postoperatively. RESULTS: Among 120 PeM patients, 26 (21.7%) experienced VTE, including 19/91 (20.9%) surgical patients, 4/23 (17.4%) patients who received systemic therapy, and 3/6 (50%) patients who underwent observation (p = 0.21). Most events were symptomatic (n = 16, 62%) and were attributable to pulmonary emboli (n = 16, 62%). The 90-day postoperative VTE rate was 4.4% (4/91), including 1 of 60 patients who underwent index surgical intervention at our institution and 3 patients with surgery elsewhere. A low serum albumin concentration was associated with VTE in non-surgical patients (odds ratio 0.12, confidence interval [CI] 0.02-0.72; p = 0.03). No significant difference in overall survival was observed between patients with and without VTE (median 46.0 months [CI 24.9-67.0] vs. 55.0 months [CI 27.5-82.5]; hazard ratio 0.98 [CI 0.54-1.81], p = 0.98). CONCLUSIONS: A high risk of VTE was observed in PeM patients, warranting suspicion throughout the disease trajectory. Postoperative VTE rates were within acceptable limits with 4-week thromboprophylaxis.

Utility of Circulating Tumor DNA Assessment in Characterizing Recurrence Sites after Optimal Resection for Metastatic Colorectal Cancer.

BACKGROUND: Plasma circulating tumor DNA (ctDNA) is a promising biomarker for metastatic colorectal cancer (mCRC); however, its role in characterizing recurrence sites after mCRC resection remains poorly understood. This single-institution study investigated the timing of ctDNA detection and its levels in the context of recurrence at different sites after mCRC resection. STUDY DESIGN: Patients who underwent optimal resection of CRC metastases involving the peritoneum, distant lymph nodes, or liver, with serial postoperative tumor-informed ctDNA assessments (Signatera) were included. Recurrence sites, as defined by surveillance imaging or laparoscopy, were categorized as peritoneal-only and other distant sites (liver, lung, lymph nodes, or body wall). RESULTS: Among the 31 included patients, ctDNA was detected in all 26 (83.4%) patients with postoperative recurrence and was persistently undetectable in 5 patients who did not experience recurrence. At 3 months postsurgery, ctDNA was detected in 2 (25%) of 8 patients with peritoneal-only recurrence and 17 (94.4%) of 18 patients with distant recurrence (p < 0.001). Beyond 3 months, ctDNA was detected in the remaining 6 patients with peritoneal-only disease and 1 patient with distant disease. ctDNA detection preceded the clinical diagnosis of recurrence by a median of 9 weeks in both groups. At recurrence, peritoneal-only recurrent cases exhibited lower ctDNA levels (median 0.4 mean tumor molecules/mL, interquartile range 0.1 to 0.8) compared with distant recurrence (median 5.5 mean tumor molecules/mL, interquartile range 0.8 to 33.3, p = 0.004). CONCLUSIONS: Peritoneal-only recurrence was associated with delayed ctDNA detection and low levels of ctDNA after optimal resection for mCRC. ctDNA testing may effectively characterize recurrence sites and may help guide subsequent treatments specific to the disease sites involved.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy postoperative symptomatology: palliative care impact.

OBJECTIVES: Palliative care (PC) for patients with advanced cancer has been associated with improved symptom burden and quality of life (QoL). This study aimed to characterise postoperative symptoms of cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC) patients and to assess PC impact by analysing symptom burden before and after PC interventions. METHODS: CRS/HIPEC patients with two PC visits within 5 months postoperatively (2016-2021) at a tertiary care centre were identified from a retrospective database. For each patient, documentation of QoL-associated symptoms at the initial PC visit and changes in symptomatology at the second PC visit were recorded. Descriptive statistics were performed. RESULTS: 46 patients were included in this study. Median age was 62.2 (range 31.9-84.6) years. Median peritoneal cancer index was 23.5 (range 0-39). The most common histologies were colorectal (32.6%) and appendiceal (30.4%). Symptoms most frequently reported were pain (84.8%), fatigue (54.3%) and appetite loss/change (52.2%). Following PC interventions, most symptoms were stable or improved. The mean number of symptoms per patient was 3.7, with an average of 3.5 improved/stable and 0.5 worse/new onset at follow-up (p<0.001). CONCLUSION: CRS/HIPEC patients experienced a high QoL-associated symptom burden. Following postoperative PC interventions, significantly more symptoms were reported as improved/stable, compared with worse/new onset.

Novel Application of a Dynamic, In-room Survey Platform to Measure Surgical Team Satisfaction.

OBJECTIVE: To elucidate the potential usage of continuous feedback regarding team satisfaction and correlations with operative performance and patient outcomes. BACKGROUND: Continuous, actionable assessment of teamwork quality in the operating room (OR) is challenging. This work introduces a novel, data-driven approach to prospectively and dynamically assess health care provider satisfaction with teamwork in the OR. METHODS: Satisfaction with teamwork quality for each case was assessed utilizing a validated prompt displayed on HappyOrNot Terminals placed in all ORs, with separate panels for circulators, scrub nurses, surgeons, and anesthesia providers. Responses were cross-referenced with OR log data, team familiarity indicators, efficiency parameters, and patient safety indicator events through continuous, semiautomated data marts. Deidentified responses were analyzed through logistic regression modeling. RESULTS: Over a 24-week period, 4123 responses from 2107 cases were recorded. The overall response rate per case was 32.5%. Greater scrub nurse specialty experience was strongly associated with satisfaction (odds ratio: 2.15, 95% CI: 1.53-3.03, P < 0.001). Worse satisfaction was associated with longer than expected procedure time (odds ratio: 0.91, 95% CI: 0.82-1.00, P = 0.047), nighttime (0.67, 95% CI: 0.55-0.82, P < 0.001), and add-on cases (0.72, 95% CI: 0.60-0.86, P < 0.001). Higher material costs (22%, 95% CI: 6-37, P = 0.006) were associated with greater team satisfaction. Cases with superior teamwork ratings were associated with a 15% shorter length of hospital stay (95% CI: 4-25, P = 0.006). CONCLUSIONS: This study demonstrates the feasibility of a dynamic survey platform to report actionable health care provider satisfaction metrics in real-time. Team satisfaction is associated with modifiable team variables and some key operational outcomes. Leveraging qualitative measurements of teamwork as operational indicators may augment staff engagement and measures of performance.

Fragmentation of Care in Patients with Peritoneal Metastases Undergoing Cytoreductive Surgery.

BACKGROUND: The delivery of multimodal treatment at a high-volume center is known to optimize the outcomes of gastrointestinal malignancies. However, patients undergoing cytoreductive surgery (CRS) for peritoneal metastases often must 'fragment' their surgical and systemic therapeutic care between different institutions. We hypothesized that this adversely affects outcomes. PATIENTS AND METHODS: Adults undergoing CRS for colorectal or appendiceal adenocarcinoma at our institution between 2016 and 2022 were identified retrospectively and grouped by care network: 'coordinated care' patients received exclusively in-network systemic therapy, while 'fragmented care' patients received some systemic therapy from outside-network providers. Factors associated with fragmented care were also ascertained. Overall survival (OS) from CRS and systemic therapy-related serious adverse events (SAEs) were compared across the groups. RESULTS: Among 85 (80%) patients, 47 (55%) had colorectal primaries and 51 (60%) received fragmented care. Greater travel distance [OR 1.01 (CI 1.00-1.02), p = 0.02] and educational status [OR 1.04 (CI 1.01-1.07), p = 0.01] were associated with receiving fragmented care. OS was comparable between patients who received fragmented and coordinated care in the colorectal [32.5 months versus 40.8 months, HR 0.95 (CI 0.43-2.10), p = 0.89] and appendiceal [31.0 months versus 27.4 months, HR 1.17 (CI 0.37-3.74), p = 0.55] subgroups. The frequency of SAEs (7.8% versus 17.6%, p = 0.19) was also similar. CONCLUSIONS: There were no significant differences in survival or SAEs based on the networks of systemic therapy delivery. This suggests that patients undergoing CRS at a high-volume center may safely receive systemic therapy at outside-network facilities with comparable outcomes.

Outcomes of parenteral nutrition in patients with advanced cancer and malignant bowel obstruction.

Background: Malignant bowel obstruction (MBO) affects 3-15% of all cancer patients. In patients with advanced cancer and inoperable MBO, the average survival varies between four to nine weeks. Parenteral nutrition (PN) may improve survival in specific patient populations with malignant bowel obstruction. Aims: This retrospective, single-center cohort study aimed to review individual patient outcomes on PN in the setting of advanced cancer with a diagnosis of MBO and identify clinical and laboratory markers predictive of short- and long-term survival to further highlight patients that would benefit from PN in the setting of an inoperable MBO. Results: In a retrospective analysis of 68 patients receiving PN for inoperable MBO, the median survival was 142 (IQR: 63.3-239.5) days. Patients experienced a median number of two hospital readmissions (range: 0-10) and spent a median of 29 days (range: 0-105) in the hospital after starting PN. Eighteen (26.5%) patients developed a catheter-related bloodstream infection (CRBSI). A diagnosis of appendiceal cancer was identified as a predictive marker of improved survival (HR: 0.53, 95% CI: 0.29-0.92, p = 0.023). Conclusions: The use of PN in the context of end-of-life cancer care is a practice that necessitates improvement. Recognizing the outcomes and patient experiences of PN utilization is essential to physicians and patients.

Early Integrated Palliative Care Within a Surgical Oncology Clinic.

Importance: Advance directive (AD) designation is an important component of advance care planning (ACP) that helps align care with patient goals. However, it is underutilized in high-risk surgical patients with cancer, and multiple barriers contribute to the low AD designation rates in this population. Objective: To assess the association of early palliative care integration with changes in AD designation among patients with cancer who underwent surgery. Design, Setting, and Participants: This cohort study was a retrospective analysis of a prospectively maintained registry of adult patients who underwent elective surgery for advanced abdominal and soft tissue malignant tumors at a surgical oncology clinic in a comprehensive cancer center with expertise in regional therapeutics between June 2016 and May 2022, with a median (IQR) postoperative follow-up duration of 27 (15-43) months. Data analysis was conducted from December 2022 to April 2023. Exposure: Integration of ACP recommendations and early palliative care consultations into the surgical workflow in 2020 using electronic health records (EHR), preoperative checklists, and resident education. Main Outcomes and Measures: The primary outcomes were AD designation and documentation. Multivariable logistic regression was performed to assess factors associated with AD designation and documentation. Results: Among the 326 patients (median [IQR] age 59 [51-67] years; 189 female patients [58.0%]; 243 non-Hispanic White patients [77.9%]) who underwent surgery, 254 patients (77.9%) designated ADs. The designation rate increased from 72.0% (131 of 182 patients) before workflow integration to 85.4% (123 of 144 patients) after workflow integration in 2020 (P = .004). The AD documentation rate did not increase significantly after workflow integration in 2020 (48.9% [89 of 182] ADs documented vs 56.3% [81 of 144] ADs documented; P = .19). AD designation was associated with palliative care consultation (odds ratio [OR], 41.48; 95% CI, 9.59-179.43; P < .001), palliative-intent treatment (OR, 5.12; 95% CI, 1.32-19.89; P = .02), highest age quartile (OR, 3.79; 95% CI, 1.32-10.89; P = .01), and workflow integration (OR, 2.05; 95% CI, 1.01-4.18; P = .048). Patients who self-identified as a race or ethnicity other than non-Hispanic White were less likely to have designated ADs (OR, 0.36; 95% CI, 0.17-0.76; P = .008). AD documentation was associated with palliative care consulation (OR, 4.17; 95% CI, 2.57- 6.77; P < .001) and the highest age quartile (OR, 2.41; 95% CI, 1.21-4.79; P = .01). Conclusions and Relevance: An integrated ACP initiative was associated with increased AD designation rates among patients with advanced cancer who underwent surgery. These findings demonstrate the feasibility and importance of modifying clinical pathways, integrating EHR-based interventions, and cohabiting palliative care physicians in the surgical workflow for patients with advanced care.

Design and Implementation of a Learner-Centered Self-Paced Peritoneal Oncology Education Program.

BACKGROUND: Current educational programs for peritoneal surface malignancies (PSM) are unstructured and often target advanced learners. The authors describe the design and implementation of a structured, self-paced course at a high-volume PSM center. METHODS: In 2020, a learner-centered course was designed using the Canvas educational platform in consultation with the Center for Teaching at the University of Chicago. The course consisted of disease-site-specific modules, perioperative care pathways, in-built voluntary quizzes, and multimedia supplements for advanced learners. Trainees were provided access during the PSM service rotation, and engagement was compared across training levels by measuring the time spent online. RESULTS: Course design and management required 71 h between 2020 and 2022, with the majority of time spent in the design phase. During 3 years, 62 personnel (21 [34%] medical students, 28 [45%] residents, 8 [13%] staff, and 5 [8%] fellows) were assigned the course. The overall engagement rate was 83.9% (86% of medical students, 75% of residents, 100% of staff and fellows), and the median time spent online was 12.4 min/week (interquartile range [IQR], 2.1-53.0 min/week). Fourth-year medical students and clinical fellows spent more time online than other learners (73 min/week [IQR, 24.5-100 min/week] vs 13.3 min/week [IQR, 7.3-26.5 min/week]) (p = 0.001). CONCLUSIONS: The design and implementation of a PSM-specific course was feasible and sustainable using an online learning platform. Higher engagement was noted among invested learners. Non-technical factors for reduced engagement need to be ascertained further to improve the next iteration of this course.

Surgical phenotype of patients with peritoneal mesothelioma and a germline mutation.

BACKGROUND: This study aimed to investigate if peritoneal mesothelioma (PM) patients with germline mutations (GM) have distinct surgical characteristics when compared to those without GM. METHODS: PM patients were selected from an ongoing prospective study that conducts germline testing of 82 susceptibility genes. Germline status was correlated with surgical data obtained from a prospectively collected database using univariate, multivariate, and receiver operating characteristic (ROC) analyses. RESULTS: Out of 88 PM patients enrolled between 2009 and 2019, 18 GMs (20.5%) were identified in BRCA1-associated protein 1 (BAP1) (n = 11, 12.5% of all patients), SDHA (n = 2) and WT1, CDKN2A, CHEK2, ATM, and BRCA2 (n = 1 patient each). Surgical procedures were performed in 71 patients, the most common of which were cytoreductive surgeries with hyperthermic intraperitoneal chemotherapy (n = 61). Patients with GM presented with a higher prevalence of other prior cancers (61.1% vs. 31.4%, p = .02) and lower platelet count (251 [160-413] vs. 367 [196-780] K/µL, p = .005) compared to those without GM (n = 70). Survival outcomes did not differ significantly between the groups. Patients with BAP1 GMs were more likely to develop bicavitary disease and to present with lower platelet count and mitotic count score, and higher peritoneal cancer index (PCI, all p ≤ .04) compared with those without GM. On ROC analysis, the combination of PCI, platelet count and mitotic score yielded an area under the curve of 0.96 (95% CI, 0.91-1.0) for BAP1 GM detection among operated PM patients. CONCLUSION: Higher intraoperative tumor burden and lower platelet count and mitotic score are suggestive of BAP1 GMs in surgical PM patients and should prompt germline testing.

Role of Tumor-informed Personalized Circulating Tumor DNA Assay in Informing Recurrence in Patients With Peritoneal Metastases From Colorectal and High-grade Appendix Cancer Undergoing Curative-intent Surgery.

OBJECTIVE: To investigate the role of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay in informing recurrence in patients with peritoneal metastases (PM) from colorectal (CRC) and high-grade appendix (HGA) cancer after curative cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). BACKGROUND: Over 50% of patients with CRC/HGA-PM recur after optimal CRS-HIPEC. The limited sensitivity of axial imaging and diagnostic biomarkers is a significant cause of delay in the detection of recurrence and initiation of further therapies. Plasma ctDNA has a promising role in monitoring response to treatment and/or recurrence after primary cancer resection. METHODS: Patients with CRC/HGA-PM who underwent curative CRS-HIPEC and serial postresection ctDNA assessments were included. Patients with rising postoperative ctDNA levels were compared with those with stable, undetectable ctDNA levels. Primary outcomes were the percentage of patients with recurrence and disease-free survival (DFS). Secondary outcomes were overall survival, ctDNA sensitivity, lead time, and performance of ctDNA compared with carcinoembryonic antigen. RESULTS: One hundred thirty serial postresection ctDNA assessments [median 4, interquartile range (IQR), 3 to 5] were performed in 33 patients (n = 13 CRC, n = 20 HGA) who underwent completeness of cytoreduction-0/1 CRS with a median follow-up of 13 months. Of the 19 patients with rising ctDNA levels, 90% recurred versus 21% in the stable ctDNA group (n = 14, < 0.001). Median DFS in the rising ctDNA cohort was 11 months (IQR, 6 to 12) and not reached in the stable ( P = 0.01). A rising ctDNA level was the most significant factor associated with DFS (hazard ratio: 3.67, 95% CI: 1.06-12.66, P = 0.03). The sensitivity and specificity of rising ctDNA levels in predicting recurrence were 85% and 84.6%, respectively. The median ctDNA lead time was 3 months (IQR, 1 to 4). Carcinoembryonic antigen was less sensitive (50%) than ctDNA. CONCLUSIONS: This study supports the clinical validity of serial ctDNA assessment as a strong prognostic biomarker in informing recurrence in patients with CRC/HGA-PM undergoing curative resection. It also holds promises for informing future clinical trial designs and further research.

Palliative Care and Characterization of Symptoms in Patients Undergoing Cytoreductive Surgery/Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: Palliative care for advanced cancer patients has been associated with improvements in symptom management and quality of life (QoL). Patients with peritoneal metastases undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) often report symptoms adversely affecting QoL. We characterized and compared symptoms elucidated by palliative care versus surgical providers in this setting. METHODS: CRS/HIPEC patients who saw both surgical oncology and palliative care providers from 2016 to 2020 at a tertiary care center were identified from a retrospective database. Documentation of QoL-associated symptoms in surgical oncology and palliative care visits was recorded and analyzed. RESULTS: A total of 118 patients were included in this study. The most common primary histologies were appendiceal (36.4%) and colorectal (28.8%). Symptoms most frequently reported by palliative care were pain (60.2%) and fatigue (54.2%). The median number of symptoms documented was three (2, 5) in palliative care notes and two (0, 3) in surgical oncology notes (P < 0.001). Palliative care providers documented most symptoms statistically more frequently than surgical oncology providers. CONCLUSIONS: Patients who underwent CRS/HIPEC experienced various QoL-associated symptoms. Palliative care providers elicited more symptoms than surgical oncology providers. Additional studies are needed to explore the impact on outcomes of perioperative palliative care in this challenging patient population.

PI3K Pathway Alterations in Peritoneal Metastases are Associated with Earlier Recurrence in Patients with Colorectal Cancer Undergoing Optimal Cytoreductive Surgery.

BACKGROUND: Colorectal cancer with peritoneal metastasis (CRC-PM) represents a biologically heterogeneous disease; yet little is known regarding the impact of tumor biology on survival outcomes following optimal cytoreductive surgery (CRS). We analyzed the frequency of alterations in cancer signaling pathways in patients with CRC-PM and their impact on recurrence-free survival (RFS) following optimal CRS. METHODS: Thirty-five consecutive CRC-PM patients who underwent optimal CRS/HIPEC and next generation sequencing of peritoneal metastases were included in the study. Alterations in eight cancer-related signaling pathways were analyzed: Wnt/APC, p53, RTK-RAS, PI3K, TGF-B, Notch, Myc, and cell cycle. The association of pathway alterations with RFS and OS following optimal cytoreduction was estimated using Cox proportional hazard modeling. RESULTS: The most frequently altered pathways were Wnt/APC (63%), p53 (63%), RTK-RAS (60%), and PI3K (23%). Among optimally cytoreduced patients with CRC-PM, PI3K pathway alterations were an independent predictor of worse RFS (hazard ratio 3.2, 95% confidence interval CI 1.3-8.3, p = 0.01) with a clinically meaningful impact on median months to recurrence (5 vs. 13 months, p = 0.02). Alterations in p53, Wnt, and RTK-RAS pathways were not significantly associated with a difference in RFS following CRS. Alterations in the four pathways were not associated with differences in OS following CRS (median OS was 50 (interquartile range 23-80) months). CONCLUSIONS: In patients with CRC-PM, PI3K pathway alterations are associated with earlier recurrence following optimal CRS, which may represent a distinct molecular subtype. This novel finding can tailor clinical trials by using PIK3CA-directed interventions to reduce risk of recurrence after optimal CRS.

Mutational profiles and prognostic impact in colorectal and high-grade appendiceal adenocarcinoma with peritoneal metastases.

BACKGROUND: Next-generation sequencing (NGS) personalizes cancer treatments. In this study, we analyze outcomes based on NGS testing for colorectal cancer (CRC) and high-grade appendiceal adenocarcinoma (HGA) with peritoneal metastases. METHODS: Retrospective review of genomic analyses and outcomes in patients with CRC or HGA with peritoneal metastases at a high-volume center from 2012 to 2019. RESULTS: Ninety-two patients (57 CRC, 35 HGA) were identified. Overall survival was longer for CRC (52.8 vs. 30.5 months, p = 0.03), though rates of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) were similar. Multiple genes were more frequently mutated in CRC, including KRAS (51% vs. 29%, p = 0.04), TP53 (47% vs. 20%, p < 0.01), and APC (46% vs. 6%, p < 0.01). For CRC, multivariate regression showed an increased hazard ratio (HR) with increasing peritoneal cancer index (1.06 [1.01-1.11], p = 0.02) and a decreased HR following CRS/HIPEC (0.30 [0.11-0.80], p = 0.02). PIK3CA mutation associated with significantly increased HR (3.62 [1.06-12.41], p = 0.04), though only in non-CRS/HIPEC patients. Multivariate analysis in the HGA group showed a benefit following CRS/HIPEC (0.18 [0.06-0.61], p = 0.01) and for mucinous disease (0.38 [0.15-0.96], p = 0.04), while there was an increased HR with TP53 mutation (6.89 [2.12-22.44], p < 0.01). CONCLUSION: CRC and HGA with peritoneal spread have distinct mutational profiles. PIK3CA and TP53 mutations are associated with survival for CRC or HGA with peritoneal metastases, respectively.

Photoredox Minisci-Type Hydroxyfluoroalkylation of Isoquinolines with N-Trifluoroethoxyphthalimide.

A straightforward photocatalytic approach has been demonstrated to incorporate a trifluoroethanol unit onto the isoquinolines. Herein, we report N-trifluoroethoxyphthalimide as a hydroxyfluoroalkyl radical precursor, enabling efficient synthesis of trifluoroethanol-substituted heteroarenes. Radical quenching experiments confirmed the involvement of a free-radical pathway under developed photocatalytic conditions. The DFT calculations confirmed the intramolecular 1,2-HAT reactivity of the O-centered trifluoroethoxy radical (generated from N-trifluoroethoxyphthalimide under photocatalytic condition) to the C-centered trifluoroethanol radical. Fluorescence quenching studies suggested that isoquinoline was responsible for the quenching of Ir-photocatalyst emission. A catalytic cycle involving trifluoroethanol radical reaction with isoquinolines has been proposed.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: Where do we stand?

PLAIN LANGUAGE SUMMARY: Patients with colorectal cancer that has spread to the lining of the abdomen (peritoneum) benefit from surgery to remove all the cancer. The addition of certain types of intra-abdominal chemotherapy during surgery improves survival for select patients.