PCI Score Research Articles

Physical Activity and Cognition: Longitudinal findings from the Thinking and Living with Cancer Study.

Physical activity can improve cognition; however, little is known regarding the relationships between longitudinal objectively-measured physical activity, cognition, and inflammation in older breast cancer survivors. Older (≥60 yrs) breast cancer survivors (n = 216) and frequency-matched non-cancer controls (n = 216) were assessed at baseline (pre-systemic therapy for survivors) and annually for up to five years. Assessments included hip-worn ActiGraphs worn for seven days, neuropsychological tests, the Functional Assessment of Cancer Therapy-Cognitive Function Perceived Cognitive Impairment (FACT-Cog PCI) subscale, and circulating levels of C-reactive protein (CRP) and interleukin-6 (IL-6). Data were analyzed using linear mixed-effect, random-effect contemporaneous fluctuation, and multi-level mediation models, considering covariates; p < .05 (two-sided) was considered significant. Survivors had fewer minutes of moderate-to-vigorous physical activity (MVPA) than controls at 36-, 48-, and 60-month time points (p < .03). Fewer survivors met Aerobic Physical Activity Guidelines at 36 months than controls (17.7% vs 33.0%, p = .030). When Guidelines were met (vs not), FACT-Cog PCI scores were 2.1 ± 1.0 (p = .034) points higher. Higher MVPA and meeting Aerobic Guidelines were not related to objective neuropsychological performance. MVPA was inversely associated with CRP and IL-6 (p < .001), but inflammation did not mediate physical activity effects on perceived cognition. Older breast cancer survivors were less physically active than older non-cancer controls, especially farther from baseline. Meeting Aerobic Guidelines was associated with better perceived cognition in survivors. Survivorship care should consider physical activity monitoring and referral to rehabilitation and supervised exercise programs to promote physical activity and improve recovery in older survivors.

Clinical Significance of Circulating Tumor Cells in Epithelial Appendiceal Neoplasms with Peritoneal Metastases.

Appendiceal tumors are uncommon and, at times, discovered incidentally during histological examination. The histopathological classification of the disease is complex and has generated some controversy. The analysis of circulating tumor cells can be used for the early detection of metastatic potential. The aim of the present study was to examine the prognostic value of circulating tumor cells in patients with appendiceal tumors and peritoneal metastases. To our knowledge, this is the first study to examine CTCs in appendiceal tumors. We performed a prospective cohort study of consecutive patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy between 2015 and 2019 at a HIPEC referral center. In total, 31 patients were included in the analysis, and circulating tumor cells were detected in 15 patients (48%). CTC positivity was not associated with overall or recurrence-free survival, nor was it correlated with PCI score or histopathological grading. Surprisingly, however, CTCs were found in almost half the patients. The presence or quantities of these cells did not, on their own, predict systemic metastatic potential during the observed time, and they did not appear to significantly correlate with the oncological outcomes recorded.

Outcomes of patients with peritoneal carcinomatosis treated with HIPEC and chemotherapy or HIPEC alone: A single center community experience.

e15578 Background: Peritoneal carcinomatosis is a common presentation of intraperitoneal malignancies. The optimal management of peritoneal carcinomatosis is currently unknown but can contain a combination of HIPEC and chemotherapy. Optimal timing and order of these interventions is controversial. HIPEC surgery alone can provide a cure rate of approximately 16% with macroscopically complete resection. The PRODIGE 7 trial demonstrated no difference in overall survival between HIPEC plus cytoreduction versus cytoreduction alone with six months of systemic chemotherapy. Which patients should receive HIPEC, chemotherapy and HIPEC or chemotherapy alone remains unknown. Methods: This is a single center, retrospective chart review assessing all patients age 18 and above who received HIPEC surgery with and without the administration of chemotherapy at Ascension Saint John Hospital. Results: We found that there was no significant difference in overall survival and progression free survival between the HIPEC and HIPEC with chemotherapy group with a OS of 57.2 months and 52.5 months; and PFS of 33.6 and 34.4 months respectively. We found that patients with a PCI score between 0 and 13, overall survival favored the HIPEC alone group versus the HIPEC with chemotherapy with a p value of 0.043. There was no difference in progression free survival and overall survival in all other groups when stratified by PCI. When stratified by disease subtype, we no differences between PFS and OS for both appendiceal and colon cancer. Conclusions: The primary objective of this study was to investigate the difference in overall survival and progression free survival among patients with peritoneal carcinomatosis when treated with either HIPEC with systemic chemotherapy versus HIPEC alone. This analysis among 100 patients showed no statistically significant differences in OS or PFS for patients receiving a combination of HIPEC with systemic chemotherapy versus HIPEC alone. The only exception to this was with respect to OS in patients with a PCI score between 0-13. In this group, 0 patients in the HIPEC along group experienced disease progression where 5 progressed in the HIPEC and chemotherapy group. Our data suggests that HIPEC alone may be a reasonable treatment approach for patients with a low PCI score. Important conclusions can be drawn from the data when compared to historical trials. The PROTEGE 7 study found that the median overall survival was approximately 41.7 months for the HIPEC and cytoreductive surgery group and 41.2 months versus cytoreductive surgery alone. The overall survival for the HIPEC alone group was 57.2 months and 52.5 months for the HIPEC plus chemotherapy group. This data suggests that the combination of HIPEC and chemotherapy is a reasonable approach to patients with peritoneal carcinomatosis.

A phase I/II study of intraperitoneal (IP) paclitaxel (PTX) in patients with metastatic appendiceal adenocarcinoma.

TPS4215 Background: Appendiceal cancer is a rare, orphan disease, that is unfortunately becoming more common. There is growing data from our lab and others that particular subtypes of AA do not respond to CRC chemotherapy. The use of CRC chemotherapy to treat patients with AA tragically results in many patients enduring side effects from chemotherapy that is ineffective; however, this practice will likely continue unless AA-specific treatments are developed. The Shen lab has recently tested IP paclitaxel (PTX) in orthotopic PDX models of AA. After allowing implanted tumors to grow for four weeks to simulate diffuse peritoneal metastases, baseline MRI was performed and mice were randomly assigned to treatment groups of four mice and intraperitoneally (IP) administered increasing doses of PTX. Marked response was seen in all three models at dose of 25 mg/kg IP weekly, with a near complete response in model AAPDX-10. This dose given IP was well tolerated by the mice, notably this dose exceeds the know lethal IV PTX dose. Methods: The Phase I component of this study will be a prospective single-arm intervention trial giving IP PTX every 2 weeks for a total of 5 doses with primary endpoint of safety and tolerability (MTD determination). Each patient will have an initial diagnostic laparoscopy where PCI score will be calculated and IP catheter placed, dx lap is repeated at the end of study after 5 biweekly doses. For the Phase 1 portion of the trial a Bayesian Optimal Interval (BOIN) approach will be used to determine recommended phase 2 dose (RP2D). All patients treated at that dose or higher will be included in Phase 2 component of the study where the primary objective is response, determined by change in PCI score. With 15 patients Based on historical data, we estimate that the proportion of patients who will demonstrate an objective response without going on trial is 0.05, i.e., the null hypothesis is a 0.05 ORR. Treatment is expected to raise this proportion to 30%. Using an exact binomial test with one-sided type I error of 0.05, we will reject the null if at least 3 patients achieve response. This test has power of 87%. Secondary end points include pathologic, biochemical and radiographic response, PFS, OS, and the influence of KRAS/GNAS/TP53 mutation on response. PK measurements will also be performed during the Phase 1 portion of the trial to determine the degree to which the IP injected PTX enters the blood stream. Patients will be followed for up to 1 year. Adverse events (AEs) will be captured and graded using the National Cancer Institute’s (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) v. 5.0 (or latest version) and will include the event term, grading, duration and attribution. Attribution to the study agent or intervention will be determined by the PI, Co-PI or treating physician. Clinical trial information: NCT06207305 . [Table: see text]

Modified scoring system for the quantitative assessment of histological regression in peritoneal carcinomatosis after pressurized intraperitoneal aerosol chemotherapy: A pilot study.

Peritoneal carcinomatosis is one of the leading causes of death in patients with gastrointestinal cancer. Newer locoregional treatment concepts include pressurized intraperitoneal aerosol chemotherapy (PIPAC), the regional application of pressurized chemotherapeutic agents to the abdominal cavity, which is usually performed every 4 to 8 weeks. One of the main challenges of PIPAC therapy remains the objective assessment of treatment response. The present study describes a new scoring system to histologically assess the regression of peritoneal cancer following PIPAC therapy, quantitative assessment of histological regression in peritoneal carcinomatosis (QARP). Peritoneal biopsies from 27 patients with peritoneal metastases undergoing PIPAC were obtained and processed in a standardized fashion. Biopsies were scored according to the QARP grading system. The five-tiered system was graded as follows, Grade 0, no residual tumor cells with regressive changes present; grade 1, 1-25% viable tumor cells per tumor focus with regressive changes present; grade 2, 26-50% viable tumor cells per tumor focus with regressive changes present; grade 3, 51-75% viable tumor cells per tumor focus with few regressive changes; grade 4, >75% viable tumor cells per tumor focus with minimal or no regressive changes. Based on the new grading system, the study cohort was divided into QARP responders and QARP non-responders following PIPAC treatment. Higher QARP scores were significantly correlated with higher PCI scores (r=0.32; P=0.007). However, no difference in overall survival was detected between QARP responders and QARP non-responders. Further studies are required to ascertain the reproducibility and prognostic significance of QARP.

Oncological outcomes and hospitalization cost of hyperthermic intraperitoneal chemotherapy (HIPEC) open and closed abdomen techniques: Results from two French expert centers

BackgroundHyperthermic intraperitoneal chemotherapy (HIPEC) associated with CC0 excision is performed using either an open (OPEN_HIPEC) or closed abdominal technique (CLOSED_HIPEC). However, little data is available on the costs of this treatment, as there is no code for HIPEC in the French Classification of Medical Acts. Oncological outcomes and the mean cost of hospitalization were compared. MethodsBetween 2017-2021, 144 patients with peritoneal carcinomatosis (all etiologies) were included (OPEN_HIPEC, n = 70; CLOSED_HIPEC, n = 74) in this retrospective two-center study. Morbi-mortality, overall survival (OS), recurrence-free-survival (RFS) and mean cost of hospitalization were compared. ResultsThe median OS and RFS were 71.3 months [63–71.5] and 26.8 months [20–35.3] respectively, and were similar for both techniques; and after stratification by histology. Multivariate analysis adjusted on PCI score of OS identified mitomycin as a protective factor (HR = 0.31 [0.10–0.90], p = 0.032) and ASA score>2 as a risk factor of RFS (HR = 2.21 [1.28–3.83], p = 0.004). Complication rates at day 30 were similar between OPEN and CLOSED_HIPEC, 31 (44.3 %) vs 42 (56.8 %); p = 0.135. OPEN_HIPEC had more severe complications (11(35.5 %) vs 6(14.3 %); p = 0.034). The mean cost of hospitalization was estimated as €15,627 for OPEN_HIPEC and €14,211 for CLOSED_HIPEC for a mean length-of-stay of 12.7 and 16.7 days respectively. The mean amount received by the hospital per hospitalization was estimated at €16,399 and €15,536 respectively. ConclusionsOS and RFS were similar for open and closed HIPEC. Severe complications at day 30 were more frequent in OPEN_HIPEC group. The amount received by hospital for both HIPEC techniques is sufficient.

Clinical outcomes of conversion surgery following immune checkpoint inhibitors and chemotherapy in stage IV gastric cancer with peritoneal metastasis.

281 Background: Although anti-PD-1 antibody in combination with chemotherapy and/or targeted therapy has shown promising antitumor activity in advanced gastric adenocarcinoma (GC), the evidence of conversion therapy for initially GC with peritoneal metastasis is limited. This study aimed to clarify the clinical outcomes of conversion therapy for such patients. Methods: In this retrospective single institution cohort study, we analyzed 83 GC patients with peritoneal metastasis who received first-line anti-PD-1 antibody and chemotherapy and/or target therapy (trastuzumab) between November 2019 and June 2023. In patients who respond well to treatment, when preoperative imaging studies, multidisciplinary team discussions, and staged laparoscopy indicated the absence of peritoneal metastasis and the possibility of R0 resection, patients were offered conversion surgery. In this study, palliative surgery was not included. Patients were divided into two groups: conversion therapy group and palliative therapy group. Results: All patients underwent staging laparoscopy at their initial visit and underwent at least 2 treatment cycle, with a median follow-up time of 20.3 (16-24.6) months. Of the 83 patients, 32 patients presented a clinical response and underwent re-laparoscopy. Negative peritoneal metastasis and peritoneal cytology were confirmed in 25 patients who proceeded to undergo the conversion surgery. Compared with palliative therapy group, surgery group had a significantly better median progression-free survival (PFS) (20.3 vs 5.1 months; p &lt; 0.001) and a prolonged median overall survival (OS) (33.4 vs 11.7 months; p &lt; 0.001). In the surgery group, 24 (96%) of 25 patients were performed laparoscopic gastrectomy radical laparoscopic gastrectomy with more than D2 lymph node dissection (only one patient underwent open gastrectomy), 19 (76%) patients achieved R0 resection, 2 (8%) patients achieved pathologic complete response (pCR) and 4 (16%) patients reached tumor regression grade (TRG) 0-1. It was observed that patients with PCI score ≤ 2 experienced a longer median OS in comparison to those with PCI scores &gt; 2 ( unreached vs 28.5 months, P &lt; 0.031). And multivariate analysis associated with PFS among surgery cases identified signet ring cell carcinoma as an independent adverse prognostic factor (HR 4.66; 95% CI 1.19–18.22; p = 0.027). No serious treatment-related adverse events resulted in termination of treatment or death. Conclusions: Conversion surgery following first-line anti-PD-1 antibody in combination with chemotherapy and/or targeted therapy represented a promising treatment strategy for GC patients with peritoneal metastasis. When immunochemotherapy is effective, active second-look staging laparoscopy should be performed to clarify the possibility of conversion surgery.

8 Self-Reported versus Performance-Based Cancer-Related Cognitive Impairment in Older Women with Nonmetastatic Breast Cancer

Objective:The Functional Assessment of Cancer Therapy-Cognitive scale (FACT-Cog) is one of the most frequently used patient-reported outcome (PRO) measures of cancer-related cognitive impairment (CRCI) and of CRCI-related impact on quality of life (QOL). Previous studies using the FACT-Cog found that &gt;75% of women with breast cancer (BCa) experience CRCI. Distress tolerance (DT) is a complex construct that encompasses both the perceived capacity (i.e., cognitive appraisal) and the behavioral act of withstanding uncomfortable/aversive/negative emotional or physical experiences. Low DT is associated with psychopathology and executive dysfunction. We previously found that women with BCa with better DT skills reported less CRCI on the FACT-Cog. However, this relationship has not been tested using a performance-based cognitive measure. Therefore, the aims of this study were to: (1) assess the relationship between the FACT-Cog and the Telephone Interview for Cognitive Status (TICS), a performance-based cognitive measure; and (2) test whether the association between DT and CRCI (using the FACT-Cog) was replicated with the TICS.Participants and Methods:Participants completed the Distress Tolerance Scale (DTS), the FACT-Cog, and the TICS after undergoing BCa surgery and prior to starting adjuvant therapy [101 women, age &gt;50 years, M(SD)= 61.15(7.76), 43% White Non-Hispanic, 34.4% White Hispanic, 10.8% Black, with nonmetastatic BCa, 55.4% lumpectomy, 36.6% mastectomy; median 29 days post-surgery].Results:Although there was a significant correlation between the TICS total score and the FACT-CogQOL subscale (r = 0.347, p &lt; 0.001), the TICS total score was not correlated with scores on the FACT-Cog perceived cognitive impairment (CogPCI), perceived cognitive abilities (CogPCA), or comments from others (CogOth) subscales. However, the TICS memory item, a 10-word list immediate recall task, had a weak statistically significant correlation with CogPCI (r = 0.237, p &lt; 0.032), CogOth (r = 0.223, p &lt; 0.044), and CogPCA (r = 0.233, p &lt; 0.036). Next, the sample was divided based on the participant’s score on TICS memory item (i.e., &lt; vs. &gt; sample mean of 5.09). Results of independent samples t-tests demonstrated significant differences in mean scores for CogPCI, f(80) = -2.09, p = 0.04, Mdt = -7.65, Cohen’s d = 0.483, and CogQOL, f(80) = -2.57, p = 0.01, Mditt = -2.38, Cohen’s d = 0.593. A hierarchical linear regression found that DTS subscale and total scores did not significantly predict performance on the TICS. However, DTS continued to be a significant predictor of poorer FACT-Cog PCI scores while controlling for TICS scores.Conclusions:We found a weak relationship between self-reported cognitive impairment and objective cognitive performance (TICS). However, greater self-reported PCI and its impact on QOL was found in participants who scored below the sample mean on a recall task from the TICS. Although perceived ability to tolerate distress continued to predict self-reported PCI on the FACT-Cog, it did not predict overall performance on the TICS. Therefore, responses on the FACT-Cog may be more representative of an individual’s ability to tolerate distress related to perceived CRCI than actual overall cognitive ability or impairment.

Bedside Testing in Acute Vestibular Syndrome-Evaluating HINTS Plus and Beyond-A Critical Review.

Acute vertigo and dizziness are frequent presenting symptoms in patients in the emergency department. These symptoms, which can be subtle and transient, present diagnostic challenges because they can be caused by a broad range of conditions that cut across many specialties and organ systems. Previous work has emphasized the value of combining structured history taking and a targeted examination focusing on subtle oculomotor signs. In this review, we discuss various diagnostic bedside algorithms proposed for the acutely dizzy patient. We analyzed these different approaches by calculating their area-under-the-curve (ROC) characteristics and sensitivity/specificity. We found that the algorithms that incorporated structured history taking and the use of subtle oculomotor signs had the highest diagnostic accuracy. In fact, both the HINTS+ bedside exam and the STANDING algorithm can more accurately diagnose acute strokes than early (<24 to 48 h after symptom onset) MRI with diffusion-weighted imaging (DWI). An important caveat is that HINTS and STANDING require moderate training to achieve this accuracy. Therefore, for physicians who have not undergone adequate training, other approaches are needed. These other approaches (e.g., ABCD2 score, PCI score, and TriAGe+ score) rely on vascular risk factors, clinical symptoms, and focal neurologic findings. While these other scores are easier for frontline providers to use, their diagnostic accuracy is far lower than HINTS+ or STANDING. Therefore, a focus on providing dedicated training in HINTS+ or STANDING techniques to frontline clinicians will be key to improving diagnostic accuracy and avoiding unnecessary brain imaging.

Parenteral nutrition after cytoreductive surgery for peritoneal malignancy: Should it be administered routinely?

Purpose/backgroundCytoreductive surgery (CRS) is complex abdominal surgery that is used to treat peritoneal malignancy. CRS is associated with major morbidity and efforts to address this include optimisation of perioperative care. There is variation in international protocols on the nutritional management after CRS, in particular whether parenteral nutrition (PN) should be routinely or selectively administered. Hypothesis/aimThis study assessed parenteral nutrition use, factors associated with PN requirement and nutritional outcomes in a centre that selectively uses PN after CRS. Methods/interventionsA retrospective analysis was undertaken on patients who underwent cytoreductive surgery ± hyperthermic intraperitoneal chemotherapy (HIPEC) at Peter MacCallum Cancer Centre between 1st January 2015 and 31st December 2020 using data entered into a prospectively maintained database. Patient characteristics, nutritional status, oncological parameters, operative details and postoperative outcome data were retrieved. Categorical variables were compared using the chi-squared test and continuous data was compared using a non-parametric Mann–Whitney U-test. A p-value <0.05 was considered statistically significant. Cox regression analysis was performed to identify independent predictors of requiring PN and postoperative weight change over admission. ResultsA total of 222 patients who had CRS between were included (mean age 56 years; female 61.3%). Preoperative nutritional characteristics of participants included a mean body mass index (BMI) of 27.6 kg/m2 and the majority (77.9%) were not at nutritional risk pre-operatively with a Patient Generated Subjective Global Assessment (PG-SGA) score of category A. A high proportion of patients had surgery for colonic adenocarcinoma (58.1%), received HIPEC (87.4%) and achieved complete cytoreduction (82%). Postoperative parenteral nutrition was required for 65 patients (29.3%). The most frequent indication for PN was postoperative ileus (63.1%) with the mean (SD) time to commencing PN being postoperative day 5. Factors associated with the requirement for postoperative PN included preoperative albumin (OR 0.89; p = 0.015), weight loss >5% of body weight in the 6 months prior to admission (OR 2.2; p = 0.05), higher PCI score (OR 1.048; p = 0.005), number of anastomoses completed (OR 1.766; p = 0.017) and development of any postoperative complication (OR 2.71; p = 0.009). PN use was not associated with postoperative weight change. ConclusionMost patients undergoing CRS did not require post-operative PN. Nutritional and operative factors may identify patients who are likely to need PN after surgery. Selective use of PN did not impact on postoperative weight change.

Impact of Body Mass Index on Postoperative Pain and Opioid Administration After Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC).

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new surgical technique, developed for the treatment of peritoneal carcinomatosis (PC). In this retrospective observational study we assessed the impact of body mass index (BMI) on postoperative pain and opioid consumption. We analyzed pain scores after 100 PIPAC procedures using either oxaliplatin or doxorubicin-cisplatin performed in 49 patients with PC between July 2016 and September 2020. The patients were divided into 3 groups (BMI <18.5, 18.5 ≥ BMI < 25, BMI≥25). Pain was self-rated on a visual analogue scale (VAS) from 0 to 10. Univariate logistic regression analysis identified oxaliplatin and PCI score to be associated with moderate to severe pain (VAS 4-10 at 8 am D1) after adjustment on BMI (OR [95% CI]; 3.26[1.00 - 10.65] p=0.050) and (OR [95% CI]; 1.09[1.01 - 1.17] p=0.019). The level of pain appeared significantly different between the treatment groups (median 2.5[0; 5] vs 0[0; 2.5] p=0.0017) irrespective of BMI (p =0.705 and p=0.118). Multivariate logistic regression analysis identified moderate to severe pain and synchronous PC to be associated with greater use of opioids (OR [95% CI]: 3.91 [1.24 - 12.32]) and (OR [95% CI]: 5.16 [1.71 - 15.58]; respectively. Opioids were administered after 45 procedures (45%) and was comparable between the treatment groups. Opioid administration and length-of-stay were similar among BMI bands. BMI is not related to postoperative pain or opioid use, howevermoderate to severe pain and synchronous PC are factors associated with requiring opioids.

Multi-institutional study evaluating the role of circulating tumor DNA (ctDNA) in management of appendiceal cancers (AC).

4170 Background: AC frequently present with peritoneal metastases (PM) which are difficult to accurately measure with imaging techniques or serum tumor markers. ctDNA is a novel, promising biomarker to assess minimal residual disease (MRD) and therapy response. Its utility in AC with PM is poorly studied due to the rarity of this disease condition. This is a report on the role of ctDNA in AC management. Methods: Patients with AC managed at two high volume centers between 01/01/2019 to 12/15/2022were included in this study. CtDNA measurements were prospectively collected using Signatera tumor informed ctDNA assay during clinical care and these data were abstracted retrospectively. Cox-proportional hazards were utilized for survival analysis. Results: 97 patients with AC were included with a median age of 57 (IQR 53-66) years, majority being non-Hispanic white (85%) and female (63%). 68 (70%) patients had ctDNA assay drawn at the time of confirmed clinical disease (radiographic or laparoscopic). The sensitivity of ctDNA was 56% (CI 44% - 67%)) for all grades, and 66% (CI 49% - 80%) for grade 3 tumors. 65 (67%) patients underwent cytoreductive surgery (CRS), of which 16 (24.6%) had preoperative ctDNA assays. Sensitivity in this cohort of surgical patients was 25% and positive ctDNA showed poor correlation with PCI score at time of surgery (n=4, r = 0.38, p = 0.14). Any positive value for post-operative ctDNA was associated with lower disease free survival (DFS) (9 months (CI 5-13) in low grade AC and 10 months (CI 7-14) in high grade AC, compared to not reached for those persistently negative (p&lt;0.001) over a median follow-up duration of 17 months. This difference persisted despite adjusting for adjuvant chemotherapy for high-grade disease (aHR = 11.2 (1.4-88.6), p = 0.023). Conclusions: This is the largest study reported to date of tumor informed ctDNA testing in patients with AC. These data show that ctDNA has low sensitivity in both the metastatic unresectable and in pre-operative settings. However, ctDNA positivity after CRS in AC has prognostic value and could be used to guide systemic therapy decisions.

Prognostic and predictive significance of pre- and post-operative plasma tumor markers in patients with appendiceal adenocarcinoma undergoing cytoreductive surgery: Insights from a single-center study.

3539 Background: Appendiceal adenocarcinomas (AA) are both rare and heterogeneous diseases. Cytoreductive (CRS) surgery followed by heated intraperitoneal chemotherapy (HIPEC) remains the best treatment for AA patients with peritoneal metastasis. This study seeks to investigate the clinical utility of pre- and post-operative plasma tumor markers (TM, CEA, CA19-9, CA-125) by association with survival outcomes. Methods: Under an approved IRB protocol the Palantir Foundry software system was used to query MD Anderson internal database to identify patients with AA who underwent CRS between 2016 to 2022. Elevation of TM was defined as above the laboratory upper limit of normal (CEA &gt; 3 ng/mL, CA 19-9 &gt; 37 U/mL, and CA-125 &gt; 37 U/mL). Relationship between normal and elevated serum TM and progression-free survival (PFS) and overall survival (OS) was evaluated using univariate and multivariate Cox-proportional hazards regression analysis, considering multiple clinicopathologic variables. Results: 296 patients were identified; preoperative CEA, CA19-9 and CA125 was elevated in 60%, 29% and 28% of patients, respectively. Preoperative elevation of any TM was associated with higher PCI score (22 vs. 15, p&lt; 0.0001). Moreover, elevated preoperative TM was associated with incompleteness of cytoreduction (OR = 6.5, p&lt; 0.0001). Compared to preoperative measurements, all TM levels dropped after surgery (Mean score 31 vs 11 for CEA, 136 vs 32 for CA19-9 and 36 vs 17 for CA125). Preoperative elevation of any TM (HR = 1.5, p= 0.0288) and post-op elevation of any TM were with poor PFS on univariate analysis, however only post-op elevated TM levels (HR = 2.3, p= 0.0001) were associated with poor PFS on multivariate analysis. Interestingly, elevated TM was not associated with OS. Post-op TM levels were analyzed to evaluate the positive and negative predictive value in prediction of relapse in 6 months from surgery, PPV was 45% and NPV was 84%. Conclusions: Preoperative elevation of TM can identify patients at higher risk for incomplete cytoreduction and relapse after surgery. Postoperative elevation of TM is a risk factor for relapse. [Table: see text]

Pressurized intraperitoneal aerosol chemotherapy, reasons for interrupting treatment: a systematic review of the literature.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) gives encouraging results in the treatment of peritoneal metastasis (PM). The current recommendations require at least 3 sessions of PIPAC. However, some patients do not complete the full treatment course and stop after only 1 or 2 procedures, hence the limited benefit. A literature review was performed, with search terms including "PIPAC" and "pressurised intraperitoneal aerosol chemotherapy." Only articles describing the causes for premature termination of the PIPAC treatment were analysed. The systematic search identified 26 published clinical articles related to PIPAC and reporting causes for stopping PIPAC. The series range from 11 to 144 patients, with a total of 1352 patients treated with PIPAC for various tumours. A total of 3088 PIPAC treatments were performed. The median number of PIPAC treatments per patient was 2.1, the median PCI score at the time of the first PIPAC was 19 and the number of patients who did not complete the recommended 3 sessions of PIPAC was 714 (52.8%). Disease progression was the main reason for early termination of the PIPAC treatment (49.1%). The other causes were death, patients' wishes, adverse events, conversion to curative cytoreductive surgery and other medical reasons (embolism, pulmonary infection, etc…). Further investigations are necessary to better understand the causes for interrupting PIPAC treatment and also improving the selection of patients who are most likely to benefit from PIPAC.

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

This study aimed to investigate if peritoneal mesothelioma (PM) patients with germline mutations (GM) have distinct surgical characteristics when compared to those without GM. 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. Out of 88 PM patients enrolled between 2009 and 2019, 18GMs (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. 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.

Development of a model to predict the risk of cerebral infarction in acute vestibular syndrome

ObjectivesThis study aimed to develop a model to predict the risk of cerebral infarction in acute vestibular syndrome and assist emergency physicians in quickly identifying patients with cerebral infarction. Materials and methodsWe looked at 262 patients who were split into cerebral infarction and peripheral vertigo groups. Stepwise regression and Lasso's approach were used to screen for variables, and Boothstrap's method was used to evaluate the model's discrimination and calibration. The model's performance was compared against TriAGe+, ABCD2, and PCI scores using the area under the receiver operator characteristic curve. Clinical decision-making was aided by the use of clinical impact and decision curves. ResultsIn the end, nine risk factors were chosen for model 2, and ten risk factors were chosen for model 1. Model 2 was adopted as the final model. The areas under the receiver operator curve value of the model2 were 0.910(P = 0.000), much higher than the areas under the receiver operator curve value of the TriAGe + scores system and that of the PCI scores system. The clinical decision curve shows that when the threshold probability is 0.05, using the nomogram to predict cerebral infarction has more benefits than either the treat-all-patients scheme or the treat-none scheme. The clinical impact curve shows that when the threshold probability is 0.6 the model predicts disease occurrence in general agreement with the occurrence of the real disease. ConclusionThis study model can help emergency room physicians quickly triage and treat patients by accurately identifying cerebral infarction patients.

Prognostic significance of acellular mucin in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for appendiceal neoplasms

Appendiceal neoplasms have a propensity for peritoneal dissemination. The standard of care for select individuals is CRS/HIPEC. In the current 8th AJCC Staging system, a finding of only intraperitoneal acellular mucin (M1a) is classified as Stage IVa. There is concern that the current AJCC system may over-stage patients. This was a single-institution retrospective review of 164 cases of mucinous appendiceal neoplasm. Patients undergoing CRS/HIPEC with M1a disease were compared to patients with peritoneal deposits containing tumor cells (well-differentiated adenocarcinoma; low-grade mucinous carcinoma peritonei-M1b,G1). Overall and recurrence-free survival were assessed. Median age was 51years, 70% were female, and 75% White. Sixty-four patients had M1a disease and 100 M1b,G1 disease. M1a disease had a lower median PCI score (11 vs. 20, p = .0001) and a higher rate of complete CRS (62% vs. 50%, p = .021). Median follow-up was 7.6years (IQR 5.6-10.5years). For M1a disease, there were no recurrences and only one patient died during the study interval. In comparison, for M1b disease, 66/100 (66%) recurred with a 5-year RFS of 40.5% (HR 8.0, 95% CI 4.9-15.1, p < .0001), and 31/100 (31%) died with a 5-year OS of 84.8% (HR 4.5, 95% CI 2.2-9.2, p < .0001). Acellular mucin (M1a disease) after CRS/HIPEC for appendiceal neoplasm is associated with longer OS and RFS compared to M1b, G1 disease. Current AJCC staging does not accurately reflect the differing outcomes of these two patient populations. The presence of acellular mucin in the peritoneal cavity should not be perceived as a metastatic equivalent.

Long-Term Survival in Patients Treated with Cytoreduction and Heated Intraperitoneal Chemotherapy for Peritoneal Mesothelioma at a Single High-Volume Center.

Malignant peritoneal mesothelioma (MPM) is a rare diagnosis with a dismal prognosis if untreated. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is shown to significantly improve survival. Our institution is uniquely positioned to report long-term outcomes in MPM with CRS-HIPEC, due to our robust peritoneal surface disease program existing over the past three decades. Our prospectively maintained, single-institution database of CRS-HIPEC cases was reviewed, identifying 111 consecutive patients with MPM over 28 years (1993-2021). Prognostic, operative, and pathologic factors were reviewed. Overall survival (OS) and conditional survival (CS) analyses were performed. The average age was 55.1 years; 58.6% of patients were male; 17 of 111 patients (15.3%) had a second CRS-HIPEC. At first CRS-HIPEC, the average PCI score was 18.7, andthe perfusate drugs were platinum-based (72.1%) and mitomycin C (27.9%). The resection statusat first CRS-HIPEC was R2a (46.4%), followed by R0-1 (29.1%), and R2b-c (24.5%). Median OS was 3.3 years for the entire cohort, with 75th and 25th percentiles at 10.7 months and 10.6 years. Median CS was improved if patients survived to the 1-year postoperative mark (4.9 years, p < 0.01) and trended toward further improvement with each passing year. If 3-year postoperative survival was achieved, the median CS improved to 6.1 years. This represents one of the largest and lengthiest, single-center, longitudinal, case series of peritoneal mesothelioma treated with CRS-HIPEC. The OS suggests efficacy for CRS-HIPEC for MPM. Long-term survival improves significantly after patients achieve the 1-year, postoperative mark.

Bidirectional Chemotherapy in Advanced Colorectal Cancer Peritoneal Metastases.

Colorectal cancer (CRC) patients with extensive peritoneal metastases who are not candidates for CRS-HIPEC have poor prognoses. We evaluated the role of systemic and intra-peritoneal (IP) chemotherapy in these patients. CRC patients with confirmed peritoneal metastasis were enrolled. After implantation of IP chemoport patients received weekly IP paclitaxel in incremental doses of 20 mg/m2 with systemic chemotherapy. The primary end-points were the feasibility, safety, and tolerance (perioperative complications), and the secondary end-point was the clinico-radiological response. Patients included in the study were registered between January 2018 and November 2021. IP chemoport was implanted in 18 patients of which 14 patients underwent successful instillation of IP chemotherapy. Four patients did not receive IP chemotherapy in view of port-site infection for which IP ports were removed. The median age was 39 years (range: 19-61 years). The site of the primary tumor was equal in the colon and rectum. Fifty percent of patients had signet ring-cell adenocarcinoma, and 21% had poorly differentiated adenocarcinoma. The median serum of CEA level was 12.27 ng/mL (1.63-116.16 ng/mL). The median PCI score was 25 (18-35). The median number of IP chemotherapy cycles (weekly) was 3.5 (1-12 cycles). In 14.3% of patients, IP chemoport had to be removed due to block and infection. Three, five, and four patients had clinico-radiologically disease progression, stable disease, and partial response, respectively. One patient underwent subsequent successful CRS-HIPEC. There were no grade 3-5 (CTCAE 3.0) complications. Incremental doses of IP paclitaxel with systemic chemotherapy is safe and feasible in selected colorectal adenocarcinoma patients with peritoneal metastases without any serious adverse events.

DETERMINATION OF THE RELATIONSHIP BETWEEN STRESS LEVELS AND PROBLEM-SOLVING SKILLS OF NURSING STUDENTS ENTERING CLINICAL PRACTICE FOR THE FIRST TIME DURING THE PANDEMIC

Aim: This study was conducted to examine the relationship between the stress levels, problem solving skills of nursing students who attended the clinic for the first time during the pandemic period. Method: the sample consisted of 168 students who went to clinical practice for the first time during the pandemic. Data were collected using the "Sociodemographic Information Form", "Clinical Stress Questionnaire (CSQ)" and "Problem Solving Inventory (PSI)". Results: 57% of the students who participated in the study stated that they thought they might experience clinical stress due to reasons such as thinking that their professional knowledge and skills were not sufficient for practice, 61% thought of making mistakes, 79% feared harming the patient, and 58% feared Covid-19 transmission during clinical practice. The mean KSA total score was 26.15±8.46 and the mean PCE total score was 79.65±17.77. There was a statistically significant and moderate negative correlation between the mean KSA scores and the mean PCI scores (p&lt;0.05). Conclusion: As a result of the study, it was found that the stress levels of nursing students who went into clinical practice for the first time during the pandemic period were low and their problem-solving skills were at a moderate level, and it was observed that as the stress levels of the students decreased, their problem-solving skills increased.