Appendiceal adenocarcinoma is both a rare and heterogenous tumor, with marked contrast in the natural history of low-grade and high-grade tumors (5-year OS 68% for low-grade vs. 7% for high-grade). The rarity of appendiceal adenocarcinoma has made it difficult to study with traditional prospective, randomized controlled trials. As a result, current national guidelines still suggest that appendiceal cancer be treated similarly to colorectal cancer (CRC) despite clear differences between the two in terms of both clinical and molecular features. While low-grade appendiceal adenocarcinoma is primarily treated with surgical resection sometimes followed by hyperthermic intraperitoneal chemotherapy (HIPEC), many inoperable candidates are treated with systemic chemotherapy although there is no prospective data supporting this practice. The purpose of our study was to objectively evaluate the effectiveness of systemic chemotherapy in low-grade mucinous appendiceal adenocarcinoma. A randomized crossover trial of surgically unresectable low-grade (well differentiated) mucinous appendiceal adenocarcinoma was performed with patients randomized to either 6 months observation followed by 6 months of chemotherapy (physician's choice), or initial chemotherapy followed by observation. In this way each patient would serve as their own control. Up to 30 patients were planned to have complete 6- and 12-month tumor measurements for 24 patients, providing 80% power at 0.05 significance level to detect a 5.0% difference in change in tumor size in observation vs. treatment periods. Patients were monitored for rate of bowel complications as a secondary endpoint for the study. The trial closed early due to slow accrual. A total of 24 patients were enrolled. The majority of patients were treated with either 5FU or capecitabine (n = 15, 63%), bevacizumab was added for 3 (13%), one patient was treated with FOLFOX, 2 (8%) were treated with FOLFIRI. Four patients did not get any chemotherapy (17%). There were 15 patients available for the primary analysis of change in tumor volume as measured by modified peritoneal RECIST. The mean difference in tumor size was -4.5 (95% CI: -12.6, 3.7), indicating a trend towards faster growth on treatment than observation, however there was no significant difference in growth of tumor during observation vs. treatment time periods (8.4% growth treatment vs. 4.0% observation, p=0.26). Separately we combined all patients with available 6- or 12-month information regardless of treatment order accounting for repeated measures again finding no significant difference (13.1% vs. 4.4%, p=0.14, n=18). There was no significant difference in overall survival between treatment first or observation first arms (76 vs. 42 months, p = 0.37). There was not a significant difference in rate of bowel obstruction between the treatment first vs. observation first arms (12.5%, (n=3) vs 8.3%, (n=2)), and no bowel perforations occurred on study. These data from a prospective, randomized crossover design trial suggest that patients with low-grade mucinous appendiceal adenocarcinoma do not appear to derive benefit from 5FU based chemotherapy. These data further highlight the unique biology of low-grade mucinous appendiceal adenocarcinomas and demonstrates the need to identify effective systemic therapies for this patient population.
This narrative review explores the utilization of machine learning (ML) and artificial intelligence (AI) models to enhance perioperative cancer care. ML and AI models offer significant potential to improve perioperative cancer care by predicting outcomes and supporting clinical decision-making. Tailored for perioperative professionals including anesthesiologists, surgeons, critical care physicians, nurse anesthetists, and perioperative nurses, this review provides a comprehensive framework for the integration of ML and AI models to enhance patient care delivery throughout the perioperative continuum.
Abstract We present a model of hepatic colorectal metastases which represents monoclonal cell lines double-labeled by luciferase and tdTomato. These cells form liver metastasis in varying numbers and patterns similar to those observed in patients. Using in vivo and ex vivo luminescent and fluorescent imaging we determine the growth kinetics and clonogenic frequency of tumor cells colonizing liver. Molecular profiling detected stable expressional differences between clones consistent with their phenotypes. The data indicate that clinically relevant phenotypes of liver metastases can be modeled in vivo .
To study NAD(P)H oxidase-dependent outcomes after oxygen stresses that are similar to those experienced by preterm infants today using a rat model of retinopathy of prematurity.
ABSTRACT Importance Appendiceal Adenocarcinoma is a rare tumor and given the inherent difficulties in performing prospective trials in such a rare disease currently there is a scant amount of high-quality data upon which to guide treatment decisions, which highlights the unmet need for more pre-clinical and clinical investigation for this orphan disease Objective To objectively evaluate the effectiveness of flouropyrimdine-based systemic chemotherapy in inoperable low-grade mucinous Appendiceal Adenocarcinoma patients. Design This open label randomized crossover trial recruited patients from September 2013 to January 2021. The data collection cutoff was May 2022. Setting Single tertiary care comprehensive cancer center. Participants Enrollment of up to 30 patients was planned. Eligible patients had histological evidence of a metastatic low grade, mucinous Appendiceal Adenocarcinoma, with radiographic images demonstrating the presence of mucinous peritoneal carcinomatosis and were not considered a candidate for complete cytoreductive surgery. Key exclusion criteria were concurrent or recent investigational therapy, evidence of a bowel obstruction, use of total parental nutrition. Interventions Patients were randomized to either 6 months observation followed by 6 months of chemotherapy, or initial chemotherapy followed by observation. The majority of patients were treated with either 5FU or capecitabine as single agent (n = 15, 63%); 3 (13%) received doublet chemotherapy (FOLFOX or FOLFIRI), bevacizumab was added to cytotoxic chemotherapy for 5 (21%) patients. Main Outcomes and Measures The difference in tumor growth and patients reported outcomes between the chemotherapy and observation periods. Also, the objective response rate, the rate of bowel complications, and differences in overall survival. Results A total of 24 patients were enrolled. Fifteen patients were available to evaluate difference in tumor growth between treatment and observation; there was not a significant difference (8.4% (1.5, 15.3%) increase from baseline on treatment vs. 4.0% (−0.1, 8.0%) increase from baseline on observation; p=0.26). Of the 18 patients who received any chemotherapy, zero had an objective response (14 (77.8%) SD, 4 (22.2 %) PD). Median OS was 53.2 months, there was no significant difference in OS between the Observation First arm (76 months) and the Treatment First arm (53 months) (HR, 0.64; 95% CI, 0.16 to 2.6; p = 0.48). Patient reported quality of life metrics identified that fatigue (Mean scores were 18.5 vs 28.9, p=0.02), peripheral neuropathy (6.7 vs 28.9, p=0.014), and financial difficulty (8.9 vs 28.9, p=0.0013) were all significantly worse while on treatment. Conclusions and Relevance These data suggest that patients with low-grade mucinous appendiceal adenocarcinoma do not derive benefit from systemic fluoropyrimidine-based chemotherapy. Trial Registration ClinicalTrials.gov Identifier: NCT01946854 . URL: https://clinicaltrials.gov/ct2/show/NCT01946854 KEY POINTS Question Is fluoropyrimidine-based systemic chemotherapy effective in treating inoperable low-grade mucinous Appendiceal Adenocarcinoma patients? Findings In this randomized clinical trial that included 24 patients, there was no significant difference in tumor growth between treatment and observation (8.4% increase from baseline on treatment vs. 4.0% increase from baseline on observation; p=0.26). Meaning Patients with low-grade mucinous appendiceal adenocarcinoma do not derive benefit from systemic fluoropyrimidine-based chemotherapy.
3522 Background: Observational cohorts have shown that detection of circulating tumor DNA (ctDNA)-defined minimal residual disease (MRD) following curative intent therapy has very high specificity and positive predictive value for future radiographic recurrence with a lead time of over 9 months. However, such data have not incorporated rigorous clinical evaluation for concomitant recurrence, nor have they established the clinical utility of MRD monitoring after completion of curative intent therapy. Methods: Pts with stages II-IV CRC (6/1/19 - 12/31/22, data cutoff) treated with curative intent at MD Anderson Cancer Center were evaluated with a tumor-informed MRD assay (Signatera, Natera), as part of the institutional INTERCEPT program that aims to integrate MRD-based testing into CRC clinical care. Surveillance visits including scans and tumor markers were performed per established guidelines. ctDNA was recommended post-operatively and q3m with each surveillance visit. Pts and providers were informed of the results and subsequent clinical courses including additional radiologic testing for ctDNA+ MRD tests were tracked. Results: 1259 pts were included in the INTERCEPT program (median 57y, [21-93]; 55% male; stage% I-III/IV 69/31; colon/rectum% 61/39), with 1049 pts tested after curative intent surgery. Of these, 159/1049 pts (15%) had ctDNA+; distribution of pts, % (+ve/total) from time of such surgery in m was: 0 - 3 (54.6/43.8); 3-6 (21.3/30); 6-12 (24/33.2). Of the pts with ctDNA+ after surgery, 49 pts (32%) were ctDNA+ prior to or during adjuvant therapy and 86 (57%) during surveillance. Of the 86 pts who were ctDNA+ during surveillance, imaging revealed concomitant new metastases in 46 (53%); i.e. only 40 (47%) were true MRD+. A total of 191 imaging studies were done (range 1-4) within 90d of the initial ctDNA+ including 99 as routine surveillance concurrent with ctDNA testing and 92 as additional follow up based on results. Of 40 pts with true MRD, majority (27 pts, 67.5%) were enrolled onto ongoing MRD trials ( https://crcmrd.com/ ). Conclusions: Our experience provides support for the feasibility of incorporation of MRD testing as part of routine surveillance. ctDNA+ results trigger a high rate of reflex imaging and, as a result, 53% of ctDNA+ patients have concomitant new radiographic findings. While clinical trials are feasible in true MRD+ pts, eligibility criteria for these trials need to be carefully specified about adequate radiographic evaluation.
