ALLIANCE A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer.

Background: Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after neoadjuvant therapy may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes. Methods: In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N+) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N+ vs N0) and distance from anal verge (0-4; 4-8; 8-12 cm). Patients will be randomized to receive neoadjuvant long course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3-4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8-12 (+/- 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 296 evaluable patients (148 per arm) will provide statistical power of 90.5% to detect an 17% increase in cCR rate, at a one-sided alpha=0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse effects. Biospecimens including archival tumor tissue, plasma and buffy coat in EDTA tubes, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and has a current accrual of 312. Support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . Discussion: Building off of data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed the current trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer. Trial Registration: Clinicaltrials.gov ID: NCT05610163 ; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).

Cadmium induced damage in Wistar rats, ameliorative potentials of progesterone.

Asides the increased human exposure to Cadmium containing products; the adverse effects of Cadmium on human health is further exacerbated by its toxicity at low dosage, long biologic half-life and low rate of excretion from the body. This study investigated the protective potential of progesterone on cadmium-induced damage in Wistar rats. Adult male Wistar rats received CdCl2 once daily for 21 days. Progesterone was given 30 min. after administration of CdCl2 while 3 other groups were given distilled water, CdCl2 and progesterone alone. Blood samples were collected from the animals for the determination of liver function and antioxidant status while the liver, kidney, cerebellar and hippocampal tissues were excised and fixed in Neutral buffered formalin for histopathological studies. While Cadmium caused changes in liver function parameters which were indicative of oxidative stress, pre-treatment with progesterone caused restoration to values which were non-significant to the control. Similar findings were made for G6PD, GSH, SOD, CAT and MDA. Histopathology revealed tissue damage in the Cd treated group; this was attenuated by prior treatment with progesterone. Progesterone ameliorated the free radical induced oxidative stress and tissue injury arising from exposure to Cadmium; attention should be given to its antioxidant role in Cadmium toxicity.

Analysis of liver-directed therapies in U.S. cancer patients.

BACKGROUND: The liver is a common site of primary and metastatic cancer. Liver-directed therapies are commonly used to treat cancer involving the liver. We report on the patterns, predictors, and outcomes of liver-directed therapies in hospitalized cancer patients in the United States. METHODS: Data were obtained from all U.S. states that contributed to the Nationwide Inpatient Sample maintained by the Agency for Healthcare Research and Quality between 2006 and 2010. Univariate and multivariate testing was used to identify factors significantly associated with patient outcome. RESULTS: For the 5-year period of interest, 12,540 patient discharges were identified. Mean age in the sample was 60 years. Primary liver lesions (n = 8840) made up 26.9% of the sample; the remaining cases were metastases. Most procedures were performed in large (79%) urban (98%) hospitals and in patients with insurance (97.9%). The most common intervention was partial hepatectomy (42.7%), followed by open (9.9%), percutaneous (7.2%), and laparoscopic (5.04%) ablation of liver lesions; embolization (9.8%); and liver transplantation (2.64%). The incidence of in-hospital mortality was very low (2.4%), and the complication rate was 12.2%. Complications such as acute liver necrosis, ascites, hepatic coma, hepatorenal syndrome, liver abscess, and high number of comorbid illnesses (>8) accounted for 60% of the in-hospital mortality. CONCLUSIONS: The low rate of morbidity and mortality associated with liver-directed therapies in hospitalized cancer patients supports the continuing utility of such procedures in the management of primary and metastatic liver cancer. The patterns of health disparities observed with respect to the use of liver-directed therapies are concerning.

Mucinous cystadenoma of the appendix: a case report.

INTRODUCTION: Tumours of the appendix are emerging as diseases of increasing concern due to a rising incidence1. We present a case of mucinous cystadenoma of the appendix in an elderly patient. To our knowledge, this is the first report of mucinous cystadenoma of the appendix from Nigeria.

Adenomatous polyposis coli in an elderly female nigerian.

Colorectal cancer is reported to occur in lower rates in Africans and some of the reasons adduced include a rarity of polyposis coli syndromes. Only two cases of polyposis coli have been documented in Nigeria in the last 15 years. The present case is an elderly lady who had radiologic and colonoscopic evidence of multiple colonic polyps. She had a colonic resection and the histology was reported as multiple polyposis coli, follicular hyperplasia and submucosal fibrosis in the appendix, and reactive hyperplasia in the mesenteric lymph nodes. There was no evidence of malignancy. This is the first case report of polyposis coli in a living elderly patient in Nigeria.