Aim: To investigate eosinophilia as a potential on-treatment biomarker for patients receiving cancer immunotherapy. Materials & methods: We evaluated the association between eosinophilia and treatm... Lay abstract Immunotherapy has revolutionized the way we treat many cancers. However, we do not have good predictors for which patients are going to respond to treatment or experience side effects....

Clonal hematopoiesis of indeterminate potential (CHIP) is the clonal expansion of hematopoietic stem cells from somatic mutations. It is a common incidental finding in cell-free DNA (cfDNA). We investigated the incidence of CHIP in cfDNA from patients with solid tumors and explored its association with treatment outcomes and adverse events. We reviewed cfDNA results from a local prospective solid tumor cohort (PREDiCT-l) and two randomized trials: Canadian Cancer Trials Group CO.26 [durvalumab + tremelimumab (D + T) or best supportive care in metastatic colorectal cancer] and Canadian Cancer Trials Group PA.7 (gemcitabine and nab-paclitaxel ± D + T in metastatic pancreatic adenocarcinoma). CHIP+ was defined as any mutation in DNMT3A, TET2, or ASXL1 with a variant allele frequency ≥2%. Presumed germline variants (variant allele frequency >40%) were removed. The first line of treatment after cfDNA was reviewed for grade ≥3 and dose-limiting toxicities. The prevalence of CHIP in the 465 included patients was 10% to 30%, and it was more common as age increased (P = 0.003). DNMT3A was the gene most frequently mutated in all cohorts. Patients with CHIP in PA.7 treated with immunotherapy showed an improved progression-free survival versus CHIP− [HR = 0.55 (0.28–1.07); P = 0.079, P-interaction = 0.098 (multivariable)]. However, patients with CHIP treated with chemotherapy in PREDiCT-l showed a trend toward worse progression-free survival [HR = 1.82 (0.98–3.38); P = 0.059]. There was no difference in adverse event rates between CHIP ± groups for those treated with chemotherapy or immunotherapy. CHIP is common in patients with solid tumors. Although not appearing to affect rates of adverse events, CHIP may affect outcomes from immunotherapy or chemotherapy. Significance: Liquid biopsy is increasingly being used in oncology for tumor molecular characterization. CHIP is a common incidental finding in cfDNA, and its prevalence increases with age. This study builds on growing evidence of common CHIP variants in patients with solid tumors. The results suggest a possible clinical impact of CHIP on treatment outcomes from immunotherapy or chemotherapy. This may have implications for treatment selection for patients with solid tumors.

PURPOSE: Based on the International Duration Evaluation of Adjuvant Chemotherapy analysis, 3 months of adjuvant chemotherapy with capecitabine and oxaliplatin (CAPOX) is an option for stage III colorectal cancer (colorectal cancer [CRC]), with cost and toxicity benefits. We examined the patterns of uptake of CAPOX versus fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and chemotherapy duration in a contemporary real-world cohort of patients in Canada. METHODS: The provincial pharmacy database was used to identify patients with resected stage III CRC receiving adjuvant chemotherapy between January 2021 and December 2022. Demographic, tumor, and treatment information was collected and compared. RESULTS: Of 452 patients, 234 (52%) and 218 (48%) were planned to receive 3 and 6 months of chemotherapy, respectively. Within the 3-month group, 226 (97%) received CAPOX. Within the 6-month group, there was a 51%-49% split between CAPOX and FOLFOX. Age >70 years ( P = .039), well/moderately differentiated ( P = .005), and low-risk disease ( P < .0001) were significantly associated with 3 months. Performance status, ileostomy, or preexisting neuropathy did not affect treatment choice. Of patients planned for 6 months, 29% had low-risk disease, with 52% of these receiving CAPOX. Patients receiving 6 months were more likely to report neuropathy (68 v 36%, P < .0001) and to stop oxaliplatin early (54 v 31%, P < .0001). The most likely reason for early adjuvant discontinuation was neuropathy in the 6-month group and gastrointestinal toxicity in the 3-month group ( P < .0001). Irrespective of duration, mean time from consult to starting chemotherapy was longer for FOLFOX versus CAPOX (24 v 19 days, P = .007). CONCLUSION: In this contemporary cohort, 6 months chemotherapy is still being offered to patients with low-risk disease and is associated with more neuropathy. Exploration of patient preferences and resource costs may improve adoption of reduced duration adjuvant CAPOX in stage III CRC.

Introduction: A comprehensive trimodality approach has become the standard of care for patients with locally advanced rectal cancer. However, the sequencing and duration of chemotherapy and chemoradiotherapy around surgery varies between clinical studies and geographical regions. Growing evidence is also mounting for strategies such as total neoadjuvant therapy and non-operative management for carefully selected patients. Areas covered: We provide a perspective review of the current evidence and controversies in the treatment of locally advanced rectal cancer including the recent updates from the 2020 ASCO annual conference. Expert opinion: With ongoing advances in the management of locally advanced rectal cancer, a multidisciplinary team approach is necessary as treatments could involve multiple approaches. Chemoradiotherapy whether short or long course followed by at least three months of systemic chemotherapy may be the preferred option to balance local and distant disease control. Albeit the choice of doublet or triplet chemotherapy is still controversial. As total neoadjuvant treatment becomes part of the standard of care in rectal cancer, modification of the surveillance schedule is needed to detect early recurrences which may be limited by resources and availability of services.