Clinical colorectal cancer最新文献

Background

A substantial proportion of patients with stage III colorectal cancer (CRC) are older than 70 years. Optimal adjuvant chemotherapy (AC) for older patients (OP) continues to be debated, with subgroup analyses of randomized trials not demonstrating a survival benefit from the addition of oxaliplatin to a fluoropyrimidine backbone.

Patients and Methods

We analyzed the multisite Australian ACCORD registry, which prospectively collects patient, tumor and treatment data along with long term clinical follow-up. We compared OP (≥70) with stage III CRC to younger patients ([YP] <70), including the proportion recommended AC and any reasons for not prescribing AC. AC administration, regimen choice, completion rates, and survival outcomes were also examined.

Results

One thousand five hundred twelve patients enrolled in the ACCORD registry from 2005 to 2018 were included. Median follow-up was 57.0 months. Compared to the 827 YP, the 685 OP were less likely to be offered AC (71.5% vs. 96.5%, P < .0001) and when offered, were more likely to decline treatment (15.1% vs. 2.8%, P < .0001). Ultimately, 60.0% of OP and 93.7% of YP received AC (P < .0001). OP were less likely to receive oxaliplatin (27.5% vs. 84.7%, P < .0001) and to complete AC (75.9% vs. 85.7%, P < .0001). The probability of remaining recurrence-free was significantly higher in OP who received AC compared to those not treated (HR 0.73, P = .04) but not significantly improved with the addition of oxaliplatin (HR 0.75, P = .18).

Conclusion

OP were less likely than YP to receive AC. Receipt of AC reduced recurrences in OP, supporting its use, although no significant benefit was observed from the addition of oxaliplatin.

Background

Human epidermal growth factor receptor 2 (HER2) is a promising therapeutic target in metastatic colorectal cancer (mCRC). This study was to evaluate the efficacy and safety of pyrotinib alone or pyrotinib with trastuzumab in patients with HER2-positive mCRC.

Patients and Methods

In this prospective observational study, patients with HER2 positive, Ras Sarcoma Viral Oncogene Homolog (RAS) wild type mCRC who received at least one standard treatment of palliative chemotherapy were enrolled. Patients were treated with oral pyrotinib alone or pyrotinib with trastuzumab. The primary endpoint was progression free survival (PFS), and the secondary endpoints were overall survival (OS), confirmed objective response rate (ORR), and safety. This trial is registered with chitcr.org, number ChiCTR2100046381.

Results

From February 15, 2021, to January 10, 2023, 32 patients were enrolled in this study. Twenty (62.5%) patients were treated with pyrotinib, while 12 (37.5%) received pyrotinib and trastuzumab. As of June 24, 2023, with a median follow-up of 11.0 months, the median PFS was 5.7 months (95%CI 4.5-10.2), while OS was not evaluable (NE), ORR and disease control rate (DCR were 34.4% and 87.5%. Patients’ PFS in the pyrotinib plus trastuzumab subgroup and pyrotinib monotherapy group were 8.6 and 5.5 months, OS was not evaluable (NE) and 10.9 months, ORR was 50.0% and 25.0%, respectively. Most treatment-related adverse events (TRAEs) were grade 1-2, diarrhea was the most frequent TRAE (81.3%, 26/32). Grade 3 TRAEs occurred in 11 patients: 9 for diarrhea, 1 for nausea, and 1 for oral mucositis.

Conclusion

Pyrotinib with or without trastuzumab showed promising anti-tumor activity and acceptable toxicities in treatment-refractory, HER2-positive mCRC.

Background

Primary tumor sidedness (PTS) is an independent prognostic factor in patients with metastatic colorectal cancer (CRC), with a worse prognosis for right-sided tumors. There are limited data on the prognostic impact of PTS in stage III CRC. The main objective of this study was to analyze the prognostic impact of PTS in stage III CRC.

Patients and Methods

A retrospective and uni-institutional cohort study was performed in an oncology reference center. Patients with stage III CRC treated with a 5-fluorouracil and oxaliplatin-based chemotherapy regimen (mFLOX regimen) from October 2007 to February 2013 were included. The primary outcome was the probability of overall survival (OS) at 5 years stratified by PTS. Secondary outcomes were the probability of disease-free survival (DFS) at 5 years and an analysis of the prognostic impact of clinical and molecular biomarkers. Kaplan‒Meier curves were used, and Cox models were used to evaluate prognostic factors associated with OS and DFS.

Results

Overall, 265 patients were evaluated. Transverse colon tumors, multicentric tumors, and undetermined primary subsites were excluded, resulting in 234 patients classified according to PTS: 95 with right sidedness (40.6%) and 139 with left sidedness (59.4%). The median follow-up time was 66 months [interquartile range (IQR): 39-81]. The 5-year OS probabilities for right-sided and left-sided tumors were 67% (95% CI: 58%-77%) and 82% (75%-89%), respectively [hazard ratio (HR): 2.02, 95% CI: 1.18-3.46; P = .010]. The 5-year probabilities of DFS for right-sided and left-sided tumors were 58% (49%-69%) and 65% (58%-74%), respectively (HR: 1.29, 0.84-1.97; P = 0.248).

Conclusion

These data suggest that there may be a worse prognosis (inferior OS at 5 years) for resected right-sided stage III CRC patients treated in the real world. However, these data need to be confirmed by prospective studies with a larger number of participants.

Immune checkpoint inhibitors have transformed the treatment paradigm for various types of cancer. Nonetheless, with the utilization of these groundbreaking treatments, immune-related adverse events (irAEs) are increasingly encountered. Colonic and hepatic involvement are among the most frequently encountered irAEs. Drug-induced side effects, infectious causes, and tumor-related symptoms are the key differentials for irAE complications. Potential risk factors for the development of irAEs include combination use of immune checkpoint inhibitors, past development of irAEs with other immunotherapy treatments, certain concomitant drugs, and a pre-existing personal or family history of autoimmune illness such as inflammatory bowel disease. The importance of early recognition, timely and proper management cannot be understated, as there are profound clinical implications on the overall cancer treatment plan and prognosis once these adverse events occur. Herein, we cover the clinical management of the well-established gastrointestinal irAEs of enterocolitis and hepatitis, and also provide an overview of several other emerging entities.

Background

Although ipilimumab plus nivolumab have significantly improved the survival of metastatic colorectal cancer (CRC) with mismatch repair deficient (dMMR) /microsatellite instability-high (MSI-H), the data on neoadjuvant setting is limited.

Patients and Methods

We enrolled 11 patients with advanced dMMR/MSI-H CRC. 10 patients were locally advanced and 1 was metastatic. Ten patients were treated with 1 dose of ipilimumab (1 mg/kg) and 2 doses of nivolumab (3 mg/kg), and 1 patient was treated with 1 dose of ipilimumab (1 mg/kg) and 2 doses of nivolumab (3 mg/kg) with 2 cycles. All the patients underwent surgery after immunotherapy. The aim of the study was to evaluate the safety and short-term efficacy of this strategy.

Results

Pathologic responses were observed in 11/11 (100%) dMMR/MSI-H tumors, with 9/11 (81.8%) achieving complete responses. Among these 9 cases with complete responses, 1 achieved a radiological noncomplete response after treatment with 1 dose of ipilimumab (1 mg/kg) and 2 doses of nivolumab (3 mg/kg), so another cycle of treatment with 1 dose of ipilimumab (1 mg/kg) and 2 doses of nivolumab (3 mg/kg) was administered, followed by surgery. The postoperative pathological evaluation was a complete response. Seven patients (63.6%) developed grade I/II adverse events. No patients developed grade III/IV adverse events or postoperative complications.

Conclusion

Neoadjuvant immunotherapy with ipilimumab plus nivolumab induced tumor regression with a major clinical and pathological response in advanced dMMR/MSI-H CRC. Notably, patients do not achieve a complete response to neoadjuvant immunotherapy, additional neoadjuvant immunotherapy may offer benefits. Further research is needed to assess the long-term efficacy of this strategy.

Background

Randomized clinical trials have defined the survival advantage with the addition of biologic drugs to chemotherapy in patients with metastatic colorectal cancer (mCRC). Under representation of Hispanics contributes to poorly defined outcomes in this group. We aim to determine whether the real-world benefit of biologics extends to Hispanics using a comparative effectiveness research approach.

Methods

This retrospective cohort study included all treatment centers contributing to SEER registry with available claims in the SEER-Medicare linked database (2001-2011) and 2 hospitals (2004-2016) catering to minorities. Metastatic CRC patients were classified as receiving chemotherapy or biochemotherapy (CT plus biologics; if initiated within 3 months of chemotherapy). The primary outcome was overall survival (OS) among the Hispanic patients calculated from time of administration of first dose of chemotherapy to death or last follow-up. A weighted Cox regression model was used to assess differences in survival.

Results

We identified 182 Hispanic patients with mCRC from the Patient Entitlement and Diagnosis Summary (PEDSF) file (n = 101) and hospital database (n = 81). Overall, 52% were women and 72% received biologics. The median OS was 11.3 and 17.0 months in chemotherapy and biochemotherapy group, respectively. Biochemotherapy offered a survival benefit compared with chemotherapy alone, with an average hazard rate reduction of 39% (95% CI 6%-60%, p = .0236) using inverse probability of treatment weighting (IPTW) based analysis.

Conclusion

In this cohort of Hispanic patients with mCRC, biochemotherapy was associated with longer survival. Clinicians may offer biochemotherapy therapy to all patients regardless of race/ethnicity to maximize clinical benefit.

Survival rates in early-stage rectal cancer patients have increased over the past few decades. Societies such as the National Comprehensive Cancer Network (NCCN), American Cancer Society (ACS), American Society of Clinical Oncology (ASCO), and European Society of Medical Oncology (ESMO) have proposed guidelines related to cancer survivorship care including formal recommendations to address the needs in early-stage rectal cancer survivors. These guidelines, in addition to new clinical research findings in survivorship will be reviewed, specifically looking at physical, psychosocial, and financial concerns in rectal cancer survivorship.

Background

For patients with initially unresectable colorectal liver metastasis (IU-CRLM) receiving conversion therapy, disease relapse after conversion hepatectomy is common. However, few studies have focused on the assessment and management of relapse following conversion hepatectomy for IU-CRLM.

Methods

In the retrospective cohort study, 255 patients with IU-CRLM received conversion therapy and underwent subsequent R0 resection. The treatment effects of repeated liver-directed treatment (RLDT) versus non-RLDT for liver relapse were examined. Survival analysis was evaluated with the use of Cox proportional hazards methods. The importance of RLDT was further confirmed in the propensity score matching (PSM) and subgroup analyses.

Results

The 5-year overall survival (OS) rate after conversion hepatectomy was 34.9%. Liver relapse was observed in 208 patients. Of these patients, 106 underwent RLDT (65 underwent repeated hepatectomy and the remainder underwent ablation treatment), while 102 received only palliative chemotherapy. The relapse patients who underwent RLDT had a significantly longer OS than those who did not (hazard ratio (HR): 0.382, 95% CI: 0.259-0.563; P<0.001). In a multivariable analysis, RLDT was independently associated to prolonged survival (HR: 0.309, 95%CI: 0.181-0.529; P<0.001). In the PSM and subgroup analyses, RLDT consistently showed evidence of prolonging OS significantly.

Conclusion

For IU-CRLM patients with liver relapse following conversion hepatectomy, the RLDT is essential for cure and prolonged survival. To avoid missing the opportunity for RLDT, intensive disease surveillance should be proposed.

Introduction

The International Duration Evaluation of Adjuvant Therapy (IDEA) collaboration in 2017 established 3 months of adjuvant therapy as an alternative to 6 months of therapy for stage III colon cancer. We determined the association between the IDEA publication, changes in clinical practice, and prescriber variation.

Patients and Methods

Using linked databases, we identified Ontarians aged ≥18 years at diagnosis of stage III colon cancer between 2007 and 2019 who received oxaliplatin-containing adjuvant therapy. The outcome was duration of therapy, categorized as ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% of a 6-month course of therapy to approximate treatment durations in the IDEA collaboration. We examined trends in duration over time using an interrupted time series regression model. We analyzed treatment duration after accounting for patient and prescriber characteristics, using multivariable mixed effects logistic regression models to quantify between-prescriber variation.

Results

We included 4695 patients with stage III colon cancer who received oxaliplatin-containing adjuvant chemotherapy, of whom 77.5% initiated treatment pre-IDEA and 22.5% initiated treatment post-IDEA. Post-IDEA, there was a 16.4% (95% CI, 12.5%-20.3%) absolute increase in the proportion of patients treated with ≤50% of a maximal course of therapy. This trend was greatest among patients with low-risk tumors. Prescriber variation increased pre-IDEA to 15.6% post-IDEA (variance partition coefficient 5.4% pre-IDEA and 15.6% post-IDEA).

Conclusion

The publication of IDEA was associated with increases in short duration adjuvant therapy and prescriber-level practice variation for stage III colon cancer. Clinicians should be better supported to make consistent recommendations about adjuvant duration under conditions of uncertainty and trade-offs.