Clinical colorectal cancer最新文献

Background

Neither TP53 mutation nor DNA methylation status has been established as a biomarker alone of metastatic colorectal cancer. We analyzed the association between TP53 mutation functional subtypes and genome-wide DNA methylation status (GWMS) as combined prognostic markers.

Methods

Patient clinical data were obtained from the TRICOLORE study, a randomized phase III trial. The TP53 mutations were classified into wild-type, gain-of-function (GOF) mutations, and non-gain-of-function (non-GOF) mutations. GWMS of the tumor tissues classified them into high-methylated colorectal cancer (HMCC) and low-methylated colorectal cancer (LMCC). Overall survival (OS) was compared based on these subgroups.

Results

Of the 209 patients, 60 (28.7%) were HMCC and 149 (71.3%) were LMCC, 35 (16.7%) were TP53 wild-type and 174 (83.3%) were TP53 mutants including 79 (45.4%) GOF mutations and 95 (54.6%) non-GOF mutations. The OS of the HMCC group was shorter than that of the LMCC group (median 25.3 vs. 40.3 months, P < .001, hazard ratio 1.87) in the total cohort. The combined subgroup analyses of GWMS and TP53 mutation subtypes showed that the HMCC/GOF group had significantly shorter OS than the HMCC/non-GOF group, the LMCC/GOF group, and the LMCC/non-GOF group (median 17.7; 35.3, 40.3, and 41.2 months, P = .007, P < .001, and P < .001, respectively), regardless of the primary tumor location. By the multivariate analysis, only HMCC (P = .009) was a poor prognostic factor in the GOF mutation group.

Conclusions

TP53 GOF with HMCC is a newly identified poorest prognostic molecular subset in metastatic colorectal cancer.

Introduction

Colorectal cancer is the second most common cancer in both genders and often presents as a metastatic, unresectable, or recurrent disease in early follow-up. It is uncertain the benefit of oxaliplatin-based palliative chemotherapy (CT) in the first line of treatment in patients with compromised performance status (PS), Eastern Cooperative Oncology Group (ECOG) 3 and 4. These patients are systematically excluded from clinical trials but may be treated in clinical practice.

Methods

We conducted a prospective observational cohort whose primary outcome was improving at least 2 points in the worst symptom in the Edmonton Symptom Assessment System Scale (ESAS-r), without grade 3 to 4 toxicity, comparing baseline and fourth week of treatment. Secondary endpoints included quality of life using the European Quality of Life-5 dimensions questionnaire, toxicity, response rate, clinical improvement of ECOG PS, and overall survival (OS).

Results

We included 28 patients, and 12 (42.8%) achieved the primary endpoint. Median overall survival was 86 days, 46% of patients did not respond to the fourth-week reevaluation due to clinical deterioration, and 17.8% presented toxicity grade ≥3, with 5 patients dying from toxicity. In addition, ECOG PS 4 or cholestasis had poorer overall survival. Finally, 25% and 53.6% of patients received these treatments in the last 14 and 30 days of life, respectively.

Conclusion

In the present study, palliative multiagent chemotherapy in poor performance status patients with non-molecularly selected colorectal cancer tended to impact tumor symptoms control; however, there is no benefit in OS and a considerable risk of toxicity and treatment-related death.

Background

Intensive surveillance of colon cancer by using the abdominopelvic computed tomography (AP-CT) is common in real world practice; however, it is still unclear whether high-frequency surveillance using AP-CT in patients with these risk factors is superior to that in the low-frequency surveillance.

Patients and Methods

We retrospectively reviewed 1803 patients with stage II-III colon cancer receiving curative surgery between January 1, 2005 to December 31, 2015. We evaluated the average scan-to-scan intervals of postoperative AP-CT testing and assigned patients with an interval of 5 to 8 and 9 to 13 months to the high-frequency (HF) and low-frequency (LF) groups, respectively. The cutoff value of preoperative and postoperative CEA levels was 5 ng/mL. We also applied propensity score matching (PSM) and inverse probability of treatment weighting to adjust clinicopathologic differences between the 2 groups.

Results

We matched 1:1 for each surveillance group yielding a cohort of 776 matched patients. After PSM, Baseline demographics were overall well balanced between 2 groups. Stage III (OR, 2.00; 95% Confidence interval [CI], 1.21-3.30) and postoperative CEA elevation (OR, 2.30; 95% CI, 1.08-4.92) were independent risk factors of recurrence in multivariate analyses. Patient in the HF group had more surgery plus chemo- or radiotherapy as postrecurrence treatment than patient in the LF group (46.2% vs. 23.1%, P = .017). This trend was retained after PSM, although it is not significant (44.4% vs. 23.1%, P = .060). However, survival outcomes of high-frequency AP-CT surveillance were not superior to those of low-frequency surveillance in all subgroups, including stage III (HR 0.99, 95% CI 0.40-2.47) and postoperative CEA elevation (HR 1.36, 95% CI 0.45-4.11).

Conclusion

High-frequency AP-CT testing is associated with a higher proportion of surgery plus chemo- or radiotherapy as postrecurrence treatment, without improvement in 5-year overall survival.

Background

Patients with unresectable Colorectal Liver Metastases (CLM) receiving palliative chemotherapy have a 5-year overall survival (OS) of less than 30%. Liver transplantation (LT) can improve OS up to 60%-83% (SECA-I and SECA-II trials). The aim of the study is to assess the efficacy of LT in liver-only metastatic CRC compared with a matched cohort of patients included in a phase III trial on triplet chemotherapy + antiEGFR.

Patients and Methods

The COLT trial is an investigator-driven, multicenter, non-randomized, open-label, controlled, prospective, parallel trial (ClinicalTrials.gov NCT03803436). Hyperselected patients with liver-limited unresectable CLM, RAS and BRAF wild-type and curatively removed primary colon cancer are included. The observed post-transplant outcomes will be prospectively compared 1:5 with those obtained in a matched cohort from the TRIPLETE trial (NCT03231722).

Results

Primary endpoint is to compare the 3 and 5-years OS of patients enrolled in the COLT trial with COLT-eligible population enrolled in the TRIPLETE trial. An expected gain in OS of 40% at 5-years is predicted for the COLT population (the expected OS at 5-years in COLT vs. TRIPLETE is 70% vs. 30%). Secondary endpoints are to compare the 5-years disease-free survival and to assess the safety of LT (Dindo-Clavien Classification and the Comprehensive Complication Index).

Conclusion

LT offers the longest OS reported in selected patients with CLM. Improving the selection strategies can give patients a 5-year OS similar to other indications for LT and a better outcome than those undergoing chemotherapy alone.

Introduction/Background

Adjuvant capecitabine monotherapy is an option for colon and upper rectum adenocarcinoma patients, providing they have stage II disease with an intermediate risk of recurrence, or stage III but they are above 70’s or they have comorbidities. We wanted to examine whether the number of chemotherapy cycles and the relative dose intensity (RDI) of capecitabine monotherapy in the adjuvant setting are affecting disease recurrence.

Patients and Methods

We included patients with completely resected stage II and III colon and upper rectum cancer who received adjuvant capecitabine monotherapy, from 2003 until May 2020. Patients with early relapse, i.e. during chemotherapy or within 6 months after the completion of adjuvant chemotherapy, and those with rectal cancer who received radiotherapy were excluded. Patients were divided into 3 groups based on the number of chemotherapy cycles received and the RDI. Group A included patients with ≤4 cycles of chemotherapy, group B patients with >4 cycles of chemotherapy and RDI ≤80%, and group C patients with >4 cycles of chemotherapy and RDI >80%. Study’s endpoint, was recurrence free survival (RFS).

Results

Two hundred twenty six patients with stage II and III disease (164 and 62 respectively) were included. Sixteen, 166 and 44 were included in groups A, B and C respectively. After a median follow-up of 41 months, 21 patients (9,3%) had relapsed. Patients belonging to group C were found to have a trend for lower relapse rate compared to patients belonging to group A or group B.

Conclusion

Number of adjuvant capecitabine cycles and RDI might play a role in RFS in patients with stage II and III colon and upper rectum adenocarcinoma.

• What is Already Known About This Subject?Hepatic arterial infusion (HAI) pumps represent 1 promising treatment strategy for patients presenting with liver only or predominant tumors. HAI therapy is a form of locoregional therapy which administers chemotherapy directly into the hepatic artery, thus limits systemic exposure and spares other organs from toxicity. According to the National Comprehensive Cancer Network Guidelines (NCCN), placement of a HAI pump, in combination with systemic chemotherapy, has a category 2B recommendation for centers with the requisite expertise to perform this procedure. However, the utility of HAI pumps for patients with previously treated relapsed/refractory colorectal cancer (CRC) with colorectal liver metastases (CRLM) remains unclear.

• What are the New Findings?Here, we describe a case of heavily pretreated patient with CRC and CRLM unusually responsive to HAI chemotherapy. Our patient had a progression free survival (PFS) of 20.2 months with HAI therapy, versus a PFS of 3 to 6 months with systemic chemotherapy therapy. Furthermore, in this case, the patient has been able to stay off systemic therapy for over a year by the time of this publication. Based on the patient's response, HAI therapy may slow the rate of disease progression compared to other therapies, as it might “reset the clock” as it did for this patient's very aggressive biology.

• How Might it Impact on Clinical Practice in the Foreseeable Future?We believe this to be the first published case report of a patient with previously treated HER2+ CRC who had progressed on anti-HER2 therapy, who had a substantial response from treatment with FUDR HAI chemotherapy. Our report adds to the dearth of the literature in this patient population, and supports use of HAI chemotherapy as a potential treatment strategy for patients with relapsed, refractory CRLM. This case suggests that HAI chemotherapy with FUDR in combination with systemic therapy has the potential to provide long-term responses even for patients with CRLM refractory to multiple lines of chemotherapy.

Background

The bCTC count is a well-established prognostic biomarker in mCRC, as well as in other tumor types. The aim of this analysis was to evaluate the prognostic/predictive role of the bCTC count (≥3 vs. <3) in previously untreated mCRC.

Patients and Methods

The study involved 589 untreated mCRC patients included in the intention-to-treat population of 2 randomized clinical trials (phase III VISNU-1 [NCT01640405] and phase II VISNU-2 [NCT01640444] studies).

Results

Of the 589 patients, 349 (59.2%) had bCTC≥3 and 240 (40.7%) had bCTC<3. Multivariate analysis showed that the bCTC count is an independent prognostic factor for overall survival (OS) (HR 0.59, 95% CI 0.48-0.72; P = 0.000) and potential for progression-free survival (PFS) (P = 0.0549). Median OS was 32.9 and 19.5 months in patients with bCTC<3 and bCTC≥3 (P <0.001), respectively. This effect was also observed comparing OS in RASwt patients from both studies. Other prognostic factors were: ECOG-PS, primary tumor site, number of metastatic sites and surgery of the primary tumor. Median OS was lower for patients treated with anti-VEGF versus anti-EGFR (22.3 vs. 33.3 months, P <0.0001) while there were no significant differences in PFS according to the targeted treatment received.

Conclusion

This post-hoc analysis of 2 randomized studies confirms the poor prognosis of patients with bCTC≥3 but this is not associated with other adverse independent prognostic factors such as RAS/BRAF mutations.

Background

High body mass index (BMI) plays a key role in the development of colon cancer (CC). Our post-hoc analysis from the TOSCA trial analyzed the association between BMI and survival outcomes in terms of relapse-free survival (RFS) and overall survival (OS) in stage II/III CC patients.

Patients and methods

Patients enrolled in the TOSCA trial between 2007-2013 with BMI data entered the study. The prognostic impact of BMI on survival outcomes was investigated through uni- and multivariable Cox regression analyses.

Results

Overall, 1455 patients with stage II/III CC patients were included. The median follow-up was of 61.5 months; 16.1% of patients relapsed, 11.2% died and 19.5% patients relapsed or died. No impact of BMI on RFS was detected at univariate or multivariable analyses. By univariate analysis for OS, a significantly impact of a BMI > 30 kg/m² was reported (HR [>30 vs <25] 1.57, 95% CI 1.00-2.47, p = 0.049; HR [>30 vs <30] 1.55, 95% CI 1.01-2.37, p = 0.045). Multivariable analyses did not confirm this data. In the subgroup of stage III patients, a negative survival impact of BMI was found in univariate and multivariable models both for RFS and for OS.

Conclusions

In our study, obesity with BMI > 30 kg/m² was an independent prognostic factor for RFS and OS in CC patients treated with adjuvant chemotherapy, regardless of its duration (3 or 6 months). However, the prognostic impact of adiposity and body composition measurement should be considered to better classify patients with high visceral fat and refine their risk assessment.

Background

Colorectal cancer (CRC) screening can prevent disease by early identification. Existing disparities in CRC screening have been associated with factors including race, socioeconomic status, insurance, and even geography. Our study takes a deeper look into how social determinants related to zip code tabulation areas affect CRC screenings.

Materials and Methods

We conducted a retrospective cross-sectional study of CRC screenings by race at a zip code level, evaluating for impactful social determinant factors such as the social deprivation index (SDI). We used publicly available data from CDC 500 Cities Project (2016-2019), PLACES Project (2020), and the American Community Survey (2019). We conducted multivariate and confirmatory factor analyses among race, income, health insurance, check-up visits, and SDI.

Results

Increasing the tertile of SDI was associated with a higher likelihood of being Black or Hispanic, as well as decreased median household income (P < .01). Lower rates of regular checkup visits were found in the third tertile of SDI (P < .01). The multivariate analysis showed that being Black, Hispanic, lower income, being uninsured, lack of regular check-ups, and increased SDI were related to decreased CRC screening. In the confirmatory factor analysis, we found that SDI and access to insurance were the variables most related to decreased CRC screening.

Conclusion

Our results reveal the top 2 factors that impact a locality's CRC screening rates are the social deprivation index and access to health care. This data may help implement interventions targeting social barriers to further promote CRC screenings within disadvantaged communities and decrease overall mortality via early screening.

Aim

Patients with loco-regional right-sided colorectal tumors have a worse overall survival (OS). Here we investigate the difference in disease free survival (DFS) between colorectal patients with right and left sided tumors in the SCOT study.

Methods

The SCOT study showed 3-months of oxaliplatin-containing adjuvant chemotherapy (OxFp) is non-inferior to 6-months for patients with stage III and high-risk stage II colorectal cancer. We divided the cohort into patients with left and right sided tumors, and evaluated the effect on DFS and the principle 3 versus 6-months analysis.

Results

6088 patients with Stage III/high risk Stage II colorectal cancers were randomized between 27^th March 2008 and 29^th November 2013 from 244 centers internationally. In February 2017 (3-years FU) information on sidedness was available for 3309 patients (1238 R-sided, 2071 L-sided). Patients with right-sided tumors had a significantly worse DFS (3-year DFS right: 73.3% (se = 1.3%), left: 80.2% (se = 0.9%) HR 1.423 (95% CI 1.237-1.637; P < .0001). Adjusting for T and N-stage reduced the HR to 1.230 (95% CI 1.066-1.420, P = .005). The data did not suggest that sidedness affected the impact of chemotherapy duration on 3-year DFS (R: HR 1.024 [0.831-1.261], L: HR 0.944 [0.783-1.139]). Test for heterogeneity, P = .571. Further sub-set analysis was limited due to cohort size.

Conclusions

This is the first study to show that unselected patients with right-sided tumors had a worse DFS compared to left-sided tumors. Tumor sidedness did not impact upon the 3-months versus 6-months comparison in SCOT.