Clinical colorectal cancer最新文献

Background

In patients with locally advanced rectal cancer (LARC) treated with preoperative (chemo) radiotherapy and surgery, adjuvant chemotherapy is poorly feasible and its benefit is questionable. In the last years, several total neoadjuvant treatment (TNT) strategies, moving the adjuvant chemotherapy to the neoadjuvant setting, have been investigated with the aim of improving compliance to systemic chemotherapy, treating micrometastases earlier and then reducing distant recurrence.

Patients and Methods

ShorTrip (NTC05253846) is a prospective, multicentre, single-arm phase II trial where 63 patients with LARC will be treated with short-course radiotherapy followed by intensified consolidation chemotherapy with FOLFOXIRI regimen and surgery. Primary endpoint is pCR. Among the first 11 patients who started consolidation chemotherapy, a preliminary safety analysis showed a high rate of grade 3 to 4 neutropenia (N = 7, 64%) during the first cycle of FOLFOXIRI. Therefore, the protocol has been emended with the recommendation to omit irinotecan during the first cycle of consolidation chemotherapy. After amendment, in a subsequent safety analysis focused on the first 9 patients treated with FOLFOX as first cycle and then with FOLFOXIRI, grade 3 to 4 neutropenia was reported in only one case during the second cycle.

Aim of the study

The aim of this study is to assess the safety and activity of a TNT strategy including SCRT, intensified consolidation treatment with FOLFOXIRI and delayed surgery. After protocol amendment, the treatment seems feasible without safety concern. Results are expected at the end of 2024.

Background

We report our long-term experience with high dose rate intraoperative radiotherapy (HDR-IORT) in a single, quaternary institution.

Patients/Methods

From 2004 to 2020, 60 HDR-IORT procedures for locally advanced colorectal cancer (LACC) and 81 for locally recurrent colorectal cancer (LRCC) were done in our institution. Preoperative radiotherapy was done prior to majority of the resections (89%, 125/141). Sixty-nine percent (58/84) of the resections involving pelvic exenterations had >3 en bloc organs resected. HDR-IORT was delivered using a Freiburg applicator. A single 10 Gy fraction was delivered. Margin status was R0 and R1 in 54% (76/141) and 46% (65/141) of the resections, respectively.

Results

With a median follow-up time of 4 years, 3-, 5-, and 7- year, overall survival (OS) rates were 84%, 58%, and 58% for LACC and 68%, 41%, and 37% for LRCC, respectively. Local progression-free survival (LPFS) rates were 97%, 93%, and 93% for LACC and 80%, 80%, 80% for LRCC, respectively. For the LRCC group, an R1 resection was associated with worse OS, LPFS, and progression-free survival (PFS), preoperative EBRT was associated with improved LPFS and PFS, and ≥2 years disease-free interval was associated with improved PFS. The most common severe adverse events were postoperative abscess (n = 25) and bowel obstruction (n = 11). There were 68 grade 3 to 4 and no grade 5 adverse events.

Conclusions

Favorable OS and LPFS can be achieved for LACC and LRCC with intensive local therapy. In patients with risk factors for poorer outcomes, optimization of EBRT and IORT, surgical resection, and systemic therapy are required.

Background and Aim

This study aimed to determine treatment outcomes and factors affecting prognosis in patients diagnosed with anal canal cancer who received radical radiotherapy (RT) or radiotherapy combined with chemotherapy (CT-RT) in radiation oncology centers in Turkey and compare the results with literature.

Material and Method

The study included 193 patients with anal canal cancer reported between 1995 and 2019, of which 162 had complete data. The study was conducted in 11 radiation oncology centers, and a joint database was shared among them. Patients received radiotherapy doses of 45 Gy to 60 Gy. Data analysis was done using SPSS for Windows version 20.

Results

Median follow-up was 48.51 months (2-214). All patients received radiotherapy, and 140 (86.4%) received concurrent chemotherapy. Radiotherapy doses of 50.4 Gy to 60 Gy were administered to 74 patients (45.7%) using 2-dimensional-3-dimensional (2D-3D) conformal therapy and 70 patients (43.2%) using intensity modulated radiotherapy technique (IMRT). Acute phase hematologic toxicity was observed in 62 patients (38.3%), and nonhematologic toxicity in 123 patients (75.9%). The 5-year overall survival (OS) rate was 75.1% and disease-specific survival (DSS) rate was 76.4%. OS without colostomy was achieved in 79,8 % at 5 years, and complete response in 112 patients (69.1%). OS rate was significantly higher in 142 patients with positive response (P < .000) and 112 with complete response (P < .000). Anemia (P < .002), local progression, and systemic progression (P < .000) resulted in lower OS (P < .002). In univariate analysis, factors affecting OS rate were: gender, age, stage, lymph node status, T stage, RT treatment duration, and treatment planning with PET fusion, which were found to be statistically significant. Completing radiotherapy in less than 45 days, concurrent chemotherapy, and continued administration of mitomycin and 5 FU as chemotherapy had a significant positive effect on overall survival. OS rate was higher in patients receiving RT dose of 58 Gy or less and undergoing IMRT planning in radiotherapy. IMRT was associated with lower acute and late side effects.

Conclusion

Radiochemotherapy is the primary treatment for anal canal cancer and advanced radiotherapy techniques may increase survival by reducing side effects and improving treatment continuation. Higher treatment doses require further investigation. The efficacy of treatment can be improved by including patients treated with modern radiotherapy techniques in multicenter prospective studies using new and more effective chemotherapy and immunotherapy agents.

Background

There are 3 widely used preoperative radiotherapy (RT) procedures in rectal cancer treatment including long-course RT (LRT), short-course RT with delayed surgery (SRTW), and short-course RT with immediate surgery (SRT). However, further evidence is required to determine which treatment option results in more optimal patient survival.

Methods

This Swedish Colorectal Cancer Registry-based retrospective study of real-world data included 7766 stage I–III rectal cancer patients, of which 2982, 1089, 763, and 2932 patients received no RT (NRT), LRT, SRTW, and SRT, respectively. The Kaplan-Meier survival curve and Cox proportional hazard multivariate model were used to identify potential risk factors and to examine the independent association of RT with patient survival after adjusting for baseline confounding factors.

Results

RT effects on survival differed by age and clinical T stage (cT) subgroups. Subsequent survival analysis by age and cT subgroups confirmed that patients ≥70 years old with cT4 benefited from any RT (P < .001, NRT as reference) and equally from any RT (P > .05 pairwise between RTs). In contrast, for cT3 patients ≥70 years, SRT and LRT were associated with better survival than SRTW (P < .001). In patients <70 years, LRT and SRTW had superior survival benefits in cT4 patients but inferior to SRT (P < .001); SRT was the only effective treatment in the cT3N+ subgroup (P = .032); patients with cT3N0 and <70 years did not benefit from any RT.

Conclusion

This study suggests that preoperative RT strategies may have varying effects on the survival of rectal cancer patients, depending on their age and clinical stage.

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.