Search

We herein report a 73-year-old woman with BRAF V600E-mutated colon cancer treated with encorafenib plus cetuximab with binimetinib as standard salvage therapy for patients with advanced colorectal cancer. She developed bilateral serous retinal detachment the next day, and the regimen was discontinued, resulting in complete resolution by the third day. Doublet therapy without binimetinib was initiated along with a weekly ophthalmologic examination for 10 weeks without recurrence of retinal detachment. Thus, binimetinib was presumed to have been the cause of the retinal detachment. This clinical course suggests the need for close monitoring of patients for vision impairment and close collaboration with ophthalmologists.

Background: Constitutional mismatch repair deficiency (CMMRD) is an extremely rare autosomal recessive hereditary disease characterized by the absence of mismatch repair gene activity from birth, which results in brain tumors, colonic polyposis, gastrointestinal cancers, and lymphomas later in life. An aggressive approach, including colectomy or proctocolectomy, is recommended for the treatment of colorectal cancer. Additionally, partial colectomy with subsequent endoscopic surveillance may be an alternative strategy due to poor patient's condition, although there is no evidence of surveillance endoscopy after partial colectomy for CMMRD., Case Presentation: A 13-year-old male patient with a history of T-lymphoblastic lymphoma underwent total gastrointestinal endoscopy, which revealed rectal cancer, colorectal polyposis, and duodenal adenoma. Differential diagnosis included constitutional mismatch repair deficiency according to its scoring system and microsatellite instability, and subsequent germline mutation testing for mismatch repair genes confirmed the diagnosis of constitutional mismatch repair deficiency based on a homozygous mutation in mutS homolog 6 (MSH6). The patient and his family refused colectomy due to the high risk of malignancies other than colorectal cancer, which could require radical surgery. Therefore, the patient underwent low anterior resection of the rectosigmoid colon for rectal cancer and intensive surveillance endoscopy for the remaining colon polyposis. During the 3-year period after initial surgery, 130 polyps were removed and the number of polyps gradually decreased during 6-months interval surveillance endoscopies, although only one polyp was diagnosed as invasive adenocarcinoma (pT1)., Conclusions: Our experience of short surveillance endoscopy illustrates that this strategy might be one of options according to patient's condition., (© 2021. The Author(s).)

Background: It has been reported that morphologic response to preoperative chemotherapy is an independent prognostic factor in patients who undergo hepatic resection of colorectal liver metastases (CLM). The aim of this study was to evaluate the predictive value of morphologic response to first-line chemotherapy in patients with CLM., Methods: We assessed 41 patients with CLM who received fluorouracil-based chemotherapy with or without bevacizumab as the first-line chemotherapy between April 2006 and June 2012. Three blinded radiologists evaluated computed tomography images and classified them as optimal, incomplete or no response according to the morphologic criteria. Response to systemic chemotherapy was also evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST). Predictive factors associated with progression-free survival (PFS) were identified in multivariate analysis., Results: Twenty-three patients (56%) received chemotherapy with bevacizumab, while 18 patients (44%) received chemotherapy without bevacizumab. Optimal morphologic response was observed in 11 patients (48%) treated with bevacizumab and in 5 patients (28%) treated without bevacizumab (p = 0.19). Eight patients (20%) underwent hepatic resection after chemotherapy. The median follow-up period was 31.3 months. The median PFS was 13.3 months for patients with optical morphologic response and 8.7 months in those with incomplete/no morphologic response (p = 0.0026). On multivariate analysis, performance status and morphologic response were significant independent predictors of PFS., Conclusion: Optimal morphologic response was significantly associated with PFS in patients with CLM who were treated with fluorouracil-based chemotherapy as the first-line chemotherapy.

Background: Retrospective analyses in the West suggest that mutations in KRAS codons 61 and 146, BRAF, NRAS, and PIK3CA are negative predictive factors for cetuximab treatment in colorectal cancer patients. We developed a novel multiplex kit detecting 36 mutations in KRAS codons 61 and 146, BRAF, NRAS, and PIK3CA using Luminex (xMAP) assay in a single reaction., Methods: Tumor samples and clinical data from Asian colorectal cancer patients treated with cetuximab were collected. We investigated KRAS, BRAF, NRAS, and PIK3CA mutations using both the multiplex kit and direct sequencing methods, and evaluated the concordance between the 2 methods. Objective response, progression-free survival (PFS), and overall survival (OS) were also evaluated according to mutational status., Results: In total, 82 of 83 samples (78 surgically resected specimens and 5 biopsy specimens) were analyzed using both methods. All multiplex assays were performed using 50 ng of template DNA. The concordance rate between the methods was 100%. Overall, 49 (59.8%) patients had all wild-type tumors, 21 (25.6%) had tumors harboring KRAS codon 12 or 13 mutations, and 12 (14.6%) had tumors harboring KRAS codon 61, KRAS codon 146, BRAF, NRAS, or PIK3CA mutations. The response rates in these patient groups were 38.8%, 4.8%, and 0%, respectively. Median PFS in these groups was 6.1 months (95% confidence interval (CI): 3.1-9.2), 2.7 months (1.2-4.2), and 1.6 months (1.5-1.7); median OS was 13.8 months (9.2-18.4), 8.2 months (5.7-10.7), and 6.3 months (1.3-11.3), respectively. Statistically significant differences in both PFS and OS were found between patients with all wild-type tumors and those with KRAS codon 61, KRAS codon 146, BRAF, NRAS, or PIK3CA mutations (PFS: 95% CI, 0.11-0.44; P < 0.0001; OS: 95% CI, 0.15-0.61; P < 0.0001)., Conclusions: Our newly developed multiplex kit is practical and feasible for investigation of a range of sample types. Moreover, mutations in KRAS codon 61, KRAS codon 146, BRAF, NRAS, or PIK3CA detected in Asian patients were not predictive of clinical benefits from cetuximab treatment, similar to the result obtained in European studies.

Objective: Metastatic colorectal cancer with KRAS codon 12 or 13 mutations is not currently treated with anti-epidermal growth factor antibodies. A recent retrospective study in Western countries raised the possibility that KRAS p.G13D mutation may not be absolutely predictive of non-response compared with other KRAS mutations from the findings of longer overall survival and progression-free survival following cetuximab treatment. We retrospectively investigated the relationship between KRAS status and cetuximab efficacy among Japanese patients., Methods: Data of 109 patients from nine institutions in Japan were retrospectively analysed. All patients were refractory or intolerant to fluoropyrimidine, oxaliplatin and irinotecan, and they were treated with a cetuximab + irinotecan regimen. The response rate, disease control rate, progression-free survival and overall survival were compared according to KRAS status., Results: Overall, 76 (70%), 7 (6%) and 26 (24%) patients had KRAS wild-type, KRAS p.G13D and other KRAS mutations. Their various parameters were as follows: response rate: 30% (23/76), 14% (1/7) and 0% (0/26); disease control rate: 71% (54/76), 71% (5/7) and 54% (14/26); median progression-free survival: 4.6 months (95% confidence interval, 2.8-6.3), 4.1 months (0-9.9) and 2.1 months (1.5-2.8); and median overall survival: 11.2 months (6.4-16.0), 8.5 months (5.3-11.8) and 6.8 months (4.1-9.6), respectively., Conclusions: Although no statistically significant difference in progression-free survival or overall survival was observed between KRAS p.G13D-mutant and other mutant tumours, the disease control rate was higher in KRAS p.G13D-mutant patients and a partial response was observed in one such patient. Our study suggested that cetuximab showed some activity in KRAS p.G13D-mutant colorectal cancer patients. Further research is warranted.

Background: A combination of 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX) is a standard regimen for the chemotherapy of metastatic colorectal cancer. The major dose-limiting toxic effect of oxaliplatin is neurotoxicity. The aim of this study was to evaluate the preventive effects of traditional Japanese medicines, goshajinkigan and shakuyakukanzoto on oxaliplatin-induced neurotoxicity with FOLFOX., Patients and Methods: Between July 2006 and November 2008, a total of 44 patients with metastatic colorectal cancer received modified FOLFOX6 or FOLFOX4, as first-line chemotherapy at three institutions. They concurrently received either goshajinkigan (group A, n=20) or shakuyakukanzoto (group B, n=24) for neurotoxicity reduction., Results: The median number of treatment cycles and the median cumulative dose of oxaliplatin were 12 cycles (range, 4-19) and 898 mg/m(2) (range, 340-1255) in group A and 10.5 cycles (range, 6-20) and 845 mg/m(2) (range, 510-1480) in group B. Eighteen patients in group A and 24 in group B received oxaliplatin in a cumulative dose exceeding 500 mg/m(2). At a dose of 500 mg/m(2) oxaliplatin, grade 1-2 toxicity occurred in 10 patients of group A and in 7 of group B, but there was no grade 3 or higher toxicity in either group. The response rate of the 38 patients with measurable lesions was 50.0% (9/18) in group A and 65% (13/20) in group B., Conclusion: The administration of traditional Japanese medicine may reduce oxalipatin-induced neurotoxicity without negatively affecting tumor response in patients with colorectal cancer who undergo FOLFOX therapy.