Conversion Surgery After Encorafenib Plus Cetuximab for Chemorefractory BRAF V600E-mutated Colorectal Cancer With Para-aortic Lymph Node Metastases.

BACKGROUND/AIM: Mutant BRAF V600E colorectal cancer accounts for 5% of metastatic colorectal cancers, and it has a poor response to systemic chemotherapy and a poor prognosis. However, combination treatment involving MAPK pathway blockade is effective for this cancer. Herein, we report a case of a patient who underwent conversion surgery after encorafenib plus cetuximab for chemorefractory BRAF V600E-mutated colorectal cancer with para-aortic lymph node metastases. CASE REPORT: A 68-year-old woman was diagnosed with ascending colon cancer and multiple para-aortic lymph node metastases. After primary tumor resection, molecular genetic testing of the primary tumor revealed a BRAF V600E mutation. She was treated with FOLFOXIRI plus bevacizumab as first-line chemotherapy. After disease progression, the regimen was changed to encorafenib plus cetuximab, and the metastatic lesions shrank. She underwent para-aortic lymph node dissection as conversion surgery, and pathology revealed complete response of the lymph nodes. She achieved long-term survival. CONCLUSION: The development of new treatments for BRAF V600E-mutated metastatic colorectal cancer will increase opportunities for conversion therapy.

Therapeutic Modifications without Discontinuation of Atezolizumab Plus Bevacizumab Therapy Are Associated with Favorable Overall Survival and Time to Progression in Patients with Unresectable Hepatocellular Carcinoma.

We retrospectively evaluated the impact of therapeutic modifications of atezolizumab (Atezo) plus bevacizumab (Bev) therapy (Atezo/Bev), including the interruption or discontinuation of both Atezo and Bev, and the reduction or discontinuation of Bev, on the outcome of patients with unresectable hepatocellular carcinoma (uHCC) (median observation period: 9.40 months). One hundred uHCC from five hospitals were included. Therapeutic modifications without discontinuation of both Atezo and Bev (n = 46) were associated with favorable overall survival (median not reached; hazard ratio (HR): 0.23) and time to progression (median: 10.00 months; HR: 0.23) with no therapeutic modification defined as the reference. In contrast, the discontinuation of both Atezo and Bev without other therapeutic modifications (n = 20) was associated with unfavorable overall survival (median: 9.63 months; HR: 2.72) and time to progression (median: 2.53 months; HR: 2.78). Patients with modified albumin-bilirubin grade 2b liver function (n = 43) or immune-related adverse events (irAEs) (n = 31) discontinued both Atezo and Bev without other therapeutic modifications more frequently (30.2% and 35.5%, respectively) than those with modified albumin-bilirubin grade 1 (10.2%) and without irAEs (13.0%). Patients with objective response (n = 48) experienced irAEs more frequently (n = 21) than those without (n = 10) (p = 0.027). Avoiding the discontinuation of both Atezo and Bev without other therapeutic modifications may be the optimal management of uHCC.

Comparison of endoscopic submucosal resection with ligation and endoscopic submucosal dissection for small rectal neuroendocrine tumors: A multicenter retrospective study.

Objectives: Endoscopic submucosal resection with band ligation (ESMR-L) and endoscopic submucosal dissection (ESD) are both standard endoscopic resection methods for rectal neuroendocrine tumors (NETs) <10 mm in size. However, there is no definitive consensus on which is better. Here, we compared the efficacy of ESMR-L and ESD for small rectal NETs. Methods: This was a multicenter retrospective cohort study including 205 patients with rectal NETs who underwent ESMR-L or ESD. Treatment outcomes were compared by univariate analysis, multivariate analysis, and inverse probability treatment weighting (IPTW) using propensity scores. Subgroup analysis evaluated the impact of the endoscopist's experience on the technical outcome. Results: Eighty-nine patients were treated by ESMR-L and 116 by ESD. The R0 resection rate was not significantly different between the two (90% vs. 92%, p = 0.73). The procedure time of ESMR-L was significantly shorter than for ESD (17 min vs. 52 min, p < 0.01) and the hospitalization period was also significantly shorter (3 days vs. 5 days, p < 0.01). These results were confirmed by multivariate analysis and also after IPTW adjustment. The procedure time of ESD was significantly prolonged by a less-experienced endoscopist (49 min vs. 70 min, p = 0.02), but that of ESMR-L was not affected (17 min vs. 17 min, p = 0.27). Conclusions: For small rectal NETs, both ESMR-L and ESD showed similar high complete resection rates. However, considering the shorter procedure time and shorter hospitalization period, ESMR-L is the more efficient treatment method, especially for less-experienced endoscopists.

[A Case of Long-Term Survival after Chemotherapy and Ablation Therapy Using Various Approaches for Multiple Colon Cancer Liver Metastases].

A 58-year-old man with unresectable sigmoid colon cancer and multiple liver metastases(H2, more than 30)received chemotherapy for 2 years. Subsequently, the patient was diagnosed with stenosis of the primary lesion and 5 bilobar, metastatic tumors. Simultaneous resection was unsuitable because of the performance status and comorbidities of the patient. The first surgery consisted of laparoscopic-assisted sigmoidectomy, laparoscopic microwave coagulation therapy(MCT), and percutaneous radiofrequency ablation(RFA). Percutaneous RFA was additionally performed after 2 months. Since 2 liver metastases(S3 and S8)were inadequately treated, 3 courses of P-mab plus FOLFIRI were administered. Finally, laparoscopic- assisted RFA was performed. Subsequently, serum CEA reduced from 288.3 ng/mL to the normal level. We used fusion imaging US, sonazoid US, laparoscopic convex probe, and ICG fluorescence imaging for ablation therapy. Chemotherapy and ablation therapy using various approaches can control unresectable multiple liver metastases and prolong survival by more than 3 years.

A 12-year Recurrence-free Survival After Multidisciplinary Treatment for a Patient With Combined Hepatocellular-Cholangiocarcinoma.

We report a 64-year-old woman with a 9-cm liver tumor in the left lateral section. The patient had neither hepatitis B or C virus infection, nor cirrhosis. Carbohydrate antigen 19-9 (CA 19-9) level was 1,889 U/ml. We also suspected bulky hilar lymph node metastasis, and a left lateral sectionectomy without lymph node dissection (R2) was performed. The pathological findings led to diagnosis of combined hepatocellular and cholangiocarcinoma. Three weeks post-operation, the patient underwent hepatic arterial infusion chemotherapy with cisplatin, fluorouracil, and mitomycin C. In addition, a total dose of 45 Gy of irradiation for the hilar lymph node was performed; while oral tegafur-uracil (UFT) has been administered for 10 years at a dose of 400 mg/day. The CA19-9 level of the patient was normalized after hepatectomy, hepatic arterial infusion, irradiation for hilar lymph node, and oral UFT administration. Currently, the patient is alive without any relapse for 12 years post-operation.

Evaluation of sorafenib treatment and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: a comparative study using the propensity score matching method.

While sorafenib (SFN) is the established worldwide standard therapeutic agent for advanced hepatocellular carcinoma (HCC), hepatic arterial infusion chemotherapy (HAIC) is also considered a favorable treatment for some advanced HCCs. This study aimed to evaluate each treatment and provide an optimal therapeutic choice for advanced HCCs. We analyzed 72 patients treated with SFN and 128 patients receiving HAIC. Both treatment groups were analyzed for prognostic and disease progression factors, and matched pair analysis was performed using the propensity score matching method. The preferable status of intrahepatic lesions, that is, no lesions or only a single (< 3 cm) intrahepetic lesion, was positively associated with good prognosis and negatively associated with disease progression in the SFN group. Maximum tumor size (> 5 cm) and low albumin (≤ 3.4 g/dL) were poor prognostic and disease progression factors in the HAIC group. Analysis of 53 patients selected from each of the SFN and HAIC groups based on the propensity score matching method showed no significant differences in survival or disease progression between the two matched subgroups. On the other hand, progression-free survival (PFS) in the HAIC-matched subgroup was significantly longer than in the SFN-matched subgroup, particularly in patients with portal vein invasion (PVI) and/or without extrahepatic spread (EHS). The treatment efficacy of HAIC is similar to that of SFN regarding survival and disease progression. Longer PFS might be expected for HAIC compared with SFN, particularly in patients with PVI and/or without EHS.