The salvage lenvatinib-based regimen provides survival benefit in patients with refractory metastatic colorectal cancer.

Salvage treatment for refractory metastatic colorectal cancer (mCRC) has yet to be identified. We aimed to evaluate the efficacy of a salvage lenvatinib-based regimen for refractory mCRC. In total, 371 patients were categorized into lenvatinib-based and non-lenvatinib-based groups. In the lenvatinib-based group, patients who received lenvatinib at a dosage of 10 mg/day were categorized into lenvatinib/chemotherapy and lenvatinib/immunotherapy subgroups. We reported overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier method. OS1 was used to measure the time from disease progression after TAS-102 and regorafenib treatment to death, while OS2 was used to measure the time from TAS-102 or regorafenib treatment to death. Propensity score matching analysis was employed to compare the characteristics between the lenvatinib-based and non-lenvatinib-based groups. Next-generation sequencing (NGS) information was analyzed using R software. The lenvatinib-based group exhibited longer OS than did the non-lenvatinib-based group (OS1, 11.4 vs. 3.7 months; OS2, 27.2 vs. 8.2 months). The disease control rate (DCR) and objective response rate (ORR) of the lenvatinib-based regimens were 69.4% and 6.1%, respectively. Lenvatinib/chemotherapy and lenvatinib/immunotherapy had similar PFS, OS, DCR, and ORR. The adverse effects were manageable. After propensity score matching, the lenvatinib-based group continued to exhibit significantly longer OS1 and OS2 than did the non-lenvatinib-based group. NGS analysis revealed that GNAS and KRAS alterations were associated with a worse treatment response and prolonged survival, respectively. In conclusion, a moderate-dose salvage lenvatinib-based regimen demonstrated promising clinical activity and tolerability in treating refractory mCRC.

Short-term outcomes of short- and long-course chemoradiotherapy prior to total mesorectal excision for locally advanced rectal tumors: A single-center study in Taiwan utilizing propensity score matching.

BACKGROUND: Locally advanced rectal tumors are typically treated with neoadjuvant chemoradiotherapy. Short-course chemoradiotherapy (SCRT, 2,500 cGy in five fractions) is a convenient alternative to concurrent chemoradiotherapy with long-course radiotherapy (CCRT, 4,500 cGy in 25 fractions) without sacrificing efficacy. We aimed to compare the short-term outcomes of SCRT and CCRT in patients with mid- and low- rectal tumors who underwent total mesorectal excision using real-world data. METHODS: We retrospectively reviewed the data of patients with locally advanced rectal cancer who underwent radical resection after neoadjuvant chemoradiotherapy from 2011 to 2022. We analyzed the clinicopathological findings and prognostic factors for disease-free and overall survival in the SCRT and CCRT groups and compared the outcomes using propensity score matching. RESULTS: Among the 66 patients in the two groups, no disparities were noted in the demographic features, pathological remission, or downstaging rates. Nonetheless, the SCRT group exhibited superior 3-year disease-free survival (81.8% vs. 62.1%, p = 0.011), whereas the overall survival did not differ significantly between the two groups. The initial carcinoembryonic antigen (CEA) levels and neoadjuvant SCRT were associated with the recurrence rates [hazard ratio (HR) 1.13-4.10; HR 0.19-0.74], but the harvested lymph node count was not (HR 0.51-1.97). CONCLUSION: Among patients with locally advanced rectal cancer, SCRT combined with four cycles of FOLFOX was shown to enhance short-term disease-free survival. Factors impacting recurrence include the initial CEA level and SCRT, but not the harvested lymph node count.

The survival outcome differs between left-sided colon cancer and middle/low rectal cancer after colorectal hepatic metastasectomy.

BACKGROUND: The clinical outcomes between left-sided colon cancer and middle/low rectal cancer seem to be different. This study aimed to examine the effect of primary tumor location regarding the left-sided colon and middle/low rectum on the overall survival (OS) of patients who underwent colorectal hepatic metastasectomy. METHODS: Patients who underwent colorectal hepatic metastasectomy were retrospectively enrolled. Patients were classified into 2 groups according to the primary tumor location (left-sided colon and middle/low rectum). Categorical variables were compared using the chi-square test or Fisher exact test, and continuous variables were analyzed using the Student t test. Survival was analyzed using the Kaplan-Meier method and log-rank test. The prognostic factors were analyzed by univariate and multivariate analyses using Cox proportional hazards regression models. RESULTS: Overall, 365 patients were enrolled. Patients with left-sided colon cancer had significantly better OS than those with middle/low rectal cancer (hazard ratio [HR], 0.725; P = .018), with median OS estimates of 48 and 38 months, respectively. In the subgroup analysis of RAS mutations, patients with left-sided colon cancer had significantly prolonged OS compared with those with middle/low rectum cancer (HR, 0.608; P = .034), with median OS estimates of 49 and 26 months, respectively. This observation was limited to patients with RAS mutations. CONCLUSION: According to our findings, patients with middle/low rectal cancer had poorer survival outcome and should not be categorized together with patients with left-sided colon cancer in terms of OS after colorectal hepatic metastasectomy.

Anti-VEGF Therapy Possibly Extends Survival in Patients With Colorectal Brain Metastasis by Protecting Patients From Neurologic Disability.

BACKGROUND: Colorectal brain metastases (CBMs) are rare with poor prognosis. There is still no standard systemic treatment for multiple or unresectable CBM. our study aimed to explore the impact of anti-VEGF therapy on overall survival, brain-specific disease control, and neurologic symptom burden in patients with CBM. METHODS: A total of 65 patients with CBM under treatment were retrospectively enrolled and divided into anti-VEGF based systemic therapy or non-anti-VEGF based therapy. A total of 25 patients who received at least 3 cycles of anti-VEGF agent and 40 patients without anti-VEGF therapy were analyzed by endpoints of overall survival (OS), progression-free survival (PFS), intracranial PFS (iPFS) and neurogenic event-free survival (nEFS). Gene expression in paired primary metastatic colorectal cancer (mCRC), liver, lung and brain metastasis from NCBI data was analyzed using top Gene Ontology (GO) and cBioPortal. RESULTS: Patients who treated with anti-VEGF therapy had significantly longer OS (19.5 vs. 5.5 months, P = .009), iPFS (14.6 vs. 4.1 months, P < .001) and nEFS (17.6 vs. 4.4 months, P < .001). Patients who received anti-VEGF therapy beyond any disease progression presented with superior OS (19.7 vs. 9.4 months, P = .039). Top GO and cBioPortal analysis revealed a stronger molecular function of angiogenesis in intracranial metastasis. CONCLUSIONS: Anti-VEGF based systemic therapy showed favorable efficacy that was reflected in longer overall survival, iPFS and NEFS in patients with CBM.

Comparison of two-stage and three-stage surgery for obstructing left-sided colon cancer.

BACKGROUND: Whether the timing of stoma reversal after emergency diversion for obstructive left-sided colon cancer affects patient outcomes is unknown. Our study compared the short- and long-term outcomes of two- and three-stage operations for obstructive left-sided colon cancer. METHODS: Patients with obstructive left-sided colon cancer who underwent staged resection at a referral hospital between January 2002 and December 2015 were retrospectively identified. Patient demographics and outcomes were analysed and compared between the two groups. Statistical significance was set as p < 0.05. RESULTS: A total of 191 patients were reviewed. The overall complication rate was higher for two-stage surgery than for three-stage surgery (57.1% versus 36.0%, p < 0.01). Surgical site infection and/or wound dehiscence were the most common complications. Other complications, including anastomotic leakage, ileus, and bowel obstruction, were not significantly different between the two groups. The five-year overall survival and disease-free survival in stage II and III patients were comparable. CONCLUSION: Among patients with obstructive left-sided colon cancer who underwent staged resection, two-stage surgery was associated with a higher complication rate, especially for surgical site infection and/or wound dehiscence, which could be managed by local treatment. The timing of stoma reversal was not associated with survival differences in patients with stage II and III disease. However, issues such as the location of the tumour and diverting stoma, along with the need to resect other upper abdominal organs, should all be considered when deciding between two- and three-stage surgeries.

Proteomic analysis of rice defense response induced by probenazole.

Here, we report the first proteomic analysis of rice defense response induced by probenazole (PBZ), an agricultural chemical that has been widely used to protect rice plants from rice blast and the bacterial blight pathogen. Two-dimensional gel electrophoresis (2-DE) was utilized to identify a total of 40 protein spots including 9 protein spots that are up-regulated by PBZ and 31 abundant protein spots. A total of 11 unique proteins from these 9 spots were identified by LC-MS/MS, and the majority of them were classified and/or possessed orthologs in defense-related functions. Five protein spots with only one protein species identified in each spot appear to be PBZ-regulated proteins. They are a putative glutathione S-transferase GSTU17, a putative phenylalanine ammonia-lyase (PAL, XP_466843), a putative caffeic acid 3-O-methyltransferase (COMT), a putative NADH-ubiquinone oxidoreductase, and a putative glucose-1-phosphate adenyltransferase. However, the other six protein species identified from the remaining four protein spots could not be conclusively described as PBZ-regulated proteins due to either the co-migration of two protein species in one spot or the presence of one protein species in two spots. Through real-time reverse transcription polymerase chain reaction (RT-PCR), it was determined that PAL (XP_466843) is likely regulated at the protein level, whereas GSTU17 and COMT were regulated at the mRNA level after PBZ application. Interestingly, the mRNA transcripts of two PAL paralogs were found to be up-regulated by PBZ. We propose that PAL, COMT, and GSTU17 are likely to confer PBZ-induced disease resistance via such functions as biosynthesis and transport of flavonoid-type phytoalexin and/or lignin biogenesis.