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The aim of this study was to determine the efficacy and the biomarkers of the CHP-NY-ESO-1 vaccine complexed with full-length NY-ESO-1 protein and a cholesteryl pullulan (CHP) in patients with esophageal squamous cell carcinoma (ESCC) after surgery. We conducted a randomized phase II trial. Fifty-four patients with NY-ESO-1-expressing ESCC who underwent radical surgery following cisplatin/5-fluorouracil-based neoadjuvant chemotherapy were assigned to receive either CHP-NY-ESO-1 vaccination or observation as control. Six doses of CHP-NY-ESO-1 were administered subcutaneously once every two weeks, followed by nine more doses once every four weeks. The endpoints were disease-free survival (DFS) and safety. Exploratory analysis of tumor tissues using gene-expression profiles was also performed to seek the biomarker. As there were no serious adverse events in 27 vaccinated patients, we verified the safety of the vaccine. DFS in 2 years were 56.0% and 58.3% in the vaccine arm and in the control, respectively. Twenty-four of 25 patients showed NY-ESO-1-specific IgG responses after vaccination. Analysis of intra-cohort correlations among vaccinated patients revealed that 5% or greater expression of NY-ESO-1 was a favorable factor. Comprehensive analysis of gene expression profiles revealed that the expression of the gene encoding polymeric immunoglobulin receptor (PIGR) in tumors had a significantly favorable impact on outcomes in the vaccinated cohort. The high PIGR-expressing tumors that had higher NY-ESO-1-specific IgA response tended to have favorable prognosis. These results suggest that PIGR would play a major role in tumor immunity in an antigen-specific manner during NY-ESO-1 vaccinations. The IgA response may be relevant.

Malnutrition and cachexia occur commonly in patients with advanced gastric cancer (AGC). This study elucidated the effect of nutritional support (NS) on survival outcomes among patients with AGC undergoing chemotherapy. We retrospectively evaluated new AGC cases at our institute between January 2015 and January 2021. Inclusion criteria were unresectable or recurrent chemotherapy-treated gastric adenocarcinoma, ECOG performance status (PS) 0-2, and adequate organ function. Time to treatment failure (TTF) and overall survival (OS) were evaluated, and univariate and multivariate analyses identified prognostic factors. A total of 103 eligible patients were separated into groups: 69 patients (67%) into NS and 34 (33%) into routine care (RC). The median follow-up time was 11.0 mo, (0.5-92). NS was offered to patients with poorer PS (

Regorafenib and trifluridine/tipiracil are standard third-line chemotherapies for colorectal cancer patients, but their efficacy is limited. Anti-epidermal growth factor receptor antibody rechallenge has been reported to be promising for patients who have obtained clinical benefit from first-line cetuximab-based chemotherapy. Moreover, panitumumab showed non-inferior efficacy to cetuximab. This study assessed the efficacy and safety of third-line panitumumab rechallenge in patients with metastatic KRAS exon 2 wild-type metastatic colorectal cancer who obtained clinical benefit from first-line panitumumab-based chemotherapy. This was a prospective, multicenter, phase II trial conducted from October 2013 to August 2017. Major eligibility criteria included KRAS exon 2 wild-type and achievement of complete response, partial response, or continued stable disease for at least 6 months in first-line panitumumab-based therapy. Irinotecan plus panitumumab treatment was continued until disease progression or unacceptable toxicity was observed. The primary endpoint was the 3-month progression-free survival (PFS) rate. Twenty-five patients were enrolled in this study. Their median age was 66.5 years, and the 3-month PFS rate was 50.0% (95% confidence interval 30.0–70.0). The median PFS and overall survival were 3.1 months and 8.9 months, respectively. The response rate and disease control rate were 8.3% and 50.0%, respectively. Common grade 3/4 adverse events were acneiform rash (17%), hypomagnesemia (13%), and dry skin (13%). No treatment-related deaths occurred. Irinotecan plus panitumumab rechallenge is a promising third-line treatment regimen in patients with metastatic wild-type KRAS colorectal cancer. UMIN000015916.

Background The aim of this study was to evaluate the efficacy and safety of first-line chemotherapy with re-introduction of oxaliplatin (OX) more than 6 months after adjuvant chemotherapy including OX. Methods Stage II/III colon cancer patients with neuropathies of grade ≤ 1 who relapsed more than 6 months after adjuvant chemotherapy including OX were considered eligible. Eligible patients were treated with 5-fluorouracil, l-leucovorin and OX plus molecularly targeted agents or capecitabine and OX plus bevacizumab (BV) or S-1 and OX plus BV. The primary endpoint was the progression-free survival (PFS), and the secondary endpoints were the overall survival (OS), response rate (RR) and toxicity. Results A total of 50 patients were enrolled between September 2013 and May 2019. Twelve patients received 5-fluorouracil, l-leucovorin and OX (FOLFOX) plus BV, 21 patients received capecitabine and OX plus BV, 10 patients received S-1 and OX plus BV and 7 patients received FOLFOX plus cetuximab or panitumumab. The median PFS was 11.5 months (95% confidence interval [CI] 8.3–16.0), the median OS was 45.4 months (95% CI 37.4–NA), and the RR was 56.0% (95% CI 42.3–68.8). Adverse events of grade ≥ 3 that occurred in ≥ 5% of cases were neutropenia in 6 patients (12%), peripheral sensory neuropathy in 5 patients (10%), diarrhea in 4 patients (8%), hypertension in 4 patients (8%), anorexia in 3 patients (6%) and allergic reactions in 3 patients (6%). Conclusions First-line chemotherapy with re-introduction of OX more than 6 months after adjuvant chemotherapy including OX can be used safely with expected efficacy for relapsed colon cancer patients.

BACKGROUND Clonal hematopoiesis is the production of a specific single clonal type of cell in the blood and is often found in cancer genomic profiling tests. When the clone carries a pathogenic variant, it may be important to differentiate between somatic or germline origin. The variant in the blood that has a lower minor allele frequency could reflect heterozygous germline origin, somatic mosaicism, and clonal hematopoiesis. It is important to evaluate suspected variants to determine the course of treatment and follow-up of the patient, depending on the patient's medical condition and family situation. CASE REPORT We report a 53-year-old Japanese man with gastric cancer who underwent a cancer genomic profiling test searching for therapeutic agents. The profiling test detected a variant, TP53 c.559+2TG minor allele frequencies of 9% (168/1865) in tumor tissue and 29.1% (58/199) in paired blood. Since the TP53 variant has the possibility of Li-Fraumeni syndrome, ancillary testing was performed using fingernails, buccal swab, and blood specimens. The genomic analysis revealed no TP53 variant in his fingernails. The patient had previously received platinum-based chemotherapies, suggesting that the variant reflected treatment-induced clonal hematopoiesis. CONCLUSIONS Identifying clonal hematopoiesis when performing genomic profiling tests for patients with cancer is important. Examining multiple tissues to determine whether a variant arises from clonal hematopoiesis or is of germline origin can provide more accurate genetic information and improve patient follow-up care.

The status and prognostic value of the disagreement between physician and patient assessments of symptomatic adverse events (AEs) remain unclear for patients with metastatic colorectal cancer treated with first‐line cetuximab plus chemotherapy. Paired data on patient‐reported outcomes using the EORTC QLQ‐C30 and physician‐reported outcomes using the NCI‐CTCAE for eight symptomatic AEs (fatigue, pain, insomnia, dyspnea, constipation, appetite loss, nausea/vomiting, and diarrhea) were collected from a prospective trial assessing the relationships between treatment efficacy, AEs, and quality of life. The overall agreement rates between patient and physician reporting at 4 weeks ranged from 40.2% to 76.5% for 129 patients. The level of agreement based on Cohen's κ statistics was slight to poor for dyspnea, pain, fatigue, and insomnia, while it was moderate to fair for the remaining AEs. No clinicopathological characteristics of disagreement were found. The underreporting by physicians ranged from 12.5% (nausea/vomiting) to 56.7% (fatigue). The 2‐year overall survival (OS) rate was more favorable for patients with high agreement than for those with low agreement (71.2% vs. 46.5%, p = .016), and the agreement status was an independent factor of OS (HR, 2.31; 95% CI, 1.13–4.71; p = .022). For patients who were reported as asymptomatic by the physician, the presence of patient‐reported symptoms resulted in a trend toward poor prognostic outcomes for appetite loss, dyspnea, diarrhea, and constipation. These findings provide the clinical importance of the monitoring of patient‐reported symptoms that can be complementary to physician‐reported data to ensure more accurate clinical outcomes., The routine use of PROs could be complementary to physician‐reported outcomes to ensure the accurate assessment of symptomatic AEs and facilitate patient‐centered healthcare in clinical practice.

PURPOSE Several trials have evaluated the efficacy of rechallenge treatment with anti–epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) in patients with metastatic colorectal cancer (mCRC). A recent trial indicated that RAS status in circulating tumor DNA (ctDNA) may potentially predict patients with RAS wild-type mCRC resistant to anti-EGFR mAb who would benefit from rechallenge treatment, and the findings should be further investigated. MATERIAL AND METHODS We enrolled patients whose plasma samples were collected in prospective phase II trials, the JACCRO CC-08 (n = 36) and CC-09 (n = 25), which evaluated rechallenge chemotherapy with anti-EGFR mAb for KRAS wild-type mCRC. RAS in ctDNA was analyzed at the time points of baseline, 8 weeks, and progression using OncoBEAM RAS CRC kit. RESULTS Sixteen patients were enrolled in this study, with a response rate of 0% and a disease control rate (DCR) of 62.5%. RAS mutations were found at baseline in six patients. The DCR was 33% in patients with RAS mutations in ctDNA, whereas it was 80% in patients without RAS mutation at baseline. Patients with RAS mutation at baseline had significantly shorter progression-free survival (PFS) and overall survival (OS) than those without RAS mutation (median PFS, 2.3 v 4.7 months; hazard ratio [HR], 6.2; P = .013; median OS, 3.8 v 16.0 months; HR, 12.4; P = .0028). Six of 10 patients without RAS mutation at baseline acquired RAS mutations at progression. Postprogression survival after rechallenge treatment was numerically shorter in patients with RAS mutation at progression. CONCLUSION RAS status in ctDNA was significantly associated with clinical outcomes in patients with mCRC receiving rechallenge treatment with anti-EGFR mAb. These findings could support the clinical utility of OncoBEAM RAS CRC kits for anti-EGFR mAb rechallenge in RAS wild-type mCRC.

Background It remains unclear whether patients’ self‐perceptions of symptoms at baseline clinically impact the prognostic relevance, treatment efficacy, or toxicity profiles in metastatic colorectal cancer (mCRC) patients treated with the first‐line cetuximab and standard chemotherapy. Methods The data were collected from a prospective trial that assessed the relationships between quality of life (QOL), treatment efficacy, and adverse events (AEs). Results The analysis of 137 mCRC patients revealed a significant association between the presence of baseline tumor‐related symptoms and a lower overall survival (OS) compared to the absence of symptoms (HR, 2.49; 95% CI, 1.37‐4.62; P = .003). The asymptomatic responders had favorable outcomes compared to the symptomatic nonresponders (2‐year OS rates: 83.6% and 35.9%, respectively), while the symptomatic responders had similar outcomes to the asymptomatic nonresponders. The median postprogression survival differed significantly: 10.2 months for the symptomatic patients and 15.9 months for the asymptomatic patients (HR, 2.29; 95% CI, 1.25‐4.29, P = .008). The objective response rates and patient toxicity profiles were similar irrespective of the severity of baseline symptoms. Conclusion Baseline symptoms were associated with worse OS but not with impaired treatment efficacy or more frequent AEs in mCRC patients treated with cetuximab in addition to chemotherapy., This study provides that the baseline patient‐reported symptoms are associated with worse OS, but not with impaired treatment efficacy or deteriorated AEs, for patients treated with cetuximab plus chemotherapy.

The second planned interim analysis (median follow-up 12.5 months) in a phase III trial of postoperative adjuvant chemotherapy for stage III gastric cancer revealed significant improvement in relapse-free survival (RFS) for S-1 plus docetaxel over S-1 alone. Although enrollment was terminated on the recommendation of the independent data and safety monitoring committee, we continued follow-up and herein report on 3-year RFS, the primary endpoint. Patients with histologically confirmed stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive adjuvant chemotherapy with either S-1 plus docetaxel or S-1 alone. In the S-1 plus docetaxel group, S-1 was given orally for 2 weeks followed by 1 week of rest for seven courses, and docetaxel was given intravenously on day 1 of the second to seventh courses. The combination therapy was followed by S-1 monotherapy for up to 1 year. The 3-year RFS rate of the S-1 plus docetaxel group was 67.7%. This was significantly superior to that of 57.4% in the S-1 group (hazard ratio [HR] 0.715, 95% CI 0.587–0.871, P = 0.0008). This translated into a significant benefit in the 3-year overall survival (OS) rate in the S-1 plus docetaxel group (77.7% versus 71.2%, HR 0.742, 95% CI 0.596–0.925, P = 0.0076). On 3-year follow-up data, postoperative adjuvant therapy with S-1 plus docetaxel was confirmed to improve both RFS and OS and can be recommended as a standard of care for patients with stage III gastric cancer treated by D2 dissection.

Objective The aim of this study was to investigate the incidence and risk factors of postoperative delirium (PD) in elderly patients after general or gastrointestinal surgery. Summary of background data Societies worldwide are rapidly aging, and the number of surgeries in elderly patients has been increasing. PD, which adversely influences postoperative course, has thus become more common. Methods The Surgery and Anesthesia Network Group of the National Hospital Organization in Japan conducted this retrospective cohort study of patients older than 70 years of age who underwent general or gastrointestinal surgery. Results A total of 219 patients from 9 participating institutes underwent surgery between July 2013 and August 2014. We excluded 2 patients who died within 2 weeks after surgery. Of the remaining 217 cases, 31 (14.3%) developed PD. These patients were older (80 versus 76 years, P = 0.013), more likely to be male (74.2 versus 54.8%, P = 0.039), and had higher American Society of Anesthesia Physical Status scores than those without PD. Emergency surgery was more common than elective surgery in the PD group (41.9 versus 10.2%, P < 0.0001). Multivariate analysis showed that male gender (odds ratio, 3.31; 95% confidence interval, 1.32 to 9.39; P = 0.0098) and emergency surgery (odds ratio, 7.47; 95% confidence interval, 2.79 to 20.83; P < 0.0001) were independent risk factors of PD. Conclusions The incidence of PD was high in male patients and those undergoing emergency surgery. Effective interventions in these groups will be necessary to improve treatment outcomes in elderly patients.

Purpose Although early tumor shrinkage (ETS) is a predictor of improved overall survival (OS), the association between ETS and health-related quality of life (HRQOL) remains unclear for patients with metastatic colorectal cancer (mCRC) treated with first-line cetuximab plus chemotherapy. Methods The data were collected from a prospective trial that assessed HRQOL using the EORTC QLQ-C30. The impact of ETS on HRQOL was estimated using a linear mixed-effects model for repeated measures. Results ETS was achieved in 82 (64.1%) of 128 mCRC patients treated with first-line cetuximab plus chemotherapy, and these patients had a significantly longer OS than those without ETS (HR, 0.38; 95% CI, 0.20–0.72; P = .002). Asymptomatic patients with ETS had a favorable OS, while symptomatic patients without ETS had a worse OS (2-year OS rates, 77.8% vs. 42.5%). Symptomatic patients with ETS had similar outcomes as asymptomatic patients without ETS (2-year OS rates, 64.1% vs. 67.0%). For symptomatic patients, ETS was associated with improved HRQOL scores between baseline and 8 weeks: the mean changes for patients with and without ETS were 5.86 and -4.94 for global health status (GHS)/QOL, 26.73 and 3.79 for physical functioning, and 13.58 and -3.10 for social functioning, respectively. The improved HRQOL was comparable to that of asymptomatic patients without ETS. For asymptomatic patients, ETS showed a decreased deterioration in HRQOL. Conclusion Our findings highlight the importance of ETS for HRQOL and prognostic estimates, and assessing ETS may provide clinically useful information for physicians and patients to make more informed decisions.

BACKGROUND: Primary tumor location is a critical prognostic factor that also impacts the efficacy of anti-epidermal growth factor receptor (EGFR) therapy in wild-type RAS (KRAS/NRAS) metastatic colorectal cancer (CRC). However, the association between the incidence of BRAF and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations and primary tumor location remains unclear. METHODS: We prospectively collected tumor samples and clinical data of patients from 15 hospitals between August 2014 and April 2016 to investigate RAS, BRAF, and PIK3CA mutations using a polymerase chain reaction-based assay. According to the primary tumor location, patients were classified to right-sided (from cecum to splenic flexure) and left-sided (from descending colon to rectum) tumor groups. RESULTS: In total, 577 patients with CRC were investigated, 331 patients (57%) had CRC with wild-type RAS; of these 331 patients, 10.5%, 4.8%, and 5.9% patients harbored BRAFV600E, BRAFnon-V600E, and PIK3CA mutations, respectively. BRAF/PIK3CA mutations were more frequent in females, patients with right-sided tumors, and patients with peritoneal metastasis cases and less frequent in patients with liver metastases. The prevalence rates of BRAFV600E and PIK3CA mutations were higher in patients with right-sided tumors than in those with left-sided tumors (32.3% vs. 4.8% and 17.2% vs. 3.6%, respectively). CONCLUSIONS: More than half of the patients with right-sided CRC and wild-type RAS harbored BRAF/PIK3CA mutations, including BRAFnon-V600E, which may contribute to the difference in the anti-EGFR efficacy between the right- and left-sided CRC.

298 Background: Although FLOT (5-fluorouracil [5-FU]/leucovorin [ l-LV] + oxaliplatin [L-OHP] + docetaxel [DTX]) is globally recognized as the standard treatment for gastric cancer (GC), the safety of FLOT in Japanese patients (pts) is unknown. Moreover, because advanced GC (AGC) pts with severe peritoneal metastasis (SPM) have often been excluded from pivotal clinical trials due to their poor condition, it is necessary to develop standardized treatment for them. Methods: This study is an open-label, multicenter, single-arm, phase I study to determine the recommended phase II dose (RP2D) of FLOT for Japanese AGC pts without (part 1) or with (part 2) SPM using a 3 + 3 design. Main eligibility criteria included histologically confirmed AGC, HER2 negative, and age 20–75 years. In part 2a, pts with ECOG Performance status (PS) 2, who simultaneously had massive ascites and inadequate oral intake, were excluded. Massive ascites was defined as continuous ascites from the pelvic cavity to the upper abdomen, based on computed tomography findings. Inadequate oral intake was defined as the requirement for daily intravenous infusions to supply water or nutrition. The dose limiting toxicity (DLT) was assessed before the start of cycle 2. The fixed dose of L-OHP, l-LV, and 5-FU was 85, 200, and 2600 mg/m2, respectively, and DTX was administered at a dose of 50, 40, and 30 mg/m2 in the level 0, −1, and −2, respectively. Results: In part 1a, one patient died of hemorrhage from the primary tumor on Cycle 1 Day 2 and was replaced. The characteristics were as follows: median age (range), 70 (51–71) years; male/female, 2/1; ECOG PS (0/1), 2/1; histological type (diffuse/intestinal), 3/0; prior gastrectomy (yes/no), 0/3; and measurable lesions (yes/no), 1/2. During DLT evaluation, grade 3 (G3) or higher adverse events (AEs) were neutropenia (n = 1), lymphocytopenia (n = 1), anemia (n = 1), and anorexia (n = 1). During follow-up, the most common G3 or higher AEs included neutropenia (n = 3), lymphocytopenia (n = 1), anemia (n = 1), febrile neutropenia (FN) (n = 1 at cycle 5), diarrhea (n = 1), anorexia (n = 1), fatigue (n = 1), and colonic perforation (n = 1) due to diverticulitis (not treatment-related AE). In part 2a, the characteristics were as follows: median age (range) 64 (49–69) years; male/female, 3/0; ECOG PS (0/1), 0/3; histological type (diffuse/intestinal), 3/0; prior gastrectomy (yes/no), 0/3; and measurable lesions (yes/no), 0/3. Two pts had massive ascites and 1 pt had both massive ascites and inadequate oral intake. During follow-up, only G3 neutropenia (n = 3) was observed. Two pts needed dose modification in cycle 2. Both in part 1a and 2a, no treatment-related deaths and no DLTs were observed and the RP2D was determined in level 0. Conclusions: We determined that DTX 50 mg/m2, L-OHP 85 mg/m2, 5-FU 2600 mg/m2, and l-LV 200 mg/m2 were the RP2D of FLOT for Japanese AGC with/without SPM. Clinical trial information: 041200044.

Fluorouracil monotherapy, instead of the FOLFOX or FOLFIRI regimen, is administered to patients intolerant to oxaliplatin or irinotecan because of their adverse effects. A prospective clinical trial was designed to evaluate the efficacy and safety of fluorouracil monotherapy combined with panitumumab administered to patients with KRAS wild-type (WT) metastatic colorectal cancer (mCRC) intolerant to oxaliplatin and irinotecan. Screening for potential serum biomarkers to predict early therapeutic responses was conducted. This single-arm, open-label multicenter phase II trial recruited patients with KRAS WT mCRC from 16 institutes between January 2012 and October 2014. Panitumumab (6 mg/kg) was intravenously administered every 2 weeks, combined with fluorouracil monotherapy, in 2-week cycles. The primary objective was overall response rate, and secondary endpoints included disease-control rate, progression-free survival, overall survival, toxicity, and blood-test data. Forty patients (male, 65.0%; median age, 74 years; colon cancer, 72.5%) met eligibility criteria and received 7 cycles (median) of fluorouracil chemotherapy combined with panitumumab. There were no treatment-related deaths. Median time to treatment failure was 3.2 months. 23 (57.5%) patients experienced at least one adverse effect ≥ grade 3. The response rate was 10.0% (95% confidence interval 2.8–23.7%). Median progression-free survival and overall survival were 4.3 and 11.3 months, respectively. Total lactase dehydrogenase (LDH) levels and those of LDH-4 and LDH-5, quickly changed with disease reduction or progression. Fluorouracil monotherapy combined with panitumumab was safely administered to patients with KRAS WT mCRC intolerant to oxaliplatin and irinotecan. Serum LDH levels may predict early responses.

Background: The current pooled analysis evaluated the efficacy of Hangeshashinto (TJ-14) in the prevention and/or treatment of chemotherapy-induced oral mucositis (COM) in gastric cancer and colorectal cancer using two prospective, multi-institutional, randomized, double-blind, placebo-controlled phase II trials. Patients and Methods: HANGESHA-G and HANGESHA-C randomly assigned patients with gastric cancer or colorectal cancer who developed moderate to severe COM (grade ≥1) during any cycle of chemotherapy to receive either TJ-14 or a placebo as a double-blind trial. The patients received a placebo or TJ-14 for four to six weeks, according to the chemotherapy regimen, from the start of their next course of chemotherapy. The primary endpoint was the incidence of grade ≥2 COM in the protocol treatment course, and the secondary endpoints were the time to disappearance of COM and the incidence of adverse events. Results: The pooled population included 181 patients. The incidence of grade ≥2 COM in the TJ-14 group was 55.7% (49 patients), while that in the placebo group was 53.8% (50 patients); there was no significant difference between the two groups (p=0.796). The median time to remission of grade ≥2 COM to grade

Background: Advantages of neoadjuvant chemotherapy combined with monoclonal antibodies for treating patients with resectable colorectal cancer liver metastasis (CLM) have not been established. The purpose of this study was to evaluate the efficacy and safety of oxaliplatin-based regimen (FOLFOX or XELOX) plus monoclonal antibodies (cetuximab or bevacizumab) treatment in patients with resectable CLM. Methods: A single-arm, open-label, multicenter, phase II trial was conducted for patients aged ≥ 20 years with resectable and untreated CLM. Patients received preoperative FOLFOX (6 cycles) or XELOX (4 cycles). Cetuximab or bevacizumab was administered to patients with wild-type or mutated KRAS codons 12 and 13, respectively. The primary endpoint was progression-free survival (PFS). Results: Between January 2010 and June 2012, 47 patients were enrolled from 12 institutions. Wild-type or mutant KRAS sequences were examined in 32 and 15 patients, respectively. Twenty-one (45 %) patients experienced Grades 3/4 adverse events, and 55 % of all patients responded to therapy. The sizes of tumors of patients in the wild-type KRAS group were significantly reduced compared with those of the mutant KRAS group. The overall rates of liver resection and postoperative morbidity were 83 and 14 %, respectively, and the median PFS was 15.6 months. The median PFS times of the KRAS wild-type and mutant groups were 22.5 months and 10.5 months, respectively. Conclusions: Neoadjuvant therapy using FOLFOX/XELOX combined with monoclonal antibodies did not improve PFS, although it was administered safely and had less adverse effects after liver resection.

208 Background: Numerous studies have demonstrated how malnutrition and cachexia are associated with poor survival in advanced gastric cancer (AGC). The impact of nutrition support involving multidisciplinary specialists is unclear, particularly among patients with AGC being treated with chemotherapy. This study aimed to clarify the differences in patient characteristics and survival outcomes between patients receiving nutrition support (NS) and routine care (RC). Methods: We retrospectively analyzed 212 consecutive patients with AGC at a single institution between January 2015 and June 2020. Inclusion criteria were: histologically confirmed metastatic or recurrent gastric and adenocarcinoma and gastroesophageal junction patients treated with chemotherapy, ECOG performance status (PS) 0-2, and adequate organ function. Time to treatment failure (TTF) in the entire cohort, patients with a positive Glasgow prognostic score (GPS) (graded as 1 and 2), and hypoalbuminemia (cutoff was 3.5 g/dl) were evaluated. Univariate and multivariate analyses were conducted to identify whether NS was an independent prognostic factor of time to treatment failure (TTF). Multivariate analysis included variables with p-values ≤0.1 in univariate analyses. Results: A total of 97 patients met the inclusion criteria with 67 (69%) and 30 (31%) patients classified into the RC or NS group, respectively. The median age was 71 years (range, 26-92). The median follow-up time was 8.4 months (range, 0.5-66). Patient characteristics revealed that NS was offered to patients with poorer prognostic nutritional index (PNI) (cutoff was 45, p=0.02), GPS positivity (p=0.01), and high neutrophil-lymphocyte ratio (NLR) (cutoff was 3, p=0.01). In the entire cohort, TTF in the RC and NS groups was 4.3 and 5.3 months (p=0.15), respectively. Among the patients with GPS positivity (graded as 1 and 2) and hypoalbuminemia, TTF in the RC and NS group were 2.3 and 5.0 months (p=0.05), and 2.3 and 5.3 months (p=0.02), respectively (Table). Variables with p-values ≤0.1 in univariate analyses for TTF were PS, NS, and prior gastrectomy. As per multivariate analyses, PS and NS were significant positive prognostic factors for TTF. Conclusions: NS was provided to patients with unfavorable clinical features. Among the AGC patients treated with chemotherapy, having GPS positivity or hypoalbuminemia seems to be a good indication for NS. [Table: see text]

The reintroduction of oxaliplatin as a third-or-later-line regimen has been a promising option for patients with metastatic colorectal cancer (mCRC) who previously received chemotherapy including oxaliplatin. In this single-arm phase II study, we evaluated the efficacy of biweekly SOX, which is the combination of oxaliplatin reintroduction and S-1, as a third-or-later-line treatment. Patients with mCRC who had previously received prior chemotherapy including oxaliplatin and irinotecan and were planned to receive the reintroduction of oxaliplatin were enrolled. Oxaliplatin (85 mg/m2) with/without bevacizumab (5 mg/kg) was given intravenously on day 1. Oral S-1 was administered on day 2–8 at a dose of 40–60 mg (calculated according to the body surface area) twice a day. Cycles were repeated every 2 weeks. The primary endpoint was the progression-free survival (PFS); our hypothesis was that the median PFS would be 3.5 months with a minimum threshold above 2.0 months. The secondary endpoints included the adverse events (AEs), response rate and overall survival (OS). A total of 41 patients from 12 institutes were enrolled. The median PFS and OS survival were 3.3 months (95% confidence interval [CI] 2.7–4.2) and 10.1 months (8.3–14.6), and response rate and disease control rate were 10.0% and 65.0%, respectively. Grade 3 AEs included thrombocytopenia (5.0%), anorexia (5.0%), pneumonia (5.0%) and fatigue (5.0%). There were no cases of grade 4 AEs or treatment-related death. Biweekly SOX regimen with reintroduction of oxaliplatin could be exploitable as the third- and/or later-line treatments for patients with mCRC.

A prospective trial has not been performed to investigate associations between quality of life (QOL), adverse events (AEs), and overall survival (OS) in the first‐line treatment with cetuximab plus standard chemotherapy for advanced/metastatic colorectal cancer (mCRC). Associations between patient outcome and health‐related QOL (HRQOL) together with skin toxicity‐related QOL were prospectively evaluated using EORTC QLQ‐C30 and DLQI questionnaires. One hundred and forty mCRC patients were analyzed in this study, and 87.8% received pre‐emptive skin treatment. Skin toxicity had no clinical impact on HRQOL or skin‐related QOL during the first 8 weeks and throughout the study period. An early skin reaction with a grade ≥2 at 8 weeks was significantly associated with a favorable OS compared with a grade of ≤1 (HR, 0.50; 95% CI, 0.24‐0.95; P = .035) and was confirmed to be an independent predictor of OS (HR, 0.48; 95% CI, 0.21‐0.97; P = .040). Patients symptomatic at baseline who responded to treatment had improved HRQOL compared to nonresponding patients. Severe mucositis/stomatitis had a statistically significant and clinically meaningful negative impact on HRQOL (mean changes from baseline throughout the study period in global health status were −12.64 for a grade of ≥2 vs −0.35 for a grade of 0 or 1 (P = .005)). In conclusion, severe early skin reactions predict favorable OS for patients treated with cetuximab plus chemotherapy without impairing QOL. In addition, mucositis/stomatitis was the most substantial AE compromising both QOL and treatment compliance.

Purpose Hangeshashinto (TJ-14, a Kampo medicine), which reduces the level of prostaglandin E2 and affects the cyclooxygenase activity, alleviates chemotherapy-induced oral mucositis (COM). We conducted a double-blind, placebo-controlled, randomized comparative trial to investigate whether TJ-14 prevents and controls COM in patients with colorectal cancer. Methods Ninety-three patients with colorectal cancer who developed moderate-to-severe COM (WHO grade ≧1) during any cycle of chemotherapy using FOLFOX, FOLFIRI, and/or XELOX treatment were randomly assigned to receive either TJ-14 (n = 46) or placebo (n = 47). Patients received the administration of placebo or TJ-14 for 2 weeks at the start of the next course of chemotherapy. Patients were assessed three times per week for safety and for COM incidence and its severity using the WHO grading. Results Ninety eligible patients (TJ-14; 43, placebo; 47) per protocol set analysis were included in the analysis after the key-opening. Although the incidence of grade ≧2 oral mucositis was lower for patients treated with TJ-14 compared to those treated with placebo, there was no significant difference (48.8 vs. 57.4 %; p = 0.41). The median duration of grade ≧2 mucositis was 5.5 versus 10.5 days (p = 0.018). No difference in other treatment toxicity was observed between the two groups, and patients exhibited high compliance in dosing administration. Conclusion The present study results did not meet the primary endpoint. However, TJ-14 demonstrated a significant effect in the treatment of grade ≧2 mucositis in patients with colorectal cancer compared to the placebo.

Background FOLFOXIRI plus bevacizumab (bev) is one of preferred 1st-line regimens for RAS mutant metastatic colorectal cancer (mCRC); however, the original dosage is slightly toxic for Japanese patients (pts) due to frequent febrile neutropenia. We have reported that modified (m)-FOLFOXIRI (IRI 150mg/m2, OHP 85mg/m2, levofolinate 200mg/m2, and 5-FU 2400mg/m2 for 46-h continuous, up to 12 cycles followed by maintenance with 5-FU/levofolinate) plus bev has good objective response rate (ORR) of 76% as well as tolerability in Japanese pts with RAS mutant mCRC [Satake H, et al. Oncotarget 2018]. However, the follow-up time was short; therefore, clinical data was immature. Methods The primary endpoint was ORR. Progression-free survival (PFS), overall survival (OS), early tumor shrinkage (ETS), depth of response (DpR), and safety were secondary endpoints. The tumor shrinkage was evaluated every 8 weeks by the external review board. Pre-planned updated analysis was performed in January 2019. Results 62 pts (median 62.5-y old, 92% PS0, 90%/10% for KRAS/NRAS mutations, 27% right-side) were evaluable for efficacy and 63 pts for toxicity. The median cycle of treatment was 15 (range 1-46). Two pts still continued the protocol treatment and 40 (67%) pts received 2nd-line chemotherapy (triplet-regimen 28%, IRI-regimen+bev 23%, FOLFIRI+ramucirumab 15%, FOLFIRI+aflibercept 3%, OHP-regimen 10%, 5-FU+bev 10%, FTD/TPI 10%). Fourteen (23%) pts underwent surgery after protocol treatment. Median PFS was 11.9 (95%CI 9.5-14.0) months, median OS was 31.2 (95%CI 25.8-37.6), ETS was 73.8%, and median DpR was 49.2% (-28.7-100). Sub-analyses in each tumor side showed that ETS, DpR, median OS were 77.3%, 49.6%, 34.0 months in the left-side and 64.7%, 40.2%, 26.2 months in the right-side. No new adverse events were observed. Conclusions Updated analysis of the JACCRO CC-11 trial shows that m-FOLFOXIRI plus bev is a clinically useful regimen as a good option for RAS mutant mCRC.