IgG4-Related Disease Complicated with Diffuse and Chronic Gastrointestinal Inflammation Leading to Small Intestinal Perforation.

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by elevated serum IgG4, IgG4+ cell infiltration, storiform fibrosis, and obliterative phlebitis. While IgG4-RD can affect various organs, gastrointestinal tract involvement is less common. Here, we report a 70-year-old female with IgG4-RD complicated with diffuse and chronic gastrointestinal inflammation which led to small intestinal perforation. She had been suffering from anorexia, abdominal pain, vomiting, and diarrhea, and hospitalized due to recurrent ileus. Consequently, she was referred due to small intestinal perforation required for surgical intervention. Pathology revealed acute and chronic inflammation with massive IgG4+ plasmacytes infiltration into mucosa of the small intestine, and ischemic change secondarily caused by chronic inflammation. Random biopsies from the mucosa of stomach, duodenum, ileum, and colon, also revealed diffuse and massive IgG4+ plasmacytes infiltration in stomach, duodenum, small intestine, and colon. She was diagnosed with IgG4-RD based on the pathological findings and elevated serum IgG4 levels. Glucocorticoid rapidly ameliorated the symptoms. IgG4-RD may cause gastrointestinal manifestations and histopathological assessment should be considered, even in the absence of specific characteristics of IgG4-RD.

Exacerbated prognostic impact of multiple intramural metastasis versus single intramural metastasis of thoracic esophageal squamous cell carcinoma: evidence from an Uzbekistan cohort.

PURPOSE: Intramural metastasis (IM) is a poor prognostic factor for patients with esophageal squamous cell carcinoma (ESCC). We conducted this study to assess the prognostic impact of IM in an Uzbekistan cohort and to identify the factors associated with the poor prognosis of patients with ESCC and IM. METHODS: The subjects of this retrospective analysis were 1083 patients with thoracic ESCC, who underwent curative esophagectomy between 2001 and 2021 at the National Cancer Center of Uzbekistan. We compared the clinicopathological characteristics and survival outcomes of patients with versus those without IM and evaluated the factors associated with the poor prognosis of patients with IM. RESULTS: Patients with pathological IM (n = 59, 5.4%) were significantly older, had a higher percentage of lymphatic invasion and worse pathological N stage, and had shorter overall survival (OS) than patients without IM. Multivariable analysis of OS identified multiple IMs as the only independent prognostic factor in patients with IM (hazard ratio, 6.04; 95% confidence interval, 2.77-13.18; P < 0.001). Patients with multiple IMs had shorter OS and recurrence-free survival than those with a single IM. CONCLUSION: IM was a poor prognostic factor for patients with ESCC in this Uzbekistan cohort and multiple IMs were associated with worse outcomes.

Multidimensional analysis of schoolteachers' occupational stress by the New Brief Job Stress Questionnaire: focusing on gender differences.

This study investigated teachers' occupational stress using a comprehensive job stress questionnaire, or the New Brief Job Stress Questionnaire, while considering gender differences. A total of 1,825 elementary and junior high school teachers participated in the study. The results revealed that female teachers significantly exhibited more psychological and physical stress reactions and perceived less job resource availability than did male teachers. Moreover, multiple regression analyses demonstrated that support from family and friends was a larger factor associated with mental health outcomes among female teachers than among male teachers. The impacts of marital status also differed between male and female teachers. Job demands were strongly associated with psychological and physical stress reactions among teachers. Meanwhile, job resources were more strongly associated with positive workplace outcomes, such as workplace engagement and social capital, than were job demands. Administrators should consider the distinctive nature of teachers' occupational stress in addition to its gender specific influence. Organizational support, such as securing teachers' autonomy, encouraging their career development, and acknowledging diversity, should be considered to foster teachers' work engagement and create a cohesive environment in the school workplace.

Meta-analysis of three randomized trials of capecitabine plus cisplatin (XP) versus S-1 plus cisplatin (SP) as first-line treatment for advanced gastric cancer.

BACKGROUND: S-1 plus cisplatin (SP) and capecitabine plus cisplatin (XP) are standard first-line regimens for advanced gastric cancer (AGC) worldwide. We conducted a meta-analysis using individual participant data (IPD) to investigate which is more suitable. METHODS: IPD from three randomized trials were collected. In these trials, patients with AGC were randomly allocated to SP (S-1 80-120 mg for 21 days plus cisplatin 60 mg/m2 (q5w)) or XP (capecitabine 2000 mg/m2 for 14 days plus cisplatin 80 mg/m2 (q3w)). RESULTS: In 211 eligible patients, median overall survival (OS) for SP versus XP was 13.5 and 11.7 months (hazard ratio [HR], 0.787; p = 0.114), progression-free survival (PFS) was 6.2 and 5.1 months (HR, 0.767; P = 0.076), and TTF was 5.1 and 4.0 months (HR, 0.611; P = 0.001). The most common grade ≥ 3 adverse events with SP or XP were neutropenia (18% vs. 29%) and anorexia (16% vs.18%). Subgroup analysis demonstrated significant interaction between treatment effect and performance status > 1 (HR, 0.685; P = 0.036), measurable lesion (HR, 0.709; P = 0.049), primary upper third tumor (HR, 0.539; P = 0.040), and differentiated type (HR, 0.549; interaction, 0.236; P = 0.019). For the differentiated type, OS was significantly longer in the SP group (13.2 months) than in the XP group (11.1 months) (HR, 0.549; P = 0.019). For the undifferentiated type, OS was similar in the SP group (14.2 months) and in the XP group (12.4 months) (HR, 0.868; P = 0.476). CONCLUSIONS: SP and XP were both effective and well tolerated. SP might be suitable for the pathological differentiated subtype of AGC. CLINICAL TRIAL REGISTRATION: The HERBIS-2, HERBIS-4A, and XParTS II trials were registered with UMIN-CTR as UMIN000006105, UMIN000006755, and UMIN000006045, respectively.

Time required for indocyanine green fluorescence emission for evaluating bowel perfusion in left-sided colon and rectal cancer surgery.

BACKGROUND: Indocyanine green fluorescence imaging (ICG-FI) has been reported to be useful in reducing the incidence of anastomotic leakage (AL) in colectomy. This study aimed to investigate the correlation between the required time for ICG fluorescence emission and AL in left-sided colon and rectal cancer surgery using the double-stapling technique (DST) anastomosis. METHODS: This retrospective study included 217 patients with colorectal cancer who underwent left-sided colon and rectal surgery using ICG-FI-based perfusion assessment at our department between November 2018 and July 2022. We recorded the time required to achieve maximum fluorescence emission after ICG systemic injection and assessed its correlation with the occurrence of AL. RESULTS: Among 217 patients, AL occurred in 21 patients (9.7%). The median time from ICG administration to maximum fluorescence emission was 32 s (range 25-58 s) in the AL group and 28 s (range 10-45 s) in the non-AL group (p < 0.001). The cut-off value for the presence of AL obtained from the ROC curve was 31 s. In 58 patients with a required time for ICG fluorescence of 31 s or longer, the following risk factors for AL were identified: low preoperative albumin [3.4 mg/dl (range 2.6-4.4) vs. 3.9 mg/dl (range 2.6-4.9), p = 0.016], absence of preoperative mechanical bowel preparation (53.8% vs. 91.1%, p = 0.005), obstructive tumor (61.5% vs. 17.8%, p = 0.004), and larger tumor diameter [65 mm (range 40-90) vs. 35 mm (range 4.0-100), p < 0.001]. CONCLUSION: The time required for ICG fluorescence emission was associated with AL.

Feasibility and Safety of Adjuvant Chemotherapy for Resected Colorectal Cancer in Patients With Renal Insufficiency: A Pooled Analysis of Individual Patient Data from Five Japanese Large-scale Clinical Trials.

BACKGROUND/AIM: The incidence of chemotherapy-related adverse events in colorectal cancer patients with renal insufficiency has been compared to patients with normal renal function in only a few studies. The purpose of this analysis was to verify the feasibility and safety of adjuvant chemotherapy for postoperative colorectal cancer patients with renal insufficiency. PATIENTS AND METHODS: Adverse events and discontinuation of adjuvant chemotherapy for patients with curatively resected locally advanced colorectal cancer were examined using a combined database of individual patient data obtained from five large-scale clinical trials (n=4,106). The renal function of patients was classified into Level (L) 1-2: ≥60 ml/min and L3-4: <60 ml/min. RESULTS: As Grade 3 adverse events, hematological toxicities, such as neutropenia and anemia, and gastrointestinal disorders, such as diarrhea and vomiting, were significantly more frequent in the L3-4 group. Moreover, the time-to-treatment discontinuation in the L3-4 group was higher (hazard ratio=1.21, p=0.0012). T factor, N factor, and creatinine clearance level were found to be independent risk factors for the discontinuation of adjuvant chemotherapy. In the subgroup analysis of FOLFOX, neutropenia and diarrhea were significantly common in the L3-4 group, but neurotoxicities were not different. There was no significant difference in the discontinuation of adjuvant FOLFOX. CONCLUSION: Adverse events of adjuvant chemotherapy in patients with resected colorectal cancer were associated with renal insufficiencies. Since adverse events have the potential to shorten the duration of treatment, especially when using chemotherapy without oxaliplatin, careful management, including dose reduction, may be important in patients with renal insufficiency.

Applying deep learning to iterative screening of medium-sized molecules for protein-protein interaction-targeted drug discovery.

We combined a library of medium-sized molecules with iterative screening using multiple machine learning algorithms that were ligand-based, which resulted in a large increase of the hit rate against a protein-protein interaction target. This was demonstrated by inhibition assays using a PPI target, Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2), and a deep neural network model based on the first-round assay data showed a highest hit rate of 27.3%. Using the models, we identified novel active and non-flat compounds far from public datasets, expanding the chemical space.

Randomized phase II study of daily versus alternate-day administrations of S-1 for the elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm)-IIIA of non-small cell lung cancer: Setouchi Lung Cancer Group Study 1201.

BACKGROUND: It is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC. METHODS: Elderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more. RESULTS: We enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11). CONCLUSION: Although several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC. TRIAL REGISTRATION: Unique ID issued by UMIN: UMIN000007819 (Date of registration: Apr 25, 2012) https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009128. Trial ID issued by jRCT: jRCTs061180089 (Date of registration: Mar 22, 2019, for a shift toward a "specified clinical trial" based on Clinical Trials Act in Japan) https://jrct.niph.go.jp/en-latest-detail/jRCTs061180089.

The clinical impacts of postoperative complications after colon cancer surgery for the clinical course of adjuvant treatment and survival.

AIM: We investigated whether or not postoperative complications (POCs) themselves have a negative survival impact or indirectly worsen the survival due to insufficient adjuvant chemotherapy in a pooled analysis of two large phase III studies performed in Japan PATIENTS AND METHODS: The study examined the patients who enrolled in 1304, phase III study comparing the efficacy of 6 and 12 months of capecitabine as adjuvant chemotherapy for stage III colon cancer patients and in 882, a phase III study to confirm the tolerability of oxaliplatin, fluorouracil, and l-leucovorin in Japanese stage II/III colon cancer patients. In our study, POCs were defined as the following major surgical complications: anastomotic leakage, pneumonia, bowel obstruction/ileus, surgical site infection, postoperative bleeding, urinary tract infection, and fistula. Patients were classified as those with POCs (C group) and those without POCs (NC group). RESULTS: A total of 2095 patients were examined in the present study. POCs were observed in 169 patients (8.1%). The overall survival (OS) rates at 5 years after surgery were 75.3% in the C group and 86.5% in the NC group (p = 0.0017). The hazard ratio of POCs for the OS in multivariate analysis was 1.70 (95% confidence interval, 1.19 to 2.45; p = 0.0040). The time to adjuvant treatment failure (TTF) of adjuvant chemotherapy was similar between the groups, being 68.6% in the C group and 67.1% in the NC group for the 6-month continuation rate of adjuvant chemotherapy. The dose reduction rate of adjuvant chemotherapy and adjuvant treatment suspension rate were also similar between the groups (C vs. NC groups: 45.0% vs. 48.7%, p = 0.3520; and 52.7% vs. 55.0%, p = 0.5522, respectively). CONCLUSION: POCs were associated with a poor prognosis but did not affect the intensity of adjuvant chemotherapy. These results suggested that POCs themselves negatively influence the survival.

Mid-term outcomes of intracorporeal versus extracorporeal anastomosis after laparoscopic colectomy: a propensity score-matched cohort study from a single institution.

PURPOSE: There is still insufficient discussion of the mid- to long-term safety of the intracorporeal anastomosis (IA) method of reconstruction after laparoscopic colectomy (LAC) for colon cancer. The present study clarified the postoperative mid-term results of IA based on recurrence and the incidence of incision hernia. METHODS: This single-institution observational retrospective study included 268 patients with colon cancer who underwent IA or extracorporeal anastomosis (EA) after LAC at our institution between 2018 and 2021. The mid-term results of the IA group were compared with those of the EA group using a propensity score matching method. RESULTS: The median follow-up periods were 36 and 25 months in the EA and IA groups, respectively (p < 0.0001). In this matched cohort study, the recurrence-free survival (RFS) rates were comparable between the IA and EA groups (each group, n = 72; 3-year RFS: IA, 92.1%; EA, 88.2%; hazard ratio, 0.78; 95% confidence interval, 0.25-2.40; p = 0.66). The cumulative incisional hernia rates were 9.8% and 9.9% (p = 0.99) for the IA and EA groups, respectively. CONCLUSION: The safety of IA after LAC was demonstrated in this study, as IA after LAC showed good mid-term results, including with regard to the rates of recurrence and incisional hernia.

Poor association between dihydropyrimidine dehydrogenase (DPYD) genotype and fluoropyrimidine-induced toxicity in an Asian population.

OBJECTIVE: Dihydropyrimidine dehydrogenase (DPYD) genotype is closely associated with fluoropyrimidine (FP)-induced toxicities in Caucasian population and European Medicines Agency now recommends DPYD genotype-based FP dosing strategy. PATIENTS AND METHODS: The current study aimed to investigate their impact on FP-related toxicities in an Asian population using genome-wide association study (GWAS) data set from 1364 patients with colon cancer. RESULTS: Among 82 variants registered in the Clinical Pharmacogenetics Implementation Consortium, 74 DPYD variants were directly genotyped in GWAS cohort; however, only 7 nonsynonymous DPYD variants (CPIC variants) were identified and none of the four recurrent DPYD variants (DPYD*2A, c.2846A>T, c.1679T>G, c.1236G>A) were included. Seven CPIC variants were investigated for their association with the incidence of FP-related toxicities; however, none of these variants revealed a significant correlation with FP-related toxicities. CONCLUSION: These data suggested that the DPYD genotype registered in CPIC plays a minor role in FP-related toxicities in an Asian population.

Histology Classification Highlights Differences in Efficacy of S-1 versus Capecitabine, in Combination with Cisplatin, for HER2-Negative Unresectable Advanced or Recurrent Gastric Cancer with Measurable Disease.

It has been suggested that the therapeutic efficacy of S-1 + cisplatin (SP) and capecitabine + cisplatin (XP) may differ depending on the histology of the tumor, but no clear evidence exists. Individual participant data were obtained from three randomized phase II trials in which such patients received either SP (S-1 [40-60 mg twice daily for 21 days] plus cisplatin [60 mg/m2 on day 8], every 5 weeks) or XP (capecitabine [1000 mg/m2 twice daily for 14 days] plus cisplatin [80 mg/m2 on day 1], every 3 weeks). A total of 162 patients were included, with 79 patients in the SP arm and 83 patients in the XP arm. Although there was also no difference between arms in ORR according to histological classification, differentiated tumors showed a significantly better OS (but not PFS) for SP versus XP that was associated with a deeper tumor shrinkage. Undifferentiated tumors showed a consistently better OS, and PFS for SP versus XP, likely because cases without tumor shrinkage tended to be fewer for SP. Our data thus showed that SP was superior to XP in this setting, but there were qualitative differences in therapeutic efficacy dependent on tumor histology.

[Usefulness of Nutritional Evaluation in Adjuvant Chemotherapy for Colorectal Cancer in Older Patients].

OBJECTIVE: To clarify the usefulness of Onodera's prognostic nutritional index(OPNI)in adjuvant chemotherapy(AC)for older patients with colorectal cancer. MATERIALS AND METHODS: This study included 39 patients aged over 70 years who underwent AC for colorectal cancer from August 2009 to February 2018. We evaluated the association of OPNI with AC toxicities and prognosis. RESULTS: OPNI was an independent predictor of toxicities of Grade 3 or higher(OR: 0.18, 95%CI: 0.043-0.75, p=0.019). The 3-year recurrence-free survival rate was significantly better in the higher OPNI group than in the lower OPNI group(89.9% and 66.7%, respectively; HR: 0.19, 95%CI: 0.04-0.92, p=0.038). There was a positive correlation with Spearman's rank correlation coefficient of 0.66 in OPNI before and after AC(p<0.001). CONCLUSION: OPNI could be one of the valuable predictors of AC toxicities and the prognosis. There was a high correlation between OPNI before and after AC. These findings suggest the importance of early nutritional support for patients with lower OPNI.

Surgical Experience Disparity Between Male and Female Surgeons in Japan.

Importance: Women are vastly underrepresented in surgical leadership and management in Japan. The lack of equal opportunities for surgical training is speculated to be the main reason for this disparity; however, this hypothesis has not been investigated thus far. Objective: To examine gender disparity in the number of surgical experiences among Japanese surgeons. Design, Setting, and Participants: This retrospective, multicenter cross-sectional study used data from the National Clinical Database, which contains more than 95% of all surgical procedures in Japan. Participants included male and female gastroenterological surgeons who performed appendectomy, cholecystectomy, right hemicolectomy, distal gastrectomy, low anterior resection, and pancreaticoduodenectomy between January 1, 2013, and December 31, 2017. Exposures: Differences in the number of surgical experiences between male and female surgeons. Main Outcomes and Measures: The primary outcomes were the total number of operations and number of operations per surgeon by gender and years of experience. Data were analyzed from March 18 to August 31, 2021. Results: Of 1 147 068 total operations, 83 354 (7.27%) were performed by female surgeons and 1 063 714 (92.73%) by male surgeons. Among the 6 operative procedures, the percentage of operations performed by female surgeons were the highest for appendectomy (n = 20 648 [9.83%]) and cholecystectomy (n = 41 271 [7.89%]) and lowest for low anterior resection (n = 4507 [4.57%]) and pancreaticoduodenectomy (n = 1329 [2.64%]). Regarding the number of operations per surgeon, female surgeons had fewer surgical experiences for all 6 types of operations in all years after registration, except for appendectomy and cholecystectomy in the first 2 years after medical registration. The largest gender disparity for each surgical procedure was 3.17 times more procedures for male vs female surgeons for appendectomy (at 15 years after medical registration), 4.93 times for cholecystectomy (at 30-39 years), 3.65 times for right hemicolectomy (at 30-39 years), 3.02 times for distal gastrectomy (at 27-29 years), 6.75 times for low anterior resection (at 27-29 years), and 22.2 times for pancreaticoduodenectomy (at 30-39 years). Conclusions and Relevance: This cross-sectional study found that female surgeons had less surgical experience than male surgeons in Japan, and this gap tended to widen with an increase in years of experience, especially for medium- and high-difficulty operations. Gender disparity in surgical experience needs to be eliminated, so that female surgeons can advance to leadership positions.

Laparoscopic Colectomy for a Patient with Situs Inversus Totalis: The Usefulness of Preoperative Assessment.

BACKGROUND Situs inversus totalis (SIT) is a rare congenital anomaly in which the patient's internal organs are positioned in a mirror image of their normal locations. Laparoscopic surgery for a patient with SIT requires modification of the standard procedure. Several studies have recently reported surgical techniques for laparoscopic colectomy in patients with SIT. Herein, we present the case of a patient with congenital SIT who underwent laparoscopic colectomy for transverse colon cancer with intracorporeal anastomosis and discuss the usefulness of preoperative assessment. CASE REPORT A 63-year-old woman with SIT was referred to our department for surgical intervention following endoscopic submucosal dissection of transverse colon cancer. We performed a successful laparoscopic colectomy with intracorporeal anastomosis. Our team had no prior experience performing laparoscopic surgery on a patient with SIT; however, preoperative image training using a horizontally flipped video of a normal laparoscopic colectomy enabled the operation to be performed safely. Preoperative image training is very useful for gaining an understanding of images similar to the actual field of view before surgery. The patient was discharged without complications on the eighth postoperative day. CONCLUSIONS Careful preoperative assessment that takes into consideration the mirror-image anatomy and the contemplated laparoscopic procedure should allow patients with SIT to fully benefit from minimally invasive surgery.

Multicenter, single-arm, phase II study of the continuous use of panitumumab in combination with FOLFIRI after FOLFOX for RAS wild-type metastatic colorectal cancer: Exploratory sequential examination of acquired mutations in circulating cell-free DNA.

This multicenter single-arm, phase II study evaluated the efficacy and safety of uninterrupted panitumumab usage combined with cytotoxic doublets for unresectable/metastatic colorectal cancer (mCRC). Additionally, clinical value of the RAS/BRAF mutation status in circulating cell-free DNA (ccfDNA) was evaluated; this evaluation was measured independently of the protocol treatment. Eligible patients with RAS wild-type mCRC who had received the first-line panitumumab plus FOLFOX treatment were recruited and administered continuous panitumumab combined with FOLFIRI. Progression-free survival (PFS) at 6 months was the primary endpoint, with threshold and expected values of 35% and 50%, respectively. In total, 54 patients were enrolled between October 2017 and October 2019. The crude 6-month PFS rate was 37.0%, with a 4.8-month median PFS. The response rate and disease control rate were 16.7% and 50.0%, respectively. Notably, of the 54 participants, 17 showed RAS/BRAF mutations until the end of the protocol treatment and of the 22 patients with progressive disease as their best response, 10 possessed RAS/BRAF mutations in their plasma ccfDNA at baseline. The median PFS significantly differed among patients harboring tumors with BRAF and RAS mutations and those with wild-type tumors. In conclusion, our study failed to show the expected efficacy of the continuous panitumumab use in the second-line treatment. Liquid biopsy discriminated the duration of PFS according to the mutation status. The effectiveness of continuous treatment with panitumumab should be evaluated in patients with RAS/BRAF wild-type mCRC determined by liquid biopsy at the start of the second-line treatment.

Impact of early tumor shrinkage on quality of life in patients treated with first-line cetuximab plus chemotherapy for unresectable metastatic colorectal cancer: results of Phase II QUACK trial.

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.

Final Analysis of 3 Versus 6 Months of Adjuvant Oxaliplatin and Fluoropyrimidine-Based Therapy in Patients With Stage III Colon Cancer: The Randomized Phase III ACHIEVE Trial.

PURPOSE: The phase III ACHIEVE trial conducted in Japan was one of six prospective studies included in the International Duration Evaluation of Adjuvant Therapy collaboration, which explored whether 3 months of adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) therapy would be noninferior to 6 months of treatment in patients with curatively resected stage III colon cancer. We report the final analyses of survival and long-term safety. PATIENTS AND METHODS: Eligible patients were randomly assigned (1:1) to either 3 or 6 months of adjuvant chemotherapy (modified [m]FOLFOX6 or CAPOX, as selected by the treating physician). Random assignment was stratified according to number of involved lymph nodes, center, regimen, primary site, and age. The primary end point was disease-free survival, assessed in the modified intention-to-treat population. Overall survival (OS) was a secondary end point. RESULTS: The modified intention-to-treat population comprised 1,291 patients: 641 in the 6-month treatment group and 650 in the 3-month treatment group. Median follow-up for this analysis was 74.7 months. Five-year OS rates were comparable: 87.0% in the 3-month treatment group and 86.4% in the 6-month treatment group (hazard ratio, 0.91; 95% CI, 0.69 to 1.20; P = .51). Subgroup analysis of OS did not reveal a significant interaction between baseline characteristics and treatment duration. Peripheral sensory neuropathy lasting longer than 5 years was more common in the 6- compared with 3-month treatment group (16% v 8%, respectively), and in those receiving mFOLFOX6 compared with CAPOX (14% v 11%, respectively). CONCLUSION: In Asian patients, shortening adjuvant therapy duration from 6 to 3 months did not compromise efficacy and reduced the rate of long-lasting peripheral sensory neuropathy. In this setting, 3 months of CAPOX therapy is an appropriate adjuvant treatment option.