Three-Year Outcomes of a Phase II Study of Perioperative Capecitabine Plus Oxaliplatin Therapy for Clinical SS/SE N1-3 M0 Gastric Cancer (OGSG 1601).

BACKGROUND: We previously reported the good feasibility and favorable efficacy of perioperative capecitabine plus oxaliplatin (CapeOx) in patients (pts) with clinical T3(SS)/T4a(SE) N1-3 M0 gastric cancer (GC) in a phase II study in which the pathological response rate, the primary endpoint, of 54.1% was demonstrated. Here, we report 3-year follow-up data. METHODS: The eligibility criteria included clinical T3(SS)/T4a(SE) N1-3 M0 GC according to the Japanese Classification of Gastric Carcinoma-3rd English Edition (JCGC). Three cycles of neoadjuvant CapeOx (capecitabine, 2000mg/m2 for 14 days; oxaliplatin, 130mg/m2 on day 1, every 3 weeks) were administered, followed by 5 cycles of adjuvant CapeOx after D2 gastrectomy. Three-year overall survival and relapse-free survival are presented here, and analyzed by cohorts based on pathologic response rate (pRR). RESULTS: Thirty-seven pts were enrolled from July 2016 to May 2017, and fully evaluated for efficacy and toxicity. Thirty-three pts (89.2%) completed the planned three cycles of neoadjuvant CapeOx and underwent gastrectomy, with an R0 resection rate of 78.4% (n = 29). The overall survival (OS) rate and relapse-free survival (RFS) rate at 3 years was 83.8% (95% CI, 72.7-96.5%) and 73.0% (95% CI, 60.0-88.8%), respectively. Further, the 3-year OS rate in pts with pathological response of grade 1a (n = 13) and grade 1b or higher (n = 20) was 69.2% (95% CI: 48.2-99.5%) and 100.0%, respectively, based on JCGC. Pathological response rate was classified according to JCGC as follows: grade 0, the tumor was not affected; grade 1a, less than one-third of the tumor was affected; grade 1b, one to two thirds of the tumor was affected; grade 2, greater than or equal to two thirds was affected; and grade 3, no residual tumor. A pathological response was defined as grade 1b or greater. CONCLUSION: Perioperative CapeOx showed good feasibility and favorable prognosis, especially in pts with pathological response of grade 1b or higher and was found to be useful in predicting prognosis. The data obtained using this novel approach warrant further investigation (Trial ID: UMIN000021641, jRCTs051180109).

A Phase II Study of Perioperative Capecitabine plus Oxaliplatin Therapy for Clinical SS/SE N1-3 M0 Gastric Cancer (OGSG 1601).

LESSONS LEARNED: Perioperative capecitabine and oxaliplatin (CapeOx) therapy showed favorable efficacy with sufficient pathological response. Small sample size limited the statistical power of this result. Perioperative CapeOx therapy showed good feasibility. Further studies with larger sample size are required to validate this novel approach. BACKGROUND: D2 gastrectomy followed by adjuvant S-1 is the standard therapy for patients (pts) with stage III gastric cancer (GC) in Japan; however, the outcome is not satisfactory. We examined the efficacy of perioperative capecitabine and oxaliplatin (CapeOx) in pts with GC. METHODS: The eligibility criteria included confirmed clinical T3(SS)/T4a(SE) N1-3 M0 GC according to the Japanese Classification (JCGC; 3rd English Edition). Three cycles of neoadjuvant CapeOx (NAC; capecitabine, 2,000 mg/m2 for 14 days; oxaliplatin, 130 mg/m2 on day 1, every 3 weeks) were administered, followed by five cycles of adjuvant CapeOx (AC) after D2 gastrectomy. The primary endpoint was the pathological response rate (pRR) according to the JCGC (≥grade 1b). RESULTS: Thirty-seven pts were enrolled on CapeOx. An R0 resection rate of 78.4% (n = 29) and a pRR of 54.1% (n = 20, p = .058; 90% confidence interval [CI], 39.4-68.2) were demonstrated. Among 27 pts who initiated AC, 21 (63.6%) completed the treatment. Grade 3-4 toxicities during NAC included neutropenia (8%), thrombocytopenia (8%), and anorexia (8%) and during AC included neutropenia (37%), diarrhea (4%), and anorexia (4%). CONCLUSION: Perioperative CapeOx showed good feasibility and favorable efficacy with sufficient pathological response, although statistical significance at .058 did not reach the commonly accepted cutoff of .05. The data obtained using this novel approach warrant further investigations.

A pathological complete response by chemotherapy with S-1 and oxaliplatin for a locally advanced duodenal adenocarcinoma in Lynch syndrome: a case report.

BACKGROUND: Although primary duodenal adenocarcinoma (DA) is a rare malignancy representing ~ 0.5% of all gastrointestinal cancers, the incidence of DA is more frequent in Lynch syndrome. Because of its rarity, treatment strategies or optimal chemotherapeutic regimens have not been clearly defined for advanced DA. CASE PRESENTATION: A 72-year-old woman with Lynch syndrome visited our hospital with a right upper abdominal pain. Computed tomography (CT) showed wall thickness with enhancement in the second portion of the duodenum and adjacent abdominal wall, which suggested direct tumor invasion to the abdominal wall. Upper gastrointestinal endoscopy (UGE) showed a large ulcerative tumor in the second portion of the duodenum, and histological analysis revealed a poorly differentiated adenocarcinoma. A cT4N0M0, cStage IIB (Union for International Control Cancer TNM staging) DA was diagnosed. After three courses of chemotherapy with S-1 and oxaliplatin (SOX), follow-up CT and UGE showed shrinkage of the duodenal tumor. Therefore, the patient underwent pancreaticoduodenectomy with lymph node dissection with curative intent. Histological examination showed a pathological complete response to SOX therapy. The postoperative course was uneventful, and the patient was discharged on postoperative day 29. The patient received no adjuvant chemotherapy, and there has been no evidence of recurrence 6 months after the operation. CONCLUSIONS: SOX therapy provided a remarkable response and can be an optimal chemotherapeutic regimen for advanced DA in Lynch syndrome.

Long-term survival outcomes of advanced gastric cancer patients who achieved a pathological complete response with neoadjuvant chemotherapy: a systematic review of the literature.

BACKGROUND: A pathologic complete response (pCR) can sometimes be induced by intensive or long-term neoadjuvant chemotherapy (NAC). This prognostic research study based on a systematic review of the literature evaluated the impact of a pCR on the long-term survival of gastric cancer (GC) patients. METHODS: Articles were extracted from PubMed and the Japanese medical search engine "Ichu-shi," using the terms "GC," "NAC," and "pCR." Articles were selected based on the following criteria: (1) full-text case report, (2) R0 resection following NAC for locally advanced GC, and (3) pathological complete response in both the primary stomach and in the lymph nodes. A questionnaire regarding the patients' prognoses was sent to the corresponding authors of the articles selected in July 2013. RESULTS: Twenty-four articles met the criteria. Twenty authors responded to the questionnaire. Finally, 22 patients from 20 articles were entered into the present study. The median follow-up time (range) of the survivors was 76 (range 13-161) months. Tumors that were stage III/IV (86%: 19/22) and of an undifferentiated histology (61.9%: 13/21) were dominant. An S1-based regimen was frequently selected for the NAC. All patients underwent R0 resection and D2/D3 lymphadenectomy. The overall survival and recurrence-free survival rates at 3 and 5 years were 96% and 85% and 91% and 75%, respectively. CONCLUSIONS: Although a pCR was a relatively rare event, a high pCR rate would be helpful to select the regimen and courses of NAC, especially when the pathological response rates are similar.

[Retrospective analysis of Charlson comorbidity index (CCI)].

Owing to the advance of supportive care and the development of molecular targeted therapies, the elderlies or patients who have comorbidities have been treated more than before. The assessment of the comorbidity is indispensable to select the appropriate treatment or the control of following therapy. Some indices to determine them have been developed in western countries but not in Japan. The index which is used most is the Charlson comorbidity index (CCI). This index has never been evaluated in Japan. So we investigated the utility of the index for Japanese population. We surveyed retrospectively 498 patients aged 65 or more patients with colon cancer, breast cancer, lung cancer that have been treated in our hospital during 2002-2007. According to CCI, patients are classified into three groups and verified 1-year and 3-year survival rate. 1-year survival rate was 76.9% in groups of 0 points, 83.5% in groups of1 -5 points, 75.0% in the group of six or more points respectively (p=0.19). 3-year survival rate were 59.0%, 63.1%, 75.0%, respectively (p=0.46). Multivariate analysis identified age (≥ 50), Sex (man), stage (III and IV) as significant predictors for worse OS at 3-year. However, there was no significant difference in CCI. There are some items which frequency is zero, so the items of CCI may not match to Japanese population. Presence of existing disease is an important factor for the cancer therapy, and it should be evaluated accurately. It is urgently necessary to develop an evaluation method and establish the scale.

[Are the Japanese guidelines for the management of hepatitis B virus reactivation being properly implemented ?].

Hepatitis B virus(HBV)reactivation has been reported as a fatal complication following systemic chemotherapy or other immunosuppressive therapies. The Japanese Guidelines for HBV reactivation were published in 2009. Despite the publication of these guidelines, there have been some reports of fulminant hepatitis B. Therefore, it was suggested that the guidelines were not yet been widely implemented. We investigated whether the guidelines had been implemented in our hospital. After the evaluation, it was determined that 89%of HBV cases were screened for the HBV surface antigen(HBs-Ag). Additionally, the screening for HBV surface antibody(HBs-Ab)and HBV core antibody(HBc-Ab)should be performed in cases negative for HBs-Ag, which was performed in only 17% of HBs-Ag-negative cases. It was concluded that the guidelines had not been implemented in our hospital. Therefore, we conducted educational activities to promote the implementation of the guidelines. Screening tests were performed in all 270 HBV cases between January and June 2013. Two antigen-positive carriers were identified. The rate of HBs-Ag-negative and/or HBc antibody -positive cases was 20.3%. Of these, 76.4%were tested using a DNA quantitative test, but DNA quantification did not increase in any case. HBV reactivation is expected to increase due to the development of new drugs and the use of diverse regimens. All physicians who perform immunotherapy and chemotherapy should immediately participate in educational activities.

Clinicopathological analysis for recurrence of stage Ib gastric cancer (according to the second English edition of the Japanese classification of gastric carcinoma).

BACKGROUND: The prognosis for patients with stage Ib (second English edition of the Japanese classification of gastric carcinoma) gastric cancer is promising, with an expected 5-year survival of 90%. Despite this relatively high survival rate, the outcome for patients who experience recurrence is poor. To date, however, prognostic and recurrence factors for stage Ib gastric cancer are poorly understood, and appropriate adjuvant chemotherapy protocols have not been developed. METHODS: We retrospectively analyzed data from 86 stage Ib gastric cancer patients who underwent curative gastrectomy to determine the rates and predictive factors of recurrence. RESULTS: Eleven patients showed recurrence, with a 12.8% 5-year cumulative recurrence rate. Nearly all of these patients were initially histologically diagnosed with poorly differentiated adenocarcinoma. Based on univariate analyses, recurrence was associated with gender and histological type. Multivariate analyses revealed that the only independent risk factor for recurrence was histologically undifferentiated-type adenocarcinoma. The 5-year survival rate of patients with undifferentiated-type adenocarcinoma was 84%. The predominant recurrence pattern was peritoneal dissemination, and was typically observed 1-3 years post-resection. CONCLUSION: This retrospective study identified undifferentiated-type adenocarcinoma as the only risk factor for recurrence in stage Ib gastric cancer patients. Although randomized controlled studies are necessary, stage Ib gastric cancer patients with this identified recurrence risk factor would be candidates for adjuvant chemotherapy.

[The new communication system about each patient's treatment from the ward to the chemotherapy center in our hospital].

Because the expert nurse of the chemotherapy center collected his profile from his chart and the hospital summary of nursing and we orientated about the induced chemotherapy regimen to the patient who got it after discharge from the ward former, we could not grasp neither his general condition nor mental status adequately. The merit of the outpatient chemotherapy is the improvement of the quality of life, but the patient feels the solitude and anxiety because of the lack of the medical and nursing staff around him. Then we changed that we have visited the patients to collect their profile and orientate about new regimen on his bedside for the smooth conversion to the outpatient chemotherapy. We visited a-total of 45 patients in 2007. Thirty-eight patients visited before their discharge answered, The orientation of the new chemotherapy before my discharge let me get with a security. The visit also enabled both staffs of the chemotherapy center and the ward to possess the common information of each patient and to do the common nursing. We thought that the visit before discharge was effective for the smooth conversion to the outpatient chemotherapy. We would like to reduce the anxiety of the patients who had chemotherapy and to support their struggle against diseases, cooperating to other department and standardizing our care program.