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PurposeWe report the safety and efficacy of nivolumab + chemotherapy for first-line treatment of advanced or recurrent gastric or gastroesophageal junction cancer in the Korean subpopulation of the ATTRACTION-4 clinical trial.Materials and methodsATTRACTION-4 (NCT02746796) was a double-blind, randomized, placebo-controlled clinical trial of patients aged ≥20 years with histologically confirmed unresectable advanced or recurrent gastric or gastroesophageal junction cancer. Patients received nivolumab or placebo, both combined with physician-choice chemotherapy (oxaliplatin plus oral S-1 [tegafur‒gimeracil‒oteracil] [SOX] or oral capecitabine [CAPOX]).ResultsOverall, 464 patients were initially screened in Korea and 291 were randomized to nivolumab + chemotherapy (total/SOX/CAPOX: 148/66/82 patients) or placebo + chemotherapy (total/SOX/CAPOX: 143/61/82 patients). Centrally assessed progression-free survival (median: 14.75 vs. 8.34 months; hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.39‒0.73, pConclusionThese findings demonstrate the clinical benefit of nivolumab combined with chemotherapy (either SOX or CAPOX) for first-line treatment of gastric cancer/gastroesophageal junction cancer in Korean patients.

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Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) is a rare pancreatic tumor and typically presents as a giant hypervascular tumor with rapid growth and intratumoral hemorrhage. UC-OGC localized in the main pancreatic duct (MPD) without extraductal invasion is extremely rare and difficult to diagnose preoperatively. Although the tumor rapidly increases in size and often becomes too large for resection, patients with UC-OGC who undergo curative resection show a better prognosis than those with other types of undifferentiated carcinomas and pancreatic ductal adenocarcinoma (PDAC). We must recognize that UC-OGC could present as an MPD-localized tumor and, therefore, should not miss the chance for resection. In this study, we present an unusual case of UC-OGC that was completely localized in the MPD without extraductal invasion. A 77-year-old Japanese man presented to our hospital with excessive thirst. Blood tests showed elevated glycosylated hemoglobin levels (11.9%). Carcinoembryonic antigen, carbohydrate antigen 19-9, Duke pancreatic monoclonal antigen type 2, Span-1, and neuron-specific enolase levels were within normal ranges. Contrast-enhanced computed tomography (CT) showed a 22-mm indistinct nodule with prolonged enhancement in the pancreatic body and dilatation of the distal MPD. Fluorine-18-fluorodeoxyglucose positron-emission tomography with CT showed uptake at the nodule but no evidence of metastasis. Endoscopic ultrasonography showed that the tumor was a heterogeneous hypoechoic nodule localized in the MPD. Pancreatic juice cytology indicated atypical cells but no evidence of malignancy. We suspected PDAC, acinar cell carcinoma, or an intraductal tubulopapillary neoplasm. We performed laparoscopic distal pancreatectomy and splenectomy, along with lymph node dissection. Histopathological examination revealed a 30-mm intraductal tumor with intratumoral hemorrhage, fibrosis, and angiogenesis. The tumor was composed of atypical spindle cells that were partly positive for cytokeratin AE1/3, CAM5.2, and vimentin and scattered osteoclast-like multinucleated giant cells that were positive for CD68. The tumor was completely localized to the MPD without extraductal invasion or lymph node metastasis. The patient received tegafur, gimeracil, and oteracil potassium as postoperative adjuvant chemotherapy for six months and has been recurrence-free for more than five years. UC-OGC demonstrates rapid growth; however, a good prognosis can be expected with curative resection.

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IntroductionAlpha-fetoprotein-producing gastric cancer (AFPGC) is a rare subtype of gastric cancer associated with poor prognosis due to early liver metastasis. There have been limited reports on conversion surgery following nivolumab combination chemotherapy in cases of AFPGC with liver metastasis. Here, we present a case of alpha-fetoprotein-producing esophagogastric junction cancer (AFP-EGJC) successfully treated with this treatment.Case presentationThe patient was a 31-year-old man. After liver tumors were incidentally detected, he was diagnosed with esophagogastric junction cancer (cT3N1M1) with multiple liver metastases and portal vein tumor thrombus. Combination therapy with S-1 (tegafur/gimeracil/oteracil), oxaliplatin, and nivolumab was initiated. The response was remarkable, with the rapid disappearance of liver metastases. Serum AFP was also abnormally high at 691.9 ng/mL, but it quickly normalized after the start of treatment. Fifteen months later, the patient was diagnosed with progressive disease, and the regimen was switched to nab-paclitaxel and ramucirumab therapy. However, there was no recurrence of liver metastases, and only the primary tumor was poorly controlled. Therefore, a laparoscopic proximal gastrectomy was performed 22 months after the initial treatment. The postoperative diagnosis was ypT2 (MP) N0M0, ypStage IB. The patient remains alive and recurrence-free 12 months after surgery, without adjuvant chemotherapy.ConclusionsConversion surgery after nivolumab combination chemotherapy may be feasible in selected patients with AFP-EGJC with liver metastasis.

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BackgroundPancreatic cancer is a highly malignant tumor with a rapid progression rate and a high susceptibility to infiltration and metastasis. Astragalus polysaccharide (APS), a pure Chinese medicine preparation primarily made from the traditional Chinese herb Astragalus, plays a positive role in the treatment of many malignant tumors.AimTo explore the recent efficacy of APS combined with gemcitabine plus tegafur gimeracil oteracil potassium capsule (S-1) (GS) regimen in the treatment of pancreatic cancer and assess its effect on the immune function and long-term survival of patients.MethodsA total of 97 patients who were diagnosed with pancreatic cancer and received GS chemotherapy at The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) from March 2021 to December 2021 were included in the retrospective analysis. Among them, 41 patients received APS combined with GS chemotherapy, and 56 patients received GS chemotherapy only. The recent efficacy, immune function, adverse reactions, and long-term survival were compared among these patients.ResultsAfter 4 cycles of treatment, the objective response rate of patients receiving the combined therapy of APS and GS was 51.22%, and the disease control rate (DCR) was 56.10%, higher than those of patients receiving the monotherapy with GS alone (30.36% and 35.71%, respectively). Besides, the percentages of CD3+ T cells (50.18% ± 9.57%) and CD4+ T cells (31.52% ± 5.33%) in the peripheral blood of patients receiving the combined therapy of APS and GS were higher compared with those treated with GS regimen alone [(44.06% ± 8.55%) and (26.01% ± 7.83%), respectively]. Additionally, the incidences of leukopenia, thrombocytopenia, and fatigue in patients receiving the combined therapy of APS and GS were significantly lower than those in patients receiving the monotherapy of GS alone (17.07%, 9.76%, 31.71% vs 37.50%, 28.57%, 60.71%). Moreover, the median survival time of patients receiving the combined therapy of APS and GS was 394 days, significantly longer than that of patients receiving the monotherapy of GS alone (339 days) (hazard ratio: 0.66; 95%CI: 0.45-0.99; P = 0.036). All these differences were statistically significant (P ConclusionThe combined therapy of APS and GS improved the recent efficacy and long-term survival of patients with pancreatic cancer and alleviated chemotherapy-induced immune suppression and adverse reactions.

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BackgroundPlatinum and anti-PD-1 antibodies are the front-line systemic therapy for recurrent or metastatic head and neck squamous cell carcinoma (RM-HNSCC). However, limited data are available on clinical outcomes and appropriate regimens for patients with RM-HNSCC following treatment failure with these agents.Patients and methodsWe retrospectively analyzed the clinical data of patients with RM-HNSCC from 10 Japanese institutions in whom platinum and nivolumab treatment failed.ResultsOf the 480 patients included in the study, 236 were treated with the best supportive care and had a median overall survival of 3.1 months. The remaining 244 patients received salvage-line chemotherapy, which was paclitaxel + cetuximab in 72 (30%), paclitaxel or docetaxel in 89 (36%), and tegafur/gimeracil/oteracil in 48 (20%); the respective objective response rates were 54.9%, 27.9%, and 25.5%, with median progression-free survival of 5.4 months and median overall survival of 13.0 months. Multivariable analysis identified disease stabilization or response on prior nivolumab and paclitaxel + cetuximab as salvage-line chemotherapy to be associated with encouraging progression-free and overall survival.ConclusionThis study sheds light on clinical outcomes and prognostic factors in patients with RM-HNSCC after failure of platinum and anti-PD-1 antibody therapy. The findings provide essential baseline data for future therapeutic development in salvage-line settings.

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BackgroundAfter the failure of second-line standard therapy, effective treatment options for metastatic colorectal cancer are limited, and the duration of remission cannot meet clinical needs. In addition, associated drug toxicity may lead to treatment interruption that may affect patient outcomes. Therefore, more safe, effective and convenient treatments are urgently needed.Case summaryHere, we describe a patient with advanced colorectal cancer with multiple metastases in both lungs. Oxaliplatin combined with 5-fluorouracil or capecitabine was given as the first-line treatment, and bevacizumab combined with irinotecan was given as the second-line treatment after disease progression. However, treatment was interrupted due to recurrent grade 2 nausea and grade 1 diarrhea. He received targeted therapy with fruquintinib starting on August 26, 2020 and responded well for 12 mo. After slow progression of the lung metastases, progression-free survival was again achieved over 13.5 mo by continued treatment of fruquintinib in combination with tegafur-gimeracil-oteracil potassium chemotherapy. Overall treatment duration was more than 25.5 mo. The treatments delayed tumor progression, reduced drug side effects, maintained a good quality of life, and further extended overall survival.ConclusionThis case report detailed preliminary evidence showing that the combination of fruquintinib with tegafur-gimeracil-oteracil potassium chemotherapy double oral therapy may result in longer progression-free survival in patients with advanced colorectal cancer.

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