Gastric cancer with Fanconi anemia in adolescent and young adult patient diagnosed by comprehensive genome profiling using next-generation sequencing.

Recently, the results of gastric cancer treatment have improved; however, its characteristics in adolescents and young adults are not well known. We report the case of a patient with advanced gastric cancer, Fanconi anemia (FA), and primary biliary cholangitis. A 26-year-old woman visited a local physician complaining of epigastralgia. Esophagogastroduodenoscopy revealed edematous changes with poor distension and circumferential thickened folds with erosions in the gastric body. Biopsy results of the lesion specimens revealed poorly differentiated adenocarcinoma. Abdominal contrast-enhanced computed tomography revealed gastric wall with irregular thickness, several nodules in the peritoneal cavity, and a mass lesion in the right ovary. We diagnosed the patient with T4N2M1 stage IV gastric cancer accompanied by peritoneal and ovarian metastases and initiated nivolumab with S-1 plus oxaliplatin as the first-line treatment regimen. Because of immune-related adverse events after one course of systemic treatment, the regimen was changed to ramucirumab combined with nab-paclitaxel chemotherapy as the second-line treatment. After three cycles of weekly nab-paclitaxel with ramucirumab, the decreased platelet count did not recover, and her general condition gradually deteriorated. Comprehensive genome profiling using next-generation sequencing was performed to determine the feasibility of genotype-matched therapies. Alterations in FA complementation group A (FANCA) F1263del (49.1%) and E484Q (12.3%), which encode a key component of the multiprotein FA complex, were identified. The patient died 10 months after treatment initiation. In conclusion, when treating malignancies in adolescent and young adult patients, the genomic background should be considered.

Mycobacterium shinjukuense infection successfully treated with clarithromycin, rifampicin, and ethambutol.

We present the case of a 59-year-old woman diagnosed with Mycobacterium shinjukuense infection using mass spectrometry of bronchioalveolar lavage fluid. We initiated treatment with clarithromycin, rifampicin, and ethambutol based on the results of drug susceptibility testing, which improved lung opacities. Most previous cases were treated with the standard regimen for Mycobacterium tuberculosis. However, our regimen may provide a therapeutic option for this rare nontuberculous Mycobacterium infection.

Inflammatory prognostic factors in advanced or recurrent esophageal squamous cell carcinoma treated with nivolumab.

BACKGROUND: In Japan, nivolumab administration is the standard treatment for patients with unresectable advanced or recurrent esophageal squamous cell carcinoma (ESCC) who are refractory or intolerant to fluoropyrimidines and platinum-based chemotherapy. We determined if inflammatory prognostic factors are useful in patients with ESCC treated with nivolumab monotherapy. METHODS: The clinical data of patients with ESCC treated with nivolumab monotherapy as the second- or later-line treatment were retrospectively analyzed. Neutrophil/lymphocyte, platelet/lymphocyte, and C-reactive protein/albumin ratios (CAR); prognostic index; and prognostic nutritional index were investigated. Cut-off values for each factor were determined according to overall survival using time-dependent receiver operating characteristic curves. RESULTS: During January 2017-June 2021, 93 consecutive patients with ESCC were enrolled from five institutions (median age, 70 years; male, 77%). With a median follow-up period of 9.1 (range, 1.0-34.7) months, the median overall and progression-free survival were 12.8 (95% confidence interval [CI], 9.0-16.6) and 4.0 (95% CI, 2.6-5.4) months, respectively. Of five inflammatory prognostic factors, the cut-off value for CAR was 0.62; prognosis was significantly longer in those with CAR < 0.62 (hazard ratio, 0.39; 95% CI, 0.22-0.67; p = 0.001). CONCLUSIONS: Inflammatory prognostic factors were useful in predicting prognosis for ESCC patients pretreated with nivolumab, especially for those with CAR < 0.62, suggesting that CAR adequately reflects prognosis.

Real-World Data of Trifluridine/Tipiracil for Patients With Advanced Gastric Cancer: A Multi-Institutional Retrospective Study.

Background: A trial with trifluridine/tipiracil (FTD/TPI) versus placebo in patients with heavily pretreated metastatic gastric cancer showed that FTD/TPI is effective with manageable toxicity in these patients. However, real-world data on the effects of FTD/TPI in patients with advanced gastric cancer (AGC) are limited. Methods: We retrospectively collected and analyzed the clinicopathological data of patients with AGC who received FTD/TPI monotherapy at our institutions (Kobe City Medical Center General Hospital, Osaka Red Cross Hospital, Himeji Red Cross Hospital, and Kansai Medical University Hospital) between September 2019 and July 2021. Tumor responses were evaluated based on the Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival (OS) and progression-free survival were estimated using the Kaplan-Meier method. Results: A total of 53 patients were included in the study. The median age was 70 (range, 37-85) years; 39 patients (74%) were men; the numbers of patients with Eastern Cooperative Oncology Group performance status scores of 0, 1, and 2 were 10 (19%), 39 (74%), and 4 (8%), respectively; and 27 patients (51%) had diffuse-type histology. A total of 29 patients (56%) had ascites. Prior nivolumab therapy was administered to 49 patients (92%). The response rate and disease control rate (DCR) were 2% and 35%, respectively. The median progression-free survival was 2.4 months, and OS was 5.8 months. Patients with ascites exhibited significantly shorter OS (8.6 vs 4.7 months, P = .0291) than those without ascites, and DCR (54% vs 18%, P = .0055) was significantly worse in patients with ascites. There was no significant difference in the frequency of adverse events of grade 3 or higher between patients with and without ascites. Conclusion: In a real-world setting, FTD/TPI has similar effectiveness as late-line chemotherapy for patients with AGC, including those who previously had received nivolumab.

Improvement of Body Weight and Nutritional Status in Gastric Cancer Patients Enhances the Benefit of Nivolumab Therapy.

Nivolumab improves overall survival (OS) in patients with advanced gastric cancer (AGC) refractory to at least two previous chemotherapy regimens. We investigated whether changes in body weight and nutrition from first-line chemotherapy to nivolumab affected its efficacy. The correlation between weight change and nutritional status up to the start of nivolumab treatment and OS and progression-free survival (PFS) after starting nivolumab treatment was determined. Nutritional status was examined using the C-reactive protein/albumin ratio (CAR). A loss in body weight (LBW) from the onset of the first treatment of <4.5% led to OS prolongation and improved PFS outcomes. The median OS values in the LBW < 4.5% and ≥4.5% groups were 11.4 and 3.6 months, respectively. Similarly, changes in CAR from first-line chemotherapy (ΔCAR) affected OS; the ΔCAR < 0.01 group had a better prognosis than the ΔCAR ≥ 0.01 group. The median OS values in the ΔCAR < 0.01 and ≥0.01 groups were 9.4 and 4.5 months, respectively. The median OS in the group with LBW < 4.5% and ΔCAR < 0.01 was 12.9 months. LBW and deterioration of nutritional status following first-line chemotherapy are poor prognostic factors in AGC patients who received nivolumab as third- or later-line therapy. Early intervention to maintain body weight and nutritional status may improve the efficacy of immune checkpoint inhibitors.

Real-World Data of Trastuzumab Deruxtecan for Advanced Gastric Cancer: A Multi-Institutional Retrospective Study.

Trastuzumab deruxtecan (T-DXd) has shown promising efficacy against HER2-positive advanced gastric cancer (AGC). However, data on its real-world efficacy in AGC patients are insufficient, and the predictive marker of T-DXd is unclear. In this multi-center retrospective study, we collected clinical information of 18 patients with HER2-positive AGC who received T-DXd after intolerant or refractory responses to at least two prior regimens and analyzed predictive factors. The median age was 71 years (range: 51-85), 13 men were included, and ECOG performance status (PS): 0/1/2/3 was 9/6/2/1. A total of 11 patients (61%) received prior immune checkpoint inhibitors (ICIs), 14 patients were HER2 3+, and 4 patients were HER2 2+/FISH positive. The median trastuzumab (Tmab)-free interval was 7.7 months (range: 2.8-28.6). The overall response rate was 41%, and the disease control rate was 76%. Median progression-free survival (PFS) was 3.9 months (95% CI: 2.6-6.5), and median overall survival (OS) was 6.1 months (95% CI: 3.7-9.4). PFS (6.5 vs. 2.9 months, p = 0.0292) and OS (9.2 vs. 3.7 months, p = 0.0819) were longer in patients who received prior ICIs than in those who had not. PFS (6.5 vs. 3.4 months, p = 0.0249) and OS (9.4 vs. 5.7 months, p = 0.0426) were longer in patients with an 8 month or longer Tmab-free interval. In patients with ascites, PFS (6.5 vs. 2.75 months, p = 0.0139) and OS (9.4 vs. 3.9 months, p = 0.0460) were shorter. T-DXd showed promising efficacy in HER2-positive AGC patients in a real-world setting. Pre-administration of ICIs and a sufficient Tmab-free interval may be predictive factors of T-DXd efficacy.

Nanoparticle albumin-bound paclitaxel and ramucirumab versus paclitaxel and ramucirumab as second-line chemotherapy for unresectable advanced or recurrent gastric cancer: a multicenter, propensity score-matched analysis (CROSS SELL study).

BACKGROUND: Paclitaxel plus ramucirumab (PTX + RAM) is the standard second-line chemotherapy for unresectable advanced or recurrent gastric cancer (AGC). Nanoparticle albumin-bound paclitaxel (nab-PTX) is an improved, more convenient form of PTX and is non-inferior to PTX. Although some retrospective and single-arm phase II studies regarding nab-PTX + RAM have been reported, comparative studies are lacking. Here, we compared the efficacy and toxicity of nab-PTX + RAM and PTX + RAM using propensity score matching. METHODS: Clinical data of 265 patients treated for AGC with nab-PTX + RAM or PTX + RAM were retrospectively collected. Nab-PTX was administered at dosages of 100 mg/m2, replacing PTX in the standard PTX + RAM regimen. Progression-free survival (PFS), overall survival (OS), and toxicity were compared using 1:1 propensity score matching. RESULTS: In total, 190 (72%) patients were matched. The median PFS was 5.3 [95% confidence interval (CI) 4.4-6.3] and 4.7 (95% CI 3.2-5.3) months in the nab-PTX + RAM and PTX + RAM groups, respectively [hazard ratio (HR) = 0.76, 95% CI 0.56-1.03, p = 0.07]. The median OS was 11.5 (95% CI 9.2-15.0) and 9.9 (95% CI 8.0-12.7) months, respectively (HR = 0.78, 95% CI 0.56-1.07, p = 0.12). Grade 3 and 4 neutropenia was observed more frequently in the nab-PTX + RAM group (72% vs. 56%, p = 0.03). No treatment-related deaths occurred. CONCLUSIONS: Nab-PTX + RAM exhibited more favorable trends in terms of PFS and OS but was more myelosuppressive than PTX + RAM. As neutropenia is commonly manageable toxicity, nab-PTX + RAM presents a treatment alternative for AGC. Further studies including randomized, controlled studies are warranted.

Risk factors and efficacy outcomes of early-onset severe neutropenia due to paclitaxel or nanoparticle albumin-bound paclitaxel combined with ramucirumab in advanced gastric cancer: a multicenter retrospective cohort study.

Background: Paclitaxel or nanoparticle albumin-bound paclitaxel combined with ramucirumab (PTX/nab-PTX + RAM) is widely used as second-line chemotherapy for advanced gastric cancer (AGC), but severe neutropenia often develops with this regimen. Although previous studies have reported that severe neutropenia is a favorable prognostic factor in cancer chemotherapy, it is unclear in AGC patients receiving PTX/nab-PTX + RAM. In addition, the risk factors for early-onset of severe neutropenia (EOSN) still remain unknown. Methods: Among patients with AGC treated with PTX/nab-PTX (on day 1, 8, and 15) + RAM (on day 1 and 15) every 4 weeks as second-line therapy from January 2017 to June 2020, those with grade 0 or 1 neutropenia before the treatment were retrospectively studied. Blood tests were performed on the day of treatment each time, and disease progression was primarily determined by computed tomography every 8±2 weeks. EOSN was defined as grade 4 neutropenia that occurred during the first 28 days. The risk factors for EOSN were investigated using multivariate logistic regression analysis. Progression-free survival (PFS) and overall survival (OS) in patients with and without EOSN were investigated using multivariate analysis with a Cox proportional hazards model. Results: The clinical data of 244 patients were analyzed. EOSN was observed in 51 (20.9%) patients. Multivariate analysis identified the following five risk factors for EOSN: age ≥65 years [odds ratio (OR), 2.75], presence of primary tumor (OR, 2.82), presence of peritoneal metastasis (OR, 2.52), grade 1 neutropenia (OR, 3.32), and high serum level of alkaline phosphatase (OR, 2.34). The PFS was significantly longer in patients with EOSN than in those without EOSN [adjusted hazard ratio (HR), 0.61; 95% CI, 0.41-0.92] and the OS tended to be longer in patients with EOSN than in those without EOSN (adjusted HR, 0.73; 95% CI, 0.47-1.12). HR was adjusted with patient background factors and blood test data considered important as predictive or prognostic factors. Conclusions: EOSN may be associated with favorable outcomes in patients with AGC treated with PTX/nab-PTX + RAM. We should carefully try to treat them keeping the risk factors in mind.

FOLFIRINOX for Advanced Pancreatic Cancer Patients After Nab-Paclitaxel Plus Gemcitabine Failure.

OBJECTIVES: There is no standard chemotherapy for advanced pancreatic cancer (APC) after gemcitabine plus nab-paclitaxel (GP) failure. The aim of this study was to evaluate the efficacy and safety of FOLFIRINOX (5-Fluorouracil, leucovorin, irinotecan, and oxaliplatin) (5-Fluorouracil, leucovorin, irinotecan, and oxaliplatin) (FFX) and modified FFX (mFFX) for APC patients after GP failure. METHODS: We retrospectively evaluated the efficacy and safety of FFX in APC patients who were refractory or intolerant of GP. RESULTS: Between July 2014 and October 2018, 23 patients received FFX after failure of GP. The overall response rate (RR) was 23%, and the disease control rate (DCR) was 68%. The median progression-free survival (PFS) was 5.3 months (95% confidence interval, 2.5-8.9), and the median overall survival (OS) was 12.1 months (95% confidence interval, 4.0-14.2). Twelve patients received FFX, and 11 patients received mFFX. In the FFX group, the RR was 9%, the DCR was 73%, the PFS was 5.3 months, and the OS was 6.9 months. In the mFFX group, the RR was 23%, the DCR was 64%, the PFS was 4.3 months, and the OS was 12.8 months. There was no significant difference between the groups. CONCLUSIONS: FOLFIRINOX has potential activity for patients with APC in whom GP failed.