2023 Japan Society of clinical oncology clinical practice guidelines update for antiemesis.

BACKGROUND: The Japan Society of Clinical Oncology Clinical Practice Guidelines for Antiemesis 2023 was extensively revised to reflect the latest advances in antineoplastic agents, antiemetics, and antineoplastic regimens. This update provides new evidence on the efficacy of antiemetic regimens. METHODS: Guided by the Minds Clinical Practice Guideline Development Manual of 2017, a rigorous approach was used to update the guidelines; a thorough literature search was conducted from January 1, 1990, to December 31, 2020. RESULTS: Comprehensive process resulted in the creation of 13 background questions (BQs), 12 clinical questions (CQs), and three future research questions (FQs). Moreover, the emetic risk classification was also updated. CONCLUSIONS: The primary goal of the present guidelines is to provide comprehensive information and facilitate informed decision-making, regarding antiemetic therapy, for both patients and healthcare providers.

Non-pharmacological treatments for anticipatory nausea and vomiting during chemotherapy: a systematic review and meta-analysis of the Clinical Practice Guidelines for Antiemesis 2023.

BACKGROUND: Anticipatory chemotherapy-induced nausea and vomiting (CINV) is a conditioned response influenced by the severity and duration of previous emetic responses to chemotherapy. We aimed to evaluate the efficacy of non-pharmacologic interventions for anticipatory CINV among patients with cancer. METHODS: We conducted a systematic search in databases, including PubMed, the Cochrane Library, CINAHL, and Ichushi-Web, from January 1, 1990, to December 31, 2020. Randomized controlled trials, non-randomized designs, observational studies, or case-control studies that utilized non-pharmacological therapies were included. The primary outcomes were anticipatory CINV, with an additional investigation into adverse events and the costs of therapies. The risk-of-bias for each study was assessed using the Cochrane risk-of-bias tool, and meta-analysis was performed using Revman 5.4 software. RESULTS: Of the 107 studies identified, six met the inclusion criteria. Three types of non-pharmacological treatments were identified: systematic desensitization (n = 2), hypnotherapy (n = 2), and yoga therapy (n = 2). Among them, systematic desensitization significantly improved anticipatory CINV as compared to that in the control group (nausea: risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.49-0.72, p < 0.00001; vomiting: RR = 0.54, 95% CI = 0.32-0.91, p = 0.02). However, heterogeneity in outcome measures precluded meta-analysis for hypnotherapy and yoga. Additionally, most selected studies had a high or unclear risk of bias, and adverse events were not consistently reported. CONCLUSIONS: Our findings suggest that systematic desensitization may effectively reduce anticipatory CINV. However, further research is warranted before implementation in clinical settings.

Switching from FOLFIRI plus cetuximab to FOLFIRI plus bevacizumab based on early tumor shrinkage in RAS wild-type metastatic colorectal cancer: A phase II trial (HYBRID).

BACKGROUND: Long-term anti-EGFR antibody treatment increases the risk of severe dermatologic toxicities. This single-arm, phase II trial aimed to investigate the strategy of switching from cetuximab to bevacizumab in combination with FOLFIRI based on early tumor shrinkage (ETS) in patients with RAS wild-type metastatic colorectal cancer (mCRC). METHODS: Radiologic assessment was performed to evaluate ETS, defined as ≥20% reduction in the sum of the largest diameters of target lesions 8 weeks after the introduction of FOLFIRI plus cetuximab. ETS-negative patients switched to FOLFIRI plus bevacizumab, whereas ETS-positive patients continued FOLFIRI plus cetuximab for eight more weeks, with a switch to FOLFIRI plus bevacizumab thereafter. The primary endpoint was progression-free survival. RESULTS: This trial was prematurely terminated due to poor accrual after a total enrollment of 30 patients. In 29 eligible patients, 7 were ETS-negative and 22 were ETS-positive. Two ETS-negative patients and 17 ETS-positive patients switched to FOLFIRI plus bevacizumab 8 weeks and 16 weeks after initial FOLFIRI plus cetuximab, respectively. Median progression-free and overall survival durations were 13.4 and 34.7 months, respectively. Six (20%) patients experienced grade ≥3 paronychia, which improved to grade ≤2 by 18 weeks. Grade ≥3 acneiform rash, dry skin, and pruritus were not observed in any patients. CONCLUSIONS: Our novel treatment strategy delivered acceptable survival outcomes and reduced severe dermatologic toxicities.

How to select and understand guidelines for patient-reported outcomes: a scoping review of existing guidance.

BACKGROUND: Over the past few decades, patient-reported outcomes (PROs) have been used to understand patient health conditions better. Therefore, numerous PRO measures (questionnaires) and guidelines or guidance have been developed. However, it is challenging to select target guidance from among the many available guidance and to understand the chosen guidance. This study comprehensively collected the existing PRO guidance for clinical trials or studies and practices to support novice PRO users in academia, industry, clinical practice, and regulatory and reimbursement decision-making. METHODS: For the scoping review, we searched the MEDLINE, Embase, Google Books, WorldCat, and the National Library of Medicine (NLM) Bookshelf databases from 2009 to 2023. The eligibility criteria were PRO guidance for clinical trials, clinical practice, or application such as health technology assessment. Those guidance cover aspects such as quality of life (QOL), PRO, health-related QOL, health state utilities, psychometric requirements, implementation methods, analysis and interpretation, or clinical practice applications. After the systematic search, three researchers individually reviewed the collected data, and the reviewed articles and books were scrutinized using the same criteria. RESULTS: We collected the PRO guidance published in articles and books between 2009 and 2023. From the database searches, 1,455 articles and 387 books were identified, of which one book and 33 articles were finally selected. The collected PRO guidance was categorized into the adoption of PRO measures, design and reporting of trials or studies using PROs, implementation of PRO evaluation in clinical trials or studies or clinical practice, analysis and interpretation of PROs, and application of PRO evaluation. Based on this categorization, we suggest the following for novices: When selecting guidance, novices should clarify the "place" and "purpose" where the guidance will be used. Additionally, they should know that the terminology related to PRO and the scope and expectations of PROs vary by "places" and "purposes". CONCLUSIONS: From this scoping review of existing PRO guidance, we provided summaries and caveats to assist novices in selecting guidance that fits their purpose and understanding it.

Perceptions regarding the concept and definition of patient-reported outcomes among healthcare stakeholders in Japan with relation to quality of life: a cross-sectional study.

Patient-reported outcomes (PROs) are frequently used in a variety of settings, including clinical trials and clinical practice. The definition of PRO and quality of life (QOL) and their relationship have been concluded through discussions among experts that has been the premise of PRO guidelines are not clearly stated in the guidelines. Therefore, the definition of PRO, especially in relation to QOL, is sometimes explained simply, as "PRO includes QOL," but this complicated matters. This study investigated the perceptions of PRO among various stakeholders (including patients and their families, the industry, clinicians, regulatory or health technology assessment personnel, and academic researchers) in Japan to clarify its definitions and that of QOL, including their relationship.We conducted a two-step survey: a qualitative interview survey and a web-based survey to ensure the validity of the survey. During the interviews, eight stakeholders described their perceptions and thoughts on PRO and its relationship to QOL, and their experience of using PRO. Overall 253 clinicians, 249 company employees, and 494 patients participated in the web survey to confirm how the findings of the interview survey supported the results.In the interview survey, patient advocates described various perspectives of PRO and QOL, including unexpected dynamic relationships, while the most other stakeholders explained PRO and QOL with the language used in the guidelines, but their responses were split. The web-based survey revealed that all stakeholders had a lower awareness of PRO than QOL. The most common perception of PRO, especially in the relationship to QOL, was "they did not fully overlap." Although there were differences in perceptions of the relationship between PRO and QOL among clinicians, company employees, and patients, all perceived PRO as a tool to facilitate communication in clinical practice.The present results are inconsistent with the simplified explanation of PRO, but consistent with the original PRO guideline definitions, which also considered the role of PRO in clinical practice. To make PRO a more potent tool, all stakeholders using PRO should confirm its definition and how it differs from QOL, have a unified recognition in each PRO use, and avoid miscommunication.

Exploratory Biomarker Analysis Using Plasma Angiogenesis-Related Factors and Cell-Free DNA in the TRUSTY Study: A Randomized, Phase II/III Study of Trifluridine/Tipiracil Plus Bevacizumab as Second-Line Treatment for Metastatic Colorectal Cancer.

BACKGROUND: The TRUSTY study evaluated the efficacy of second-line trifluridine/tipiracil (FTD/TPI) plus bevacizumab in metastatic colorectal cancer (mCRC). OBJECTIVE: This exploratory biomarker analysis of TRUSTY investigated the relationship between baseline plasma concentrations of angiogenesis-related factors and cell-free DNA (cfDNA), and the efficacy of FTD/TPI plus bevacizumab in patients with mCRC. PATIENTS AND METHODS: The disease control rate (DCR) and progression-free survival (PFS) were compared between baseline plasma samples of patients with high and low plasma concentrations (based on the median value) of angiogenesis-related factors. Correlations between cfDNA concentrations and PFS were assessed. RESULTS: Baseline characteristics (n = 65) were as follows: male/female, 35/30; median age, 64 (range 25-84) years; and RAS status wild-type/mutant, 29/36. Patients in the hepatocyte growth factor (HGF)-low and interleukin (IL)-8-low groups had a significantly higher DCR (risk ratio [95% confidence intervals {CIs}]) than patients in the HGF-high (1.83 [1.12-2.98]) and IL-8-high (1.70 [1.02-2.82]) groups. PFS (hazard ratio {HR} [95% CI]) was significantly longer in patients in the HGF-low (0.33 [0.14-0.79]), IL-8-low (0.31 [0.14-0.70]), IL-6-low (0.19 [0.07-0.50]), osteopontin-low (0.39 [0.17-0.88]), thrombospondin-2-low (0.42 [0.18-0.98]), and tissue inhibitor of metalloproteinase-1-low (0.26 [0.10-0.67]) groups versus those having corresponding high plasma concentrations of these angiogenesis-related factors. No correlation was observed between cfDNA concentration and PFS. CONCLUSION: Low baseline plasma concentrations of HGF and IL-8 may predict better DCR and PFS in patients with mCRC receiving FTD/TPI plus bevacizumab, however further studies are warranted. CLINICAL TRIAL REGISTRATION NUMBER: jRCTs031180122.

Dexamethasone-sparing on days 2-4 with combined palonosetron, neurokinin-1 receptor antagonist, and olanzapine in cisplatin: a randomized phase III trial (SPARED Trial).

BACKGROUND: This study evaluated the non-inferiority of dexamethasone (DEX) on day 1, with sparing on days 2-4 in cisplatin-based chemotherapy. METHODS: Patients with malignant solid tumors who were treated with cisplatin (≥50 mg/m²) were randomly assigned (1:1) to receive either DEX on days 1-4 (Arm D4) or DEX on day 1 (Arm D1) plus palonosetron, NK-1 RA, and olanzapine (5 mg). The primary endpoint was complete response (CR) during the delayed (24-120 h) phase. The non-inferiority margin was set at -15%. RESULTS: A total of 281 patients were enrolled, 278 of whom were randomly assigned to Arm D4 (n = 139) or Arm D1 (n = 139). In 274 patients were included in the efficacy analysis, the rates of delayed CR in Arms D4 and D1 were 79.7% and 75.0%, respectively (risk difference -4.1%; 95% CI -14.1%-6.0%, P = 0.023). However, patients in Arm D1 had significantly lower total control rates during the delayed and overall phases, and more frequent nausea and appetite loss. There were no significant between-arm differences in the quality of life. CONCLUSION: DEX-sparing is an alternative option for patients receiving cisplatin; however, this revised administration schedule should be applied on an individual basis after a comprehensive evaluation. CLINICAL TRIALS REGISTRY NUMBER: UMIN000032269.

A Phase II Trial of Trifluridine/Tipiracil in Combination with Cetuximab Rechallenge in Patients with RAS Wild-Type mCRC Refractory to Prior Anti-EGFR Antibodies: WJOG8916G Trial.

BACKGROUND: Trifluridine/tipiracil (FTD/TPI) improved the overall survival in patients with metastatic colorectal cancer (mCRC) who had previously received standard chemotherapies; however, the clinical outcomes remain poor. OBJECTIVE: A multicenter phase II study aimed to assess the efficacy and safety of FTD/TPI plus cetuximab rechallenge. PATIENTS AND METHODS: Patients with histologically confirmed RAS wild-type mCRC refractory to prior anti-epidermal growth factor receptor (anti-EGFR) antibody were enrolled and treated with FTD/TPI (35 mg/m2 twice daily on days 1-5 and 8-12) plus cetuximab (initially 400 mg/m2, followed by weekly 250 mg/m2) every 4 weeks. The primary endpoint was disease control rate (DCR), expecting a target DCR of 65% and null hypothesis of 45% with 90% power and 10% one-sided alpha error. Gene alterations of RAS, BRAF, EGFR, PIK3CA, ERBB2, and MET in pre-treatment circulating tumor DNA were evaluated using the Guardant360 assay. RESULTS: A total of 56 patients (median age 60 years; left-sided tumors 91%; objective partial or complete response during the prior anti-EGFR therapy 61%) were enrolled. The DCR was 54% (80% confidence interval [CI] 44-63; P = 0.12), with a partial response rate of 3.6%. Median progression-free survival (PFS) was 2.4 months (95% CI 2.1-3.7). In the circulating tumor DNA analysis, patients without any alterations of the six genes (n = 20) demonstrated higher DCR (75% vs. 39%; P = 0.02) and longer PFS (median 4.7 vs. 2.1 months; P < 0.01) than those with any gene alterations (n = 33). The most common grade 3/4 hematologic adverse event was neutropenia (55%). No treatment-related deaths occurred. CONCLUSIONS: FTD/TPI plus cetuximab rechallenge did not demonstrate clinically meaningful efficacy in all mCRC patients, but might be beneficial for the molecularly selected population.

Impaired CD4+ T cell response in older adults is associated with reduced immunogenicity and reactogenicity of mRNA COVID-19 vaccination.

Whether age-associated defects in T cells impact the immunogenicity and reactogenicity of mRNA vaccines remains unclear. Using a vaccinated cohort (n = 216), we demonstrated that older adults (aged ≥65 years) had fewer vaccine-induced spike-specific CD4+ T cells including CXCR3+ circulating follicular helper T cells and the TH1 subset of helper T cells after the first dose, which correlated with their lower peak IgG levels and fewer systemic adverse effects after the second dose, compared with younger adults. Moreover, spike-specific TH1 cells in older adults expressed higher levels of programmed cell death protein 1, a negative regulator of T cell activation, which was associated with low spike-specific CD8+ T cell responses. Thus, an inefficient CD4+ T cell response after the first dose may reduce the production of helper T cytokines, even after the second dose, thereby lowering humoral and cellular immunity and reducing systemic reactogenicity. Therefore, enhancing CD4+ T cell response following the first dose is key to improving vaccine efficacy in older adults.

Trifluridine/tipiracil+bevacizumab (BEV) vs. fluoropyrimidine-irinotecan+BEV as second-line therapy for metastatic colorectal cancer: a randomised noninferiority trial.

BACKGROUND: This open-label, multicentre, phase II/III trial assessed the noninferiority of trifluridine/tipiracil (FTD/TPI) plus bevacizumab vs. fluoropyrimidine and irinotecan plus bevacizumab (control) as second-line treatment for metastatic colorectal cancer (mCRC). METHODS: Patients were randomised (1:1) to receive FTD/TPI (35 mg/m2 twice daily, days 1-5 and days 8-12, 28-day cycle) plus bevacizumab (5 mg/kg, days 1 and 15) or control. The primary endpoint was overall survival (OS). The noninferiority margin of the hazard ratio (HR) was set to 1.33. RESULTS: Overall, 397 patients were enrolled. Baseline characteristics were similar between the groups. Median OS was 14.8 vs. 18.1 months (FTD/TPI plus bevacizumab vs. control; HR 1.38; 95% confidence interval [CI] 0.99-1.93; Pnoninferiority = 0.5920). In patients with a baseline sum of the diameter of target lesions of <60 mm (n = 216, post hoc analyses), the adjusted median OS was similar between groups (FTD/TPI plus bevacizumab vs. control, 21.4 vs. 20.7 months; HR 0.92; 95% CI 0.55-1.55). Grade ≥3 adverse events (FTD/TPI plus bevacizumab vs. control) included neutropenia (65.8% vs. 41.6%) and diarrhoea (1.5% vs. 7.1%). CONCLUSIONS: FTD/TPI plus bevacizumab did not demonstrate noninferiority to fluoropyrimidine and irinotecan plus bevacizumab as second-line treatment for mCRC. CLINICAL TRIAL REGISTRATION: JapicCTI-173618, jRCTs031180122.

Current Status and Issues of the Japan Oncofertility Registry.

Purpose: Fertility preservation (FP) is becoming increasingly common among child, adolescent, and young-adult (CAYA) patients with cancer. However, Japan has long lacked definite estimates of utilization rates for FP services among CAYA patients with cancer, and little is known about disease/FP outcomes among users. Therefore, the Japan Society for Fertility Preservation (JSFP) launched the Japan Oncofertility Registry (JOFR) in 2018 and started the online registration of information regarding primary disease, FP, and data on prognosis and pregnancy outcomes. This study reports the analytical results of FP data registered in the JOFR as of 2021. Methods: Data about patients' primary disease(s), treatment courses, cancer and pregnancy outcomes, and specific procedures were extracted from the JOFR and analyzed. Results: In 2021, 1244 patients received counseling or treatment related to FP (540 males, 704 females). While the numbers of males in each age group were approximately equal, most females were aged between 31 and 40 years. In total, 490 male and 540 female patients underwent FP procedures. Leukemia, testicular cancer, and malignant lymphoma accounted for the majority of male cases seeking treatment, whereas breast cancer was the primary disease in two-thirds of the females. Since 1999, 395 patients have accumulatively experienced subsequent pregnancy. Conclusions: As of January 2022, >7000 cases from >100 fertility facilities have been registered in the JOFR. In the future, maintaining JOFR to disseminate information on cancer prognoses, pregnancy rates, and other oncofertility outcomes is expected to drive further expansion of oncofertility services in Japan.

Phase I study of envafolimab (KN035), a novel subcutaneous single-domain anti-PD-L1 monoclonal antibody, in Japanese patients with advanced solid tumors.

Envafolimab is the first and only globally approved subcutaneously injectable PD-L1 antibody. This open-label, multicenter Phase 1 trial assessed the safety, tolerability, pharmacokinetic (PK) profile, and efficacy of envafolimab as a single agent in Japanese patients with advanced solid tumors. In the dose-escalation phase, 10 patients received subcutaneous (SC) envafolimab QW at 1.0 mg/kg, 2.5 mg/kg and 5.0 mg/kg. In the dose-expansion phase, 16 patients were treated at 2.5 or 5.0 mg/kg Q2W in part-1 and 9 patients received SC envafolimab 300 mg Q4W in part-2. No dose-limiting toxicities (DLTs) were reported. Envafolimab was well tolerated and no new safety signals were identified compared with other marketed products of the same class. Three patients reported Grade ≥ 3 envafolimab-related treatment-emergent adverse events (TEAE), including adrenal insufficiency, cerebral infarction, and immune-mediated enterocolitis. Envafolimab demonstrated dose-proportional increases in area under the time-concentration curve (AUC) and maximum serum concentration (Cmax). The overall response rate (ORR) was 11.4% (n = 4) and disease control rate (DCR) was 34.3% (n = 12). Consistent with that observed in other envafolimab Phase 1 trials and approved PD-1/PD-L1 inhibitors, the safety profile of SC envafolimab in Japanese patients with advanced solid tumors was well tolerated with efficacy comparable to IV administered treatments. Pharmacokinetics data and preliminary anti-tumor response support dose regimens with longer dosing intervals (Q2W or Q4W). As such, envafolimab offers patients a more convenient treatment option than currently available intravenously administered PD-1/PD-L1 inhibitors. CLINICALTRIALS.GOV IDENTIFIER: NCT03248843(August 14, 2017).

Nursing Students' Use of Recovery Stories of People with Mental Illness in Their Experiences: A Qualitative Study.

This study clarified nursing students' experiences of an educational program where they listened to the recovery stories of individuals with mental illness in a classroom setting. In this qualitative study, the program was delivered to third year nursing students in December 2019 (n = 62), after which they completed an anonymous free-response questionnaire. The responses were classified into seven clusters: understanding how patients perceive and appraise nursing care practices; interpreting experiences of disease realistically; deciphering patients' histories based on their recovery stories; exploring ways to engage with patients based on knowledge of determinants of nursing care quality; finding ways to engage with patients grounded in respect; recognizing the importance of creating a therapeutic environment; gaining a sensitive understanding based on real-world stories. These clusters were grouped into "understanding the quality of nursing practices" and "gaining knowledge for application to nursing practices."

Genomic Landscape of Primary Tumor Site and Clinical Outcome for Patients with Metastatic Colorectal Cancer Receiving Standard-of-Care Chemotherapy.

BACKGROUND: Primary tumor site and genomic status are utilized for regimen selection in metastatic colorectal cancer; however, the impact on clinical practice is not well known. OBJECTIVE: We aimed to clarify the impact of primary tumor site and genomic status on clinical practice in metastatic colorectal cancer. METHODS: The relationship between primary tumor site, genomic alterations, and clinical outcomes was evaluated in patients with untreated metastatic colorectal cancer using real-world data of a prospective observational study, SCRUM-Japan GI-SCREEN with clinical and genomic data set in 1011 patients enrolled from February 2015 to March 2017. RESULTS: Five hundred and sixty-one patients were eligible for this study. Patients with right-sided tumors had a significantly worse survival, left-sided tumors with wild-type RAS had favorable outcomes when treated with anti-epidermal growth factor receptor monoclonal antibodies, and cecum tumors had poor prognosis when treated with bevacizumab. The rate of gene alterations varied considerably depending on the primary site. In addition, gene alterations of KRAS, BRAF, SMAD4, or TP53 had individually different contributions to survival from site to site. KRAS, BRAF, PTEN, or SMAD4 mutations were associated with efficacy of bevacizumab or anti-epidermal growth factor receptor monoclonal antibodies. CONCLUSIONS: Primary tumor site is a clinically useful biomarker to predict survival in patients with metastatic colorectal cancer treated with first-line chemotherapy. Moreover, the prognostic or predictive value of several gene alterations by primary tumor site should be considered in clinical practice.

An exploration of trifluridine/tipiracil in combination with irinotecan in patients with pretreated advanced gastric cancer.

BACKGROUND: Trifluridine/tipiracil (FTD/TPI) and irinotecan are treatment options for heavily pretreated patients with advanced gastric cancer, but their efficacies are limited. We investigated the combination of FTD/TPI and irinotecan for such patients. METHODS: Patients who were refractory to fluoropyrimidine, platinum and taxane were enrolled into four cohorts (Level 1A/1B/2A/2B) and treated with irinotecan (100 [Level 1] or 125 [Level 2] mg/m2 on days 1 and 15) and FTD/TPI (35 mg/m2/dose, twice daily, on days 1-5 and 8-12 [Level A] or on days 1-5 and days 15-19 [Level B]) of a 28-day cycle. The primary endpoints were the maximum tolerated dose, dose-limiting toxicities (DLTs), and recommended phase II dose (RP2D); the secondary endpoint was the disease control rate (DCR). RESULTS: Eleven patients were enrolled: 2 at Level 1A, 3 at Level 1B, and 6 at Level 2B. DLTs occurred in 2/2 patients at Level 1A and 2/6 patients at Level 2B. Grade 3 or higher treatment-related adverse events were neutropenia (90.9%), leukopenia (54.5%), anemia (45.5%) and febrile neutropenia (18.2%). One patient at Level 2B achieved a partial response, and the DCR was 72.7% (95% CI, 39.0%-94.0%). The median progression-free survival and overall survival periods were 3.0 months (95% CI, 0.92-not reached) and 10.2 months (95% CI, 2.2-not reached), respectively. CONCLUSION: The RP2D of FTD/TPI combined with irinotecan was determined to be Level 1B; this level was associated with manageable hematologic toxicities and feasible non-hematologic toxicities. Further evaluation of the efficacy of RP2D treatment is necessary.

Poncet's Disease (Reactive Arthritis Associated with Tuberculosis).

An 82-year-old man with miliary tuberculosis was admitted to our hospital. Approximately six weeks after starting anti-tuberculosis treatment, he complained of pain in the fingers, wrists, and ankles. A histopathological examination of the synovial biopsy revealed nonspecific chronic inflammation with no granulomas. Culture of the biopsy specimen yielded no acid-fast bacilli. Poncet's disease was diagnosed based on the clinical presentation, with no findings suggestive of other diseases. His joint pain rapidly improved with steroid therapy. Tuberculosis can cause arthritis through immune-mediated mechanisms without direct invasion in an entity known as Poncet's disease.

Real-world effectiveness of nivolumab in advanced gastric cancer: the DELIVER trial (JACCRO GC-08).

BACKGROUND: There is no large real-world data regarding efficacy and safety of immunotherapy in gastric cancer (GC). Although some tumors can grow rapidly after immunotherapy, the patient proportions and survival outcomes are unclear in GC. METHODS: A multicenter, prospective observational study was performed to evaluate clinical outcomes including survival time, safety, and tumor behavior of nivolumab treatment for patients with advanced GC. Primary endpoint was overall survival (OS), and secondary endpoints included response rate (RR), disease control rate (DCR), progression-free survival (PFS), tumor growth rate (TGR) at first evaluation, and safety. RESULTS: Of 501 enrolled patients, 487 were evaluable (median age 70 years, 71% male, performance status 0/1/2 [42%/44%/14%], 21% HER2-pos, 42% patients with ascites). Median OS was 5.82 months (95% CI 5.29-7.00) with a 1-year survival rate of 30% and median PFS of 1.84 months (95% CI 1.71-1.97). The DCR was 39.4% and the RR was 14.2% (95% CI 10.3-18.8) in 282 patients with measurable lesions. In 219 patients evaluable for TGR, 20.5% were identified as hyperprogressive disease (HPD). OS from the first evaluation of patients with HPD was shorter compared with non-HPD (HR 1.77, 95% CI 1.25-2.51, P = 0.001), but it was not worse than that of patients with progression and non-HPD (HR 1.05, 95% CI 0.72-1.53, P = 0.8). A multivariate analysis revealed the presence of peritoneal metastasis was a prognostic factor for OS and PFS. CONCLUSIONS: Our real-world data demonstrated the comparable survival time to a previous clinical trial and revealed the frequency and prognosis of patients with HPD in advanced GC treated with nivolumab.

Impact of Body Weight Loss on Survival in Patients with Advanced Gastric Cancer Receiving Second-Line Treatment.

Limited information is available regarding the impact of body weight loss (BWL) in patients with advanced gastric cancer (AGC) who receive second-line chemotherapy. We retrospectively reviewed data for consecutive AGC patients who received second-line treatment with taxane-based chemotherapy at our institution between January 2014 and September 2018. We calculated variables, including percent BWL per month during chemotherapy (%BWL/m), and analyzed the correlations between BWL and other clinicopathological parameters with survival. Forty-four AGC patients were registered (median age, 67.5 years; females, n = 16 [36.3%]; severe ascites, n = 12 [27.3%]). The median overall survival was significantly shorter among patients with a %BWL/m of 1% or more, compared with patients with less weight loss (6.3 mo, vs. 12.3 mo, P = 0.038). The %BWL/m (≥1% vs. <1%) was significantly correlated with survival in a univariate analysis (HR = 2.11, P = 0.04), and the survival period was shorter for patients with severe ascites (HR = 1.92; 95% CI, 0.90-3.90) and if their %BWL/m was 1% or more (HR = 2.01; 95% CI, 0.98-4.10) in a multivariate analysis. In conclusion, BWL during second-line chemotherapy was associated with a poor prognosis among patients with AGC.