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BACKGROUND: The expenses related to fertility preservation or subsequent assisted reproductive treatments are significant for adolescents and young adult patients in Japan's current healthcare system. With fertility preservation becoming more widespread in developed countries, it is expected that these costs will be covered by insurance or subsidies. It is critical for patients, healthcare providers, and the government to know the costs that patients will be responsible for. In Japan, the costs of fertility preservation and subsequent assisted reproductive technology are not covered by insurance, but patients can apply for subsidies from the local and central governments if certain conditions are met. Presently, the above-mentioned costs, as well as the amount paid by the patient, vary by facility. Therefore, it is essential to ensure patients' continued access to necessary medical care despite the associated costs. METHODS: In this study, questionnaires were mailed to 186 certified fertility preservation facilities in Japan to assess patients who had undergone fertility preservation or assisted reproduction. The questionnaires were sent between October 27, 2023 and March 31, 2024, with 140 of the 186 facilities responding (response rate: 75.3%). RESULTS: Our findings show that approximately one-third of the costs was borne by the patients. CONCLUSION: Given these circumstances, sustainable pricing and insurance coverage are necessary for both patients and facilities.
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BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) commonly affects patient quality of life and the overall effectiveness of chemotherapy. This study aimed to evaluate whether adding neurokinin-1 receptor antagonists (NK1RAs) to 5-hydroxytryptamine-3 receptor antagonists (5-HT3RAs) and corticosteroids provides clinically meaningful benefits in preventing CINV in patients receiving moderately emetogenic chemotherapy (MEC). METHODS: We conducted a systematic review of PubMed, Cochrane Library, and Ichushi-Web to identify clinical studies evaluating NK1RAs combined with 5-HT3RAs and dexamethasone for managing CINV in MEC. The endpoints were complete response (CR), complete control (CC), total control (TC), adverse events, and costs. The data were analyzed using a random effects model. RESULTS: From 142 articles identified, 15 randomized controlled trials (RCTs), involving 4,405 patients, were included in the meta-analysis. Approximately 60% of the patients received carboplatin (CBDCA)-based chemotherapy. The meta-analysis showed that triplet antiemetic prophylaxis with NK1RA was significantly more effective for achieving CR than doublet prophylaxis in each phase. Regarding CC, the triplet antiemetic prophylaxis was significantly more effective than the doublet in the overall (risk difference [RD]: 0.11, 95% confidence interval [CI]: 0.06-0.17) and delayed (RD: 0.08, 95% CI: 0.02-0.13) phases. For TC, no significant differences were observed in any phase. Adding NK1RA did not cause adverse events. CONCLUSIONS: Adding NK1RA to CBDCA-based chemotherapy has shown clinical benefits. However, the clinical benefits of NK1RA-containing regimens for overall MEC have not yet been established and require RCTs that exclusively evaluate MEC regimens other than CBDCA-based chemotherapy.
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BACKGROUND: Proximal femoral fractures in geriatric patients are a major challenge in orthopedics, often leading to major functional impairment. Early surgical intervention is crucial for improving patient recovery and overall health outcomes. Thus, Japan's Ministry of Health, Labour and Welfare initiated a reimbursement policy in April 2022 to encourage early surgery for these fractures in patients aged ≥75 years. This study investigated the impact of this policy on early surgery rates in Japan and identified factors influencing the timing of surgical interventions. METHODS: We retrospectively analyzed the data of patients who underwent surgery for proximal femoral fractures at our institution between April 2022 and March 2023. Patients were categorized into two groups based on the timing of surgery relative to the injury: ≤48 h and >48 h. Demographic and clinical data, including age, sex, fracture type, and various health- and admission-related factors, were assessed. RESULTS: Of the 192 patients, 152 were included in the study. Among them, 38% underwent early surgery (≤48 h), and 15% of the patients arrived more than 48 h post-injury. Significant differences were found in admission routes and residence types between the groups. The ≤48 h group had shorter intervals from injury to admission and surgery than the >48 h group. Factors such as the admission process, day of the week, and C-reactive protein levels significantly influenced the timing of surgery. CONCLUSIONS: After introducing incentives for early surgery in Japan, 38% of patients with proximal femoral fractures underwent surgery within 48 h of injury. Factors contributing to patients not receiving early surgery included transport from another hospital, weekend hospitalization, and elevated CRP levels. These findings suggest that achieving surgery within 48 h of injury is challenging through hospital efforts alone, and the time criteria might be more appropriate if changed to "admission to surgery."
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PURPOSE: This study aimed to assess the viability of definitive chemoradiotherapy (dCRT) as an organ-preservation strategy for remarkable responders who were downstaged to stage IA after receiving induction chemotherapy for resectable esophageal squamous cell carcinoma (ESCC). METHODS AND MATERIALS: Chemotherapy-naïve patients with resectable ESCC (stage IB-III, Union for International Cancer Control, International Cancer Control seventh edition) were eligible for the study. All patients received 3 cycles of docetaxel, cisplatin, and 5-FU (DCF) therapy (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and 5-fluorouracil [5-FU] 750 mg/m2 on days 1-5, repeated every 3 weeks). Remarkable response was defined as a reduction in the tumor to T1, metastatic lymph nodes <1 cm on the short axis, and downstaging to stage IA after 3 cycles of DCF therapy. Remarkable responders then underwent dCRT, which included 2 courses of cisplatin 75 mg/m2 and 5-FU 1000 mg/m2 on days 1 to 4, repeated every 4 weeks, along with 50.4 Gy of concurrent radiation therapy. The primary endpoint was 1-year progression-free survival in remarkable responders following DCF therapy and subsequent dCRT. Secondary endpoints included 3-year overall survival (OS) and esophagectomy-free survival. RESULTS: Of the 92 patients registered, 90 were analyzed. A remarkable response to 3 courses of DCF therapy was observed in 58.4% of patients. Among these responders, 89.8% achieved a complete response after dCRT. During the median follow-up period of 33 months (range, 1-85 months), the 1-year progression-free survival was 89.8% (95% confidence interval [CI], 77.2%-95.6%, primary endpoint), and the 3-year OS was 83.7%. The 3-year OS and esophagectomy-free survival rates in the analysis group were 74.1% and 45.3%, respectively. An 18F-fluorodeoxyglucose-positron emission tomography response after 2 courses of DCF therapy was significantly associated with OS (P = .0049). CONCLUSIONS: In patients with resectable ESCC, dCRT for remarkable responders downstaging to stage IA after induction chemotherapy with 3 courses of DCF therapy is a feasible treatment option and provides an optimizing organ-preservation strategy of chemotherapy-based selection.
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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.
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Antieméticos , Oncología Médica , Vómitos , Humanos , Japón , Oncología Médica/normas , Antieméticos/uso terapéutico , Vómitos/prevención & control , Vómitos/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Sociedades Médicas , Náusea/prevención & control , Náusea/tratamiento farmacológicoRESUMEN
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.
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Antineoplásicos , Náusea , Neoplasias , Humanos , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Náusea/inducido químicamente , Náusea/prevención & control , Neoplasias/tratamiento farmacológico , Vómitos/inducido químicamente , Vómitos/prevención & control , Vómitos/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Vómito Precoz , Hipnosis , Yoga , Antieméticos/uso terapéuticoRESUMEN
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.
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Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Humanos , Bevacizumab/efectos adversos , Cetuximab/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Camptotecina/efectos adversos , Fluorouracilo/efectos adversos , Neoplasias del Colon/etiología , Neoplasias del Recto/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Leucovorina/efectos adversosRESUMEN
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.
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Medición de Resultados Informados por el Paciente , Humanos , Calidad de Vida , Guías de Práctica Clínica como Asunto , PsicometríaRESUMEN
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.
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Medición de Resultados Informados por el Paciente , Calidad de Vida , Humanos , Estudios Transversales , Japón , Atención a la SaludRESUMEN
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.
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Ácidos Nucleicos Libres de Células , Neoplasias del Colon , Neoplasias Colorrectales , Demencia Frontotemporal , Pirrolidinas , Timina , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Bevacizumab/farmacología , Bevacizumab/uso terapéutico , Neoplasias Colorrectales/patología , Interleucina-8/uso terapéutico , Uracilo/uso terapéutico , Trifluridina/farmacología , Trifluridina/uso terapéutico , Angiogénesis , Demencia Frontotemporal/tratamiento farmacológico , Inhibidor Tisular de Metaloproteinasa-1/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Ácidos Nucleicos Libres de Células/uso terapéutico , Biomarcadores , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
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.
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Antieméticos , Antineoplásicos , Humanos , Palonosetrón/uso terapéutico , Cisplatino/efectos adversos , Antagonistas del Receptor de Neuroquinina-1/uso terapéutico , Antieméticos/uso terapéutico , Olanzapina/uso terapéutico , Dexametasona/efectos adversos , Vómitos/inducido químicamente , Calidad de Vida , Quinuclidinas/efectos adversos , Antineoplásicos/efectos adversosRESUMEN
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.
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ADN Tumoral Circulante , Neoplasias del Colon , Neoplasias Colorrectales , Demencia Frontotemporal , Humanos , Persona de Mediana Edad , Cetuximab/farmacología , Cetuximab/uso terapéutico , Neoplasias Colorrectales/patología , Trifluridina/farmacología , Trifluridina/uso terapéutico , Demencia Frontotemporal/inducido químicamente , Demencia Frontotemporal/tratamiento farmacológico , Neoplasias del Colon/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
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.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , Anciano , Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , Vacunación/efectos adversos , Inmunidad Celular , Linfocitos T CD4-PositivosRESUMEN
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.
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Neoplasias del Colon , Neoplasias Colorrectales , Demencia Frontotemporal , Neoplasias del Recto , Humanos , Bevacizumab , Neoplasias Colorrectales/patología , Irinotecán , Trifluridina/efectos adversos , Demencia Frontotemporal/inducido químicamente , Demencia Frontotemporal/tratamiento farmacológico , Timina/uso terapéutico , Pirrolidinas , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Recto/inducido químicamente , Combinación de Medicamentos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
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.
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Preservación de la Fertilidad , Neoplasias , Neoplasias Testiculares , Adulto , Embarazo , Adolescente , Niño , Humanos , Masculino , Femenino , Preservación de la Fertilidad/métodos , Japón , Consejo , Neoplasias/complicaciones , Neoplasias/terapia , Neoplasias/psicología , Sistema de RegistrosRESUMEN
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).
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Inhibidores de Puntos de Control Inmunológico , Neoplasias , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Humanos , Japón , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Receptor de Muerte Celular Programada 1RESUMEN
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."
RESUMEN
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.