Assessments of patient-reported outcomes and health-related quality of life in cancer clinical tr... more Assessments of patient-reported outcomes and health-related quality of life in cancer clinical trials have been increasingly emphasized recently because patient and public involvement in cancer treatment development has been promoted by regulatory authorities and academic societies. To assess patient experiences during and after cancer treatment, there is interest in implementing patient-reported outcome and health-related quality of life assessments into cancer clinical trials. The Japan Clinical Oncology Group quality of life ad hoc committee previously created a version of the Quality of Life Assessment Policy in 2006. Recently, there has been increasing demand from Japan Clinical Oncology Group researchers to assess patient-reported outcome/healthrelated quality of life in clinical trials. Although guidelines are available regarding planning and reporting clinical trials that include patient-reported outcome/health-related quality of life as an endpoint, there are still issues regarding the lack of consensus on standardized methods for analysing and interpreting the results. Hence, it was considered necessary to reorganize the Japan Clinical Oncology Group patient-reported outcome/quality of life research committee and to revise the former patient-reported outcome/quality of life research policy to promote patient-reported outcome/health-related quality of life research in future Japan Clinical Oncology Group trials. The purpose of this Japan Clinical Oncology Group patient-reported outcome/quality of life research policy is to define patient-reported outcome/health-related quality of life research and provide guidelines for including patient-reported outcome/health-related quality of life as an endpoint in Japan Clinical Oncology Group trials.
Purpose The purpose of this study was to investigate the impact of the type of data capture on th... more Purpose The purpose of this study was to investigate the impact of the type of data capture on the time and help needed for collecting patient-reported outcomes as well as on the proportion of missing scores. Methods In a multinational prospective study, thyroid cancer patients from 17 countries completed a validated questionnaire measuring quality of life. Electronic data capture was compared to the paper-based approach using multivariate logistic regression. Results A total of 437 patients were included, of whom 13% used electronic data capture. The relation between data capture and time needed was modified by the emotional functioning of the patients. Those with clinical impairments in that respect needed more time to complete the questionnaire when they used electronic data capture compared to paper and pencil (OR adj 24.0; p = 0.006). This was not the case when patients had sub-threshold emotional problems (OR adj 1.9; p = 0.48). The odds of having the researcher reading the questions out (instead of the patient doing this themselves) (OR adj 0.1; p = 0.01) and of needing any help (OR adj 0.1; p = 0.01) were lower when electronic data capture was used. The proportion of missing scores was equivalent in both groups (OR adj 0.4, p = 0.42). Conclusions The advantages of electronic data capture, such as real-time assessment and fewer data entry errors, may come at the price of more time required for data collection when the patients have mental health problems. As this is not uncommon in thyroid cancer, researchers need to choose the type of data capture wisely for their particular research question.
Background: Driver mutations at BRAF V600 are frequently identified in papillary thyroid cancer a... more Background: Driver mutations at BRAF V600 are frequently identified in papillary thyroid cancer and anaplastic thyroid cancer (ATC), in which BRAF inhibitors have shown clinical effectiveness. This Japanese phase 2 study evaluated the efficacy and safety of a BRAF inhibitor, encorafenib, combined with an MEK inhibitor, binimetinib, in patients with BRAF V600-mutated thyroid cancer. Methods: This phase 2, open-label, uncontrolled study was conducted at 10 institutions targeted patients with BRAF V600-mutated locally advanced or distant metastatic thyroid cancer not amenable to curative treatment who became refractory/intolerant to ‡1 previous vascular endothelial growth factor receptor-targeted regimen(s) or were considered ineligible for those. The primary endpoint was centrally assessed objective response rate (ORR). The secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: We enrolled 22 patients with BRAF V600E -mutated thyroid cancer: 17 had differentiated thyroid cancer (DTC), and 5 had ATC. At data cutoff (October 26, 2022), the median follow-up was 11.5 (range = 3.4-19.0) months. The primary endpoint of centrally assessed ORR was 54.5% (95% confidence interval [CI] 32.2-75.6; partial response in 12 patients and stable disease in 10). The ORRs in patients with DTC and ATC were 47.1% (8 of 17) and 80.0% (4 of 5), respectively. The medians for DOR and PFS by central assessment and for OS were not reached in the overall population, the DTC subgroup, or the ATC subgroup. At 12 months, the rate of ongoing response was 90.9%, and the PFS and OS rates were 78.8% and 81.8%, respectively. All patients developed ‡1 adverse events (AEs): grade 3 AEs in 6 patients (27.3%). No patients developed grade 4-5 AEs. The most common grade 3 AE was lipase increased (4 patients [18.2%]). Those toxicities were mostly manageable with appropriate monitoring and dose adjustment. Conclusions: Treatment with encorafenib plus binimetinib met the primary endpoint criteria and demonstrated clinical benefit in patients with BRAF V600E -mutated thyroid cancer regardless of its histological type, such as
Surgery remains a foundation of treatment for locally advanced squamous cell carcinoma of the hea... more Surgery remains a foundation of treatment for locally advanced squamous cell carcinoma of the head and neck. For postoperative patients at high risk of recurrence, however, surgery by itself is not enough, and improvement in survival requires postoperative treatment. Unlike the case with most other malignancies, the standard postoperative treatment for locally advanced squamous cell carcinoma of the head and neck patients with high-risk factors for recurrence is radiotherapy or chemoradiotherapy with cisplatin. However, chemoradiotherapy with cisplatin at a dose of 100 mg/m 2 once every 3 weeks has raised discussion over insufficient cisplatin delivery due to highdose-related toxicity. As a possible solution, a recent randomized trial of the JCOG1008 has proved the non-inferiority of postoperative chemoradiotherapy with weekly cisplatin at a dose of 40 mg/m 2 to 3-weekly cisplatin in terms of overall survival. Here, this review article focuses on current evidence and future perspectives of postoperative treatment for locally advanced squamous cell carcinoma of the head and neck.
The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life En... more The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) initiative was established in 2016 to assess the quality and standardization of patientreported outcomes (PRO) data analysis in randomized controlled trials (RCTs) on advanced breast cancer. The initiative identified deficiencies in PRO data reporting, including nonstandardized methods for handling missing data. This study evaluated the reporting of health-related quality of life (HRQOL) in Japanese cancer RCTs to provide insights into the state of PRO reporting in Japan. The study reviewed PubMed articles published from 2010 to 2018. Eligible studies included Japanese cancer RCTs with ≥50 adult patients (≥50% were Japanese) with solid tumors receiving anticancer treatments. The evaluation criteria included clarity of the HRQOL hypotheses, multiplicity testing, primary analysis methods, and reporting of clinically meaningful differences. Twenty-seven HRQOL trials were identified. Only 15% provided a clear HRQOL hypothesis, and 63% examined multiple HRQOL domains without adjusting for multiplicity. Model-based methods were the most common statistical methods for the primary HRQOL analysis. Only 22% of the trials explicitly reported clinically meaningful differences in HRQOL. Baseline assessments were reported in most trials, but only 26% reported comparisons between the treatment groups. HRQOL analysis was based on the intention-to-treat population in 19% of the trials, and 74% reported compliance at follow-up; however, 41% did not specify how missing values were handled. Although the rates of reporting clinical hypotheses and clinically meaningful differences were relatively low, the current state of HRQOL evaluation in the Japanese cancer RCT appears comparable to that of previous studies. Categories: Oncology, Quality Improvement Keywords: health-related quality of life (hrqol), randomized trials, pro, hrqol, randomized controlled trial, statistical methods, health-related quality of life, patient reported outcomes 1 1 2 3 4 5
Background: In a randomized phase II/III trial (JCOG1008), weekly cisplatin (40 mg/m 2 ) was non-... more Background: In a randomized phase II/III trial (JCOG1008), weekly cisplatin (40 mg/m 2 ) was non-inferior to 3-weekly cisplatin (100 mg/m 2 ) for postoperative high-risk head and neck cancer. We investigated how acute kidney injury (AKI), a major dose-limiting toxicity effect of cisplatin, affects overall survival (OS). We analyzed 251 patients from JCOG1008 receiving chemoradiotherapy. AKI was defined based on AKI Network criteria (serum creatinine increase of ≥0.3 mg/dL or ≥1.5fold [≥ stage I]) within 30 days after completing chemoradiotherapy. OS in the two arms was compared according to AKI development using the log-rank test. The total incidence of AKI was lower in the weekly arm than in the 3-weekly arm (38/122 [31.1%] vs. 56/129 [43.4%]). Additionally, stage II/III AKI occurred less frequently in the weekly arm than in the 3-weekly arm (8/122 [6.6%] vs. 19/129 [14.7%]). Cisplatin doses were similar in the weekly arm for patients with and without AKI (median, 238.6 mg/m 2 vs. 239.2 mg/m 2 ; p = 0.94), but lower in the 3-weekly arm for those who developed AKI (median, 276.3 mg/ m 2 vs. 297.4 mg/m 2 ; p = 0.007). In the weekly arm, there was no difference in OS between patients with and without AKI (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.53 to 2.10). However, in the 3-weekly arm, patients with AKI had poorer OS than those without AKI (HR, 1.83; 95% CI, 1.04 to 3.21). In this supplementary analysis of JCOG1008 data, AKI impacted the OS of patients with head and neck cancer undergoing postoperative chemoradiotherapy in the 3-weekly arm but not in the weekly arm. Our results further endorse the utilization of weekly cisplatin at 40 mg/m 2 in this setting.
Japanese journal of clinical oncology, Mar 7, 2024
Surgery remains a foundation of treatment for locally advanced squamous cell carcinoma of the hea... more Surgery remains a foundation of treatment for locally advanced squamous cell carcinoma of the head and neck. For postoperative patients at high risk of recurrence, however, surgery by itself is not enough, and improvement in survival requires postoperative treatment. Unlike the case with most other malignancies, the standard postoperative treatment for locally advanced squamous cell carcinoma of the head and neck patients with high-risk factors for recurrence is radiotherapy or chemoradiotherapy with cisplatin. However, chemoradiotherapy with cisplatin at a dose of 100 mg/m 2 once every 3 weeks has raised discussion over insufficient cisplatin delivery due to highdose-related toxicity. As a possible solution, a recent randomized trial of the JCOG1008 has proved the non-inferiority of postoperative chemoradiotherapy with weekly cisplatin at a dose of 40 mg/m 2 to 3-weekly cisplatin in terms of overall survival. Here, this review article focuses on current evidence and future perspectives of postoperative treatment for locally advanced squamous cell carcinoma of the head and neck.
PURPOSE The standard treatment for postoperative high-risk locally advanced squamous cell carcino... more PURPOSE The standard treatment for postoperative high-risk locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) is chemoradiotherapy with 3-weekly cisplatin (100 mg/m 2). However, whether chemoradiotherapy with weekly cisplatin (40 mg/m 2) yields comparable efficacy with 3-weekly cisplatin in postoperative high-risk LA-SCCHN is unknown. PATIENTS AND METHODS In this multi-institutional open-label phase II/III trial, patients with postoperative high-risk LA-SCCHN were randomly assigned to receive either chemoradiotherapy with 3-weekly cisplatin (100 mg/m 2) or with weekly cisplatin (40 mg/m 2) to confirm the noninferiority of weekly cisplatin. The primary end point of phase II was the proportion of treatment completion, and that of phase III was overall survival. A noninferiority margin of hazard ratio was set at 1.32. RESULTS Between October 2012 and December 2018, a total of 261 patients were enrolled (3-weekly cisplatin, 132 patients; weekly cisplatin, 129 patients). At the planned third interim analysis in the phase III part, after a median follow-up of 2.2 (interquartile range 1.19-3.56) years, chemoradiotherapy with weekly cisplatin was noninferior to 3-weekly cisplatin in terms of overall survival, with a hazard ratio of 0.69 (99.1% CI, 0.374 to 1.273 [, 1.32], one-sided P for noninferiority 5 .0027 , .0043). Grade 3 or more neutropenia and infection were less frequent in the weekly arm (3-weekly v weekly, 49% v 35% and 12% v 7%, respectively), as were renal impairment and hearing impairment. No treatment-related death was reported in the 3-weekly arm, and two (1.6%) in the weekly arm. CONCLUSION Chemoradiotherapy with weekly cisplatin is noninferior to 3-weekly cisplatin for patients with postoperative high-risk LA-SCCHN. These findings suggest that chemoradiotherapy with weekly cisplatin can be a possible treatment option for these patients.
BACKGROUND: Radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) is an aggressive for... more BACKGROUND: Radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) is an aggressive form of thyroid cancer. Lenvatinib is a multikinase inhibitor approved for treatment of RAI-R DTC. The impact of tumor response and tumor burden on overall survival (OS) after lenvatinib treatment in patients with RAI-R DTC was assessed. METHODS: Data from patients treated with lenvatinib (N = 261) in SELECT were retrospectively analyzed. Patients were divided into lenvatinib responder or nonresponder subgroups and into low (≤40 mm) or high (>40 mm) tumor burden subgroups based on baseline sums of diameters of target lesions using Response Evaluation Criteria in Solid Tumors, version 1.1 (cutoff values were determined by receiver-operating characteristic analyses). Associations of tumor response and tumor burden with OS were assessed. RESULTS: Median OS was prolonged in lenvatinib responders versus nonresponders (52.2 vs 19.0 months; hazard ratio [HR], 0.32; 95% CI, 0.23-0.46). Patients with a lower tumor burden who received lenvatinib had prolonged OS versus those with a higher tumor burden (median OS, not reached vs 29.1 months, respectively; HR, 0.42; 95% CI, 0.28-0.63). Baseline tumor burden was associated with OS by multivariate analysis (HR, 0.56; 95% CI, 0.35-0.89; P = .0138). CONCLUSIONS: Patients with a lower tumor burden receiving lenvatinib had prolonged OS compared with those with a higher tumor burden receiving lenvatinib. Baseline tumor burden may be a prognostic factor for OS in patients with RAI-R DTC treated with lenvatinib.
Assessments of patient-reported outcomes and health-related quality of life in cancer clinical tr... more Assessments of patient-reported outcomes and health-related quality of life in cancer clinical trials have been increasingly emphasized recently because patient and public involvement in cancer treatment development has been promoted by regulatory authorities and academic societies. To assess patient experiences during and after cancer treatment, there is interest in implementing patient-reported outcome and health-related quality of life assessments into cancer clinical trials. The Japan Clinical Oncology Group quality of life ad hoc committee previously created a version of the Quality of Life Assessment Policy in 2006. Recently, there has been increasing demand from Japan Clinical Oncology Group researchers to assess patient-reported outcome/healthrelated quality of life in clinical trials. Although guidelines are available regarding planning and reporting clinical trials that include patient-reported outcome/health-related quality of life as an endpoint, there are still issues regarding the lack of consensus on standardized methods for analysing and interpreting the results. Hence, it was considered necessary to reorganize the Japan Clinical Oncology Group patient-reported outcome/quality of life research committee and to revise the former patient-reported outcome/quality of life research policy to promote patient-reported outcome/health-related quality of life research in future Japan Clinical Oncology Group trials. The purpose of this Japan Clinical Oncology Group patient-reported outcome/quality of life research policy is to define patient-reported outcome/health-related quality of life research and provide guidelines for including patient-reported outcome/health-related quality of life as an endpoint in Japan Clinical Oncology Group trials.
Background Chemoradiotherapy (CRT) with concurrent cisplatin is the standard of care as a nonsurg... more Background Chemoradiotherapy (CRT) with concurrent cisplatin is the standard of care as a nonsurgical definitive treatment for patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, CRT is associated with increased severe late adverse events, including swallowing dysfunction, xerostomia, ototoxicity, and hypothyroidism. Few strategies aimed at less invasive CRT without compromising treatment outcomes have been successful. The purpose of this study is to confirm the non-inferiority of reduced dose prophylactic radiation with 40 Gy compared to standard dose prophylactic radiation with 56 Gy in terms of the time to treatment failure (TTF) among patients with clinical stage III-IVB LA-SCCHN.
Surgery remains a foundation of treatment for locally advanced squamous cell carcinoma of the hea... more Surgery remains a foundation of treatment for locally advanced squamous cell carcinoma of the head and neck. For postoperative patients at high risk of recurrence, however, surgery by itself is not enough, and improvement in survival requires postoperative treatment. Unlike the case with most other malignancies, the standard postoperative treatment for locally advanced squamous cell carcinoma of the head and neck patients with high-risk factors for recurrence is radiotherapy or chemoradiotherapy with cisplatin. However, chemoradiotherapy with cisplatin at a dose of 100 mg/m 2 once every 3 weeks has raised discussion over insufficient cisplatin delivery due to highdose-related toxicity. As a possible solution, a recent randomized trial of the JCOG1008 has proved the non-inferiority of postoperative chemoradiotherapy with weekly cisplatin at a dose of 40 mg/m 2 to 3-weekly cisplatin in terms of overall survival. Here, this review article focuses on current evidence and future perspectives of postoperative treatment for locally advanced squamous cell carcinoma of the head and neck.
Encorafenib plus binimetinib showed promising efficacy for the patients with BRAF mutated thyroid... more Encorafenib plus binimetinib showed promising efficacy for the patients with BRAF mutated thyroid cancer.
International Journal of Clinical Oncology, Nov 29, 2020
Background To promote precision oncology in clinical practice, the Japanese Society of Medical On... more Background To promote precision oncology in clinical practice, the Japanese Society of Medical Oncology, the Japanese Society of Clinical Oncology, and the Japanese Cancer Association, jointly published "Clinical practice guidance for nextgeneration sequencing in cancer diagnosis and treatment" in 2017. Since new information on cancer genomic medicine has emerged since the 1st edition of the guidance was released, including reimbursement for NGS-based multiplex gene panel tests in 2019, the guidance revision was made. Methods A working group was organized with 33 researchers from cancer genomic medicine designated core hospitals and other academic institutions. For an impartial evaluation of the draft version, eight committee members from each society conducted an external evaluation. Public comments were also made on the draft. The finalized Japanese version was published on the websites of the three societies in March 2020. Results The revised edition consists of two parts: an explanation of the cancer genomic profiling test (General Discussion) and clinical questions (CQs) that are of concern in clinical practice. Particularly, patient selection should be based on the expectation that the patient's post-test general condition and organ function will be able to tolerate drug therapy, and the optimal timing of test should be considered in consideration of subsequent treatment plans, not limited to treatment lines. Conclusion We expect that the revised version will be used by healthcare professionals and will also need to be continually reviewed in line with future developments in cancer genome medicine.
BackgroundSquamous cell carcinoma of the external auditory canal (EACSCC) is a rare condition. Ho... more BackgroundSquamous cell carcinoma of the external auditory canal (EACSCC) is a rare condition. However, a standard treatment has not yet been established. We retrospectively evaluated the efficacy, adverse events, and feasibility of TPF‐CCRT (concomitant chemoradiotherapy with docetaxel, cisplatin, and 5‐fluorouracil) in patients with advanced EACSCC.MethodsThirty‐five consecutive patients with advanced EACSCC (T3, T4) initially treated with TPF‐CCRT at Kobe University Hospital were included. T4 diseases with invasion of the brain, internal carotid artery, or internal jugular vein were classified as T4b, and those without these features were classified as T4a.ResultsFive‐year overall survival rates for T3 and T4 were 100% and 64.2%, respectively. A significant difference was observed between T4a and T4b (82.4% vs. 30%, p = 0.007). Five‐year progression‐free survival rates of T3, T4a, and T4b were 100%, 68%, and 20% (p = 0.022), respectively.ConclusionsTPF‐CCRT should be considered as a plausible treatment option for advanced EACSCC.
Purpose/Objectives: Salivary gland cancer (SGC) is a rare malignancy with various pathological ty... more Purpose/Objectives: Salivary gland cancer (SGC) is a rare malignancy with various pathological types. Although immune checkpoint inhibitors for SGC have been investigated in clinical trials, details of the tumor immune microenvironment (TIME) in SGC remain unclear. The aim of this study was to elucidate the TIME of SGC. Materials/Methods: We selected five typical pathological types of SGC, namely adenoid cystic carcinoma (ACC); adenocarcinoma, not otherwise specified (ANOS); salivary duct carcinoma (SDC); and low/high-grade mucoepidermoid carcinoma (MEC low/high). We investigated the TIME as well as the tumor mutation burden (TMB) of each pathological type in surgical archival tissues obtained from 1999 to 2017 (7 patients in each type, stage III/IVA/IVB [UICC 8th]). TIME was evaluated by multiplexed immunofluorescent staining, including CD3, CD4, CD8, Foxp3, CD204, PD-1, PD-L1, and PD-L2. Tumors with > 1% tumor cells expressing PD-L1 were considered positive for PD-L1. TMB was measured by the Oncomine Tumor Mutation Load Assay, and a high TMB was defined by 10 or more mutations/Mb. Correlation analyses were performed using Pearson’s product moment correlation coefficient. Results: Multiplexed immunofluorescent staining was performed in all 35 archival tissues. ACC showed the lowest infiltration of immune effector cells (ICeff) and suppressor cells (ICsup) in both the tumor and stroma, and a low proportion of cases was positive for PD-L1 (14%). Compared with ACC, MEC high showed higher infiltration of ICeff and ICsup in both the tumor and stroma, and a higher proportion of cases was positive for PD-L1 (71%). Although ANOS, SDC, and MEC low showed modest infiltration of ICeff in the tumor, these subtypes showed higher infiltration of ICeff in the stroma than ACC. TMB was measured in 29 samples; the proportion of TMB high was lower in ACC (33%) and MEC low (0%) than in the other pathological types (ANOS/SDC/MEC high: 60/67/57%). Regarding multiplexed immunofluorescent staining, correlation analysis showed a positive correlation between TMB and CD3+CD8+ T cells in the tumor (r=0.647, P<0.0001). In addition, CD3+CD8+ T cells in the tumor showed a positive correlation with PD-L1 expression in tumor cells (r=0.513, P=0.002) and with CD3+CD4+Foxp3+ T cells in the tumor (r=0.399, P=0.018). However, no correlation was seen between CD3+CD8+ T cells and CD204+ cells in the tumor (r=-0.049, P=0.779). Conclusion: ACC showed less PD-L1 expression in tumor cells and the lowest infiltration of immune cells in both the tumor and stroma compared with other pathological types. These results suggest that the TIME of ACC is the so-called immune desert type, which may in turn explain the mechanisms of the poor response to immune check point inhibitors seen in clinical trials. Citation Format: Yoshiaki Nagatani, Naomi Kiyota, Yoshinori Imamura, Taiji Koyama, Yohei Funakoshi, Masato Komatsu, Masanori Teshima, Ken-Ichi Nibu, Kazuko Sakai, Kazuto Nishio, Manami Shimomura, Tetsuya Nakatsura, Daiki Ikarashi, Takayuki Nakayama, Shigehisa Kitano, Hironobu Minami. Tumor immune microenvironment in salivary gland cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6143.
Japanese Journal of Clinical Oncology, Apr 5, 2022
It was not until around 2000 that human papillomavirus-related oropharyngeal carcinoma was recogn... more It was not until around 2000 that human papillomavirus-related oropharyngeal carcinoma was recognized as carcinoma with clinical presentations different from nonrelated head and neck carcinoma. Twenty years after and with the revision of the tumor–node–metastasis classification in 2017, various clinical trials focused on human papillomavirus-related oropharyngeal carcinoma to improve the prognosis and quality of life of patients with this disease. However, the incidence of human papillomavirus-related cancers is increasing, which is expected to be particularly prominent in Japan, where human papillomavirus vaccination is not widely available. In this review, we describe the current status of clinical trials (mainly focused on initial surgery and radiation dose reduction) for, primary and secondary prevention of, and the present status of human papillomavirus-related oropharyngeal carcinoma in Japan.
Regorafenib is an oral multi-kinase inhibitor which targets tumor angiogenesis, the tumor microen... more Regorafenib is an oral multi-kinase inhibitor which targets tumor angiogenesis, the tumor microenvironment and oncogenesis. Based on this mode of action, regorafenib has a broad spectrum of toxicities. However, at present, few reports have focused on autoimmune adverse events. We report a first case of regorafenib-induced exacerbation of chronic immune thrombocytopenic purpura in remission during treatment for the patients with heavily treated advanced colorectal cancer. This case report highlights the need for caution with regard to regorafenib treatment in patients with cancer with concomitant immune thrombocytopenic purpura.
Assessments of patient-reported outcomes and health-related quality of life in cancer clinical tr... more Assessments of patient-reported outcomes and health-related quality of life in cancer clinical trials have been increasingly emphasized recently because patient and public involvement in cancer treatment development has been promoted by regulatory authorities and academic societies. To assess patient experiences during and after cancer treatment, there is interest in implementing patient-reported outcome and health-related quality of life assessments into cancer clinical trials. The Japan Clinical Oncology Group quality of life ad hoc committee previously created a version of the Quality of Life Assessment Policy in 2006. Recently, there has been increasing demand from Japan Clinical Oncology Group researchers to assess patient-reported outcome/healthrelated quality of life in clinical trials. Although guidelines are available regarding planning and reporting clinical trials that include patient-reported outcome/health-related quality of life as an endpoint, there are still issues regarding the lack of consensus on standardized methods for analysing and interpreting the results. Hence, it was considered necessary to reorganize the Japan Clinical Oncology Group patient-reported outcome/quality of life research committee and to revise the former patient-reported outcome/quality of life research policy to promote patient-reported outcome/health-related quality of life research in future Japan Clinical Oncology Group trials. The purpose of this Japan Clinical Oncology Group patient-reported outcome/quality of life research policy is to define patient-reported outcome/health-related quality of life research and provide guidelines for including patient-reported outcome/health-related quality of life as an endpoint in Japan Clinical Oncology Group trials.
Purpose The purpose of this study was to investigate the impact of the type of data capture on th... more Purpose The purpose of this study was to investigate the impact of the type of data capture on the time and help needed for collecting patient-reported outcomes as well as on the proportion of missing scores. Methods In a multinational prospective study, thyroid cancer patients from 17 countries completed a validated questionnaire measuring quality of life. Electronic data capture was compared to the paper-based approach using multivariate logistic regression. Results A total of 437 patients were included, of whom 13% used electronic data capture. The relation between data capture and time needed was modified by the emotional functioning of the patients. Those with clinical impairments in that respect needed more time to complete the questionnaire when they used electronic data capture compared to paper and pencil (OR adj 24.0; p = 0.006). This was not the case when patients had sub-threshold emotional problems (OR adj 1.9; p = 0.48). The odds of having the researcher reading the questions out (instead of the patient doing this themselves) (OR adj 0.1; p = 0.01) and of needing any help (OR adj 0.1; p = 0.01) were lower when electronic data capture was used. The proportion of missing scores was equivalent in both groups (OR adj 0.4, p = 0.42). Conclusions The advantages of electronic data capture, such as real-time assessment and fewer data entry errors, may come at the price of more time required for data collection when the patients have mental health problems. As this is not uncommon in thyroid cancer, researchers need to choose the type of data capture wisely for their particular research question.
Background: Driver mutations at BRAF V600 are frequently identified in papillary thyroid cancer a... more Background: Driver mutations at BRAF V600 are frequently identified in papillary thyroid cancer and anaplastic thyroid cancer (ATC), in which BRAF inhibitors have shown clinical effectiveness. This Japanese phase 2 study evaluated the efficacy and safety of a BRAF inhibitor, encorafenib, combined with an MEK inhibitor, binimetinib, in patients with BRAF V600-mutated thyroid cancer. Methods: This phase 2, open-label, uncontrolled study was conducted at 10 institutions targeted patients with BRAF V600-mutated locally advanced or distant metastatic thyroid cancer not amenable to curative treatment who became refractory/intolerant to ‡1 previous vascular endothelial growth factor receptor-targeted regimen(s) or were considered ineligible for those. The primary endpoint was centrally assessed objective response rate (ORR). The secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: We enrolled 22 patients with BRAF V600E -mutated thyroid cancer: 17 had differentiated thyroid cancer (DTC), and 5 had ATC. At data cutoff (October 26, 2022), the median follow-up was 11.5 (range = 3.4-19.0) months. The primary endpoint of centrally assessed ORR was 54.5% (95% confidence interval [CI] 32.2-75.6; partial response in 12 patients and stable disease in 10). The ORRs in patients with DTC and ATC were 47.1% (8 of 17) and 80.0% (4 of 5), respectively. The medians for DOR and PFS by central assessment and for OS were not reached in the overall population, the DTC subgroup, or the ATC subgroup. At 12 months, the rate of ongoing response was 90.9%, and the PFS and OS rates were 78.8% and 81.8%, respectively. All patients developed ‡1 adverse events (AEs): grade 3 AEs in 6 patients (27.3%). No patients developed grade 4-5 AEs. The most common grade 3 AE was lipase increased (4 patients [18.2%]). Those toxicities were mostly manageable with appropriate monitoring and dose adjustment. Conclusions: Treatment with encorafenib plus binimetinib met the primary endpoint criteria and demonstrated clinical benefit in patients with BRAF V600E -mutated thyroid cancer regardless of its histological type, such as
Surgery remains a foundation of treatment for locally advanced squamous cell carcinoma of the hea... more Surgery remains a foundation of treatment for locally advanced squamous cell carcinoma of the head and neck. For postoperative patients at high risk of recurrence, however, surgery by itself is not enough, and improvement in survival requires postoperative treatment. Unlike the case with most other malignancies, the standard postoperative treatment for locally advanced squamous cell carcinoma of the head and neck patients with high-risk factors for recurrence is radiotherapy or chemoradiotherapy with cisplatin. However, chemoradiotherapy with cisplatin at a dose of 100 mg/m 2 once every 3 weeks has raised discussion over insufficient cisplatin delivery due to highdose-related toxicity. As a possible solution, a recent randomized trial of the JCOG1008 has proved the non-inferiority of postoperative chemoradiotherapy with weekly cisplatin at a dose of 40 mg/m 2 to 3-weekly cisplatin in terms of overall survival. Here, this review article focuses on current evidence and future perspectives of postoperative treatment for locally advanced squamous cell carcinoma of the head and neck.
The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life En... more The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) initiative was established in 2016 to assess the quality and standardization of patientreported outcomes (PRO) data analysis in randomized controlled trials (RCTs) on advanced breast cancer. The initiative identified deficiencies in PRO data reporting, including nonstandardized methods for handling missing data. This study evaluated the reporting of health-related quality of life (HRQOL) in Japanese cancer RCTs to provide insights into the state of PRO reporting in Japan. The study reviewed PubMed articles published from 2010 to 2018. Eligible studies included Japanese cancer RCTs with ≥50 adult patients (≥50% were Japanese) with solid tumors receiving anticancer treatments. The evaluation criteria included clarity of the HRQOL hypotheses, multiplicity testing, primary analysis methods, and reporting of clinically meaningful differences. Twenty-seven HRQOL trials were identified. Only 15% provided a clear HRQOL hypothesis, and 63% examined multiple HRQOL domains without adjusting for multiplicity. Model-based methods were the most common statistical methods for the primary HRQOL analysis. Only 22% of the trials explicitly reported clinically meaningful differences in HRQOL. Baseline assessments were reported in most trials, but only 26% reported comparisons between the treatment groups. HRQOL analysis was based on the intention-to-treat population in 19% of the trials, and 74% reported compliance at follow-up; however, 41% did not specify how missing values were handled. Although the rates of reporting clinical hypotheses and clinically meaningful differences were relatively low, the current state of HRQOL evaluation in the Japanese cancer RCT appears comparable to that of previous studies. Categories: Oncology, Quality Improvement Keywords: health-related quality of life (hrqol), randomized trials, pro, hrqol, randomized controlled trial, statistical methods, health-related quality of life, patient reported outcomes 1 1 2 3 4 5
Background: In a randomized phase II/III trial (JCOG1008), weekly cisplatin (40 mg/m 2 ) was non-... more Background: In a randomized phase II/III trial (JCOG1008), weekly cisplatin (40 mg/m 2 ) was non-inferior to 3-weekly cisplatin (100 mg/m 2 ) for postoperative high-risk head and neck cancer. We investigated how acute kidney injury (AKI), a major dose-limiting toxicity effect of cisplatin, affects overall survival (OS). We analyzed 251 patients from JCOG1008 receiving chemoradiotherapy. AKI was defined based on AKI Network criteria (serum creatinine increase of ≥0.3 mg/dL or ≥1.5fold [≥ stage I]) within 30 days after completing chemoradiotherapy. OS in the two arms was compared according to AKI development using the log-rank test. The total incidence of AKI was lower in the weekly arm than in the 3-weekly arm (38/122 [31.1%] vs. 56/129 [43.4%]). Additionally, stage II/III AKI occurred less frequently in the weekly arm than in the 3-weekly arm (8/122 [6.6%] vs. 19/129 [14.7%]). Cisplatin doses were similar in the weekly arm for patients with and without AKI (median, 238.6 mg/m 2 vs. 239.2 mg/m 2 ; p = 0.94), but lower in the 3-weekly arm for those who developed AKI (median, 276.3 mg/ m 2 vs. 297.4 mg/m 2 ; p = 0.007). In the weekly arm, there was no difference in OS between patients with and without AKI (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.53 to 2.10). However, in the 3-weekly arm, patients with AKI had poorer OS than those without AKI (HR, 1.83; 95% CI, 1.04 to 3.21). In this supplementary analysis of JCOG1008 data, AKI impacted the OS of patients with head and neck cancer undergoing postoperative chemoradiotherapy in the 3-weekly arm but not in the weekly arm. Our results further endorse the utilization of weekly cisplatin at 40 mg/m 2 in this setting.
Japanese journal of clinical oncology, Mar 7, 2024
Surgery remains a foundation of treatment for locally advanced squamous cell carcinoma of the hea... more Surgery remains a foundation of treatment for locally advanced squamous cell carcinoma of the head and neck. For postoperative patients at high risk of recurrence, however, surgery by itself is not enough, and improvement in survival requires postoperative treatment. Unlike the case with most other malignancies, the standard postoperative treatment for locally advanced squamous cell carcinoma of the head and neck patients with high-risk factors for recurrence is radiotherapy or chemoradiotherapy with cisplatin. However, chemoradiotherapy with cisplatin at a dose of 100 mg/m 2 once every 3 weeks has raised discussion over insufficient cisplatin delivery due to highdose-related toxicity. As a possible solution, a recent randomized trial of the JCOG1008 has proved the non-inferiority of postoperative chemoradiotherapy with weekly cisplatin at a dose of 40 mg/m 2 to 3-weekly cisplatin in terms of overall survival. Here, this review article focuses on current evidence and future perspectives of postoperative treatment for locally advanced squamous cell carcinoma of the head and neck.
PURPOSE The standard treatment for postoperative high-risk locally advanced squamous cell carcino... more PURPOSE The standard treatment for postoperative high-risk locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) is chemoradiotherapy with 3-weekly cisplatin (100 mg/m 2). However, whether chemoradiotherapy with weekly cisplatin (40 mg/m 2) yields comparable efficacy with 3-weekly cisplatin in postoperative high-risk LA-SCCHN is unknown. PATIENTS AND METHODS In this multi-institutional open-label phase II/III trial, patients with postoperative high-risk LA-SCCHN were randomly assigned to receive either chemoradiotherapy with 3-weekly cisplatin (100 mg/m 2) or with weekly cisplatin (40 mg/m 2) to confirm the noninferiority of weekly cisplatin. The primary end point of phase II was the proportion of treatment completion, and that of phase III was overall survival. A noninferiority margin of hazard ratio was set at 1.32. RESULTS Between October 2012 and December 2018, a total of 261 patients were enrolled (3-weekly cisplatin, 132 patients; weekly cisplatin, 129 patients). At the planned third interim analysis in the phase III part, after a median follow-up of 2.2 (interquartile range 1.19-3.56) years, chemoradiotherapy with weekly cisplatin was noninferior to 3-weekly cisplatin in terms of overall survival, with a hazard ratio of 0.69 (99.1% CI, 0.374 to 1.273 [, 1.32], one-sided P for noninferiority 5 .0027 , .0043). Grade 3 or more neutropenia and infection were less frequent in the weekly arm (3-weekly v weekly, 49% v 35% and 12% v 7%, respectively), as were renal impairment and hearing impairment. No treatment-related death was reported in the 3-weekly arm, and two (1.6%) in the weekly arm. CONCLUSION Chemoradiotherapy with weekly cisplatin is noninferior to 3-weekly cisplatin for patients with postoperative high-risk LA-SCCHN. These findings suggest that chemoradiotherapy with weekly cisplatin can be a possible treatment option for these patients.
BACKGROUND: Radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) is an aggressive for... more BACKGROUND: Radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) is an aggressive form of thyroid cancer. Lenvatinib is a multikinase inhibitor approved for treatment of RAI-R DTC. The impact of tumor response and tumor burden on overall survival (OS) after lenvatinib treatment in patients with RAI-R DTC was assessed. METHODS: Data from patients treated with lenvatinib (N = 261) in SELECT were retrospectively analyzed. Patients were divided into lenvatinib responder or nonresponder subgroups and into low (≤40 mm) or high (>40 mm) tumor burden subgroups based on baseline sums of diameters of target lesions using Response Evaluation Criteria in Solid Tumors, version 1.1 (cutoff values were determined by receiver-operating characteristic analyses). Associations of tumor response and tumor burden with OS were assessed. RESULTS: Median OS was prolonged in lenvatinib responders versus nonresponders (52.2 vs 19.0 months; hazard ratio [HR], 0.32; 95% CI, 0.23-0.46). Patients with a lower tumor burden who received lenvatinib had prolonged OS versus those with a higher tumor burden (median OS, not reached vs 29.1 months, respectively; HR, 0.42; 95% CI, 0.28-0.63). Baseline tumor burden was associated with OS by multivariate analysis (HR, 0.56; 95% CI, 0.35-0.89; P = .0138). CONCLUSIONS: Patients with a lower tumor burden receiving lenvatinib had prolonged OS compared with those with a higher tumor burden receiving lenvatinib. Baseline tumor burden may be a prognostic factor for OS in patients with RAI-R DTC treated with lenvatinib.
Assessments of patient-reported outcomes and health-related quality of life in cancer clinical tr... more Assessments of patient-reported outcomes and health-related quality of life in cancer clinical trials have been increasingly emphasized recently because patient and public involvement in cancer treatment development has been promoted by regulatory authorities and academic societies. To assess patient experiences during and after cancer treatment, there is interest in implementing patient-reported outcome and health-related quality of life assessments into cancer clinical trials. The Japan Clinical Oncology Group quality of life ad hoc committee previously created a version of the Quality of Life Assessment Policy in 2006. Recently, there has been increasing demand from Japan Clinical Oncology Group researchers to assess patient-reported outcome/healthrelated quality of life in clinical trials. Although guidelines are available regarding planning and reporting clinical trials that include patient-reported outcome/health-related quality of life as an endpoint, there are still issues regarding the lack of consensus on standardized methods for analysing and interpreting the results. Hence, it was considered necessary to reorganize the Japan Clinical Oncology Group patient-reported outcome/quality of life research committee and to revise the former patient-reported outcome/quality of life research policy to promote patient-reported outcome/health-related quality of life research in future Japan Clinical Oncology Group trials. The purpose of this Japan Clinical Oncology Group patient-reported outcome/quality of life research policy is to define patient-reported outcome/health-related quality of life research and provide guidelines for including patient-reported outcome/health-related quality of life as an endpoint in Japan Clinical Oncology Group trials.
Background Chemoradiotherapy (CRT) with concurrent cisplatin is the standard of care as a nonsurg... more Background Chemoradiotherapy (CRT) with concurrent cisplatin is the standard of care as a nonsurgical definitive treatment for patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, CRT is associated with increased severe late adverse events, including swallowing dysfunction, xerostomia, ototoxicity, and hypothyroidism. Few strategies aimed at less invasive CRT without compromising treatment outcomes have been successful. The purpose of this study is to confirm the non-inferiority of reduced dose prophylactic radiation with 40 Gy compared to standard dose prophylactic radiation with 56 Gy in terms of the time to treatment failure (TTF) among patients with clinical stage III-IVB LA-SCCHN.
Surgery remains a foundation of treatment for locally advanced squamous cell carcinoma of the hea... more Surgery remains a foundation of treatment for locally advanced squamous cell carcinoma of the head and neck. For postoperative patients at high risk of recurrence, however, surgery by itself is not enough, and improvement in survival requires postoperative treatment. Unlike the case with most other malignancies, the standard postoperative treatment for locally advanced squamous cell carcinoma of the head and neck patients with high-risk factors for recurrence is radiotherapy or chemoradiotherapy with cisplatin. However, chemoradiotherapy with cisplatin at a dose of 100 mg/m 2 once every 3 weeks has raised discussion over insufficient cisplatin delivery due to highdose-related toxicity. As a possible solution, a recent randomized trial of the JCOG1008 has proved the non-inferiority of postoperative chemoradiotherapy with weekly cisplatin at a dose of 40 mg/m 2 to 3-weekly cisplatin in terms of overall survival. Here, this review article focuses on current evidence and future perspectives of postoperative treatment for locally advanced squamous cell carcinoma of the head and neck.
Encorafenib plus binimetinib showed promising efficacy for the patients with BRAF mutated thyroid... more Encorafenib plus binimetinib showed promising efficacy for the patients with BRAF mutated thyroid cancer.
International Journal of Clinical Oncology, Nov 29, 2020
Background To promote precision oncology in clinical practice, the Japanese Society of Medical On... more Background To promote precision oncology in clinical practice, the Japanese Society of Medical Oncology, the Japanese Society of Clinical Oncology, and the Japanese Cancer Association, jointly published "Clinical practice guidance for nextgeneration sequencing in cancer diagnosis and treatment" in 2017. Since new information on cancer genomic medicine has emerged since the 1st edition of the guidance was released, including reimbursement for NGS-based multiplex gene panel tests in 2019, the guidance revision was made. Methods A working group was organized with 33 researchers from cancer genomic medicine designated core hospitals and other academic institutions. For an impartial evaluation of the draft version, eight committee members from each society conducted an external evaluation. Public comments were also made on the draft. The finalized Japanese version was published on the websites of the three societies in March 2020. Results The revised edition consists of two parts: an explanation of the cancer genomic profiling test (General Discussion) and clinical questions (CQs) that are of concern in clinical practice. Particularly, patient selection should be based on the expectation that the patient's post-test general condition and organ function will be able to tolerate drug therapy, and the optimal timing of test should be considered in consideration of subsequent treatment plans, not limited to treatment lines. Conclusion We expect that the revised version will be used by healthcare professionals and will also need to be continually reviewed in line with future developments in cancer genome medicine.
BackgroundSquamous cell carcinoma of the external auditory canal (EACSCC) is a rare condition. Ho... more BackgroundSquamous cell carcinoma of the external auditory canal (EACSCC) is a rare condition. However, a standard treatment has not yet been established. We retrospectively evaluated the efficacy, adverse events, and feasibility of TPF‐CCRT (concomitant chemoradiotherapy with docetaxel, cisplatin, and 5‐fluorouracil) in patients with advanced EACSCC.MethodsThirty‐five consecutive patients with advanced EACSCC (T3, T4) initially treated with TPF‐CCRT at Kobe University Hospital were included. T4 diseases with invasion of the brain, internal carotid artery, or internal jugular vein were classified as T4b, and those without these features were classified as T4a.ResultsFive‐year overall survival rates for T3 and T4 were 100% and 64.2%, respectively. A significant difference was observed between T4a and T4b (82.4% vs. 30%, p = 0.007). Five‐year progression‐free survival rates of T3, T4a, and T4b were 100%, 68%, and 20% (p = 0.022), respectively.ConclusionsTPF‐CCRT should be considered as a plausible treatment option for advanced EACSCC.
Purpose/Objectives: Salivary gland cancer (SGC) is a rare malignancy with various pathological ty... more Purpose/Objectives: Salivary gland cancer (SGC) is a rare malignancy with various pathological types. Although immune checkpoint inhibitors for SGC have been investigated in clinical trials, details of the tumor immune microenvironment (TIME) in SGC remain unclear. The aim of this study was to elucidate the TIME of SGC. Materials/Methods: We selected five typical pathological types of SGC, namely adenoid cystic carcinoma (ACC); adenocarcinoma, not otherwise specified (ANOS); salivary duct carcinoma (SDC); and low/high-grade mucoepidermoid carcinoma (MEC low/high). We investigated the TIME as well as the tumor mutation burden (TMB) of each pathological type in surgical archival tissues obtained from 1999 to 2017 (7 patients in each type, stage III/IVA/IVB [UICC 8th]). TIME was evaluated by multiplexed immunofluorescent staining, including CD3, CD4, CD8, Foxp3, CD204, PD-1, PD-L1, and PD-L2. Tumors with > 1% tumor cells expressing PD-L1 were considered positive for PD-L1. TMB was measured by the Oncomine Tumor Mutation Load Assay, and a high TMB was defined by 10 or more mutations/Mb. Correlation analyses were performed using Pearson’s product moment correlation coefficient. Results: Multiplexed immunofluorescent staining was performed in all 35 archival tissues. ACC showed the lowest infiltration of immune effector cells (ICeff) and suppressor cells (ICsup) in both the tumor and stroma, and a low proportion of cases was positive for PD-L1 (14%). Compared with ACC, MEC high showed higher infiltration of ICeff and ICsup in both the tumor and stroma, and a higher proportion of cases was positive for PD-L1 (71%). Although ANOS, SDC, and MEC low showed modest infiltration of ICeff in the tumor, these subtypes showed higher infiltration of ICeff in the stroma than ACC. TMB was measured in 29 samples; the proportion of TMB high was lower in ACC (33%) and MEC low (0%) than in the other pathological types (ANOS/SDC/MEC high: 60/67/57%). Regarding multiplexed immunofluorescent staining, correlation analysis showed a positive correlation between TMB and CD3+CD8+ T cells in the tumor (r=0.647, P<0.0001). In addition, CD3+CD8+ T cells in the tumor showed a positive correlation with PD-L1 expression in tumor cells (r=0.513, P=0.002) and with CD3+CD4+Foxp3+ T cells in the tumor (r=0.399, P=0.018). However, no correlation was seen between CD3+CD8+ T cells and CD204+ cells in the tumor (r=-0.049, P=0.779). Conclusion: ACC showed less PD-L1 expression in tumor cells and the lowest infiltration of immune cells in both the tumor and stroma compared with other pathological types. These results suggest that the TIME of ACC is the so-called immune desert type, which may in turn explain the mechanisms of the poor response to immune check point inhibitors seen in clinical trials. Citation Format: Yoshiaki Nagatani, Naomi Kiyota, Yoshinori Imamura, Taiji Koyama, Yohei Funakoshi, Masato Komatsu, Masanori Teshima, Ken-Ichi Nibu, Kazuko Sakai, Kazuto Nishio, Manami Shimomura, Tetsuya Nakatsura, Daiki Ikarashi, Takayuki Nakayama, Shigehisa Kitano, Hironobu Minami. Tumor immune microenvironment in salivary gland cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6143.
Japanese Journal of Clinical Oncology, Apr 5, 2022
It was not until around 2000 that human papillomavirus-related oropharyngeal carcinoma was recogn... more It was not until around 2000 that human papillomavirus-related oropharyngeal carcinoma was recognized as carcinoma with clinical presentations different from nonrelated head and neck carcinoma. Twenty years after and with the revision of the tumor–node–metastasis classification in 2017, various clinical trials focused on human papillomavirus-related oropharyngeal carcinoma to improve the prognosis and quality of life of patients with this disease. However, the incidence of human papillomavirus-related cancers is increasing, which is expected to be particularly prominent in Japan, where human papillomavirus vaccination is not widely available. In this review, we describe the current status of clinical trials (mainly focused on initial surgery and radiation dose reduction) for, primary and secondary prevention of, and the present status of human papillomavirus-related oropharyngeal carcinoma in Japan.
Regorafenib is an oral multi-kinase inhibitor which targets tumor angiogenesis, the tumor microen... more Regorafenib is an oral multi-kinase inhibitor which targets tumor angiogenesis, the tumor microenvironment and oncogenesis. Based on this mode of action, regorafenib has a broad spectrum of toxicities. However, at present, few reports have focused on autoimmune adverse events. We report a first case of regorafenib-induced exacerbation of chronic immune thrombocytopenic purpura in remission during treatment for the patients with heavily treated advanced colorectal cancer. This case report highlights the need for caution with regard to regorafenib treatment in patients with cancer with concomitant immune thrombocytopenic purpura.
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Papers by Naomi Kiyota
assess patient experiences during and after cancer treatment, there is interest in implementing patient-reported outcome and health-related quality of life assessments into cancer clinical trials.
The Japan Clinical Oncology Group quality of life ad hoc committee previously created a version of the Quality of Life Assessment Policy in 2006. Recently, there has been increasing demand from Japan Clinical Oncology Group researchers to assess patient-reported outcome/healthrelated quality of life in clinical trials. Although guidelines are available regarding planning and reporting clinical trials that include patient-reported outcome/health-related quality of life as an endpoint, there are still issues regarding the lack of consensus on standardized methods for analysing and interpreting the results. Hence, it was considered necessary to reorganize the Japan Clinical Oncology Group patient-reported outcome/quality of life research committee and to revise the former patient-reported outcome/quality of life research policy to promote patient-reported outcome/health-related quality of life research in future Japan Clinical Oncology Group trials. The purpose of this Japan Clinical Oncology Group patient-reported outcome/quality of life research
policy is to define patient-reported outcome/health-related quality of life research and provide guidelines for including patient-reported outcome/health-related quality of life as an endpoint in Japan Clinical Oncology Group trials.
assess patient experiences during and after cancer treatment, there is interest in implementing patient-reported outcome and health-related quality of life assessments into cancer clinical trials.
The Japan Clinical Oncology Group quality of life ad hoc committee previously created a version of the Quality of Life Assessment Policy in 2006. Recently, there has been increasing demand from Japan Clinical Oncology Group researchers to assess patient-reported outcome/healthrelated quality of life in clinical trials. Although guidelines are available regarding planning and reporting clinical trials that include patient-reported outcome/health-related quality of life as an endpoint, there are still issues regarding the lack of consensus on standardized methods for analysing and interpreting the results. Hence, it was considered necessary to reorganize the Japan Clinical Oncology Group patient-reported outcome/quality of life research committee and to revise the former patient-reported outcome/quality of life research policy to promote patient-reported outcome/health-related quality of life research in future Japan Clinical Oncology Group trials. The purpose of this Japan Clinical Oncology Group patient-reported outcome/quality of life research
policy is to define patient-reported outcome/health-related quality of life research and provide guidelines for including patient-reported outcome/health-related quality of life as an endpoint in Japan Clinical Oncology Group trials.