華井 明子

Purpose Although exercise is recommended for cancer survivors with chemotherapy-induced peripheral neuropathy (CIPN), the effective types of exercise for preventing and treating CIPN remain unclear. This systematic review and network meta-analysis (NMA) aimed to evaluate the comparative effects of exercise on CIPN. Methods We included relevant randomized controlled trials (RCTs) identified in a 2019 systematic review that evaluated the effects of exercise on CIPN and conducted an additional search for RCTs published until 2023. We evaluated the risk of bias for each RCT; the comparative effectiveness of exercise on patient-reported quality of life (QOL) through an NMA; and the effectiveness of exercise on QOL scores, patient-reported CIPN symptoms, and pain through additional meta-analyses. Results Twelve studies (exercise, n = 540; control, n = 527) comparing 8 exercise interventions were included in the analysis. All studies were determined to have a high risk of bias. The meta-analyses showed significantly improved QOL [standard mean differences (SMD) 0.45; 95% confidence interval (CI) = 0.12 to 0.78] and CIPN symptoms (SMD 0.46; 95% CI = 0.11 to 0.82). No severe adverse events were reported. Pain tended to improve with exercise (SMD 0.84; 95% CI = −0.11 to 1.80). An NMA suggested that the interventions of a combination of balance and strength training showed a significant improvement in QOL scores compared to the control. Conclusion Exercise interventions may be beneficial for improving QOL and CIPN symptoms. High-quality large clinical trials and data are needed to conclude that exercise is beneficial and safe.

Purpose: Although treatment outcomes for childhood cancer have improved in recent years, some patients continue to experience physical symptoms and psychological stress several years after the end of treatment. This study aimed to examine the correlation between the quality-of-life (QOL) scores of childhood cancer survivors (CCSs) aged 18-39 and (1) their families and (2) the time since the end of treatment. Methods: Measuring the QOL of CCSs attending the long-term follow-up (LTFU) and those of their families. The Short-Form Health Survey (SF-36) was used for CCSs and the Caregiver Quality of Life Index-Cancer (CQOLC) for their families. Spearman's rank correlation analyses were used to examine the relationship between the CCSs' and their families' QOL and the time since the end of treatment. Results: Twenty-nine CCSs (mean age, 24.2 years; mean the time since the end of treatment, 13.9 years), each paired with one family member, were included. Time since the end of treatment was positively correlated with the CCSs' QOL on the physical component score (ρ = 0.42, p = 0.03) and negatively correlated with mental health (MH) (ρ = -0.50, p = 0.01), a subscale of the mental component score (MCS). Furthermore, the CCSs' QOL on the MCS was positively correlated with their families' QOL scores (ρ = 0.58, p < 0.01). Conclusion: Psychological stress may persist in CCSs long after treatment, even when physical symptoms improve. Therefore, it is necessary to establish a comprehensive support system for the LTFU of CCSs, including MH care and QOL monitoring for patients and their families.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common adverse events that can significantly impair the quality of life of patients. Although limb cooling may be beneficial for preventing CIPN, logistical challenges exist in ensuring consistent efficacy and safety. The purpose of this randomized controlled trial is to validate whether limb cooling with strict temperature control can reduce CIPN in patients with breast cancer receiving weekly paclitaxel as a perioperative treatment. METHODS: This study is a multicenter, double-blinded, randomized controlled trial. We plan to enroll patients with breast cancer who are scheduled to receive 12 weekly doses of paclitaxel (60 min 80 mg/m2 intravenous infusion) as perioperative chemotherapy. Patients will be randomly divided into the intervention or control groups and undergo limb cooling therapy maintained at a constant temperature of 13°C and 25°C, respectively. The primary endpoint is the proportion of patients who report Patient Neurotoxicity Questionnaire (PNQ) ≥ D in their limbs by the end of the study treatment or at the time of discontinuation. DISCUSSION: The results of this trial will contribute to the establishment of new evidence for limb cooling therapy in the mitigation of CIPN and present a safe and stable cooling device that may be suitable for use in the clinic. CLINICAL TRIAL REGISTRATION: https://jrct.niph.go.jp/en-latest-detail/jRCT2032210115, identifier jRCT2032210115.

近年,高齢化や新型コロナウイルスなどの影響で,日常的健康状態モニタリングと,未然に大きな変化を防ぐ予防医療の必要性が高まっている。患者のアウトカム改善と予防医療の実現に向けて,診断だけでなく疾患予防,治療選択,予後予測においても機械学習が導入され,成果を上げつつある。本稿では,ウェアラブルデバイスによる健康状態モニタリング,強化学習を用いた治療選択,機械学習を用いた予後予測という3つのデータ駆動型アプローチを取り上げ,活用事例を紹介するとともに,実臨床への導入に向けた課題を議論する。(著者抄録)

Young adult survivors of childhood cancer may have a perception gap with their families. Patients aged 18-39 years after treatment of cancer and their families (28 pairs) completed a survey that contained questions on health-related quality of life using the 36-item short form survey. There was a significant difference in the role-social component score (mean difference -2.23; p = 0.04) with family reporting higher scores than patients. Families may overestimate the social function of cancer survivors, emphasizing the importance of the long-term follow-up by taking into account the risk of a gap (IRB approval No.: R2257-1).

INTRODUCTION: Although topical use of moisturisers is slightly effective for the prevention and avoiding the aggravation of hand-foot syndrome induced by multikinase inhibitors, there is still room for improvement. Hydrocolloid dressing is a type of wound dressing often used for wounds such as decubitus ulcers. The purpose of this study is to verify the usefulness of application of hydrocolloid dressings as prophylaxis against development of hand-foot syndrome induced by multikinase inhibitors by comparing the effects of this dressing and standard supportive care (moisturising care alone) within the same individuals. METHODS: This study is a phase 3 randomised, self-controlled study to compare prophylactic moisturising care with or without hydrocolloid dressing for hand-foot syndrome induced by multikinase inhibitors. Patients with radically unresectable advanced or recurrent colorectal carcinoma, gastrointestinal stromal tumour and hepatocellular carcinoma who scheduled to receive regorafenib or sorafenib therapy are eligible for enrolment.Supportive care for hand-foot syndrome will consist of basic moisturising care with or without hydrocolloid dressing. If hand-foot syndrome occurs, a steroid ointment will be applied two times per day at the affected sites. The primary endpoint is an incidence rate of grade 2 or more severe hand-foot syndrome (soles of the feet only) assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events V.4.0. Grading of hand-foot syndrome will be performed by central review using photographs taken weekly by blinded trained physicians. The ethical approval was obtained from National Cancer Center Hospital. The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conference. DISCUSSION: If the positive results are found in this study, it is shown that hydrocolloid dressing is effective not only as a symptom management but also as a prevention in hand-foot syndrome induced by multikinase. TRIAL STATUS: The enrolment was started in January 2019, and planned to closed in January 2021. As of February 2020, 26 patients enrolled in this study. TRIAL REGISTRATION NUMBER: UMIN Clinical Trial Registry (UMIN000034853). PROTOCOL VERSION: V.1.4, 9 January 2020.

Health-related web content is constantly increasing, and cancer survivors use it to manage their health and activities of daily living. However, the actual usage of and satisfaction with web contents among cancer survivors is unclear. Therefore, we conducted a web-based cross-sectional survey to understand the satisfaction with web content in those cancer survivors who use the Internet to cope with their anxiety/stress, sleeplessness, or cognitive difficulties. The survey questionnaire was e-mailed to 1.2 million voluntary registrants at a research company. Cancer survivors who accessed any content via the Internet and experienced anxiety/stress, sleeplessness, or cognitive difficulties were included in the study. Out of the 412 survivors who completed the survey, 357 experienced some degree of anxiety or stress, 258 experienced sleeplessness, and 161 experienced some cognitive difficulties, such as forgetfulness or lack of attention. They used web contents to record their health or (n = 205), relieve their anxiety or stress (n = 238), and devise activities of daily living (n = 232) during cancer therapy, including surgery, chemotherapy, and radiation. The web contents included "interactive contents" (users engage with the web content by responding to it in some form), "non-interactive contents" (information medium without any user engagement), "web-storage," or "scrolling." Multivariate logistic regression revealed greater satisfaction with "interactive contents" in cancer survivors. This reflects that the sharing of personal experiences as well as objective information should be considered to create satisfying and effective web contents.

化学療法起因性末梢神経障害(chemotherapy induced peripheral neuropathy:CIPN)は、タキサン系、プラチナ系をはじめとする抗がん薬の副作用として生じる手足のしびれ症状であり、有効な予防法や治療法が確立していない。そのため一度発症すると長期にわたり症状が残存し、歩行能力(転倒リスクの上昇)や就労といった生活活動に障害をきたす。抗がん薬の副作用対策として、副作用を起こす部位への局所冷却が用いられており、脱毛予防や口内炎予防、手足の皮膚・爪障予防の効果が報告されていた。そこで、冷却がCIPN予防に有効であるか、パクリタキセル療法を受ける乳がん患者を対象とした臨床試験による検討を実施した。40症例を対象に利き手側手足に抗がん薬投与15分前から投与終了15分後まで計90分間フローズングローブソックスを装着して、無介入の非利き手側手足と比較した。その結果、モノフィラメントテストで評価した触覚閾値の変化、質問紙により評価した自覚症状、グローブドペグボードテストで評価した手指巧緻性の変化について、臨床的・統計学的に有意な差が得られた。冷却は疼痛、炎症の予防等に広く使用されているが、凍傷のリスクも伴うため、医療者による管理を行うことが望ましい。しかしながら、がん化学療法領域における冷却介入に関しては、現在設備や人的リソースの不足により、普及と実装が実現していない状況である。今後より安全で効果的な標準冷却療法を確立し、広く本予防法を届けることが喫緊の課題である。(著者抄録)

BACKGROUND: Optimal cancer survivorship care needs its comprehensive guidelines. We aimed to identify English and Japanese guidelines that include cancer survivorship in their title, the issues highlighted in such guidelines, and any existing oncology practice guidelines in Japan that address these issues. METHODS: This literature review was performed in three stages. First, guidelines published in English or Japanese that included cancer survivorship in the title were identified. Then, the issues that each cancer survivorship guideline addressed were defined. Lastly, Japanese guidelines that include survivorship issues were sought. RESULTS: Six guidelines published in English addressed 31 cancer survivorship issues. No specific cancer survivorship guideline was available in Japanese. Thirty-four Japanese guidelines mentioned cancer survivorship issues. These guidelines addressed screening/surveillance for detecting recurrence or secondary cancer but did not address coordination of care, implications for practice, or inclusion of family. At present, Japanese guidelines poorly address the issue of promotion of a healthy lifestyle in cancer survivors. Also, poorly addressed were long-term and late effects such as pain, psychological distress, fatigue, cognitive dysfunction, cardiovascular effects (including anthracycline-induced cardiac toxicity), sleep disorders, and sexual dysfunction in cancer survivors. CONCLUSION: There is a need for guidelines on optimal coordination of care between oncologists and other health care providers to support patients along the cancer care continuum and specifically to encourage a healthy lifestyle as part of cancer survivorship. The development of a comprehensive Japanese guideline that addresses these issues would help to improve the clinical outcome for cancer survivors in Japan.

Objectives: Sarcopenia is characterized by loss of muscle strength and mass, leading to falls and adverse health outcomes. Our aim was to determine the prevalence of sarcopenia in patients with rheumatoid arthritis (RA) and to identify factors associated with sarcopenia in these patients. Methods: A cross-sectional study of 388 consecutive women with RA was conducted, assessing muscle mass and strength, and walking speed. Falls and bone fractures sustained over the prior year were evaluated. The association between sarcopenia and RA characteristics, falls, and bone fractures was evaluated using logistic regression analyses. Results: The prevalence of sarcopenia was 37.1% (14.7%, severe sarcopenia; 22.4%, sarcopenia), with 49.0% classified as having low muscle mass. The incidence of falls, fractures, and lower bone mineral density was higher in patients with than without sarcopenia. Age, RA duration, Steinbrocker's stage, the high Mini-Nutritional Assessment-Short Form score and the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) were independent factors associated with sarcopenia. Conclusion: We confirmed that sarcopenia develops in a significant proportion of patients with RA. Age, longer disease duration, joint destruction and malnutrition were positively associated with sarcopenia, with the use of bDMARDs being negatively associated.

京滋摂食嚥下を考える会は地域の食支援体制を構築することを目的に設立され、地域伝統工芸との協業により晴れの日の食事にふさわしい介護食器の開発に取り組んだ。本開発プロジェクトには作業療法士、料亭の女将、デザイナー、陶芸家、漆器老舗といった地域の多職種の人に参加いただいた。各業界におけるルールを尊重しつつ食事を違和感なく楽しめることに主眼をおいて、デザインをすり合わせ機能を保ちながらも京焼・京漆器による意匠をこらした介護食器を完成した。摂食嚥下障害をもつ対象者と家族にこの介護食器を用いた松花堂弁当を提供したところ積極的な摂食がみられ、当事者より高い評価を得た。嚥下食とともに生活する対象者にとって、晴れの日の食事を楽しむ機会は重要であるにもかかわらず、極めて少ないのが現状である。今後より多くの人に食べる喜びを届けられるよう企業連携など発展を検討中である。(著者抄録)

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting and disabling side effect of taxane anticancer agents. We prospectively evaluated the efficacy of cryotherapy for CIPN prevention. Methods: Breast cancer patients treated weekly with paclitaxel (80 mg/m2 for one hour) wore frozen gloves and socks on the dominant side for 90 minutes, including the entire duration of drug infusion. Symptoms on the treated sides were compared with those on the untreated (nondominant) sides. The primary end point was CIPN incidence assessed by changes in tactile sensitivity from pretreatment baseline in a monofilament test at a cumulative dose of 960 mg/m2. We also assessed thermosensory deficits, subjective symptoms (Patient Neuropathy Questionnaire [PNQ]), manipulative dexterity, and the time to events and hazard ratio by PNQ. All statistical tests were two-sided. Results: Among the 40 patients, four did not reach the cumulative dose (due to the occurrence of pneumonia, severe fatigue, severe liver dysfunction, and macular edema), leaving 36 patients for analysis. None dropped out due to cold intolerance. The incidence of objective and subjective CIPN signs was clinically and statistically significantly lower on the intervention side than on the control (hand: tactile sensitivity = 27.8% vs 80.6%, odds ratio [OR] = 20.00, 95% confidence interval [CI] = 3.20 to 828.96, P < .001; foot: tacile sensitivity = 25.0% vs 63.9%, OR = infinite, 95% CI = 3.32 to infinite, P < .001; hand: warm sense = 8.8% vs 32.4%, OR = 9.00, 95% CI = 1.25 to 394.48, P = .02; foot: warm sense: 33.4% vs 57.6%, OR = 5.00, 95% CI = 1.07 to 46.93, P = .04; hand: PNQ = 2.8% vs 41.7%, OR = infinite, 95% CI = 3.32 to infinite, P < .001; foot: PNQ = 2.8% vs 36.1%, OR = infinite, 95% CI = 2.78 to infinite, P < .001; hand: hazard ratio [HR] = 0.13, 95% CI = 0.05 to 0.34; foot: HR = 0.13, 95% CI = 0.04 to 0.38, dexterity mean delay = -2.5 seconds, SD = 12.0 seconds, vs + 8.6 seconds, SD = 25.8 seconds, P = .005). Conclusions: Cryotherapy is useful for preventing both the objective and subjective symptoms of CIPN and resultant dysfunction.

OBJECTIVE: To determine the factors associated with gait parameters in female patients with rheumatoid arthritis (RA). METHODS: The gait analysis was performed in a large cohort of RA patients, and three basic gait parameters (step length, cadence and gait speed) were calculated. Clinical and laboratory data were also collected. Factors associated with gait parameters were analyzed using multivariable linear regression in the three models with forced entry. Then, we divided those patients with Health Assessment Questionnaire disability index (HAQ) scores ≤ 0.5 into two groups according to their gait speed that were compared to identify the characteristics of patients with a good HAQ score but poor walking ability. RESULTS: A total of 318 female patients were analyzed. Knee extension strength had the strongest positive association with all three gait parameters (P < 0.0001), while methotrexate use was also positively associated with all three gait parameters (step length: P < 0.05, cadence: P < 0.05 in model 1 and 2; P < 0.01 in model 3, gait speed: P < 0.01). The disease activity score was negatively associated with step length and gait speed (step length, gait speed: P < 0.01 in model 1 and 2; P < 0.05 in model 3). 26% of patients with good HAQ scores showed slow gait speed. Patients with good HAQ scores and slow gait speed had higher disease activity scores (P < 0.05) and lower knee extension strength (P < 0.0001) than those with good HAQ scores and normal gait speed. CONCLUSIONS: High knee extension strength, low disease activity and administration of methotrexate were strongly associated with good walking ability in female patients with RA. And, even if patients showed good HAQ scores, about quarter of those patients had poor walking ability, and they showed higher disease activity, lower knee extension strength, compared to the patients with normal gait speed.

Background/Purpose We examined whether a 3-month Japanese drum exercise program can ameliorate depressive mood and improve physical fitness in community-dwelling older women. Methods The participants were 40 community-dwelling older women aged 65 years and older who satisfied one or more of the mood items on the Kihon checklist. They were divided into two groups: a 3-month Japanese drum exercise group and a control group. The study included 21 women who participated in Japanese drum exercises (mean age, 76.8 ± 5.2 years) and 19 control participants (79.8 ± 5.4 years). To evaluate the participants’ psychological status, we used the depression item (D) on the short form of the profile of mood states. The body composition of participants was determined using bioelectrical impedance analysis. In addition, gait speed, grip strength, and scores on the morale scale, the geriatric depression scale, the trail making test, and the mini-mental state examination were measured before and after the intervention. Results After the 3-month intervention, we found no significant main effect-induced differences (p = 0.135) in Profile of Mood States between the groups. No significant difference was found between groups for any of the psychophysiological or physical fitness measures after the intervention. Conclusion Our results did not support the hypothesis that the Japanese drum exercise can improve depressive mood in older women. However, depressive mood showed a slight improvement in the intervention group, suggesting that a longer or more frequent session of intervention might have had an effect.

Docetaxel is frequently used in the treatment of a wide variety of solid tumors, including breast cancer. The aim of this study is to obtain the population pharmacokinetic parameters of docetaxel in Japanese female patients with breast cancer. Blood samples from 24 patients were collected sequentially before and after docetaxel infusion. Genomic DNA was isolated from the peripheral blood and genotyped for the selected polymorphisms in the candidate genes of drug transporters and metabolizing enzymes. The influence of patient characteristics on the pharmacokinetics of docetaxel was evaluated using the nonlinear-mixed-effect modeling program, NONMEM. As a basis for comparison, the pharmacokinetics of another taxane paclitaxel in 41 separate female patients with breast cancer was calculated. A two-compartment model adequately described the pharmacokinetic profiles of docetaxel. The population mean estimates of the total body clearance for patients aged 58 years or less and the central volume of distribution for docetaxel were 32.6 L/h and 5.77 L, respectively. In patients over 58 years, the clearance was 24 % higher than that in the younger patients. No influences of the genotypes examined were noted on the clearance of docetaxel. The clearance of paclitaxel was not affected by patient age. Patients over the age of 58 years showed significantly higher clearance of docetaxel than that in patients aged 58 years or less. Since the clearance of paclitaxel was not affected by the age, it is possible that the pharmacokinetic mechanisms of docetaxel might be specifically affected by age in females.

Research on patient-reported outcomes indicates that constipation is a common adverse effect of chemotherapy, and the use of 5-hydroxytryptamine (serotonin; 5HT(3)) receptor antagonists aggravates this condition. As cancer patients take multiple drugs as a part of their clinical management, a non-pharmacological self-management (SM) of constipation would be recommended. We aimed to evaluate the effectiveness of a SM program on antiemetic-induced constipation in cancer patients. Thirty patients with breast cancer, receiving 5HT3 receptor antagonists to prevent emesis during chemotherapy were randomly assigned to the intervention or control group. The SM program consisted of abdominal massage, abdominal muscle stretching, and education on proper defecation position. The intervention group started the program before the first chemotherapy cycle, whereas patients in the wait-list control group received the program on the day before their second chemotherapy cycle. The primary outcome was constipation severity, assessed by the constipation assessment scale (CAS, sum of eight components). The secondary outcome included each CAS component (0-2 points) and mood states. A self-reported assessment of satisfaction with the program was performed. The program produced a statistically and clinically significant alleviation of constipation severity (mean difference in CAS, 3.00; P = 0.02), decrease in the likelihood of a small volume of stool (P = 0.03), and decrease in depression and dejection (P = 0.02). With regards to program satisfaction, 43.6 and 26.4 % patients rated the program as excellent and good, respectively. Our SM program is effective for mitigating the symptoms of antiemetic-induced constipation during chemotherapy.