Outcomes of patients with initially unresectable pancreatic cancer who underwent conversion surgery after FOLFIRINOX or gemcitabine plus nab-paclitaxel chemotherapy: A multicenter retrospective cohort study (PC-CURE-1).

BACKGROUND: The efficacy and safety of conversion surgery (CS) after FOLFIRINOX or gemcitabine plus nab-paclitaxel (GnP) chemotherapy in patients with initially unresectable pancreatic cancer (PC) remains unclear. METHODS: This multicenter retrospective cohort study enrolled patients, between 2014 and 2018, with initially locally advanced or metastatic PC who were considered candidates for CS following FOLFIRINOX or GnP chemotherapy. They were classified into surgery (207 patients [194 resection and 13 exploratory laparotomy only]) and continued chemotherapy (10 patients, control) groups. The primary endpoint was overall survival (OS) from the day of diagnosis of potentially curative resection on imaging studies, with an expected hazard ratio (HR) of 0.7. RESULTS: OS in the surgery group was longer than that in the control group (HR, 0.47; 95% confidence interval [CI]: 0.24-0.93). The median OS was 34.4 (95% CI: 27.9-43.4) and 19.8 (95% CI: 14.9-31.1) months in the surgery and control groups, respectively. The Clavien-Dindo grade ≥ IIIa postoperative complication and in-hospital mortality rates were 19.6% and 0.5%, respectively. Multivariate analysis revealed that preoperative chemotherapy duration was not associated with OS. CONCLUSIONS: CS, following a favorable response to FOLFIRINOX or GnP chemotherapy, improved initially unresectable PC prognosis (specifically, OS), regardless of the chemotherapy duration.

Trastuzumab Deruxtecan in Human Epidermal Growth Factor Receptor 2-Expressing Biliary Tract Cancer (HERB; NCCH1805): A Multicenter, Single-Arm, Phase II Trial.

PURPOSE: Treatment options for patients with unresectable or recurrent biliary tract cancer (BTC) who progress on a gemcitabine-containing regimen are limited. In addition, the significance of anti-human epidermal growth factor receptor 2 (HER2) therapy in HER2-expressing BTC has not been sufficiently investigated. METHODS: In this phase II trial, participants from five institutions in Japan were enrolled. Eligible patients had pathologically confirmed unresectable or recurrent BTC with centrally confirmed HER2-positive (immunohistochemistry [IHC]3+ or IHC2+ and in situ hybridization [ISH]+) or HER2-low (IHC2+ and ISH-, IHC1+, and IHC0 and ISH+) and were refractory or intolerant to a gemcitabine-containing regimen. The patients received 5.4 mg/kg trastuzumab deruxtecan (T-DXd) once every 3 weeks until disease progression or unacceptable toxicity. The primary end point was the confirmed objective response rate (ORR) in HER2-positive BTC by an independent central review (threshold ORR, 15%; expected ORR, 40%). RESULTS: A total of 32 patients were enrolled and treated. Among these patients, 22 with HER2-positive disease comprised the primary efficacy population and had a confirmed ORR of 36.4% (90% CI, 19.6 to 56.1; P = .01), meeting the primary end point. Eight with HER2-low disease comprised the exploratory population and had a confirmed ORR of 12.5%. The most common ≥grade 3 treatment-related adverse events were anemia (53.1%) and neutropenia (31.3%). Eight patients (25.0%) had interstitial lung disease (ILD), including two grade 5 events. CONCLUSION: T-DXd showed promising activity in patients with HER2-positive BTC and a signal of efficacy in patients with HER2-low BTC. Although the safety profile was generally manageable, ILD requires careful monitoring and early intervention.

The SCRUM-MONSTAR Cancer-Omics Ecosystem: Striving for a Quantum Leap in Precision Medicine.

The SCRUM-Japan MONSTAR-SCREEN consortium is a nationwide molecular profiling project employing artificial intelligence-driven multi-omics analyses for patients with advanced malignancies, aiming to develop novel therapeutics and diagnostics and deliver effective drugs to patients. Concurrently, studies assessing molecular residual disease-based precision medicine for resectable solid tumors, including CIRCULATE-Japan, are ongoing. The substantial data generated by these platforms are stored within a state-of-the-art supercomputing infrastructure, VAPOR CONE. Since 2015, our project has registered over 24,000 patients as of December 2023. Among 16,144 patients with advanced solid tumors enrolled in MONSTAR-SCREEN projects, 5.0% participated in matched clinical trials, demonstrating a 29.2% objective response rate and 14.8-month median survival (95% confidence interval, 13.4-16.3), for patients treated in the matched clinical trials. Notably, patients who received matched therapy demonstrated significantly prolonged overall survival compared with those who did not (hazard ratio 0.77; 95% confidence interval, 0.71-0.83).

Quality-of-life survey of pancreatic cancer patients: a comparison between general public and physicians.

Background: Quality-of-life (QOL) is important for cancer patients with poor prognosis. However, conducting a QOL survey with patients is difficult. Therefore, we conducted a QOL survey with physicians. Specifically, this study aimed to clarify how physicians assess QOL in patients with pancreatic cancer by conducting a survey and comparing the results between physicians and the general public. Methods: A survey was conducted by interviewing physicians administering chemotherapy to patients for recurrent/metastatic pancreatic cancer. This method is similar to that of the QOL survey conducted among the general public. Responses were evaluated using the composite time trade-off (cTTO) and the visual analog scale (VAS) for 11 pancreatic cancer status scenarios (survey scenarios). These scenarios consisted of patients' health states as well as the types and grades of adverse events (AEs). Health status was classified into two categories: Stable disease (SD) and Progressive disease (PD). In addition, we conducted a survey using the EuroQol 5 Dimensions 5-Level (EQ-5D-5l) as reference values. Results: Twenty physicians responded to the survey. SD had the highest mean QOL value for both assessment methods (Physicians: 0.78, General public: 0.63), whereas PD had the lowest mean QOL value (Physicians: 0.15, General public: -0.12). The physicians assigned higher QOL values on both the VAS and cTTO than the general public did in all survey scenarios. Conclusions: The QOL values obtained from physicians were consistent with the degree of status in any assessment scenarios. Based on the differences in the QOL survey results between physicians and the general public, physicians tended to assign higher QOL values than the general public in cTTO and VAS assessments.

Japanese classification of pancreatic carcinoma by the Japan Pancreas Society: Eighth edition.

In 2023, the Japan Pancreas Society (JPS) published the new eighth edition of the Japanese classification of pancreatic carcinoma. We present here an excerpted version in English, based on the latest edition. The major changes in this revision are as follows: In the eighth edition of the Union for International Cancer Control (UICC), the T category was changed to be based on tumor size; however, the eighth edition of the Japanese classification retains the previous T category based on local invasion factors. Lymph nodes have been renamed, and regional lymph nodes have been defined by location. Peritoneal cytology, which was not previously included in distant metastasis (M), has now been included in the M category. Moreover, significant additions have been made regarding the pathological diagnosis of endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) and criteria for histological assessment of the effects after chemotherapy and radiation therapy. Although this classification is aimed at carcinoma originating in the pancreas, not in the bile duct or duodenum, if the differentiation of the primary organ is difficult, this classification should be applied. It is also desirable to describe tumors other than carcinoma and metastatic tumors to the pancreas in accordance with this classification.

Phase II Placebo-Controlled Study of the Effect and Safety of Nanvuranlat in Patients with Advanced Biliary Tract Cancers Previously Treated by Systemic Chemotherapy.

PURPOSE: To evaluate the efficacy and safety of nanvuranlat (a LAT1 inhibitor) monotherapy as a later-line treatment in advanced, metastatic, and refractory BTCs. PATIENTS AND METHODS: The multicenter, randomized, double-blind, placebo-controlled, phase II study was conducted across 14 leading Japanese cancer centers and hospitals. Nanvuranlat 25 mg/m2/day or placebo was given intravenously in cycles of five consecutive days, followed by nine days off. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and disease control rate (DCR). Subgroup analysis was performed in patients with high LAT1 expression and BTC-subtypes. RESULTS: A total of 211 patients were screened, 105 eligible patients were randomized, and then 70 received nanvuranlat and 35 received placebo. Nanvuranlat demonstrated an improvement in PFS when compared to placebo (Hazard Ratio (HR) 0.56; 95% CI, 0.34 - 0.90; P = 0.02). Grade 3 or higher adverse events were reported in 30.0% and 22.9% of those in the nanvuranlat and placebo groups, respectively. The overall survival (OS) was not statistically different between nanvuranlat- and placebo-treated patients. An exploratory analysis indicated that nanvuranlat is warranted to evaluate its long-term clinical benefit in patients with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer. CONCLUSION: Compared with placebo, nanvuranlat improved PFS in patients with advanced and refractory BTC with an acceptable safety profile. Further studies of this promising compound are warranted in the population of patients who are exhausted from treatment options.

Early tumor shrinkage as a prognostic predictor in chemotherapy-naïve patients with locally advanced pancreatic cancer treated with modified FOLFIRINOX or gemcitabine plus nab-paclitaxel combination therapy: An exploratory analysis of JCOG1407.

BACKGROUND: Early tumor shrinkage (ETS) is a prognostic predictor for patients treated with chemotherapy in colorectal cancer, although scarce studies evaluated its potential in locally advanced pancreatic cancer (LAPC). In this exploratory analysis of JCOG1407, a randomized phase II study comparing modified 5-fluorouracil, levofolinate, irinotecan, and oxaliplatin (mFOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP), we evaluated whether ETS can predict prognosis of patients with LAPC. METHODS: Of the 126 patients enrolled in JCOG1407, 112 with measurable lesions were included in this study. ETS was defined as a ≥20 % reduction in tumor diameter compared with baseline at the initial imaging assessment 6-10 weeks after initiating chemotherapy. Patients were divided into the ETS (achieved ETS) and non-ETS (failed to achieve ETS) groups based on their ETS status. The impact of ETS on overall survival (OS) was compared using multivariable Cox regression analysis. RESULTS: Fourteen of 55 (25.5 %) and 24 of 57 (42.1 %) patients in the mFOLFIRINOX and GnP arms, respectively, achieved ETS. In the overall population, mFOLFIRINOX arm, and GnP arm, the median OS in the ETS and non-ETS groups was 27.1 and 20.4, 29.8 and 20.6, and 24.1 and 20.4, months, respectively. The adjusted hazard ratios of OS for the ETS group in the overall population, mFOLFIRINOX arm, and GnP arm were 0.451 (95 % confidence interval [CI]: 0.270-0.754), 0.371 (95 % CI: 0.149-0.926), and 0.508 (95 % CI: 0.255-1.004), respectively. CONCLUSIONS: ETS may be a prognostic predictor in chemotherapy-naïve patients with LAPC treated with mFOLFIRINOX or GnP.

Real-world evidence of systemic treatment practices for biliary tract cancer in Japan: Results of a database study.

PURPOSE: To describe the real-world treatment patterns of systemic therapies for biliary tract cancer (BTC) and to examine the frequency and management of biliary infection in Japan. METHODS: Patients diagnosed with BTC and prescribed systemic therapy between January 2011 and September 2020 were retrieved from the Japanese Medical Data Vision database. The look-back period was set to 5 years. Patient characteristics, treatment patterns, and biliary infection-induced treatment interruption were analyzed. RESULTS: The full analysis set comprised 22 742 patients with a mean age of 71.0 years and 61.6% were male. The most common BTC type was extrahepatic cholangiocarcinoma (44.6%). The three most common first-line regimens were S-1 monotherapy (33.0%), gemcitabine+cisplatin (32.5%), and gemcitabine monotherapy (18.7%) over the entire observation period (January 2011-September 2021). Patients who received monotherapies tended to be older. Biliary infection-induced treatment interruption occurred in 29.5% of patients, with a median time to onset of 64.0 (interquartile range 29.0-145.0) days. The median duration of intravenous antibiotics was 12.0 (interquartile range 4.0-92.0) days. CONCLUSIONS: These results demonstrated potential challenges of BTC in Japanese clinical practice particularly use of multiple regimens, commonly monotherapies, which are not recommended as first-line treatment, and the management of biliary infections during systemic therapy.

Protocol digest of a randomized phase III trial comparing S-1-based chemoradiotherapy with/without nivolumab for unresectable locally advanced or borderline resectable pancreatic cancer: JCOG1908E (PENETRATE).

Pancreatic cancer remains a highly lethal disease with a 5-year survival proportion of <10%. Chemoradiotherapy is a treatment option for unresectable locally advanced (UR-LA) or borderline resectable (BR) pancreatic cancer, but its efficacy is not sufficient. Induction of the synergistic effect of irradiation and immune checkpoint inhibitors can be an attractive strategy. An open-label randomized phase III trial has been conducted since October 2020 to confirm the superiority of nivolumab plus S-1-based chemoradiotherapy over S-1-based chemoradiotherapy alone in patients with UR-LA or BR pancreatic cancer. A total of 216 patients will be enrolled in 14 institutions within 3.5 years. The primary endpoint of the safety run-in part is dose-limiting toxicity, and that of the phase III part is overall survival. This trial was registered at the Japan Registry of Clinical Trials as jRCT2080225361 (https://jrct.niph.go.jp/latest-detail/jRCT2080225361).

Current status of the cost burden of first-line systemic treatment for patients with advanced hepatocellular carcinoma in Japan, 2021-22.

BACKGROUND: Although recent advances in systemic therapies for hepatocellular carcinoma (HCC) have led to prolonged patient survival, the high costs of the drugs place a heavy burden on both patients and society. The objectives of this study were to examine the treatment regimens used as first-line systemic treatment for patients with advanced HCC in Japan and to estimate the treatment costs per regimen. METHODS: For this study, we aggregated the data of patients who had received first-line systemic treatment for advanced HCC between July 2021 and June 2022. The treatment cost per month of each regimen was estimated based on standard usage, assuming an average weight of 60 kg for male patients. The data were categorized by the treatment regimen, and the treatments were categorized based on the cost into very high-cost (≥1 000 000 Japanese yen [JPY]/month), high-cost (≥500 000 JPY/month) and other (<500 000 JPY/month) treatments. RESULTS: Of the total of 552 patients from 24 institutions whose data were analyzed in this study, 439 (79.5%) received atezolizumab plus bevacizumab, 98 (17.8%) received lenvatinib and 15 (2.7%) received sorafenib as the first-line treatment. The treatment cost per month for each of the above regimens was as follows: atezolizumab plus bevacizumab, 1 176 284 JPY; lenvatinib, 362 295 JPY and sorafenib, 571 644 JPY. In total, 82.2% of patients received high-cost regimens, and the majority of these patients received a very high-cost regimen of atezolizumab plus bevacizumab. CONCLUSIONS: Advances in systemic therapies for HCC have led to prolonged patient survival. However, the treatment costs are also increasing, imposing a burden on both the patients and society.

The correlation between immune-related adverse events and efficacy of immune checkpoint inhibitors.

Immune checkpoint inhibitors have revolutionized cancer treatment by targeting the cytotoxic T lymphocyte antigen-4 and programmed death-1/ligand-1. Although immune checkpoint inhibitors show promising therapeutic efficacy, they often cause immune-related adverse events. Immune-related adverse events differ from the side effects of conventional chemotherapy and require vigilant monitoring. These events predominantly affect organs, such as the colon, liver, lungs, pituitary gland, thyroid and skin, with rare cases affecting the heart, nervous system and other tissues. As immune-related adverse events result from immune activation, indicating the reinvigoration of exhausted immune cells that attack both tumors and normal tissues, it is theoretically possible that immune-related adverse events may signal a better response to immune checkpoint inhibitor therapy. Recent retrospective studies have explored the link between immune-related adverse event development and clinical efficacy; however, the predictive value of immune-related adverse events in the immune checkpoint inhibitor response remains unclear. Additionally, studies have focused on immune-related adverse events, timing of onset and immunosuppressive treatments. This review focuses on pivotal studies of the association between immune-related adverse events and outcomes in patients treated with immune checkpoint inhibitors.

Pemigatinib in previously treated solid tumors with activating FGFR1-FGFR3 alterations: phase 2 FIGHT-207 basket trial.

Fibroblast growth factor receptor (FGFR) alterations drive oncogenesis in multiple tumor types. Here we studied pemigatinib, a selective, potent, oral FGFR1-FGFR3 inhibitor, in the phase 2 FIGHT-207 basket study of FGFR-altered advanced solid tumors. Primary end points were objective response rate (ORR) in cohorts A (fusions/rearrangements, n = 49) and B (activating non-kinase domain mutations, n = 32). Secondary end points were progression-free survival, duration of response and overall survival in cohorts A and B, and safety. Exploratory end points included ORR of cohort C (kinase domain mutations, potentially pathogenic variants of unknown significance, n = 26) and analysis of co-alterations associated with resistance and response. ORRs for cohorts A, B and C were 26.5% (13/49), 9.4% (3/32) and 3.8% (1/26), respectively. Tumors with no approved FGFR inhibitors or those with alterations not previously confirmed to be sensitive to FGFR inhibition had objective responses. In cohorts A and B, the median progression-free survival was 4.5 and 3.7 months, median duration of response was 7.8 and 6.9 months and median overall survival was 17.5 and 11.4 months, respectively. Safety was consistent with previous reports. The most common any-grade treatment-emergent adverse events were hyperphosphatemia (84%) and stomatitis (53%). TP53 co-mutations were associated with lack of response and BAP1 alterations with higher response rates. FGFR1-FGFR3 gatekeeper and molecular brake mutations led to acquired resistance. New therapeutic areas for FGFR inhibition and drug failure mechanisms were identified across tumor types. ClinicalTrials.gov identifier: NCT03822117 .

Phase II trial of niraparib for BRCA-mutated biliary tract, pancreatic and other gastrointestinal cancers: NIR-B.

Due to the widespread use of cancer genetic testing in gastrointestinal cancer, the BRCA1/2 genetic mutation has been identified in biliary tract cancer as well as pancreatic cancer. Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor, and PARP inhibitors exert their cytotoxicity against cancer cells in the context of homologous recombination deficiency, such as BRCA mutations, via the mechanism of synthetic lethality. The aim of this phase II NIR-B trial is to evaluate the efficacy and safety of niraparib for patients with unresectable advanced or recurrent biliary tract cancer, pancreatic cancer or other gastrointestinal cancers with germline or somatic BRCA1/2 mutations revealed by genetic testing. The primary end point is an investigator-assessed objective response rate in each cohort.Clinical Trial Registration: jRCT2011200023 (ClinicalTrials.gov).

A clinical study to confirm the efficacy and safety of niraparib for people with advanced biliary tract, pancreatic and other abdominal cancers with the BRCA genetic mutation: the NIR-B trial.BRCA gene is involved in repairing DNA injury and plays an important role in cancer growth. Cells with a mutation in the BRCA gene cannot repair DNA using a method called homologous recombination repair. Niraparib is part of a class of drugs called 'PARP inhibitors' that inhibit enzymes called 'PARP' involved in repairing DNA injury, and has shown efficacy against cancers with BRCA gene mutations. BRCA gene mutations are infrequent but have been found in a variety of cancers. The NIR-B trial is a clinical trial to evaluate the efficacy and safety of niraparib for people with advanced biliary tract, pancreatic and other abdominal cancers with BRCA gene mutations.

Multicenter validation study of a treatment selection MAP for pancreatic neuroendocrine tumors.

BACKGROUND: Somatostatin analogs, molecular-targeted agents and cytotoxic anticancer agents are available as therapeutic agents for the systemic treatment of pancreatic neuroendocrine tumors, and we have developed a first-line treatment selection MAP to enable selection of the optimal treatment strategy for pancreatic neuroendocrine tumors. The purpose of this study was to validate the usefulness of the treatment selection MAP. METHODS: Patients who had received systemic therapy for a pancreatic neuroendocrine tumor between January 2017 and December 2020 were compared according to whether they had been treated as recommended by the MAP (matched patients) or not (unmatched patients) to determine whether better outcomes were achieved by the matched patients. The primary endpoint was progression-free survival of the matched group and unmatched groups in the somatostatin analog, molecular-targeted agent and cytotoxic anticancer agents areas of the MAP. RESULTS: There were 41 (55%) MAP-matched patients in all areas among the 74 patients registered at seven hospitals. The MAP-matched rates were 100, 77 and 38% in the somatostatin analog area, molecular-targeted agent area and cytotoxic anticancer agents area, respectively. All of the unmatched patients had been selected for less intensive treatment. The median progression-free survival in the matched group and unmatched group in the molecular-targeted agent area of the MAP were 46.6 and 15.4 months, respectively, and a multivariate analysis identified MAP-matched (hazard ratio 0.18 [95% confidence interval: 0.04-0.87], P = 0.032) as the only significant independent favorable predictive factor. CONCLUSION: The usefulness of the MAP for treatment selection was validated in the molecular-targeted agent area of the MAP.

Development of a PCR-based assay for specific and sensitive detection of Fusarium buharicum from infected okra plant.

Fusarium wilt, caused by the fungus Fusarium buharicum, is an emerging disease of okra in Japan. The disease was first reported in Japan in 2015, causing significant damage to okra seedlings. Due to the potential threat in okra cultivation, the development of an accurate detection method for F. buharicum is needed for the surveillance and management of the disease. In this study, we designed a primer set and developed conventional and nested PCR assays for the specific detection of F. buharicum in infected okra plants and contaminated soil, respectively. We compared the diversity of the translation elongation factor 1 alpha (EF-1α) gene of F. buharicum with 103 other fungal species/isolates to design a species-specific primer. This primer pair successfully amplified approximately 400 bp of PCR product that was only detected in the F. buharicum isolate, not in the other fungal isolates. The developed nested PCR method was highly sensitive and could detect the fungus from a 0.01 fg DNA sample. The primer successfully detected the pathogen in artificially infected plants and soil by conventional and nested PCR, respectively. This is the first report of the development of the F. buharicum-specific primer set and detection assays, which can be used for the specific and sensitive detection of F. buharicum in field samples and for taking early control measures.

Clinical Impact of Preoperative Prognostic Nutritional Index in Surgical Patients With Pancreatic Cancer Treated With Perioperative Adjuvant Chemotherapy.

BACKGROUND/AIM: The prognostic nutritional index (PNI) is used as a marker to evaluate the nutritional and immunological status of patients with various cancers. This study aimed to investigate whether preoperative PNI is a prognostic factor in patients with pancreatic cancer who underwent perioperative adjuvant chemotherapy and surgical resection. PATIENTS AND METHODS: We retrospectively enrolled 232 pancreatic cancer patients who underwent surgical resection with perioperative adjuvant chemotherapy between January 2013 and December 2022. Overall survival (OS) and relapse-free survival (RFS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards regression models. RESULTS: The optimal cutoff value for the preoperative PNI was 44.3 in the present study. PNI <44.3 was associated with older age (p<0.001) and affected the clinical course of postoperative adjuvant chemotherapy. The PNI <44.3 had an important influence on the decreased OS (25.1 vs. 39.0 months) and RFS (13.1 vs. 22.8 months). In univariate and multivariate analyses, the preoperative PNI was an independent prognostic factor for OS [hazard ratio (HR)=1.682, 95% confidence interval (CI)=1.059-2.673, p=0.028] and RFS (HR=1.559, 95% CI=1.037-2.344, p=0.033). CONCLUSION: Preoperative PNI is a prognostic factor for both OS and RFS in patients with pancreatic cancer who underwent perioperative adjuvant chemotherapy and surgical resection. This study suggests that a low PNI may cause a lack of full-dose adjuvant chemotherapy, leading to recurrence and resulting in a poor prognosis for surgical pancreatic cancer patients treated with perioperative adjuvant chemotherapy.

Combined repetitive facilitative exercise under continuous neuromuscular electrical stimulation and task-oriented training for hemiplegic upper extremity during convalescent phase after stroke: before-and-after feasibility trial.

Introduction: Whereas repetitive facilitative exercise (RFE) affects primarily recovery of motor impairment after stroke, task-oriented training (TOT) focuses on facilitating daily use of the affected upper extremity. However, feasibility of combined RFE and TOT has not been reported. We originated "task-oriented RFE," as a new combination therapy for patients with hemiplegic upper extremity after subacute stroke, to examine its feasibility in convalescent rehabilitation wards. Methods: This is a before-and-after pilot study. Eight patients with hemiplegic upper extremity after subacute stroke received the task-oriented RFE program for 6 weeks at 80 min per day (20-60 min of TOT applied after 60-20 min of RFE under continuous neuromuscular electrical stimulation) in a convalescent rehabilitation ward. In the current program, we introduced the Aid for Decision-making in Occupation Choice (ADOC) iPad application as a goal-setting method for determining tasks. Feasibility was assessed with adherence to the protocol, adverse events in response to the intervention, and preliminary efficacy. Motor functions, amount of use and quality of movement in the hemiparetic upper extremity, and satisfaction of the patients were evaluated with Fugl-Meyer Assessment (FMA), the Action Research Arm Test (ARAT), the motor activity log (MAL) for the amount of use (AOU) and quality of movement (QOM) of the paralyzed hand, and ADOC. Results: All participants accomplished the program, which was implemented as originally planned; neither nonattendance nor an adverse event occurred during the study. Favorable outcomes were obtained with all measures; mean changes in FMA, ARAT in the dominant hand, MAL-AOU, and MAL-QOM were greater than minimal clinically important differences. Mean changes in ADOC were greater than the minimal detectable change. Discussion: The task-oriented RFE program was safe, well-tolerated, beneficial, and feasible within 80 min a day of occupational therapy, which means also within the procedural constraints of the Japanese health insurance system during the convalescent phase. Future studies are warranted to examine whether combined RFE and TOT enhances the efficacies of each program alone.

Progression pattern and post-progression survival following atezolizumab and bevacizumab treatment in advanced hepatocellular carcinoma.

BACKGROUND: Although the combination of atezolizumab and bevacizumab (ATZ + BEV) is a standard treatment for advanced hepatocellular carcinoma (HCC), strategies for addressing treatment failure and prognostic factors of post-progression survival (PPS) remain unestablished. METHODS: We conducted a multicentre retrospective study to evaluate PPS following ATZ + BEV treatment in patients with advanced HCC. We classified the patients into three groups: BCLC stage B and BCLC stage C without or with new extrahepatic lesions (BCLCp-C1 and BCLCp-C2, respectively) at the time of progression. RESULTS: Of the 204 patients who started ATZ + BEV treatment between October 2020 and September 2022, 110 showed disease progression, with 33, 55 and 22 showing the BCLCp-B, BCLCp-C1 and BCLCp-C2 stages of the disease, respectively. Specifically, patients with the BCLCp-B stage of the disease showed better overall survival than those with the BCLCp-C1 and BCLCp-C2 stages (hazard ratios: 1.93 [95% confidence interval, CI, 1.06-3.51] and 2.64 [95% CI, 1.32-5.30] for HCC stages BCLCp-C1 and BCLCp-C2, respectively). Via multivariable analysis, we identified the BCLCp-C1 and BCLCp-C2 stages, as well as performance status, Child-Pugh class and alpha-fetoprotein as poor prognostic factors for PPS. CONCLUSIONS: BCLCp-B1 stage was identified as a better prognostic factor for PPS following ATZ + BEV treatment compared with BCLCp-C1 and BCLCp-C2 stages. This may help in making decisions regarding subsequent treatment after ATZ + BEV.