Clinical Response of Primary Malignant Pericardial Mesothelioma with Peritoneal Dissemination to Nivolumab.

Malignant pericardial mesothelioma (MPM) is extremely rare, and peritoneal dissemination has not yet been reported. There is no consensus regarding appropriate pharmacological treatment for MPM, including immune checkpoint inhibitors (ICIs). We herein report a 36-year-old man with MPM diagnosed by peritoneal dissemination and treated with an ICI. Cytology of the ascites revealed malignant peritonitis, and a re-evaluation of a pericardial biopsy performed at the previous hospital led to a diagnosis of MPM. The patient was treated with nivolumab and showed a clinical response despite several complications, such as renal dysfunction and performance status deterioration. This case report provides suggestive information for the diagnosis and ICI therapy of a rare type of mesothelioma.

Disseminated gonococcal infection of the shoulder mimicking rheumatoid arthritis.

Introduction: Gonococcal arthritis is a characteristic of disseminated gonococcal infection (DGI). DGI arthritis is one of the most serious orthopedic emergencies because it can result in rapidly progressive joint damage, but it is often difficult to diagnose. Delayed treatment can result in the development of osteomyelitis in the adjacent bone, similar to other types of bacterial arthritis. Method: We report a case of gonococcal osteomyelitis associated with DGI that was initially treated as rheumatoid arthritis. The diagnosis was confirmed by DNA testing of synovium collected during arthroscopic debridement. Results: Seven years after the initial consultation, there was no acute-phase reactant, the arthritic changes had improved over time and the range of motion had increased. DGI may be difficult to confirm, but it is one of the most important entities that should be differentiated in the treatment of arthritis. Conclusion: Clinicians need to keep in mind that blood and synovial fluid cultures often do not lead to a definitive diagnosis.

Prevalence of Precursory Signs of Atypical Femoral Fractures in Patients Receiving Bone-Modifying Agents for Bone Metastases: A Cross-Sectional Study.

Patients on bone-modifying agents (BMAs) for bone metastases are at risk of atypical femoral fractures (AFFs), which can lead to a sudden deterioration in performance status. In this study, we sought to determine the prevalence of radiographic precursory signs of AFF in patients on oncologic BMAs. Forty-two patients (23 men, 19 women; mean age 68.8 ± 10.0 years) on oncologic BMAs (zoledronate for >3 years and/or denosumab for >1 year) and without clinical symptoms were enrolled between 2019 and 2021. All patients were receiving denosumab at enrollment and 5 had previously used zoledronate. The mean duration of BMA use was 31.2 ± 18.5 months. Radiographs of both femurs were screened for precursory signs of AFF (e.g., thickening of the lateral cortex). The patients were divided into two groups according to thickening status and compared by duration of BMA use. They were also divided into three groups by duration of BMA use (12-23 months, n = 18; 24-59 months, n = 19; ≥60 months, n = 5), and the prevalence of apparent thickenings was examined. As a result, 18 patients (42.9%) showed minute local or diffuse thickening and 10 (23.8%) showed apparent local thickening. The duration of BMA use was significantly longer in patients with apparent thickening than in those without (47.3 ± 23.6 months [n = 10] versus 26.2 ± 13.5 months [n = 32]; p < 0.05). The prevalence of apparent thickening increased with increasing duration of BMA use (12-23 months, 5.6%; 24-59 months, 31.6%; ≥60 months, 60.0%). In conclusion, radiographic precursory signs of AFF are common in patients on oncologic BMAs. Radiographic screening for AFF could be relevant in patients who have been on long-term oncologic BMAs, even if asymptomatic. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Efficacy of bone marrow stimulation for arthroscopic knotless suture bridge rotator cuff repair: a prospective randomized controlled trial.

BACKGROUND: The purpose of this study was to investigate the efficacy of bone marrow stimulation (BMS) on the repair integrity of the rotator cuff insertion treated with arthroscopic knotless suture bridge (K-SB) rotator cuff repair. We hypothesized that BMS during K-SB repair can improve the healing of the rotator cuff insertion. METHODS: Sixty patients who underwent arthroscopic K-SB repair of full-thickness rotator cuff tears were randomly allocated to 2 treatment groups. Patients in the BMS group underwent K-SB repair augmented with BMS at the footprint. Patients in the control group underwent K-SB repair without BMS. Cuff integrity and retear patterns were evaluated by postoperative magnetic resonance imaging. The clinical outcomes included the Japanese Orthopaedic Association score, University of California at Los Angeles score, Constant-Murley score, and Simple Shoulder Test. RESULTS: Clinical and radiological evaluations were completed in 60 patients at 6 months postoperatively, in 58 patients at 1 year postoperatively, and in 50 patients at 2 years postoperatively. Both treatment groups showed significant improvements in the clinical outcome from baseline to the 2-year follow-up, but no significant differences were found between the 2 groups. At 6 months postoperatively, the retear rate at the tendon insertion was 0.0% (0 of 30) in the BMS group and 3.3% (1 of 30) in the control group (P = .313). The retear rate at the musculotendinous junction was 26.7% (8 of 30) in the BMS group and 13.3% (4 of 30) in the control group (P = .197). All retears in the BMS group occurred at the musculotendinous junction, and the tendon insertion was preserved. There was no significant difference in the overall retear rate or retear patterns between the 2 treatment groups during the study period. CONCLUSIONS: No significant differences were detected in the structural integrity or retear patterns regardless of the use of BMS. The efficacy of BMS for arthroscopic K-SB rotator cuff repair was not proven in this randomized controlled trial.

Excessively High Repair Tension Decreases Microvascular Blood Flow Within the Rotator Cuff.

BACKGROUND: Repair tension and microvascular blood flow within the rotator cuff has a critical impact on tendon healing after rotator cuff repair. However, the relationship between repair tension and microvascular blood flow within the rotator cuff remains unclear. PURPOSE/HYPOTHESIS: The purpose of this study was to determine how much tension adversely affects microvascular blood flow within the rotator cuff. The hypothesis was that as the repair tension increases, the microvascular blood flow within the rotator cuff decreases. STUDY DESIGN: Controlled laboratory study. METHODS: Repair tension and microvascular blood flow within the rotator cuff of 30 patients with full-thickness rotator cuff tears were simultaneously measured using a digital tension meter and a contact-type laser Doppler flowmeter, respectively. Microvascular blood flow was measured under 4 levels of tension (0, 10, 20, and 30 N) at 5 points on the rotator cuff. The obtained values were statistically analyzed by a linear mixed-effects model to clarify the effect of tension on microvascular blood flow within the rotator cuff. RESULTS: There was no statistically significant difference in microvascular blood flow (mL/min/100 g) within the rotator cuff between 0 N (mean, 3.51; 95% CI, 3.0-4.0) and 10 N (mean, 3.74; 95% CI, 3.2-4.3) of tension (P = .716). However, there were statistically significant differences in microvascular blood flow within the rotator cuff between 0 and 20 N of tension (mean, 2.84; 95% CI, 2.3-3.4) (P = .002) and between 0 and 30 N of tension (mean, 2.45; 95% CI, 1.9-3.0) (P < .001). CONCLUSION/CLINICAL RELEVANCE: Our findings indicate that tension of ≥10 N during rotator cuff repair significantly decreases the microvascular blood flow within the rotator cuff. These data will contribute to determining the optimal repair tension during rotator cuff repair.

Comprehensive Genomic Profiling Reveals Clinical Associations in Response to Immune Therapy in Head and Neck Cancer.

Comprehensive genomic profiling (CGP) provides information regarding cancer-related genetic aberrations. However, its clinical utility in recurrent/metastatic head and neck cancer (R/M HNC) remains unknown. Additionally, predictive biomarkers for immune checkpoint inhibitors (ICIs) should be fully elucidated because of their low response rate. Here, we analyzed the clinical utility of CGP and identified predictive biomarkers that respond to ICIs in R/M HNC. We evaluated over 1100 cases of HNC using the nationwide genetic clinical database established by the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) and 54 cases in an institution-based study. The C-CAT database revealed that 23% of the cases were candidates for clinical trials, and 5% received biomarker-matched therapy, including NTRK fusion. Our institution-based study showed that 9% of SCC cases and 25% of salivary gland cancer cases received targeted agents. In SCC cases, the tumor mutational burden (TMB) high (≥10 Mut/Mb) group showed long-term survival (>2 years) in response to ICI therapy, whereas the PD-L1 combined positive score showed no significant difference in progression-free survival. In multivariate analysis, CCND1 amplification was associated with a lower response to ICIs. Our results indicate that CGP may be useful in identifying prognostic biomarkers for immunotherapy in patients with HNC.

Assessing the need for a question prompt list that encourages end-of-life discussions between patients with advanced cancer and their physicians: A focus group interview study.

OBJECTIVE: Early integration of palliative and cancer care improves the quality of life and is facilitated by discussions about the end of life after cessation of active cancer treatment between patients with advanced cancer and their physicians. However, both patients and physicians find end-of-life discussions challenging. The aim of this study was to assess the need for a question prompt list (QPL) that encourages end-of-life discussions between patients with advanced cancer and their physicians. METHODS: Focus group interviews (FGIs) were conducted with 18 participants comprising 5 pancreatic cancer patients, 3 family caregivers, 4 bereaved family members, and 6 physicians. Three themes were discussed: question items that should be included in the QPL that encourages end-of-life discussions with patients, family caregivers, and physicians after cessation of active cancer treatment; when the QPL should be provided; and who should provide the QPL. Each interview was audio-recorded, and content analysis was performed. RESULTS: The following 9 categories, with 57 question items, emerged from the FGIs: (1) preparing for the end of life, (2) treatment decision-making, (3) current and future quality of life, (4) current and future symptom management, (5) information on the transition to palliative care services, (6) coping with cancer, (7) caregivers' role, (8) psychological care, and (9) continuity of cancer care. Participants felt that the physician in charge of the patient's care and other medical staff should provide the QPL early during active cancer treatment. SIGNIFICANCE OF RESULTS: Data were collected to develop a QPL that encourages end-of-life discussions between patients with advanced cancer and their physicians.

Alteration of coracoacromial ligament thickness at the acromial undersurface in patients with rotator cuff tears.

Background: Some researchers have stated that magnetic resonance imaging (MRI) is useful for assessing the coracoacromial ligament (CAL) at the acromial undersurface. However, few studies have investigated the reliability and clinical significance of MRI findings for the CAL at the acromial undersurface. The purpose of this study was to determine the association between CAL thickness at the acromial undersurface and rotator cuff tear size. Methods: The CAL thickness at the acromial undersurface was evaluated in 182 patients with rotator cuff tears (mean age: 64.9 ± 8.4 years) using a 3.0-Tesla MRI system. The association between CAL thickness at the acromial undersurface and rotator cuff tear size determined by the DeOrio and Cofield classification (partial; small: <1 cm; medium: 1-3 cm; and large or massive: >3 cm) was analyzed statistically. The intraobserver and interobserver reliabilities for MRI measurements of CAL thickness at the acromial undersurface were determined by calculation of intraclass correlation coefficients and their 95% confidence intervals. Results: The mean CAL thickness at the acromial undersurface was 2.7 ± 1.4 mm (range: 0-6.5 mm). Increasing rotator cuff tear size was significantly associated with decreasing CAL thickness at the acromial undersurface (P = .004). The intraobserver and interobserver intraclass correlation coefficients for CAL thickness at the acromial undersurface were almost perfect (0.98 and 0.91, respectively). Conclusion: The present study clarified that (1) MRI was a reliable tool for evaluation of CAL thickness at the acromial undersurface and (2) increasing rotator cuff tear size was significantly associated with decreasing CAL thickness at the acromial undersurface. These findings may assist toward understanding the progressive pathology in rotator cuff disease.

[Future Cancer Professional Training Plan].

As one of the 11 third-stage"cancer professional plan", we will outline the activities and results of the"Future Cancer Professional Training Plan"consisting of 8 universities in the Tokyo metropolitan area and the Northern Tohoku area of Japan. In this project, as joint activities of 8 universities, we held the activity reports and joint symposiums with faculty/student exchange meetings at the management council twice a year. In addition, joint international symposiums with other cancer professional hub were held. We carried out subcommittee activities for each theme. In the graduate school courses of each university, we provided education with various contents and exchanged credits between universities. We also focused on holding seminars and public lectures, and collaborating with patients'association. These activities were reflected for the next year based on the results of the annual external evaluation.

Are there differences in arthroscopic and histological features between traumatic and degenerative rotator cuff tears in elderly patients? A prospective dual-center analysis.

BACKGROUND: Discriminating traumatic rotator cuff tears (RCTs) from degenerative RCTs is sometimes difficult in elderly patients because the prevalence of asymptomatic RCTs increases with age. Little intraoperative information is available on the characteristics of traumatic and degenerative RCTs in elderly patients. The purpose of this study was to compare the arthroscopic findings and histological changes of the coracoacromial ligament (CAL) between traumatic and degenerative RCTs in elderly patients. METHODS: Forty-two shoulders of 42 patients aged ≥ 65 years underwent arthroscopic rotator cuff repair. Nineteen patients had traumatic full-thickness RCTs (Group T), and 23 had degenerative full-thickness RCTs (Group D). The quality of the rotator cuff tissue and the condition of the long head of the biceps were examined. The grade of CAL was evaluated both arthroscopically and histologically. The stiffness of the musculotendinous unit was calculated by measuring the force and displacement using a tensiometer. The arthroscopic and histological findings of the two groups were compared. RESULTS: Although the mean tendon displacement was comparable, the stiffness was different between Group T and Group D (0.56 ± 0.31 and 1.09 ± 0.67 N/mm, respectively; p < 0.001). Both arthroscopic and histological analysis of the CAL showed that the degenerative changes in the CAL were milder in Group T than in Group D (p < 0.001 and p < 0.001, respectively). There was a moderate positive correlation between the arthroscopic findings of CAL degeneration and the histopathological changes in this ligament (r = 0.47, p = 0.002). CONCLUSIONS: Traumatic RCTs were characterized by preserved elasticity of the musculotendinous unit and milder CAL degeneration compared with degenerative RCTs even in elderly patients.

Association between oral health and advisability of oral feeding in advanced cancer patients receiving palliative care: a cross-sectional study.

PURPOSE: Maintenance of oral feeding is important in terms of maintaining and improving the quality of life in terminal cancer patients receiving palliative care. Although adequate oral health status is essential for oral feeding in hospitalized patients, the relationship between oral health and oral feeding in patients receiving palliative care remains unclear. This cross-sectional study aimed to examine how the general condition and oral health status of these patients relate to decisions regarding their nutritional intake methods. METHODS: This retrospective cross-sectional study included 103 terminal cancer patients (59 men and 44 women; mean age, 73.8 ± 10.9 years) who received palliative care between April 2017 and August 2019. The nutritional method was assessed using the Functional Oral Intake Scale (FOIS). We assessed two types of nutritional methods: (1) the method advised by the attending physician until the initial dental examination (FOIS-I) and (2) the recommended method based on consultation with a palliative care doctor and dentist after the initial oral examination (FOIS-R). Furthermore, the participants' basic information and Dysphagia Severity Scale (DSS) and Oral Health Assessment Tool (OHAT) scores were assessed. RESULTS: There was a divergence between FOIS-I and FOIS-R. FOIS-R was significantly higher than FOIS-I (p < 0.001). Multiple regression analysis revealed that the time until death, DSS score, and OHAT score had a significant impact on determining the food form for oral feeding. CONCLUSIONS: Appropriate oral health assessment is important in determining the food form and indication for oral feeding among patients receiving palliative care.

Clinical utility of comprehensive genomic profiling in Japan: Result of PROFILE-F study.

INTRODUCTION: Clinical sequencing has provided molecular and therapeutic insights into the field of clinical oncology. However, despite its significance, its clinical utility in Japanese patients remains unknown. Here, we examined the clinical utility of tissue-based clinical sequencing with FoundationOne® CDx and FoundationOne® Heme. Between August 2018 and August 2019, 130 Japanese pretreated patients with advanced solid tumors were tested with FoundationOne® CDx or FoundationOne® Heme. RESULTS: The median age of 130 patients was 60.5 years (range: 3 to 84 years), and among them, 64 were males and 66 were females. Major cancer types were gastrointestinal cancer (23 cases) and hepatic, biliary, and pancreatic cancer (21 cases). A molecular tumor board had been completed on all 130 cases by October 31, 2019. The median number of gene alterations detected by Foundation testing, excluding variants of unknown significance (VUS) was 4 (ranged 0 to 21) per case. Of the 130 cases, one or more alterations were found in 123 cases (94.6%), and in 114 cases (87.7%), actionable alterations with candidates for therapeutic agents were found. In 29 (22.3%) of them, treatment corresponding to the gene alteration was performed. Regarding secondary findings, 13 cases (10%) had an alteration suspected of a hereditary tumor. Of the 13 cases, only one case received a definite diagnosis of hereditary tumor. CONCLUSIONS: Our study showed that clinical sequencing might be useful for detecting gene alterations in various cancer types and exploring treatment options. However, many issues still need to be improved.

Trastuzumab and fulvestrant combination therapy for women with advanced breast cancer positive for hormone receptor and human epidermal growth factor receptor 2: a retrospective single-center study.

BACKGROUND: Trastuzumab and fulvestrant combination therapy is one of the treatment options for patients with hormone receptor- and human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer; however, there are limited studies evaluating the efficacy of this combination therapy. METHODS: We retrospectively reviewed the data of women with hormone receptor- and HER2-positive metastatic breast cancer who received trastuzumab and fulvestrant combination therapy between August 1997 and August 2020 at the Cancer Institute Hospital. The primary endpoint of this study was progression-free survival, and the secondary endpoints were response rate, overall survival and safety. RESULTS: We reviewed the data of 1612 patients with recurrent or metastatic breast cancer, of which 118 patients were diagnosed with hormone receptor- and HER2-positive breast cancer. Of these, 28 patients who received trastuzumab and fulvestrant combination therapy were eligible for this study. The median treatment line for advanced breast cancer was 6 (range, 1-14), the median progression-free survival was 6.4 months (95% confidence interval [CI], 3.46-8.17), and the median overall survival was 35.3 months (95% CI, 20.0-46.7). Of the 28 patients, partial response was observed in 1 (4%), stable disease in 17 (61%), and progressive disease in 10 (36%) patients. The disease control rate was 64%. Adverse events of grade ≥ 3 were not observed. CONCLUSIONS: Trastuzumab and fulvestrant combination therapy showed moderate clinical efficacy and no severe toxicity after standard anti-HER2 treatment, which is a reasonable treatment option for patients with hormone receptor- and HER2-positive metastatic breast cancer. These data contribute to understanding the efficacy of trastuzumab and fulvestrant combination therapy as control data for further development of anti-HER2 agents plus hormone therapy.

Factors affecting the oral health of inpatients with advanced cancer in palliative care.

PURPOSE: Patients with terminal cancer undergoing multidisciplinary palliative care often have oral health problems, but these details are still unclear. This cross-sectional study aimed to elucidate the oral health of patients with terminal-stage cancer who are inpatient recipients of acute-phase palliative care, and to unveil the factors affecting their oral health. METHODS: Participants were 121 patients with terminal-stage cancer (68 males, 53 females, mean age: 73.6 ± 11.1 years) and oral health complaints. They received palliative care at Tokyo Medical and Dental University Medical Hospital between April 2017 and August 2019. Their demographic and medical details were extracted, retrospectively, from their medical records, and their oral health status, such as the number of natural teeth, removable denture usage, Oral Health Assessment Tool (OHAT), and Dysphagia Severity Scale, were evaluated. All outcomes were assessed by a dentist from the palliative care team. RESULTS: The problems with soft tissue, saliva, and oral cleanliness were observed. The absence of posterior occlusal support was common, and the use of removable dentures was often inadequate. In contrast, swallowing function was relatively well-conserved and 46.3% of the participants were capable of nutrition intake solely by mouth. Multiple regression analysis revealed a significant association between total OHAT score and age, consciousness level, prognostic level, and method of nutritional intake. CONCLUSION: The results revealed that the oral health of terminal cancer patients under palliative care declined despite receiving routine oral care from nurses, and suggest the importance of including dental professionals in multidisciplinary palliative care.

Influence of scapular neck length on the extent of impingement-free adduction after reverse total shoulder arthroplasty.

BACKGROUND: Following reverse total shoulder arthroplasty, a short scapular neck length (SNL) decreases postoperative impingement-free adduction, and impingement between the neck of the scapula and the humeral polyethylene cup may cause scapular notching. However, no reports have evaluated the influence of SNL on impingement-free adduction. The purposes of this study were to evaluate the influence of SNL on impingement-free adduction and to examine the effect of glenoid component lateralization and inferiorization on impingement-free adduction. METHODS: By use of 3-dimensional templating software, a virtual reverse total shoulder arthroplasty model was created in 15 patients who had no osteoarthritic change or any other bony deformity. We measured SNLs separately before implant placement (preoperative SNL) and after implant placement (postoperative SNL). The implant used was the Comprehensive Reverse Shoulder System (Zimmer Biomet, Warsaw, IN, USA), and baseplate bony lateralization of 0, 5, and 10 mm, with inferior eccentricity of 0.5 or 4.5 mm, was tested for impingement-free adduction. Correlations between the preoperative and postoperative SNLs and impingement-free adduction were analyzed. RESULTS: The mean preoperative SNL was 8.2 ± 1.9 mm (range, 5.0-11.7 mm), and the mean postoperative SNL was 6.0 ± 2.0 mm (range, 2.1-9.8 mm). There was a moderate correlation between the preoperative SNL and impingement-free adduction (r = 0.628, P = .12) and a strong correlation between the postoperative SNL and impingement-free adduction (r = 0.771, P = .001). Use of the model with 10 mm of bony lateralization and 4.5 mm of inferior eccentricity provided the best results in terms of impingement-free adduction. CONCLUSION: There were correlations between both the preoperative and postoperative SNLs and impingement-free adduction. Although the lateralized and inferiorized center of rotation may increase the risk of loosening of the glenoid component, this offset significantly increased impingement-free adduction.

MYC-PDL1 axis reduces sensitivity to nivolumab in recurrent head and neck squamous cell carcinoma.

Patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) have a poor prognosis. Recently, the use of immune checkpoint inhibitors (ICIs) for drug treatment has been expanding . However, the response rate to immunotherapy is low. Therefore, the identification of predictive biomarkers of response and resistance to ICIs is required for various types of malignant tumors. We report the case of a patient with recurrent and metastatic HNSCC who simultaneously showed different responses to nivolumab in metastatic lesions. After administering nivolumab, metastasis to the multiple cervical lymph node metastases showed a significant reduction, whereas a new metastasis to the right axillary lymph node occurred . Each surgical specimen was analyzed using the cancer gene panel test (FoundationOne CDx) to elucidate why treatment response is distinct among the same patient. Next-generation sequencing revealed MYC amplification and programmed cell death-1 loss in the right axillary lymph nodes but not cervical lymph nodes. Furthermore, t he histopathological findings suggested that MYC amplification regulated programmed death-ligand 1 expression and was involved in a decreased response to ICIs. This result is expected to help predict the efficacy of ICI treatment and select therapeutic agents.

Treatment of advanced lung cancer based on genomic profiling using liquid biopsy (plasma): A review of three cases.

Of the 80 solid tumor cases in which liquid biopsy (LB) was performed using Guardant360 in the PROFILE study, nine were lung cancer cases. Here, we review three cases in which LB was useful in diagnosing ALK fusion-positive lung cancer, selecting sequential ALK-tyrosine kinase inhibitors, confirming uncommon EGFR mutations, and receiving biomarker-compatible therapy.

Effects of parenteral nutrition and hydration on survival in advanced cancer patients with malignant bowel obstruction: secondary analysis of a multicenter prospective cohort study.

PURPOSE: The benefits of parenteral nutrition and hydration (PNH) in patients with advanced cancer remain unknown. Therefore, we conducted a prospective multicenter cohort study to assess the effects of PNH on survival in patients with malignant bowel obstruction (MBO). METHODS: The present study was a secondary analysis. Data on primary nutritional administration routes during the first week of admission to palliative care units, i.e., parenteral nutrition and parenteral hydration, were obtained. Data on the averaged calorie sufficiency rate/total calorie intake (75% ≤ or 750 kcal/day ≤ , 50-75% or 500-750 kcal/day, 25-50% or 250-500 kcal/day, and < 25% or < 250 kcal/day) were also obtained. Participants with MBO were included and divided into two groups: PNH-high (25% ≤ or 250 kcal/day ≤) and PNH-low (< 25% or < 250 kcal/day). We performed time-to-event analyses using the Kaplan-Meier method, log-rank test, and univariate and multivariate Cox regression analyses. RESULTS: Patients were divided into the PNH-high (n = 68) and PNH-low (n = 76) groups. A significant difference was observed in survival rates between the two groups (log-rank P < 0.001). Median survival times were 35.5 (95% CI 27-44) and 17.5 (95% CI 13-21) days, respectively. In the multivariate-adjusted model, a significantly lower risk of mortality was observed in Cox's proportional hazard model in the PNH-high group (HR 0.55 (95% CI 0.36-0.83), P = 0.005) than in the PNH-low group. CONCLUSION: The present results indicated the beneficial effects of PNH for prolonging survival in advanced cancer patients with MBO in palliative care units.

A Pilot Study Analyzing the Clinical Utility of Comprehensive Genomic Profiling Using Plasma Cell-Free DNA for Solid Tumor Patients in Japan (PROFILE Study).

BACKGROUND: The clinical utility of plasma cell-free DNA in precision cancer medicine has not been established. A pilot study was conducted to investigate the clinical utility of comprehensive genomic profiling by liquid biopsy in a Japanese population. METHODS: In this PROFILE study, 102 patients with advanced solid tumors who showed progression with standard systemic therapy underwent liquid biopsy between August 2017 and February 2020. Liquid biopsy was performed using Guardant360. RESULTS: Of the 102 patients, 56 were women, and the median age was 65 years. Regarding the types of cancer, 31 were hepatobiliary and pancreatic cancer, 17 were gastrointestinal cancer, and 13 were breast cancer. Frequently altered genes were TP53 (53.9%, 46/102), KRAS (25.5%, 26/102), PIK3CA (19.6%, 20/102), and EGFR (17.6%, 18/102). At least one genetic aberration was detected in 92 patients (90.2%). Actionable mutation was discovered in 88 patients (86.3%), and 67 patients (65.7%) were clinical trial candidates. Of the 102 patients, 22 (21.6%) were able to receive biomarker-matched therapy. Their best responses were as follows: 1 complete response, 3 partial responses, 7 stable diseases, and 11 progressive diseases. Additionally, the treated patients were divided on the basis of matching scores (≥ 50% vs. < 50%). The patients were divided into high and low groups. The high group had a higher disease control rate (DCR) of 75% compared with 20% in the low group (P = 0.010). CONCLUSIONS: The results indicate that liquid biopsy is useful for identifying actionable mutations associated with the clinical response of selected patients.