Structure-activity relationships of middle-size cyclic peptides, KRAS inhibitors derived from an mRNA display.

Cyclic peptides are attracting attention as therapeutic agents due to their potential for oral absorption and easy access to tough intracellular targets. LUNA18, a clinical KRAS inhibitor, was transformed-without scaffold hopping-from the initial hit by using an mRNA display library that met our criteria for drug-likeness. In drug discovery using mRNA display libraries, hit compounds always possess a site linked to an mRNA tag. Here, we describe our examination of the Structure-Activity Relationship (SAR) using X-ray structures for chemical optimization near the site linked to the mRNA tag, equivalent to the C-terminus. Structural modifications near the C-terminus demonstrated a relatively wide range of tolerance for side chains. Furthermore, we show that a single atom modification is enough to change the pharmacokinetic (PK) profile. Since there are four positions where side chain modification is permissible in terms of activity, it is possible to flexibly adjust the pharmacokinetic profile by structurally optimizing the side chain. The side chain transformation findings demonstrated here may be generally applicable to hits obtained from mRNA display libraries.

Prescription Pattern of Anamorelin; a Therapeutic Agent for Cancer Cachexia.

Background: The commercial availability of anamorelin, Japan's first therapeutic agent for cancer cachexia in 2021, led to an investigation into its prescription patterns at Toyama University Hospital. Objective: We aimed to analyze anamorelin prescription trends and outcomes among cancer cachexia patients. Methods: A retrospective study from July 2021 to December 2022 examined 88 cases, assessing demographics, cancer types, prescription locations, and meal intake changes. Results: Anamorelin usage was predominant during chemotherapy, especially for pancreatic cancer in outpatient settings. Approximately 30% experienced increased meal intake. Chemotherapy-initiated cases had a longer median duration (55 days) compared with best supportive care only cases (12 days). Conclusion: Anamorelin demonstrated significant prescription patterns, particularly during chemotherapy for pancreatic cancer in outpatient settings, suggesting potential efficacy enhancements when administered with chemotherapy in cancer cachexia management. The study underscores the importance of tailored approaches to optimize anamorelin's therapeutic benefits.

Comparison of the efficacy of first­/second­generation EGFR­tyrosine kinase inhibitors and osimertinib for EGFR­mutant lung cancer with negative or low PD­L1 expression.

In epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) with negative or low programmed death ligand-1 (PD-L1) expression, the acquisition rate of the T790M mutation is higher after treatment with first-/second-generation EGFR-tyrosine kinase inhibitors (TKIs) and the progression-free survival (PFS) is longer in patients treated with osimertinib. The present study compared the clinical course after the initiation of each EGFR-TKI monotherapy in patients with EGFR-mutant NSCLC with negative or low PD-L1 expression. Data of patients with EGFR-mutant NSCLC with negative or low PD-L1 expression who were treated with EGFR-TKI monotherapy were retrieved and retrospectively analyzed. Between June 2013 and November 2023, 26 and 29 patients were treated with first-/second-generation EGFR-TKIs and osimertinib, respectively. The PFS time was longer in patients treated with osimertinib (median, 22.5 months) than in those treated with first-/second-generation EGFR-TKIs (median, 12.9 months). However, the EGFR-TKI treatment duration, defined as the PFS for osimertinib, or the sum of the PFS for first-/second-generation EGFR-TKIs and sequential osimertinib therapy after the acquisition of the T790M mutation, was similar between patients treated with first-/second-generation EGFR-TKIs (median, 23.0 months) and osimertinib (median, 22.5 months). The Cox proportional hazard model suggested that there was no significant difference in the EGFR-TKI treatment duration between patients treated with first-/second-generation EGFR-TKIs and patients treated with osimertinib (hazard ratio, 1.31, 95% CI, 0.55-3.13). In conclusion, first-/second-generation EGFR-TKIs and osimertinib were associated with a similar EGFR-TKI treatment duration in patients with EGFR-mutant NSCLC with negative or low PD-L1 expression. The findings suggested that both treatments are promising for this population.

Pure Red Cell Aplasia and Chromosomal Abnormality in a Patient With Lung Adenocarcinoma Receiving Immune Checkpoint Inhibitors: A Case Report.

BACKGROUND/AIM: Immune checkpoint inhibitors can induce immune-related adverse events in various organs, thus careful observation is required. CASE REPORT: A 69-year-old man was diagnosed with advanced lung adenocarcinoma and treated with combined therapy of carboplatin plus pemetrexed plus pembrolizumab. After two cycles of treatment, anemia was noted. Myelosuppression due to cytotoxic anticancer agents was suspected and the cytotoxic agents were discontinued, followed by three courses of pembrolizumab monotherapy. However, the anemia persisted, requiring red blood cell transfusions. A bone marrow biopsy revealed erythroblast hypoplasia and chromosomal abnormalities, resulting in a diagnosis of pure red cell aplasia. These adverse events were considered immune-related because of the treatment history with an immune checkpoint inhibitor, and 60 mg/day (1 mg/kg/day) of prednisolone was initiated. Anemia improved, and it did not recur during the tapering of prednisolone. CONCLUSION: Immune-related pure red cell aplasia should be considered for patients presenting anemia during treatment with immune checkpoint inhibitors.

Immune Checkpoint Inhibitor Therapy for Patients With Non-small Cell Lung Cancer Ineligible for Platinum Doublet Chemotherapy.

BACKGROUND/AIM: Combined therapy with immune checkpoint inhibitors plus platinum doublet chemotherapy has a survival advantage over platinum doublet chemotherapy in patients with non-small cell lung cancer. However, a variety of factors make it difficult to administer treatment with platinum doublet chemotherapy in many patients in clinical practice and there are few reports on the efficacy and safety of first-line treatments with immune checkpoint inhibitors for patients who are ineligible for platinum doublet chemotherapy. This observational study aimed to evaluate the efficacy and safety of first-line immune checkpoint inhibitor therapy for this population. PATIENTS AND METHODS: We retrospectively assessed the survival and adverse events from the initiation of first-line immune checkpoint inhibitor therapy, including pembrolizumab or nivolumab plus ipilimumab in patients with non-small cell lung cancer who were ineligible for platinum doublet chemotherapy. RESULTS: Data from 48 patients were analyzed. Seventeen patients showed a performance status (PS) of ≥2 while 16 and 15 patients were considered ineligible for platinum doublet chemotherapy because of age and comorbidities, respectively. The median (95% confidential interval, CI) progression-free survival (PFS) and overall survival (OS) of the 48 patients were 7.1 (1.7-13.7) and 31.7 (8.8-not estimated) months, respectively. The two-year PFS and OS rates (95% CI) were 30.8% (18.2%-47.2%) and 50.7% (33.7%-67.7%), respectively. In patients with a PS of ≥2, the median (95% CI) PFS and OS were 1.6 (1.2-not estimated) and 5.5 (2.3-not estimated) months, respectively. The two-year PFS and OS rates (95% CI) were 34.3% (15.8%-59.2%) and 45.3% (22.2%-70.7%), respectively. CONCLUSION: Patients with non-small cell lung cancer and a PS of 0-1 who were ineligible for platinum doublet chemotherapy had favorable outcome after the initiation of ICI therapy, and even in patients with a PS of ≥2, they achieved high two-year PFS and OS rates.

Multifocal fatty liver nodules mimicking a metastatic disease: A case report.

Multifocal fatty liver nodules can present a diagnostic challenge due to their resemblance to metastatic liver disease. This case report illustrates the complexity of such scenarios through the presentation of a middle-aged male patient. Despite the common nature of fatty liver disease, characterized by hepatocyte fat accumulation leading to diffuse and uniform liver lesions, rare instances exhibit heterogeneous appearances. The case underlines the potential confusion arising from imaging modalities when multiple small nodules disperse throughout the liver, mimicking multifocal tumors or metastases. The report emphasizes the critical role of comprehensive diagnostic procedures in preventing misdiagnosis and unwarranted interventions. Effective management hinges on multidisciplinary collaboration among specialists, ensuring accurate differentiation and appropriate treatment. This study serves as a reminder of the intricacies involved in interpreting multifocal fatty liver nodules that may masquerade as metastatic disease, highlighting the need for precision in clinical practice.

Pituitary apoplexy in endocrinologically silent adenoma during somatostatin analog administration for pancreatic neuroendocrine tumor: A case report.

A dopamine agonist administered for prolactinoma treatment and pituitary stimulation tests are reported as risk factors for pituitary apoplexy. We report a case of an 82-year-old patient who suffered from pituitary apoplexy in an endocrinologically silent adenoma during lanreotide administration. The patient was diagnosed with a pancreatic neuroendocrine tumor with lymph node metastasis and treated with lanreotide for two years. An endoscopic endonasal transsphenoidal approach was used for tumor and hematoma removal. The specimen showed growth hormone and prolactin positivity and was diagnosed as pit1-lineage plurihormonal adenoma. The tumor also showed positivity for somatostatin receptor 2. Thus, lanreotide treatment is a risk factor for pituitary apoplexy even in silent adenoma.

Discharge to home from a palliative care unit: impact on survival and factors associated with home death after the discharge: a cohort study.

BACKGROUND: Staying at home during the dying process is important for many patients; and palliative care units (PCUs) can help facilitate home death. This study compared patient survival between those who were discharged to home from a palliative care unit and those who were not, and aimed to identify the factors associated with home death after the discharge. METHODS: This retrospective cohort study used a database of patients admitted to a palliative care unit at Kouseiren Takaoka Hospital in Japan. All consecutive patients admitted to the hospital's PCU between October 2016 and March 2020 were enrolled. Patient survival and factors potentially associated with survival and place of death were obtained. A total of 443 patients with cancer were analyzed, and 167 patients were discharged to home and 276 were not. RESULTS: Propensity score matching analyses revealed that median survival time was significantly longer in patients who were discharged to home than those who were not (57 vs. 27 days, P < 0.001). Multiple logistic regression analysis identified that worse Palliative Prognostic Index (odds ratio [OR] = 1.21, 95% confidence interval [CI] = 1.03-1.44, p = 0.025) and family members' desire for home death (OR = 6.30, 95% CI = 2.32-17.1, p < 0.001) were significantly associated with home death after their discharge. CONCLUSIONS: Discharge to home from palliative care units might have some positive impacts on patient survival.

Validation of a New Methodology to Create Oral Drugs beyond the Rule of 5 for Intracellular Tough Targets.

Establishing a technological platform for creating clinical compounds inhibiting intracellular protein-protein interactions (PPIs) can open the door to many valuable drugs. Although small molecules and antibodies are mainstream modalities, they are not suitable for a target protein that lacks a deep cavity for a small molecule to bind or a protein found in intracellular space out of an antibody's reach. One possible approach to access these targets is to utilize so-called middle-size cyclic peptides (defined here as those with a molecular weight of 1000-2000 g/mol). In this study, we validated a new methodology to create oral drugs beyond the rule of 5 for intracellular tough targets by elucidating structural features and physicochemical properties for drug-like cyclic peptides and developing library technologies to afford highly N-alkylated cyclic peptide hits. We discovered a KRAS inhibitory clinical compound (LUNA18) as the first example of our platform technology.

Epidemiological and therapeutic profiles of lung cancer patients in the Hokushin Region Japan: a retrospective hospital administrative database study.

OBJECTIVE: This study was performed to validate the epidemiology, initial treatment, and clinical practice of lung cancer patients in the Hokushin region, Japan. METHODS: We retrospectively surveyed data of 5503 newly diagnosed and registered lung cancer patients in 22 principal hospital-based cancer registries in Hokushin region linked with health insurance claims data for registered patients between 2016 and 2017. RESULTS: The patients consisted of 3677 (66.8%) men and 1826 (33.2%) women with a mean (range) age of 72.2 (27-103) years). Diagnoses were small cell lung cancer (n = 512, 9.4%), squamous cell carcinoma (n = 1083, 19.7%), and non-squamous non-small cell lung cancer (NSCLC; n = 3906, 70.9%). The population with stage I disease in Toyama prefecture (41.1%) was smaller than in the other three prefectures associated with reduced selection of initial surgical therapy and increased frequencies of stage IV disease (33.2%) and best supportive care (18.6%). Initial chemotherapy for stage IV non-squamous NSCLC consisted of tyrosine kinase inhibitors in 39.3% of cases for EGFR and 4% of cases for ALK-positive non-squamous NSCLC, followed by platinum compounds (25.9%) non-platinum compounds (12.9%), and immune checkpoint inhibitors (10.2%). Carboplatin was the commonly prescribed first-line cytotoxic chemotherapeutic agent (65.4% of patients under 75 years and in 96.7% of patients over 75 years). CONCLUSION: This study revealed real-world data on epidemiological and treatment status in lung cancer in four prefectures in Hokushin region, Japan. Simultaneous analysis of nationwide registry and insurance data could provide valuable insights for the development of lung cancer screening and medical treatment strategies. In addition, the comparative data analysis with other lesions or countries will be useful for evaluating the differences in clinical practice of cancer managements.

Calorie Restriction Impairs Anti-Tumor Immune Responses in an Immunogenic Preclinical Cancer Model.

(1) Background: Although the important role of dietary energy intake in regulating both cancer progression and host immunity has been widely recognized, it remains unclear whether dietary calorie restriction (CR) has any impact on anti-tumor immune responses. (2) Methods: Using an immunogenic B16 melanoma cell expressing ovalbumin (B16-OVA), we examined the effect of the CR diet on B16-OVA tumor growth and host immune responses. To further test whether the CR diet affects the efficacy of cancer immunotherapy, we examined the effect of CR against anti-PD-1 monoclonal antibody (anti-PD-1 Ab) treatment. (3) Results: The CR diet significantly slowed down the tumor growth of B16-OVA without affecting both CD4+ and CD8+ T cell infiltration into the tumor. Although in vivo depletion of CD8+ T cells facilitated B16-OVA tumor growth in the control diet group, there was no significant change in the tumor growth in the CR diet group with or without CD8+ T cell-depletion. Anti-PD-1 Ab treatment lost its efficacy to suppress tumor growth along with the activation and metabolic shift of CD8+ T cells under CR condition. (4) Conclusions: Our present results suggest that a physical condition restricted in energy intake in cancer patients may impair CD8+ T cell immune surveillance and the efficacy of immunotherapy.

First-Line Genomic Profiling in Previously Untreated Advanced Solid Tumors for Identification of Targeted Therapy Opportunities.

IMPORTANCE: Precision oncology using comprehensive genomic profiling (CGP) by next-generation sequencing is aimed at companion diagnosis and genomic profiling. The clinical utility of CGP before the standard of care (SOC) is still not resolved, and more evidence is needed. OBJECTIVE: To investigate the clinical utility of next-generation CGP (FoundationOne CDx [F1CDx]) in patients with previously untreated metastatic or recurrent solid tumors. DESIGN, Setting, and Participants: This multicenter, prospective, observational cohort study enrolled patients with previously untreated advanced solid tumors between May 18, 2021, and February 16, 2022, with follow-up through August 16, 2022. The study was conducted at 6 hospitals in Japan. Eligible patients were aged 20 years or older and had Eastern Cooperative Oncology Group performance status of 0 to 1 with previously untreated metastatic or recurrent cancers in the gastrointestinal or biliary tract; pancreas, lung, breast, uterus, or ovary; and malignant melanoma. EXPOSURE: Comprehensive genomic profiling testing before SOC for advanced solid tumors. MAIN OUTCOMES AND MEASURES: Proportion of patients with actionable or druggable genomic alterations and molecular-based recommended therapy (MBRT). RESULTS: A total of 183 patients met the inclusion criteria and 180 patients (92 men [51.1%]) with a median age of 64 years (range, 23-88 years) subsequently underwent CGP (lung [n = 28], colon/small intestine [n = 27], pancreas [n = 27], breast [n = 25], biliary tract [n = 20], gastric [n = 19], uterus [n = 12], esophagus [n = 10], ovary [n = 6], and skin melanoma [n = 6]). Data from 172 patients were available for end point analyses. Actionable alterations were found in 172 patients (100.0%; 95% CI, 97.9%-100.0%) and druggable alternations were identified in 109 patients (63.4%; 95% CI, 55.7%-70.6%). The molecular tumor board identified MBRT for 105 patients (61.0%; 95% CI, 53.3%-68.4%). Genomic alterations included in the companion diagnostics list of the CGP test were found in 49 patients (28.5%; 95% CI, 21.9%-35.9%) in a tumor-agnostic setting. After a median follow-up of 7.9 months (range, 0.5-13.2 months), 34 patients (19.8%; 95% CI, 14.1%-26.5%) received MBRT. CONCLUSIONS AND RELEVANCE: The findings of this study suggest that CGP testing before SOC for patients with advanced solid tumors may be clinically beneficial to guide the subsequent anticancer therapies, including molecularly matched treatments.

Development of Orally Bioavailable Peptides Targeting an Intracellular Protein: From a Hit to a Clinical KRAS Inhibitor.

Cyclic peptides as a therapeutic modality are attracting a lot of attention due to their potential for oral absorption and accessibility to intracellular tough targets. Here, starting with a drug-like hit discovered using an mRNA display library, we describe a chemical optimization that led to the orally available clinical compound known as LUNA18, an 11-mer cyclic peptide inhibitor for the intracellular tough target RAS. The key findings are as follows: (i) two peptide side chains were identified that each increase RAS affinity over 10-fold; (ii) physico-chemical properties (PCP) including Clog P can be adjusted by side-chain modification to increase membrane permeability; (iii) restriction of cyclic peptide conformation works effectively to adjust PCP and improve bio-activity; (iv) cellular efficacy was observed in peptides with a permeability of around 0.4 × 10-6 cm/s or more in a Caco-2 permeability assay; and (v) while keeping the cyclic peptide's main-chain conformation, we found one example where the RAS protein structure was changed dramatically through induced-fit to our peptide side chain. This study demonstrates how the chemical optimization of bio-active peptides can be achieved without scaffold hopping, much like the processes for small molecule drug discovery that are guided by Lipinski's rule of five. Our approach provides a versatile new strategy for generating peptide drugs starting from drug-like hits.

Peripheral CD4 memory T cells predict the efficacy of immune checkpoint inhibitor therapy in patients with non-small cell lung cancer.

Immune checkpoint inhibitors have significantly improved the prognosis in patients with non-small cell lung cancer, compared with cytotoxic agents. However, the prediction of treatment response is often difficult, even after assessing the tumor programmed death-ligand 1 expression. We conducted this observational study to analyze the association between the differentiation of peripheral CD4 + T cells and the efficacy of immune checkpoint inhibitor therapy. We enrolled patients who were diagnosed with non-small cell lung cancer and received immune checkpoint inhibitor therapy between 2020 and 2022. Blood samples were collected at the start of immune checkpoint inhibitor therapy, and the expressions of PD-1, CCR7, and CD45RA in peripheral CD4 + T cells were analyzed by flow cytometry. The association between the findings of flow cytometry and survival after the initiation of the immune checkpoint inhibitor therapy was evaluated. Forty patients with non-small cell lung cancer were enrolled. The Cox proportional hazards model showed that an increased proportion of CD45RA-CD4 + T cells was associated with a reduced risk of progression after adjustment for performance status, tumor programmed death-ligand 1 expression level, mutation status of the epidermal growth factor receptor gene, and combined therapy with cytotoxic agents. The present study showed that the proportion of peripheral CD45RA- CD4 + T cells was associated with progression-free survival after the initiation of immune checkpoint inhibitor therapy, independent of several clinical factors.

Association Between the Severity of Immune-related Adverse Events and the Prognosis in Patients With Non-small Cell Lung Cancer Receiving Treatment With Immune Checkpoint Inhibitors.

BACKGROUND/AIM: Among patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI), survival is reported to be longer in those experiencing immune-related adverse events (irAEs). We evaluated the progression-free survival (PFS) in the absence of further treatment after ICI therapy was discontinued because of the emergence of irAEs in patients with NSCLC. PATIENTS AND METHODS: Data from patients with NSCLC in whom ICI therapy was discontinued because of the development of irAEs were retrospectively analyzed. The primary endpoint was the PFS from the last day of administration of ICIs, in the absence of any further treatment. RESULTS: A total of 162 patients with NSCLC received treatment with ICIs between January 2016 and December 2021. Among them, ICI therapy was discontinued in 33 patients because of the appearance of irAEs. The median (95% confidence interval) PFS in the absence of any treatment after the last administration of ICIs was 7.2 (4.2-12.3) months. According to the Common Terminology Criteria for Adverse Events, the Cox proportional hazards model was used to identify the severity of irAEs, which were determined to be significantly associated with the PFS in the absence of any further treatment after the last administration of ICI therapy. CONCLUSION: Although the present study showed that the PFS in patients with NSCLC was relatively long in the absence of any further treatment after the last administration of ICIs, the PFS was associated with the severity of the irAEs, and some patients showed early disease progression or death.

Multi-institutional survey of antiemetic therapy in lung cancer patients treated with carboplatin in Hokushin region.

OBJECTIVE: Appropriate monitoring and management of chemotherapy-induced nausea and vomiting (CINV) with prophylactic antiemetics is important for cancer patients. This study was performed to validate the clinical practice of antiemetic use with carboplatin-based chemotherapy in lung cancer patients in the Hokushin region (Toyama, Ishikawa, Fukui, and Nagano prefectures), Japan. METHODS: We surveyed retrospective data of newly diagnosed and registered lung cancer patients initially treated with carboplatin-based chemotherapy in 21 principal hospitals in the Hokushin region linked with health insurance claims data between 2016 and 2017. RESULTS: A total of 1082 lung cancer patients (861 [79.6%] men, 221 [20.4%] women; median age 69.4 years [range, 33-89 years]). All patients received antiemetic therapy, with 613 (56.7%) and 469 patients (43.3%) receiving 5-hydroxytryptamine-3 receptor antagonist/dexamethasone double regimen and 5-hydroxytryptamine-3 receptor antagonist/dexamethasone/neurokinin-1 receptor antagonist triple regimen, respectively. However, the rates of double regimen and use of palonosetron were higher in Toyama and Fukui prefectures. Thirty-nine patients (3.6%) changed from double to triple regimen, while 41 patients (3.8%) changed from triple to double regimen after the second cycle, but six of these returned to triple antiemetics in subsequent cycles. CONCLUSION: Adherence to antiemetic guidelines in clinical practice was high in Hokushin region. However, rates of double and triple antiemetic regimens differed between the four prefectures. Simultaneous analysis of nationwide registry and insurance data was valuable for evaluating and comparing the differences in the status of antiemesis and management.

Associations of immune checkpoint inhibitor therapy efficacy with clinical parameters and tumor­infiltrating CD68­positive cell counts in patients with EGFR­mutant non­small cell lung cancer.

Immune checkpoint inhibitor (ICI) therapy has been less effective in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations than in patients with EGFR wild-type NSCLC. This retrospective study was conducted to investigate the associations of clinical parameters with the efficacy of ICI therapy in patients with EGFR-mutant NSCLC. Clinical information was retrieved from the medical charts, and immunohistochemical analysis was performed in some cases to determine the tumor-infiltrating CD68-positive cell count. Data from 46 patients were included in the analysis. The median (95% confidence interval) progression-free survival and overall survival from the initiation of ICI therapy was 1.4 months (1.0-1.7 months) and 6.4 months (3.9-19.0 months), respectively. Analysis using a Cox proportional hazards model revealed that tumor programmed death-ligand 1 expression was associated with the overall survival of patients with EGFR-mutant NSCLC after ICI treatment. The tumor-infiltrating CD68-positive cell count was evaluated in 11 patients. Comparison using the log-rank test revealed that the progression-free survival time after ICI treatment was longer in the patients with lower tumor-infiltrating CD68-positive cell counts than those with higher tumor-infiltrating CD68-positive cell counts. The present analysis demonstrated that PD-L1 expression and the tumor-infiltrating CD68-positive cell count may be associated with the efficacy of ICI therapy in patients with NSCLC harboring EGFR mutations.

Diagnostic accuracy of a predictive scoring tool for patients who are eligible for home discharge from a palliative care unit.

BACKGROUND: Staying at a preferred place, principally at home, is of great value for dying patients, and palliative care units (PCUs) have an important role in providing adequate support so that patients can be discharged and go home. We attempted to create and validate a scoring tool to predict whether a cancer patient admitted to a PCU will be discharged home. METHODS: All 369 cancer patients admitted to the PCU of a 533-bed general hospital in Japan from October 2016 to October 2019 were enrolled. As outcomes, we recorded whether patients were discharged to home, died in hospitals, or were discharged to other hospitals. Attending physicians recorded 22 potential scale items at admission, including (I) demographic variables, (II) patient general conditions, (III) vital signs, (IV) medications, and (V) patient symptoms. Training-testing procedure to develop a screening score was performed. RESULTS: Among 369 cancer patients admitted to the PCU, we excluded 10 cases for whom a death location could not be identified. Among the remaining 359 patients, 180 were analyzed in the development phase and 179 in the validation phase. Multivariate logistic regression analysis identified five items as independent factors associated with discharge to home, and a prediction equation was created using the regression coefficients: sex (female, 4 points), calorie intake (520 kcal or more, 19 points), availability of daytime caregivers (11 points), family's preferred place of care (home, 139 points), and symptoms that resulted in hospitalization (not fatigue, 7 points). Using a cutoff point of 155, the area under the curve (AUC) value was 0.949 with 95% confidence intervals of 0.918 to 0.981. In the validation sample, the sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and error rate were 75.3%, 86.3%, 82.2%, 80.6%, and 18.4%, respectively. CONCLUSIONS: Whether a patient admitted to a PCU can discharge to home could be predicted using the simple clinical tool. Further validation and outcome studies are warranted.

Efficacy of immune checkpoint inhibitor therapy in patients with pulmonary sarcomatoid carcinoma in clinical practice.

OBJECTIVE: Studies have suggested the potential efficacy of immune checkpoint inhibitors (ICIs) for pulmonary sarcomatoid carcinoma. This multicenter observational study was conducted to evaluate the efficacy of systemic ICI therapy and chemoradiation followed by durvalumab therapy for pulmonary sarcomatoid carcinoma. METHODS: We analyzed the data of patients with pulmonary sarcomatoid carcinoma who received systemic ICI therapy or chemoradiation followed by durvalumab therapy between 2016 and 2022. RESULTS: In this study, data of a total of 22 patients who received systemic ICI therapy and four patients who received chemoradiation followed by durvalumab therapy were analyzed. In the patients who received systemic ICI therapy, the median progression-free survival after initiation of therapy was 9.6 months, and the overall survival did not reach the median. The 1-year progression-free survival rate and overall survival rate were estimated to be 45.5% and 50.1%, respectively. Although the log-rank test revealed no significant association between the tumor expression level of programmed death ligand-1 (tumor proportion score evaluated using 22C3 antibody: ≥50% vs. <50%) and the survival duration, the majority of patients showing long-term survival showed a tumor proportion score of ≥50%. Of four patients treated with chemoradiation followed by durvalumab therapy, two patients showed an overall survival of ≥30 months, whereas the remaining two patients died within 12 months. CONCLUSION: The progression-free survival of patients who received systemic ICI therapy was 9.6 months, suggesting that ICI therapy might be effective in patients with pulmonary sarcomatoid carcinoma.