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Purpose: Although the treatment of nonsmall cell lung cancer (NSCLC) has rapidly progressed recently, there is little evidence of treatment for patients with symptomatic brain metastases (BM) and poor performance status (PS). However, in symptomatic BM patients, appropriate upfront intracranial treatment can often lead to rapid improvement in PS and effective systemic therapy. Thus, this study investigated the prognostic factors for the survival of poor PS NSCLC patients with synchronous BM. Methods: Data of patients with BM and Karnofsky PS (KPS) ≤70 at the first diagnosis of NSCLC who were treated in our hospital between January 2017 and December 2021 were reviewed. Patient survival was compared among patients stratified by type of first-line regimen of systemic treatment. Correlations between patient characteristics and survival were examined. Results: Fifty patients receiving aggressive treatment were enrolled. The median survival times for tyrosine kinase inhibitor (TKI), immune checkpoint inhibitor (ICI), and chemotherapy alone groups were 19 (95 % confidence interval [CI], 2.8–68.5), 19 (3.0–62.0), and 13 (1.2–24.8) months, respectively. Survival in the TKI and ICI groups was significantly longer than in the chemotherapy alone group (p = 0.046, TKI vs. chemo; p = 0.022, ICI vs. chemo; p = 0.023). Both sex and type of systemic treatment correlated to survival time on univariate analysis. Chemotherapy alone for systemic treatment [p = 0.034; hazard ratio (HR), 0.44 (0.20–0.94)] remained significant for predicting overall survival in the multivariate analysis. Conclusion: Even in patients with poor PS and BM at the initial diagnosis of NSCLC, the ICI group had a survival time comparable to that of the TKI group when combined with tailor-made intracranial treatment. There is a subgroup in the patient population that was previously considered unsuitable for ICI, whose PS improves with individualized intracranial treatment, and who may benefit from immunotherapy.

Objective: Treatment of H3K27M-altered midline gliomas is a significant challenge. This study aims to assess the efficacy of radiotherapy for these patients. Materials and Methods: Thirteen patients with histologically confirmed H3K27M-altered midline glioma, treated with radiotherapy+/- temozolomide between 2019 and 2021, were retrospectively analyzed. Clinical and radiological responses, survival times, and prognostic factors were evaluated. All patients were treated with hypofractionated radiotherapy, with a dose of 25-40 Gy. Results: The median age was 42 years (ranging from 19 to 55). Karnofsky Performance Status scores ranged from 50 to 70, with a median score of 50. Hypofractionated radiotherapy was administered to all patients, with 25 Gy given in 5 fractions to 7 patients (53.8%), 39 Gy in 13 fractions to 3 patients (23.1%), and 40 Gy in 15 fractions to 3 patients (23.1%). Clinically, two patients (15.4%) showed symptomatic improvement, five patients (38.8%) remained stable, and six patients (46.2%) had neurological deterioration. Radiologically, one patient had a partial response, six patients (46.2%) had stable disease, and radiological progression occurred in three patients (23.1%). The median progression-free survival and median overall survival time were 123 and 154 days, respectively. Karnofsky Performance Status 50 was associated with a worse prognosis. Conclusion: These results suggest that the efficacy of radiotherapy might be limited for adults with H3K27M-altered midline gliomas with poor performance status. New studies are necessary for a more comprehensive understanding of effective therapeutic strategies. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to retrospectively analyzed the feasibility of fast four-dimensional computed tomography (4DCT)-based O-ring LINAC treatment for patients with an average respiratory amplitude was< 0.5 cm and who cannot endure long treatment times due to poor performance status in lung 4Dstereotactic body radiotherapy (SBRT). Methods: This study included data of 38 patients who received lung 4D-SBRT and had average respiratory amplitude< 0.5 cm in the full phase. C-arm LINAC plans were based on 4DCT data obtained at phase values ranging from 20–70% using a C-arm LINAC. O-ring LINAC plans were retrospectively established based on 4DCT data obtained at phase values of 0–90% using an O-ring LINAC. The conformity index (CI), homogeneity index (HI), and gradient measurement of the planning target volumes (PTV) were analyzed to compare dosimetric data between C-arm LINAC and O-ring LINAC plans. Organs at risk were analyzed in accordance with the Radiation Therapy Oncology Group 0915 protocol. Treatment delivery time and total monitor units were analyzed to compare the efficiency of treatment delivery. Statistical comparisons were performed using the Wilcoxon signed-rank test (P< 0.05). Results: For the PTV, there was no significant difference in the CI or HI between C-arm LINAC and O-ring LINAC plans. For organs-at-risk, all plans met the criteria for dose constraint. There was a significant difference between C-arm LINAC and O-ring LINAC plans except in the spinal cord. Treatment delivery time was 92% longer for C-arm LINAC plans than for O-ring LINAC plans. The total MU value for C-arm LINAC plans was 9.6% higher than that for O-ring LINAC plans. Conclusion: We verified the feasibility of fast 4DCT-based O-ring LINAC treatment for patients with average respiratory amplitude< 0.5 cm and who cannot endure long treatment times due to poor performance status in lung 4D-SBRT. [ABSTRACT FROM AUTHOR]

PurposeWe aimed to retrospectively analyzed the feasibility of fast four-dimensional computed tomography (4DCT)-based O-ring LINAC treatment for patients with an average respiratory amplitude was< 0.5 cm and who cannot endure long treatment times due to poor performance status in lung 4D-stereotactic body radiotherapy (SBRT).MethodsThis study included data of 38 patients who received lung 4D-SBRT and had average respiratory amplitude< 0.5 cm in the full phase. C-arm LINAC plans were based on 4DCT data obtained at phase values ranging from 20–70% using a C-arm LINAC. O-ring LINAC plans were retrospectively established based on 4DCT data obtained at phase values of 0–90% using an O-ring LINAC. The conformity index (CI), homogeneity index (HI), and gradient measurement of the planning target volumes (PTV) were analyzed to compare dosimetric data between C-arm LINAC and O-ring LINAC plans. Organs at risk were analyzed in accordance with the Radiation Therapy Oncology Group 0915 protocol. Treatment delivery time and total monitor units were analyzed to compare the efficiency of treatment delivery. Statistical comparisons were performed using the Wilcoxon signed-rank test (P< 0.05).ResultsFor the PTV, there was no significant difference in the CI or HI between C-arm LINAC and O-ring LINAC plans. For organs-at-risk, all plans met the criteria for dose constraint. There was a significant difference between C-arm LINAC and O-ring LINAC plans except in the spinal cord. Treatment delivery time was 92% longer for C-arm LINAC plans than for O-ring LINAC plans. The total MU value for C-arm LINAC plans was 9.6% higher than that for O-ring LINAC plans.ConclusionWe verified the feasibility of fast 4DCT-based O-ring LINAC treatment for patients with average respiratory amplitude< 0.5 cm and who cannot endure long treatment times due to poor performance status in lung 4D-SBRT.

Purpose: This phase II trial is designed to test whether the performance status (PS) of metastatic non-small cell lung cancer (mNSCLC) patients (pts) can improve with chemotherapy if their poor PS (Eastern Cooperative Oncology Group (ECOG) PS of ≥ 2) is due to disease burden rather than comorbidities. Methods: Age18–65 years, Charlson's comorbidity index < 9, serum albumin ≥ 3.5 g/dl, adequate bone marrow and organ function, & ECOG PS ≥ 2 as judged by the worst score of three independent physicians were administered 3 doses of weekly paclitaxel at 60 mg/m2/dose. The primary endpoint was an improvement in ECOG PS by 1 point at 4 weeks; others: toxicity (CTCAE v 5.0), quality of life (QoL) assessment at baseline and 4 weeks by EORTC QLQ-C30 and EORTC QLQ-LC13. Optimal Simon's 2-stage design was used. Results: Forty-six patients were included with a median age of 56 years (interquartile range, IQR 54–59), 12 (26%) had comorbid conditions, and 87% with ECOG PS 3/4. PS improved in 11 pts at 4 weeks and in 7 beyond this time point. Grade 3/4 toxicities are seen in 20% (most common: anemia and diarrhea). At a median follow-up of 4.8 m (95% CI 3.27–14.9), the median progression-free survival and overall survival were 3.3 months (95% CI 2.36–5.6) and 6.8 months (95% CI 2.47–8.8), respectively. QoL improved for global QoL, role functioning, pain, dyspnea, insomnia, pain in the chest, pain in other parts, and worsened for alopecia and sore mouth. Conclusions: Abbreviated chemotherapy is a useful, well-tolerated strategy in carefully selected poor PS mNSCLC patients that can improve PS and QoL. Clinical trial: Clinical trial information: CTRI/2020/01/022617. [ABSTRACT FROM AUTHOR]

Abstract Background Patients with advanced non‐small cell lung cancer (NSCLC) are a heterogeneous population with short lifespan. We aimed to develop methods to better differentiate patients whose survival was >90 days. Methods We evaluated 83 characteristics of 106 treatment‐naïve, stage IV NSCLC patients with Eastern Cooperative Oncology Group Performance Status (ECOG‐PS) >1. Automated machine learning was used to select a model and optimize hyperparameters. 100‐fold bootstrapping was performed for dimensionality reduction for a second (“lite”) model. Performance was measured by C‐statistic and accuracy metrics in an out‐of‐sample validation cohort. The “lite” model was validated on a second independent, prospective cohort (N = 42). Network analysis (NA) was performed to evaluate the differences in centrality and connectivity of features. Results The selected method was ExtraTrees Classifier, with C‐statistic of 0.82 (p

Abstract Background Cancer chemotherapy indications for patients with poor performance status and advanced lung cancer are limited. Molecular targeted drugs, including epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors, can be used in patients with poor performance status owing to their high efficacy and safety. The third-generation EGFR-tyrosine kinase inhibitor osimertinib has demonstrated effectiveness in the initial treatment of advanced EGFR mutation-positive non-small cell lung cancer in patients with good performance status; however, no evidence exists of the drug’s effectiveness in patients with poor performance status in a prospective study. We designed a study that aims to investigate the efficacy and safety of first-line osimertinib treatment in patients with advanced non-small cell lung cancer harboring sensitive EGFR mutations and with poor performance status. Methods The OPEN/TORG2040 study is a multicenter, single-arm, phase II trial for patients with unresectable, advanced EGFR mutation-positive non-small cell lung cancer with a poor performance status (≥ 2). Eligible patients will receive osimertinib until disease progression or unacceptable toxicity. The primary endpoint is the objective response rate of the first-line osimertinib treatment. Considering a threshold value of 45%, expected value of 70% for objective response rate, one-sided significance level of 5%, statistical power of 80%, and ineligible patients, the sample size was set to 30. The secondary endpoints are disease control rate, performance status improvement rate, and safety and patient-reported outcomes using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Quality of Life Questionnaire and Lung Cancer 13. Time to treatment failure, progression-free survival, and overall survival will also be assessed. Discussion Our study can determine the clinical benefits of osimertinib treatment in patients with poor performance status, since the clinical outcomes of patients with EGFR mutation-positive non-small cell lung cancer with poor performance status treated with this drug as a first-line treatment have not been sufficiently evaluated. Trial registration Japan Registry of Clinical Trials: jRCTs041200100 (registration date: February 12, 2021).

Abstract Rhabdomyosarcoma (RMS) is a common soft tissue sarcoma usually observed in children. However, RMS rarely occurs in adults. The prognosis of adult RMS is poor and a standard chemotherapy regimen has not yet been established. Herein, we report the case of a 60‐year‐old Japanese woman with primary anterior mediastinal alveolar RMS (T3N0M0, stage III). The tumor increased aggressively despite first‐line treatment with doxorubicin (60 mg/m2 every 3 weeks for 1 cycle) and second‐line treatment with eribulin (1.4 mg/m2 every 3 weeks for 2 cycles). Although her shortness of breath and chest tightness worsened as the tumor compressed her heart and left main bronchus, and her performance status (PS) decreased to 3, third‐line treatment with pazopanib (800 mg once daily) was commenced. The treatment led to suppression of tumor growth and resulted in 4‐month progression‐free survival. Therefore, in cases of adult RMS, considering pazopanib treatment as an option may be beneficial, even with previous ineffective treatments or poor PS.

Abstract Background Small-cell lung cancer (SCLC) accounts for 12–15% of lung cancers and has a limited prognosis, with approximately one-third of SCLC patients having a poor performance status (PS). Patients with extensive-stage (ES) SCLC and a poor PS have a poor prognosis. For this population, overall survival from carboplatin and etoposide treatment is 7–8 months, and treatment development is an unmet medical need. Recently, the combination of an anti-PD-L1 (a ligand for programmed cell death 1) antibody and platinum-based chemotherapy has become the standard of care for ES-SCLC patients with a good PS (PS 0–1). We hypothesized that the combination of the anti-PD-L1 antibody durvalumab with carboplatin and etoposide would be feasible and effective for such patients. Methods We initiated a multicenter phase II study of durvalumab combined with carboplatin and etoposide in previously untreated ES-SCLC patients with a poor PS (PS 2–3). Eligible patients will receive durvalumab plus carboplatin and etoposide every 3 to 4 weeks for up to 4 cycles, followed by durvalumab every 4 weeks until progression or unacceptable toxicity. The dosages of carboplatin and etoposide for the second and subsequent cycles will be adaptively determined based on the adverse events of the first cycle. A total of 56 patients (43 patients with a PS of 2 and 13 patients with a PS of 3) will be enrolled in this study, with a 24-month enrollment period and a 12-month follow-up. The primary endpoint is the tolerability of carboplatin and etoposide plus durvalumab in previously untreated ES-SCLC patients with a poor PS. The secondary endpoints are the 1-year survival rate, objective response rate, progression-free survival, overall survival, ratio of PS improvement, and safety. Discussion The results of this study are intended to establish the safety and efficacy of carboplatin and etoposide plus durvalumab in patients with ES-SCLC and a poor PS. Trial registration Japan Registry of Clinical Trials (jRCT), jRCTs031200319. Registered 21 January 2021, https://jrct.niph.go.jp/en-latest-detail/jRCTs031200319

Background: Constipation is a concern among patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 3 and 4. Objectives: To assess naldemedine's efficacy and safety in cancer patients on opioids with poor PS. Design: Multicenter, retrospective study. Setting/Subjects: Japanese cancer patients with ECOG performance status 3 or 4 who received naldemedine. Measurements: Frequency of defecations before/after naldemedine use. Responders were patients whose defecation frequency increased to ≥3 times/week, from baseline ≥1 defecations/week over seven days after naldemedine administration. Results: Seventy-one patients were analyzed; 66.1% were responders (95% confidence interval: 54.5%–76.1%). Defecation frequency increased significantly after naldemedine in the overall population (6 vs. 2, p < 0.0001) and among those who defecated <3 times/week before naldemedine (4.5 vs. 1, p < 0.0001). Diarrhea (38.0%) of all grades was the most common adverse event; 23 (85.2%) events were classified as Grade 1 or 2. Conclusion: Naldemedine is effective and safe among cancer patients with poor PS. [ABSTRACT FROM AUTHOR]

Introduction: Landmark trials testing immune checkpoint inhibitors (ICIs) in advanced NSCLC are difficult to extrapolate to real-world practice given the exclusion of patients with poor (i.e., ≥2) Eastern Cooperative Oncology Group performance status (ECOG PS). We sought to evaluate the impact of ECOG PS on clinical outcomes and health care utilization in patients with NSCLC treated with ICIs in real-world practice. Methods: Patients with advanced NSCLC who received at least one dose of pembrolizumab or nivolumab were retrospectively identified from the Alberta Immunotherapy Database. The primary outcome was median overall survival, as stratified by ECOG PS. Secondary outcomes included median time-to-treatment failure and metrics of health care utilization, including emergency department visits, hospitalizations, and death in hospital. Results: A total of 790 patients were included, with 29.2% having poor ECOG PS at initiation of ICI. These patients had significantly lower median overall survival (3.3 versus 13.4 mo) and median time-to-treatment failure (1.4 versus 4.9 mo) compared with those with favorable ECOG PS (p < 0.0001 for both outcomes). Patients with poor ECOG PS were also more likely to present to the emergency department, be admitted to the hospital, and die in the hospital during their first admission (risk ratio = 1.6, 2.3–2.7, p < 0.001). Conclusions: Patients with NSCLC with poor ECOG PS treated with ICI had significantly worse survival outcomes and were significantly more likely to use health care services than those with favorable ECOG PS. The large proportion of patients with poor ECOG PS further justifies the urgent need for randomized trials evaluating the efficacy of ICI in this high-risk population.

Background: Patients with advanced non‐small cell lung cancer (NSCLC) are a heterogeneous population with short lifespan. We aimed to develop methods to better differentiate patients whose survival was >90 days. Methods: We evaluated 83 characteristics of 106 treatment‐naïve, stage IV NSCLC patients with Eastern Cooperative Oncology Group Performance Status (ECOG‐PS) >1. Automated machine learning was used to select a model and optimize hyperparameters. 100‐fold bootstrapping was performed for dimensionality reduction for a second ("lite") model. Performance was measured by C‐statistic and accuracy metrics in an out‐of‐sample validation cohort. The "lite" model was validated on a second independent, prospective cohort (N = 42). Network analysis (NA) was performed to evaluate the differences in centrality and connectivity of features. Results: The selected method was ExtraTrees Classifier, with C‐statistic of 0.82 (p < 0.01) and accuracy of 0.81 (p = 0.01). The "lite" model had 16 variables and obtained C‐statistic of 0.84 (p < 0.01) and accuracy of 0.75 (p = 0.039) in the first cohort, and C‐statistic of 0.706 (p < 0.01) and accuracy of 0.714 (p < 0.01) in the second cohort. The networks of patients with lower survival were more interconnected. Features related to cachexia, inflammation, and quality of life had statistically different prestige scores in NA. Conclusions: Machine learning can assist in the prognostic evaluation of advanced NSCLC. The model generated with a reduced number of features showed high accessibility and reasonable metrics. Features related to quality of life, cachexia, and performance status had increased correlation and importance scores, suggesting that they play a role at later disease stages, in line with the biological rationale already described. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor-based combination therapy (ICI-based combination) is a new standard of care for metastatic clear cell renal cell carcinoma (mRCC) in the frontline setting. Patients with poor performance status (PS) (≥2) were excluded from pivotal trials. Hence, the activity and safety of ICI-based combination therapy in this group of patients is still unknown. We performed a multicentre retrospective study of PS ≥2 mRCC patients who received frontline ICI-based combination, either nivolumab-ipilimumab (NI) or pembrolizumab-axitinib (AP). Patients' characteristics, clinical outcomes, and toxicity were collected. We analysed overall response rate (ORR), median progression-free survival (mPFS), median overall survival (mOS) and grade ≥3 adverse events (G ≥ 3AEs). The association between the predictive biomarker IPI (immune prognostic index) and ORR/PFS/OS was also evaluated. We identified 70 mRCC patients with PS ≥2 treated with ICI-based combination across 14 institutions between October 2017 and December 2021, including 45 and 25 patients were treated with NI and AP, respectively. Median age at diagnosis was 63 years, 51 (73%) were male, only 17 (24%) had prior nephrectomy, 50 (71%) had synchronous metastatic disease at diagnosis, and 16 (23%) had brain metastases. Sixty-one (87%) and 9 (13%) patients had ECOG (Eastern Cooperative Oncology Group) PS 2 and 3, respectively, and 25 (36%) and 45 (64%) patients were intermediate and poor International Metastatic RCC Database Consortium (IMDC) risk, respectively. Among all, 91% were clear cell RCC, 7 patients had sarcomatoid features. At the time of the analysis (median follow-up 11.1 months), 41% patients were dead. Median PFS and mOS in the entire cohort were 5.4 months and 16.0 months, respectively; ORR was 31%. No significant differences in ORR, PFS, OS, or G ≥3AEs were seen between NI and AP. The intermediate and poor IPI groups were significantly associated with reduced ORR and shorter PFS. We report the first cohort of PS ≥2 mRCC patients treated with frontline ICI-based combination therapy. The survival outcomes in our cohort were inferior to that reported in pivotal trials. No significant differences in ORR, PFS, OS or toxicity were seen between NI and AP. Prospective real-world studies are needed to confirm these results. • First cohort of poor PS mRCC treated with front line ICI-based combination therapy. • The survival outcomes were inferior to that reported in pivotal trials. • No significant differences in ORR, PFS or OS were seen between NI and AP. • Both NI and AP were well tolerated without significant differences between them. [ABSTRACT FROM AUTHOR]

Background: Cancer chemotherapy indications for patients with poor performance status and advanced lung cancer are limited. Molecular targeted drugs, including epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors, can be used in patients with poor performance status owing to their high efficacy and safety. The third-generation EGFR-tyrosine kinase inhibitor osimertinib has demonstrated effectiveness in the initial treatment of advanced EGFR mutation-positive non-small cell lung cancer in patients with good performance status; however, no evidence exists of the drug's effectiveness in patients with poor performance status in a prospective study. We designed a study that aims to investigate the efficacy and safety of first-line osimertinib treatment in patients with advanced non-small cell lung cancer harboring sensitive EGFR mutations and with poor performance status. Methods: The OPEN/TORG2040 study is a multicenter, single-arm, phase II trial for patients with unresectable, advanced EGFR mutation-positive non-small cell lung cancer with a poor performance status (≥ 2). Eligible patients will receive osimertinib until disease progression or unacceptable toxicity. The primary endpoint is the objective response rate of the first-line osimertinib treatment. Considering a threshold value of 45%, expected value of 70% for objective response rate, one-sided significance level of 5%, statistical power of 80%, and ineligible patients, the sample size was set to 30. The secondary endpoints are disease control rate, performance status improvement rate, and safety and patient-reported outcomes using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Quality of Life Questionnaire and Lung Cancer 13. Time to treatment failure, progression-free survival, and overall survival will also be assessed. Discussion: Our study can determine the clinical benefits of osimertinib treatment in patients with poor performance status, since the clinical outcomes of patients with EGFR mutation-positive non-small cell lung cancer with poor performance status treated with this drug as a first-line treatment have not been sufficiently evaluated. Trial registration: Japan Registry of Clinical Trials: jRCTs041200100 (registration date: February 12, 2021). [ABSTRACT FROM AUTHOR]

Background: Small-cell lung cancer (SCLC) accounts for 12-15% of lung cancers and has a limited prognosis, with approximately one-third of SCLC patients having a poor performance status (PS). Patients with extensive-stage (ES) SCLC and a poor PS have a poor prognosis. For this population, overall survival from carboplatin and etoposide treatment is 7-8 months, and treatment development is an unmet medical need. Recently, the combination of an anti-PD-L1 (a ligand for programmed cell death 1) antibody and platinum-based chemotherapy has become the standard of care for ES-SCLC patients with a good PS (PS 0-1). We hypothesized that the combination of the anti-PD-L1 antibody durvalumab with carboplatin and etoposide would be feasible and effective for such patients.Methods: We initiated a multicenter phase II study of durvalumab combined with carboplatin and etoposide in previously untreated ES-SCLC patients with a poor PS (PS 2-3). Eligible patients will receive durvalumab plus carboplatin and etoposide every 3 to 4 weeks for up to 4 cycles, followed by durvalumab every 4 weeks until progression or unacceptable toxicity. The dosages of carboplatin and etoposide for the second and subsequent cycles will be adaptively determined based on the adverse events of the first cycle. A total of 56 patients (43 patients with a PS of 2 and 13 patients with a PS of 3) will be enrolled in this study, with a 24-month enrollment period and a 12-month follow-up. The primary endpoint is the tolerability of carboplatin and etoposide plus durvalumab in previously untreated ES-SCLC patients with a poor PS. The secondary endpoints are the 1-year survival rate, objective response rate, progression-free survival, overall survival, ratio of PS improvement, and safety.Discussion: The results of this study are intended to establish the safety and efficacy of carboplatin and etoposide plus durvalumab in patients with ES-SCLC and a poor PS.Trial Registration: Japan Registry of Clinical Trials (jRCT), jRCTs031200319. Registered 21 January 2021, https://jrct.niph.go.jp/en-latest-detail/jRCTs031200319. [ABSTRACT FROM AUTHOR]

Rhabdomyosarcoma (RMS) is a common soft tissue sarcoma usually observed in children. However, RMS rarely occurs in adults. The prognosis of adult RMS is poor and a standard chemotherapy regimen has not yet been established. Herein, we report the case of a 60‐year‐old Japanese woman with primary anterior mediastinal alveolar RMS (T3N0M0, stage III). The tumor increased aggressively despite first‐line treatment with doxorubicin (60 mg/m2 every 3 weeks for 1 cycle) and second‐line treatment with eribulin (1.4 mg/m2 every 3 weeks for 2 cycles). Although her shortness of breath and chest tightness worsened as the tumor compressed her heart and left main bronchus, and her performance status (PS) decreased to 3, third‐line treatment with pazopanib (800 mg once daily) was commenced. The treatment led to suppression of tumor growth and resulted in 4‐month progression‐free survival. Therefore, in cases of adult RMS, considering pazopanib treatment as an option may be beneficial, even with previous ineffective treatments or poor PS. [ABSTRACT FROM AUTHOR]

Background: Delirium, poor performance status, and dyspnea predict short survival in the palliative care setting.Objective: Our goal was to determine whether these three conditions, which we refer to as a "triple threat," also predict mortality among patients with advanced cancers in the emergency department (ED).Methods: The study sample included 243 randomly selected, clinically stable patients with advanced cancer who presented to our ED. The analysis included patients who had delirium (Memorial Delirium Assessment Scale score ≥ 7), poor performance status (Eastern Cooperative Oncology Group performance status score of 3 or 4), or dyspnea as a presenting symptom. We obtained survival data from medical records. We calculated predicted probability of dying within 30 days and association with number of symptoms after the ED visit using logistic regression analysis.Results: Twenty-eight patients died within 30 days after presenting to the ED. Death within 30 days occurred in 36% (16 of 44) of patients with delirium, 28% (17 of 61) of patients with poor performance status, and 14% (7 of 50) of patients with dyspnea, with a predicted probability of 30-day mortality of 0.38 (95% confidence interval [CI] 0.25-0.53), 0.28 (95% CI 0.18-0.40), and 0.15 (95% CI 0.07-0.29), respectively. The predicted probability of death within 30 days for patients with two or three of the conditions was 0.49 (95% CI 0.34-0.66) vs. 0.05 (95% CI 0.02-0.09) for patients with none or one of the conditions.Conclusions: Patients with advanced cancers who present to the ED and have at least two triple threat conditions have a high probability of death within 30 days. [ABSTRACT FROM AUTHOR]

Background: There is a dearth of studies on the efficacy and safety of the tyrosine kinase inhibitors osimertinib (OSI) and gefitinib (GEF) in treating epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC), even in patients with poor performance status (PS)., Methods: We retrospectively reviewed and compared data of 113 patients with EGFR mutation-positive NSCLC with Eastern Cooperative Oncology Group PS 2-4 who were administered OSI 80 mg/day or GEF 250 mg/day from May 2016 to March 2022., Results: The GEF group (39 patients; median age: 74 years) included 20 patients with a PS of 2, 17 with a PS of 3, and 2 with a PS of 4. The OSI group (74 patients; median age: 76 years) included 48 patients with a PS of 2, 24 with a PS of 3, and 2 with a PS of 4. The overall response rates were 69% and 66% in the GEF and OSI groups, respectively. The disease control and PS improvement rates were 89% and 51% in both groups, respectively. The median progression-free survival in the GEF and OSI groups was 6.9 and 9.2 months, respectively (p = 0.15). The OSI group experienced better overall survival than the GEF group (median: 20.9 vs. 13.0 months, p = 0.0031). The incidence of pneumonitis was 10% and 11% in the GEF and OSI groups, respectively. One treatment-related death owing to pneumonitis occurred in the GEF group., Conclusions: OSI may be a useful treatment for untreated EGFR mutation-positive NSCLC with poor PS., Competing Interests: Declaration of competing interest Kazuhisa Nakashima has received personal fees from Taiho Pharmaceutical, Chugai Pharma, AstraZeneca, Eli Lilly Japan, Nippon Kayaku, and Bristol-Myers Squibb. Hiroaki Kodama has received personal fees from Chugai Pharma and Novartis Pharma. Haruyasu Murakami has received personal fees from Chugai Pharma, Daiichi Sankyo, AstraZeneca, Takeda, Amgen, Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Pfizer, Novartis, Eli Lilly Japan, Taiho Pharmaceutical, Eisai, and Nippon Kayaku, grants from Chugai Pharma, AstraZeneca, Abbvie, Daiichi Sankyo, IQvia, Taiho Pharmaceutical and Bayer. Toshiaki Takahashi has received personal fees from AstraZeneca and MSD, and grants from Chugai Pharma, MSD, Eli Lilly Japan, Merck Biopharma Japan, AnHeart Therapeutics Inc., and Amgen. Kosuke Hamai has received personal fees from Boehringer Ingelheim, Eli Lilly Japan, AstraZeneca, Ono Pharmaceutical, Chugai Pharma, Merck & Co., and Taiho Pharmaceutical. Nobuhisa Ishikawa has received personal fees from AstraZeneca, Boehringer Ingelheim, Novartis, Ono Pharmaceutical, Eli Lilly Japan, Chugai Pharma, Taiho Pharmaceutical, MSD, Takeda, and Pfizer. Shoichi Kuyama has received personal fees from Chugai Pharma, Boehringer Ingelheim, Pfizer, MSD, Kyowa Kirin, Daiichi Sankyo, Novartis, Bristol-Myers Squibb, Eli Lilly Japan, AstraZeneca, Taiho Pharmaceutical, Hisamitsu Pharmaceutical, and Nippon Kayaku. Takeshi Isobe has received personal fees from MSD, AstraZeneca, Ono Pharmaceutical, Daiichi Sankyo, Amgen, Taiho Pharmaceutical, Takeda. Chugai Pharma, Nippon Kayaku, Eli Lilly Japan, Boehringer Ingelheim, Pfizer, and Bristol-Myers Squibb Japan, and grants from Daiichi Sankyo, Novartis, Chugai Pharma, Ono Pharmaceutical, Taiho Pharmaceutical, and Boehringer Ingelheim. Yukari Tsubata has received personal fees from MSD, AstraZeneca, Amgen, Daiichi Sankyo, Taiho Pharmaceutical, Takeda, Chugai Pharma, Eli Lilly Japan, Nippon Kayaku, Novartis, Pfizer, and Bristol-Myers Squibb, and grants from Pfizer and Ono Pharmaceutical. The other authors declare that they have no conflict of interest., (Copyright © 2024 [The Author]. Published by Elsevier B.V. All rights reserved.)

Purpose: Although the treatment of nonsmall cell lung cancer (NSCLC) has rapidly progressed recently, there is little evidence of treatment for patients with symptomatic brain metastases (BM) and poor performance status (PS). However, in symptomatic BM patients, appropriate upfront intracranial treatment can often lead to rapid improvement in PS and effective systemic therapy. Thus, this study investigated the prognostic factors for the survival of poor PS NSCLC patients with synchronous BM., Methods: Data of patients with BM and Karnofsky PS (KPS) ≤70 at the first diagnosis of NSCLC who were treated in our hospital between January 2017 and December 2021 were reviewed. Patient survival was compared among patients stratified by type of first-line regimen of systemic treatment. Correlations between patient characteristics and survival were examined., Results: Fifty patients receiving aggressive treatment were enrolled. The median survival times for tyrosine kinase inhibitor (TKI), immune checkpoint inhibitor (ICI), and chemotherapy alone groups were 19 (95 % confidence interval [CI], 2.8-68.5), 19 (3.0-62.0), and 13 (1.2-24.8) months, respectively. Survival in the TKI and ICI groups was significantly longer than in the chemotherapy alone group (p = 0.046, TKI vs. chemo; p = 0.022, ICI vs. chemo; p = 0.023). Both sex and type of systemic treatment correlated to survival time on univariate analysis. Chemotherapy alone for systemic treatment [p = 0.034; hazard ratio (HR), 0.44 (0.20-0.94)] remained significant for predicting overall survival in the multivariate analysis., Conclusion: Even in patients with poor PS and BM at the initial diagnosis of NSCLC, the ICI group had a survival time comparable to that of the TKI group when combined with tailor-made intracranial treatment. There is a subgroup in the patient population that was previously considered unsuitable for ICI, whose PS improves with individualized intracranial treatment, and who may benefit from immunotherapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

ObjectivesWe investigated the efficacy and safety of pembrolizumab monotherapy as first-line treatment for poor Eastern Cooperative Oncology Group performance status (PS) and elderly patients with programmed cell death-ligand 1 (PD-L1)-positive advanced non-small cell lung cancer (NSCLC). We also investigated clinical prognostic factors for the efficacy of pembrolizumab monotherapy, based on patient characteristics.Materials and methodsIn this prospective observational study, PS-2 and elderly NSCLC patients with PD-L1 tumor proportion score (TPS) ≥1% who received first-line pembrolizumab monotherapy, from October 2019 to March 2021, at 10 institutions in Japan were enrolled. Patients judged eligible by their physicians for combined chemotherapy and PD-1/PD-L1 inhibitors as first-line treatment were excluded. Clinicopathological characteristics and adverse events were investigated for correlation with clinical outcomes.ResultsForty patients were enrolled in the study. The median progression-free survival (PFS) of patients with PS 2 and those aged ≥ 75 years were 4.4 (95% confidence interval [CI]: 0.9–14.4) months and 5.3 (95% CI 2.9–9.4) months, respectively. The median overall survival (OS) of patients with PS 2 and those aged ≥ 75 years were 11.6 (95% CI: 1.4–not evaluable [NE]) months and 11.6 (95% CI 7.4–18.1) months, respectively. Immune-related adverse events (irAEs) were observed in 19 patients; 6 patients had severe irAEs of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or higher. Patients who achieved stable disease or better, had a statistically significant increase in PFS (p < 0.001) and OS (p < 0.001). In the multivariate analysis, the acquisition of disease control with pembrolizumab monotherapy was an independent prognostic factor for PFS and OS.ConclusionPembrolizumab monotherapy was relatively effective and tolerable as a first-line treatment for patients with PD-L1-positive advanced NSCLC who had poor PS or were elderly. Our results suggest that disease control might be an independent prognostic factor for PFS and OS in this population. (UMIN000044052 https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000050176)

Introduction: To date, the efficacy and safety of programmed death-ligand 1 (PD-L1) inhibitor plus platinum-etoposide chemotherapy for patients with extensive-stage SCLC (ES-SCLC), with real-world evidence, stratified on the basis of age and performance status (PS), have not been fully investigated. The aim of this study was to evaluate the efficacy and safety of PD-L1 inhibitor plus platinum-etoposide chemotherapy in patients with ES-SCLC. Methods: This multicenter prospective study evaluated patients with ES-SCLC who received PD-L1 inhibitor plus platinum-etoposide chemotherapy between September 2019 and October 2021. Results: A total of 45 patients with ES-SCLC received the aforementioned treatment, including 18 elderly (≥75 y old) patients and six patients with a PS of 2. Multivariate analysis indicated that a PS of 2 was a significant independent prognostic factor for progression-free survival and overall survival (p = 0.008 and p = 0.001, respectively). Of patients with PS of 2 at the initial phase, those that achieved PS improvement during treatment had significantly longer progression-free survival and overall survival than those who did not (p = 0.02 and p = 0.02, respectively). The incidence of adverse events accompanied with treatment discontinuation was significantly higher in the elderly patients than in the non-elderly patients (p = 0.03). Conclusions: This real-world prospective study found that PD-L1 inhibitor plus platinum-etoposide chemotherapy had limited efficacy in patients with ES-SCLC with a PS of 2, except for cases with improvement of PS during treatment. Owing to the emergence of adverse events and treatment discontinuation, this treatment should be administered with caution in elderly patients with ES-SCLC.

Summary: Objective. The clinical outcomes of poor performance status (PS) patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who are treated with osimertinib as a first-line treatment have not been sufficiently evaluated. This study aimed to assess the efficacy and safety of osimertinib in chemotherapy-naive and poor PS (2 or more) patients with NSCLC harboring sensitive EGFR mutations. Materials and Methods. We assessed the clinical effects of osimertinib as a first-line treatment for patients with poor PS NSCLC with an exon 19 deletion or exon 21 L858R mutation in EGFR. All patients were administered osimertinib (80 mg/day) as the initial treatment. Results. Sixteen patients (nine women and seven men) who were treated between August 2018 and July 2021 were included in this study; their median age was 78 years. The overall objective response rate was 56.3%. The median progression-free survival (PFS) of the entire patient population was 10.5 months and the PS score improved in 8 of 16 patients (50%). The most common adverse event was acneiform rash (42%), followed by diarrhea (36%) and paronychia (36%); none of these were of grade ≥ 3. Interstitial lung disease occurred in 2 patients (12.5%); however, no treatment-related deaths occurred. Conclusion. Considering the findings of this study, osimertinib appears to be an effective and safe treatment option for patients with poor PS and advanced NSCLC harboring sensitive EGFR mutations. To obtain conclusive results, further studies with larger cohorts are warranted. [ABSTRACT FROM AUTHOR]

Background: Osimertinib is effective in patients with T790M mutation-positive advanced non-small-cell lung cancer (NSCLC) resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, its effectiveness and safety in patients with poor performance status (PS) are unknown. Methods: Enrolled patients showed disease progression after treatment with gefitinib, erlotinib, or afatinib; T790M mutation; stage IIIB, IV, or recurrent disease; and PS of 2–4. Osimertinib was orally administered at a dose of 80 mg/day. The primary endpoint of this phase II study (registration, jRCTs061180018) was response rate and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate, and safety. Results: Thirty-three patients were enrolled, of which 69.7% and 24.2% had PS of 2 and 3, respectively. One patient was excluded due to protocol violation; in the remaining 32 patients, the response rate was 53.1%; disease control rate was 75.0%; PFS was 5.1 months; and OS was 10.0 months. The most frequent adverse event of grade 3 or higher severity was lymphopenia (12.1%). Interstitial lung disease (ILD) was observed at all grades and at grades 3–5 in 15.2% (5/33) and 6.1% (2/33) of patients, respectively. Treatment-related death due to ILD occurred in one patient. Patients negative for activating EGFR mutations after osimertinib administration had longer median PFS than those positive for these mutations. Conclusion: Osimertinib was sufficiently effective in EGFR-TKI-resistant, poor PS patients with T790M mutation-positive advanced NSCLC. Plasma EGFR mutation clearance after TKI treatment could predict the response to EGFR-TKIs. [ABSTRACT FROM AUTHOR]

Objective Airway stenting is an established procedure for treating various airway disorders. The AERO stent (Merit Medical Systems, South Jordan, USA) is a fully covered self-expandable metallic stent approved for use in Japan in 2014. However, its effectiveness in treating malignant airway disorders in patients with a poor performance status remains unclear. Therefore, we investigated the safety and efficacy of the AERO stent in patients with malignant airway disorders and a poor performance status. Methods We retrospectively reviewed the medical records of all patients who underwent AERO stent placement at our institute between April 2016 and March 2022, and 21 patients underwent 25 procedures for malignant airway disorders. All AERO stenting procedures were performed using an over-the-wire delivery system with flexible and/or rigid bronchoscopy. Results Eighteen of the 21 patients (85.7%) had a poor general condition (Eastern Cooperative Oncology Group performance status 3 or 4). AERO stents were successfully placed in 23 of the 25 procedures and migrated in the remaining 2 cases. Complications occurred in 10 cases, with infection being the most common (3 cases). Fourteen patients (66.6%) showed an improvement in their performance status. In addition, 5 of the 6 intubated patients were extubated following AERO stenting, and 11 patients subsequently received anticancer treatment. Conclusion The placement of the AERO stent is useful in patients with a poor performance status, including those who are intubated and afflicted with malignant airway disorders.

Background/aim: The efficacy, safety, and liver toxicity of enfortumab vedotin (EV) for elderly advanced urothelial carcinoma (UC) patients and patients with a poor performance status (PS) are unclear., Patients and Methods: We retrospectively analyzed the efficacy, safety, and liver toxicity of EV in elderly patients and patients with a poor PS between December 2021 and August 2023., Results: Sixty-two patients (≥75 years old, n=22; PS≥2, n=10) were enrolled. Patients with PS≥2 had significantly lower albumin levels than those with PS<2 (p=0.023). The objective response and disease control rates did not differ significantly between patients <75 and ≥75 years old (p=0.598 and p=0.769, respectively) or between those with PS<2 and PS≥2 (p>0.99 and p=0.178, respectively). Progression-free survival (PFS) and overall survival (OS) were not significantly different in patients <75 years and ≥75 years (p=0984, 0.368). A significant difference in PFS (p=0.047) but not OS (p=0.086) was observed between the PS<2 and PS≥2 groups. The rates of any-grade and severe (grade ≥3) adverse events did not differ significantly between patients <75 and ≥75 years (p=0.471, p=0.136) or between PS<2 and PS≥2 groups (p>0.99, 0.99). Aspartate aminotransferase (AST) levels significantly increased, but alanine aminotransferase levels did not, following EV treatment (p<0.001). Multivariate analyses revealed that the albumin level was an independent prognostic factor (hazard ratio=0.159; p<0.001)., Conclusion: EV demonstrated similar efficacy and safety in elderly and younger patients with advanced UC. In patients with a poor PS, although the safety was similar, survival was significantly worse in terms of PFS, while the AST levels were significantly elevated., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: In advanced non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations, those with impaired performance status (PS) treated with EGFR-tyrosine kinase inhibitors (TKIs) have demonstrated comparable activities to good-PS patients. Due to the limited sample size and inclusion of older adult patients with good PS, these findings may not accurately depict the efficacy of EGFR-TKI in poor-PS patients. We investigated the benefit of EGFR-TKIs in this population and identified relevant prognostic factors., Patients and Methods: This nationwide prospective registry study included 9872 patients with local or advanced NSCLC. Outcomes were compared between poor- and good-PS patients treated with EGFR-mutated lung cancer therapies., Results: Of 9872 NSCLC patients, 1965 (19.9%) had EGFR mutations, with 1846 (93.9%) presenting common EGFR mutations. Poor PS (PS score ≥ 3) was noted in 171 patients (8.7%) and identified as an independent prognostic factor; those with poor PS had a significantly lower 1-year survival rate. The median overall survival (OS) for EGFR-TKI-treated good-PS patients was 31.5 (95% confidence interval, 29.6-33.4) months. Among poor-PS patients with EGFR mutations, 135 (78.9%) of whom were treated with EGFR-TKI had an OS of 15.5 (12.7-18.3) months, while those receiving only supportive care had an OS of 2.5 (1.4-3.6) months (P < .001). Hypoalbuminemia (< 3.5 g/dL), liver metastasis, and uncommon EGFR mutations were associated with poor prognosis., Conclusion: Poor PS at diagnosis was rare and associated with limited EGFR-TKI efficacy and a dismal prognosis. Liver metastasis and hypoalbuminemia may reduce EGFR-TKI efficacy in these patients., Competing Interests: Disclosure The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

• No studies about optimal treatment for patients with LAPC and poor performance status. • SBRT and S-1 showed favorable outcomes and acceptable toxicity in those patients. • Improvement of quality of life and significant pain relief were found after treatment. The optimal treatment for a particularly neglected group of patients with locally advanced pancreatic cancer (LAPC) and poor performance status, who are usually excluded from most clinical trials, is required. Therefore, we aim to investigate the efficacy and safety of stereotactic body radiation therapy (SBRT) with sequential S-1 for those patients. Eligible patients had histologically and radiographically confirmed LAPC and ECOG performance status of 2 or more points determined by two independent physicians. Radiation doses ranged from 35-40 Gy/5f. S-1 was taken orally, twice daily, at a dose of 80 mg/m2 for 28 days, followed by a 14-day interval, which repeated for 6 cycles and was initiated one month after SBRT. The primary endpoint was 1-year overall survival (OS). The secondary endpoints were OS, progression free survival (PFS), treatment-related toxicity and quality of life. The study was registered at ClinicalTrials.gov: NCT02704143. Sixty-three patients were enrolled. At the time of data cut-off, all patients died. No patients were lost to follow-up. Median follow-up was 15.8 months (95%CI 12.9–18.7 months). One-year OS was noted in 46 of 63 patients (73.0%, 95%CI 67.4%-78.6%). The median OS and PFS was 14.4 (95%CI 13.2–15.6 months) and 10.1 months (95%CI 9.7–10.5 months) respectively. Eighteen patients (28.6%) had grade 3 toxicity. According to Quality of Life Questionnaire-Core 30, significant improvements of abdominal pain were found, and patients with poorer baseline global health status had greater improvement of health status and pain relief after treatment. SBRT with sequential S-1 shows promising efficacy and acceptable toxicity in poor performance status patients with LAPC. [ABSTRACT FROM AUTHOR]

The echinoderm microtubule‐associated protein‐like 4 (EML4)–anaplastic lymphoma kinase (ALK) fusion gene, a driver mutation in lung carcinoma, is fairly common in lung adenocarcinoma but rare in large cell neuroendocrine carcinoma (LCNEC). Here we report a case of stage IV LCNEC positive for this fusion gene in a patient with a poor performance status (PS) who was effectively treated with alectinib. The patient was a 72‐year‐old non‐smoking man diagnosed as LCNEC with multiple metastases. Because of his poor PS, cytotoxic chemotherapy was not indicated, but he was later found to be positive for the ALK fusion gene and treated with alectinib as first‐line therapy. One month later, the tumour had shrunk remarkably, and the therapeutic effect was rated as a partial response. The PS also improved from 4 to 1. Investigating actionable driver mutations seems worth doing for advanced LCNEC, especially if the patient's PS is poor. [ABSTRACT FROM AUTHOR]

Abstract The echinoderm microtubule‐associated protein‐like 4 (EML4)–anaplastic lymphoma kinase (ALK) fusion gene, a driver mutation in lung carcinoma, is fairly common in lung adenocarcinoma but rare in large cell neuroendocrine carcinoma (LCNEC). Here we report a case of stage IV LCNEC positive for this fusion gene in a patient with a poor performance status (PS) who was effectively treated with alectinib. The patient was a 72‐year‐old non‐smoking man diagnosed as LCNEC with multiple metastases. Because of his poor PS, cytotoxic chemotherapy was not indicated, but he was later found to be positive for the ALK fusion gene and treated with alectinib as first‐line therapy. One month later, the tumour had shrunk remarkably, and the therapeutic effect was rated as a partial response. The PS also improved from 4 to 1. Investigating actionable driver mutations seems worth doing for advanced LCNEC, especially if the patient's PS is poor.

Background: A significant proportion of non-small cell lung cancer (NSCLC) patients present with poor performance status (PS) at baseline are almost always excluded from the clinical trials leading to availability of only limited data in this subgroup. Patients and methods: This was an observational single institutional study. The eligibility criteria for inclusion were a histologic or cytologic diagnosis of advanced NSCLC and Eastern Cooperative Oncology Group PS 3 or 4. All patients coming between June 2015 and December 2018 were evaluated for inclusion in this study. Results: A total of 245 patients were enrolled in the study. The median age of the patients was 63 years (range 25-89), 142 (58%) were male, 196 (80%) had adenocarcinoma histology and 192 (78.4%) has PS 3 while rest (21.6%) had PS 4. Out of 245 patients, 192 (78.4%) received oral tyrosine kinase inhibitors (TKI) and supportive care, 45 (18.4%) received supportive care alone, while 8 (3.2%) patients received chemotherapy along with supportive care. Median overall survival (OS) was 3 months (95% CI: 1.8-4.2) in patients who received oral TKI versus 1 month (1.0-2.9) in patients who received supportive care alone (log-rank p = 0.013). The median OS for epidermal growth factor receptor (EGFR) mutant patients who received oral TKI was 12 months (95% CI: 7.7-16.3), while it was 3 months (95% CI: 1.5-4.5) for patients who were EGFR wild-type and received TKI on compassionate basis (HR = 0.50; 95% CI: 0.32-0.77; p = 0.001). Conclusions: The use of oral TKI on a compassionate basis led to improvement in survival in the overall cohort of the patients; this was principally driven by EGFR-mutated patients. [ABSTRACT FROM AUTHOR]

Small-cell lung cancer (SCLC) is highly sensitive to platinum-based chemotherapy. However, its indication in patients with a poor performance status (PS) at initial diagnosis is controversial. We retrospectively reviewed all clinical courses of pathologically diagnosed SCLC patients with poor PS, Eastern Cooperative Oncology Group PS 3 and 4. Among 18 patients, 12 were treated with chemotherapy and 6 with supportive care alone. During the chemotherapy courses, PS improved in 7 (58.3%, including the PS 4 cases), remained stable in 2 (16.7%), and deteriorated in 3 (25%) patients. Moreover, 5 patients showed partial responses to chemotherapy (response rate of 41.7%). Grade 3–4 neutropenia developed in 10 (83.3%) patients and grade 3 febrile neutropenia occurred in 5 (41.7%) patients, but no grade 4 non-hematological toxicity was noted. Mortality associated with lung toxicity (grade 5) due to treatment occurred in a 77-year-old-male patient with PS 3. No substantial difference in survival was observed between patients with PS 3 and 4, even when including those treated with supportive care alone. Treatment had a positive effect on survival: after chemotherapy, the 6-month survival rate of PS 3 and 4 patients was 66.7%. In contrast, all patients treated with supportive care alone died within 5 months. These findings suggest that chemotherapy is indicated in selected SCLC patients not only with PS 3, but also with PS 4.

Background: Outcomes based on liquid biopsy in poor performance, older, biopsy-ineligible advanced non-small cell lung cancer (NSCLC) patients are unknown. Aim: The aim of the study was to evaluate the outcomes of patients treated on the basis of liquid biopsy to determine the epidermal growth factor receptor (EGFR) status. Objectives: The objective was to evaluate the progression-free survival (PFS) and overall survival (OS) of patients treated based on EGFR mutation status, determined on a liquid biopsy. Materials and Methods: This was a retrospective audit of prospectively maintained database of patients who underwent liquid biopsy EGFR mutation testing between July 2017 and January 2019 and received treatment based on that report. The primary end point was PFS defined as duration between the date of sample collection and disease progression or death, whereas OS was calculated as the interval between the date of sample collection and death. Kaplan–Meier survival was used for the above two end points. Results: Out of 28 patients, 11 (39%) were EGFR mutation positive, and 17 (61%) were EGFR mutation negative. The median age was 62 years, with 15 out of the 28 being females (54%). Nine (82%) and 13 (76%) patients had performance status (PS) 2 or 3 in the EGFR mutation-positive and EGFR mutation-negative cohorts, respectively. In the EGFR mutation-positive cohort, 4 (36%) were exon 19, 6 (54%) were exon 21, and 1 (9%) was T790M positive. After receiving tyrosine kinase inhibitors or physician's choice of chemotherapy in EGFR mutation-positive and negative cohorts, the response rates were 63% and 12%, respectively. The median follow-up was 14 months (range: 10–17 months). The median PFS was 8 months versus 2 months (P = 0.002), whereas the median OS was 17 months versus 5 months (P = 0.004) in the EGFR mutation-positive and EGFR mutation-negative cohorts, respectively. Conclusion: In patients with advanced NSCLC in whom a tissue biopsy is not feasible, especially in older, poor PS patients, treatment based on the results of liquid biopsy gives comparable outcomes to those of a tissue-based biopsy.

Background: Poor Performance Status (PS) of cancer patients, defined as PS score 2–3, is an impediment for many drug- and irradiation-based treatments, supported by the trials that exclude subjects with PS < 1. Reports on the benefits of stereotactic radiotherapy (SRT) for brain metastases (BMs) in poor PS patients are scarce. We sought to review the characteristics and survival outcomes of this cohort, to assess who may benefit most from SRT. Methods: We retrospectively evaluated 73 patients with PS 2 or 3 (63 and 10 cases) treated with SRT for 150 BMs from 2012 to 2018. Patients' characteristics and post-SRT survival, stratified by concomitant systemic treatment (CST) were assessed using the Kaplan–Meier method (p-value < 0.05). Results: Non-small cell lung cancer was the most frequent primary tumor. Extracranial metastases were present in 86.3% of patients. The median overall survival (mOS) after SRT was estimated as 6.0 months (range 0.2–37.7), with 6- and 12-month survival rates of 51.0% and 21.0%, respectively. CST was administrated to 59.7% of patients (immunotherapy, target therapy or chemotherapy). Patients treated with CST presented larger mOS (6.7 vs. 4.4 months for patients treated with SRT alone, p = 0.3), and better 6- and 12-month survival rates (59% and 24% vs. 37% and 18% in patients not treated with CST). Conclusions: Survival rate after SRT for BMs in poor performance patients, especially with PS 2, can justify SRT, in particular if an effective systemic treatment is available. Both SRT and CST should be more accessible for these patients in clinical practice. [ABSTRACT FROM AUTHOR]

• Treatment of poor ECOG PS Non-Small Cell Lung Cancer patients is an unmet need. • Our findings highlight worst outcomes and good safety of immunotherapy in poor PS patients. • Clinical-pathological and laboratory biomarkers could help to refine selection for frail patients candidate to immunotherapy. The introduction of immunotherapy has improved the prognosis of patients with Non-Small Cell Lung Cancer (NSCLC). However, data in poor ECOG Performance Status (PS) patients remain scant due to their exclusion from randomized trials. We analyzed data of patients with advanced NSCLC treated with immunotherapy in two Italian Centers, to evaluate the impact of PS (0-1 vs 2) on disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Chi-square test was used to compare clinical-pathological variables, their impact on survival was evaluated through Cox proportional hazard models. Among 404 patients included, PS was 0 in 137 (33.9 %), 1 in 208 (51.5 %) and 2 in 59 (14.6 %) patients; 143 were female and 90 had squamous NSCLC. Clinical-pathological variables were uniformly distributed except for higher prevalence of liver metastases in patients with poor PS. We found that PS2 patients showed worse outcomes in terms of DCR (21.8 % vs 50.3 %, p = 0.001), PFS [2.0 (95 % CI 1.6–3.0) vs 3.0 (95 % CI 2.7–4.0) months, p < 0.0001] and OS [4.0 (95 % CI 2.8–5.7) vs 13.2 (95 % CI 11.0−15.8) months, p < 0.0001]. PS2 status, negative PDL1 expression and early corticosteroids exposure as well as higher Neutrophil to Lymphocyte Ratio and LDH at baseline were associated with worse outcomes at univariate and multivariable analysis. Subgroup analysis confirmed poor outcomes in PS2 patients with high LDH and concomitant corticosteroid therapies. The incidence of Grade 3/4 adverse events was 11.3 % in PS 0−1 and 10.2 % in PS 2 patients (p = 0.81). Our data confirm reduced efficacy of immunotherapy in patients with poor PS even though a good safety. Despite PS remains the most powerful independent prognostic factor for NSCLC, LDH levels and steroids exposure could support the decision making in PS2 patients. [ABSTRACT FROM AUTHOR]

Pembrolizumab is the standard first‐line treatment for advanced non‐small cell lung cancer (NSCLC) with programmed death‐ligand 1 (PD‐L1) expression tumor proportion score (TPS) ≥50%. The benefit of pembrolizumab in patients with advanced NSCLC and poor performance status (PS ≥3) is limited, even when the tumor is PD‐L1‐expression‐positive. We retrospectively reviewed a total of four NSCLC cases with high PD‐L1 expression (TPS ≥50%) and poor PS. The only patient with very high PD‐L1 expression (TPS 100%) responded to pembrolizumab, but none of the three patients with high PD‐L1 expression (50%–80%) responded to pembrolizumab. In conclusion, pembrolizumab can serve as a treatment option for patients with poor PS, if PD‐L1 expression TPS is 100%. [ABSTRACT FROM AUTHOR]

Summary: Osimertinib is a molecularly targeted agent used to treat non-small cell lung cancer (NSCLC) patients with an epidermal growth factor receptor (EGFR) T790M mutation. However, its efficacy and safety profile when patients have poor performance status (PS) is unknown. Therefore, we conducted an open-label, multi-center, single-arm phase II study to evaluate its efficacy and safety in EGFR T790M mutation-positive NSCLC patients with Eastern Cooperative Oncology Group PS scores of between 2 and 4. Patients received 80 mg of osimertinib once daily. Our primary endpoint was progression-free survival. Eighteen patients were enrolled between June 2017 and November 2018. The median age was 77 years (range: 55–85 years). Ten, six, and two patients had PS scores of 2, 3, and 4, respectively. All patients had adenocarcinoma with common EGFR mutations and had been treated with first- or second-generation EGFR- tyrosine kinase inhibitors previously. The overall median progression-free survival was 7.0 months (90% confidence interval: 5.5–8.9 months). The overall response rate and median overall survival were 53% and 12.7 months, respectively. Moreover, improved PS scores were observed in 72% of the patients. Although the incidence of grade 3 adverse events was low, with no grade 4 or 5 events observed, three patients required treatment cessation due to the development of interstitial lung disease. Osimertinib therapy could be beneficial for EGFR T790M mutation-positive advanced NSCLC patients with poor PS. This trial was registered with the Japan Registry of Clinical Trials on March 12, 2019 (trial no. jRCT1041180081). [ABSTRACT FROM AUTHOR]

Most clinical trials of non‐small‐cell lung cancer (NSCLC) exclude patients with poor ECOG performance status (PS). Thus, the efficacy of immune checkpoint inhibitors (ICIs) in patients with poor PS remains unclear. Herein, we used data from a retrospective cohort to assess the potential clinical benefits of ICIs in NSCLC patients with poor PS. Data from NSCLC patients who received ICI monotherapy at 9 institutions between December 2015 and May 2018 were retrospectively analyzed. After excluding 4 patients who lacked PS data, a total of 527 ICI‐treated patients, including 79 patients with PS 2 or higher, were used for our analyses. The progression‐free survival (PFS) and overall survival (OS) of patients with PS 2 or higher were significantly shorter compared with those of PS 0‐1 patients (median PFS, 4.1 vs 2.0 months; P <.001 and median OS, 17.4 vs 4.0 months; P <.001). Among NSCLC patients with programmed cell death protein‐ligand 1 (PD‐L1) expression of 50% or higher who were treated with pembrolizumab as first‐line therapy, the median PFS times of patients with PS 2 and 0‐1 were 7.3 and 8.1 months, respectively. There was no significant difference in PFS between patients with PS 2 and 0‐1 (P =.321). Although poor PS was significantly associated with worse outcomes in NSCLC patients treated with ICIs, pembrolizumab as a first‐line treatment in NSCLC patients expressing high levels of PD‐L1 could provide a clinical benefit, even in patients with PS 2. [ABSTRACT FROM AUTHOR]

There are few treatment guidelines for locally recurrent esophageal cancer after trimodality treatment (pre-operative chemoradiation followed by surgery) in patients with a poor performance status. The purpose of this single institutional, retrospective study was to evaluate the clinical outcomes and toxicities of definitive-intent re-irradiation for patients with recurrent esophageal cancer with a poor performance status [ECOG (Eastern Cooperative Oncology Group) ≥2]. Seven patients were identified with a median age of 74 years (range, 61-81 years). Four patients were ECOG 2 and three patients were ECOG 3. The median follow-up time after re-irradiation was 49 months. The median interval between initial radiotherapy and re-treatment was 32 months. Six patients received concurrent chemotherapy [carboplatin + paclitaxel in three patients; folinic acid, fluorouracil, oxaliplatin (FOLFOX) + 5-fluorouracil in one patient; FOLFOX in one patient, and capecitabine in one patient]. At the last follow-up, the six patients who underwent concurrent chemotherapy had stable disease (86%), while the one who did not receive chemotherapy progressed (14%). Two patients developed metastases. Three patients developed acute (<6 months) grade 4 toxicities (dysphagia, anemia, esophagitis). There were no early deaths attributable to treatment. Late toxicities (>6 months) were limited to grades 1 and 2 dysphagia and pneumonitis in four patients. In conclusion, definitive re-irradiation of recurrent esophageal cancer in patients with a poor performance status appears to be safe with acceptable acute toxicity and late complications. It also appears to result in durable local control when combined with chemotherapy, albeit with a small number of patients and limited follow-up. [ABSTRACT FROM AUTHOR]

• ICIs are safe and effective in patients with autoimmune disease and chronic viral infections. • A high risk of organ rejection has been associated with the treatment with ICIs in solid organ recipients. • Patients with brain metastases may benefit of the treatment with ICIs. • Mild to moderate organ dysfunction is not an absolute contraindication for the use of ICIs. Immune checkpoint inhibitors (ICIs), including those targeting programmed cell death 1 (PD-1), its ligand 1 (PD-L1), or cytotoxic T-lymphocyte antigen 4 (CTLA-4) have become the standard treatment for several malignancies, including lung cancer. However, some patient populations have been routinely excluded from clinical trials or are underrepresented in these studies, as is the case of elderly patients or patients with poor performance status, brain metastases, solid organ transplant, autoimmune diseases, chronic viral infections (such as human immunodeficiency virus or chronic viral hepatitis B and C), or organ dysfunction. Thus, the safety and efficacy of ICIs in these special populations is still unclear, despite regulatory approval of these agents. This review analyzes and summarizes the available information on the efficacy and safety of ICIs in these special populations, focusing on patients with lung cancer. [ABSTRACT FROM AUTHOR]

Introduction: c-MET is a tyrosine kinase receptor, which is encoded in part by mesenchymal-epidermal transition (MET) exon 14. Mutations in the MET gene can cause increased c-MET signaling and oncogenic stimulation. Although c-MET mutation is rare, it is a targetable driver mutation. Although the guidelines do not recommend routine screening before treatment decision, there are drugs that can be used in patients who have c-MET mutation or amplification. Case report: We present a metastatic c-MET-amplified non-small cell lung cancer (NSCLC) patient who was treated with crizotinib. He was not eligible for chemotherapy because of poor performance score; c-MET amplification was investigated after the other common driver mutations were negative. Management and outcome: After c-MET amplification was shown, crizotinib 250 mg BID was started. A partial response was achieved with the initiation of crizotinib, and his performance score improved after treatment. Discussion: We presented a metastatic c-MET-amplified NSCLC patient, who was not eligible for standard platin doublet chemotherapy, to emphasize the importance of investigating all driver mutations, including c-MET amplification especially in patients who cannot tolerate cytotoxic chemotherapy. [ABSTRACT FROM AUTHOR]

Non-Small Cell Lung Cancer (NSCLC) with bone metastasis and poor performance status has the worst prognosis even in strong PD-L1 expression patients. Treatment approach includes immuno- or chemo-immunotherapy, Radiotherapy (RT) and Bone-Targeted Therapy (BTT) but there is insufficient data to suggest the best time to use each of them, alone or in combination. Using an integrated and synergistic treatment strategy with immunotherapy, radiotherapy, and Denosumab as BTT is probably the best treatment planning for metastatic NSCLC for both good and poor performance status patients, although more data are needed to confirm this approach. Here we describe an interesting case report on patient with extensive bone involvement from NSCLC and PS >2 treated simultaneously with radiotherapy, immunotherapy and BTT, achieving an excellent clinical benefit, radiological and metabolic complete response, as a sort of Lazarus effect. We analyzed our result comparing with currently published data about radio-immunotherapy or immunotherapy and BTT combination even though there is no published experience about integration of all 3 treatments. Approval studies often do not represent real-world experience (RWE), so we analyzed data from both RWE and clinical trials. [ABSTRACT FROM AUTHOR]

Abstract Background It remains controversial as to whether active stone removal should be performed in patients with poor performance status because of their short life expectancy and perioperative risks. Our objectives were to evaluate treatment outcomes of active stone removal in patients with poor performance status and to compare life prognosis with those managed conservatively. Methods We retrospectively reviewed 74 patients with Eastern Cooperative Oncology Group performance status 3 or 4 treated for upper urinary tract calculi at our four hospitals between January 2009 and March 2016. Patients were classified into either surgical treatment group or conservative management group based on the presence of active stone removal. Stone-free rate and perioperative complications in surgical treatment group were reviewed. In addition, we compared overall survival and stone-specific survival between the two groups. Cox proportional hazards analysis was performed to investigate predictors of overall survival and stone-specific survival. Results Fifty-two patients (70.3%) underwent active stone removal (surgical treatment group) by extracorporeal shock wave lithotripsy (n = 6), ureteroscopy (n = 39), percutaneous nephrolithotomy (n = 6) or nephrectomy (n = 1). The overall stone-free rate was 78.8% and perioperative complication was observed in nine patients (17.3%). Conservative treatment was undergone by 22 patients (29.7%) (conservative management group). Two-year overall survival rates in surgical treatment and conservative management groups were 88.0% and 38.4%, respectively (p

Small-cell lung cancer (SCLC) is highly sensitive to platinum-based chemotherapy. However, its indication in patients with a poor performance status (PS) at initial diagnosis is controversial. We retrospectively reviewed all clinical courses of pathologically diagnosed SCLC patients with poor PS, Eastern Cooperative Oncology Group PS 3 and 4. Among 18 patients, 12 were treated with chemotherapy and 6 with supportive care alone. During the chemotherapy courses, PS improved in 7 (58.3%, including the PS 4 cases), remained stable in 2 (16.7%), and deteriorated in 3 (25%) patients. Moreover, 5 patients showed partial responses to chemotherapy (response rate of 41.7%). Grade 3–4 neutropenia developed in 10 (83.3%) patients and grade 3 febrile neutropenia occurred in 5 (41.7%) patients, but no grade 4 non-hematological toxicity was noted. Mortality associated with lung toxicity (grade 5) due to treatment occurred in a 77-year-old-male patient with PS 3. No substantial difference in survival was observed between patients with PS 3 and 4, even when including those treated with supportive care alone. Treatment had a positive effect on survival: after chemotherapy, the 6-month survival rate of PS 3 and 4 patients was 66.7%. In contrast, all patients treated with supportive care alone died within 5 months. These findings suggest that chemotherapy is indicated in selected SCLC patients not only with PS 3, but also with PS 4. [ABSTRACT FROM AUTHOR]

The combination of standard-dose chemotherapy and immunotherapy has been shown to be beneficial for patients with non-small cell lung cancer (NSCLC) with good performance status (PS). However, treatment options for patients with poor PS are limited. In the present study, the feasibility and immunological effects of low-dose chemotherapy with carboplatin and paclitaxel combined with immunotherapy with pembrolizumab were examined in patients with metastatic NSCLC and a poor PS. Patients with advanced NSCLC and a PS of 2 were randomized to single-agent pembrolizumab at 200 mg every 3 weeks or pembrolizumab combined with weekly carboplatin area under the curve 1 and paclitaxel 25 mg/m2. Blood for circulating immune cell phenotyping, soluble program death ligand 1 (sPD-L1) and immune-modulatory microRNAs (miRNAs) was collected prior to treatment and at weeks 4 and 7. Ten patients were randomized to the combination arm and 10 to the single-agent arm. Therapy was well tolerated. Four patients discontinued carboplatin due to hypersensitivity reactions but continued pembrolizumab and paclitaxel treatments. Increases in activated CD4+ T cells and in immune-regulatory miRNA, and decreases in myeloid derived suppressor cells were observed in the blood of patients in the combination arm and not in the single-agent arm. Changes in circulating regulatory T cells and sPD-L1 were not observed. Seven patients in the combination arm manifested a partial response compared with only two in the single-agent arm. Weekly low-dose chemotherapy carboplatin and paclitaxel was well tolerated and immunologically active when combined with pembrolizumab in patients with advanced NSCLC and a PS of 2. This combination merits further study in this patient population. [ABSTRACT FROM AUTHOR]

ALK inhibitors are promising for treating ALK rearrangement non-small-cell lung cancer (NSCLC), but secondary mutations of ALK can sometimes inhibit their effectiveness. A 54-year-old woman with lung adenocarcinoma harboring ALK rearrangement previously treated with first-line alectinib and second-line cisplatin/pemetrexed showed poor performance status (PS) with rapid progression. She was treated with ceritinib as salvage treatment, upon which tumor shrinkage was demonstrated on CT and her PS gradually improved. The best supportive care is recommended for patients with advanced NSCLC with poor PS due to lower treatment efficacy and more toxicities than those with good PS. In this case, rapid progression led to a poor PS; however, ceritinib achieved a breakthrough in this case. The optimal treatment sequence and key drugs in ALK-positive NSCLC remain controversial. [ABSTRACT FROM AUTHOR]