First-line osimertinib for poor performance status patients with EGFR mutation-positive non-small cell lung cancer: A prospective observational study.

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.

A phase II study of carboplatin and etoposide plus durvalumab for previously untreated extensive-stage small-cell lung cancer (ES-SCLC) patients with a poor performance status (PS): NEJ045A study protocol.

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.

Rationale and protocol design of a phase II study of first-line osimertinib treatment for patients with poor performance status and EGFR mutation-positive non-small cell lung cancer (OPEN/TORG2040).

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).

Osimertinib in poor performance status patients with T790M-positive advanced non-small-cell lung cancer after progression of first- and second-generation EGFR-TKI treatments (NEJ032B).

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.

"Triple Threat" Conditions Predict Mortality Among Patients With Advanced Cancer Who Present to the Emergency Department.

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.

Poor performance status and brain metastases treatment: who may benefit from the stereotactic radiotherapy?

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.

Utility of immune checkpoint inhibitors in non-small-cell lung cancer patients with poor performance status.

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.

Osimertinib for patients with poor performance status and EGFR T790M mutation-positive advanced non-small cell lung cancer: a phase II clinical trial.

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).

An advanced c-MET-amplified NSCLC patient that was treated with crizotinib.

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.

Osimertinib for patients with EGFR T790M mutation-positive non-small-cell lung cancer and a poor performance status.

BACKGROUND: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is effective against EGFR T790M mutation-positive non-small-cell lung cancer (NSCLC) in patients who have good performance status (PS). However, the efficacy and safety of osimertinib for patients with poor PS is unknown. METHODS: We retrospectively evaluated the efficacy and safety of osimertinib in patients with EGFR T790M mutation-positive NSCLC who had Eastern Cooperative Oncology Group PS scores of 2-4 and who were administered 80 mg of osimertinib once daily between March 2016 and February 2017. RESULTS: Thirty patients (8 men and 22 women) with EGFR T790M mutation-positive NSCLC were evaluated; their median age was 66 years (range: 39-89 years). Twenty-four and six patients had PS scores of 2 and 3, respectively; none had a PS score of 4. All patients had previously been treated with first- or second-generation EGFR-TKIs. T790M was detected in the tumor samples of 23 patients, the blood samples of two patients, and both the tumor and blood samples of five patients. The overall response rate was 53% (95% confidence interval: 36-70%), and the PS score improvement rate was 63%. The median progression-free survival was 8.2 months (95% confidence interval: 4.3-13.2 months), while the median overall survival time was not reached. No patient required treatment cessation owing to adverse events, and no treatment-related deaths occurred. CONCLUSIONS: Osimertinib therapy demonstrates promising efficacy and acceptable safety in patients with EGFR T790M mutation-positive NSCLC who have poor PS.

Efficacy of Platinum-Based Chemotherapy for Relapsed Small-Cell Lung Cancer after Amrubicin Monotherapy in Elderly Patients and Patients with Poor Performance Status.

BACKGROUND: Previous studies have shown amrubicin to be an effective first- or second-line treatment option for small-cell lung cancer (SCLC). However, there have been few studies reporting the efficacy of platinum-based chemotherapy after amrubicin therapy. We aimed to evaluate the efficacy of platinum-based chemotherapy as second-line treatment for elderly patients and those with SCLC with poor performance status (PS) previously treated with amrubicin monotherapy. METHODS: The records of SCLC patients who received platinum-based chemotherapy as a second-line chemotherapy after first-line treatment with amrubicin monotherapy were retrospectively reviewed and the treatment outcomes were evaluated. RESULTS: A total of 48 patients were enrolled in this study. Forty-one patients (85%) received carboplatin plus etoposide. The overall response rate was 39.6%. The median progression-free survival and overall survival were 3.7 and 7.6 months, respectively. The efficacy of the platinum-based regimen did not differ with the type of relapse after amrubicin monotherapy. The most common adverse events were hematological toxicities, including grade 3 or 4 neutropenia (38%), leukopenia (33%), and thrombocytopenia (10%). CONCLUSIONS: Platinum-based chemotherapy is potentially a valid treatment option for elderly patients or those with extensive-stage SCLC with poor PS as second-line chemotherapy, who progressed after first-line treatment with amrubicin monotherapy.

Upper urinary tract stone disease in patients with poor performance status: active stone removal or conservative management?

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 < 0.01) and two-year stone-specific survival rates in the two groups were 100.0% and 61.3%, respectively (p < 0.01). On multivariate analysis, stone removal was not significant, but was considered a possible favorable predictor for overall survival (p = 0.07). Moreover, stone removal was the only independent predictor of stone-specific survival (p < 0.01). CONCLUSIONS: Active stone removal for patients with poor performance status could be performed safely and effectively. Compared to conservative management, surgical stone treatment achieved longer overall survival and stone-specific survival.

Efficacy of metronomic vinorelbine in elderly patients with advanced non-small-cell lung cancer and poor performance status.

BACKGROUND: Metronomic chemotherapy-administration of low-dose chemotherapy-allows for a prolonged treatment duration and minimizes toxicity for unfit patients diagnosed with advanced non-small-cell lung cancer (nsclc). METHODS: Oral metronomic vinorelbine at 30 mg thrice weekly was given to 35 chemotherapy-naïve patients who were elderly and vulnerable to toxicity and who had been diagnosed with advanced nsclc. RESULTS: Median age in this male-predominant cohort (29:6) was 76 years (range: 65-86 years). Histology was squamous cell carcinoma in 21 patients and adenocarcinoma in 14. There were no complete responses and 9 partial responses, for an overall response rate of 26%. Stable disease was seen in 15 patients (43%), and 11 patients (31%) had progressive disease. The 1-year survival rate was 34%, and the 2-year survival rate was 8%. The survival analysis showed a median progression-free survival duration of 4 months (range: 2-15 months) and an overall survival duration of 7 months (range: 3-24 months). CONCLUSIONS: Metronomic vinorelbine had an acceptable efficacy and safety profile in elderly patients with multiple comorbidities who had been diagnosed with advanced nsclc. Metronomic vinorelbine could be a treatment option for elderly patients with poor performance status who are unfit for platinum-based chemotherapy and intravenous single-agent chemotherapy, and who are not candidates for combination modalities.

Poor performance status (PS) is an indication for an aggressive approach to neoadjuvant chemotherapy in patients with advanced epithelial ovarian cancer (EOC).

BACKGROUND: Some guidelines suggest that poor performance status (PS) is a contraindication to 1st line chemotherapy. Poor PS is a known adverse prognostic factor in advanced epithelial ovarian cancer (EOC). We show in this retrospective analysis that 1st line chemotherapy in this patient group is not only safe but is associated with good outcomes. PATIENTS AND METHODS: A retrospective review of 114 patients with stage III/IV EOC, who presented with a PS ≥3 at diagnosis and treated as inpatients with upfront platinum-based chemotherapy between 2000 and 2013, at the Royal Marsden Hospital, was conducted. The association between clinical parameters and the likelihood of completion of chemotherapy and overall survival (OS) was assessed. RESULTS: 66% of patients completed ≥6cycles of platinum-based chemotherapy. Prognostic factors for completion of chemotherapy were improvement of PS during hospital stay (p<0.001) and doublet-chemotherapy with carboplatin/paclitaxel compared to single-agent carboplatin (p=0.004). A negative trend for completion of treatment was seen for patients with low albumin (<25g/l) and low CA125 levels at baseline. The median OS for all patients was 13.1months (95% CI: 10.4-15.8) and 21.2months (95% CI: 16.5-25.8) for those who completed 6cycles of chemotherapy. CONCLUSION: Upfront platinum-based chemotherapy is feasible, beneficial and tolerable for the majority of patients with advanced EOC and poor PS. Guidelines suggesting that best supportive care is the preferred option for poor PS patients with solid tumours should be revised to exclude those with advanced EOC. An aggressive approach utilising neoadjuvant carboplatin plus paclitaxel should be regarded as standard of care.

Efficacy of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in Metastatic Non-Small Cell Lung Cancer Patients with Poor Performance Status and Epidermal Growth Factor Receptor Mutations: Findings from the Japanese Lung Cancer Registry Database.

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.

Effectiveness of AERO Stent Placement for Malignant Airway Disorder in Patients with a Poor Performance Status.

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.

Enfortumab Vedotin for Elderly Advanced Urothelial Carcinoma Patients or Those With a Poor Performance Status.

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.

Combination of immunotherapy, radiotherapy and denosumab as the best approach even for NSCLC poor prognosis patients: a case report with strong response, prolonged survival and a review of literature.

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.

Feasibility of fast, four-dimensional computed tomography-based O-ring LINAC plans for lung stereotactic body radiotherapy in patients with poor performance status.

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 4D-stereotactic 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.

Predicting survival in metastatic non-small cell lung cancer patients with poor ECOG-PS: A single-arm prospective study.

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.