A randomized phase III study of docetaxel alone versus docetaxel plus S-1 in patients with previously treated non-small cell lung cancer: JMTO LC09-01.

BACKGROUND: This study evaluated the efficacy and safety of the combination chemotherapy of docetaxel plus S-1 in patients with previously treated non-small cell lung cancer (NSCLC) compared to docetaxel alone. METHODS: Patients with previously treated NSCLC were randomly assigned to docetaxel alone (arm A) or a combination of docetaxel and S-1 (arm B) for a maximum of four cycles. The primary endpoint was overall survival (OS). RESULTS: The study was terminated early because of poor accrual. The number of patients evaluated were 74 and 77 in arm A and arm B, respectively. The median OS was 9.8 months (95% confidence interval [CI]: 6.8-15.2) and 12.3 months (95% CI: 9.2-14.5) in arms A and B, respectively. In arms A and B, the median progression-free survival was 3.5 months (95% CI: 2.7-4.0) and 4.1 months (95% CI: 3.2-4.7), respectively. No statistically significant difference was observed in OS (hazard ratio [HR]: 0.984, 95% CI: 0.682-1.419, p = 0.4569) or progression-free survival (HR: 0.823, 95% CI: 0.528-1.282, p = 0.0953). The major toxicity was myelosuppression. The incidence of grade 3 or more neutropenia was higher in arm A than in arm B (44.6% vs. 35.1%). However, the incidence of grade 3 or more febrile neutropenia and infection with neutropenia (12.2% vs. 22.1%) was more frequently observed in arm B. CONCLUSIONS: The prematurely terminated study did not show the benefit of two cytotoxic agents over single-agent therapy for previously treated NSCLC patients.

A retrospective study of pulse steroid therapy for acute respiratory failure associated with tuberculosis.

BACKGROUND: Tuberculosis can cause acute respiratory failure, which is associated with a high mortality rate, even in patients receiving effective anti-tuberculosis therapy. We retrospectively analyzed patients with acute respiratory failure associated with tuberculosis who underwent pulse steroid therapy to describe the clinical characteristics and effectiveness of pulse steroid therapy in this condition. METHODS: The medical records of patients admitted to our hospital for culture-proven tuberculosis treatment from April 1, 2017, to March 31, 2022, who received pulse steroid therapy for acute respiratory failure associated with tuberculosis were reviewed. RESULTS: In total, 10 patients were included in this study. Chest computed tomography (CT) revealed diffuse ground-glass opacities and consolidation in these patients. Overall, 70% of the patients (7/10) showed an adjudicated response to pulse steroid therapy, with improved respiratory condition and radiological findings. Three patients died without response to pulse steroid therapy. One patient died of pancreatic cancer after recovering from respiratory failure. The remaining six patients were discharged without supplemental oxygen and completed anti-tuberculosis therapy. CONCLUSIONS: Pulse steroid therapy can lead to dramatic improvements in some patients with acute respiratory failure associated with tuberculosis.

Poncet's Disease (Reactive Arthritis Associated with Tuberculosis).

An 82-year-old man with miliary tuberculosis was admitted to our hospital. Approximately six weeks after starting anti-tuberculosis treatment, he complained of pain in the fingers, wrists, and ankles. A histopathological examination of the synovial biopsy revealed nonspecific chronic inflammation with no granulomas. Culture of the biopsy specimen yielded no acid-fast bacilli. Poncet's disease was diagnosed based on the clinical presentation, with no findings suggestive of other diseases. His joint pain rapidly improved with steroid therapy. Tuberculosis can cause arthritis through immune-mediated mechanisms without direct invasion in an entity known as Poncet's disease.

High neutrophils and low lymphocytes percentages in bronchoalveolar lavage fluid are prognostic factors of higher in-hospital mortality in diffuse alveolar hemorrhage.

BACKGROUND: Diffuse alveolar hemorrhage (DAH) is a syndrome resulting from bleeding in the microcirculation of the lung, with a poor prognosis. The study aim was to identify prognostic factors of DAH, especially bronchoalveolar lavage fluids (BALF) cell pattern. METHODS: We conducted a single-center retrospective cohort study of patients diagnosed as having DAH and hospitalized at our hospital between October 2008 and July 2020. We performed univariate logistic regressions to identify variables associated with in-hospital death. RESULTS: Sixty-eight patients were included in our analysis. In-hospital mortality was 26.5%. Variables associated with in-hospital death were neutrophils percentage in BALF ≥ 44.5% [Odds Ratio (OR) 16.0, 95% confidence interval (CI) 4.33-58.9)], lymphocytes percentage in BALF < 14% (OR 7.44, 95% CI 2.11-26.2), idiopathic DAH (OR 0.31, 95% CI 0.10-0.95), oxygen flow ≥ 4L/min (OR 3.90, 95% CI 1.20-12.6), and estimated glomerular filtration rate < 60 mL/min (OR 5.00, 95%CI 1.29-19.4). CONCLUSIONS: High neutrophils and low lymphocytes percentages in BALF were associated with poor prognosis.

Pulmonary Adenosquamous Cell Carcinoma With Systemic Lymphadenopathy due to Immunoglobulin G4-Related Disease: A Case Report.

A 75-year-old man with diabetes mellitus showed elevated C-reactive protein (CRP) level at his regular visit. Computed tomography scan showed a lung tumor in his left lower lobe and systemic lymphadenopathy including abdominal lymph nodes. The patient was diagnosed as primary pulmonary squamous cell carcinoma with systemic lymph node metastasis. Thereafter, unexpected steroid pulse therapy for accidental acute exacerbation of interstitial pneumonia rapidly shrank lymphadenopathy. At this time, we also found elevated serum immunoglobulin G4 (IgG4) level (385 mg/dL). Considering these findings, we doubted the lymph nodes metastases at the initial staging, and then corrected cancer-staging (C-staging) from inferior vena cava (IVC) to inferior abdomen (IA). In addition, during the steroid tapering, sudden onset and uncontrollable left pneumothorax required surgical approach. Curative-intent left lower lobectomy with lymphadenectomy was performed for the lung cancer. Pathological findings revealed coexistence of adenosquamous carcinoma and infiltration of IgG4-positive plasma cells in the resected mediastinal lymph node. We detected 384 IgG4-positive cells per high power field. IgG4/IgG-positive cell ratio was 54%. Based on these findings, the diagnosis of IgG4-related disease with primary adenosquamous carcinoma (p-stage IIIA) was confirmed. The patient died 24 days after surgery because of another acute exacerbation of interstitial pneumonia. Our case alerts oncologists to IgG4-related disease as a possible underlying comorbidity which may confuse pretreatment clinical stage.

Secondary organizing pneumonia after coronavirus disease 2019: Two cases.

Coronavirus disease 2019 (COVID-19) has been reported to induce persistent symptoms even after an acute phase. However, the pathophysiology and treatment of this condition have been unclear. We report two patients who recovered from COVID-19, but presented persistent respiratory symptoms. Their respiratory conditions deteriorated, and computed tomography showed remaining ground glass opacities and consolidations. The pathological findings of transbronchial lung biopsy corresponded to organizing pneumonia. We diagnosed them with secondary organizing pneumonia after COVID-19. Subsequently, we administered systemic corticosteroids. Their symptoms, oxygenations, radiologic findings, and pulmonary functions rapidly improved after the treatment of corticosteroids. The two cases showed that secondary organizing pneumonia may be a cause of persistent respiratory failure after COVID-19. In this condition, corticosteroids may be effective.

Osimertinib-induced cardiac failure with QT prolongation and torsade de pointes in a patient with advanced pulmonary adenocarcinoma.

Osimertinib-induced cardiotoxicity is a well-known but rare disorder. An 84-year-old woman was diagnosed with recurrence of lung adenocarcinoma showing an epidermal growth factor receptor mutation of exon 19 deletion, which was initially treated by curative-intent thoracic radiotherapy 4 years prior. She started taking osimertinib (80 mg/day). She had no history of heart disease and showed no signs of cardiac problems. However, 2 months later she presented with symptoms of cardiac failure and QT prolongation on electrocardiogram. Cardiac enzyme levels were not elevated and coronary computed tomography angiography showed no significant stenosis. On admission, sudden-onset torsade de pointes required electrocardioversion. Thus, drug-induced cardiac failure was strongly suspected and we stopped osimertinib therapy. Cardiac function and the electrocardiogram abnormality improved. To our knowledge, this is the third case of coincidence of cardiac failure and QT prolongation and the second case of sudden-onset torsade de pointes associated with osimertinib treatment. In our case, osimertinib-induced cardiac failure with QT prolongation was recovered by stopping the drug treatment. The potential for cardiotoxicity should be considered with osimertinib treatment.

Effectiveness of EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer patients with uncommon EGFR mutations: A multicenter observational study.

BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy is the standard treatment for advanced non-small cell lung cancer (NSCLC) harboring common EGFR mutations, such as exon 19 deletion or L858 point mutation. However, the effectiveness of EGFR-TKIs for patients with uncommon EGFR mutations remains unclear. METHODS: We retrospectively surveyed a consecutive database of NSCLC patients with EGFR mutations at five participating institutions. Data from NSCLC patients with uncommon mutations (including single or compound mutations), who were treated with systemic therapy between May 2016 and October 2018, were collected and analyzed. RESULTS: A total of 23 of the 524 patients whose data were collected had uncommon EGFR mutations. Of these, 22 received EGFR-TKIs (gefitinib = 6, erlotinib = 4, and afatinib = 12). Patients who received first EGFR-TKIs had overall response and disease control rates of 59.1% and 81.8%, respectively. The median progression-free survival (PFS) of patients with G719X mutation (n = 13, median PFS = 32.9 months) was favorable, compared with those of patients with L861Q mutation (n = 4, median PFS = 6.4 months) and compound mutations (n = 4, median PFS = 7.3 months). The PFS of patients who received first- and second-generation EGFR-TKIs was 14.0 months (n = 10) and 7.3 months (n = 12), respectively. The median cumulative duration of treatment (DOT) with EGFR-TKIs was 30.4 months, which was longer than those of cytotoxic chemotherapy (median DOT = 10.7 months) or immune checkpoint inhibitors (median DOT = 6.6 months). CONCLUSIONS: EGFR-TKIs elicit favorable responses and contribute to long-term disease control in NSCLC patients with uncommon EGFR mutations. KEY POINTS: Significant findings of the study: Our results demonstrate that both first- and second-generation EGFR-TKIs elicit favorable responses in NSCLC patients with uncommon EGFR mutations. What this study adds This study revealed all clinical courses for NSCLC patients with uncommon EGFR mutations. In addition to EGFR-TKIs, CCT and ICIs were found to contribute to long-term disease control in this cohort.

Sarcopenia and Visceral Adiposity Are Not Independent Prognostic Markers for Extensive Disease of Small-Cell Lung Cancer: A Single-Centered Retrospective Cohort Study.

BACKGROUND: Sarcopenia and visceral adiposity have been suggested to affect prognosis and treatment efficacy in various types of cancers. The aim of our study was to evaluate whether pretreatment sarcopenia and visceral adiposity are associated with prognosis in patients with extensive-disease small-cell lung cancer (ED-SCLC). METHODS: Between September 2007 and March 2018, 128 ED-SCLC patients received first-line and platinum-based chemotherapy at our hospital. Based on pretreatment body mass index (BMI), psoas muscle index (PMI), intramuscular adipose tissue content (IMAC) and visceral-to-subcutaneous fat ratio (VSR) at lumbar vertebra L3 level, we divided these patients into two groups, and then compared overall survival (OS) and progression-free survival (PFS). Adjusted by age, serum albumin, lactate dehydrogenase (LDH), clinical stage and performance status, we detected independent prognostic factors by multivariate Cox proportional hazard analyses. RESULTS: We did not find any significant differences in OS and PFS between two groups divided by BMI, PMI, IMAC and VSR. According to multivariate analyses, none of BMI, PMI, IMAC and VSR was an independent prognostic factor of OS and PFS. CONCLUSIONS: Neither pretreatment sarcopenia nor visceral adiposity is a prognostic marker of patients with ED-SCLC treated with standard regimen of platinum-based chemotherapy.

Real-world osimertinib for EGFR mutation-positive non-small-cell lung cancer with acquired T790M mutation.

Aim: Osimertinib is a key drug for EGFR mutation-positive non-small-cell lung cancer (NSCLC). As the hazards ratio of overall survival in comparison with first-generation EGFR-tyrosine kinase inhibitors was almost similar between FLAURA and ARCHER 1050, salvage use of osimertinib is still a treatment option. Patients & methods: We retrospectively analyzed the clinical courses of EGFR mutation-positive NSCLC patients who were potential candidates for salvage osimertinib. Results: Among 524 patients enrolled from five hospitals, 302 patients underwent biopsy, with 52.6% detection rate of T790M. Osimertinib was administered in 93.6% of the T790M-positive patients. The overall response rate and median progression-free survival time of osimertinib were calculated with 147 patients, to be 55.6% and 17.2 months, respectively. Conclusion: Osimertinib is active for T790M-driven acquired resistance in EGFR-mutant NSCLC, but the detection of T790M was unsatisfactory. Clinical Trial Registration: UMIN000028989 (UMIN Clinical Trials Registry).

Gustave Roussy Immune Score and Royal Marsden Hospital Prognostic Score Are Prognostic Markers for Extensive Disease of Small Cell Lung Cancer.

BACKGROUND: The Royal Marsden Hospital prognostic score (RMH score) and the Gustave Roussy immune score (GRIm-score) were developed in order to select more suitable patient for phase I trials. Lactate dehydrogenase (LDH) and serum albumin concentration are common risk factors to these two systems. As the third risk factor, the RMH score and the GRIm-score adopt number of metastatic sites and neutrophil-to-lymphocyte ratio (NLR), respectively. We aimed to investigate whether these two systems are also useful for extensive disease of small cell lung cancer (ED-SCLC). METHODS: We retrospectively collected 128 patients who had initiated platinum-based chemotherapy at our hospital between September 2007 and March 2018. We divided our patients into low (score 0 - 1) and high (2 - 3) score groups, and compared overall survival (OS) and progression-free survival (PFS) between them. Multivariate Cox proportional hazard analyses found prognostic factors of survival times. RESULTS: Regarding GRIm-score, OS was significantly shorter in high score group than in low score group (median 6.1 vs. 11.4 months, P < 0.01), while no significant difference was observed in PFS (median 4.7 vs. 5.0 months, P = 0.12). Both OS (median 6.9 vs. 12.4 months, P < 0.01) and PFS (median 4.4 vs. 5.4 months, P = 0.01) were significantly shorter in high RMH score group than in low group. Multivariate analyses detected both high GRIm-score (hazard ratio (HR) 1.80, 95% confidence interval (CI) 1.20 - 2.72, P < 0.01) and high RMH score (HR 1.93, 95% CI 1.27 - 2.92, P < 0.01) as independent worse prognostic factors of OS, and then only high RMH score (HR 1.53, 95% CI 1.04 - 2.25, P = 0.03) as independent worse prognostic factor of PFS. CONCLUSIONS: Both RMH score and GRIm-score are useful as independent prognostic factors of OS in ED-SCLC. However, only RMH score is an independent prognostic factor of PFS.

Sarcopenia and Visceral Adiposity Did Not Affect Efficacy of Immune-Checkpoint Inhibitor Monotherapy for Pretreated Patients With Advanced Non-Small Cell Lung Cancer.

BACKGROUND: This study aimed to investigate the association of computed tomography (CT)-assessed sarcopenia and visceral adiposity with efficacy and prognosis of immune-checkpoint inhibitor (ICI) therapy for pretreated non-small cell lung cancer (NSCLC). METHODS: We retrospectively collected 74 patients with pretreated NSCLC who had initiated programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitor monotherapy between December 2015 and November 2018 at our hospital. As CT-assessed pretreatment markers, we used psoas muscle index (PMI), intramuscular adipose tissue content (IMAC), visceral-to-subcutaneous ratio (VSR) and visceral fat area (VFA) at lumbar vertebra L3 level. We divided 74 patients into high and low groups according to each Japanese sex-specific cut-off value. Using Kaplan-Meier curves and log-rank tests, we compared overall survival (OS) and progression-free survival (PFS). Adjusted by serum albumin, neutrophil-to-lymphocyte ratio, performance status and driver mutations, multivariate Cox proportional hazard analyses evaluated various variables as independent prognostic factors of OS and PFS. RESULTS: We could not find significant difference in response rate (RR) and disease control rate (DCR) between low and high groups according to any factors. The OS of patients with body mass index (BMI) < 18.5 was significantly shorter than that of patients with BMI ≥ 18.5 (median 3.3 vs. 15.8 months, P < 0.01), while there was no significant difference in OS and PFS according to PMI, IMAC, VSR and VFA. Multivariate analyses detected no significant prognostic factor in OS and PFS, except for low IMAC (hazard ratio 0.43, 95% confidence interval 0.18 - 0.998, P = 0.0496) as a favorable prognostic factor of longer OS. CONCLUSIONS: Neither PMI nor VSR, VFA might be a significant prognostic factor of PFS and OS of ICI monotherapy for pretreated NSCLC. According to our multivariate analyses, IMAC was a significant prognostic factor of OS, but not of PFS. Thus, neither sarcopenia nor visceral adiposity may be associated with the efficacy of ICI therapy.

Successful Treatment of Allergic Bronchopulmonary Aspergillosis Using a Combination of Inhaled Fluticasone Furoate/Vilanterol and Oral Voriconazole.

Systemic corticosteroids are considered to be the standard treatment for allergic bronchopulmonary aspergillosis (ABPA). However, there is controversy regarding use of inhaled corticosteroid (ICS) therapy for ABPA. Here we report a case of ABPA that was successfully treated with inhaled fluticasone furoate/vilanterol (FF/VI) and oral voriconazole (VRCZ). The patient was a 62-year-old Japanese man with bronchiectasis and diabetes mellitus who presented with fever, cough, and purulent sputum. Computed tomography scans of the chest showed consolidation in the left upper and lower lobes. Laboratory investigations revealed an abnormal increase in the number of eosinophils (3,340/mm3) and elevated levels of C-reactive protein (3.04 mg/dL) and serum immunoglobulin E (IgE) (763 U/mL). Eight days after admission, he experienced a sudden attack of asthma. Aspergillus-precipitating antibodies were positive and Aspergillus fumigatus was detected in sputum culture. These results were consistent with a diagnosis of ABPA, and he was started on inhaled FF/VI and oral VRCZ. Systemic corticosteroids were not used because of the patient's history of diabetes mellitus and left atrial thrombus. His symptoms and consolidation improved significantly after treatment. He has not experienced an exacerbation for more than 3 years. In mild cases of ABPA in which total IgE is relatively low, inhaled FF/VI in combination with oral VRCZ can be considered as an alternative treatment to systemic corticosteroids in patients with ABPA.

Metachronous rectal metastasis from pulmonary adenocarcinoma after 11 years of chemo-, immuno-, and radiotherapy for recurrent lesions: a case report.

BACKGROUND: Rectal metastasis from pulmonary adenocarcinoma is rare, and it has been regarded as an end-stage phenomenon. Recently, however, advances in lung cancer treatment have improved the chance of long-term survival of patients with unresectable distant metastases. We describe the occurrence and management of metastatic spread of a pulmonary carcinoma to the rectum. CASE PRESENTATION: The patient was a 79-year-old woman who had undergone thoracoscopic left lobectomy for pulmonary adenocarcinoma and then, over the next 11 years, various drugs (carboplatin + paclitaxel (as adjuvant therapy), gefitinib, gemcitabine + vinorelbine, S1 (an oral 5-fluorouracil-based drug), carboplatin + pemetrexed + bevacizumab, erlotinib, nivolumab, afatinib, and carboplatin+ S1) were administered, especially for hilar and mediastinal lymph node recurrences. During the eleventh postoperative year, left and right iliac bone metastases were detected, and radiation therapy was undertaken for local control of these lesions. When 18F-fluorodeoxyglucose positron emission tomography was performed for evaluation of the disease, tracer accumulation in the upper rectum was seen. Colonoscopic examination of the rectum revealed an intramural mass with central ulceration, and the mass was diagnosed histologically as an adenocarcinoma. The bone metastases appeared to be controlled, and the patient's performance status was good, but she had suffered constipation for about a year and desired treatment. Thus, laparoscopic low anterior resection was performed. Histopathologic analysis revealed a moderately differentiated adenocarcinoma existing mainly between the submucosa and serosa, and immunohistochemical analysis showed the tumor to be positive for cytokeratin (CK) 7, negative for CK20, positive for thyroid transcription factor-1, and negative for special AT-rich sequence-binding protein 2 and caudal type homeobox 2, confirming the diagnosis of rectal metastasis from the primary pulmonary adenocarcinoma. The patient recovered well without any change in her functional status. Systemic chemotherapy was resumed, and she continues to do well, now 6 months after surgery. CONCLUSIONS: Surgery may be a good option for the management of an isolated rectal metastasis from pulmonary cancer in patients whose functional status is good.

Gustave Roussy Immune Score and Royal Marsden Hospital Prognostic Score Are Biomarkers of Immune-Checkpoint Inhibitor for Non-Small Cell Lung Cancer.

BACKGROUND: The Gustave Roussy Immune Score (GRIm-Score) and the Royal Marsden Hospital prognostic score (RMH score) were recently developed in order to improve a better participant selection for phase I trials. The GRIm-Score is formed by combination of lactate dehydrogenase (LDH), serum albumin concentration, and neutrophil-to-lymphocyte ratio (NLR). The RMH score is calculated by LDH, albumin, and number of metastases. These two scores have been validated only in phase I trials. The purpose of this study was to assess whether these scores are useful for practical treatment of immune-checkpoint inhibitor (ICI) monotherapy in pretreated non-small cell lung cancer (NSCLC). METHODS: This was a retrospective and single-centered study of 76 NSCLC patients treated with ICI monotherapy between December 2015 and October 2018 at our hospital. We divided 76 patients into high and low GRIm-Score and RMH score groups. Comparison of overall survival (OS) and progression free survival (PFS) was performed by Kaplan-Meier curves and log-rank tests. Independent prognostic factors of OS and PFS were analyzed by multivariate Cox proportional hazard analyses. RESULTS: The OS of the high GRIm-Score group was significantly shorter than that of the low score group (low vs. high; median 19.9 vs. 3.2 months, P < 0.01), while no significant difference was observed in PFS (2.6 vs. 2.1 months, P = 0.13). The PFS of the high RMH score was significantly shorter than that of the low score group (low vs. high; 2.6 vs. 1.8 months, P = 0.01), while there was no significant difference in OS (16.0 vs. 10.4, P = 0.24). Multivariate analyses detected high GRIm-Score (hazard ratio (HR) 3.93, 95% confidence interval (CI) 2.04 - 7.58, P < 0.01), and high RMH score (HR 1.76, 95% CI 1.03 - 3.02, P = 0.04) as poor prognostic factors of OS and PFS, respectively. CONCLUSIONS: Baseline GRIm-Score and RMH score were independent prognostic factors of OS and PFS of ICI monotherapy for pretreated NSCLC patients, respectively. These two scores are not only selection biomarkers for patients in experimental trials, but also useful prognostic biomarkers for NSCLC patients practically treated with ICI therapy.

Pretreatment Lung Immune Prognostic Index Is a Prognostic Marker of Chemotherapy and Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor.

BACKGROUND: Lung immune prognostic index (LIPI) was recently developed on the basis of the combination of baseline derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH). This index was demonstrated as a specific biomarker of immune checkpoint inhibitors for non-small cell lung cancer (NSCLC). We aimed to show that LIPI may be a useful biomarker of cytotoxic chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for NSCLC. METHODS: We retrospectively collected 175 wild-type EGFR adenocarcinomas, 131 NSCLCs harboring mutant EGFR and 110 squamous cell carcinomas. All patients initiated first-line cytotoxic chemotherapy or EGFR-TKI monotherapy between July 2007 and August 2017 at our hospital. These patients were divided into good, intermediate and poor LIPI groups. We compared their overall survival (OS) and progression-free survival (PFS). Multivariate analyses detected prognostic and predictive factors of OS and PFS. RESULTS: The good LIPI group survived longer than the intermediate and poor LIPI groups in wild-type EGFR adenocarcinoma (good, intermediate and poor LIPI groups: median 19.6, 11.5 and 3.3 months, P < 0.01, respectively) and mutant EGFR NSCLC (45.4, 25.6 and 15.7 months, P < 0.01). The PFS of good LIPI group was significantly longer that those of the other two groups in mutant EGFR NSCLC (16.6, 12.6 and 8.3 months, P < 0.01). The intermediate group (hazard ratio (HR) 1.49, 95% confidential interval (CI) 1.03 - 2.15, P = 0.04) of wild-type EGFR adenocarcinoma, intermediate (HR 2.30, 95% CI 1.33 - 3.99, P < 0.01) and poor (HR 2.76, 95% CI 1.03 - 7.42, P = 0.04) groups of mutant EGFR NSCLC were independent prognostic factors of poor OS. The intermediate (HR 1.57, 95% CI 1.01 - 2.44, P = 0.04) and poor (HR 2.63, 95% CI 1.14 - 6.07, P = 0.02) groups were significant prognostic factors of PFS of mutant EGFR NSCLC. CONCLUSIONS: LIPI was an independent prognostic factor of chemotherapy for adenocarcinoma with wild-type EGFR and of EGFR-TKI for NSCLC harboring mutant EGFR. Thus, LIPI was not a specific biomarker for ICI therapy, but a useful biomarker for chemotherapy and EGFR-TKI therapy in specific subsets of NSCLC.

Gustave Roussy Immune Score Is a Prognostic Factor for Chemotherapy-Naive Pulmonary Adenocarcinoma With Wild-Type Epidermal Growth Factor Receptor.

BACKGROUND: The Gustave Roussy Immune Score (GRIm-Score) was developed based on the Royal Marsden Hospital (RMH) prognostic score for the purpose of a better patient selection for immunotherapy phase I trials. This scoring system is simply calculated by neutrophil-to-lymphocyte ratio, lactate dehydrogenase (LDH), and serum albumin concentration. The aim of our study was to determine whether GRIm-Score is a practically useful prognostic biomarker for advanced non-small cell lung cancer (NSCLC) patients treated with cytotoxic chemotherapy or epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). METHODS: This retrospective and single institutional study collected 185 adenocarcinomas without active EGFR mutation, 115 squamous cell carcinomas treated with first-line cytotoxic chemotherapy, and 140 NSCLCs with mutant EGFR treated with first- or second-generation EGFR-TKI monotherapy. These treatments were initiated between July 2007 and March 2018 at our hospital. We compared overall survival (OS) and progression-free survival (PFS) between high and low GRIm-Score groups. Using multivariate Cox proportional hazard analyses, we also found prognostic factors of survival times. RESULTS: The OS and PFS of low GRIm-Score group were significantly longer than those of high-score group in wild-type EGFR adenocarcinoma (low vs. high; median OS, 18.4 vs. 5.1 months, P < 0.01, and median PFS, 5.8 vs. 3.7 months, P = 0.01) and EGFR-mutant NSCLC (median OS, 38.9 vs. 10.4 months, P < 0.01, and median PFS, 15.9 vs. 5.0 months, P < 0.01). Subsequent multivariate analyses detected high GRIm-Score in wild-type EGFR adenocarcinoma as a poor prognostic factor of OS (hazard ratio (HR) 2.20, 95% CI 1.47 - 3.31, P < 0.01), and in the EGFR-mutant NSCLC as a poor prognostic factor of PFS (HR 1.89, 95% CI 1.00 - 3.55, P = 0.049). CONCLUSIONS: High GRIm-Score was an independent prognostic biomarker of OS of first-line cytotoxic chemotherapy for wild-type EGFR adenocarcinoma and of PFS of first- or second-generation EGFR-TKI for EGFR-mutant NSCLC. Therefore, GRIm-Score is not only a specific selection marker for experimental immunotherapy trials, but may also be a promising and useful pretreatment prognostic maker for specific NSCLC subsets in the real-world practice.

A Phase II Study of Tailored-dose S-1 Plus Carboplatin Followed by Maintenance S-1 for Advanced Squamous Cell Lung Cancer: OSAKA-LCSG 1102.

Objective A subset analysis of the LETS study suggested that S-1 plus carboplatin was more beneficial than paclitaxel plus carboplatin in terms of the overall survival (OS) in squamous cell lung cancer. However, the benefit of maintenance therapy for squamous cell non-small cell lung cancer (NSCLC) patients is still unknown. We herein report a phase II study to evaluate the efficacy and safety of a tailored dose of S-1 plus carboplatin followed by maintenance S-1 in chemotherapy-naive advanced squamous cell NSCLC. Methods Patients received carboplatin on day 1 plus S-1 on days 1 to 14 every 21 days. The dose of S-1 was determined by the body surface area and creatinine clearance. After four cycles of induction, non-progressive patients continued to receive S-1 until disease progression or unacceptable toxicity occurred. The primary endpoint was an objective response rate (RR) with a threshold value of 15%. The secondary endpoints were the progression-free survival (PFS) and OS from enrollment, the PFS in the maintenance phase, and safety. Results In the 33 patients analyzed, the rate of patients who met the primary endpoint was 30.3% (95% confidence interval: 15.6-48.7%), and the disease control rate was 75.8%. The median PFS and OS were 3.5 and 11.3 months, respectively. Ten patients received maintenance S-1, and the median PFS from the beginning of induction treatment was 5.3 months. Grade 3/4 toxicities with a frequency of more than 5% were all controllable. Conclusion Tailored-dose S-1 plus carboplatin followed by maintenance S-1 is an effective and feasible treatment for advanced squamous cell NSCLC.

Growth of Mediastinal Bronchial Artery Aneurysms in a Patient With Bronchiectasis.

Mediastinal bronchial artery aneurysm (BAA) is a rare and life-threatening disease. We experienced the first case confirming that, despite only slight deterioration of bronchiectasis, mediastinal BAAs expanded remarkably. A 61-year-old female was hospitalized because of hemoptysis. Her respiratory condition required intubated mechanical ventilation. Bronchial artery angiography unexpectedly found unruptured mediastinal BAAs. These BAAs were enlarged compared with those seen in a computed tomography (CT) taken 5 years before. We successfully embolized both BAAs and peripheral arteries. Mediastinal BAAs are capable of increasing more rapidly than a slightly deteriorated underlying bronchiectasis. For rapid and accurate diagnosis of BAA, bronchial artery angiography is important.

Low Body Mass Index Is an Independent Prognostic Factor in Patients With Non-Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor.

BACKGROUND: Sarcopenia and obesity have been suspected as factors associated with efficacy of treatment and prognosis in various malignancies. This study aimed to investigate the association of pretreatment sarcopenia and visceral obesity with efficacy and prognosis of first- and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for patients with non-small cell lung cancer (NSCLC) and positive EGFR mutation. METHODS: We retrospectively collected 167 NSCLC patients with mutant EGFR who had started EGFR-TKI monotherapy between October 2007 and August 2018 at our hospital. We classified 167 patients into two groups, according to the definition of underweight based on the World Health Organization (WHO) body mass index (BMI) classification and the Japanese sex-specific cut-off values of the following computed tomography (CT) images-assessed markers of pretreatment sarcopenia or visceral obesity, such as psoas muscle index (PMI), intramuscular adipose tissue content (IMAC) and visceral-to-subcutaneous fat ratio (VSR) at lumbar vertebra L3 level. We compared overall survival (OS) and progression-free survival (PFS) of two groups by Kaplan-Meier curves and log-rank tests. Using multivariate Cox proportional hazard analyses adjusted by age, neutrophil-to-lymphocyte ratio, performance status, EGFR mutation types and EGFR-TKI lines, and extra-pulmonary metastases or three or more than 3 metastatic sites, we searched independent prognostic factors of OS and PFS of EGFR-TKI therapy. RESULTS: The OS (median 26.0 vs. 32.3 months, P = 0.02) and PFS (9.1 vs. 14.8 months, P = 0.03) of patients with BMI < 18.5 were significantly shorter than those of patients with BMI ≥ 18.5. However, there was no significant difference in OS and PFS according to PMI, IMAC and VSR. The multivariate analyses detected only BMI < 18.5 as an unfavorable prognostic factor of shorter OS (hazard ratio (HR) 1.70, 95% confidence interval (CI) 1.03 - 2.81, P = 0.04) and PFS (HR 1.72, 95% CI 1.11 - 2.67, P = 0.02). CONCLUSIONS: Pretreatment underweight was a significant prognostic factor of poor PFS and OS of EGFR-TKI therapy. However, neither pretreatment sarcopenia nor visceral obesity was associated with prognosis of EGFR-TKI. Underweight may be a surrogate for advanced disease burden.