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.

Clinical benefit of platinum doublet combination therapy in older adults with advanced non-small cell lung cancer: A prospective multicenter study by the National Hospital Organization in Japan.

BACKGROUND: Previous trials suggest that older adults with non-small cell lung cancer (NSCLC) derive benefit from platinum doublet combination therapy, but its superiority is controversial. Although geriatric assessment variables are used to assess the individual risk of severe toxicity and clinical outcomes in older patients, the standard first-line treatment is still debated. Therefore, we aimed to identify the risk factors for clinical outcomes in older patients with NSCLC. METHODS: Patients aged ≥75 years with advanced NSCLC treated at any of 24 National Hospital Organization institutions completed a pre-first-line chemotherapy assessment, including patient characteristics, treatment variables, laboratory test values, and geriatric assessment variables. We evaluated whether these variables were the risk factors for progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 148 patients with advanced NSCLC were treated with combination therapy (n = 90) or monotherapy (n = 58). Median PFS was 5.3 months and OS was 13.6 months. We identified that hypoalbuminemia (hazard ratio [HR] 2.570, 95% confidence interval [CI]: 1.117-5.913, p = 0.0264) was a risk factor for PFS and monotherapy (HR 1.590, 95% CI: 1.070-2.361, p = 0.0217), lactate dehydrogenase (HR 3.682, 95% CI: 1.013-13.39, p = 0.0478), and high C-reactive protein (HR 2.038, 95% CI: 1.141-3.642, p = 0.0161) were risk factors for OS. The median OS was significantly longer in patients treated with combination therapy than in those who received monotherapy (16.5 months vs. 10.3 months; HR 0.684, 95% CI: 0.470-0.995, p = 0.0453). DISCUSSION: Platinum doublet combination therapy may be beneficial in older patients with NSCLC. Identification of risk factors will assist in the development of a personalized treatment strategy.

First-Line Pembrolizumab Monotherapy for Advanced NSCLC With Programmed Death-Ligand 1 Expression Greater Than or Equal to 50%: Real-World Study Including Older Patients in Japan.

Introduction: Pembrolizumab became available in Japan in February 2017 for first-line monotherapy of unresectable advanced and metastatic NSCLC with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) greater than or equal to 50%. This retrospective chart review study aimed to describe real-world clinical outcomes of first-line pembrolizumab monotherapy, including for patients 75 years or older, who are under-represented in clinical trials. Methods: We identified patients (≥20 y old) at 23 sites initiating first-line pembrolizumab monotherapy from July 1, 2017, to December 20, 2018, for stages IIIB, IIIC, and IV NSCLC with PD-L1 TPS greater than or equal to 50% and Eastern Cooperative Oncology Group performance status of 0 to 2 or unknown. Patients with actionable genomic alterations (EGFR, ALK, ROS1, BRAF) and clinical trial participants were excluded. Time-to-event outcomes were estimated using Kaplan-Meier, with data cutoff on September 30, 2019. Results: Of 441 eligible patients (78% men), 303 (69%) were younger than 75 years and 138 (31%) were 75 years or older; median age was 70 years. With median follow-up of 13.5 months, median overall survival (OS) was not reached (NR); 12- and 24-month OS rates were 72% and 58%, respectively. For ages younger than 75 and 75 years or older, median OS was NR and 23.5 months (95% confidence interval: 16.2-NR), respectively; 12-month OS rates were 74% and 67% and 24-month OS rates were 62% and 48%, respectively. Median real-world progression-free survival was similar in the two age groups (10.1 and 9.5 mo, respectively), as was median real-world time on treatment with pembrolizumab (5.7 and 5.6 mo). Conclusions: These findings complement clinical trial results, adding real-world evidence supporting benefits of first-line pembrolizumab monotherapy for advanced NSCLC with PD-L1 TPS greater than or equal to 50%, including for patients 75 years or older.

Predicting systemic therapy toxicity in older adult patients with advanced non-small cell lung cancer: A prospective multicenter study of National Hospital Organization in Japan.

INTRODUCTION: Previous studies have developed risk stratification schemas to assess systemic therapy toxicity. However, it is controversial which geriatric assessment variables should be used to assess the individual risk of severe treatment-associated toxicity in older adult patients. MATERIALS AND METHODS: Patients aged ≥70 years with advanced non-small cell lung cancer (NSCLC) treated at 24 National Hospital Organization institutions completed a pre-first-line systemic therapy assessment, including patient characteristics, treatment variables, laboratory test values, and geriatric assessment variables. Patients were followed through one cycle of systemic therapy to assess grade 3 (severe) to grade 5 (death) adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: In total, 348 advanced NSCLC patients with a median age of 76 years (range, 70 to 95 years) joined this prospective study. Severe adverse events ≥grade 3 occurred in 136 patients (39.1%). Predictors of hematologic toxicity were treatment variables, body mass index, body weight loss, and limitation in daily living due to dementia. These predictors provided the predictive model of hematologic toxicity ≥grade 3; 0 point (22.2%), 1 point (33.8%), 2 points (59.6%), ≥3 points (73.3%). Sex, daily living independence level, and lactate dehydrogenase levels were associated with non-hematologic toxicity ≥grade 3 in multivariate analysis. A scoring system using these predictors distinguished the risk levels of non-hematologic toxicity ≥grade 3; 0 point (6.6%), 1 point (12.2%), 2 points (39.0%), 3 points (75.0%). DISCUSSION: A stratification using individual extracted risk factors may be useful to predict the vulnerability to systemic therapy in older adult NSCLC patients.

A randomized phase II study of docetaxel or pemetrexed with or without the continuation of gefitinib after disease progression in elderly patients with non-small cell lung cancer harboring EGFR mutations (JMTO LC12-01).

BACKGROUND: Gefitinib (G) is a recommended molecular-targeted agent for elderly patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Docetaxel (Doc) and pemetrexed (Pem) have similar efficacies, and either is often used as the sole agent during treatment. The efficacy of continuing G after progressive disease (PD) develops has been reported. It remains unclear whether the continuation of G in combination with a single cytotoxic agent beyond PD is beneficial for elderly patients. Here, we conducted a randomized phase II study to assess the efficacy and safety of cytotoxic chemotherapy with G for elderly patients with progressive EGFR-mutant NSCLC. METHODS: Elderly patients with EGFR-mutant NSCLC with PD previously treated with G were enrolled. Patients received Pem 500 mg/m or Doc 60 mg/m every 21 days and were randomly assigned to receive chemotherapy with 250 mg G (G+ Doc/Pem arm) or without G (Doc/Pem arm) until further disease progression or unacceptable toxicity. RESULTS: This trial was terminated early owing to slow accrual. A group of 22 patients underwent analysis. The primary endpoint, progression-free survival (PFS), was significantly longer in the G + Doc/Pem arm (median: 1.6 months vs. 5.6 months, hazard ratio = 0.40, 95% CI: 0.16-0.99, p = 0.0391). Adverse events ≥ grade 3 were more frequent in the G + Doc/Pem arm (45.5% vs. 90.9%, p = 0.032). CONCLUSIONS: Patients on G and Pem or Doc beyond PD showed a longer PFS than those on single-agent chemotherapy; however, it was associated with increased toxicity.

Impact of lung cancer surgery on comorbid Mycobacterium avium complex lung disease-A case series.

The number of cases with Mycobacterium avium and Mycobacterium intracellulare lung diseases (Mycobacterium avium complex lung disease [MACLD]) are increasing globally. Lung cancer can sometimes present as a comorbidity with MACLD; however, the clinical presentation and outcomes of comorbid MACLD following lung cancer resection remain unclear. Therefore, we retrospectively assessed 17 patients with MACLD undergoing lung cancer resection to determine the impact of lung cancer surgery on comorbid MACLD. Of the 17 patients, Mycobacterium avium and Mycobacterium intracellulare were present in 15 and 2 patients, respectively; 14 patients had stage I lung cancer and underwent lobectomy. Ten patients were postoperatively observed for MACLD without any further intervention, five patients underwent additional resection for conspicuous MACLD lesions, and the remaining two patients underwent complete resection for MACLD and lung cancer within the same lobe followed by rifampicin, ethambutol, and clarithromycin (RECAM) therapy. Seven patients exhibited postoperative MACLD exacerbation, six of whom developed exacerbation in the operated ipsilateral residual lobes. Six of these seven patients received RECAM, three of whom (43%) subsequently exhibited improvement. Attention should be paid to MACLD exacerbation during postoperative follow-up, especially in ipsilateral lobes. Although RECAM therapy may be beneficial in alleviating MACLD exacerbation, further investigation is warranted to validate these results.

Tuberculosis during lung cancer treatment-A case series.

This study aimed to clarify the characteristics of patients with lung cancer undergoing treatment until the onset of tuberculosis. Between 2005 and 2019, patients who were admitted to Tokyo National Hospital due to tuberculosis during lung cancer treatment were examined retrospectively. There were 42 patients, and detailed medical information was obtained in 39 patients. The median age of the 39 patients were 75 years (range: 47-92 years), of which 33 were males and 36 were Japanese Baby Boomers or older. Regarding risk factors for developing tuberculosis, smoking was noted in 34 cases, oral corticosteroid use in 13, and previous tuberculosis in six. Thirty-seven patients had one risk factor and 19 had two or more risk factors, but diagnosis of latent tuberculosis infection (LTBI) was obtained in only one patients, and none had received LTBI treatment. The first-line treatment for lung cancer was resection in 13 cases, chemoradiotherapy in 6, chemotherapy in 10, radiation therapy in 3, laser therapy in 1, and best supportive care (BSC) alone in 6. At tuberculosis onset, BSC accounted for 17 cases, but other situations were considerably existed such as anticancer medication (12 cases), and observation after lung cancer treatment (10 cases). Tuberculosis occurred in various situations in elderly patients with lung cancer. It is critical to actively evaluate the risk of tuberculosis and consider LTBI screening and treatment.

Diaphragmatic hernia during treatment of lung cancer harboring an EGFR mutation.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a first-line treatment for patients with nonsmall-cell lung cancer harboring EGFR mutations. We report a 65-year-old Japanese woman with nonsmall-cell lung cancer taking an EGFR-TKI who visited the emergency department with acute nausea and vomiting. Imaging studies demonstrated an incarcerated diaphragmatic hernia. Urgent diagnostic surgery revealed a gap in the diaphragm acting as a hernial orifice, where a metastatic tumor was detected. We consider that regression of the diaphragmatic metastasis by EGFR-TKI therapy resulted in perforation of the diaphragm, causing the diaphragmatic hernia. Gastrointestinal adverse events, e.g. nausea, vomiting and diarrhea, are common during EGFR-TKI treatment. However, this case suggests that in patients with diaphragmatic metastasis, we should consider the rare possibility of diaphragmatic perforation and a subsequent hernia.

Sequential therapy of crizotinib followed by alectinib for non-small cell lung cancer harbouring anaplastic lymphoma kinase rearrangement (WJOG9516L): A multicenter retrospective cohort study.

BACKGROUND: The data of sequential therapy of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) in clinical practice have been limited. METHODS: We reviewed the clinical data of patients with ALK-rearranged non-small cell lung cancer who received crizotinib (CRZ) or alectinib (ALEC) between May 2012 and December 2016. Patients were divided into two groups based on the first-administered ALK-TKI, the CRZ or ALEC group. The combined time-to-treatment failure (TTF) was defined as the sum of the 'TTF of CRZ' plus the 'TTF of ALEC' if patients were treated with CRZ followed by ALEC in the CRZ group. The primary end-point is the comparison between the combined TTF and the TTF of ALEC in the ALEC group. RESULTS: Of 864 patients enrolled from 61 institutions, 840 patients were analysed. There were 535 of 305 patients in the CRZ/ALEC groups. The combined TTF in the CRZ group was significantly longer than TTF in the ALEC group (median, 34.4 versus 27.2 months; hazard ratio [HR], 0.709; P = 0.0044). However, there was no significant difference in overall survival (OS) between the patients who received ALEC after CRZ in the CRZ group and the patients in the ALEC group (median, 88.4 months versus. not reached; HR, 1.048; P = 0.7770). In the whole population, the CRZ group had a significantly shorter OS than the ALEC group (median, 53.6 months versus not reached; HR, 1.821, P < 0.0001). CONCLUSION: The combined TTF in the CRZ group was significantly longer than the TTF in the ALEC group; however, OS benefit of sequential therapy against ALEC as the first ALK-TKI was not shown.

Usefulness of Rapid Desensitization Therapy for Severe Rash Caused by Molecularly Targeted Drugs Used in the Treatment of Non-small-cell Lung Cancer.

Molecular-targeted drugs (MTDs), such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and anaplastic lymphoma kinase inhibitors, are used to treat non-small-cell lung cancer (NSCLC). The incidence of rash caused by EGFR-TKIs and discontinuation of MTDs because of rash are issues. Rapid desensitization therapy (RDT) was performed in five patients who developed severe rash after introduction of MTDs and was successful in four, all of whom showed no rash relapse. RDT may thus be useful for treating rash in patients receiving MTDs for NSCLC.

Patency Capsule Aspiration.

A 77-year-old man with anemia who had undergone 2 abdominal surgeries for colon and gastric cancer experienced dyspnea after swallowing a patency capsule before endoscopy for investigating the cause of anemia. Chest radiography and computed tomography revealed that the patency capsule was located within the bronchus intermedius. It was successfully removed by flexible bronchoscopy. The balloon was placed over the capsule and inflated. Subsequently, the catheter was pulled, while thus dragging the capsule with it and preventing its destruction. In cases of patency capsule aspiration, the capsule must be removed without deformity, before it causes inflammation by releasing barium into the airway.

Recent trends in the incidence of latent tuberculosis infection in Japanese patients with lung cancer: A small retrospective study.

Active tuberculosis is an important complication in Japanese lung cancer patients. We studied the generation-wise trend of latent tuberculosis infection (LTBI) among lung cancer patients. We analyzed background data including birth year, lung cancer status, and interferon-gamma release assay (IGRA) data of lung cancer patients who were admitted to National Hospital Organization Tokyo National Hospital from 2010 to 2016. Of the 1450 cases, 7 showed active tuberculosis and 45 had previous tuberculosis. Of the remaining 1398 patients, 795 underwent IGRAs and 120 (15%) of them were found to have LTBI. Patients with LTBI were older (p = 0.0005), and the proportion of smokers was also higher in this group (p = 0.0159) than among those without LTBI. LTBI incidence decreased from 33% among patients born in the 1920s to 21%, 15%, 9.8%, and 5.1% among those born in the 1930s, 1940s, 1950s, and after 1960, respectively. A significant decrease in the smoking adjusted risk ratio was also observed with every generation (p < 0.0001). Our study suggests that the total number of patients with active tuberculosis comorbid with lung cancer will greatly decrease in the future in Japan. However, owing to recent improvements in lung cancer prognosis due to advances in cancer medication, careful monitoring for active tuberculosis development may be required in lung cancer patients with LTBI.

Exacerbation of chronic pulmonary aspergillosis was associated with a high rebleeding rate after bronchial artery embolization.

BACKGROUND: Hemoptysis is a common symptom associated with chronic pulmonary aspergillosis (CPA). While surgery is the primary choice to manage hemoptysis, it is often avoided because patients with CPA are more likely to have complications such as respiratory insufficiency and low pulmonary function. Bronchial artery embolization (BAE) may be considered one of the treatments of massive and persistent hemoptysis for such patients. METHODS: We retrospectively reviewed medical records of 41 patients, admitted to National Hospital Organization Tokyo National Hospital, Tokyo, Japan with hemoptysis arising from CPA between January 2011 to December 2016, who were considered inoperable and had undergone BAE. RESULTS: Out of the 41 cases analyzed in this study, 21 (51.2%) developed rebleeding after BAE within the mean follow-up duration of 24 months. The non-rebleeding rate of patients after BAE was 92.7% within a month and 65.8% within a year. Patients who developed rebleeding had significantly more non-bronchial systemic arteries responsible for the bleeding compared with patients who did not develop rebleeding (mean of 2.55 vs. 4.86, respectively, P = 0.011). Patients with stable or improved radiological findings demonstrated significantly lower rebleeding rates than those with radiological deterioration (P < 0.001). The non-rebleeding patients had significantly better survival than those with rebleeding (79.7% vs. 39.9% over 5 years, P = 0.046). CONCLUSIONS: Bronchial artery embolization was effective in controlling hemoptysis in patients with CPA, especially those who could not undergo surgical resection. However, disease control of CPA was important to prevent rebleeding over the long term and to improve survival after BAE.

A successful pembrolizumab treatment case of lung adenocarcinoma after becoming resistant to ALK-TKI treatment due to G1202R mutation.

BACKGROUND: In current guidelines, the role of immune checkpoint inhibitors is not yet determined in the treatment strategy for NSCLC harboring ALK translocations. CASE: A 51-year-old woman with lung adenocarcinoma harboring ALK translocation was treated with alectinib until PD. After the second (CDDP/PEM) and third (crizotinib) line treatment, a second biopsy was performed, revealing PD-L1 tumor proportion score of 70-80% and G1202R mutation of ALK. Pembrolizumab was selected for the fourth line, leading to PR for more than 6 months. CONCLUSIONS: While alectinib might induce resistance to ALK-TKI, it could increase PD-L1 positive cells to become sensitive to PD-1/PD-L1 inhibitors.

Pulmonary Adenocarcinoma, Harboring Both an EGFR Mutation and ALK Rearrangement, Presenting a Stable Disease to Erlotinib and a Partial Response to Alectinib.

A 63-year-old woman with pulmonary adenocarcinoma (stage IIIB) that was positive for an epidermal growth factor receptor (EGFR) mutation and an anaplastic lymphoma kinase (ALK) rearrangement was treated with erlotinib as the first-line treatment, resulting in a stable disease. Due to skin rashes, fatigue and anorexia, erlotinib was suspended on erlotinib day 44. Alectinib was administered as the second-line treatment, exhibiting a partial response. On alectinib day 56, drug-induced lung injury forced suspension of alectinib, which was cured with corticosteroid therapy. ALK-tyrosine kinase inhibitors may be more effective for patients positive for both EGFR mutation and ALK rearrangement than other agents.

The Evaluation of Interstitial Abnormalities in Group B of the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Classification of Chronic Obstructive Pulmonary Disease (COPD).

Objective In 2011, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification categorized chronic obstructive pulmonary disease (COPD) patients into 4 groups. A report demonstrated that the mortality in Group B was higher than that in Group C. Ischemic heart disease and cancer were suggested to be the cause. The aim of the present study was to test the hypothesis that interstitial lung abnormalities (ILAs) are more prevalent in Group B than Group C and that they may be responsible for the higher mortality in Group B. Methods Patients were selected based on their pulmonary function test results. The inclusion criterion was a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) of <70% after the inhalation of a bronchodilator. Patients without a smoking history or computed tomography (CT) scan were excluded. The medical records of the patients were retrospectively reviewed, and the selected patients were categorized into Groups A to D. High-resolution CT scans were used to investigate the presence of ILAs and determine the low attenuation area (LAA). Results Among the 349 COPD patients, ILAs were detected in 10.3% of the patients in Group A, 22.5% of the patients in Group B, 5.6% of the patients in Group C, and 23.1% of the patients in Group D. In Group B, the frequency of ILAs was significantly higher and the area affected by the ILAs was significantly greater in comparison to Group C. Among the patterns of interstitial abnormalities, the area of honeycombing in Group B was significantly greater than that in Group C. Furthermore, among the patients in Group B, the LAA in the ILA-positive patients was significantly greater than that in the ILA-negative patients. Conclusion In Group B, the area occupied by ILAs-especially honeycombing-was greater than that in Group C. This contributed to the preserved %FEV1 and possibly to the poorer prognosis of the patients in Group B.

Clinical and Angiographic Characteristics of 35 Patients With Cryptogenic Hemoptysis.

BACKGROUND: Hemoptysis can cause a life-threatening condition and often needs to be treated urgently. Nearly 20% of hemoptysis cases are diagnosed as cryptogenic after clinical investigation. The purpose of this study was to clarify the clinical and angiographic characteristics of cryptogenic hemoptysis. METHODS: We retrospectively reviewed medical records of 35 patients admitted to our hospital with cryptogenic hemoptysis from October 2010 to September 2014. RESULTS: In the 35 cases, bronchial artery embolization was successfully performed in 33 patients (94.3%), whereas bronchoscopic hemostatic therapy was added in one patient (2.8%), and embolization was not performed in one patient (2.8%) because the bronchial artery was too narrow. In the successful embolization group, the non-rebleeding rate was 97.0% for 20 months. The angiographic findings revealed that the diameter of the bronchial arteries was < 2 mm in 13 patients, 2 to 3 mm in 17 patients, and > 3 mm in five patients. Hypervascularization was detected in 29 patients (82.9%) and small bronchial aneurysms in eight patients (22.9%). The amount of hemoptysis was slight (< 50 mL/d) in 12, mild (50-100 mL/d) in 11, moderate (100-200 mL/d) in eight, and massive (> 200 mL/d) in four patients. No obvious relationship was found between the diameter of bronchial arteries and the amount of hemoptysis. CONCLUSIONS: BAE was highly effective for the management of cryptogenic hemoptysis. Most cases of cryptogenic hemoptysis have angiographic abnormalities, including small or microaneurysms, which were suspected as the cause in some cases.

[Evaluation of the Efficacy and Safety of Platinum Doublet Re-Challenge Chemotherapy in Patients with Recurrent Advanced Non-Small Cell Lung Cancer].

BACKGROUND: Docetaxel or pemetrexed is the standard treatment for recurrent advanced non-small cell lung cancer (NSCLC). Until now, combination chemotherapy has failed to demonstrate superiority in patients with recurrent advanced NSCLC, compared to single-agent chemotherapy. The aim of the present study was to assess the efficacy and safety of platinum doublet re-challenge chemotherapy in patients with recurrent advanced NSCLC. METHODS: Fifty-eight patients with recurrent advanced NSCLC who underwent platinum doublet re-challenge chemotherapy were retrospectively analyzed. RESULTS: The response rate was 6.9%(95%CI: 1.9-16.7%), the disease control rate was 70.7% (95%CI: 57.3-81.9%), the median progression-free survival (PFS) was 123 days, and the median survival time (MST) after re-challenge chemotherapy was 470 days. The disease control rate and the PFS were significantly better in patients who achieved a partial response to first-line chemotherapy than in patients who had stable or progressive disease. In addition, the PFS and MST were significantly longer in patients whose treatment-free interval was more than 90 days. Toxicities were tolerable in most patients, except for 1 patient who showed drug-induced pneumonia. CONCLUSION: Platinum doublet re-challenge chemotherapy is a treatment option for patients with advanced NSCLC who achieved a partial response to first-line chemotherapy or for patients whose treatment-free interval lasted longer than 90 days.

Relationship Between Lung Cancer and Mycobacterium Avium Complex Isolated Using Bronchoscopy.

INTRODUCTION: The incidence of Mycobacterium avium complex (MAC)-positive respiratory specimen cultures and MAC lung disease (MACLD) is increasing worldwide. This retrospective study aimed to assess the association between MAC culture-positive bronchoscopy specimens and lung cancer. MATERIALS AND METHODS: The medical records of 1382 untreated lung cancer patients between 2003 and 2011 were collected using our hospital database. Of them, records for 1258 that had undergone bronchoscopy together with sampling for mycobacterial culture were reviewed. Patient characteristics were compared between those with MAC-positive/other nontuberculous mycobacteria (NTM)-negative bronchial washings and those with MAC-negative/other NTM-negative bronchial washings. Patients with MAC-positive lung cancer were cross-sectionally divided into MACLD and non-MACLD groups, and their features were assessed. Follow-up data for patients with lung cancer but without MACLD were reviewed for subsequent development of MACLD. RESULTS: Of the 1258 patients with lung cancer, 25 (2.0%) had MAC-positive/other NTM-negative bronchial washings. The proportion of women (52% vs 30%; P = 0.0274) and patient age (72 years vs 69 years; P = 0.0380) were significantly higher in the MAC-positive/other NTM-negative lung cancer group (n = 25) than in the MAC-negative/other NTM-negative lung cancer group (n = 1223). There were 10 patients with lung cancer and MACLD and 15 without MACLD; significant differences in patient characteristics were not found between the two groups, and none of the 15 patients without MACLD subsequently developed MACLD. CONCLUSION: MAC culture-positive bronchial washing is positively associated with lung cancer. Female sex and advanced age, but not lung cancer characteristics, were found to be associated with MAC infection in patients with lung cancer.

TUBERCULOSIS AND LUNG CANCER.

The occurrence of pulmonary tuberculosis (PTB) and lung cancer as comorbidities has been extensively discussed in many studies. In the past, it was well known that lung cancer is a specific epidemiological successor of PTB and that lung cancer often develops in scars caused by PTB. In recent years, the relevance of the two diseases has drawn attention in terms of the close epidemiological connection and chronic inflammation-associated carcinogenesis. In Japanese case series studies, most lung cancer patients with tuberculous sequelae received supportive care alone in the past, but more recently, the use of aggressive lung cancer treatment is increasing. Many studies on PTB and lung cancer as comorbidities have revealed that active PTB is noted in 2-5% of lung cancer cases, whereas lung cancer is noted in 1-2% of active PTB cases. In such instances of comorbidity, many active PTB cases showed Type II (non-extensively cavitary disease) and Spread 2-3 (intermediate-extensive diseases) on chest X-rays, but standard anti-tuberculosis treatment easily eradicates negative conversion of sputum culture for M. tuberculosis; lung cancer cases were often stage III- IV and squamous cell carcinoma predominant, and the administration of aggressive treatment for lung cancer is increasing. The major clinical problems associated with PTB and lung cancer as comorbidities include delay in diagnosis (doctor's delay) and therapeutic limitations. The former involves two factors of radiographic interpretation: the principles of parsimony (Occam's razor) and visual search; the latter involves three factors of lung cancer treatment: infectivity of M.tuberculosis, anatomical limitation due to lung damage by tuberculosis, and drug-drug interactions between rifampicin and anti-cancer drugs, especially molecularly targeted drugs. The comorbidity of these two diseases is an important health-related issue in Japan. In the treatment of PTB, the possibility of concurrent lung cancer should be kept in mind, while in the treatment of lung cancer, the possibility of concurrent PTB should also be considered.