Prevalence of non-bronchial systemic culprit arteries in patients with hemoptysis with bronchiectasis and chronic pulmonary infection who underwent de novo bronchial artery embolization.

OBJECTIVES: To identify the prevalence of non-bronchial systemic culprit arteries and their relationship to bleeding lobes in patients with hemoptysis with bronchiectasis and chronic pulmonary infection who underwent de novo bronchial artery embolization (BAE). METHODS: Data of 83 consecutive patients with bronchiectasis and chronic pulmonary infection (non-tuberculous mycobacteriosis, aspergillosis, and tuberculosis) who underwent de novo BAE between January 2019 and December 2020 were retrospectively reviewed. The prevalence of culprit arteries was investigated. RESULTS: Fifty-five patients (66%) had 172 non-bronchial systemic culprit arteries. The bleeding lobes were the right upper, right middle, right lower, left upper, and left lower lobes in 14 (17%), 20 (24%), 7 (8%), 31 (37%), and 11 (13%) patients, respectively. The internal thoracic (49%; n = 41), intercostal (28%; n = 23), and inferior phrenic (28%; n = 23) arteries were the top three non-bronchial systemic culprit arteries, which were involved in all five types of bleeding lobes. The costocervical trunk and thoracoacromial and lateral thoracic arteries were predominant in patients with upper lobe bleeding. Ligament arteries were predominant in patients with left lower lobe bleeding. CONCLUSIONS: These findings will better ensure the identification of non-bronchial systemic culprit arteries in patients with hemoptysis with bronchiectasis and chronic pulmonary infection. All systemic arteries, especially those which are adjacent to the lung lesions, should be evaluated carefully using MDCT; the internal thoracic, intercostal, and inferior phrenic arteries should be proactively assessed using angiography. KEY POINTS: • Non-bronchial systemic culprit arteries were identified in 66% of patients with hemoptysis with bronchiectasis and chronic pulmonary infection who underwent de novo bronchial artery embolization. • The internal thoracic (49%), intercostal (28%), and inferior phrenic (28%) arteries were the top three arteries, which were involved in all five types of bleeding lobes. • The costocervical trunk and thoracoacromial and lateral thoracic arteries were prominent in patients with upper lobe bleeding, and the ligament artery was prominent in patients with left lower lobe bleeding.

Successful bronchial artery embolization using hydrogel coils for hemoptysis during extracorporeal membrane oxygenation.

A 58-year-old woman with bronchiectasis presented with massive hemoptysis and severe respiratory failure, which required long-term extracorporeal membrane oxygenation with continuous heparin infusion. Bronchial artery embolization using hydrogel coils, which provide a greater volume occlusion than bare platinum coils, was performed; hemoptysis stopped and she fully recovered. No recanalization was observed on follow-up computed tomography angiography 2 months postbronchial artery embolization, and there had been no recurrence of bleeding at the time of this report (at least 6 months). Although continuous anticoagulation during extracorporeal membrane oxygenation might hinder complete vessel occlusion by metallic coils or induce early recanalization (because the homeostatic mechanism of coils depends on the patient's coagulability), our experience showed that bronchial artery embolization using hydrogel coils was effective and safe. Additionally, this case presents a successful example of anticoagulation management for patients with hemoptysis on extracorporeal membrane oxygenation who undergo bronchial artery embolization using coils.

Bronchial Artery Aneurysm: Prevalence, Clinical Characteristics, and Long-Term Prognosis Following Bronchial Artery Embolization.

PURPOSE: To investigate the prevalence, clinical characteristics, and long-term prognosis of bronchial artery aneurysm (BAA) following bronchial artery embolization (BAE). MATERIALS AND METHODS: The medical records of consecutive patients who underwent bronchial artery angiography between August 2013 and December 2019 were retrospectively reviewed. Patients who were diagnosed with BAA during this period were included in this study. The prevalence, patients' characteristics, symptoms, comorbidities, angiographic findings, and long-term prognosis following BAE were investigated. RESULTS: BAA was observed in 20 of 508 patients who underwent bronchial artery angiography (3.9%). The patients' median age was 69 (interquartile range [IQR], 63.5-76.7) years. The main causes of BAA were cryptogenic, bronchiectasis or cystic fibrosis, and pulmonary aspergillosis. The median diameter of ruptured BAAs was significantly smaller than that of unruptured BAAs (5.4 mm [IQR, 4.8-7.3 mm] vs 9.0 mm [IQR, 7.2-13.9 mm], P = .009). All the patients were successfully treated with BAE, without major adverse events. The median follow-up period after BAE was 970 (IQR, 561-1,796) days. The BAA-related survival rate was 100% at 2 and 3 years after BAE, and the overall survival rate after BAE was 89.2% (95% confidence interval [CI] 89.0-89.3) at 2 years and 74.3% (95% CI 74.0-74.5) at 3 years. BAA-related adverse events and mortality did not occur during the follow-up period. CONCLUSIONS: BAA was observed in 3.9 % (20/508) of the patients who underwent bronchial artery angiography. All the patients with BAA were successfully treated with BAE. BAA rupture and consequent mortality did not occur during the follow-up period.

The impact of bronchial artery embolisation on the quality of life of patients with haemoptysis: a prospective observational study.

OBJECTIVES: Patients with haemoptysis often experience daily physical and mental impairment. Bronchial artery embolisation is among the first-line treatment options used worldwide; however, no evidence exists regarding the health-related quality of life (HRQoL) after bronchial artery embolisation. Therefore, this study aimed to evaluate the effects of bronchial artery embolisation on the HRQoL of patients with haemoptysis. METHODS: We prospectively enrolled 61 consecutive patients who visited our hospital from July 2017 to August 2018 and received bronchial artery embolisation for haemoptysis. The primary outcome was the HRQoL evaluated using the Short Form Health Survey, which contains physical and mental components, before and after bronchial artery embolisation. The secondary outcomes were procedural success, complications, and recurrence-free survival rate at 6 months. RESULTS: The mean age of the patients was 69 years (range, 31-87 years). The procedural success rate was 98%. No major complications occurred. The recurrence-free survival rate estimated using the Kaplan-Meier analysis at 6 months after bronchial artery embolisation was 91.8% (95% confidence interval, 91.1-92.5%). Compared with the pre-treatment scores, the physical and mental scores were significantly improved at 6 months after bronchial artery embolisation (p < 0.05). CONCLUSION: Bronchial artery embolisation improved the HRQoL of patients with haemoptysis. KEY POINTS: • Bronchial artery embolisation improved the HRQoL of patients with haemoptysis. • Vessel dilation on computed tomography and systemic artery-pulmonary artery direct shunting on angiography were the most common abnormalities. • The recurrence-free survival rate estimated using the Kaplan-Meier analysis at 6 months after bronchial artery embolisation was 91.8%.

Spinal Cord Infarction after Bronchial Artery Embolization for Hemoptysis: A Nationwide Observational Study in Japan.

Background The most serious complication of bronchial artery embolization (BAE) for hemoptysis is spinal cord infarction. However, because it is rare, previous reports from single institutions have been insufficient to determine the actual prevalence of spinal cord infarction after BAE. Purpose To investigate the actual prevalence of spinal cord infarction as a complication of BAE using a nationally representative inpatient database. Materials and Methods This retrospective study was performed using data from the Japanese Diagnosis Procedure Combination database between July 2010 and March 2018. The authors identified patients who were diagnosed with hemoptysis and underwent BAE during hospitalization. The overall prevalence of spinal cord infarction after BAE was determined. The authors also compared the prevalence of spinal cord infarction using the Fisher exact test according to the embolic agent used for BAE: coils, gelatin sponge (GS) particles, and N-butyl-2-cyanoacrylate (NBCA). Results During the study period, 8563 patients (mean age ± standard deviation, 68 years ± 13; 5103 men) met the inclusion criteria. Among these 8563 patients, 1577 (18%), 6561 (77%), and 425 (5%) underwent BAE with coils, GS particles, and NBCA, respectively. The overall prevalence of spinal cord infarction as a complication of BAE was 0.19% (16 of 8563 patients). The prevalence of spinal cord infarction after BAE with coils, GS particles, and NBCA was 0.06% (one of 1577 patients), 0.18% (12 of 6561 patients), and 0.71% (three of 425 patients), respectively (P = .04). Conclusion With use of a nationwide real-world inpatient database, the results of this study demonstrated that the actual prevalence of spinal cord infarction as a complication of bronchial artery embolization (BAE) for hemoptysis was 0.19%. Patients who underwent BAE with coils had a lower prevalence of spinal cord infarction than patients who underwent BAE with gelatin sponge particles or N-butyl-2-cyanoacrylate. © RSNA, 2021.

Erratic coil migration in the bronchus after bronchial artery embolization.

Herein, we report two cases of erratic coil migration from the bronchial artery to the bronchus after bronchial artery embolization (BAE). Neither patient exhibited haemoptysis recurrence, but chest radiographs revealed that part of the coil had disappeared. In Case 1, the patient coughed up the coil 4.5 years after BAE. We performed repeat BAE to minimize the possibility of haemoptysis considering bronchoscopic and angiographic findings. In Case 2, the patient had severe dry cough 2 years after BAE. Chest radiography showed migrated coils in the trachea; bronchoscopy revealed a migrated fragment of the coil protruding from the elevated mucosa. We used a loop cutter to split the coil and then removed it using forceps. Coil migration to the bronchus is an infrequent late-stage complication of super-selective bronchial artery coil embolization, and only one other case has been reported. Accordingly, we propose treatment strategies and speculate on the mechanism of fistula formation.

Mechanisms of recurrent haemoptysis after super-selective bronchial artery coil embolisation: a single-centre retrospective observational study.

OBJECTIVES: In recognition of the significant impairment caused by haemoptysis on a patient's quality of life, bronchial artery embolisation has been introduced worldwide as one of the first-line treatment options. Since little evidence is available on the mechanisms of recurrent haemoptysis after super-selective bronchial artery coil embolisation (ssBACE), the purpose of the present study is to evaluate these. METHODS: We retrospectively evaluated the mechanisms of recurrent haemoptysis using both enhanced computed tomography and cineangiography following ssBACE by reviewing 299 haemoptysis-related arteries (HRAs) in 57 consecutive patients who underwent 2nd series ssBACE for the management of recurrent haemoptysis between April 2010 and December 2015. RESULTS: Median age of patients was 69 (interquartile range 64-74) years, and 43.9% were men. This study revealed that (1) recanalisation was the most common mechanism (45.2%) followed by development of new HRA (38.5%), bridging collaterals (14.7%) and conventional collaterals (1.7%); (2) these trends could be modified in several situations such as with antiplatelet or anticoagulant medications; (3) relatively large-diameter HRAs were more likely to recanalise compared with small-diameter HRAs and (4) recurrent haemoptysis could be managed by 2nd series ssBACE with a procedural success rate of 97.7% without any major complications. CONCLUSIONS: Recanalisation was the most common mechanism of recurrent haemoptysis after ssBACE. Our results provide interventionists with indispensable insights. KEY POINTS: • Recanalisation was the most common mechanism of recurrent haemoptysis after super-selective bronchial artery coil embolisation, followed by development of new haemoptysis-related arteries • These trends could be modified in several situations such as with antiplatelet or anticoagulant medications • Recurrent haemoptysis could be managed by 2nd series super-selective bronchial artery coil embolisation with a procedural success rate of 97.7% without any major complications.

Phase1 study of cisplatin plus pemetrexed with erlotinib and bevacizumab for chemotherapy-naïve advanced non-squamous non-small cell lung cancer with EGFR mutations.

Background Cisplatin and pemetrexed are very effective against advanced non-squamous non-small cell lung cancer (NSCLC) without EGFR mutations. Erlotinib plus bevacizumab are highly effective against advanced NSCLCs with activating EGFR mutations. We performed this phase I 'Quartet Trial' to determine the safety and efficacy of all 4 agents as a first-line treatment for non-squamous NSCLC patients harboring activating EGFR mutations. Patients and Methods Patients received escalating quartet-agent doses every 3 weeks for 4 cycles. We examined the dose-limiting toxicity (DLT) to determine the maximum tolerated dose (MTD) and recommended dose (RD). Results Ten patients (3 men and 7 women) with a median age of 69 years were enrolled. Four and 6 patients had exon 19 and 21 mutations, respectively; 8 received maintenance therapy without unexpected or cumulative toxicities. One of 6 patients experienced grade 3 vagal reflex at 60 mg/m2 cisplatin plus 500 mg/m2 pemetrexed with 150 mg erlotinib and 15 mg/kg bevacizumab, which was designated the RD. Four patients experienced no DLT with 75 mg/m2 cisplatin plus 500 mg/m2 pemetrexed with 150 mg erlotinib and 15 mg/kg bevacizumab (designated the MTD); however, 3 underwent dose reduction due to severe toxicities (grade 3 gastrointestinal hemorrhage, skin rash, nausea, and febrile neutropenia) during induction chemotherapy. The most frequent DLT-phase adverse events were nausea, anorexia, and fatigue. The overall response rate was 100%. Furthermore, the progression-free and overall survival rates were 17.9 and 32.0 months, respectively. Conclusions This quartet chemotherapy regimen was tolerable and effective in our patient population (UMIN000012536).

Efficacy of nanoparticle albumin-bound paclitaxel regimens for relapsed small cell lung cancer: A retrospective analysis.

Although small cell lung cancer (SCLC) is initially sensitive to chemotherapy, it recurs in most cases. Standard regimens for salvage chemotherapy have not been established, and the prognosis of relapsed SCLC remains poor. In the present study, we investigated the clinical efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) regimens for the treatment of relapsed SCLC.In this retrospective multicenter analysis, 14 patients (3 women and 11 men; median age 71 years) with relapsed SCLC received nab-paclitaxel alone or in combination with carboplatin between February 2013 and July 2014. The safety and efficacy of the regimens were evaluated.The response rates, disease control rates, and median overall survival for the total patient population were 36%, 64%, and 7.8 months, respectively. Response rates, disease control rates, and the median overall survival were 11%, 44%, and 4 months, respectively, in the monotherapy group; and 80%, 100%, and 10.6 months, respectively, in the combination therapy group. The most common adverse events were hematological toxicities such as neutropenia and anemia. Severe neutropenia appeared in some patients, although it was resolved by treatment in all. The most common nonhematological toxicity was anorexia (64%), followed by neurotoxicity and constipation. All nonhematological toxicities were mild and manageable.Our results suggest that chemotherapy with nab-paclitaxel regimens for relapsed SCLC exhibits moderate clinical efficacy and is well-tolerated. Further clinical trials in relapsed SCLC patients are warranted.

Combination of virtual bronchoscopic navigation, endobronchial ultrasound, and rapid on-site evaluation for diagnosing small peripheral pulmonary lesions: a prospective phase II study.

BACKGROUND: The diagnostic yield of peripheral pulmonary lesions (PPLs) by flexible bronchoscopy (FB) is still insufficient. To improve the diagnostic yield of bronchoscopy, several techniques such as endobronchial ultrasound (EBUS), virtual bronchoscopic navigation (VBN), and rapid on-site evaluation (ROSE) have been examined. The primary purpose of the present study was to evaluate the usefulness of combining EBUS, VBN, and ROSE for diagnosing small PPLs. METHODS: Patients with PPLs 30 mm or less on chest computed tomography (CT) were prospectively enrolled. We determined the responsible bronchus for the target lesions using VBN before bronchoscopy was performed. EBUS and ROSE were performed during the examination to determine whether the bronchus and specimen were adequate. On the basis of previous studies, we assumed that the diagnostic yield of 85% among eligible patients would indicate potential usefulness, whereas, the diagnostic yield of 75% would indicate the lower limit of interest. The required number of patients was estimated as 45 for a one-sided α value of 0.2 and a ß value of 0.8. The primary study endpoint was the diagnostic yield. RESULTS: Between June 2014 and July 2015, we enrolled 50 patients in the present study, and we excluded 5 patients. The total diagnostic yield of 45 PPLs was 77.7%. In cases of lung cancer, the diagnostic yield was 84.2%. The sensitivity, specificity, positive predictive value, and negative predictive value of ROSE were 90.6%, 92.3%, 96.7%, and 80.0%, respectively. The diagnostic yield of PPLs from 20 to 30 mm was 87.5%, and the diagnostic yield of PPLs less than 20 mm was 66.7%. PPLs for which the probe was located within the lesion had the highest diagnostic yield. CONCLUSIONS: We could not demonstrate usefulness for diagnosing small PPLs by combining EBUS, VBN, and ROSE. However, combining these techniques may be useful for diagnosing lung cancer.

Cerebrospinal Fluid Penetration Rate and Efficacy of Afatinib in Patients with EGFR Mutation-positive Non-small Cell Lung Cancer with Leptomeningeal Carcinomatosis: A Multicenter Prospective Study.

BACKGROUND: Afatinib is an effective first-line treatment for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC). However, few reports have addressed the influence of cerebrospinal fluid (CSF) penetration rate on the efficacy of afatinib in patients with central nervous system metastases. Therefore, we conducted a prospective multicenter trial to evaluate the CSF penetration rate and efficacy of afatinib in patients with EGFR mutation-positive NSCLC with leptomeningeal carcinomatosis. PATIENTS AND METHODS: Eleven patients with histologically-proven EGFR mutation-positive NSCLC with leptomeningeal carcinomatosis were enrolled in the study between April 2014 and November 2015. They were treated with afatinib (40 mg/day), and blood and CSF levels of afatinib were analyzed on day 8. The primary endpoint was CSF penetration rate. Secondary endpoints included the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: The median age of patients was 66 years. Five patients harbored an exon 19 deletion, three harbored a p.L858R point mutation, and three harbored an uncommon exon 18 mutation. The levels of afatinib in blood and CSF (mean±SD) were 233.26±195.40 nM and 3.16±1.95 nM, respectively. The CSF penetration rate was 2.45±2.91%. The ORR was 27.3% (three out of 11 patients), and two out of these three responders had uncommon EGFR mutations. The median PFS and OS were 2.0 and 3.8 months, respectively. CONCLUSION: The median CSF penetration rate of afatinib was higher than previously reported. Afatinib was effective against leptomeningeal carcinomatosis particularly in patients with NSCLC harboring uncommon EGFR mutations. The criteria for selecting a specific EGFR tyrosine kinase inhibitor for therapy of NSCLC should include its ability to penetrate CSF and its efficacy against specific mutation types.

Duration of Twice-Daily Thoracic Radiotherapy and Time From the Start of Any Treatment to the End of Chest Irradiation as Significant Predictors of Outcomes in Limited-Disease Small-Cell Lung Cancer.

BACKGROUND: The hypothesis of this retrospective study was that the duration of twice-daily (BID) thoracic radiotherapy (TRT) and time from the start of any treatment to the end of chest irradiation (SER) would predict outcomes in limited-disease small-cell lung cancer. MATERIALS AND METHODS: All 81 patients received 45 Gy in 30 fractions BID with a ≥ 6-hour interval and concurrent chemotherapy of platinum and etoposide. RESULTS: The median radiotherapy duration was 25 days (range, 21-38 days). The 5-year overall survival rates were 26.2% (95% confidence interval [CI], 14.3%-38.0%), and the median survival time was 30 months (95% CI, 15.5-44.5 months). Using multivariate regression analysis, the significant predictors of survival were the sum of the diameters of the primary tumor and metastatic lymph nodes, male gender, age ≥ 60 years, and the duration of BID-TRT (hazard ratio [HR], 1.15; 95% CI, 1.06-1.25; HR, 2.38; 95% CI, 1.13-5.02; HR, 2.38; 95% CI, 1.10-5.17; and HR, 1.08; 95% CI, 1.01-1.15, respectively). A total of 70 of 81 patients (86%) received radiotherapy during the first chemotherapy cycle. The median SER was 29 days (range, 21-109 days). The 5-year local control rate was 48.7% (95% CI, 33.9%-63.6%). The significant predictors of local control were the sum of the diameters of the primary tumor and metastatic lymph nodes, age ≥ 60 years, and SER (HR, 1.18; 95% CI, 1.06-1.31; HR, 4.18; 95% CI, 1.23-14.24; and HR, 1.02; 95% CI, 1-1.04, respectively). CONCLUSIONS: The duration of BID-TRT and SER were identified as one of the significant predictors of survival and local control in limited-disease small-cell lung cancer treated with concurrent chemoradiotherapy at 45 Gy in 30 fractions, respectively.

Impact of metastatic status on the prognosis of EGFR mutation-positive non-small cell lung cancer patients treated with first-generation EGFR-tyrosine kinase inhibitors.

The aim of the present study was to analyze the impact of metastatic status on the prognosis of epithelial growth factor receptor (EGFR) mutation-positive patients with non-small cell lung cancer (NSCLC) treated with first-generation EGFR-tyrosine kinase inhibitors (TKIs). A total of 178 EGFR mutation-positive patients with stage IIIB-IV and relapsed NSCLC who were treated with gefitinib or erlotinib as the first-line treatment were enrolled in the present study. Metastatic status, progression-free survival (PFS), overall survival (OS) and treatment-response rates were investigated. The association between the number of metastatic organ sites and patient prognosis was also investigated. The median age at the time of treatment was 72 (range, 39-91) years. A total of 168 patients had adenocarcinoma; 156 were treated with gefitinib. Patients with brain metastases, bone metastases, liver metastases and pleural effusion exhibited a significantly reduced PFS and OS time in the univariate analysis, compared with patients without each of these symptoms. In the multivariate analysis, bone metastasis was associated with a poorer PFS (hazard ratio, 2.11; 95% confidence interval, 1.44-3.09; P<0.001) and brain metastasis was associated with a poorer OS (hazard ratio, 2.41; 95% confidence interval, 1.46-3.95; P<0.001). No association was observed between metastatic status and treatment response rates. Higher numbers of different sites of organ metastases were associated with significantly poorer PFS and OS. Bone, brain metastasis and higher numbers of metastatic organ sites are negative prognostic factors for EGFR mutation-positive NSCLC patients treated with first-generation EGFR-TKIs.

Vascular Endothelial Growth Factor in Plasma and Pleural Effusion Is a Biomarker for Outcome After Bevacizumab plus Carboplatin-Paclitaxel Treatment for Non-small Cell Lung Cancer with Malignant Pleural Effusion.

AIM: Malignant effusion is associated with high serum and plasma levels of vascular endothelial growth factor (VEGF). There are no biomarkers of outcome for bevacizumab treatment in patients with malignant pleural effusion (MPE). We previously reported that carboplatin-paclitaxel plus bevacizumab was effective for patients with advanced non-squamous non-small cell lung cancer (NSCLC) and MPE, although we did not evaluate the relationship between treatment outcomes and plasma or pleural effusion levels of VEGF. Therefore, this study evaluated whether plasma or pleural effusion VEGF might predict bevacizumab treatment outcome. PATIENTS AND METHODS: We enrolled 23 patients with NSCLC and MPE between September 2010 and June 2012. Plasma VEGF levels were measured in 19 patients and pleural VEGF levels were measured in 22 patients. RESULTS: Compared to patients with a low plasma VEGF level, patients with a high level exhibited significantly shorter overall survival (OS: 13.8 vs. 6.5 months, p=0.04), progression-free survival (PFS: 8.7 vs. 4.8 months, p<0.01), and period to re-accumulation of MPE (pPFS: 9.7 vs. 6.2 months, p=0.02). Compared to patients with a low VEGF level in pleural effusion, patients with a high VEGF level exhibited significantly shorter OS (19.6 vs. 6.9 months, p<0.01) and pPFS (9.6 vs. 6.7 months, p=0.04), although there was no significant difference in their PFS (6.6 vs. 5.9 months, p=0.18). CONCLUSION: VEGF levels in the plasma and pleural effusion may predict the outcome of bevacizumab treatment in patients with NSCLC and MPE.

Life-threatening and Rapidly Growing Teratoma in the Anterior Mediastinum.

This report describes the case of a 23-year-old man with a mediastinal teratoma. Five months before admission, a chest radiograph during a routine health checkup was normal. Four months before admission, the patient developed sudden onset of mild right-sided chest pain. He gradually developed dyspnea and was admitted to our hospital. Computed tomography revealed a giant tumor that was markedly compressing the right atrium. Urgent surgery was performed, and a ruptured, benign mature teratoma was diagnosed. Mature mediastinal teratomas are benign tumors, but they can rupture and have the potential to grow rapidly, potentially leading to life-threatening complications.

Molecular analysis of human papillomavirus in never-smokers with non-small cell lung cancer.

The causes of lung cancer in never-smokers remain unclear. The potential contribution of human papillomavirus (HPV) to the carcinogenesis of non-small cell lung cancer (NSCLC) has been reported. In 2008, a prospective registry of never-smokers with NSCLC was established at the Kinki-Chuo Chest Medical Center, Sakai, Osaka, Japan. Never-smokers with NSCLC were consecutively enrolled onto the registry. Of these patients, 114 with large tumor specimens, the majority of which were surgical tissues, were selected. In total, 23 of the most clinically relevant HPV types were assayed using polymerase chain reaction amplification of the viral genome. Following exclusion of samples with suboptimal quality, DNA was extracted from 96 formalin-fixed paraffin-embedded samples. These 96 cases consisted of 82 females (85.4%) and 14 males (14.6%), with a median age of 67 years (range, 29-83). Almost all cases (93.8%) were of the adenocarcinoma histological subtype. Despite confirmation of the quality and amount of DNA, HPV type 6 was detected in only one case (1.1%). Furthermore, no other samples examined were positive for any other HPV types. The results therefore suggest that HPV does not play a major role as the driving oncogenic event in never-smokers with NSCLC.

Phase II trial of carboplatin, S-1, and gefitinib as first-line triplet chemotherapy for advanced non-small cell lung cancer patients with activating epidermal growth factor receptor mutations.

Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is an effective treatment for advanced non-small cell lung cancer (NSCLC) in patients with activating EGFR mutations. However, there have been little evidence-based studies of gefitinib in combination with platinum-doublet therapy in these patients. We performed a phase II trial to determine the efficacy and safety of triplet chemotherapy with gefitinib, carboplatin, and S-1 as a first-line treatment. This was a multicentre, single-arm, phase II trial of carboplatin, S-1, and gefitinib in advanced NSCLC patients with activating EGFR mutations. Patients received four courses of these drugs in 3-4 week cycles. In each cycle, carboplatin (area under curve = 5) was administered on day 1, S-1 (80 mg/m(2)) on days 1-14, and gefitinib (250 mg) every day. Subsequently, the same regimen without carboplatin was administered until disease progression or unacceptable toxicity occurred. The 1-year progression-free survival (PFS) was the primary endpoint, while response rate (RR), PFS, overall survival (OS), and safety were secondary endpoints. Thirty-five patients were enrolled into this study. The 1-year PFS was 74.3% and the overall RR was 85.7%. The median PFS for all patients was 17.6 months (95% confidence interval 15.5-∞), but the median OS was not reached, because 28 patients were still alive after a median follow-up time of 21.4 months. Haematological adverse events (grade 3 or higher) included neutropaenia (17.1%), thrombocytopenia (14.3%), and anaemia (5.7%), while non-haematological adverse events (grade 3 or higher) included elevated aminotransferase (20.0%), diarrhoea (14.3%), and febrile neutropaenia (2.9%). No interstitial lung disease or treatment-related deaths occurred. Combination chemotherapy with carboplatin, S-1, and gefitinib is efficacious and well tolerated as a first-line treatment in advanced NSCLC patients with activating EGFR mutations.

Prospective phase II study of cisplatin plus pemetrexed with maintenance of pemetrexed for advanced non-squamous cell non-small cell lung cancer in Japan.

BACKGROUND: A previous study showed a survival benefit with maintenance therapy with pemetrexed in patients with advanced non-small cell lung cancer (NSCLC). However, it remains unclear whether continuation maintenance therapy with pemetrexed is beneficial in Japanese patients. Here, we present our phase II study that assessed the efficacy and safety of cisplatin plus pemetrexed as induction chemotherapy, followed by maintenance therapy with pemetrexed in advanced NSCLC patients in Japan. METHODS: Chemotherapy-naïve patients received 500 mg/m(2) pemetrexed and 75 mg/m(2) cisplatin on day one every three weeks for four cycles. In patients who responded to therapy or achieved stable disease, pemetrexed was continued until disease progression. The primary endpoint of this study was the progression-free survival rate at six months (PFS-6). RESULTS: Of the 35 patients initially enrolled in the study, 18 (51%) received maintenance chemotherapy with pemetrexed. The median PFS was 6.7 months, and the PFS-6 was 60% (95% confidence interval [CI], 42-76%). Median overall survival (OS) was 15.5 months (95% CI, 8.3-22.7 months). The median PFS and OS in patients who received maintenance chemotherapy with pemetrexed were 9.5 months and 25.3 months, respectively. The most frequently noted severe toxicity during induction chemotherapy was neutropenia, which occurred in seven patients. Two patients discontinued maintenance therapy owing to prolonged grade 2 edema in one patient and grade 3 neutropenia in another. CONCLUSION: Continuation maintenance chemotherapy with pemetrexed is associated with a survival benefit in patients who have completed induction chemotherapy for non-squamous NSCLC.

Continued treatment with gefitinib beyond progressive disease benefits patients with activating EGFR mutations.

BACKGROUND: Gefitinib is an effective treatment for patients with non-small cell lung cancer who harbor activating epidermal growth factor receptor (EGFR) mutations. However, no optimal strategy has been established for these patients after gefitinib fails. The aim of this retrospective study was to assess the survival benefit of continued gefitinib treatment in these cases. PATIENTS AND METHODS: We analyzed gefitinib responders with activating EGFR mutations who developed progressive disease (PD) during the course of therapy. Prognostic variables were analyzed using a Cox proportional-hazards model. RESULTS: A total of 134 patients were retrospectively reviewed. Exon-19 deletion mutations and L858R point mutations were detected in 71 and 63 patients, respectively. Median survival time after PD with gefitinib was 14.3 months (95% confidence interval: 11.7-16.9). The median duration of continued gefitinib therapy beyond PD was 3.2 months. Statistical analysis showed that good performance status (0-1) (hazard ratio [HR]: 0.6), progression of a previously evaluated lesion (HR: 0.6), and at least 3 months of continued treatment (HR: 0.4) were independent prognostic factors. CONCLUSION: Continuation of gefitinib beyond PD is an effective optional treatment in EGFR-mutated patients.