Lung Cancer: Targets and Therapy最新文献

{"title":"Amifostine- and chemoradiotherapy-related esophagitis in small cell lung cancer: a single institutional series and literature update.","authors":"Ariel E Pollock,&nbsp;Lowell Shinn,&nbsp;Richard Anderson,&nbsp;Sarah Butler,&nbsp;Jondavid Pollock","doi":"10.2147/LCTT.S155315","DOIUrl":"https://doi.org/10.2147/LCTT.S155315","url":null,"abstract":"<p><strong>Objectives: </strong>Concurrent chemoradiotherapy is considered a standard option for patients with stage 3 small cell lung carcinoma. A 25% risk of acute esophagitis is experienced by patients as a result of the volume of esophagus encompassed within a conformal radiotherapy technique. We reviewed our institutional experience administering the radioprotectant amifostine prior to daily radiotherapy to determine its effects on the onset of esophagitis.</p><p><strong>Materials and methods: </strong>From 2005 to 2016, 49 patients diagnosed with stage 3 small cell lung carcinoma received concurrent chemoradiotherapy. Chemotherapy (CT) consisted of cisplatin and etoposide with radiotherapy (RT) encompassing CT-identified gross tumor volume. In 32 patients (group 1), amifostine was delivered (500 mg subcutaneously divided in two injections) prior to the second daily RT fraction. The remaining 17 patients (group 2) did not receive amifostine due to choice or drug intolerance.</p><p><strong>Results: </strong>Metrics of esophagitis included weight loss and opiate requirement during treatment. About 31% of group 1 required opiates at a median RT dose of 3300 cGy, and 41% of group 2 required opiates at a median dose of 2250 cGy. The dose of radiotherapy delivered to 50% of the esophageal volume for group 1 was significantly greater than that in group 2 (3000 cGy vs 576 cGy).</p><p><strong>Conclusion: </strong>In this modern retrospective series of thoracic chemoradiotherapy in the treatment of stage 3 small cell lung cancer, amifostine that was delivered subcutaneously postponed the onset of esophagitis.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2018-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S155315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36511861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypersensitivity in ALK-positive lung cancers exposed to ALK inhibitors: a case of successful switch to an alternative ALK inhibitor and systematic review of the literature.","authors":"Lei Deng,&nbsp;Janaki Sharma,&nbsp;Elizabeth Ravera,&nbsp;Balazs Halmos,&nbsp;Haiying Cheng","doi":"10.2147/LCTT.S173948","DOIUrl":"https://doi.org/10.2147/LCTT.S173948","url":null,"abstract":"<p><p>Alectinib can cause rare, but severe hypersensitivity. The cross-reactivity between different ALK inhibitors is unknown and desensitization is the only reported management. We hereby report the first case of severe delayed hypersensitivity developed in a lung cancer patient treated by alectinib, who was successfully managed by switching to brigatinib, another ALK inhibitor. The patient achieved excellent anti-tumor response to brigatinib. Our case provides an alternative and safe strategy in patients with alectinib-related hypersensitivity.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2018-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S173948","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36504509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1-, 3-, and 5-year survival among early-stage lung cancer patients treated with lobectomy vs SBRT.","authors":"Denise Albano,&nbsp;Thomas Bilfinger,&nbsp;Barbara Nemesure","doi":"10.2147/LCTT.S166320","DOIUrl":"https://doi.org/10.2147/LCTT.S166320","url":null,"abstract":"<p><strong>Background: </strong>Lobectomy has traditionally been recommended for fit patients diagnosed with early-stage non-small-cell lung cancer (NSCLC). Recently, however, stereotactic body radiotherapy (SBRT) has been introduced as an alternative treatment option. The purpose of this investigation is to compare survival outcomes for individuals with stage I/II NSCLC treated with lobectomy vs SBRT.</p><p><strong>Methods: </strong>This retrospective study included 191 patients (100 surgery, 91 SBRT) identified through the Lung Cancer Evaluation Center, Stony Brook, NY, between 2008 and 2012. Survival and recurrence rates were compared using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models to adjust for possible confounders. A subset of cases was propensity-matched to address potential differences in health status between groups.</p><p><strong>Results: </strong>1-, 3-, and 5-year survival outcomes were significantly better among patients undergoing lobectomy vs SBRT. Survival rates at 3 years were 92.8% and 59.0% (<i>p</i><0.001) in the 2 groups, respectively. Propensity-matched analyses indicated similar findings. Recurrence rates were likewise lower among patients undergoing surgery (7.1% vs 21.0%, <i>p</i><0.01 at 3 years); however, statistical significance was not maintained in the propensity-matched analysis.</p><p><strong>Conclusion: </strong>These findings add to a growing evidence base supporting the use of lobectomy vs SBRT in the treatment of lung cancer among healthy, early-stage NSCLC patients.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2018-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S166320","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36476587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive review of fetal adenocarcinoma of the lung.","authors":"Luisa María Ricaurte,&nbsp;Oscar Arrieta,&nbsp;Zyanya Lucia Zatarain-Barrón,&nbsp;Andrés F Cardona","doi":"10.2147/LCTT.S137410","DOIUrl":"10.2147/LCTT.S137410","url":null,"abstract":"<p><p>Fetal adenocarcinoma of the lung (FLAC) is a rare tumor. It accounts for ~0.1%-0.5% of all pulmonary neoplasms. Due to its rarity, much of the world literature regarding FLAC comes from case reports and case series. FLAC is an adenocarcinoma resembling developing fetal lung in its pseudoglandular stage (8-16 weeks of gestation). It is distinguishable from pulmonary blastoma (PB) because it lacks the mesenchymal component which is a hallmark finding in PB. Due to differences in histopathology and clinical course, FLAC has been further categorized into low-grade (L-FLAC) and high-grade (H-FLAC) forms. L-FLAC displays low nuclear atypia and prominent morule formation and has a pure pattern. H-FLAC typically presents with at least 50% fetal morphology, and is often associated with other conventional types of lung adenocarcinoma. FLAC expresses neuroendocrine markers and thyroid transcription factor 1 in most cases. L-FLAC has an aberrant nuclear/cytoplasmic expression of β-catenin and presents mutations in this gene. H-FLAC overexpresses p53. These tumors have a very low frequency of mutations in <i>KRAS</i> and <i>EGFR</i>; it is thought that they are different from a molecular point of view to conventional lung adenocarcinomas. Approximately 25%-40% of patients are asymptomatic at presentation; most of them are incidental findings on chest radiographs. H-FLAC is more common in elderly male patients, with a heavy smoking history. L-FLAC tends to occur in young females. Patients with L-FLAC are usually diagnosed with stage I-II disease, while patients with H-FLAC usually present with a more advanced-stage disease. Poor prognostic factors for FLAC are thoracic lymphadenopathy, metastases at diagnosis, and tumor recurrence; however, the 10-year survival for FLAC is estimated at 75%.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2018-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S137410","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36476668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prophylactic cranial irradiation in small-cell lung cancer: update on patient selection, efficacy and outcomes.","authors":"Farkhad Manapov,&nbsp;Lukas Käsmann,&nbsp;Olarn Roengvoraphoj,&nbsp;Maurice Dantes,&nbsp;Nina-Sophie Schmidt-Hegemann,&nbsp;Claus Belka,&nbsp;Chukwuka Eze","doi":"10.2147/LCTT.S137577","DOIUrl":"https://doi.org/10.2147/LCTT.S137577","url":null,"abstract":"<p><p>Over 10% of small-cell lung cancer (SCLC) patients have brain metastases (BM) at initial diagnosis; more than 50% will develop BM within 2 years. BM are detected in up to 80% of all patients at autopsy. After primary treatment, prophylactic cranial irradiation (PCI) has been established as standard of care in SCLC patients responding to initial therapy. Based on level I evidence, PCI significantly decreases the risk of intracranial relapse and shows a modest survival benefit after 3 years. However, the role of PCI in defined patient subgroups such as resected SCLC, elderly and extensive stage patients with access to magnetic resonance imaging surveillance and stereotactic radiotherapy is yet to be fully clarified. Furthermore, strategies to effective prevention of neurocognitive decline after PCI remain unclear. All these factors significantly impact treatment decision making and should be evaluated in prospective settings. New concepts such as hippocampal avoidance and drug neuroprotection prevent chronic neurocognitive effects reducing treatment-related side effects of PCI. The aim of this review is to present a summary and update of the latest evidence for patient selection, efficacy and outcome of PCI.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2018-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S137577","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36631944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to rapamycin analogs but not PD-1 inhibitors in PTEN-mutated metastatic non-small-cell lung cancer with high tumor mutational burden.","authors":"Ankur R Parikh,&nbsp;Siraj M Ali,&nbsp;Alexa B Schrock,&nbsp;Lee A Albacker,&nbsp;Vincent A Miller,&nbsp;Phil J Stephens,&nbsp;Pamela Crilley,&nbsp;Maurie Markman","doi":"10.2147/LCTT.S161738","DOIUrl":"https://doi.org/10.2147/LCTT.S161738","url":null,"abstract":"<p><p>In non-small-cell lung cancer (NSCLC) refractory to standard therapy and which lacks well-known oncogenic drivers, genomic profiling can still identify genomic alterations that may suggest potential sensitivity to targeted therapy. PTEN mutation in NSCLC may be sensitizing to analogs of rapamycin such as everolimus or temsirolimus, but more investigation is needed. We report the case of a patient with metastatic NSCLC harboring a PTEN mutation as well as high tumor mutational burden and PD-L1 positivity with a durable response to temsirolimus, but refractory to a checkpoint inhibitor. Even in the event of failure of treatment with checkpoint inhibitors in the background of a case with a higher tumor mutational burden and PD-L1 positivity, targeting specific genomic alterations may still result in patient benefit.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2018-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S161738","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36174135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role and inhibition of GLI1 protein in cancer.","authors":"Eloise Mastrangelo,&nbsp;Mario Milani","doi":"10.2147/LCTT.S124483","DOIUrl":"https://doi.org/10.2147/LCTT.S124483","url":null,"abstract":"<p><p>GLI1 is a transcriptional regulator involved in the development of different types of cancer. GLI1 transcriptional activity is regulated within the Hedgehog pathway (canonical activity), but can also be controlled independently (non-canonical activity) in the context of other signaling pathways. Experimental evidences show GLI1 involvement in both small- and non-small-cell lung cancers. Direct inhibition of the protein, in combination with other chemotherapeutic agents, represents a promising strategy for the treatment of different malignancies.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2018-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S124483","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35985736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncommon <i>EGFR</i> mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients.","authors":"Elisna Syahruddin,&nbsp;Laksmi Wulandari,&nbsp;Nunuk Sri Muktiati,&nbsp;Ana Rima,&nbsp;Noni Soeroso,&nbsp;Sabrina Ermayanti,&nbsp;Michael Levi,&nbsp;Heriawaty Hidajat,&nbsp;Grace Widjajahakim,&nbsp;Ahmad Rusdan Handoyo Utomo","doi":"10.2147/LCTT.S154116","DOIUrl":"https://doi.org/10.2147/LCTT.S154116","url":null,"abstract":"<p><strong>Purpose: </strong>We aimed to evaluate the distribution of individual epidermal growth factor receptor (<i>EGFR</i>) mutation subtypes found in routine cytological specimens.</p><p><strong>Patients and methods: </strong>A retrospective audit was performed on <i>EGFR</i> testing results of 1,874 consecutive cytological samples of newly diagnosed or treatment-naïve Indonesian lung cancer patients (years 2015-2016). Testing was performed by ISO15189 accredited central laboratory.</p><p><strong>Results: </strong>Overall test failure rate was 5.1%, with the highest failure (7.1%) observed in pleural effusion and lowest (1.6%) in needle aspiration samples. <i>EGFR</i> mutation frequency was 44.4%. Tyrosine kinase inhibitor (TKI)-sensitive common <i>EGFR</i> mutations (ins/dels exon 19, L858R) and uncommon mutations (G719X, T790M, L861Q) contributed 57.1% and 29%, respectively. Approximately 13.9% of mutation-positive patients carried a mixture of common and uncommon mutations. Women had higher <i>EGFR</i> mutation rate (52.9%) vs men (39.1%; <i>p</i><0.05). In contrast, uncommon mutations conferring either TKI responsive (G719X, L861Q) or TKI resistance (T790M, exon 20 insertions) were consistently more frequent in men than in women (67.3% vs 32.7% or 69.4% vs 30.6%; <i>p</i><0.05). Up to 10% <i>EGFR</i> mutation-positive patients had baseline single mutation T790M, exon 20 insertion, or in coexistence with TKI-sensitive mutations. Up to 9% patients had complex or multiple <i>EGFR</i> mutations, whereby 48.7% patients harbored TKI-resistant mutations. One patient presented third-generation TKI-resistant mutation L792F simultaneously with T790M.</p><p><strong>Conclusion: </strong>Routine diagnostic cytological techniques yielded similar success rate to detect <i>EGFR</i> mutations. Uncommon <i>EGFR</i> mutations were frequent events in Indonesian lung cancer patients.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2018-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S154116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35976228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stereotactic body radiation therapy (SBRT) in the management of non-small-cell lung cancer: Clinical impact and patient perspectives.","authors":"Elysia K Donovan,&nbsp;Anand Swaminath","doi":"10.2147/LCTT.S129833","DOIUrl":"https://doi.org/10.2147/LCTT.S129833","url":null,"abstract":"<p><p>Stereotactic body radiation therapy (SBRT) has emerged as a new technology in radiotherapy delivery, allowing for potentially curative treatment in many patients previously felt not to be candidates for radical surgical resection of stage I non-small-cell lung cancer (NSCLC). Several studies have demonstrated very high local control rates using SBRT, and more recent data have suggested overall survival may approach that of surgery in operable patients. However, SBRT is not without unique toxicities, and the balance of toxicity, and effect on patient-reported quality of life need to be considered with respect to oncologic outcomes. We therefore aim to review SBRT in the context of important patient-related factors, including quality of life in several domains (and in comparison to other therapies such as conventional radiation, surgery, or no treatment). We will also describe scenarios in which SBRT may be reasonably offered (i.e. elderly patients and those with severe COPD), and where it may need to be approached with some caution due to increased risks of toxicity (i.e. tumor location, patients with interstitial lung disease). In total, we hope to characterize the physical, emotional, and functional consequences of SBRT, in relation to other management strategies, in order to aid the clinician in deciding whether SBRT is the optimal treatment choice for each patient with early stage NSCLC.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2018-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S129833","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35956431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non-small cell lung cancer.","authors":"Vidya H Veldore,&nbsp;Anuradha Choughule,&nbsp;Tejaswi Routhu,&nbsp;Nitin Mandloi,&nbsp;Vanita Noronha,&nbsp;Amit Joshi,&nbsp;Amit Dutt,&nbsp;Ravi Gupta,&nbsp;Ramprasad Vedam,&nbsp;Kumar Prabhash","doi":"10.2147/LCTT.S147841","DOIUrl":"https://doi.org/10.2147/LCTT.S147841","url":null,"abstract":"<p><p>Plasma cell-free tumor DNA, or circulating tumor DNA (ctDNA), from liquid biopsy is a potential source of tumor genetic material, in the absence of tissue biopsy, for <i>EGFR</i> testing. Our validation study reiterates the clinical utility of ctDNA next generation sequencing (NGS) for EGFR mutation testing in non-small cell lung cancer (NSCLC). A total of 163 NSCLC cases were included in the validation, of which 132 patients had paired tissue biopsy and ctDNA. We chose to validate ctDNA using deep sequencing with custom designed bioinformatics methods that could detect somatic mutations at allele frequencies as low as 0.01%. Benchmarking allele specific real time PCR as one of the standard methods for tissue-based <i>EGFR</i> mutation testing, the ctDNA NGS test was validated on all the plasma derived cell-free DNA samples. We observed a high concordance (96.96%) between tissue biopsy and ctDNA for oncogenic driver mutations in Exon 19 and Exon 21 of the <i>EGFR</i> gene. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the assay were 91.1%, 100% 100%, 95.6%, and 97%, respectively. A false negative rate of 3% was observed. A subset of mutations was also verified on droplet digital PCR. Sixteen percent EGFR mutation positivity was observed in patients where only liquid biopsy was available, thus creating options for targeted therapy. This is the first and largest study from India, demonstrating successful validation of circulating cell-free DNA as a clinically useful material for molecular testing in NSCLC.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2018-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S147841","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35776290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}