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Lung Cancer: Targets and Therapy

Giuseppe Bronte, Paola Ulivi, Alberto Verlicchi, Paola Cravero, Angelo Delmonte, Lucio Crinò
Non-small-cell lung cancer (NSCLC) patients with mutated or rearranged oncogene drivers can be treated with upfront selective inhibitors achieving higher response rates and longer survival than chemotherapy. The RET gene can undergo chromosomal rearrangements in 1%-2% of all NSCLC patients, involving various upstream fusion partners such as KIF5B, CCDC6, NCOA4, and TRIM33. Many multikinase inhibitors are active against rearranged RET. Cabozantinib, vandetanib, sunitinib, lenvatinib, and nintedanib achieved tumor responses in about 30% of these patients in retrospective studies...
2019: Lung Cancer: Targets and Therapy
Viola W Zhu, Alexa B Schrock, Siraj M Ali, Sai-Hong Ignatius Ou
Exploring resistance mechanisms in patients with EGFR -mutant non-small-cell lung cancer (NSCLC) upon disease progression on EGFR tyrosine kinase inhibitors (TKIs) has been an area of great interest as it may lead to effective next-line treatment strategies. Here we report a case of emergent MET amplification detected in a tumor sample from a patient with NSCLC harboring EGFR L858R mutation after disease progression on erlotinib. The patient subsequently had a sustained partial response to a combination of full-dose osimertinib and crizotinib with excellent tolerance but eventually had central nervous system (CNS) progression...
2019: Lung Cancer: Targets and Therapy
Stephanie M Barrows, Kelly Wright, Catherine Copley-Merriman, James A Kaye, Marc Chioda, Robin Wiltshire, Knut Martin Torgersen, Elizabeth T Masters
The objective of this study was to understand outcomes of patients treated with ALK inhibitors, especially when ALK inhibitors are followed by other ALK inhibitors. A systematic literature review was conducted in PubMed, Embase, and Cochrane through July 17, 2017. Conference abstracts (three meetings in past 2 years) also were searched. Of 504 unique publications, 80 met inclusion criteria (47 clinical trials, 33 observational studies). Observational studies have the potential to provide information for ALK inhibitors used sequentially...
2019: Lung Cancer: Targets and Therapy
Shruti Kate, Anuradha Chougule, Amit Joshi, Vanita Noronha, Vijay Patil, Rohit Dusane, Leena Solanki, Priyanka Tiwrekar, Vaishakhi Trivedi, Kumar Prabhash
Background: The significance of uncommon EGFR mutations in newly diagnosed advanced non-small-cell lung cancer (NSCLC) patients is incompletely known. We aimed to analyze the demographic profile, outcome, and treatment attributes of these patients. Patients and methods: We retrospectively surveyed 5,738 advanced NSCLC patients who underwent EGFR testing in our center from 2013 to 2017 by in-house primer probes on real time PCR platform. Descriptive data were accumulated from electronic medical records...
2019: Lung Cancer: Targets and Therapy
Viola W Zhu, Alexa B Schrock, Thangavijayan Bosemani, Bryan S Benn, Siraj M Ali, Sai-Hong Ignatius Ou
ALK -rearranged lung cancer defines a distinctive molecular cohort of patients whose outcomes are significantly improved by the availability of ALK inhibitors. Thus, it is imperative for clinicians to screen appropriate patients for this driver mutation with a molecular testing platform capable of capturing all ALK fusions. Here, we report a novel VKORC1L1-ALK fusion and an ALK T1151K resistance mutation detected in a lung cancer patient who had been on crizotinib for over 8 years. Alectinib induced a dramatic response in this patient demonstrating its clinical activity against T1151K...
2018: Lung Cancer: Targets and Therapy
Takashi Sato, Takeshi Shimosato, Dennis M Klinman
"Silica" refers to crystalline particles formed by the combination of silicon with oxygen. Inhalation of silica particles promotes the development of pulmonary fibrosis that over prolonged periods increases the risk of lung cancer. The International Agency for Research on Cancer (IARC) classified crystalline silica as a human carcinogen in 1997. This categorization was questioned due to 1) the absence of dose-response findings, 2) the presence of confounding variables that complicated interpretation of the data and 3) potential selection bias for compensated silicosis...
2018: Lung Cancer: Targets and Therapy
Nadine Abdallah, Misako Nagasaka, Eman Abdulfatah, Dongping Shi, Antoinette J Wozniak, Ammar Sukari
Introduction: Histologic transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a well-recognized mechanism of resistance in EGFR -mutant adenocarcinoma upon treatment with TKIs, but rarely reported with programmed death1 (PD-1) inhibitors. We report two cases of potential transformation during treatment with PD-1 inhibitors. Case presentations: Case 1, a 65-year-old man was diagnosed with stage IVa lung adenocarcinoma on pleural fluid cytology...
2018: Lung Cancer: Targets and Therapy
Paul Aridgides, Tamara Nsouli, Rishabh Chaudhari, Russell Kincaid, Paula F Rosenbaum, Sean Tanny, Michael Mix, Jeffrey Bogart
Purpose: To report the outcomes of stereotactic body radiation therapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) according to respiratory motion management method. Methods: Patients with stage I NSCLC who received SBRT from 2007 to 2015 were reviewed. Computed tomography (CT) simulation with four-dimensional CT was performed for respiratory motion assessment. Tumor motion >1 cm in the craniocaudal direction was selectively treated with advanced respiratory management: either respiratory gating to a pre-specified portion of the respiratory cycle or dynamic tracking of an implanted fiducial marker...
2018: Lung Cancer: Targets and Therapy
Farkhad Manapov, Lukas Käsmann, Olarn Roengvoraphoj, Maurice Dantes, Nina-Sophie Schmidt-Hegemann, Claus Belka, Chukwuka Eze
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...
2018: Lung Cancer: Targets and Therapy
Ariel E Pollock, Lowell Shinn, Richard Anderson, Sarah Butler, Jondavid Pollock
Objectives: 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. Materials and methods: From 2005 to 2016, 49 patients diagnosed with stage 3 small cell lung carcinoma received concurrent chemoradiotherapy...
2018: Lung Cancer: Targets and Therapy
Lei Deng, Janaki Sharma, Elizabeth Ravera, Balazs Halmos, Haiying Cheng
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...
2018: Lung Cancer: Targets and Therapy
Denise Albano, Thomas Bilfinger, Barbara Nemesure
Background: 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. Methods: This retrospective study included 191 patients (100 surgery, 91 SBRT) identified through the Lung Cancer Evaluation Center, Stony Brook, NY, between 2008 and 2012...
2018: Lung Cancer: Targets and Therapy
Luisa María Ricaurte, Oscar Arrieta, Zyanya Lucia Zatarain-Barrón, Andrés F Cardona
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...
2018: Lung Cancer: Targets and Therapy
Ankur R Parikh, Siraj M Ali, Alexa B Schrock, Lee A Albacker, Vincent A Miller, Phil J Stephens, Pamela Crilley, Maurie Markman
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...
2018: Lung Cancer: Targets and Therapy
Eloise Mastrangelo, Mario Milani
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...
2018: Lung Cancer: Targets and Therapy
Elisna Syahruddin, Laksmi Wulandari, Nunuk Sri Muktiati, Ana Rima, Noni Soeroso, Sabrina Ermayanti, Michael Levi, Heriawaty Hidajat, Grace Widjajahakim, Ahmad Rusdan Handoyo Utomo
Purpose: We aimed to evaluate the distribution of individual epidermal growth factor receptor ( EGFR ) mutation subtypes found in routine cytological specimens. Patients and methods: A retrospective audit was performed on EGFR 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. Results: Overall test failure rate was 5...
2018: Lung Cancer: Targets and Therapy
Elysia K Donovan, Anand Swaminath
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...
2018: Lung Cancer: Targets and Therapy
Vidya H Veldore, Anuradha Choughule, Tejaswi Routhu, Nitin Mandloi, Vanita Noronha, Amit Joshi, Amit Dutt, Ravi Gupta, Ramprasad Vedam, Kumar Prabhash
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 EGFR 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...
2018: Lung Cancer: Targets and Therapy
Alessia E Russo, Domenico Priolo, Giovanna Antonelli, Massimo Libra, James A McCubrey, Francesco Ferraù
Non-small-cell lung cancer (NSCLC) represents about 85% of all lung cancers, and more than half of NSCLCs are diagnosed at an advanced stage. Chemotherapy has reached a plateau in the overall survival curve of about 10 months. Therefore, in last decade novel targeted approaches have been developed to extend survival of these patients, including antiangiogenic treatment. Vascular endothelial growth factor (VEGF) signaling pathway plays a dominant role in stimulating angiogenesis, which is the main process promoting tumor growth and metastasis...
2017: Lung Cancer: Targets and Therapy
Seigo Minami, Yoshitaka Ogata, Shouichi Ihara, Suguru Yamamoto, Kiyoshi Komuta
Background: Various biomarkers have been shown to predict prognosis in various types of cancers. However, these biomarkers have not been studied in advanced small cell lung cancer (SCLC). The modified Glasgow prognostic score (mGPS) is based on serum albumin level and C-reactive protein (CRP). The prognostic nutritional index (PNI) is a combination of serum albumin level and absolute lymphocyte count. This study aimed to evaluate the prognostic value of mGPS and PNI in SCLC. Methods: We retrospectively reviewed and calculated mGPS and PNI for patients with stage IIIB or IV SCLC who initiated platinum-based combination chemotherapy between November 2007 and June 2016...
2017: Lung Cancer: Targets and Therapy
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