Severity of Chronic Obstructive Pulmonary Disease and the Prognosis of Non-Small Cell Lung Cancer Patients

Objectives: We retrospectively analyzed whether the severity of Chronic Obstructive Pulmonary Disease (COPD) affected disease-specific survival in Non-Small-Cell Lung Cancer (NSCLC) patients after surgical resection. Methods: We enrolled 210 NSCLC patients who underwent curative surgery between 2009 and 2011. Classification of COPD severity was based on guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Results: A total of 55 patients were diagnosed with COPD. The 5-year disease-specific survival of patients with COPD was not different compared with that of patients without COPD. Among the COPD patients, 40 were classified as GOLD 1, 13 as GOLD 2, and 2 as GOLD 3. Although the number of patients with GOLD 2 - 3 was small, the 5-year disease-specific survival of patients with GOLD 2 - 3 was significantly poorer. We found the prognostic significance of GOLD 2 - 3 in univariate analysis, but failed to find this in multivariate analysis. Conclusions: There is a possibility that the severity of COPD might be useful to predict the prognosis of NSCLC patients. Further studies with large study population are needed.

Radiation-Induced Lung Cancers in Murine Models

Radiation therapy is a key weapon in the modern arsenal of cancer treatment. However, this effective treatment comes with risks of its own, and the sheer number of patients that undergo radiation as a part of their therapy regimen is only increasing. As this number increases, so does the incidence of secondary, radiation-induced neoplasias, creating a need for therapeutic agents targeted specifically towards reduction in the incidence of and treatment of these cancers. Development and efficacy testing of these agents requires not only extensive?in vitro?testing, but also a set of reliable animal models to accurately recreate the complex situations of radiation-induced carcinogenesis. The laboratory mouse?Mus musculus?remains the most relevant animal model in cancer research due to the molecular and physiological similarities it shares with man, its small size and high rate of breeding in captivity, and its fully sequenced genome. In this work, we review relevant?M. musculusinbred and?F1?hybrid animal models, as well as methods of induction of radiation-induced lung cancers. Associated molecular pathologies are also included.

Heparin versus Saline Solution for Locking of Totally Implantable Venous Access Port (TIVAP): Cohort Study of the First Kurdistan Series of TIVAP

Introduction: Totally implantable venous access port (TIVAP) is essential prerequisite for most of chemotherapy protocols. Flushing with 0.9% sodium chloride becomes an alternative to heparinized solution. As flushing and locking solutions are still controversial, this study was conducted to compare efficacy of heparinized solution versus normal saline solution for locking in ports TIVAP. Patients and Methods: Prospective Cohort study performed in teaching hospital Sulaymaniyah-University of Kurdistan, Iraq, including 384 TIVAP implanted in cancer and non-cancer patients. The study reports the TIVAP outcome in 2 groups of patients where 2 different solutions used for maintaining catheter’s patency by heparinized solution in group (A), versus normal saline for group (B). Results: In group A, the rate of complications was 8.2% (n = 16) while in group B complications rate was 7.9% (n = 15). Thrombosis in group A occurred in 1.03% of the cases and in group B was 1.57%. There were no significant differences between the two groups regarding the causes for unwanted removals of the TIVAP. Conclusions: The results of our study suggest that heparin has no role in preventing the early or late complications of TIVAP and we do not recommend using it as a locking solution.

Missing the Target?—Targeted Therapy in Small Cell Lung Cancer

Small cell lung cancer [SCLC] is a devastating form of cancer, with most patients harbouring extensive disease at diagnosis and survival of less than 5% at five years. Progress in novel therapies has been limited. This specialist review explores current targeted therapy options and potential areas of development.

The bisulfite genomic sequencing protocol

The bisulfite genomic sequencing (BGS) protocol has gained worldwide popularity as the method of choice for analyzing DNA methylation. It is this popular because it is a powerful protocol and it may be coupled with many other applications. However, users often run into a slew ofproblems, including incomplete conversion,overly degraded DNA, sub-optimal PCR amplifications, false positives, uninformative results, or altogether failed experiments. We pinpoint the reasons why these problems arise and carefully explain the critical steps toward accomplishing a successful experiment step-by-step. This protocol has worked successfully (>99.9% conversion) on as little as 100 ng of DNA derived from nearly 10-year-old DNA samples extracted from whole blood stored at -80°C and resulted in enough converted DNA for more than 50 PCRreactions. The aim of this article is to makelearning and usage of BGS easier, more efficient and standardized for all users.

The Outcome of the Chemotherapy and Oncothermia for Far Advanced Adenocarcinoma of the Lung: Case Reports of Four Patients

Lung cancer is one of the most aggressive and lethal form of cancers. Patients with far advanced lung cancer are treated by chemotherapy with or without radiotherapy. However, median survival of these patients is less than 6 months. To increase survival and quality of life for these patients, various forms of complementary treatments have been tried in clinical practices, and oncothermia is supposed to be one of the promising candidates. From May 2008 to November 2013, 4 patients with far advanced lung adenocarcinoma (stages IIIB and IV) were treated with oncothermia in addition to conventional chemotherapy at Gangnam Severance Hospital and Bundang CHA Hospital. All these patients have survived for more than 2 years.

Prognostic Role of miR-205 in Early-Stage (T1N0) Non-Small Cell Lung Cancer

Background: Published data have shown that microRNAs (miRNAs) could play a potential role as diagnostic and prognostic indicators in cancers. Data for the predictive value of miRNA let-7, miR-21, and miR-205 are inconclusive. The aim of the present analysis was therefore to evaluate the expression and the prognostic role of the above mentioned miRNAs?in early-stage?(T1N0) NSCLC patients. Methods: Quantification of let-7g, miR-21, and miR-205 expression was carried out into 105 early-stage NSCLC by quantitative Real Time-PCR (qRT-PCR).?Results: a significant association between the low miR-205 expression and ADC histotype (p??0.0001) compared to SCC?was found;moreover, survival analysis showed thattumors with a high?miR-205 expression had a significantly shorter mean PFS and OS compared to the patients with a low expression of this miRNA (p = 0.02 and p = 0.03, respectively). No other statistically significant correlations were observed between the analysed miRNAs and the main clinico-pathological characteristics of the NSCLC patients. Conclusion: The results indicated that miR-205 could represent a useful marker in the prognostic management of the early-stage (T1N0) NSCLC patients.

Targeting TIGIT in NSCLC—Is There Light on the Horizon?

Non-small cell lung cancers (NSCLCs) represent over 80% of all malignant lung tumours and are one of the leading causes of cancer death throughout the world. First- and second-line treatment of advanced or metastatic NSCLCs has changed dramatically during the last two decades with the development of novel immunotherapies (e.g., checkpoint inhibitors targeting PD-1, PD-L1, and CTLA-4) sparing NSCLC patients from the toxic effects of chemotherapy. However, only 15% - 20% of all patients respond to treatment. In order to improve response rates, experimental and clinical evidence has provided the basis for further evaluating the combination of co-stimulatory and inhibitory monoclonal antibodies to improve the anti-tumour immune response. Innovative second- and third-generation immuno-oncology drugs are currently evaluated in ongoing phase I-III trials (either alone or in combination) including the new checkpoint inhibitor target TIGIT (T cell immunoreceptor with Ig and ITIM domains). TIGIT functions as an inhibitory immunoglobin receptor which is overexpressed by different immune cells including effector and memory CD4+ T and CD8+ T cells, regulatory T cells (Tregs), follicular T helper cells (Tfh), and natural killer cells. Targeting the interaction between the receptors of the TIGIT receptors (e.g., CD96, CD112R, CD226, TIGIT and their corresponding binding partners) has become an innovative strategy for the next concepts of cancer immunotherapy that has the potential to synergize with PD-1/PD-L1checkpoint inhibition. Currently, four anti-TIGIT monoclonal antibodies are currently being studied in phase III trials in NSCLCs: 1) tiragolumab (SKYSCRAPER programme);2) vibostolimab (KEYVIVE programme);3) domvanalimab (ARC programme), and 4) ociperlimab (AdvanTIG programme). The vast majority of these studies are ongoing;however, the SKYSCRAPER-01 trial (tiragolumab in NSCLC) and the SKYSCRAPER-02 trial (tiragolumab in SCLC) were negative and did not meet their primary endpoint. The underlying preclinical and clinical mechanisms of these unexpectedly negative studies are currently far from being clear and the results from currently recruiting clinical studies are eagerly awaited to shed some additional light on these results. From 2021 onwards different TIGIT family receptors are currently evaluated in over 25 clinical trials (phase I-III), however, a lot of preclinical and clinical research is ongoing at different research sites which will help to identify novel immune checkpoint targets with improved activity against malignancies across all histologies.

A Phase II Study of Erlotinib in Patients with Previously Treated Non-Small Cell Lung Cancer

Background: Erlotinib has been reported to be effective for the treatment of non-small cell lung cancer (NSCLC). To evaluate the efficacy and safety of erlotinib under conditions similar to daily clinical practice, a phase II trial was conducted in Japanese patients with previously treated NSCLC. Methods: The eligibility criteria were stage IIIB/IV NSCLC, a performance status (PS) of 0 - 2, and previous treatment with 1 - 2 non-EGFR-TKI regimens. Patients received erlotinib (150 mg/day) orally until disease progression or intolerable toxicity occurred. The primary endpoint was the objective response rate (ORR). In addition, the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and EGFR gene mutation status were evaluated. Results: Thirty-eight patients were enrolled, and 37 patients were evaluated. The median age was 69 years (range, 50 - 80 years). Patient characteristics were as follows: 26 were male and 11 were female;12 had a PS of 0, 20 had a PS of 1, and 5 had a PS of 2;and 26 had adenocarcinoma, and 11 had non-adenocarcinoma histology. The ORR and DCR were 21.6% (95% confidence interval [CI], 11.4% - 37.2%) and 54.1% (95% CI, 35.9% - 66.6%), respectively. Twenty-seven patients could be evaluated for EGFR gene status (12, mutated;15, wild-type). The ORR for EGFR-mutated patients was 41.7%, while that for patients with wild-type EGFR was 13.3%. The median PFS was evaluated as 4.4 months (95% CI, 2.2 - 10.7 months). The median OS was 14.9 months (95% CI, 9.2 months - not reached). Common adverse events were tolerable skin toxicities, diarrhea, and stomatitis. In addition, interstitial lung disease occurred in 8.1% of patients. Conclusion: As efficacy and safety were similar to previous studies, erlotinib was found to be effective for Japanese patients with previously treated NSCLC in clinical practice.

A phase I study with Satraplatin and simultaneous chest radiation for non-small cell lung cancer

Introduction: Satraplatin has been given in combination therapy for lung cancer to utilize its radio-sensitizing properties. The optimal dose of satra-platin given concurrently with radiation therapy for locally advanced non-small cell lung cancer (NSC-LC) has not been defined. This phase I trial attempts to identify a maximally tolerated dose (MTD) and dose limiting toxicity (DLT) for Satraplatin given con-currently with radiation for locally advanced N-SCLC. Patients and Methods: 15 patients with histologically confirmed Stage IIIA/B NSCLC entered onto this study with four dose escalations (10 to 40 mg daily) of Satraplatin. Eligibility included patients with NSCLC and one of the following criteria: 1) previously untreated, inoperable disease and planned to receive radiation therapy to primary disease site;2) previously resected disease with mediastinal relapse;or 3) metastatic disease in no more than one distant site. Results: The most common toxicities reported were all grades of fatigue (n = 9), nausea (n = 9), constipation (n = 7), fever (n = 7), and vomiting (n = 6). No DLT at the 1st, 2nd, and 3rd dose levels was identified. At the 4th dose level, one patient developed grade III elevation of liver function tests (LFTs) and a second patient developed grade III diarrhea with fever requiring hospitalization. There were 8 partial responses out of 11 evaluable patients for response (RR 67%). Conclusion: Elevated LFTs and diarrhea appear to be the principal DLTs of concurrent daily oral Satraplatin and thoracic radiation in the outpatient setting. The MTD of concurrent Satraplatin with thoracic radiation therapy appears to be 40 mg daily.

Expression of STAT3 in non-small cell lung cancer and its clinical significance

Signal transducer and activator of transcription 3(STAT3) plays an important role in tumor occurrence and development. Here we attempt to evaluate the clinical diagnostic value of STAT3 as a potential tumor marker by detecting the expression of STAT3 in blood of non-small cell lung cancer (NSCLC) patients. Immunohistochemistry was applied to detect STAT3 protein in A549 cells and MRC-5 cell, real time PCR was applied to detect STAT3 mRNA and ELISA was applied to detect the expression of STAT3 protein in NSCLC patients, benign lung disease group and healthy controls. The expression levels of STAT3 mRNA and STAT3 protein in A549 cells and NSCLC patients were significantly higher (P < 0.01). The areas under ROC curves (Az) of STAT3 mRNA and STAT3 protein were 0.870 and 0.860 respectively, which had no significant difference (P > 0.05). When comparing the Az of STAT3 protein with CEA, CA125 and CYFRA21-1 respectively, there was no significant difference (P > 0.05). And we compared the Az of the four joint detection (STAT3 + CEA + CA125 + CYFRA21-1) with the three joint detection (CEA + CA125 + CYFRA21-1), 0.930 and 0.841, respectively, P < 0.05. It appears that the diagnostic value and accuracy of STAT3 is equivalent with CEA, CA125, and CYFRA21-1 in NSCLC, and to joint with other three can achieve higher diagnosis value.

Five-Year Survivors of Non-Small Cell Lung Cancer Patients with Positive Pleural Lavage Cytology

Background: The pleural lavage cytology (PLC) for non-small cell lung cancer (NSCLC) patients has been reported as a significant prognostic factor. The aim of this study is to clarify the clinicopathological characteristics of 5-year survivors of patients with positive PLC. Methods: Among 401 resected NSCLC patients, 30 (7.48%) patients with positive PLC were reviewed retrospectively. Results: Only 7 of 30 patients (23.3%) survived more than 5-year. There were no differences in age, gender, histology, pT status and pN status between 5-year survivors and non-survivors. On the other hand, the serum carcinoembryonic antigen (CEA) level was significantly higher in non-survivors. Among these 5-year survivors, 4 of 7 patients died of NSCLC recurrences more than 5 years after surgery. Remaining 3 patients survived without cancer recurrences. Interestingly these 3 survivors had not received any adjuvant therapies after surgery. Conclusion: None of the 5-year survivor with positive PLC had high serum CEA level. Furthermore 5-year survival did not equal to cure in NSCLC patients with positive PLC.

Advances in the Treatment of Advanced Non-Small Cell Lung Cancer

In recent years, the incidence of lung adenocarcinoma has been increasing, and now it has become the largest type of non-small cell lung cancer (NSCLC). Currently, treatment of advanced NSCLC consists of several modalities: systemic chemotherapy, local radiation therapy, and targeted therapy (including most recently immunotherapy). In the past decade, the discovery of new molecular subtypes, the search for tumor driver gene mutations, the development of targeted molecular targeted drugs, or targeted therapy to suppress tumor angiogenesis and regulate tumor immune response have been the main directions of NSCLC research and clinical diagnosis and treatment. At present, platinum-based chemotherapy is widely used in NSCLC patients clinically. Platinum-based chemotherapy drugs can effectively prolong the survival time of patients and improve their quality of life, but the incidence of adverse reactions is still high. Therefore, it is necessary to find a drug that can improve the efficacy of patients and reduce the adverse reactions of platinum chemotherapy drugs to NSCLC patients.

Patient-Reported Outcomes of Chemotherapy Involving Non-Small Cell Lung Cancer: Evaluation by Questionnaires of Quality of Life Regarding Anti-Aging and Anti-Cancer Drugs

Background: Patient-reported outcomes (PROs) of quality of life (QOL) during chemotherapy involving lung cancer are very important for the medical staffs. Patients’ satisfaction and healthy changes were evaluated by the patient-self assessment. Materials and Methods: From July 2007 to April 2008, a total of 19 patients received chemotherapy. The QOL data were collected by using the QOL questionnaire for cancer patients treated with anticancer drugs (QOL-ACD) and the anti-aging QOL assessment (AA-QOL). The AA-QOL contained 51 items: 30 of physical and 21 of mental symptoms of the elderly and the aging population. The patients replied to the questions at two different times, i.e., at pre-chemotherapy (baseline) and at post-chemotherapy (2 weeks after the chemotherapy). Results: Regarding the hematological toxicities, for the grade 3/4 toxicities, there were 12 neutropenia (12/19, 63.2%) and 3 thrombocytopenia (3/19, 15.8%). For the grade 3 febrile neutropenia, there were 5 cases (5/19, 26.3%). Regarding the non-hematological toxicities, there was no grade 3 and grade 4 toxicities. Based on the outcomes of the QOL-ACD, the three items (“physical condition”, “social attitude”, and “overall QOL”) at post-chemotherapy became significantly worse compared to the baseline. Regarding the outcomes of the AA-QOL, 4 items of physical symptoms (“thirst”, “anorexia”, “early satiety”, and “diarrhea”) became significantly worse compared to the baseline. Regarding the mental symptoms, 2 items (“nothing to look forward in life” and “a sense of uselessness”) became significantly worse compared to the baseline. Conclusion: Regarding the PROs of the QOL during the chemotherapy term, both the physical and mental symptoms had become worse. To clarify the changes in the QOL during chemotherapy is very important for multidisciplinary teamwork, which should play the role of providing the appropriate cares and treatment as patient-support.

Pulmonary metastasis from gastric cancer: A case report and review of literature

We present a case report of a 63-year-old male who underwent lung resections for metastases originating from gastric cancer 18-year after total gastrectomy with lymphadenectomy. The gastrectomy was performed in 1994;histological examination of the original tumor revealed stage II poorly differentiated adenocarcinoma [pT2 (MP), N0, M0]. Chest X-ray and computed tomography in 2012 showed a well-defined tumor, 9 mm in size, at the left S3 of the lung. Thoracoscopic partial resection was performed. The tumor was diagnosed as poorly differentiated carcinoma, most likely metastatic gastric adenocarcinoma. Although rarely performed, resection of pulmonary metastases from carcinoma of the stomach was done to improve the patient’s chances for long-term survival.

Unusual Cystic and Papillary Appearance of Brain Metastasis from Papillary Lung Adenocarcinoma on MRI. Radiologic-Pathologic Correlations in Two Similar Cases

We report two cases of brain metastasis from a lung adenocarcinoma. Magnetic Resonance Imaging (MRI) appearance was closely correlated with the macroscopic and microscopic findings that showed multiples nodules of a well-differentiated papillary adenocarcinoma with secreting tubules, surrounded by mucoid fluid.

Association between the TP53 Arg72Pro Polymorphisms and Gastric Cancer Risk: An Updated Meta-Analysis and Re-Analysis of Systematic Meta-Analyses

Background: A latest Meta-analysis on TP53 Arg72Pro polymorphism with gastric cancer (GC) risk was published in 2015 including 20 literatures, while our study included 43 studies. Moreover, the results of previously published original studies were inconsistent and the credibility of the significant correlation between the statistical results has been ignored. Therefore, an updated Meta-analysis was conducted to further explore these associations. Objective: To explore whether these two gene polymorphisms are related to the risk, clinical manifestations, and pathological features of GC. Methods: We searched several Chinese and English databases. The crude odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the correlation. In addition, false positive reporting probability (FPRP), bayesian false discovery probability (BFDP), and Venice criteria were used to assess the reliability of statistically significant correlation. Results: Overall, the TP53 Arg72Pro polymorphism was related to a significantly increased GC risk (AP vs. AA: OR = 1.12, 95% CI = 1.02 - 1.24;PP + AP vs. AA: OR = 1.12, 95% CI = 1.02 - 1.24;P vs. A: OR = 1.07, 95% CI = 1.00 - 1.15). However, after excluding the low quality and Hardy–Weinberg Disequilibrium (HWD) studies, significant changes were found on the TP53 Arg72Pro polymorphism with GC risk in Caucasians (PP vs. AA: OR = 1.48, 95% CI = 1.01 - 2.16) and non-gastric cancer control groups (PP vs. AP + AA: OR = 1.33, 95% CI = 1.07 - 1.64)). However, the above significant results were considered unreliable after being adjusted with Bayesian error detection probability (BFDP) and false positive reporting probability (FPRP). These unreliable results were confirmed again, and no new reliable results were found in the further sensitivity analysis (only studies that met the quality assessment criteria). Conclusions: After considering the quality of the study and the reliability of the results, this Meta-analysis showed that TP53 codon 72 polymorphisms had no significant correlation with GC risk. Because of various confounding factors, the result that these polymorphisms increase GC risk is more likely to be a false positive result.

Survival of Patients with Small-Cell Lung Cancer Treated at Tertiary Hospitals in the East of Thailand, 2007-2016: A Retrospective Study

Objective:?The objective of the study was to determine the survival of patients?with small-cell lung cancer treated at tertiary hospitals in the East of?Thailand. Materials and methods:?The researchers conducted this retrospective?study by reviewing medical records of patients with small-cell lung cancer?treated at Chonburi Cancer Hospital and Prapokklao Hospital from January?2007 to December 2016 and monitored via follow-up until December?2018. Results:?This study enrolled 54 patients with a median follow-up time?of 8.5 months. The median age of patients was 63 years old. Most patients?were male (83.3%) and had a history of smoking (90.7%), and 31.4% had?clinical superior vena cava obstruction at initial treatment. The Eastern Cooperative?Oncology Group performance status 0-1 was noted for 61.1% of the?study population. Median survival time of patients with limited-stage and extensive-stage small cell lung cancer who received systemic chemotherapy?and/or radiotherapy was 17.01 months (95% CI, 12.01 - 22.01) and 8.14?months (95% CI, 7.19 - 9.10), respectively, and that of patients receiving?supportive care was 2.3 months (95% CI, 0.75 - 4.03). However, the median?survival time of patients with extensive-stage small-cell lung cancer receiving?only palliative chemotherapy was 5.9 months (95% CI, 0.32 - 17.51). Conclusions:?The median survival time of patients with limited-stage small-cell lung?cancer treated in the East of Thailand was comparable to those of landmark?studies;however, the survival of patients with extensive-stage small-cell lung?cancer was shorter than those of Phase III trials. A multidisciplinary team was?necessary to improve the quality of patient care.

Gender Does Not Have a Potential Predictive Value for the Presence of Epidermal Growth Factor Receptor Mutation in Lung Adenocarcinoma

Background: Previous studies reported that non-small cell carcinoma patients characterized by female gender, never-smoking status and adenocarcinoma histology were more likely to harbor epidermal growth factor receptor (EGFR) mutations. However, some studies failed to find the relationship between EGFR mutation and gender. Methods: One hundred and eighty-four consecutive patients (90 men and 94 women) of resected lung adenocarcinoma were studied retrospectively. Since the smoking rate is significantly higher in men, we assumed that gender difference might be a seeming factor affected by smoking. Therefore we subdivided the patients into 2 groups: never- and ever-smokers. Results: The number of ever-smokers was 94.44% in men, whereas 8.51% in women. EGFR mutation was positive in 48.9%. For overall patients, EGFR mutation status was associated with gender, pStage, pT status, lepidic dominant histologic subtype, pure/mixed groundglass opacity (GGO) on computed tomography (CT) and smoking status. However, in ever-smokers, EGFR mutation status was associated with lepidic histologic subtype and GGO on CT, but not others including gender. Similar results were also found in never-smokers, and gender was not also related to EGFR mutation in never smokers. Conclusion: The EGFR mutational frequency among men and women was not significantly different when lung adenocarcinoma patients were stratified into never- and ever-smokers.

C-MET Inhibitors as New Members of the NSCLC Treatment Armamentarium—A Pooled Analysis

Objective: Capmatinib and tepotinib, two recently FDA-approved and highly specific small-molecule inhibitors of c-MET exon 14 skipping mutations are new and important therapeutic options for the treatment of NSCLC patients harbouring c-MET alterations. However, the precise role of these molecules as a new treatment option is still not fully defined. Methods: In an attempt to further evaluate the contributions of c-MET inhibitors to the armamentarium of treatment options for advanced and metastatic NSCLCs, relevant phase II and III studies were retrospectively analyzed in terms of ORR and mPFS (mOS numbers are still not available for current c-MET trials and therefore not considered for statistical purposes). Results: Treatment of advanced and metastatic NSCLC patients harbouring c-MET exon 14 skipping mutations with the novel and highly selective c-MET inhibitors is significantly superior (p Conclusion: The novel and highly selective c-MET inhibitors capmatinib and tepotinib are promising novel treatment options for patients with c-MET-dysregulated NSCLC primarily in the first-line setting, albeit a clear mOS benefit has not yet been established. Since immunotherapy did not appear to be particularly effective in NSCLC patients harbouring c-MET alterations, the vast majority of these patients are treated with immunotherapy plus chemotherapy. C-Met inhibitors appear to be equally effective and thereby sparing patients from the toxic effects of the chemotherapy. The routine testing of c-MET exon 14 skipping mutations should be performed as the GEOMETRY mono-1 data clearly showed higher response rates with capmatinib in treatment-naive than in pretreated patients, indicating that c-MET exon 14 skipping mutations should preferably be molecularly assessed at baseline. C-MET exon 14 skipping mutations are, therefore, clear biomarkers of response to c-MET inhibitors.