Breast cancer

2018 ◽  
Author(s):  
Jim Cassidy ◽  
Donald Bissett ◽  
Roy A. J. Spence OBE ◽  
Miranda Payne ◽  
Gareth Morris-Stiff ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Symptom Relief ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Presenting Symptoms ◽  
Metastatic Nsclc ◽  
Symptoms And Signs

Thoracic cancer examines the epidemiology, aetiology, and role of screening and prevention in the reduction of deaths from lung cancer, the majority caused by cigarette smoking. The pathology and genetics of lung cancer, with particular note of the driver mutations, are followed by the symptoms and signs of the disease. Appropriate investigations are described to stage the tumour. The optimum treatment for localised non-small cell lung cancer (NSCLC) is surgical resection, followed in some cases by adjuvant chemotherapy. However, most cases present with disease too advanced for surgery, and for these chemotherapy and radiotherapy are appropriate. Metastatic NSCLC can be treated with platinum based doublet chemotherapy with modest palliative benefits. Metastatic NSCLC with specific driver mutations are amenable to control by targeted therapy. Locally advanced NSCLC is often treated with similar chemotherapy and radiotherapy, ideally administered concurrently, to achieve symptom relief but also improved survival rates. Short course simple radiotherapy offers symptom relief in patients not fit for chemotherapy. Patients with localised NSCLC who are not fit for surgery, may benefit from radical radiotherapy, particularly stereotactic radiotherapy. Small cell lung cancer (SCLC) is characterised by almost universal systemic spread, so that surgery is rarely appropriate. Staging is similar to NSCLC, and chemotherapy is the mainstay of treatment, usually cisplatin or carboplatin combined with etoposide. When possible, this is combined with concurrent thoracic irradiation covering all radiological sites of disease. Prophylactic cranial irradiation reduces the risk of CNS disease. Malignant pleural mesothelioma is caused by occupational asbestos exposure. Symptoms and signs, investigation and staging, and management are discussed. Thymic tumours, their pathology, presenting symptoms including paraneoplastic syndromes, investigation, staging and treatment are reviewed.

scholarly journals Does the Waiting Period for Genetic Tests Affect the Prognosis in Chemotherapy-Treated de novo Metastatic Non-Small Cell Lung Cancer Patients without a Driver Mutation?

2020 ◽  
pp. 1-7
Author(s):  
Serdar Arici ◽  
Abdullah Sakin ◽  
Ruhper Cekin ◽  
Saban Secmeler ◽  
Nurgül Yasar ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
De Novo ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Metastatic Nsclc ◽  
Group A ◽  
Nsclc Patients

<b><i>Introduction:</i></b> The length of the necessary waiting period to test driver mutations may generate anxiety in patients and clinicians. For this reason, an investigation was conducted to determine whether the duration between diagnosis and the start of first-line chemotherapy (DDC) in non-small cell lung cancer (NSCLC) patients without driver mutations has an impact on prognosis. <b><i>Methods:</i></b> The study included 303 de novo metastatic NSCLC patients without a driver mutation and patients were divided into 2 groups according to DDC: ≤30 days (group A) or &#x3e;30 days (group B). The determinant factors for progression-free survival (PFS) and overall survival (OS) were examined by Cox regression analysis. <b><i>Results:</i></b> The mean DDC was calculated as 38.2 ± 54.5 days. The number of patients in group A and B were 183 and 120, respectively. The median PFS in groups A and B was 5.0 and 6.0 months (<i>p</i> = 0.268) and the median OS was 10.0 and 11 months, respectively (<i>p</i> = 0.341). Univariate and multivariate analyses revealed that DDC was not a factor associated with PFS and OS. <b><i>Conclusion:</i></b> Our results show that a higher DDC was not associated with a worse prognosis in metastatic NSCLC patients without driver mutations. In this context, it is safer for patients and their physicians to wait for test results before starting chemotherapy.

scholarly journals Molecular profile of KRAS G12C-mutant colorectal and non-small-cell lung cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Luiz Henrique Araujo ◽  
Bianca Mendes Souza ◽  
Laura Rabelo Leite ◽  
Sabrina A. F. Parma ◽  
Natália P. Lopes ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Driver Mutations ◽  
Molecular Profile ◽  
Common Mutation ◽  
Small Cell Lung ◽  
The South ◽  
Nsclc Patients

Abstract Background KRAS is the most frequently mutated oncogene in cancer, however efforts to develop targeted therapies have been largely unsuccessful. Recently, two small-molecule inhibitors, AMG 510 and MRTX849, have shown promising activity in KRAS G12C-mutant solid tumors. The current study aims to assess the molecular profile of KRAS G12C in colorectal (CRC) and non-small-cell lung cancer (NSCLC) tested in a clinical certified laboratory. Methods CRC and NSCLC samples submitted for KRAS testing between 2017 and 2019 were reviewed. CRC samples were tested for KRAS and NRAS by pyrosequencing, while NSCLC samples were submitted to next generation sequencing of KRAS, NRAS, EGFR, and BRAF. Results The dataset comprised 4897 CRC and 4686 NSCLC samples. Among CRC samples, KRAS was mutated in 2354 (48.1%). Most frequent codon 12 mutations were G12D in 731 samples (14.9%) and G12V in 522 (10.7%), followed by G12C in 167 (3.4%). KRAS mutations were more frequent in females than males (p = 0.003), however this difference was exclusive of non-G12C mutants (p < 0.001). KRAS mutation frequency was lower in the South and North regions (p = 0.003), but again KRAS G12C did not differ significantly (p = 0.80). In NSCLC, KRAS mutations were found in 1004 samples (21.4%). As opposed to CRC samples, G12C was the most common mutation in KRAS, in 346 cases (7.4%). The frequency of KRAS G12C was higher in the South and Southeast regions (p = 0.012), and lower in patients younger than 50 years (p < 0.001). KRAS G12C mutations were largely mutually exclusive with other driver mutations; only 11 NSCLC (3.2%) and 1 CRC (0.6%) cases had relevant co-mutations. Conclusions KRAS G12C presents in frequencies higher than several other driver mutations, and may represent a large volume of patients in absolute numbers. KRAS testing should be considered in all CRC and NSCLC patients, independently of clinical or demographic characteristics.

scholarly journals Differential influence of antibiotic therapy and other medications on oncological outcomes of patients with non-small cell lung cancer treated with first-line pembrolizumab versus cytotoxic chemotherapy

2021 ◽  
Vol 9 (4) ◽  
pp. e002421
Author(s):  
Alessio Cortellini ◽  
Massimo Di Maio ◽  
Olga Nigro ◽  
Alessandro Leonetti ◽  
Diego L Cortinovis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Multivariable Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Metastatic Nsclc ◽  
The Impact

BackgroundSome concomitant medications including antibiotics (ATB) have been reproducibly associated with worse survival following immune checkpoint inhibitors (ICIs) in unselected patients with non-small cell lung cancer (NSCLC) (according to programmed death-ligand 1 (PD-L1) expression and treatment line). Whether such relationship is causative or associative is matter of debate.MethodsWe present the outcomes analysis according to concomitant baseline medications (prior to ICI initiation) with putative immune-modulatory effects in a large cohort of patients with metastatic NSCLC with a PD-L1 expression ≥50%, receiving first-line pembrolizumab monotherapy. We also evaluated a control cohort of patients with metastatic NSCLC treated with first-line chemotherapy. The interaction between key medications and therapeutic modality (pembrolizumab vs chemotherapy) was validated in pooled multivariable analyses.Results950 and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Corticosteroid and proton pump inhibitor (PPI) therapy but not ATB therapy was associated with poorer performance status at baseline in both the cohorts. No association with clinical outcomes was found according to baseline statin, aspirin, β-blocker and metformin within the pembrolizumab cohort. On the multivariable analysis, ATB emerged as a strong predictor of worse overall survival (OS) (HR=1.42 (95% CI 1.13 to 1.79); p=0.0024), and progression free survival (PFS) (HR=1.29 (95% CI 1.04 to 1.59); p=0.0192) in the pembrolizumab but not in the chemotherapy cohort. Corticosteroids were associated with shorter PFS (HR=1.69 (95% CI 1.42 to 2.03); p<0.0001), and OS (HR=1.93 (95% CI 1.59 to 2.35); p<0.0001) following pembrolizumab, and shorter PFS (HR=1.30 (95% CI 1.08 to 1.56), p=0.0046) and OS (HR=1.58 (95% CI 1.29 to 1.94), p<0.0001), following chemotherapy. PPIs were associated with worse OS (HR=1.49 (95% CI 1.26 to 1.77); p<0.0001) with pembrolizumab and shorter OS (HR=1.12 (95% CI 1.02 to 1.24), p=0.0139), with chemotherapy. At the pooled analysis, there was a statistically significant interaction with treatment (pembrolizumab vs chemotherapy) for corticosteroids (p=0.0020) and PPIs (p=0.0460) with respect to OS, for corticosteroids (p<0.0001), ATB (p=0.0290), and PPIs (p=0.0487) with respect to PFS, and only corticosteroids (p=0.0033) with respect to objective response rate.ConclusionIn this study, we validate the significant negative impact of ATB on pembrolizumab monotherapy but not chemotherapy outcomes in NSCLC, producing further evidence about their underlying immune-modulatory effect. Even though the magnitude of the impact of corticosteroids and PPIs is significantly different across the cohorts, their effects might be driven by adverse disease features.

scholarly journals Molecular profile of KRAS G12C-mutant colorectal and non-small-cell lung cancer

2020 ◽  
Author(s):  
Luiz H. Araujo ◽  
Bianca Souza ◽  
Laura Leite ◽  
Sabrina Parma ◽  
Natália Lopes ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Driver Mutations ◽  
Molecular Profile ◽  
Common Mutation ◽  
Small Cell Lung ◽  
The South ◽  
Kras Mutations

Abstract Background: KRAS is the most frequently mutated oncogene in cancer, however efforts to develop targeted therapies have been largely unsuccessful. Recently, two small-molecule inhibitors, AMG 510 and MRTX849, have shown promising activity in KRAS G12C-mutant solid tumors. The current study aims to assess the molecular profile of KRAS G12C in colorectal (CRC) and non-small-cell lung cancer (NSCLC) tested in a clinical certified laboratory.Methods: CRC and NSCLC samples submitted for KRAS testing between 2017 and 2019 were reviewed. CRC samples were tested for KRAS and NRAS by pyrosequencing, while NSCLC samples were submitted to next generation sequencing of KRAS, NRAS, EGFR, and BRAF. Results: The dataset comprised 4,897 CRC and 4,686 NSCLC samples. Among CRC samples, KRAS was mutated in 2,354 (48.1%). Most frequent codon 12 mutations were G12D in 731 samples (15.2%) and G12V in 462 (9.6%), followed by G12C in 167 (3.4%). KRAS mutations were more frequent in females than males (p=0.003), however this difference was exclusive of non-G12C mutants (p<0.001). KRAS mutation frequency was lower in the South and North regions (p=0.003), but again KRAS G12C did not differ significantly (p=0.80). In NSCLC, KRAS mutations were found in 1,004 samples (21.4%). As opposed to CRC samples, G12C was the most common mutation in KRAS, in 346 cases (7.4%). The frequency of KRAS G12C was higher in the South and Southeast regions (p=0.012), and lower in patients younger than 50 years (p<0.001). KRAS G12C mutations were largely mutually exclusive with other driver mutations; only 11 NSCLC (3.2%) and 3 CRC (1.8%) cases had relevant co-mutations. Conclusions: KRAS G12C presents in frequencies higher than several other driver mutations, represent a large volume of patients in absolute numbers. KRAS testing should be considered in all CRC and NSCLC patients, independently of clinical or demographic characteristics.

scholarly journals Paradigm shift in the management of metastatic Non-small Cell Lung Cancer

2021 ◽  
Author(s):  
Ruby Gupta ◽  
Melanie Smalley ◽  
Nwabundo Anusim ◽  
Vishal Jindal ◽  
Mandeep Singh Rahi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Paradigm Shift ◽  
Survival Rates ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Cancer Management ◽  
Chemotherapeutic Approach

Background: Lung cancer is one of the leading causes of cancer mortality in the US. The use of precision medicine in the past 10 years has significantly changed the therapeutic landscape of lung cancer. Management of advanced non-small cell lung cancer (NSCLC) has transitioned from a chemotherapeutic approach to targeted treatments and immunotherapeutic agents. Several tyrosine kinase inhibitors (TKIs) have been approved for patients with targeted mutations while patients who do not have driver mutations; immunotherapy has been recently approved as frontline therapy, which has resulted in marked improvement in overall survival and added a new tool in our armamentarium. Aims: The purpose of this review is to highlight recent advancements in diagnostic approach and management strategies in patients with metastatic NSCLC. Materials and methods: Published studies included in Medline (via PubMed) and National Comprehensive Cancer Network Guidelines were reviewed for data gathering. Conclusion: The use of next generation sequencing has significantly changed our understanding of molecular oncogenic mechanisms of lung cancer. These advancements have created a paradigm shift in the treatment strategies of metastatic lung cancer from primarily chemotherapeutic approach to increasing use of targeted therapies and immune check point inhibitors (ICI) leading to better survival rates and lesser toxicity.

Systemic and Radiation Therapy Approaches for Locally Advanced Non–Small-Cell Lung Cancer

2022 ◽  
Author(s):  
Kristin A. Higgins ◽  
Sonam Puri ◽  
Jhanelle E. Gray
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Concurrent Chemoradiation ◽  
Driver Mutations ◽  
Small Cell Lung

The treatment for locally advanced non–small-cell lung cancer has changed dramatically over the past several years, with consolidative immunotherapy after concurrent chemoradiation becoming the new standard of care. Five-year survival outcomes have substantially improved with this approach. Despite these advances, further improvements are needed as the majority of patients ultimately develop progression of disease. The next-generation immunotherapy trials are currently being conducted that include approaches such as concurrent immunotherapy and addition of other therapeutic agents in the concurrent and consolidative settings. Specific unmet needs continue to exist for patients who develop disease progression after concurrent chemoradiation and immunotherapy, as well as defining the best treatment for patients with driver mutations. Future directions also include refinement of radiation techniques to reduce toxicities as much as possible, as well as the use of circulating tumor DNA in the surveillance setting. The current scientific landscape shows promising approaches that may further improve outcomes for patients with locally advanced non–small-cell lung cancer.

scholarly journals Concomitant driver mutations in advanced EGFR-mutated non-small-cell lung cancer and their impact on erlotinib treatment

Oncotarget ◽  
2018 ◽  
Vol 9 (40) ◽  
pp. 26195-26208 ◽  
Author(s):  
Jan Nyrop Jakobsen ◽  
Eric Santoni-Rugiu ◽  
Morten Grauslund ◽  
Linea Melchior ◽  
Jens Benn Sørensen
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Egfr Mutated

scholarly journals Efficacy and safety of PD-1/PD-L1 inhibitors plus nab-paclitaxel for patients with non-small cell lung cancer who have progressed after platinum-based chemotherapy

2020 ◽  
Vol 12 ◽  
pp. 175883592093688
Author(s):  
Fan Zhang ◽  
Di Huang ◽  
Lei Zhao ◽  
Tao Li ◽  
Sujie Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Monotherapy Group ◽  
Small Cell Lung ◽  
Metastatic Nsclc ◽  
Platinum Based Chemotherapy ◽  
Paclitaxel Group ◽  
Nsclc Patients

Background: Immunotherapy combined with platinum-based chemotherapy is now the standard first-line treatment for non-small cell lung cancer (NSCLC) patients. However, limited evidence exists to show the efficacy of immunotherapy plus taxanes for patients who have progressed after platinum-based chemotherapy. Methods: The immunotherapy naïve patients with metastatic NSCLC who received anti-PD-1/PD-L1 monotherapy or combined with nab-paclitaxel after prior platinum-based chemotherapy from 2015 to 2018 in PLA General Hospital were identified. The progression-free survival, overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety were assessed. Results: Of 57 patients, 40 were treated with anti-PD-1/PD-L1 monotherapy and 17 were treated with anti-PD-1/PD-L1 plus nab-paclitaxel. With a median OS follow-up of 16.3 months, the nab-paclitaxel group showed significantly longer OS compared with the immune monotherapy group (median, 28.6 months versus 15.9 months, log-rank p = 0.020). When adjusted by covariates in COX proportional regression model, both the treatment group [ p = 0.009, hazard ratio (HR) 0.361; 95% confidence interval (CI) 0.168–0.773] and performance status ( p = 0.003, HR 0.372; 95% CI 0.192–0.721) demonstrated independent association with the longer OS from combination therapy. In addition, ORR was 23.5% (4/17) in the immune checkpoints inhibitors (ICIs) plus nab-paclitaxel group versus 13.5% (5/37) in immune monotherapy group ( p = 0.439), with a DCR of 88.2% (15/17) and 59.5% (22/37) ( p = 0.034), respectively. The incidence of grade 3/4 adverse events was 23.5% (4/17) in the combination group and 2.5% (1/40) in the immune monotherapy group. Conclusion: PD-1/PD-L1 inhibitor plus nab-paclitaxel resulted in significantly longer OS and higher response versus ICI single agent in metastatic NSCLC patients who have progressed after platinum-based chemotherapy. These findings need to be further explored by prospective studies.

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