scholarly journals Dual TMPRSS2:ERG Fusion in a Patient with Lung and Prostate Cancers

Diagnostics ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1109
Author(s):  
Francesca Giunchi ◽  
Francesco Massari ◽  
Annalisa Altimari ◽  
Elisa Gruppioni ◽  
Elisabetta Nobili ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Objective Response ◽  
Lung Nodule ◽  
Thoracic Wall ◽  
Lung Cancers ◽  
Molecular Alterations ◽  
First Case ◽  
Prostate Cancers ◽  
Cancer Of The Prostate ◽  
Antiandrogen Therapy

The TMPRSS2:ERG fusion is considered prostate specific and has been rarely described in other tumors. We describe the case of a patient who developed lung and prostate cancers, both harboring the TMPRSS2:ERG fusion. The patient developed a cancer of the prostate with lymph node metastases and after two years a nodule of the thoracic wall. The histology and immunohistochemical profile of the two tumors were typical of prostate and lung cancers. The presence of the TMPRSS2:ERG fusion was demonstrated by next-generation sequencing on both malignancies, leading to the assumption that the lung nodule was a metastasis from the prostate cancer. The patient failed to respond to antiandrogen therapy, while chemotherapy for lung cancer led to a significant objective response. To our knowledge, this is the first case of a lung cancer harboring the TMPRSS2:ERG fusion, widening the spectrum of lung cancer-associated molecular alterations.

scholarly journals Other cancers in lung cancer families are overwhelmingly smoking-related cancers

2017 ◽  
Vol 3 (2) ◽  
pp. 00006-2017 ◽  
Author(s):  
Hongyao Yu ◽  
Christoph Frank ◽  
Akseli Hemminki ◽  
Kristina Sundquist ◽  
Kari Hemminki
Keyword(s):  
Lung Cancer ◽  
Unknown Primary ◽  
Upper Aerodigestive Tract ◽  
Lung Cancers ◽  
Lung Cancer Patients ◽  
Relative Risks ◽  
Novel Approach ◽  
Cancer Clusters ◽  
Familial Relative Risk ◽  
Prostate Cancers

Familial risks of lung cancer are well-established, but whether lung cancer clusters with other discordant cancers is less certain, particularly beyond smoking-related sites, which may provide evidence on genetic contributions to lung cancer aetiology.We used a novel approach to search for familial associations in the Swedish Family-Cancer Database. This involved assessment of familial relative risk for cancer X in families with increasing numbers of lung cancer patients and, conversely, relative risks for lung cancer in families with increasing numbers of patients with cancers X. However, we lacked information on smoking.The total number of lung cancers in the database was 125 563. We applied stringent statistical criteria and found that seven discordant cancers were associated with lung cancer among family members, and six of these were known to be connected with smoking: oesophageal, upper aerodigestive tract, liver, cervical, kidney and urinary bladder cancers. A further novel finding was that cancer of unknown primary also associated with lung cancer. We also factored in histological evidence and found that anal and connective tissue cancers could be associated with lung cancer for reasons other than smoking. For endometrial and prostate cancers, suggestive negative associations with lung cancer were found.Although we lacked information on smoking it is prudent to conclude that practically all observed discordant associations of lung cancer were with cancers for which smoking is a risk factor.

Safety of retreatment with immunotherapy after immune-related toxicity in patients with lung cancers treated with anti-PD(L)-1 therapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9012-9012 ◽  
Author(s):  
Fernando Costa Santini ◽  
Hira Rizvi ◽  
Olivia Wilkins ◽  
Martine van Voorthuysen ◽  
Elizabeth Panora ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Disease Progression ◽  
Early Onset ◽  
Objective Response ◽  
Treatment Delay ◽  
Subsequent Treatment ◽  
Lung Cancers ◽  
Grade 3 ◽  
The One

9012 Background: Anti-PD(L)-1 therapy is generally well tolerated, but immune-related adverse events (irAEs) can occur. No data currently exists to guide decisions related to considering re-treatment following an irAE. Methods: Patients (pts) with lung cancer treated with anti-PD(L)-1 (+/- anti-CTLA-4) between 4/2011 to 5/2016 who had a treatment delay of at least one week were identified. Those in whom delay was a result of a definite irAE were included, and subsequent treatment details and outcomes were captured. Pts with an irAE concurrent with disease progression were excluded. Results: Among 482 pts treated, 71 (14.7%) had treatment delay related to an irAE. Most events were Grade 2 (38/71, 54%) or Grade 3 (30/71, 42%), and predominantly included pneumonitis (21%), colitis (17%), rash (14%), or hepatitis (13%). 32 pts (45%) were permanently discontinued after the irAE and 39 (55%) were later retreated with anti-PD(L)-1 therapy. In retreated pts, the same irAE recurred in 10/39 (26%), a new irAE occurred in 9/39 (23%), and 20/39 (51%) had no subsequent irAE. The rate of recurrent/new irAEs was similar in those with Grade 3 compared to Grade 2 irAEs (p = 1.0), but were more common following initial irAE that occurred early ( < 3 months) compared to later (≥3 months) in treatment course (16/24 [67%] vs 3/15 [20%], p = 0.0079). The rate of recurrent/new irAE was 33% (2/6) in those with pneumonitis, 40% (2/5) with rash, 57% (4/7) with colitis, and 80% (4/5) with arthralgia. Recurrent/new irAEs were successfully managed with immunosuppression in 17/19 (90%) pts. However, 2 pts died, both related to a new irAE different from the one initially experienced. Of the pts retreated, 3 (8%) had onset of objective response to anti-PD(L)-1 therapy following resumption of treatment. Conclusions: In pts who develop irAEs and improve, re-treatment with anti-PD(L)-1 therapy was associated with recurrent or new irAEs in half of pts, and was more common in early-onset irAEs. The majority of the pts with recurrent/new irAEs were managed successfully, but two deaths occured. Few objective responses occurred following retreatment.

Correlation of microsatellite-instable (MSI) status and genomic characteristics in 12,000 Chinese lung cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21019-e21019
Author(s):  
Liufu Su ◽  
Xinyi Liu ◽  
Xiaochun Huang ◽  
Mengli Huang
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Large Scale ◽  
Objective Response ◽  
The Other ◽  
Egfr Mutations ◽  
Molecular Characteristics ◽  
Genetic Profile ◽  
Lung Cancers ◽  
Lung Cancer Patients

e21019 Background: Microsatellite-instable-high (MSI-H) is a strong biomarker for favorable response to immune checkpoint blockade (ICI) therapies. The objective response rate was 30%̃40% in advanced MSI-H solid tumors receiving ICI treatment, while MSI status is rarely considered in lung cancer in setting of ICI treatment. MSI-H occurred in 0.8%̃2% lung cancer patients tested by PCR method. Immune microenvironment of MSI-H lung cancer had not been studied on a large scale. We explored the association of MSI status, genetic profile and PD-L1 expression in a large Chinese lung cancer cohort to elucidate the molecular characteristics of MSI-H lung cancer. Methods: MSI status was determined by PCR test in tumor tissue and by an in-house algorithm in blood specimen. The tumor samples were sequenced by next-generation sequencing to call single nucleotide variants (SNVs) and copy number variants (CNVs). PD-L1 expression was evaluated by TPS. Results: 67 pts were determined as MSI-H in total of 12,485 pts, namely the frequency of MSI-H was 0.5% in Chinses lung cancer. 26 MSI-H pts were harboring EGFR mutations, including Ex19del in 10 pts, L858R in 6 pts, T790M in 5 pts, EGFR gain in 4 pts, and other uncommon mutations such as C797, L861Q. Interestingly, no EGFR Ex20ins was detected. In the other 41 non-EGFR-mutant pts, RET fusion were detected in 2 pts, FGFR2/3 SNV were detected in 5 pts, KRAS activating SNVs were detected in 5 pts, and PIK3CA SNV/amplification were detected in 8 pts. No ICI response negative alterations (CDKN2A/B loss, MDM2/4 gain) were detected in MSI-H patients. 125 genes, including MSH6, MLH1, BRCA2, NOTCH1, TGFBR2, ACVR2A and etc, had higher frequency in MSI-H lung cancers than MSS lung cancers in our cohort. Moreover, only MAP3K1 gene SNV occurred more frequently in MSS lung cancers (4.5% vs 7.7%, p < 0.001). MSI-H lung cancer had a trend for enrichment of PD-L1 positivity (TPS > 1%) but no significance (58% vs 43%, p = 0.205). Conclusions: About 50% MSI-H lung cancers harbored actionable mutations for targeted agents (EGFR TKIs or other TKIs), while EGFR Ex20ins might exist mutually exclusively with MSI-H. MSI-H lung cancer had much more mutational genes than MSS lung cancer, which was consistent with previous studies. On the other hand, MAP3K1 was the only gene with lower mutational frequency in MSI-H lung cancer. Our results revealed the genetic mutational characteristics of MSI-H lung cancer and provided suggestions for treatment decisions of this patient population.

scholarly journals Immunotherapy in Non-Small Cell Lung Cancer With Actionable Mutations Other Than EGFR

2021 ◽  
Vol 11 ◽  
Author(s):  
Karan Seegobin ◽  
Umair Majeed ◽  
Nathaniel Wiest ◽  
Rami Manochakian ◽  
Yanyan Lou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Standard Of Care ◽  
Small Cell ◽  
Published Data ◽  
Small Cell Lung ◽  
Current Standard ◽  
Lung Cancers

While first line targeted therapies are the current standard of care treatment for non-small cell lung cancer (NSCLC) with actionable mutations, the cancer cells inevitably acquire resistance to these agents over time. Immune check-point inhibitors (ICIs) have improved the outcomes of metastatic NSCLC, however, its efficacy in those with targetable drivers is largely unknown. In this manuscript, we reviewed the published data on ICI therapies in NSCLC with ALK, ROS1, BRAF, c-MET, RET, NTRK, KRAS, and HER2 (ERBB2) alterations. We found that the objective response rates (ORRs) associated with ICI treatments in lung cancers harboring the BRAF (0–54%), c-MET (12–49%), and KRAS (18.7-66.7%) alterations were comparable to non-mutant NSCLC, whereas the ORRs in RET fusion NSCLC (less than10% in all studies but one) and ALK fusion NSCLC (0%) were relatively low. The ORRs reported in small numbers of patients and studies of ROS1 fusion, NTRK fusion, and HER 2 mutant NSCLC were 0–17%, 50% and 7–23%, respectively, making the efficacy of ICIs in these groups of patients less clear. In most studies, no significant correlation between treatment outcome and PD-L1 expression or tumor mutation burden (TMB) was identified, and how to select patients with NSCLC harboring actionable mutations who will likely benefit from ICI treatment remains unknown.

scholarly journals Lung Cancer: A Classic Example of Tumor Escape and Progression While Providing Opportunities for Immunological Intervention

2012 ◽  
Vol 2012 ◽  
pp. 1-21 ◽  
Author(s):  
Martin R. Jadus ◽  
Josephine Natividad ◽  
Anthony Mai ◽  
Yi Ouyang ◽  
Nils Lambrecht ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Escape ◽  
Newly Diagnosed ◽  
Hallmarks Of Cancer ◽  
Lung Cancers ◽  
Defensive Strategies ◽  
The World ◽  
History Of ◽  
Prostate Cancers ◽  
Castrate Resistant

Lung cancers remain one of the most common and deadly cancers in the world today (12.5% of newly diagnosed cancers) despite current advances in chemo- and radiation therapies. Often, by the time these tumors are diagnosed, they have already metastasized. These tumors demonstrate the classic hallmarks of cancer in that they have advanced defensive strategies allowing them to escape various standard oncological treatments. Immunotherapy is making inroads towards effectively treating other fatal cancers, such as melanoma, glioblastoma multiforme, and castrate-resistant prostate cancers. This paper will cover the escape mechanisms of bronchogenic lung cancer that must be overcome before they can be successfully treated. We also review the history of immunotherapy directed towards lung cancers.

scholarly journals Sarcoidosis and Lung Cancer

2010 ◽  
Vol 53 (2) ◽  
pp. 115-118 ◽  
Author(s):  
Naohiro Kobayashi ◽  
Ryota Nakamura ◽  
Koichi Kurishima ◽  
Yukio Sato ◽  
Hiroaki Satoh
Keyword(s):  
Lung Cancer ◽  
Differential Diagnosis ◽  
Cancer Patients ◽  
Epithelioid Cell ◽  
Lung Cancers ◽  
Lung Cancer Patients ◽  
Sarcoid Reaction ◽  
The Third ◽  
First Case ◽  
Systemic Sarcoidosis

Background: Although sarcoidosis as well as lung cancer are frequently encountered common diseases, their metachronous or synchronous occurrence in the same patient is very rare. Methods: The charts of lung cancer patients, diagnosed between 1980 and 2007 in our hospital, were reviewed. Results: We found 3 cases with sarcoidosis and lung cancer. The first case had lung cancer 16 years after the diagnosis of sarcoidosis. The second case had two different metachronous lung cancers 18 and 10 years after the diagnosis of sarcoidosis. The third case detected these two diseases simultaneously. In simultaneously detected cases, it is difficult to determine whether noncaseating epithelioid cell granulomas coexisting with lung cancer represent sarcoid reaction or genuine systemic sarcoidosis. Conclusions: Either causality or coincidence, lung cancer, a condition that can be observed in patients with sarcoidosis, should be considered in the differential diagnosis when suspicious findings of it are discovered.

scholarly journals Association between lung cancer somatic mutations and occupational exposure in never-smokers

2017 ◽  
Vol 50 (4) ◽  
pp. 1700716 ◽  
Author(s):  
Christophe Paris ◽  
Pascal Do ◽  
Bénédicte Mastroianni ◽  
Adrien Dixmier ◽  
Patrick Dumont ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Risk Factor ◽  
Occupational Exposure ◽  
Lung Cancers ◽  
Molecular Alterations ◽  
Molecular Pattern ◽  
Exhaust Fumes ◽  
Polycyclic Aromatic ◽  
Never Smokers ◽  
Molecular Patterns

Occupational exposure constitutes a common risk factor for lung cancer. We observed molecular alterations in 73% of never-smokers, 35% of men and 8% of women were exposed to at least one occupational carcinogen. We report herein associations between molecular patterns and occupational exposure.BioCAST was a cohort study of lung cancer in never-smokers that reported risk factor exposure and molecular patterns. Occupational exposure was assessed via a validated 71-item questionnaire. Patients were categorised into groups that were unexposed and exposed to polycyclic aromatic hydrocarbons (PAH), asbestos, silica, diesel exhaust fumes (DEF), chrome and paints. Test results were recorded for EGFR, KRAS, HER2, BRAF and PIK3 mutations, and ALK alterations.Overall, 313 out of 384 patients included in BioCAST were analysed. Asbestos-exposed patients displayed a significantly lower rate of EGFR mutations (20% versus 44%, p=0.033), and a higher rate of HER2 mutations (18% versus 4%, p=0.084). ALK alterations were not associated with any occupational carcinogens. The DEF-exposed patients were diagnosed with a BRAF mutation in 25% of all cases. Chrome-exposed patients exhibited enhanced HER2 and PIK3 mutation frequency.Given its minimal effects in the subgroups, we conclude that occupational exposure slightly affects the molecular pattern of lung cancers in never-smokers. In particular, asbestos-exposed patients have a lower chance of EGFR mutations.

Lung cancer diagnosed by an incidental lung nodule program or lung cancer screening.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8546-8546
Author(s):  
Matthew Smeltzer ◽  
Walter Stevens ◽  
Nicholas Ryan Faris ◽  
Jennifer Kethireddy ◽  
Meghan Brooke Meadows ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Screening ◽  
Early Detection ◽  
Proportional Hazards ◽  
Smoking Status ◽  
Lung Nodule ◽  
Lung Cancer Screening ◽  
Eligibility Criteria ◽  
Curative Intent ◽  
Lung Cancers

8546 Background: Early detection reduces lung cancer (LC) mortality. We prospectively evaluated LC patients diagnosed through Lung Cancer Screening (LCS) or an Incidental Lung Nodule Program (ILNP) (‘early detection’ programs) compared to routinely diagnosed LC patients in a multidisciplinary program (MDP). Methods: We compare demographics, tumor characteristics, and survival between the three groups diagnosed within the same healthcare system from 2015-2018. The ILNP prospectively tracks patients with suspicious lung lesions on routinely-performed studies flagged by radiologists using a standard macro text. LCS used Medicare eligibility criteria. Statistical methods include the chi-square test, Kruskal-Wallis test, and proportional hazards models with hazard ratios (HR) and 95% confidence intervals. Results: ILNP detected 201 lung cancers from 4713 scans (4.3%), LCS yielded 35 lung cancers from 1540 low-dose CT scans (2.3%), while MDC had 926 LC cases not detected by LCS or ILNP. Mean age at diagnosis for ILNP/LCS/MDC was 70/69/67 years (p = 0.0083); African Americans were under-represented in LCS (25%/11%/32%, p = 0.0104). LCS had the highest proportion with commercial insurance (46%/54%/43%, p = 0.3442). Early detection groups were more likely to have adenocarcinoma histology (ILNP/LCS/MDC: 61%/57%/49%, p = 0.0113). Smoking exposure was highest in LCS cohort (mean pack years: 48/64/52, p = 0.0500); 11% of ILNP, 8% MDC patients were never-smokers. Only 36% ILNP and 39% MDC patients were eligible for LCS by NLST criteria and 30%/40% by NELSON criteria. Reasons for ineligibility included smoking status in 73-90% and age in 7-27% of patients. Stage I/II distribution was (66%/58%/21%, p < 0.0001), stage IV 15%/20%/36%; surgical resection rates were (56%/55%/31%, p < 0.0001). Overall survival was longer in early detection groups (LCS HR: 0.31 [0.11,0.82]; ILNP HR: 0.51[0.33,0.81]) compared to MDC (p = 0.0011). Conclusions: The majority of LC patients were ineligible for LCS, but the ILNP identified LC in a high proportion of such patients, with similar stage re-distribution, curative-intent treatment, and survival rates. Structured ILNP complement LCS for early LC detection, such programs need to be built out.

LUNGRADS AND UPDATE OF LUNG NODULES SCREENING BY LOW DOSE COMPUTED TOMOGRAPHY

2015 ◽  
pp. 12-19
Author(s):  
Thi Ngoc Ha Hoang ◽  
Trong Khoan Le
Keyword(s):  
Lung Cancer ◽  
Low Dose ◽  
False Negative ◽  
Lung Nodule ◽  
Lung Cancer Mortality ◽  
Smoking History ◽  
Low Dose Ct ◽  
History Of ◽  
Chest X Ray ◽  
Low Dose Computed Tomography

Background: A pulmonary nodule is defined as a rounded or irregular opacity, well or poorly defined, measuring up to 3 cm in diameter. Early detection the malignancy of nodules has a significant role in decreasing the mortality, increasing the survival time and consider as early diagnosis lung cancer. The main risk factors are those of current or former smokers, aged 55 to 74 years with a smoking history of at least 1 pack-day. Low dose CT: screening individuals with high risk of lung cancer by low dose CT scans could reduce lung cancer mortality by 20 percent compared to chest X-ray. Radiation dose has to maximum reduced but respect the rule of ALARA (As Low as Resonably Archivable). LungRADS 2014: Classification of American College of Radiology, LungRADS, is a newly application but showed many advantages in comparison with others classification such as increasing positive predict value (PPV), no result of false negative and cost effectiveness. Key words: LungRADS, screening lung nodule, low dose CT, lung cancer

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