Thymidylate synthase polymorphisms and immunohistochemistry in non-small cell lung cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11101-11101
Author(s):  
J. Stoehlmacher ◽  
E. Goekkurt ◽  
G. Hoeffken ◽  
R. Zinsky ◽  
F. Lynch ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Cell Lung Cancer ◽  
Staining Intensity ◽  
Small Cell ◽  
Small Cell Lung ◽  
Histological Subtypes ◽  
Group A ◽  
Group B

11101 Background: Recently, pemetrexed has been introduced into the treatment of non-small cell lung cancer (NSCLC). There's evidence that pemetrexed appears to be more efficient in non squamous NSCLC including adenocarcinoma (AC) and large cell carcinoma (LCC). TS represents a major target enzyme of pemetrexed. We evaluated the expression of TS among different histological types of NSCLC and its association with functional genetic polymorphisms of the TS gene. Methods: Archived tumor samples from 312 individuals with NSCLC were analyzed. Immunohistochemistry (IHC) was performed using a mouse monoclonal antibody to TS. TS stained sections were scored for cytoplasmic and nuclear localization. For each compartment, the tumor was evaluated for the estimated percentage of positive cells with the greatest intensity within the tumor. Intensity was scored on a scale of 0–4. A score of 3–4 was classified as high expression. Genotyping of TS-VNTR including the G/C SNP and TS1394del6 was performed by PCR based RFLP techniques. Genotypes supposed to be associated with low expression were grouped (group A: 2R/2R or 2R/3RC or 3RC/3RC + -6/-6) and compared to genotype groups associated with high expression (group B: 2R/3RG or 3RC/3RG or 3RG/3RG + -6/+6 or +6/+6). Results: IHC and polymorphisms could be performed successfully in 312 (100%) and 287 (92%), respectively. Distribution of histology was as follows: 50% AC, 42% squamous cell carcinoma (SCC), 3% LCC and 5% mixed or other histological subtypes. Group B genotypes were significantly more present in SCC than in AC (49% vs 23%, p=.002). Tumors with group B genotypes were more likely to display high nuclear staining intensity than group A tumors (30% vs. 17%, p=.077). A similar but not significant trend was seen for cytoplasmic staining intensity. There was no significant difference between histological subtypes of NSCLC with respect to TS protein expression. AC were more common than SCC to show a G1 differentiated tumors (8% vs 1%, p<.001). No difference between genotype groups were observed with respect to grading. Conclusions: TS polymorphisms are significantly associated with histology subtypes in NSCLC. These results represent a potential explanation for efficacy differences of pemetrexed in NSCLC and warrants further investigations. [Table: see text]

The association between STK11/LKB1 and/or KEAP1 mutations and response to PD-1/PD-L1 inhibitors in patients with advanced non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21538-e21538
Author(s):  
Meagan Elizabeth Miller ◽  
Meera Patel ◽  
Sandra K. Althouse ◽  
Nasser H. Hanna ◽  
Hirva Mamdani
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Concurrent Chemotherapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Disease Characteristics ◽  
Clinical Databases ◽  
Group A ◽  
Group B

e21538 Background: Advanced non-small cell lung cancer (NSCLC) patients with tumors harboring STK11/LKB1 or KEAP1 mutations have inferior treatment outcomes when treated with PD-1/PD-L1 blockade, regardless of KRAS status, PD-L1 score, or TMB score (Skoulidis et al, Cancer Discovery 2018, ASCO abstract 102, 2019). Methods: Retrospective clinical databases from Indiana University and Karmanos Cancer Institute were queried to identify patients from 2008-2019 with advanced NSCLC treated with PD-1/PD-L1 monotherapy (group A) or concurrent chemotherapy + PD-1/PD-L1 inhibitors (group B) whose tumors harbored STK11/LKB1 and/or KEAP1 mutations. Patients were characterized by best response, progression of disease (PD) or non-PD (complete response (CR) + partial response (PR) + stable disease (SD)). Patient and disease characteristics, response, and duration of response (> vs. < 6 months) were recorded. Results: A total of 77 patients met the above criteria (55 in group A, 22 in group B). 52 of 55 patients in group A received prior chemo. Patient and disease characteristics and outcomes are summarized in the table. Conclusions: STK11/LKB1 and/or KEAP1 mutations are independent of PD-L1/TMB status, although most patients had PD-L1 of <1%. Nearly ½ of patients with STK11/LKB1 and/or KEAP1 mutations achieve at least SD with PD-1/PD-L1 inhibitor monotherapy and more than 50% of those with non-PD maintain that response status for > 6 mos. The frequency and duration of non-PD in this population is higher in patients receiving chemotherapy + PD-1/PD-L1 concomitantly. [Table: see text]

Paclitaxel Plus Carboplatin Versus Gemcitabine Plus Paclitaxel in Advanced Non–Small-Cell Lung Cancer: A Phase III Randomized Trial

2002 ◽  
Vol 20 (17) ◽  
pp. 3578-3585 ◽  
Author(s):  
Paris Kosmidis ◽  
Nick Mylonakis ◽  
Costas Nicolaides ◽  
Charalabos Kalophonos ◽  
Epaminontas Samantas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Response Rate ◽  
Randomized Study ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Group A ◽  
Group B

PURPOSE: We conducted this randomized study comparing the activity and toxicity of paclitaxel and gemcitabine (PG) and paclitaxel and carboplatin (PC) combinations for the treatment of advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients were randomized to paclitaxel 200 mg/m2 on day 1 plus either carboplatin at an area under the concentration-time curve of 6 on day 1 (group A) or gemcitabine 1,000 mg/m2 on days 1 and 8 (group B) every 3 weeks. A retrospective cost analysis was conducted using Student’s t test to compare independent samples between groups. RESULTS: A total of 509 patients (group A, 252 patients; group B, 257 patients) were enrolled; all characteristics were well balanced. The median survival time was 10.4 months (95% confidence interval [CI], 8.8 to 12 months) for group A and 9.8 months (95% CI, 8.0 to 11.7 months) for group B (P = .32). Respective 1-year survival rates were 41.7% and 41.4%. The response rate for group A was 28.0% (2% complete response [CR], 26% partial response [PR] [95% CI, 22% to 34%]), and the response rate for group B was 35.0% (5% CR, 30% PR) [95% CI, 29% to 41%]) (P = .12). Toxicity was mild. Grades 3/4 neutropenia, thrombocytopenia, and anemia for groups A and B were seen in 15% and 15%, 2% and 1%, and 5% and 2%, respectively. The mean total cost (outpatient clinic visits plus chemotherapy drug fee) for group A (€ 7,612.64) versus group B (€ 7,484.77) was not statistically significant (P < .66). CONCLUSION: The PG combination is as equally active and well tolerated as the PC combination in patients with advanced NSCLC.

A re-evaluation of squamous cell carcinoma antigen (SCC) as a serum marker for non-small cell lung cancer

2007 ◽  
Vol 25 (2) ◽  
pp. 187-189 ◽  
Author(s):  
Katsunori Kagohashi ◽  
Hiroaki Satoh ◽  
Hiroichi Ishikawa ◽  
Morio Ohtsuka ◽  
Kiyohisa Sekizawa
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Serum Marker ◽  
Small Cell ◽  
Squamous Cell Carcinoma Antigen ◽  
Small Cell Lung

scholarly journals Epidemiologic trends in lung cancer over two decades in Northern Greece: an analysis of bronchoscopic data

2016 ◽  
Vol 71 (4) ◽  
Author(s):  
T. Kontakiotis ◽  
N. Manolakoglou ◽  
F. Zoglopitis ◽  
D. Iakovidis ◽  
L. Sacas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Northern Greece ◽  
Female Ratio

Background and Aim. The relative frequency of histological subtypes of lung cancer in Europe has changed dramatically during the 20th century. The aim of this study was to explore the changing epidemiology of lung cancer in Northern Greece over the last two decades. Methods. From the extensive database of the Bronchoscopy Unit of the G. Papanicolaou General Hospital, Thessaloniki, Greece, we identified all patients with a histologic and/or cytologic report positive for lung cancer over two consecutive decades. Results. Between 1/1/1986 and 31/12/2005 we identified 9981 patients with specimens positive for lung cancer. A significant increase in mean patient age was observed during the second decade (64.8±9.4 vs. 62.1±8.9, p=0.001). Men developed lung cancer ten times more often than women. The predominant histological type was squamous cell cancer in males (4203 cases, 45.7%) and adenocarcinoma (418 cases, 52.6%) in females. The number of lung cancer cases was significantly higher during the second decade compared to the first decade (5766 cases [57.8%] vs. 4215 cases [42.2%], respectively, p&lt;0.001). There was a significant decrease in the percentage of squamous cell carcinoma in males in the second decade (2317 cases [44.1%] vs. 1886 cases [48.0%], p&lt;0.001), and an increase in adenocarcinoma (1021 cases [19.4%] vs. 609 [11.6%], p&lt;0.001). In females, the relative incidence of adenocarcinoma was decreased and that of squamous cell carcinoma was increased, but not significantly. There was no obvious change in the incidence of small cell lung cancer. Neoplastic lesions were most often located in the upper lobes. Conclusion. The number of lung cancer cases has increased in the last decade. Squamous lung cancer appears to be decreasing in men and increasing in women. Adenocarcinoma appears to be increasing in men and decreasing in women. There appears to be no change in small cell lung cancer. During the second decade there has been a significant decrease in the male: female ratio.

scholarly journals Predictors of immunotherapy-induced immune-related adverse events

2018 ◽  
Vol 25 (5) ◽  
Author(s):  
A. Kartolo ◽  
J. Sattar ◽  
V. Sahai ◽  
T. Baetz ◽  
J. M. Lakoff
Keyword(s):  
Lung Cancer ◽  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Cell Lung Cancer ◽  
Renal Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
Goodness Of Fit Test

Purpose We aimed to elucidate predictive factors for the development of immune-related adverse events (iraes) in patients receiving immunotherapies for the management of advanced solid cancers.Methods This retrospective study involved all patients with histologically confirmed metastatic or inoperable melanoma, non-small-cell lung cancer, or renal cell carcinoma receiving immunotherapy at the Cancer Centre of Southeastern Ontario. The type and severity of iraes, as well as potential protective and exacerbating factors, were collected from patient charts.ResultsThe study included 78 patients receiving ipilimumab (32%), nivolumab (33%), or pembrolizumab (35%). Melanoma, non-small-cell lung cancer, and renal cell carcinoma accounted for 70%, 22%, and 8% of the cancers in the study population. In 41 patients (53%) iraes developed, with multiple iraes developing in 12 patients (15%). In most patients (70%), the iraes were of severity grade 1 or 2. Female sex [adjusted odds ratio (oradj): 0.094; 95% confidence interval (ci): 0.021 to 0.415; p = 0.002] and corticosteroid use before immunotherapy (oradj: 0.143; 95% ci: 0.036 to 0.562; p = 0.005) were found to be associated with a protective effect against iraes. In contrast, a history of autoimmune disease (oradj: 9.55; 95% ci: 1.34 to 68.22; p = 0.025), use of ctla-4 inhibitors (oradj: 6.25; 95% ci: 1.61 to 24.25; p = 0.008), and poor kidney function of grade 3 or greater (oradj: 10.66; 95% ci: 2.41 to 47.12; p = 0.025) were associated with a higher risk of developing iraes. A Hosmer–Lemeshow goodness-of-fit test demonstrated that the logistic regression model was effective at predicting the development of iraes (chi-square: 1.596; df = 7; p = 0.979).Conclusions Our study highlights several factors that affect the development of iraes in patients receiving immunotherapy. Although future studies are needed to validate the resulting model, findings from the study can help to guide risk stratification, monitoring, and management of iraes in patients given immunotherapy for advanced cancer.

Non-Small Cell Lung Cancer with Ipsilateral Intrapulmonary Metastasis

2000 ◽  
Vol 8 (2) ◽  
pp. 141-145
Author(s):  
Mitsuhiro Kamiyoshihara ◽  
Osamu Kawashima ◽  
Shuji Sakata ◽  
Susumu Ishikawa ◽  
Yasuo Morishita
Keyword(s):  
Lung Cancer ◽  
Lymph Node ◽  
Blood Vessel ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Pulmonary Metastasis ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Blood Vessel Invasion ◽  
Small Cell Lung

From 1981 through 1997, lobectomy or pneumonectomy with mediastinal lymph node dissection was performed in 604 patients with non-small cell lung cancer, of whom 42 (7%) were diagnosed as having ipsilateral pulmonary metastasis. There were 23 males and 19 females, the mean age was 66 years. Lobectomy was carried out in 37 cases and pneumonectomy in 5. Postoperative histology identified 29 adenocarcinomas, 11 squamous cell carcinomas, 1 large cell carcinoma, and 1 adenosquamous cell carcinoma. Two cases were classified as pathologic stage I, 1 as stage II, 26 as IIIA, and 13 as IIIB. Blood vessel invasion was present in 33 cases and absent in 2 cases. Five and 10-year survival rates were 34.3% and 17.1%, respectively. Patients with pulmonary metastasis had a poorer prognosis than those without metastasis; there were local recurrences in 6 patients, distant metastases in 9, and 15 deaths. There were no significant differences in recurrence sites between patients with and without pulmonary metastasis. Multivariate analysis showed that lymph node involvement and blood vessel invasion were useful prognostic factors. Ipsilateral pulmonary metastasis in the same lobe was regarded as local invasion for which surgical resection is the optimal treatment.

scholarly journals Mutation profile of non-small cell lung cancer revealed by next generation sequencing

2020 ◽  
Author(s):  
Ya-Sian Chang ◽  
Siang-Jyun Tu ◽  
Yu-Chia Chen ◽  
Ting-Yuan Liu ◽  
Ya-Ting Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Small Cell ◽  
Small Cell Lung ◽  
Whole Exome

Abstract Background: Precision therapy for lung cancer requires comprehensive genomic analyses. Specific effects of targeted therapies have been reported in Asia populations, including Taiwanese, but genomic studies have rarely been performed in these populations. Method: We enrolled 72 patients with non-small cell lung cancer, of whom 61 had adenocarcinoma, 10 had squamous cell carcinoma, and 1 had combined adenocarcinoma and squamous cell carcinoma. Whole-exome or targeted gene sequencing was performed. To identify trunk mutations, we performed whole-exome sequencing in two tumor regions in four patients. Results: Nineteen known driver mutations in EGFR, PIK3CA, KRAS, CTNNB1, and MET were identified in 34 of the 72 tumors evaluated (47.22%). A comparison with the Cancer Genome Atlas dataset showed that EGFR was mutated at a much higher frequency in our cohort than in Caucasians, whereas KRAS and TP53 mutations were found in only 5.56% and 25% of our Taiwanese patients, respectively. We also identified new mutations in ARID1A, ARID2, CDK12, CHEK2, GNAS, H3F3A, KDM6A, KMT2C, NOTCH1, RB1, RBM10, RUNX1, SETD2, SF3B1, SMARCA4, THRAP3, TP53, and ZMYM2. Moreover, all ClinVar pathogenic variants were trunk mutations present in two regions of a tumor. RNA sequencing revealed that the trunk or branch genes were expressed at similar levels among different tumor regions.Conclusions: We identified novel variants potentially associated with lung cancer tumorigenesis. The specific mutation pattern in Taiwanese patients with non-small cell lung cancer may influence targeted therapies.

Sign in / Sign up

Export Citation Format

Share Document