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Background: The goal of the study was to evaluate the efficacy of tyrosine kinase inhibitors in patients with epidermal growth factor receptor (EGFR)-mutant metastatic non-small cell cancer and to determine the factors that predict objective response., Materials and Methods: In the study, data from metastatic non-small cell lung cancer patients with EGFR mutations treated with tyrosine kinase inhibitors were retrospectively reviewed. Factors predicting objective response were evaluated with logistic regression analysis., Results: The study evaluated the data of 105 patients. The most common EGFR mutations detected in patients were exon 19 (56.2%) and exon 21 (23.8%). The median progression-free survival (PFS) associated with EGFR tyrosine kinase inhibitors was 20.1 (95% confidence interval [CI], 13.4-26.7) months. The median overall survival (OS) in the post-metastasis period was found to be 30.8 (95% CI, 20.2-41.4) months. Five- and seven-year OS was determined as 28.7% and 22.9%, respectively. Factors predicting the objective response were analyzed. Presence of drug-related toxicity (P = 0.02), histopathologic type (P = 0.01), metastasis burden (P = 0.03), and EGFR mutation type (P = 0.04) were found to be statistically significant in multivariate analysis., Conclusions: In our study, we found that EGFR tyrosine kinase inhibitors are effective and safe. Better response to EGFR inhibitors was observed in the presence of drug-induced toxicity, adenocarcinoma histology, low metastasis burden, and exon 19 mutation., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

ALK (anaplastic lymphoma kinase) inhibitors may be used to treat patients with ALK mutant metastatic nonsmall cell cancer (NSCLC). This study aimed to investigate the factors affecting the patients response to treatment with ALK-positive metastatic NSCLC. Data of the patients were investigated retrospectively. Binary regression analysis was performed to evaluate response predictors of treatment. Furthermore, we determined the cut-off value of the ALK-positivity for objective response to the therapy using ROC analysis. A total of 68 patients were included in the research. The median overall survival was observed 39.2 months. The overall response rate was 66.2%. The ratio of ALK positivity (P = .02), gender (P = .04), and the total number of metastatic sites (P = .02) all were detected as predictors of the response to ALK inhibitor in binary regression analysis. ALK inhibitor type (P = .56), primary tumor location (P = .35), pathological subtype (P = .68), de-novo metastatic disease (P = .28), and age (P = .94) were not predictive indicators for response. The cut-off level of ALK positivity was found to be 33% in patients with an objective response. The real-life effectiveness of ALK inhibitors in NSCLC patients with ALK mutations was shown in this research. We determined that having less than 3 metastatic sites, having a high ALK positivity ratio, and being female were all good predictors of ALK inhibitor response., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Immune checkpoint inhibitors have taken an important place in the field of oncologic immunotherapy, especially for patients in whom conventional treatment regimens have failed. Nivolumab prevents programmed cell death 1 (PD-1) and programmed cell death ligand-1 (PD-L1) binding, resulting in blockage of the inhibitory signal and thus facilitating an immunologic antitumor response. Nivolumab has been shown to be effective in thoracic malignancies, including non-small cell lung cancer (NSCLC). Here is a case of 52-year male patient with metastatic lung adenocarcinoma progressing after 4 cycles of chemotherapy. We started nivolumab q2 weeks therapy. Firstly, his dyspnea relieved, carcinoembryonic antigen (CEA) and C-reactive protein (CRP) levels regressed, and then their levels remained constant at a stable level. Radiologically stable response was seen. Progression was seen after about one and half year. Patient died in a short time after progression. In conclusion, this observation provides a strong indication of the potential value of immune checkpoint inhibitors for the management of metastatic lung cancers.

Presently, there is no consensus regarding which chemotherapy regimen is best to administer with radiotherapy in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). Herein, our aim was to compare the outcome of patients treated with either etoposide-cisplatin (EP) or docetaxel-cisplatin (DP) in this curative setting.Patients treated with either EP or DP and concurrent radiotherapy from 2004 to2012 were identified and their detailed medical records and follow-up information were obtained for analysis in this retrospective study. Survival rates were compared using Cox proportional hazards regression models with adjustments for confounding parameters provided by propensity score methods.A total of 105 patients were treated with concurrent chemoradiotherapy for LA-NSCLC (stage IIB-IIIA-IIIB). The median ages were 54 years (range, 32-70 years) and 55 years (range, 37-73 years) in the EP (n = 50) and DP (n = 55) groups, respectively. The median follow-up time was 27 months (range, 1-132 months) in the EP group and 19 months (range, 1-96 months) in DP group. There was no significant difference in baseline clinicopathologic features including age, sex, performance status, histologic subtype, and clinical TNM stages between groups. In the univariate analysis, the median overall survival of patients treated with EP was higher than that of patients treated with DP (41 vs. 20 months, P = 0.003). Multivariate analysis further revealed a survival advantage with EP compared with DP (hazard ratio [HR], 0.46; 95% confidence interval: 0.25-0.83; P = 0.009). The toxicity profile of the 2treatment groups was similar except that pulmonary toxicity was higher in the DP group (grade 3-4: 0% vs. 6%, P = 0.024).Concurrent chemoradiotherapy with EP may provide more favorable outcomes than DP and with an acceptable safety profile., Competing Interests: The authors report no conflicts of interests.

Aims: Glutathione S-transferase P1 (GSTP1) plays an important role in cellular protection against oxidative stress and toxic chemicals. Polymorphisms within GSTP1 are associated with alterations in enzyme activity, which may lead to development of lung disease and cancer. In this study, we aimed to investigate the GSTP1 Ile105Val and Ala114Val polymorphisms in patients with small cell lung cancer (SCLC)., Patients/methods: GSTP1 Ile105Val polymorphism in exon 5 and GSTP1 Ala114Val polymorphism in exon 6 were determined by using polymerase chain reaction-restriction fragment length polymorphism techniques in 89 patients with SCLC and 108 control patients with chronic obstructive pulmonary disease (COPD). Genotype frequencies and cigarette smoking intensities were compared among SCLC and COPD patients., Results: There were significantly less SCLC patients with variant exon 6 genotypes than COPD patients (7.9% vs. 20.4%, p=0.007), while the number of patients with variant exon 5 genotypes were comparable among groups. SCLC and COPD patients with variant exon 6 genotype showed trends toward exhibiting reduced cigarette consumption., Conclusions: The variant GSTP1 exon 6 genotype might be conferring protection against SCLC development. Whether this effect is associated with exposure to cigarette smoking needs to be clarified.

Purpose: The aim of this study was to evaluate efficacy and feasibility of a combination of weekly docetaxel and cisplatin administered concomitantly with radiotherapy followed by surgery in addition to consolidation chemotherapy with docetaxel and cisplatin administered every 3 weeks in stage III non-small cell lung cancer (NSCLC)., Methods: A total of 31 histologically proven, locally advanced (stage IIIA-N2 = 9, stage IIIB-T4N0-2 = 22) NSCLC patients were investigated. After administration of 4-6 cycles of weekly docetaxel (20 mg/m(2)) and weekly cisplatin (20 mg/m(2)) concurrently with radiotherapy, patients underwent operation if their disease was appropriately downstaged. Combination chemotherapy with docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks was administered as a consolidation regimen. The treatment response, toxicity, time to progression (TTP) and overall survival (OS) were evaluated., Results: After concomitant chemoradiotherapy, complete response and partial response occurred in 16.1 and 67.7% of patients, respectively. Thirteen percentage of patients progressed on treatment, and 3.2% had stable disease. Grade 3-4 hematologic and skin toxicities did not occur, whereas 17.9% of them experienced grade 3-4 oesophageal toxicity. Grade 3 pulmonary toxicity and grade 3-4 emesis developed in 9.7 and 6.4% of patients, respectively. Thirteen responsive patients (41.9%) underwent surgery. The toxicity of consolidation chemotherapy was tolerable. Median OS and TTP were 22 ± 5 (range 13-31) and 12 ± 3 (range 7-17) months, respectively. Median follow-up was 22 (range 2-57) months., Conclusions: Weekly administration of docetaxel and cisplatin concurrently with radiotherapy followed by consolidation chemotherapy is an effective treatment with acceptable toxicity for patients with locally advanced NSCLC especially in combination with surgery.

Aims and Background: It has been appreciated for some time that the lack of detection of ovarian cancer at clinical and pathological (second-look laparotomy) evaluation is not synonymous with cure. The goal of this study was to define clinical risk factors for recurrence after complete pathological response to postoperative chemotherapy in patients with epithelial ovarian cancer., Methods: Fifty-seven patients who met the inclusion criteria of our study were evaluated. The characteristics (age, menopausal status, histological subtype, tumor grade, presence of ascites at diagnosis, type of omentectomy, FIGO stage, and residual tumor volume after primary surgery) of patients with and those without tumor recurrence were compared., Results: The median follow-up was 52 months (range, 15-142 months). The overall survival rates of the patients were 100%, 96%, and 87% at 1, 3 and 5 years, respectively. At the time of the study analysis, 21 of 57 (37%) patients had recurrent disease. The median time to recurrence was 16 months. Recurrences were most frequent in the pelvis and abdominal cavity (38%). Age, menopausal status, stage at diagnosis, and residual tumor volume after initial surgery were significantly related to the risk of recurrence in univariate analysis (P = 0.039, 0.038, 0.004, and 0.000, respectively). Residual tumor volume after initial surgery was found to be the only significant independent prognostic factor (P = 0.049, HR: 0.16, 95% CI: 0.02-0.99)., Conclusion: We believe it is necessary to conduct randomized studies on this issue because insight into predictors of recurrence after pathological complete response to postoperative chemotherapy could be used to select patients for trials of consolidation therapy.

Objectives: Small cell lung cancer (SCLC) has a rapid growth rate and is characterized by early metastases. Tumor growth is dependent on angiogenesis. Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. Whether surveillance of pre- and post-treatment serum VEGF and especially its receptors VEGF-1 and VEGF-2 levels in SCLC patients have impact on clinical outcome is unknown., Methods: From February 2001 to January 2003, 39 consecutive patients with histological proven SCLC were enrolled into the study. Pre-treatment (n: 39) and post-treatment (n: 25) samples of the same patients were collected at the time of their response evaluation. The levels of VEGF and its receptors VEGFR-1 and VEGFR-2 were measured in the serum by quantitative sandwich enzyme immunoassay technique., Results: The median pre-treatment serum VEGF, VEGFR-1, and VEGFR-2 levels which were significantly higher than the normal controls were 1,200 pg/ml (range, 1,414.3 +/- 956.2 pg/ml), 85 pg/ml (range, 97.8 +/- 70.7 pg/ml), and 11,550 pg/ml (range, 14,481 +/- 6,267 pg/ml), respectively. We detected a poor but positive correlation between VEGF and VEGFR-2 (r: 0.46, p: 0.003). Pre-treatment low serum VEGF (<728.5 pg/ml) value (p: 0.02) and good response to treatment (p: 0.008) were found as good prognostic factors by multivariate analysis., Conclusions: Low serum VEGF concentration is a significant and independent prognostic factor in SCLC patients. Surveillance of VEGF and its receptors to predict chemotherapy response is not useful. Whether the levels of serum VEGF and its receptors VEGFR-1 and VEGFR-2 have value in detecting treatment modalities of SCLC need further studies.

Purpose: The primary objective of this randomized phase III study was to show significant difference in median time to progression (TTP) in patients with advanced NSCLC treated with single-agent gemcitabine maintenance therapy versus best supportive care following gemcitabine plus cisplatin initial first-line therapy., Patients and Methods: Chemonaive patients with stage IIIB/IV NSCLC received gemcitabine 1,250 mg/m(2) (days 1 and 8) plus cisplatin 80 mg/m(2) (day 1) every 21 days. Patients achieving objective response or disease stabilization following initial gemcitabine plus cisplatin therapy were randomized (2:1 fashion) to receive maintenance gemcitabine (1,250 mg/m(2) on days 1 and 8 every 21 days) plus best supportive care (GEM arm), or best supportive care only (BSC arm)., Results: Between November 1999 and November 2002, we enrolled 352 patients (median age: 57 years; stage IV disease: 74%; Karnofsky performance status (KPS) >80: 41%). Following initial therapy, 206 patients were randomized and treated with gemcitabine (138) or best supportive care (68). TTP throughout the study period was 6.6 and 5 months for GEM and BSC arms, respectively, while values for the maintenance period were 3.6 and 2.0 months (for p < 0.001 for both). Median overall survival (OS) throughout study was 13.0 months for GEM and 11.0 months for BSC arms (p = 0.195). The toxicity profile was mild, with neutropenia being most common grade 3/4 toxicities., Conclusion: Maintenance therapy with gemcitabine, following initial therapy with gemcitabine plus cisplatin, was feasible, and produced significantly longer TTP compared to best supportive care alone. Further studies are warranted to establish the place of maintenance chemotherapy in patients with advanced NSCLC.

Background: Expression of neuroectodermal markers is a key feature of small cell lung carcinoma (SCLC). Although immune responses against a number of these proteins have been associated with paraneoplastic neuronal disease (PND), most patients with SCLC have anti-neuroectodermal antibodies in the absence of PND. Whether these immune responses affect the clinical outcome in SCLC is critical in understanding the potential value of these proteins as cancer vaccine targets as well as in the pathogenesis of PND., Methods: The authors investigated the frequency of immunoglobulin G autoantibodies against Sry-like high-mobility group box (SOX)1, 2, 3 and Zinc-finger gene of the cerebellum (ZIC)2 proteins in stored serum samples from 90 patients utilizing the lambda-phage plaque assay. Data obtained from patient records were utilized to measure clinical correlates of seroreactivity., Results: Antibodies to SOX1 were present in 28% of patients and another 28% had anti-ZIC2 antibodies, classifying these as some of the most frequent antibody responses observed in SCLC. None had autoimmune paraneoplastic disease. Antibody titers were frequently as high as > or = 1:10(6) and were stable for < or = 6 months after diagnosis. Seroreactivity against either SOX1 or ZIC2 correlated with younger age, lower lactate dehydrogenase levels, and better response to initial therapy., Conclusions: The frequent and stable presence of SOX Group B and/or ZIC2 antibodies in SCLC, but not in healthy individuals examined, indicates they are serological markers of SCLC. However, the correlation between known clinical parameters of less aggressive disease and seroreactivity suggests that these antibodies are indicators of better prognosis in SCLC and warrants further studies to clarify the nature of the underlying immune responses., (Copyright 2005 American Cancer Society.)

The aim of this study is to assess the clinical usefulness of serum assays of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and CYFRA 21.1 in the diagnosis of squamous cell lung cancer. Sixty patients with squamous cell, and twenty-four patients with nonsquamous cell histology of nonsmall cell lung cancer were enrolled in this study. Serum CEA, SCC, and CYFRA 21.1 levels were obtained by commercially available kits. Upper cutoff levels were 10 ng/ml, 3.5 ng/ml, and 3.5 ng/ml, respectively. In squamous cell lung cancer, percentages and 95% confidence interval (CI) of the patients with elevated levels were as follows: for CEA 23.3% (13-36), for SCC 20.0% (10-32), and for CYFRA 21.1 85.0% (73-93). The positivity rate of CYFRA 21.1 was more significant than CEA and SCC in both squamous and nonsquamous cell lung cancer. None of the markers were significant in differentiating squamous/nonsquamous histology. Only tumor marker CEA was significantly elevated in metastatic squamous cell lung cancer (p=0.004). A novel tumor marker CYFRA 21.1 can be used as a reliable tumor marker in diagnosing squamous cell lung cancer. In addition, CEA has an important role in determining metastatic disease.

This study was conducted to investigate the distribution of metastatic lesions and their influence on survival, as well as other prognostic factors previously shown to have an impact on the outcome of patients with extensive small cell lung cancer (SCLC). Of the 207 patients were included and retrospectively analyzed; 124 patients had extended disease at initial presentation and the remaining 83 developed metastatic disease during follow-up. Patients who relapsed presented most frequently with distant metastases. The brain was the most frequent organ targeted for metastatic disease following the completion of chemotherapy (p<0.05). Serum LDH levels correlated significantly with the presence of liver metastasis (p<0.001). The site of involvement did not seem to have an impact on survival. Nevertheless, patients with multiple metastatic sites had a significantly poor survival rate (p = 0.001). Weight loss, performance status, gender, clinical stage, serum LDH and albumin levels were all shown to correlate with survival (p<0.05). Response to chemotherapy was determined to be the most important prognostic factor.