• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.321-326
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• 2015

Background: The aim of this study was to explore the prognostic role of metabolic response to chemotherapy, determined by FDG-PET, in patients with metastatic non-small-cell lung cancer (NSCLC). Materials and Methods: Thirty patients with metastatic NSCLC were analyzed for prognostic factors related to overall survival (OS) and progression free survival (PFS). Disease evaluation was conducted with FDG-PET/CT and contrast-enhanced CT prior to and at the end of first-line chemotherapy. Response evaluation of 19 of 30 patients was also performed after 2-3 cycles of chemotherapy. Morphological and metabolic responses were assessed according to RECIST and PERCIST, respectively. Results: The median OS and PFS were 11 months and 6.2 months, respectively. At the end of first-line chemotherapy, 10 patients achieved metabolic and anatomic responses. Of the 19 patients who had an interim response analysis after 2-3 cycles of chemotherapy, 3 achieved an anatomic response, while 9 achieved a metabolic response. In univariate analyses, favorable prognostic factors for OS were number of cycles of first-line chemotherapy, and achieving a response to chemotherapy at completion of therapy according to the PERCIST and RECIST. The OS of patients with a metabolic response after 2-3 cycles of chemotherapy was also significantly extended. Anatomic response at interim analysis did not predict OS, probably due to few patients with anatomic response. In multivariate analyses, metabolic response after completion of therapy was an independent prognostic factor for OS. Conclusions: Metabolic response is at least as effective as anatomic response in predicting survival. Metabolic response may be an earlier predictive factor for treatment response and OS in NSCLC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1281-1284
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• 2012

Background: Platinum-hased chemotherapy for advanced non-small cell lung cancer (NSCLC) is still considered the first choice, presenting a modest survival advantage. However, the patients eventually experience disease progression and require second-line therapy. While there are reliable predictors to identify patients receiving first-line chemotherapy, very little knowledge is available about the prognostic factors in patients who receive second-line treatments. The present study was therefore performed. Methods: We retrospectively reviewed 107 patients receiving second-line treatments from August 2002 to March 2012 in the Dicle University, School of Medicine, Department of Medical Oncology. Fourteen potential prognostic variables were chosen for analysis in this study. Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. Result: The results of univariate analysis for overall survival (OS) were identified to have prognostic significance: performance status (PS), stage, response to first-line chemotherapy response to second-line chemotherapy and number of metastasis. PS, diabetes mellitus (DM), response to first-line chemotherapy and response to second-line chemotherapy were identified to have prognostic significance for progression-free survival (PFS). Multivariate analysis showed that PS, response to first-line chemotherapy and response to second-line chemotherapy were considered independent prognostic factors for OS. Furthermore, PS and response to second-line chemotherapy were considered independent prognostic factors for PFS. Conclusion: In conclusion, PS, response to first and second-line chemotherapy were identified as important prognostic factors for OS in advanced NSCLC patients who were undergoing second-line palliative treatment. Furthermore, PS and response to second-line chemotherapy were considered independent prognostic factors for PFS. It may be concluded that these findings may facilitate pretreatment prediction of survival and can be used for selecting patients for the correct choice of treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4917-4920
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• 2016

For advanced non-small-cell lung cancer (NSCLC) cases, a platinum-based regimen is the first-line chemotherapy treatment. The excision repair cross-complementing group 1 (ERCC1) plays an important role in DNA repair and has been related to resistance to platinum chemotherapy. This study aimed to investigate the effects of the ERCC1 (C118T) polymorphism on treatment response in 26 Thai advanced NSCLC patients receiving first line platinum-based chemotherapy during January to July 2015 at King Chulalongkorn Memorial Hospital (KCMH). DNA was extracted from peripheral blood lymphocytes and the single nucleotide polymorphism of ERCC1 was genotyped using a real-time PCR method with the TaqMan assay. The distribution of C/C, C/T and T/T genotypes was 57.7 %, 34.6 % and 7.7 %, respectively. The response rate to platinum-based chemotherapy in the wild type (C/C) of ERCC1 (C118T) was better than with the variant types (C/T and T/T) but the difference was not statistically significant (29.7% vs 9.1%, P=0.274). The results showed that a genetic polymorphism in ERCC1 might influence patient response to platinum-based chemotherapy. Further multicenter studies are now required to confirm the results of our study.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.87-91
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• 2016

To investigate whether excision repair cross complementing-group1 (ERCC1) expression status could serve as a bio-predictor of response to platinum-based induction chemotherapy for head and neck cancers (HNCs) patients with a diagnosis of epithelial HNC were studied retrospectively. Paraffin embedded tumor samples of the patients were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) to determine ERCC1 expression status and its correlation with response to platinum-based induction chemotherapy was investigated. Of 44 included patients, 33 were male (75%) and 11 were female (25%) with a mean age of 53 years. Some 36% of patients whose tumor samples had high ERCC1 expression showed no response to induction chemotherapy. The value for patients with low ERCC1 expression was 9% and the difference was statistically significant (p=0.03). The ERCC1 expression state did not significantly vary between patient groups according to sex, age, primary tumor site, and tumor and node stage. Our study indicates that ERCC1 expression status detected by RT-PCR might serve as a bio-predictor of response to platinum-based induction chemotherapy for epithelial HNCs.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7203-7206
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• 2013

Recent studies suggested that the ovarian cancers with negative excision repair cross-complementation group 1 enzyme (ERCC1) expression have a better response to platinum-based chemotherapy than those with positive ERCC1 expression. The objective of this study was to evaluate whether ERCC1 expression is associated with response to platinum-based chemotherapy in ovarian cancers. MEDLINE, PubMed, Web of Science and CNKI databases were used for searching studies relating to ERCC1 protein expression and response to platinum-based chemotherapy in ovarian cancers. Statistical analysis was based on the method for a fixed effects meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals for ERCC1 protein expression and response to platinum-based chemotherapy were generated. Publication bias was investigated with Begg's test. Five studies involving 306 patients with ovarian cancer were included. Compared to patients with positive ERCC1 expression, those with negative ERCC1 expression had a better response to platinum-based chemotherapy. The pooled OR was 5.264 (95% CI: 2.928-9.464, P < 0.001) and publication bias was not found (P = 0.904). The result was similar in both in Asians and Caucasians (P < 0.001 and P = 0.028, respectively). ERCC1 protein expression status is significantly associated with response to platinum-based chemotherapy in ovarian cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2401-2406
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• 2013

From January 1, 2008 to March 31, 2010, 101 patients with stage II-III breast cancer were enrolled in this study and subjected to an anthracycline-based neoadjuvant chemotherapy regimen with or without docetaxel. Surgery was performed after 2-6 cycles of chemotherapy, and the clinical response was determined by pathological and histochemical assessments. The clinical response rate, as indicated by complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), were 6.9, 52.5, 36.6, and 4.0%, respectively. A multivariable correlation analysis indicated that the overall clinical response rate correlated with the number of metastatic lymph nodes, number of chemotherapy cycles, and vessel invasion status. Importantly, the CR rate was only associated with the number of chemotherapy cycles. Nonparametric tests failed to detect a correlation between HER2 or Topo $II{\alpha}$ status and clinical response to neoadjuvant chemotherapy in these patients. When they were stratified by HER2 or HR status, for HER2-positive patients the CR rate was associated with vessel invasion and Topo $II{\alpha}$ status. Based on our findings, we propose that HR, HER-2 and Topo $II{\alpha}$ are not putative predictive biomarkers of chemotherapy outcome for breast cancer patients. Topo $II{\alpha}$ expression level was only inversely correlated with CR rate among HR-positive patients. Importantly, the achievement of CR was largely related to the number of chemotherapy cycles.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5883-5886
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• 2012

Osteosarcoma is the most common primary bone malignancy in children and adolescents, and its clinical outcome is poor. We evaluated the response of GSTP1, ERCC1 and ERCC2 to chemotherapy among osteosarcoma patients, and the role of these genes on the prognosis of osteosarcoma. 187 patients with osteosarcoma were administered with methotrexate, cisplatin/adriamycin, actinomycin D, cyclophosphamide, or vincristine treatment. GSTP1, ERCC1 and ERCC2 polymorphism was genotyped by PCR-RFLP assay. The results showed the average survival time of 187 patients were 38.4 months. 97 patients showed response to neoadjuvant chemotherapy. The GSTP1 Val and ERCC2 A/A genotypes had significantly higher rates of response to chemotherapy, with adjusted OR (95% CI) of 2.19 (1.15-6.21) and 2.88 (1.14-13.25). Individuals with ERCC2 A/A genotype were likely to have a lower risk of death from oseosarcoma, and the adjusted HR was 0.32 (0.13-0.95). Our study indicated test of GSTP1 and ERCC2 Lys751Gln polymorphisms might be a candidate pharmacogenomic factors to be explored in the future to identify the osteosarcoma patients who might benefit from chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3323-3326
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• 2014

Breast cancer is the most common cancer in Jamaican women. Locally advanced breast cancer (LABC) is associated with aggressive biology and poor prognosis, and has a predilection for African-American women. In this retrospective review, we assessed the prevalence of LABC as a breast cancer presentation in a population of mainly Afro-centric ethnicity, and determined disease characteristics and response to pre-operative chemotherapy. LABC was prevalent (20%), and had a low pathological response rate to pre-operative chemotherapy, with a high risk of disease recurrence. Increased utilization of breast cancer screening may help detect cancer at less advanced stages, and optimizing pre-operative chemotherapy is recommended to improve response rates and ultimately survival.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1341-1347
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• 2012

Introduction: Diffuse large B-cell lymphomas (DLBCL) can be divided into germinal centre (GC-DLBCL) and post germinal centre (post GC-DLBCL) groups by applying immunohistochemical antibodies. As these subgroups respond differently to chemotherapy, it is possible at diagnosis to select a poor prognostic subgroup for aggressive treatment. Objective: To determine the frequencies of GC-DLBCL and post GC-DLBCL in patients by immunohistochemistry (IHC) and the clinical response after six cycles of chemotherapy. Subjects and Methods: In this descriptive study conducted in AFIP and CMH, Rawalpindi and NORI, Islamabad, from September 2010 to September 2011, a total of 75 pretreatment cases of DLBCL diagnosed during the study period were included. Cases were segregated in to GC-DLBCL and post GC-DLBCL groups according to results of immunohistochemistry markers CD10, BCL6 and MUM1. Immediate clinical response was assessed after 6 cycles of chemotherapy. Response was divided into complete response, partial response, stable disease or relapse or progression. Results: The mean age was $54.2{\pm}15$. Males were 53 (70.7%). Forty (53.3%) cases comprised the GC-DLBCL group; 25(62.5%) of them showed a complete response. Most patients of the post GC-DLBCL 19(54%) showed relapse/progression. Results of immediate clinical response in both prognostic subgroups were significant (p<0.05). Results regarding positivity with immunohistochemical antibodies CD10 (p 0.011), BCL6 (p 0.013) and MUM1 (p 0.000) regarding immediate clinical response were also significant. Conclusion: GC-DLBCL group shows better response to CHOP chemotherapy regimen. Immunohistochemistry should be used to further classify DLBCL as this can enable us to select aggressive group for aggressive treatment. This manuscript is important because the study is the first to becarried out exclusively in Pakistan or our part of the world.

• Tuberculosis and Respiratory Diseases
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• v.70 no.4
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• pp.301-306
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• 2011

Background: It is well-known that cell-free nucleic acids rise in patients with many types of malignancies. Several recent experimental studies using cancer cell lines have shown that changes in cell-free RNA are predictive of the response to chemotherapy. The objective of this study was to determine whether quantification of free RNA can be used as a biomarker for clinical responses to chemotherapy in patients with lung cancer. Methods: Thirty-two patients with lung cancer (non-small cell lung cancer, n=24; small cell lung cancer, n=8) were divided into 2 groups according to their responses to chemotherapy (response group, n=19; non-response group, n=13). Blood samples were collected before and after two cycles of chemotherapy. Real-time quantitative RT-PCR was used for transcript quantification of the glyceraldehyde-3-phosphate dehydrogenase gene. Results: The pre chemotherapy values (Response group $41.36{\pm}1.72$ vs. Non-response group $41.33{\pm}1.54$, p=0.78) and post chemotherapy values (Response group $39.92{\pm}1.81$ vs. Non-response group $40.41{\pm}1.47$, p=0.40) for cell free RNA concentrations, expressed as Ct GAPDH (threshold cycle glyceraldehyde-3-phosphate dehydrogenase gene) levels, was not different between the two groups. There was no significant relationship between changes in the cell free RNA level clinical responses after chemotherapy (p=0.43). Conclusion: We did not find a correlation between quantification of serum cell free RNA levels and clinical responses to chemotherapy in patients with lung cancer. Further investigations are needed to determine whether the cell free RNA level is a useful predictor of responses to chemotherapy in patients with lung cancer.