Copy number variations and protein expression of Cyclin E1 and Epithelial cell transforming sequence 2 genes predict the chemotherapeutic response in patients with serous ovarian carcinoma.

Background & Objectives: Serous ovarian carcinoma (SOC) is characterized by extreme genomic instability, chromosomal rearrangements and copy number variations (CNVs) leading to the development of early metastasis and chemo-resistance. The present study was designed to observe the role of CNVs of Cyclin E1 (CCNE1) and Epithelial cell transforming sequence- 2 (ECT2) genes and their encoded proteins in predicting the chemotherapeutic response in SOC patients. Methods: This observational analytical study was conducted at University of Health Sciences, Lahore, Pakistan from December 2019 till June 2022.The study included twenty-five SOC patients with resectable ovarian tumors and twenty-five control subjects. The patients were followed-up for six months for their response to chemotherapy. The CNVs in CCNE1 and ECT-2 genes were determined by real time PCR while serum levels of encoded proteins were determined in controls and cases, before and after six months of treatment, through ELISA. The response to chemotherapy was categorized as sensitive or resistant based on serum CA-125 levels and radiological scans. Results: The copy number variations in CCNE1 and ECT2 genes showed association with the clinic-pathological characteristics and chemotherapy response. Statistically significant difference was found between the mean pre-chemotherapy protein levels of CCNE1 in cases than controls (p-value <0.001) and between the mean pre and post-chemotherapy protein levels of CCNE1 and ECT2 (p-value <0.001) in SOC patients. Conclusion: The copy number variations of CCNE1 and ECT2 genes and their protein expression are positively associated with chemotherapeutic response in SOC patients.

Potential prognostic role of somatic mutations in a set of cancer susceptibility genes in ovarian carcinoma: A follow-up multicentric study from Pakistan.

BACKGROUND: Genetic mutations, peritoneal metastasis and frequent development of chemoresistance worsen the prognosis of ovarian carcinoma. OBJECTIVE: The objective of the study is to determine mutations in cancer susceptibility genes in relation with chemotherapy response. METHODS: In this follow up descriptive study, 47 consenting female patients diagnosed with surface epithelial ovarian cancer were observed for six months after completion of chemotherapy to see the treatment response. For genetic analysis, the DNA extraction was done and the genomic regions of different exons of BRCA1/2, PALB2, CHEK2, BAP1, CTNNB1, HOXB13, and PIK3CA were amplified using gene specific primers followed by Sanger Sequencing. RESULTS: 86.7% of the patients were sensitive to chemotherapy whereas 13.3% showed resistance. Genetic variants of BRCA1 in 7%, BRCA2 in 4.7%, PIK3CA in 9.3%, PALB2 in 7%, CHEK2 in 2.3%, BAP1 in 2.3%, and CTNNB1 in 2.3% of the patients were found. There was also a significant association between TNM stage and the treatment response (p< 0.01). Of the patients with no mutations, 90.9% showed chemosensitivity as opposed to 70% in mutations group. CONCLUSION: Our study exhibits the pivotal role of genetic analysis in predicting the treatment response and paving pathway for patient tailored targeted therapy in Pakistani population.

Acute Side Effects with High Dose Rate Computed Tomography-guided Three-dimensional Brachytherapy in Carcinoma Cervix.

OBJECTIVES: To determine the frequency and grades of acute side effects with three-dimensional brachytherapy in carcinoma cervix using RTOG/EORTC acute radiation morbidity scoring criteria. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Radiotherapy, Institute of Nuclear Medicine and Oncology (INMOL), Lahore, Pakistan from July 2016 to September 2017. METHODOLOGY: A total of 55 histologically proven patients of squamous cell carcinoma of the cervix, aged between 16-70 years, were included. Patients with previous radiotherapy in pelvic area, inflammatory bowel diseases and known diabetics, were excluded. All patients were given a radiation dose of 7 Gray in 4 insertions through 3-dimensional conformal brachytherapy planning. Acute vaginal, gastrointestinal, and genitor-urinary side effects of brachytherapy were assessed. RESULTS: Mean age of the patient population was 47.09 ±13.10 years (Range: 21-68). Mean time to presentation was 5.65 ±2.32 months and mean tumor size was 3.67 ±1.47 cm. Majority, i.e. 18 (32.7%) patient presented in stage III. Most of the patients, 26 (47.3%), had ECOG-2 performance status. Grade-1 genitourinary toxicity was significantly high (p <0.001). In lower gastrointestinal toxicity, Grade-1 was the highest being 54.5%. Conversely, vaginal toxicities of grade-2 and 3 were most commonly seen. Stratification of acute side effectswith respect toage, stage and tumor size revealed no significant association except in mucosal membrane toxicity, which was affected by tumor size (p = 0.004). CONCLUSION: Three-dimensional brachytherapy in carcinoma cervix is a safe and tolerable procedure with minimal acute side effects. Key Words: Cervical cancer, Brachytherapy, Acute toxicities, Computed tomography.

Efficacy and Toxicity of Concurrent Chemoradiation in Inoperable Oral Carcinoma in Pakistani Population.

OBJECTIVE: To evaluate the efficacy of concurrent chemoradiation in patients with locally advanced inoperable squamous cell carcinoma of oral cavity in terms of local control and toxicity. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Institute of Nuclear Medicine and Oncology (INMOL), Lahore, from January 2008 to December 2013. METHODOLOGY: Sixty-nine patients with locally advanced inoperable oral cavity cancer, registered in INMOL hospital from January 2008 to December 2013 who fulfilled a pre-defined eligibility criteria, were enrolled in the study. Concurrent chemoradiation protocol consisted of conventional fractionation delivering 70 Gy with weekly Cisplatin (50 mg/m2) during the course of radiation. Tumor response was calculated by RECISTcriteria version 1.1 along with the median overall survival and disease-free survival. Acute treatment related toxicities were graded as (G). RESULTS: Thirty-six (52.17%) patients showed complete response; while 19 (27.54%), 8 (11.59%) and 6 (8.7%) were observed with partial response, stable and progressive disease, respectively. Treatment response was significant (p<0.001) in terms of responders vs. non responders to treatment. Median overall survival was 18.00 months; whereas, median disease-free survival remained 14.00 months. Main toxicities included mucositis (G3 and G4, 71%), xerostomia (G2 and G3, 82.5%), vomiting (G3 and G4, 51%), myelosuppression (G3 and G4, 26.2%), dermatitis (G3 and G4, 49.2%), and fatigue (G3 and G4, 57.9%). CONCLUSION: Platinum based CCR Tremained effective for inoperable oral cancer patients.