Anitha Thomas

Survival outcomes of epithelial ovarian cancer treated at a tertiary-level hospital in India

Abstract Background: One needs to choose wisely between primary neoadjuvant chemotherapy and primary cytoreductive surgery in ovarian cancer. The aim was to determine the recurrence free survival and overall survival after surgery for epithelial ovarian cancer and also the risk factors for recurrence and death. Methods: Electronic medical records of 322 women operated for ovarian, fallopian or primary peritoneal cancer between 2011 and 2015 were reviewed. Descriptive statistics were used to describe patients and their clinical outcomes. Cox proportional hazard models were used for risk factor analysis. Adjusted hazard ratios were obtained for recurrence and death, adjusted for stage, primary treatment modality, residual disease and histology. Kaplan-Meier curves were drawn for probability of recurrence-free survival and overall survival. The log rank test was used to compare survival probabilities. Results: The majority were stage III or stage IV (78%), serous histology (71%) and high grade (64%). Primary cytoreduction was done in 48% and interval cytoreduction in 52%. The median duration of follow up (survival) was 77 months (95% CI 72-82). There were 179 known recurrences (55.6 %). The estimated median time to recurrence was 22 (95% CI 14.5- 29.5) months. The independent risk factors for recurrence were neoadjuvant chemotherapy [HR 2.14, 95% CI 1.48-3.09], stage III/IV [HR 2.75; 95% CI 1.40-5.41], high grade serous histology [HR 1.69; 95% CI 1.12-2.54] and sub-optimal debulking [HR 3.15, 95% CI 2.19-4.55]. There were 78 known deaths (24.2 %) with a mean time to death of 24.3 (SD 16.1) months. The independent risk factors for death were sub-optimal debulking [HR 3.07; 95% CI 1.78-5.29] and stages III and IV cancer [HR 3.07; 95% CI 1.14-8.27]. Conclusions: Most ovarian cancers recur within 2 years. Risk factors for mortality are advanced stage and sub-optimal debulking. Maximal efforts at down staging and surgical resection will increase survival.

Analysis of patients with endometrial carcinoma using the ProMise classifier: a pilot study from India

Molecular subtyping of endometrial carcinomas (EC) has been shown to classify tumors into prognostically relevant groups. Characterizing EC with a limited number of markers viz., POLE mutations, p53 mutations, and MMR status, can provide valuable information. Paraffin sections of a cohort of 48 EC from a tertiary care center were characterized for the above-mentioned molecular markers and analyzed in the context of survival. Formalin fixed paraffin embedded tissues from 48 EC were characterized for POLE mutations by Sanger sequencing (exons 9-14), for MMR (MLH1, MH2, MSH6) using immunohistochemistry (IHC) and copy number (high/low) using p53 IHC. Mutational status was integrated along with the clinicopathological details and survival analysis performed. Eleven (22.9%) patients were MMR deficient, 3 (6.3%) had POLE mutation, while 2 (4.1%) had both POLE and P53 mutations (regarded as multiple classifiers). Twelve (25%) patients were found to have P53 mutations, while the remaining 20 (41.7%) had no specific molecular profile (NSMP). Median follow-up duration was 43.5 (2-62) months with 8 recurrences and 9 deaths. Tumors with POLE mutation had the most favorable prognosis followed by the NSMP and the MMR mutated group while the P53 and multiple classifier groups had the worst prognosis in terms of OS (Log-rank p: 0.006) and PFS (Log-rank p: 0.001). The integration of molecular-clinicopathologic data for endometrial cancer classification, through cost-effective, clinically applicable assays appears to be a highly objective tool that can be adopted even in resource-limited settings. It has the potential to cause a shift in the paradigm of EC pathology and management practice.

Endometriosis and malignancy: The intriguing relationship

AbstractObjectiveTo determine the prevalence and study the association of ovarian, uterine, and breast cancers with endometriosis.MethodsA cross‐sectional study of all women with a tissue‐proven diagnosis of endometriosis postoperatively in a tertiary care hospital between January 1, 2010, and December 31, 2019, was conducted to determine the prevalence of coexistent malignancy. Patient details were obtained from electronic clinical records. Univariate analysis followed by multivariate analysis was done to find independent risk factors associated with malignancy.ResultsOut of 800 patients, 104 (13.0%) were found to have coexistent malignancy: ovarian (50, 6.2%); endometrial (33, 4.1%); synchronous ovarian and endometrial (7, 0.9%); and breast (14, 1.8%). Increasing age (odds ratio [OR] 1.13; 95% confidence interval [CI] 1.09–1.16), higher levels of cancer antigen 125 (CA 125) (OR 1.002; 95% CI 1.001–1.005), postmenopausal status (OR 6.2; 95% CI 2.0–19.2), duration of endometriosis over 5 years (OR 4.7; 95% CI 2.5–9.0), and endometriomas larger than 8 cm (area under the curve 0.83) were predictive of coexistent malignancy.ConclusionEndometriosis is associated with an increased risk of ovarian, endometrial, and breast malignancy. Increasing age, postmenopausal status, higher levels of CA 125, larger endometrioma, and long‐standing disease are predictive risk factors.

Diagnostic Accuracy of Fluorescein Sodium for Targeted Cervical Biopsies

Visual inspection methods for cervical cancer screening are widely used in low resource settings. Fluorescent sodium could improve accuracy of cancer screening. This study aimed to assess diagnostic accuracy of fluorescein sodium (FNa) to detect cervical neoplasia. Seventy consecutive patients referred for colposcopy were enrolled prospectively. Acetic acid, Lugol's iodine, and FNa were used sequentially. Biopsies were taken from all abnormal areas. If there was no obvious abnormality, two random biopsies and endocervical curettage were done. Reference standard was the highest grade lesion on cervical biopsy with a threshold of CIN2+. The patterns of each staining agent were recorded as absent, faint, or distinct. Diagnostic accuracy estimates with 95% confidence intervals were calculated. Correlation between the various tests were also determined using the kappa statistic. There were 27 cases of CIN2+ (38.6%). The sensitivity of any fluorescence for CIN2+ was 82% (62, 94) and for distinct fluorescence was 59% (39, 78). The specificity was 65% (49, 79) for any fluorescence and 95% (84, 99) for distinct fluorescence, the same as for Swede score > 7. For any fluorescence, the positive likelihood ratio was 2.34 (1.5, 3.65) and the negative likelihood ratio was 0.28 (0.13, 0.65). For distinct fluorescence, the positive likelihood ratio was 12.74 (3.18, 51.1) and the negative likelihood ratio was 0.43 (0.27, 0.68). There was moderate correlation between FNa and the other tests. Distinct fluorescence with FNa was very specific, low cost, and easy to perform and may contribute to confirm CIN2+ disease.

Diagnostic study of human papillomavirus DNA detection in cervical and vaginal samples using the filter paper card

AbstractObjectiveTo determine the accuracy of high‐risk human papillomavirus (HPV) DNA samples on filter paper in comparison to specimen transport medium (STM).MethodsThis was a cross‐sectional diagnostic study of 42 consecutive women who were prospectively recruited. Each had self‐collected vaginal samples on filter paper, physician‐collected cervical samples on filter paper, and physician‐collected cervical samples in STM. HPV DNA testing was performed with a Hybrid Capture 2 system (Qiagen). Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and agreement of filter paper methods with the standard procedure were calculated.ResultsThe overall prevalence of HPV in STM was 67.5%. Detection of HPV DNA in the physician‐collected cervical samples on filter paper had a sensitivity of 77.8%, a specificity of 100%, a PPV of 100%, and an NPV of 68.4%. The patient's self‐sampling on filter paper had a sensitivity of 66.7%, a specificity of 100%, a PPV of 100%, and an NPV of 59.1%. The agreement between STM method and physician‐collected sample on filter paper was substantial, (κ = 0.695, P < 0.001), while the agreement between STM and self‐collected samples on filter paper was moderate (κ = 0.565, P < 0.001). Most patients reported that self‐collection was acceptable (100%), painless (95%), and not embarrassing (95%).ConclusionFilter paper, with dried self‐collected vaginal samples, can be used to detect high‐risk HPV with acceptable accuracy.