Cost-Effectiveness of Novel Agent Regimens for Transplant-Eligible Newly Diagnosed Multiple Myeloma Patients in India.

BACKGROUND: Survival outcomes for multiple myeloma have improved dramatically since the introduction of novel therapeutic agents. While these drugs are highly effective in improving survival outcomes and quality of life in patients with multiple myeloma, they come at a significant cost. We assessed the cost-effectiveness of bortezomib-based triplet or quadruplet drug regimens in isolation and followed by autologous hematopoietic stem cell transplantation (AHSCT) for the treatment of newly diagnosed multiple myeloma (NDMM) in the Indian context. METHODS: A Markov model was developed to assess the health and economic outcomes of novel drug regimens with and without AHSCT for the treatment of NDMM in India. We estimated the lifetime quality-adjusted life-years (QALYs) and costs in each scenario. The incremental cost-effectiveness ratios (ICERs) were computed and compared against the current willingness-to-pay threshold of a one-time per capita gross domestic product of ₹146,890 (US$1,927.70) for India. Parameter uncertainty was assessed through Monte Carlo probabilistic sensitivity analysis. RESULTS: Among seven treatment sequences, the VCd (bortezomib, cyclophosphamide, dexamethasone) alone arm has the lowest cost and health benefits as compared to four treatment sequences, namely VTd (bortezomib, thalidomide, dexamethasone) alone, VRd (bortezomib, lenalidomide, dexamethasone) alone, VRd plus AHSCT and DVRd (Daratumumab, bortezomib, lenalidomide, dexamethasone) plus AHSCT. It was found that VTd plus AHSCT and VCd plus AHSCT arms were extendedly dominated (ED) by combination of two alternative treatments. Among the five non-dominated strategies, VRd has a lowest incremental cost of ₹ 2,20,093 (US$2,888) per QALY gained compared to VTd alone followed by VRd plus AHSCT [₹3,14,530 (US$4,128) per QALY gained] in comparison to VRd alone. None of the novel treatment sequences were found to be cost-effective at the current WTP threshold of ₹1,46,890 (US$1,927.7). CONCLUSION: At the current WTP threshold of one-time per capita GDP (₹ 146,890) of India, VRd alone and VRd plus AHSCT has 38.1% and 6.9% probability to be cost-effective, respectively. Reduction in current reimbursement rates of novel drugs, namely VRd, lenalidomide, and pomalidomide plus dexamethasone under national insurance program and societal cost of transplant by 50%, would make VRd plus AHSCT and VTd plus AHSCT cost-effective at an incremental cost of ₹40,671 (US$34) and ₹97,639 (US$1,281) per QALY gained, respectively.

Household cooking fuel and gallbladder cancer risk: a multi-centre case-control study in India.

PURPOSE: Gallbladder cancers (GBC), unique to certain geographical regions, are lethal digestive tract cancers, disproportionately affecting women, with limited information on risk factors. METHODS: We evaluated the association between household cooking fuel and GBC risk in a hospital-based case-control study conducted in the North-East and East Indian states of Assam and Bihar. We explored the potential mediation by diet, fire-vents, 'daily exposure duration' and parity (among women). We recruited biopsy-confirmed GBC (n = 214) men and women aged 30-69 years between 2019 and 2021, and controls frequency-matched by age, sex and region (n = 166). Information about cooking fuel, lifestyle, personal and family history, female reproductive factors, socio-demographics, and anthropometrics was collected. We tested associations using multivariable logistic regression analyses. RESULTS: All participants (73.4% women) were categorised based on predominant cooking fuel use. Group-1: LPG (Liquefied Petroleum Gas) users in the previous 20 years and above without concurrent biomass use (26.15%); Group-2: LPG users in the previous 20 years and above with concurrent secondary biomass use (15.9%); Group-3: Biomass users for ≥ 20 years (57.95%). Compared to group-1, accounting for confounders, GBC risk was higher in group-2 [OR: 2.02; 95% CI: 1.00-4.07] and group-3 [OR: 2.01; 95% CI: 1.08-3.73] (p-trend:0.020). These associations strengthened among women that attenuated with high daily consumption of fruits-vegetables but not with fire-vents, 'daily exposure duration' or parity. CONCLUSION: Biomass burning was associated with a high-risk for GBC and should be considered as a modifiable risk factor for GBC. Clean cooking fuel can potentially mitigate, and a healthy diet can partially reduce the risk among women.

Financial toxicity of cancer treatment in India: towards closing the cancer care gap.

Background: The rising economic burden of cancer on patients is an important determinant of access to treatment initiation and adherence in India. Several publicly financed health insurance (PFHI) schemes have been launched in India, with treatment for cancer as an explicit inclusion in the health benefit packages (HBPs). Although, financial toxicity is widely acknowledged to be a potential consequence of costly cancer treatment, little is known about its prevalence and determinants among the Indian population. There is a need to determine the optimal strategy for clinicians and cancer care centers to address the issue of high costs of care in order to minimize the financial toxicity, promote access to high value care and reduce health disparities. Methods: A total of 12,148 cancer patients were recruited at seven purposively selected cancer centres in India, to assess the out-of-pocket expenditure (OOPE) and financial toxicity among cancer patients. Mean OOPE incurred for outpatient treatment and hospitalization, was estimated by cancer site, stage, type of treatment and socio-demographic characteristics. Economic impact of cancer care on household financial risk protection was assessed using standard indicators of catastrophic health expenditures (CHE) and impoverishment, along with the determinants using logistic regression. Results: Mean direct OOPE per outpatient consultation and per episode of hospitalization was estimated as ₹8,053 (US$ 101) and ₹39,085 (US$ 492) respectively. Per patient annual direct OOPE incurred on cancer treatment was estimated as ₹331,177 (US$ 4,171). Diagnostics (36.4%) and medicines (45%) are major contributors of OOPE for outpatient treatment and hospitalization, respectively. The overall prevalence of CHE and impoverishment was higher among patients seeking outpatient treatment (80.4% and 67%, respectively) than hospitalization (29.8% and 17.2%, respectively). The odds of incurring CHE was 7.4 times higher among poorer patients [Adjusted Odds Ratio (AOR): 7.414] than richest. Enrolment in PM-JAY (CHE AOR = 0.426, and impoverishment AOR = 0.395) or a state sponsored scheme (CHE AOR = 0.304 and impoverishment AOR = 0.371) resulted in a significant reduction in CHE and impoverishment for an episode of hospitalization. The prevalence of CHE and impoverishment was significantly higher with hospitalization in private hospitals and longer duration of hospital stay (p < 0.001). The extent of CHE and impoverishment due to direct costs incurred on outpatient treatment increased from 83% to 99.7% and, 63.9% to 97.1% after considering both direct and indirect costs borne by the patient and caregivers, respectively. In case of hospitalization, the extent of CHE increased from 23.6% (direct cost) to 59.4% (direct+ indirect costs) and impoverishment increased from 14.1% (direct cost) to 27% due to both direct and indirect cost of cancer treatment. Conclusion: There is high economic burden on patients and their families due to cancer treatment. The increase in population and cancer services coverage of PFHI schemes, creating prepayment mechanisms like E-RUPI for outpatient diagnostic and staging services, and strengthening public hospitals can potentially reduce the financial burden among cancer patients in India. The disaggregated OOPE estimates could be useful input for future health technology analyses to determine cost-effective treatment strategies.

Cost-effectiveness analysis of different combination therapies for the treatment of chronic lymphocytic leukaemia in India.

Background: Over the years, there has been introduction of newer drugs, like bendamustine and ibrutinib, for the management of chronic lymphocytic leukaemia (CLL). Though these drugs lead to better survival, they are also associated with higher cost. The existing evidence on cost effectiveness of these drugs is from high-income countries, which has limited generalisability for low-income and middle-income counties. Therefore, the present study was undertaken to assess the cost-effectiveness of three therapeutic regimens, chlorambucil plus prednisolone (CP), bendamustine plus rituximab (BR) and ibrutinib for CLL treatment in India. Methods: A Markov model was developed for estimating lifetime costs and consequences in a hypothetical cohort of 1000 CLL patients following treatment with different therapeutic regimens. The analysis was performed based on a limited societal perspective, 3% discount rate and lifetime horizon. The clinical effectiveness of each regime in the form of progression-free survival and occurrence of adverse events were assessed from various randomised controlled trials. A structured comprehensive review of literature was undertaken for the identification of relevant trials. The data on utility values and out of pocket expenditure was obtained from primary data collected from 242 CLL patients across six large cancer hospitals in India. Findings: As compared to the most affordable regimen comprising of CP as first-line followed by BR as second-line therapy, none of the other therapeutic regimens were cost-effective at one time per capita gross-domestic product of India. However, if the current price of either combination of BR and ibrutinib or even ibrutinib alone could be reduced by more than 80%, regimen comprising of BR as first-line therapy followed by second-line ibrutinib would become cost-effective. Interpretation: At the current market prices, regimen comprising of CP as first-line followed by BR as second-line therapy is the most cost-effective strategy for CLL treatment in India. Funding: Department of Health Research, Government of India.

Chronic Exposure to Drinking Water Arsenic and Gallbladder Cancer Risk: Preliminary Evidence from Endemic Regions of India.

BACKGROUND: Evidence linking arsenic in drinking water to digestive tract cancers is limited. We evaluated the association between arsenic levels in groundwater and gallbladder cancer risk in a case-control study (2019-2021) of long-term residents (≥10years) in two arsenic-impacted and high gallbladder cancer risk states of India-Assam and Bihar. METHODS: We recruited men and women aged 30 to 69 years from hospitals (73.4% women), with newly diagnosed, biopsy-confirmed gallbladder cancer (N = 214) and unrelated controls frequency-matched for 5-year age, sex, and state (N = 166). Long-term residential history, lifestyle factors, family history, socio-demographics, and physical measurements were collected. Average-weighted arsenic concentration (AwAC) was extrapolated from district-level groundwater monitoring data (2017-2018) and residential history. We evaluated gallbladder cancer risk for tertiles of AwAC (µg/L) in multivariable logistic regression models adjusted for important confounders [Range: 0-448.39; median (interquartile range), T1-0.45 (0.0-1.19); T2-3.75 (2.83-7.38); T3-17.6 (12.34-20.54)]. RESULTS: We observed a dose-response increase in gallbladder cancer risk based on AwAC tertiles [OR = 2.00 (95% confidence interval, 1.05-3.79) and 2.43 (1.30-4.54); Ptrend = 0.007]. Participants in the highest AwAC tertile consumed more tubewell water (67.7% vs. 27.9%) and reported more sediments (37.9% vs. 18.7%) with unsatisfactory color, odor, and taste (49.2% vs. 25.0%) than those in the lowest tertile. CONCLUSIONS: These findings suggest chronic arsenic exposure in drinking water at low-moderate levels may be a potential risk factor for gallbladder cancer. IMPACT: Risk factors for gallbladder cancer, a lethal digestive tract cancer, are not fully understood. Data from arsenic-endemic regions of India, with a high incidence of gallbladder cancer, may offer unique insights. Tackling 'arsenic pollution' may help reduce the burden of several health outcomes.

Reason for improper simple hysterectomy in invasive cervical cancer in Northeast India.

Objective: The objective of the study was to determine the reasons for improper simple hysterectomy in the presence of invasive cervical cancer in Northeast India. Materials and Methods: The medical records of 52 patients who had undergone improper simple hysterectomy in the presence of invasive cervical cancer and were referred to a tertiary regional cancer Institute at Guwahati, Assam, between January 2015 and December 2019 were reviewed. Results: Most of the patients presented with abnormal vaginal bleeding (40.4%). The failure to perform cervical cytology before the operation was quite high at 48.1% (25 patients). Interestingly, normal cytologic smear could still be found in 15.4% (8 patients) despite the presence of invasive cervical cancer. Failure to perform preoperative Papanicolaou smear, incomplete evaluation of cervical intraepithelial neoplasia (CIN) on cervical biopsy, and negative Papanicolaou smear accounted for 75% of the patients undergoing inappropriate simple hysterectomy. The most common indications for inappropriate operation were abnormal vaginal bleeding (40.4%) and CIN (19.2%). The reasons for inappropriate simple hysterectomy included lack of preoperative cervical cytology (48.1%), false-negative cervical cytology (15.4%), incomplete evaluation of cervical dysplasia or microinvasion on biopsy (11.5%). failure to perform indicated conization( 5.8%), emergency hysterectomy (3.8%), errors in colposcopic examination (3.8%), incomplete evaluation of an abnormal cervical cytology (3.8%), failure to review slide (3.8%) and failure to biopsy a gross cervica lesion (3.8%). Conclusion: Most improper simple hysterectomy resulted from deviation from guideline for cervical cancer detection protocols. Improper simple hysterectomy in the presence of invasive cervical cancer can be avoided if one sticks to the diagnostic guideline for patients with an abnormal cervical cytology.

Cost Effectiveness of Bevacizumab Plus Chemotherapy for the Treatment of Advanced and Metastatic Cervical Cancer in India-A Model-Based Economic Analysis.

PURPOSE: Patients with advanced and metastatic cervical cancer have a poor prognosis with a 1-year survival rate of 10%-15%. Recently, an antiangiogenic humanized monoclonal antibody bevacizumab has shown to improve the survival of these patients. This study was designed to assess the cost effectiveness of incorporating bevacizumab with standard chemotherapy for the treatment of patients with advanced and metastatic cervical cancer in India. METHODS: Using a disaggregated societal perspective and lifetime horizon, a Markov model was developed for estimating the costs and health outcomes in a hypothetical cohort of 1,000 patients with advanced and metastatic cervical cancer treated with either standard chemotherapy alone or in combination with bevacizumab. Effectiveness data for each of the treatment regimen were assessed using estimates from Gynecologic Oncology Group 240 trial. Data on disease-specific mortality in metastatic cervical cancer, health system cost, and out-of-pocket expenditure were derived from Indian literature. Multivariable probabilistic sensitivity analysis was undertaken to account for parameter uncertainty. RESULTS: Over the lifetime of one patient with advanced and metastatic cervical cancer, bevacizumab along with standard chemotherapy results in a gain of 0.275 (0.052-0.469) life-years (LY) and 0.129 (0.032-0.218) quality-adjusted life-years (QALY), at an additional cost of $3,816 US dollars (USD; 2,513-5,571) compared with standard chemotherapy alone. This resulted in an incremental cost of $19,080 USD (7,230-52,434) per LY gained and $34,744 USD (15,782-94,914) per QALY gained with the use of bevacizumab plus standard chemotherapy. CONCLUSION: Addition of bevacizumab to the standard chemotherapy is not cost effective for the treatment of advanced and metastatic cervical cancer in India at a threshold of 1-time per-capita gross domestic product.

RUNX1T1, a potential prognostic marker in breast cancer, is co-ordinately expressed with ERα, and regulated by estrogen receptor signalling in breast cancer cells.

BACKGROUND: RUNX1T1 is extensively studied in the context of AML1-RUNX1T1 fusion protein in acute myeloid leukemia. Little is known about the function of RUNX1T1 itself, although data on its function and regulation have begun to emerge from clinical, and in vitro studies. It is a putative tumor suppressor, whose expression is altered in a variety of solid tumors. Recently, reduced expression of RUNX1T1 in triple-negative breast tumors, and its influence on prognosis was reported. METHODS AND RESULTS: The Kaplan-Meier Plotter online tool was used to study the relationship between RUNX1T1 expression and survival of breast cancer patients. High RUNX1T1 expression was associated with longer overall survival (OS), relapse-free survival (RFS) and distant metastasis free survival (DMFS). RUNX1T1 expression positively and negatively influenced OS of patients with ERα-positive and ERα-negative breast tumors, respectively. It was also associated with prolonged RFS, and DMFS in tamoxifen-treated patients. Expression of RUNX1T1 and ERα mRNA was analyzed in 40 breast tumor samples, and breast cancer cell lines using RT-PCR. TCGA-BRCA data was mined to study the relationship between RUNX1T1 and ERα mRNA expression. ERα-positive breast tumors showed significantly higher RUNX1T1 mRNA expression compared to ERα-negative tumors. RUNX1T1 mRNA expression was analyzed by qRT-PCR in MCF-7 or T47D cells, which were treated with 17ß-estradiol, or the ERα agonist PPT, alone or in combination with 4-hydroxytamoxifen. Effect of ERα knockdown was also investigated. Results indicate that estrogen downmodulated RUNX1T1 mRNA expression via ERα. CONCLUSION: Higher expression of RUNX1T1 in breast tumors is associated with favourable prognosis. RUNX1T1 and ERα show co-ordinated expression in breast tumors, and breast cancer cell lines. Estrogen-ERα signalling downmodulates the expression of RUNX1T1 mRNA in ERα-positive breast cancer cells. In-depth investigations on the interaction between RUNX1T1 and ERα are warranted to unravel the role and relevance of RUNX1T1 in breast cancer.

Cancer in patients of and above 90 years: A hospital-based retrospective study.

BACKGROUND AND OBJECTIVE: Cancers in a nonagenarian patient are rarely seen, and there is always a moral dilemma for the family members and patient of whether to opt for the treatment or not. The main objective was to identify the survival differences between treated and not treated nonagenarian cancer patients. MATERIALS AND METHODS: This was a retrospective study of Hospital-Based Cancer Registry data from 2010 to 2016. The data of all nonagenarian cancer patients were analyzed for gender distribution, leading sites of cancer, stage distribution, types of treatment received, and survival. The survival was calculated from the date of the first diagnosis. Kaplan-Meier analysis was done to present the survival. RESULTS: Of 60,087 patients, 146 (0.2%) patients were of 90 years and above. Hypopharynx in males (20.5%) and tongue (20.5%) in females were the top cancer sites, 60% patient data were in Stages III and IV, 37 (25.3%) patients received treatment, and 86% patients were treated by radiotherapy. The overall survival (OS) was 14.3%. OS in the treatment group was 21.3% versus 7.7% (P = 0.001) in the no treatment group. The unadjusted hazard ratio for no treatment group was 3.8 (P = 0.003, confidence interval = 1.5-9.7). CONCLUSION: Selected nonagenarian cancer patients from our population with a good performance status should receive curative treatments in all possible ways.

Influence of hormone receptors in breast cancer survival with correlation to place of residence.

INTRODUCTION: Breast cancer is commonly diagnosed cancer in women. Tumor receptors estrogen receptor (ER) and progesterone receptor (PR) are well recognized prognostic factors for breast cancer. MATERIALS AND METHOD: Data from the department of pathology for the 5-year period (2010 to 2014) is used for analysis for Kamrup district of Assam, India. Kaplan Meir method was used to evaluate survival rate. RESULT: The overall 5-year survival is observed as 54.6%. There is a 10.6% improvement in survival was recorded among those who living in the urban areas. The risk of death was 40% higher for those who were resides in rural areas compared to urban areas (P = 0.070). There is a 6 fold variation in survival was observed according to their stage at presentation. Hormone receptors found to be play an important role in survival outcome. Patients with ER/PR+ (positive) status have 13.6% higher survival rate than those with ER/PR-. The overall survival for ER/PR positive is 72.1% compared to 58.5% of ER/PR negative. CONCLUSION: From the study it is observed that population with positive hormone receptors (ER/PR +) and living in the urban areas is experiencing survival rate.

Fungal profile and antifungal susceptibility pattern of candidiasis in esophageal cancer patients.

AIM: This study was carried out to determine the fungal profile and antifungal susceptibility pattern in the brushing samples of candidiasis in patients with carcinoma of esophagus. MATERIALS AND METHODS: The study was carried out in the Departments of Microbiology and Surgical Oncology of a regional cancer center from January 2017 to December 2017. Samples were collected under all aseptic precaution and Clinical Laboratory Standards Institute guidelines 2017 was followed for antifungal susceptibility testing. RESULTS: A total of 132 endoscopy brushing samples were collected from histological proven esophageal cancer patients and processed for fungal culture. Of which, 75 (56.81%) samples showed culture positivity and were recruited. Candida albicans in 40 (53.33%), Candida krusei in 25 (33.33%), Candida tropicalis in 7 (9.33%), and Candida glabrata in 3 (4%) patients were seen. Among the 40 C. albicans isolates, all were sensitive to caspofungin - 40 (100%), 34 (85%) showed sensitivity to fluconazole, and 32 (80%) showed sensitivity to flucytosine. C. krusei and C. tropicalis showed 100% sensitivity to caspofungin, and C. glabrata isolates showed 100% resistance to caspofungin and 80% resistance to Amphotericin B. CONCLUSION: The present study revealed the emergence of multidrug-resistant, nonalbicans Candida isolates in cancer esophagus patients with candidiasis in northeast India.

Bacteriological Profile and Antibiotic Sensitivity Pattern of Clinical Isolates in a Tertiary Cancer Care Center in the Northeast India.

Background This study was performed to determine the bacteriological profile and antibiotic sensitivity pattern of culture samples of patients with cancer at our institute. The study was undertaken to formulate an antibiotic policy for the treatment of infection in these patients. Materials and Methods The study was performed in the Department of Microbiology of a regional cancer center during the period from January 2017 to December 2017. Samples were collected under all aseptic precaution, and they were processed as per the Clinical and Laboratory Standard Institute Guideline 2017. Results A total of 464 clinical samples (urine, blood, sputum, pus, etc.) were collected and processed for culture, of which 198 (42.67%) samples showed culture positive that were identified as per standard recommended procedures and antibiotic susceptibility testing was performed on isolates as per the Clinical Laboratory Standard Institute guidelines 2017. Escherichia coli (48), Staphylococcus aureus, (45) Klebsiella pneumoniae (52), Coagulase-negative Staphylococcus (17), and Pseudomonas aeruginosa (15) were most commonly encountered. Of the 132 Gram-negative isolates, 101 (76.5%) were extended-spectrum ß-lactamase producers. Among the 45 staphylococcal isolates, 18 (40%) were methicillin-resistant S . aureus. Conclusion The present study reveals microbiological profile in patients attending our cancer institute.

A Survival Analysis of Hypopharyngeal Cancer Patients: A Hospital-Cancer registry Based Study.

To study the survival in patients affected with hypopharyngeal cancer among treatment groups and different stages. Data of hypopharyngeal cancer patients diagnosed from 1st January 2010 to 31st December 2010 was used in the present study. The cases were analyzed for gender, age group distribution, sub-sites at presentation, stage at diagnosis and the type of treatments. Survival from the date of first diagnosis was estimated and hazard ratios were calculated. Survival probability and hazards ratios (HR) were calculated by Kaplan-Meier method and Cox-proportional regression analysis respectively. Censoring of patient who survived longer than 5 years was done. Active follow-up was done for the survival analysis. The study cohort included 217 patients and treatment compliance was observed in 46.9% of cases. The median age at diagnosis was 57 years (range 24-90), 86.2% of cases were locally advanced cases (stage III and IV), pyriform sinus was major sub-site (96%), radiotherapy was main treatment modality alone in 84.8% of cases, median survival was 31 months and 5-year overall survival was 36.9%, and HR for stage IV was 1.9 (P = 0.03, 95% CI - 1.04 to 3.7). In developing setting of North East India, radiotherapy was the main modality of treatment for hypopharyngeal cancer patients, and understanding the clinical parameters and survival of this group of cancers is crucial for its control.

Assessment and clinicopathological correlation of matrix metalloproteinase 9 expression in nasopharyngeal carcinoma.

INTRODUCTION: Nasopharyngeal cancer is not a common disease in most parts of the world. In India also, nasopharyngeal carcinoma (NPC) is not a common cancer, except for the Northeastern region of the country. Expression of matrix metalloproteinase 9 (MMP9) in the tumor cells is related to tumor invasion and metastasis. The aim of the present study is to analyze the expression of MMP9 in NPC and evaluate its prognostic implications. MATERIALS AND METHODS: A total of 32 histologically confirmed tissue samples of NPC were examined by immunohistochemical staining to assess the expression of MMP9. Clinicopathological parameters and levels of MMP9 expression in the tumor tissue were analyzed using Chi-square test. Survival analysis was done using the Kaplan-Meier method and was compared using log-rank test. P <0.05 was considered statistically significant. RESULTS: Of the 32 tissue samples of NPC, 23 (71.9%) were male and 9 (28.1%) were female. 7 (21.9%) patients presented in T1 Stage, 8 (25.0%) in T2, 12 (37.5%) in T3, and 5 (15.6%) in T4 Stages, respectively. 29 (90.6%) patients presented with lymph node metastasis. MMP9 expression level was significantly correlated with patient's age (P = 0.033), tumor histology (P = 0.017), tumor stage (P = 0.021), and lymph node metastasis (P = 0.011). The 5-year overall survival is higher for low-level expression as compared to high-level expression of MMP9 (P = 0.046). CONCLUSION: MMP9 is an important prognostic factor for NPC. High expression of MMP9 is associated with cervical lymph nodes metastasis and poor survival outcome.

Epigenetic deregulations of Wnt/ß-catenin and transforming growth factor beta-Smad pathways in esophageal cancer: Outcome of DNA methylation.

BACKGROUND: Promoter methylation of tumor suppressor genes (TSGs) is a well-reported portent in carcinogenesis; hence, it is worthy to investigate this in high-risk Northeast population of India. The study was designed to investigate methylation status of 94 TSGs in esophageal squamous cell carcinoma (ESCC). Further, the effect of OPCML promoter methylation on gene expression was analyzed by immunohistochemistry. Moreover, in silico protein-protein interactions were examined among 8 TSGs identified in the present study and 23 epigenetically regulated genes reported previously by our group in ESCC. MATERIALS AND METHODS: Methylation profiling was carried out by polymerase chain reaction array and OPCML protein expression was examined by tissue microarray-based immunohistochemistry. RESULTS: OPCML, NEUROG1, TERT, and WT1 genes were found hypermethylated and SCGB3A1, CDH1, THBS1, and VEGFA were hypomethylated in Grade 2 tumor. No significant change in OPCML expression was observed among control, Grade 1, and Grade 2 tumor. Conclusively, hypermethylation of the studied OPCML promoter in Grade 2 tumor produced no effect on expression. Unexpectedly, OPCML expression was downregulated in Grade 3 tumor in comparison to other groups signifying that downregulation of OPCML expression may lead to higher grade of tumor formation at the time of diagnosis of ESCC in patients. Significant interactions at protein level were found as VEGFA:PTK2, CTNNB1:CDH1, CTNNB1:VEGFA, CTNNB1:NEUROG1, CTNND2:CDH1, and CTNNB1:TERT. These interactions are pertinent to Wnt/ß-catenin and TGF-ß-Smad pathways. CONCLUSIONS: Deranged OPCML expression may lead to high-grade ESCC as well as epigenetically regulated genes, that is, CDH1, CTNNB1, CTNND2, THBS1, PTK2, WT1, OPCML, TGFB1, and SMAD4 may alter the Wnt/ß-catenin and TGF-ß-Smad pathways in ESCC. Further study of these genes could be useful to understand the molecular pathology of ESCC with respect to epithelial-mesenchymal transition (EMT) mediated by Wnt/ß-catenin and TGF-ß signaling pathways.

Squamous cell carcinoma of upper alveolus: An experience of a tertiary care center of Northeast India.

OBJECTIVE: The main objective of this study was to analyze the clinical behavior and the impact of nodal metastasis on the prognosis of upper alveolus squamous cell carcinoma (SCC). MATERIALS AND METHODS: The medical records of 110 patients with SCC of the upper alveolus (International Classification of Diseases-10-C03.0) diagnosed during 2010-2015 were reviewed. Survival analysis was done using the Kaplan-Meier method and was compared using log rank-test. P < 0.05 was considered statistically significant. RESULTS: Of the 110 patients, 59 were males and 51 were females. Forty-six (41.8%) patients presented with lymph node metastasis. Fifty-three (51.8%) patients presented in Stage IVA, thirty (27.3%) patients in Stage IVB, ten (9.1%) patients in Stage III, 12 (10.9%) patients in Stage II. The 5-year overall survival (OS) was 71.1% in Stage II, in Stage III it was 65.6%, in Stage it was IVA 56.7%, and in Stage IVB it was 19.4% (P = 0.02). The 5-year OS for node negative compared with node positive was 66.3% versus 37.3%, respectively (P = 0.019). CONCLUSION: Presence of lymph node metastasis is associated with lower survival rates. Adequate surgical resection with adjuvant treatment, where necessary, offers the best chance of disease control.

A survival study of uterine cervical patients in the North East India: Hospital-cancer registry-based analysis.

BACKGROUND: Uterine cervical cancer constitutes a major proportion of cancer in females of our population. The objective of this study was to conduct a clinical study of uterine cervical cancers including their survival from hospital-cancer registry data. MATERIALS AND METHODS: Data of uterine cervical cancer patients diagnosed from January 1, 2010 to December 31, 2010 and that were treated at a regional cancer center in North East (NE) India was recruited. The cases were analyzed for age group distribution, stage, and treatment types. Survival from the date of first diagnosis and hazard ratios (HRs) was estimated. Survival probability and HRs were calculated by Kaplan-Meier method and Cox-proportional regression analysis, respectively. Active follow-up was done for the survival analysis. RESULTS: One hundred and ninety-three patients (53.4%) were included for the analysis. Median age was 48 years, 56.5% (108/193) of patients were in the age group of 45-64 years, 56.5% (109/193) were Stage II patients, radiotherapy alone was the main treatment modality in 65.8% (127/193) of cases, 5-year overall survival (OS) was 40.7%, median survival was 44 months, early staged and advanced stage patients had 47.7%, and 29.4% 5-year OS (P = 0.002), respectively, and HR for advanced stages was 1.8 (P = 0.003, confidence interval (CI) = 1.2 to 2.7). CONCLUSION: Describing the clinical characteristics and survival of uterine cervical cancer patients is important for planning and identifying the gaps for its control in the NE India.

Patterns of tobacco use in patients with upper aero digestive tract cancers: A hospital-based study.

BACKGROUND: Tobacco use is a major risk factor for increasing the burden of upper aero digestive tract (UADT) cancer in the population of Northeast India. OBJECTIVE: The objective of this study was to investigate the pattern of tobacco use in different UADT cancer. MATERIALS AND METHODS: This was a retrospective study of electronically recorded data of the Hospital Cancer Registry for the period of May 2014 to December 2014. The UADT cancers were evaluated for gender and age-group distribution, their relative proportion, and association with tobacco use and tobacco-associated risk in males to develop UADT cancers. The type of tobacco usage was clustered as chewable, smoking, and both. Relative risk (RR) of UADT with tobacco usage was identified for males. RESULTS: A total of 1965 (n) UADT cancer patients were identified, male:female was 2.9, tobacco habits was in 1608 (81.8%) patients, both forms of tobacco use in 705 (43.8%), chewable tobacco use in 588 (36.6%) and smoking in 315 (19.6%) patients, tobacco habits in males ranges from 67.3% to 94.3% and in females range from 5.7% to 32.7%, RR of UADT cancer in males for tongue cancer was 1.5 (confidence interval [CI] =1.2-1.9), oropharynx was 1.4 (CI = 1.0-1.8), hypopharynx 1.4 (CI = 1.1-1.7), esophageal cancer was 1.4 (CI = 1.3-1.7), and for laryngeal cancer RR was 1.7 (CI = 1.0-3.0). CONCLUSION: Consumption of chewable tobacco is the major form of tobacco use alone or in combination in UADT cancer patients of our population.

Decreased Survival With Mastectomy Vis-à-Vis Breast-Conserving Surgery in Stage II and III Breast Cancers: A Comparative Treatment Effectiveness Study.

PURPOSE: The primary purpose of hospital-based cancer registries is assessing patient care. Clinical stage-based survival and treatment-based survival are some of the key parameters for such assessment. Because of the challenges in obtaining follow-up parameters, a separate study on patterns of care and survival was undertaken by the Indian National Cancer Registry Program. The results for cancer of the female breast are presented here. PATIENTS AND METHODS: Data abstracted in a standardized patient information form were transmitted online to a central repository. Treatment patterns were assessed for 9,903 patients diagnosed between January 1, 2006, and December 31, 2008, from 13 institutions. Survival analysis was restricted to 7,609 patients from nine institutions wherein follow-up details (as of December 31, 2012) were available for at least 60% of patients. RESULTS: The overall 5-year survival rates with breast-conserving surgery (BCS) and mastectomy (MS) were 94.0% and 85.8%, respectively, for stage II disease (adjusted hazard ratio, 2.40; 95% CI, 1.8 to 3.2) and 87.1% and 69.0%, respectively, for stage III disease (hazard ratio, 2.82; 95% CI, 2.2 to 3.7). Patients who had MS did better with systemic therapy (chemotherapy and/or hormone therapy), whereas patients with BCS required just local radiation therapy to achieve best survival. CONCLUSION: This observational study in the natural setting of care of patients with cancer in India showed significantly decreased survival with MS when compared with BCS. The reasons for lower survival with MS and the biologic or scientific rationale of the necessity of systemic therapy to achieve optimal survival in patients undergoing MS but not in those with BCS need further investigation.