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IJCRR - 10(7), April, 2018

Pages: 22-27

Date of Publication: 14-Apr-2018

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Efficacy of Pemetrexed or Pemetrexed Plus Cisplatin/Carboplatin in Pretreated Patients with Advanced Non\?Small-Cell Lung Cancer

Author: Nurgul Yasar, Caglayan Geredeli

Category: Healthcare

Abstract:Introduction: In this study, the efficacy and safety of pemetrexed alone and platinum-pemetrexed combination chemotherapy were evaluated in patients who have demonstrated progression after the first-line treatments in advanced non-small cell lung cancer (NSCLC).
Material and Method: 263 patients, who were diagnosed NSCLC in years 2008 - 2014, were assessed retrospectively in single center. Patients were given pemetrexed 500 mg/m2, and the ones receiving combined treatment were given pemetrexed 500 mg/ m2 and cisplatin 75 mg/m2 or carboplatin area under the curve 5 according to the Calvert formula (AUC 5 ) once in every 21 days.
Results: One hundred ninety (72%) of the patients had received pemetrexed, seventy three (28%) of the patients had received platinum- pemetrexed. Median PFS (progression-free survival) was 2 months (95% CI, 1. 6 - 2.4 ) for pemetrexed arm versus 4 months (95% CI, 2.6 to 5.3 ) for platinum- pemetrexed arm (p=0.001). The HR ( hazard ration) for disease progression was 0.45 (95% CI, 0.25 to 0.65) in favor of the combination arm (p=0.001). Median OS (overall survival) was 7 months (95% CI, 5.9 - 8 ) for pemetrexed arm versus 10 months (95% CI, 8 to 11.9 ) platinum-pemetrexed arm, respectively (p=0.001). The 1-year survival
rate was 24% and 42% for pemetrexed arm and combination arm, respectively. Toxicities in both arm was manageable.
Conclusion: Our study has shown that adding platinum compound to second-line pemetrexed chemotherapy significantly increases ORR (overall response rate), PFS and OS in patients with advanced NSCLC after having received first-line platinumbased chemotherapy.

Keywords: NSCLC, Second line treatment, Pemetrexed

DOI: 10.7324/IJCRR.2018.1075

Full Text:

Introduction

Lung cancer, estimating for approximately 13% of total cancer cases, pursues one of the major causes of cancer-related death worldwide with an estimated 1.8 million new lung cancer cases occured in 2012(1). Non-small cell lung cancer (NSCLC) accounts for 80-85 % of all lung cancers, and 75%of patients are diagnosed at the advanced stages of disease (2). First-line treatment for patients with stage IIIB or stage IV NSCLC usually consists of platinum-based doublet chemotherapy was found to produce a survival benefit(3,4). Nonetheless, disease progression ultimately occurs for most patients and further treatment is reguired.(5). When compared with best supportive care, second-line chemotherapy with docetaxel, pemetrexed or other agents are associated with (OS) benefit and improvement of quality of life (5,6,7).

Pemetrexed, an analogue of folic acid, was approved for first-line, second-line and maintenance treatmentof advanced NSCLC (4,7). It inhibits three enzymes which necessary for de novo pyrimidine and purine synthesis:thymidylate synthase (TYMS), dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase (4,7). In the first-line setting, pemetrexed/platinum combination is more effective than gemcitabine/platinum combination for advanced NSCLC patients with adenocarcinoma histologic subtype (4). In the second-line therapy, pemetrexed was associated with more favorable toxicity profile compared with docetaxel and comparable efficacy (median survival of 8.3 months vs 7.9 months)(7).

Combinations of chemotherapy agents have been competent in increasing efficacy over single agents in the first-line treatment(8,9). On the other hand, role of combinations is less clear in the second-line treatment (8,9). In this study, the efficacy and safety of pemetrexed alone and platinum-pemetrexed combination chemotherapy were evaluated retrospectively in patients who were non-responders or who have demonstrated progression after the first-line treatments in local advanced and metastatic NSCLC.

Materials and methods

We performed a retrospective screening of 263 patients who had pathologically or cytologically confirmed as stage IIIB to IV lung adenocarcinoma in SB Okmeydani Training and Researh Hospital between November 2008 and May 2014. These patients had failed prior chemotherapy regimen and received pemetrexed alone or platinum-pemetrexed combination chemoterapy rejimens in the second-line setting. Data were collected on baseline characteristics including age, gender, Eastern Cooperative Group (ECOG) performance status (PS), histology, stage, single agent or combined administration of treatment, third or further-line treatment intake and length of progression-free period after the first-line treatment.

Pemetrexed 500 mg/m2 administered as an intravenous (IV) bolus infusion of 10 minutes duration every 3 weeks. Folic acid and vitamin B12 supplementation was mandatory for all patients. Dexamethasone 4 mg tablet, three times a day for 3 days, was administered routinely to prevent allergic reactions. Cisplatin 75 mg/m2 administration intravenously over a 2-h infusion or carboplatin area under the curve 5 according to the Calvert formula (AUC 5 ) a 30-min infusion after pemetrexed administration every 3 weeks.

Patients underwent baseline computed tomography (CT) at the beginning of second-line chemotherapy and computed tomography repeated every 2-3 cycles of chemotherapy. Evaluation of treatment response was based on the Response Evaluation Criteria in Solid Tumors (RECIST) (10). Patients achieving complete response and partial response were recognized to be responders. Adverse events (AEs) were classified according to National Cancer Institute Common Terminology Criteria for Advers Events (CTCAE), version 3.

statistical analysis

The baseline characteristics of the patients were analyzed using descriptive statistics. PFS of second-line chemotherapy was measured from the date of initiation of second-line chemotherapy to the date of disease progression or any cause of death. OS for second-line chemotherapy was calculated from the date of initiation of second-line chemotherapy to the date of death from any cause. The Kaplan-Meier method was used to estimate PFS and OS. The difference between the survival curves of the treatment groups was tested using the log-rank test. In multivariate analysis with the Cox proportional hazards model, including age, gender, ECOG performance status, stage, the length of progression-free period after first- line treatment and the number of course for first and second-line chemotherapy, were used to estimate for PFS and OS. The chi-square test or Fisher exact test was used to compare the ORRs and adverse events (AEs) between two groups. A two-sided p value of ≤0.05 was considered statistically significant. All statistical analyses were performed using SPSS statistics 17.0 (SPSS, Inc, Chicago, IL).

Results

From November 2008 to May 2014, 263 patient files were screened onto this study. The median follow-up period was 7 months (range, 1 to 74 months). Two hundred thirty-seven patients (90%) died during the follow-up. Patients characteristics were listed in Table 1.Two hundred twelve (81%)males and 51 (19%) females were included. Median age at diagnosis was 55 years (range,28-83), 85% had PS of 0 to 1, 91% had stage IV disease, and 94% of the patients were diagnosed with adenocarcinoma.

The length of progression-free period after first-line of treatment was 6 months (range, 1- 88 months) for patient groups. The median time off platinum treatment was 6 months (range, 1 to 49 months) in pemetrexed arm and 7 months (range, 6 to 88 months) in platinum-pemetrexed arm. Median number of courses was five for the first-line setting. One hundred ninety (72%) of the patients had received pemetrexed, seventy three (28%) of the patients had received platinum- pemetrexed as second-line treatment. None of the patients had received pemetrexed as part of first-line treatment. Median number of cycles was four in patient groups for the second-line treatment. Two patients stopped treatment because of an adverse event. Three percent of patients had a dose reduction for pemetrexed arm, and 4%%of patients had a dose reduction for platinum-pemetrexed arm.

With the exception of hematologic toxicity, fatigue, nasuea and vomiting, the frequency of treatment-related toxicity exceeding CTCAE grade 2 was less than 5% for all categories (Table 2). Neutropenia (12,5%), nasuea and vomiting (12%) and fatique (10%) were all more frequently observed in the platinum-pemetrexed arm, significantly (p<0,05) .In particular, the incidence of hospitalization cause of febrile neutropenia was 3,4% in both treatment arms.

Two complete response were observed, whereas 39 patients (15%) had a confirmed partial response as the best response (Table 3). Nineteen (26%) of these patients were the combination of platinum and pemetrexed, whereas 20 (10% ) patients received pemetrexed alone (p=0,001). The median duration of response was 3 months. More patients in the pemetrexed arm had disease progression as compared with the combination arm (119 patients [63%] versus 31 patients [42%],(p=0,003) ).

Median PFS of the patients treated with pemetrexed alone was 2 months (95% CI, 1.6 to 2.4 months) and median PFS was 4 months (95% CI, 2.6 to 5.3 months) for patients treated with platinum and pemetrexed (Figure1). The HR for disease progression was 0.45 (95% CI, 0.25 to 0.65) in favor of the combination arm (p=0,001).Median overall survival was 7 months (95% CI, 5.9 to 8 months) versus 10 months (95% CI,8 to 11.9 months) for pemetrexed arm and platinum-pemetrexed arm, respectively (p=0,001, HR =0.67 [95%CI,0.20 to2.3]) (Table 3 figure 2). The 1-year survival rate was 24% and 42% for pemetrexed arm and combination arm, respectively.

Log-rank tests stratified by the treatment arm indicated that performance status and gender were significantly related to OS (p=0,034, p=0,032 ). Female gender had a better prognosis than male gender. . This model indicated that survival was worse for patients with higher performance status (p=0, 001). In addition, multivariate analysis, age, gender, stage, progression-free interval of more than 6 months after first- line were not found to be effective on survival.

Discussion

Several prospective trials and meta-analyses clearly defined the role of combination chemotherapy particularly for platinum-based rejimens in the first-line treatment of advanced NSCLC (11,12). Unfortunately, these patients show progression after the first-line treatment and most of them are the candidates for the second-line treatment (5,7,1). In the second-line treatment, docetaxel, pemetrexed and erlotinib have been registered by the European Medicines Agency (EMA) and US Food and Drug Administration for treatment of advanced NSCLC (5,6,7,13). Although these treatments are efficient for the second-line, these patients show progression readily and survival of patients with advanced NSCLC is poor (5,7). In this retrospective study for the second-line treatment, we aimed to invastigate the efficiency of pemetrexed alone and platinum-pemetrexed combination rejimens for the patients received platin-based combination chemotherapy before.

               In advanced NSCLC patients who received first-line setting  pemetrexed-platinum combination chemotherapy,  approximately 28-45% ORR and 4.8-6.9 months of  PFS  were announced by the studies had carried out before (14,15). Meta analysis of  Di Maio et al (16) included 847 eligible patient showed that in comparison of combination chemotherapy and  single-agent therapy for the second-line treatment of advanced NSCLC, combination chemotherapy increased RR (p=0.0004) and PFS(p=0.0009) significantly but not OS (p=0.32).   OS was not significantly different between arms (p= 0.32)(16) (16). Median OS was 37.3 and 34.7 weeks in the doublet and single-agent arms, respectively. HR was 0.92 (95% CI, 0.79 to 1.08). Response rate was 15.1% with doublet and 7.3% with single-agent (p=.0004) (16). Median progression-free survival was 14 weeks for doublet and 11.7 weeks for single agent (p = .0009; HR, 0.79; 95% CI, 0.68 to 0.91). According to this meta analysis, toxicity was higher in combination rejimen, as well (16).

               Smit et al (17) reported that median PFS was 2.8 month for patients second line treated with pemetrexed alone and 4.2 months for those treated with carboplatin and pemetrexed  and the HR for disease progression was 0.67 (95% CI, 0.51 to 0.89) in favor of the combination arm (p=.005). Whereas, median overall survival was 7.6 months  to 8.0 months (HR, 0.85; 95% CI, 0.63 to 1.2; p=not significant) (17). Our results (PFS was 2 month and OS was 4 month) are quite similar to those of Smit et al with 2.8 months of PFS and 4.2 months of OS. Ardizonni et al(GOIRC 02-2006 Trial and NVALT7) pooled analysis (18) recently published that median OS was not different between the two treatment arms: 8.2 months for pemetrexed alone (95% CI, 6.9 to 9.1 month) as compared with 8.7 months for carboplatin- pemetrexed (95% CI, 7.5 to 10.5 months; HR, 0.90; 95% CI, 0.74 to 1.10; p=0.316). However, RR was higher (15% v 9%) in the carboplatin-pemetrexed arm, with an OR of 1.72 (95% CI, 0.97 to 3.02; p=0.062).(18)  A non istatistically significant increase in PFS from 3 months (95% CI, 2.7 to 3.3) to 3.9 months (95% CI, 3.4 to 4.4), favoring the combined chemotherapy arm, was also observed, with an HR of 0.85 (95% CI, 0.70 to 1.02; p=0.07)(18). Our PFS results (PFS was 2 month ) was shorter than to those of Ardizonni et al with 2.8 months of PFS.

In our study we demostrated that median PFS was 2 months (95% CI, 1.6 to 2.4 months) and 4 months (95% CI, 2.6 to 5.3 months) for patients treated with pemetrexed alone and platinum- pemetrexed combination, respectively. HR for disease progression was 0.45 (95% CI, 0.25 to 0.65) in favor of the combination arm (p=0,001). Median overall survival was 7 months (95% CI, 5.9 to 8 months) versus 10 months (95% CI,8 to 11.9 months) for pemetrexed arm and platinum-pemetrexed arm, respectively (p=0,001, HR =0.67[95%CI, 0.20 to2.3]). One-year survival rate was 24% and 42% for pemetrexed arm and combination arm, respectively. In our study, both PFS and OS was statistically different in favour of the combination arm. Although our study was retrospective, the number of cencored case was low due to 90% of the patients death at the end of the study. Additionally, our patient group consisted of only the patients who had non-squamous histology and 85% of the patients had 0-1 PS. Partial response rate was higher in combination arm and progression rate was higher in pemetrexed arm significantly (p=0.001, p=0.003, respectively).

In comparison of pemetrexed arm and platinum-pemetrexed arm, in the means of grade 2 or more toxicity; although, fatique, neutropenia, nasuea and vomiting were observed more in combination arm, there was no difference in febrile neutropenia and quiting due to side affects.

Pemetrexed is a chemotherapy agent used in advanced NSCLC patients for the first-line, second-line and maintenance treatments, which has favourable toxicity profile (7,13,14,15). Contrarily, since its survival in advanced NSCLC is disappointing, more effective treatment options are being invastigated continously. Studies of pemetrexed combination with other chemotherapy agents except platinium compounds like targeted agents and immunotherapy agents are being carried out (19-25). While some of these studies are promising, some of them are fail. It was demostrated that the EGFR mutant patients treated with first-line platinum-pemetrexed combinations, ORR was significantly higher than that of the wild-type patients treated with similar regimens (43 vs. 21 %, p=0.039) (26). Additionally, in another study erlotinib statistically decreased TS expression and activity, maybe means that it increases the sensitivity of pemetrexed (27). Pemetrexed can be used for second-line treatment with good response rate in patients having TKIs resistance (27). All these studies shows that pemetrexed usage is going to continue in advanced NSCLC treatment.

There was several limitations in our study. First, this was a retrospective study and population of the study may not represent the average population. Second, the number of the patients in pemetrexed group and combination chemotherapy group were not the same. Third, treatments after second-line is not specified. Fourth, Although very few patients had received anti-EGFR therapy after the second-line treatment, situation of EGFR mutation in patients was not known. Fifth, the choice of cisplatin or carboplatin, and response evaluation are dependent to the clinical practice of oncology physicians. This study design has a lack of standardization and quality control.

In conclusion, our study has shown that adding platinum compound to second-line pemetrexed chemotherapy significantly increases ORR, PFS and OS in patients with advanced NSCLC after having received first-line platinum-based chemotherapy and the toxicity profile of pemetrexed/ platinum combination rejimen is manageable. It is needed that further randomized prospective studies with larger samples on efficiency of platinum-pemetrexed combination or less toxic pemetrexed- based combinations in second-line chemotherapy for advanced NSCLC.

Acknowledgements

Author acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The author is also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.

Source of funding: No funding source

Conflict of interest: No conflict of interest

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A Study by Isha Gaurav et al. entitled "Association of ABO Blood Group with Oral Cancer and Precancer – A Case-control Study" is awarded Best Article for Vol 13 issue 20

A Study by Amr Y. Zakaria et al. entitled "Single Nucleotide Polymorphisms of ATP-Binding Cassette Gene(ABCC3 rs4793665) affect High Dose Methotrexate-Induced Nephrotoxicity in Children with Osteosarcoma" is awarded Best Article for Vol 13 issue 19

A Study by Kholis Ernawati et al. entitled "The Utilization of Mobile-Based Information Technology in the Management of Dengue Fever in the Community Year 2019-2020: Systematic Review" is awarded Best Article for Vol 13 issue 18

A Study by Bhat Asifa et al. entitled "Efficacy of Modified Carbapenem Inactivation Method for Carbapenemase Detection and Comparative Evaluation with Polymerase Chain Reaction for the Identification of Carbapenemase Producing Klebsiella pneumonia Isolates" is awarded Best Article for Vol 13 issue 17

A Study by Gupta R. et al. entitled "A Clinical Study of Paediatric Tracheostomy: Our Experience in a Tertiary Care Hospital in North India" is awarded Best Article for Vol 13 issue 16

A Study by Chandran Anand et al. entitled "A Prospective Study on Assessment of Quality of Life of Patients Receiving Sorafenib for Hepatocellular Carcinoma" is awarded Best article for Vol 13 issue 15

A Study by Rosa PS et al. entitled "Emotional State Due to the Covid – 19 Pandemic in People Residing in a Vulnerable Area in North Lima" is awarded Best Article for Vol 13 issue 14

A Study by Suvarna Sunder J et al. entitled "Endodontic Revascularization of Necrotic Permanent Anterior Tooth with Platelet Rich Fibrin, Platelet Rich Plasma, and Blood Clot - A Comparative Study" is awarded Best Article for Vol 13 issue 13

A Study by Mona Isam Eldin Osman et al. entitled "Psychological Impact and Risk Factors of Sexual Abuse on Sudanese Children in Khartoum State" is awarded Best Article for Vol 13 issue 12

A Study by Khaw Ming Sheng & Sathiapriya Ramiah entitled "Web Based Suicide Prevention Application for Patients Suffering from Depression" is awarded Best Article for Vol 13 issue 11

A Study by Purushottam S. G. et al. entitled "Development of Fenofibrate Solid Dispersions for the Plausible Aqueous Solubility Augmentation of this BCS Class-II Drug" is awarded Best article for Vol 13 issue 10

A Study by Kumar S. et al. entitled "A Study on Clinical Spectrum, Laboratory Profile, Complications and Outcome of Pediatric Scrub Typhus Patients Admitted to an Intensive Care Unit from a Tertiary Care Hospital from Eastern India" is awarded Best Article for Vol 13 issue 09

A Study by Mardhiah Kamaruddin et al. entitled "The Pattern of Creatinine Clearance in Gestational and Chronic Hypertension Women from the Third Trimester to 12 Weeks Postpartum" is awarded Best Article for Vol 13 issue 08

A Study by Sarmila G. B. et al. entitled "Study to Compare the Efficacy of Orally Administered Melatonin and Clonidine for Attenuation of Hemodynamic Response During Laryngoscopy and Endotracheal Intubation in Gastrointestinal Surgeries" is awarded Best Article for Vol 13 issue 07

A Study by M. Muthu Uma Maheswari et al. entitled "A Study on C-reactive Protein and Liver Function Tests in Laboratory RT-PCR Positive Covid-19 Patients in a Tertiary Care Centre – A Retrospective Study" is awarded Best Article of Vol 13 issue 06 Special issue Modern approaches for diagnosis of COVID-19 and current status of awareness

A Study by Gainneos PD et al. entitled "A Comparative Evaluation of the Levels of Salivary IgA in HIV Affected Children and the Children of the General Population within the Age Group of 9 – 12 Years – A Cross-Sectional Study" is awarded Best Article of Vol 13 issue 05 Special issue on Recent Advances in Dentistry for better Oral Health

A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" is awarded Best Article of Vol 13 issue 06

A Study by Chen YY and Ghazali SRB entitled "Lifetime Trauma, posttraumatic stress disorder Symptoms and Early Adolescence Risk Factors for Poor Physical Health Outcome Among Malaysian Adolescents" is awarded Best Article of Vol 13 issue 04 Special issue on Current Updates in Plant Biology to Medicine to Healthcare Awareness in Malaysia

A Study by Kumari PM et al. entitled "Study to Evaluate the Adverse Drug Reactions in a Tertiary Care Teaching Hospital in Tamilnadu - A Cross-Sectional Study" is awarded Best Article for Vol 13 issue 05

A Study by Anu et al. entitled "Effectiveness of Cytological Scoring Systems for Evaluation of Breast Lesion Cytology with its Histopathological Correlation" is awarded Best Article of Vol 13 issue 04

A Study by Sharipov R. Kh. et al. entitled "Interaction of Correction of Lipid Peroxidation Disorders with Oxibral" is awarded Best Article of Vol 13 issue 03

A Study by Tarek Elwakil et al. entitled "Led Light Photobiomodulation Effect on Wound Healing Combined with Phenytoin in Mice Model" is awarded Best Article of Vol 13 issue 02

A Study by Mohita Ray et al. entitled "Accuracy of Intra-Operative Frozen Section Consultation of Gastrointestinal Biopsy Samples in Correlation with the Final Histopathological Diagnosis" is awarded Best Article for Vol 13 issue 01

A Study by Badritdinova MN et al. entitled "Peculiarities of a Pain in Patients with Ischemic Heart Disease in the Presence of Individual Combines of the Metabolic Syndrome" is awarded Best Article for Vol 12 issue 24

A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23

A Study by Habiba Suhail et al. entitled "Effect of Majoon Murmakki in Dysmenorrhoea (Usre Tams): A Standard Controlled Clinical Study" is awarded Best Article for Vol 12 issue 22

A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21

A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20

A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19

A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18

A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17

A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16

A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15

A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020

A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"

A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13

A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for Vol 12 issue 12

A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for Vol 12 issue 11

A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for Vol 12 issue 10

A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for Vol 12 issue 09

A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for Vol 12 issue 08

A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for Vol 12 issue 07

A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20

A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR

A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13

A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR

A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR.

A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award

A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award

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