Eight Year Survival Analysis of Patients with Triple Negative Breast Cancer in India

Doval, Dinesh Chandra,Suresh, P,Sinha, Rupal,Azam, Saud,Batra, Ullas,Talwar, Vineet,Kumar, Kapil,Mehta, Anurag Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.6

Background: Triple-negative breast cancer (TNBC) often presents as an interval cancer with short survival upon metastasis and thus represents an important clinical challenge. The present study investigated the clinicopathologic characteristics and long term survival outcome of early and locally advanced TNBC. Materials and Methods: Medical records were reviewed retrospectively for 148 consecutive confirmed cases of TNBC treated in a single unit at our centre. Demographic profile, tumor type, histopathology details, treatment and follow-up information was recorded and immunohistochemistry was performed. Results: Age group >50 years was associated with tumors of clinical stage 3 (53.8%), pathological stage 3 (46.2%), pathological grade 3 (45.7%), presence of extracapsular extension (ECE, 48.5%) and lymphovascular invasion (LVI, 64.9%). Locally advanced breast cancers (LABCs) were characterized by pathological stage 3 (96.2%), presence of ECE (100%) and absence of LVI (46.7%) as compared to early breast cancers (EBCs) which had higher incidence of lower stage tumors (100%), absence of ECE (82%) and presence of LVI (91.9%; p-value <0.001. Better relapse free survival was observed in patients with no axillary involvement (69%; p-value <0.001) and absence of ECE (64%; p-value <0.001). Improved overall survival was seen in patients with EBC (90%; p-value 0.008), clear axilla (86%; p-value <0.001), absence of ECE (87%; p-value <0.001) and negative lymph nodes (90%; p-value 0.006). Conclusions: TNBCs are aggressive tumors which show poor long term survival. Patients with TNBC benefit from chemotherapy, thus better and less toxic treatment options are needed. Identification of newer targets and development of targeted therapies are the need of the hour.

Immunohistochemical Profile of Breast Cancer Patients at a Tertiary Care Hospital in New Delhi, India

Doval, Dinesh Chandra,Sharma, Anila,Sinha, Rupal,Kumar, Kapil,Dewan, Ajay Kumar,Chaturvedi, Harit,Batra, Ullas,Talwar, Vineet,Gupta, Sunil Kumar,Singh, Shailendra,Bhole, Vidula,Mehta, Anurag Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.12

Background: To assess the immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor-2 (HER2) neu receptor in breast cancer and their associations with various clinicopathological characteristics. Materials and Methods: This is a retrospective analysis of women who presented with primary, unilateral breast cancer in the Department of Medical Oncology at Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India during the period from January 2008 to December 2011. Data were retrieved from the medical records of the hospital including both early and locally advanced cancer cases. ER, PgR and HER2neu expression in these patients was assessed and triple negative patients were identified. Associations of triple negative and non-triple negative groups with clinicopathological characteristics were also evaluated. Results: A total of 1,284 women (mean age 52.1 years, 41.9% premenopausal) were included in the analysis. Hormone receptor positivity (ER and/or PgR) was seen in 63.4% patients, while 23.8% of tumors were triple negative. Only 23.0% were HER2 positive. Around 10.0% of tumors were both ER and HER2 positive. ER and PgR positivity was significantly associated with negative HER2 status (p-value <0.0001). Younger age, premenopausal status, higher tumor grade, lymph node negativity, advanced cancer stage, and type of tumor were strongly associated with triple negativity. Significantly, a smaller proportion of women had ductal carcinoma in situ in the triple negative group compared with the non-triple negative group (35.6% versus 60.8%, p-value<0.01). Conclusions: The present analysis is one of the largest studies from India. The majority of the Indian breast cancer patients seen in our hospital present with ER and PgR positive tumors. The triple negative patients tended to be younger, premenopausal, and were associated with higher tumor grades, negative lymph nodes status and lower frequency of ductal carcinoma in situ.

Lifestyle and Sporadic Colorectal Cancer in India

Sinha, Rupal,Doval, Dinesh Chandra,Hussain, Showket,Kumar, Kapil,Singh, Shivendra,Basir, Seemi Farhat,Bharadwaj, Mausumi Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.17

Background: The study evaluated the patient, lifestyle and tumor profile in patients undergoing upfront surgery for sporadic colorectal cancer (CRC) in Indian population. Materials and Methods: One hundred consecutive patients were included. Details related to their demographic profile, habits, signs and symptoms, tumor profile, further treatment and follow up were recorded. Results: The majority of the patients had colonic cancer (68%), advanced tumor stage 3 & 4 (46%), moderately differentiated tumors (70%) with absence of lymphatic invasion (60%) and metastasis (90%). Correlations between tumor location and abdominal pain (p-value 0.002), bleeding per rectum (p-value <0.001), difficulty in micturition (p-value 0.012) and constipation (p-value 0.007) were found to be statistically significant. Abdominal pain was more frequently reported in patients with metastasis (p-value 0.031). Loss of weight statistically correlated with absence of lymphatic invasion (p-value 0.047). Associations between tumor stage and alcohol intake (p-value 0.050) and non vegetarian diet (p-value 0.006); lymphatic invasion and intake of spicy food (p-value 0.040) and non vegetarian diet (p-value 0.001) and metastasis and alcohol intake (p-value 0.041) were also observed. Age and tumor grade were also correlated (p-value 0.020). Conclusions: Minimizing the adverse lifestyle factors can help in reducing the overall incidence of CRC in the Indian population.

Clinicopathological Characteristics of Triple Negative Breast Cancer at a Tertiary Care Hospital in India

Dogra, Atika,Doval, Dinesh Chandra,Sardana, Manjula,Chedi, Subhash Kumar,Mehta, Anurag Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

Background: Triple-negative breast cancer (TNBC), characterized by the lack of expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2, is typically associated with a poor prognosis. The majority of TNBCs show the expression of basal markers on gene expression profiling and most authors accept TNBC as basal-like (BL) breast cancer. However, a smaller fraction lacks a BL phenotype despite being TNBC. The literature is silent on non-basal-like (NBL) type of TNBC. The present study was aimed at defining behavioral differences between BL and NBL phenotypes. Objectives: i) Identify the TNBCs and categorize them into BL and NBL breast cancer. ii) Examine the behavioral differences between two subtypes. iii) Observe the pattern of treatment failure among TNBCs. Materials and Methods: All TNBC cases during January 2009-December 2010 were retrieved. The subjects fitting the inclusion criteria of study were differentiated into BL and NBL phenotypes using surrogate immunohistochemistry with three basal markers $34{\beta}E12$, c-Kit and EGFR as per the algorithm defined by Nielsen et al. The detailed data of subjects were collated from clinical records. The comparison of clinicopathological features between two subgroups was done using statistical analyses. The pattern of treatment failure along with its association with prognostic factors was assessed. Results: TNBC constituted 18% of breast cancer cases considered in the study. The BL and NBL subtypes accounted for 81% and 19% respectively of the TNBC group. No statistically significant association was seen between prognostic parameters and two phenotypes. Among patients with treatment failure, 19% were with BL and 15% were with NBL phenotype. The mean disease free survival (DFS) in groups BL and NBL was 30.0 and 37.9 months respectively, while mean overall survival (OS) was 31.93 and 38.5 months respectively. Treatment failure was significantly associated with stage (p=.023) among prognostic factors. Conclusions: Disease stage at presentation is an important prognostic factor influencing the treatment failure and survival among TNBCs. Increasing tumor size is related to lymph node positivity. BL tumors have a more aggressive clinical course than that of NBL as shown by shorter DFS and OS, despite having no statistically significant difference between prognostic parameters. New therapeutic alternatives should be explored for patients with this subtype of breast cancer.

International benchmark study of advanced thermal hydraulic safety analysis codes against measurements on IEA-R1 research reactor

Hainoun, A.,Doval, A.,Umbehaun, P.,Chatzidakis, S.,Ghazi, N.,Park, S.,Mladin, M.,Shokr, A. North-Holland Pub. Co 2014 Nuclear engineering and design Vol.280 No.-

In the framework of the IAEA Coordination Research Project on ''Innovative methods in research reactor analysis: Benchmark against experimental data on neutronics and thermal hydraulic computational methods and tools for operation and safety analysis of research reactors'' the Brazilian research reactor IEA-R1 has been selected as reference facility to perform benchmark calculations for a set of thermal hydraulic codes being widely used by international teams in the field of research reactor (RR) deterministic safety analysis. The goal of the conducted benchmark is to demonstrate the application of innovative reactor analysis tools in the research reactor community, validation of the applied codes and application of the validated codes to perform comprehensive safety analysis of RR. The IEA-R1 is equipped with an Instrumented Fuel Assembly (IFA) which provided measurements for normal operation and loss of flow transient. The measurements comprised coolant and cladding temperatures, reactor power and flow rate. Temperatures are measured at three different radial and axial positions of IFA summing up to 12 measuring points in addition to the coolant inlet and outlet temperatures. The considered benchmark deals with the loss of reactor flow and the subsequent flow reversal from downward forced to upward natural circulation and presents therefore relevant phenomena for the RR safety analysis. The benchmark calculations were performed independently by the participating teams using different thermal hydraulic and safety analysis codes that comprise of CATHARE, RELAP5, MERSAT and PARET. The code RELAP5 was used independently by four of the participating teams and therefore the user effect and its impact on the code results can be characterized. The benchmark results demonstrate that most of the codes have the capability to correctly predict the SS case. However, for the LOFA case the simulation results show discrepancies to the measurement although the majority of the applied codes predict a qualitative correct time evolution of the corresponding transients for the coolant and clad temperatures. It is noted that the peak temperatures and the gradients around them are predicted conservatively. The quantitative assessments of benchmark results indicate different amounts of discrepancy between predictions and measurements ranging between 7% and 20% for peak clad temperatures during LOFA. The comparative prediction capability of the employed codes is addressed by additional code-to-code comparisons based on selected TH parameters that comprise flow rate, pressure drop and heat transfer coefficient during natural circulation phase.

Harmonic Identification Algorithms Based on DCT for Power Quality Applications

Alejandro G. Yepes,Francisco D.Freijedo,Jesús Doval-Gandoy,Óscar López Sánchez,Pablo Fernández-Comesaña,Jano Malvar Álvarez 한국전자통신연구원 2010 ETRI Journal Vol.32 No.1

The increasing demand for non-sinusoidal currents affects the quality of distribution networks. Harmonic detection is a crucial step in the cancellation of those components by active power filters. In this paper, the discrete cosine transform (DCT) is compared with different implementations based on Fourier transforms, demonstrating their equivalences and the advantages provided by the former. We demonstrate that the phase error in the presence of grid frequency deviations and the transient length are reduced by half in comparison to the discrete Fourier transform. A novel algorithm is developed to provide frequency adaptation to the DCT, taking advantage of its good features. The window width is adjusted in real time according to the actual value of the grid fundamental frequency by means of a phase-locked loop. A technique based on dithering is employed to overcome the limitation caused by the truncation of the window number of samples, so the frequency resolution is enhanced. The theoretical approach is verified by simulated and experimental results.

Reduced graphene oxide modified smart conducting paper for cancer biosensor

Kumar, Saurabh,Kumar, Suveen,Srivastava, Saurabh,Yadav, Birendra K.,Lee, Seung H.,Sharma, Jai G.,Doval, Dinesh C.,Malhotra, Bansi D. Elsevier 2015 Biosensors & bioelectronics Vol.73 No.-

<P><B>Abstract</B></P> <P>We report results of the studies relating to the fabrication of a paper based sensor comprising of poly (3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and reduced graphene oxide (RGO) composite. The effect of various solvents like methanol, ethylene glycol and H<SUB>2</SUB>SO<SUB>4</SUB> on the electrical conductivity of PEDOT:PSS coated Whatman paper has been investigated. The conductivity of this solution processed conducting paper significantly increases from ~1.16×10<SUP>−4</SUP> Scm<SUP>−1</SUP> up to ~3.57×10<SUP>−2</SUP> Scm<SUP>−1</SUP> (~300 times) on treatment with ethylene glycol. The observed significant increase in electrical conductivity is due to conformational rearrangement in the polymer and is due to strong non-covalent cooperative interaction between PEDOT and the cellulose molecules. Further, incorporation of RGO into the conducting paper results in improved electrochemical performance and signal stability. This paper electrode is a promising alternative over the expensive conventional electrodes (ITO, gold and glassy carbon), that are known to have limited application in smart point-of-care (POC) devices. This low cost, flexible and environment friendly conducting paper based biosensor utilized for cancer biomarker (carcinoembryonic antigen, CEA) detection reveals high sensitivity of 25.8µAng<SUP>−1</SUP> mLcm<SUP>−2</SUP> in the physiological range, 1–10ngmL<SUP>−1</SUP>.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Solution processed reduced graphene oxide modified conducting paper sensor is reported for cancer detection. </LI> <LI> This paper sensor is exceptionally low cost, flexible and disposable. </LI> <LI> It exhibits high sensitivity of 25.8µAng<SUP>−1</SUP> mLcm<SUP>−2</SUP> in the detection range of 1–10ngmL<SUP>−1</SUP> for cancer biomarker (carcinoembryonic antigen, CEA) detection. </LI> <LI> This conducting paper electrode is a promising alternative over the expensive conventional electrodes (ITO, gold and glassy carbon) for application to POC devices. </LI> </UL> </P>

International comparison CCQM-K84-carbon monoxide in synthetic air at ambient level

Lee, Jeongsoon,Moon, Dongmin,Lee, Jinbok,Lim, Jeongsik,Hall, Brad,Novelli, Paul,Brewer, Paul J,Miller, Michael,Murugun, Arul,Minarro, Marta Doval,Qiao, Han,Shuguo, Hu,Konopelko, L A,Kustikov, Y A,Kolo BUREAU INTERNATIONAL DES POIDS ET MESURES 2017 METROLOGIA -BERLIN- Vol.54 No.1