Publications by authors named "Sanjoy Chatterjee"

47 Publications

Prioritizing Delivery of Cancer Treatment During a COVID-19 Lockdown: The Experience of a Clinical Oncology Service in India.

JCO Glob Oncol 2021 01;7:99-107

Department of Radiation Oncology, Tata Medical Center, Kolkata, India.

Purpose: A COVID-19 lockdown in India posed significant challenges to the continuation of radiotherapy (RT) and systemic therapy services. Although several COVID-19 service guidelines have been promulgated, implementation data are yet unavailable. We performed a comprehensive audit of the implementation of services in a clinical oncology department.

Methods: A departmental protocol of priority-based treatment guidance was developed, and a departmental staff rotation policy was implemented. Data were collected for the period of lockdown on outpatient visits, starting, and delivery of RT and systemic therapy. Adherence to protocol was audited, and factors affecting change from pre-COVID standards analyzed by multivariate logistic regression.

Results: Outpatient consults dropped by 58%. Planned RT starts were implemented in 90%, 100%, 92%, 90%, and 75% of priority level 1-5 patients. Although 17% had a deferred start, the median time to start of adjuvant RT and overall treatment times were maintained. Concurrent chemotherapy was administered in 89% of those eligible. Systemic therapy was administered to 84.5% of planned patients. However, 33% and 57% of curative and palliative patients had modifications in cycle duration or deferrals. The patient's inability to come was the most common reason for RT or ST deviation. Factors independently associated with a change from pre-COVID practice was priority-level allocation for RT and age and palliative intent for systemic therapy.

Conclusion: Despite significant access limitations, a planned priority-based system of delivery of treatment could be implemented.
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http://dx.doi.org/10.1200/GO.20.00433DOI Listing
January 2021

Nodal yield and topography of nodal metastases from oral cavity squamous cell carcinoma - An audit of 1004 cases undergoing primary surgical resection.

Oral Oncol 2021 Feb 16;113:105115. Epub 2020 Dec 16.

Head and Neck Surgery, Tata Medical Center, Kolkata, India.

Objectives: Nodal metastasis is an important prognostic factor in oral squamous cell carcinoma (OSCC). Detailed topographic study of metastasis can guide surgical and adjuvant radiation treatment protocols.

Methods: Retrospective analysis of distribution of nodal spread was done by auditing pathology records of 1004 patients who underwent primary surgical management at our center.

Results: The median nodal yield was 41 (range of 9-166) nodes, per patient. Metastasis was present in 42.9% patients, of which 52.3% demonstrated extranodal extension. Reclassification by AJCC8 criteria resulted in up-staging in 35.6% patients (pN1, pN2a, pN2b, pN2c, pN3a and pN3b in 13.1%, 3.7%, 6.9%, 0.9%, 0%, 18.1% respectively). Ipsilateral levels Ib and IIa were involved in a quarter of patients each, while IIb, IV and V were involved in < 4%, 3% and 1% of patients, respectively. Contralateral nodal metastasis was present in 5.4%. Skip metastases to level IV were 2.2% and 1.2% for tongue and gingivobuccal primaries. Tongue primaries had a lower likelihood of involving level Ib, but higher of level IIa and III, compared to gingivobuccal primaries, and a lower likelihood of extranodal extension. Primary site did not influence nodal metastasis to levels IIb, IV or V, but other factors like lymphovascular invasion, pT stage and margin status had an influence.

Conclusion: This large series with high nodal yield, shows low level of metastasis to level IIb, IV and V, which can help modify future guidelines for extent of surgery and avoid targeted adjuvant radiation to specific levels.
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http://dx.doi.org/10.1016/j.oraloncology.2020.105115DOI Listing
February 2021

Hypofractionated radiation therapy comparing a standard radiotherapy schedule (over 3 weeks) with a novel 1-week schedule in adjuvant breast cancer: an open-label randomized controlled study (HYPORT-Adjuvant)-study protocol for a multicentre, randomized phase III trial.

Trials 2020 Sep 30;21(1):819. Epub 2020 Sep 30.

Department of Radiation Oncology, Tata Medical Center, Kolkata, India.

Background: Hypofractionated radiotherapy is the current standard for adjuvant radiotherapy across many centres. Further hypofractionation may be possible but remains to be investigated in non-Caucasian populations with more advanced disease, with a higher proportion of patients requiring mastectomy as well as tumour bed boost. We are reporting the design of randomized controlled trial testing the hypothesis that a 1-week (5 fractions) regimen of radiotherapy will be non-inferior to a standard 3-week (15 fractions) schedule.

Methods: We describe a multicentre, randomized controlled trial recruiting patients at large academic centres across India. Patients without distant metastases who merit adjuvant radiotherapy will be eligible for inclusion in the study. Patients in the control arm will receive adjuvant radiotherapy to the breast or chest wall (with/without regional nodes) to a dose of 40 Gy/15 fractions/3 weeks, while those in the experimental arm will receive a dose of 26 Gy/5 fractions/1 week (to the same volume). The use of a simultaneous integrated boost (dose of 8 Gy and 6 Gy, respectively) is allowed in patients who have undergone breast conservation. A sample size of 2100 patients provides an 80% power to detect a non-inferiority of 3% in the 5-year locoregional recurrence rate with a one-sided type I error of 2.5%, assuming that the locoregional recurrence rate in the control arm is 5% at 5 years (corresponding to a hazard ratio of 1.63). Patients will be recruited over a period of 5 years and followed up for a further 5 years thereafter.

Discussion: If a five-fraction regimen of breast cancer is proven to be non-inferior, this will result in a significant improvement in the access to radiotherapy, as well as reduced costs of treatment. The trial gives an opportunity to standardize and quality-assure radiotherapy practices across the nation at the same time. Along with the results of the FAST-Forward trial, the safety of this intervention in advanced node-positive disease requiring regional nodal radiation will be established.

Trial Registration: The trial has been registered at the Clinical Trial Registry of India (CTRI) vide registration number: CTRI/2018/12/016816 (December 31, 2018) as well as the ClinicalTrial.gov website at NCT03788213 (December 28, 2018).
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http://dx.doi.org/10.1186/s13063-020-04751-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526182PMC
September 2020

Setting up a lung stereotactic body radiotherapy service in a tertiary center in Eastern India: The process, quality assurance, and early experience.

J Cancer Res Ther 2020 Jul-Sep;16(4):888-899

Department of Radiation Oncology, Tata Medical Center, Kolkata, West Bengal, India.

Context: Stereotactic body radiotherapy (SBRT) is increasingly being used for early-stage lung cancer and lung oligometastases.

Aims: To report our experience of setting up lung SBRT and early clinical outcomes.

Settings And Design: This was a retrospective, interventional, cohort study.

Subjects And Methods: Patients were identified from multidisciplinary tumor board meetings. They underwent four-dimensional computed tomography-based planning. The ROSEL trial protocol, the Radiation Therapy Oncology Group (RTOG) 0236, and the UK-Stereotactic Ablative Body Radiotherapy Consortium guidelines were used for target volume and organs-at-risks (OARs) delineation, dosimetry, and plan quality assessment. Each SBRT plan underwent patient-specific quality assurance (QA). Daily online image guidance using KVCT or MVCT was done to ensure accurate treatment delivery.

Statistical Analysis Used: Microsoft Excel 2010 was used for data analysis.

Results: Fifteen patients were treated to one or more lung tumors. One patient received helical tomotherapy in view of bilateral lung oligometastases at similar axial levels. All the remaining patients received volumetric modulated arc therapy (VMAT)-based treatment. The prescription dose varied from 40 to 60 Gy in 5-8 fractions with alternate-day treatment. The mean and median lung V20 was 5.24% and 5.16%, respectively (range, 1.66%-9.10%). The mean and median conformity indexes were 1.02 and 1.06, respectively (range, 0.70-1.18). After a median follow-up of 17 months, the locoregional control rate was 93.3%.

Conclusions: SBRT was implemented using careful evaluation of OAR dose constraints, dosimetric accuracy and plan quality, patient-specific QA, and online image guidance for accurate treatment delivery. It was safe and effective for early-stage nonsmall cell lung cancer and lung metastases. Prospective data were collected to audit our outcomes.
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http://dx.doi.org/10.4103/jcrt.JCRT_427_18DOI Listing
November 2020

AutoIHC-Analyzer: computer-assisted microscopy for automated membrane extraction/scoring in HER2 molecular markers.

J Microsc 2021 Jan 27;281(1):87-96. Epub 2020 Aug 27.

Electronics and Electrical Communication Engineering, IIT Kharagpur, Kharagpur, West Bengal, India.

Human epidermal growth factor receptor 2 (HER2) is one of the widely used Immunohistochemical (IHC) markers for prognostic evaluation amongst the patient of breast cancer. Accurate quantification of cell membrane is essential for HER2 scoring in therapeutic decision making. In modern laboratory practice, expert pathologist visually assesses the HER2-stained tissue sample under the bright field microscope for cell membrane assessment. This manual assessment is time consuming, tedious and quite often results in interobserver variability. Further, the burden of increasing number of patients is a challenge for the pathologists. To address these challenges, there is an urgent need with a rapid HER2 cell membrane extraction method. The proposed study aims at developing an automated IHC scoring system, termed as AutoIHC-Analyzer, for automated cell membrane extraction followed by HER2 molecular expression assessment from stained tissue images. A series of image processing approaches have been used to automatically extract the stained cells and membrane region, followed by automatic assessment of complete and broken membrane. Finally, a set of features are used to automatically classify the tissue under observation for the quantitative scoring as 0/1+, 2+ and 3+. In a set of surgically extracted cases of HER2-stained tissues, obtained from collaborative hospital for the testing and validation of the proposed approach AutoIHC-Analyzer and publicly available open source ImmunoMembrane software are compared for 90 set of randomly acquired images with the scores by expert pathologist where significant correlation is observed [(r = 0.9448; p < 0.001) and (r = 0.8521; p < 0.001)] respectively. The output shows promising quantification in automated scoring. LAY DESCRIPTION: In cancer prognosis amongst the patient of breast cancer, human epidermal growth factor receptor 2 (HER2) is used as Immunohistochemical (IHC) biomarker. The correct assessment of HER2 leads to the therapeutic decision making. In regular practice, the stained tissue sample is observed under a bright microscope and the expert pathologists score the sample as negative (0/1+), equivocal (2+) and positive (3+) case. The scoring is based on the standard guidelines relating the complete and broken cell membrane as well as intensity of staining in the membrane boundary. Such evaluation is time consuming, tedious and quite often results in interobserver variability. To assist in rapid HER2 cell membrane assessment, the proposed study aims at developing an automated IHC scoring system, termed as AutoIHC-Analyzer, for automated cell membrane extraction followed by HER2 molecular expression assessment from stained tissue images. The input image is preprocessed using modified white patch and CMYK and RGB colour space were used in extracting the haematoxylin (negatively stained cells) and diaminobenzidine (DAB) stain observed in the tumour cell membrane. Segmentation and postprocessing are applied to create the masks for each of the stain channels. The membrane mask is then quantified as complete or broken using skeletonisation and morphological operations. Six set of features were assessed for the classification from a set of 180 training images. These features are: complete to broken membrane ratio, amount of stain using area of Blue and Saturation channels to the image size, DAB to haematoxylin ratio from segmented masks and average R, G and B from five largest blobs in segmented DAB-masked image. These features are then used in training the SVM classifier with Gaussian kernel using 5-fold cross-validation. The accuracy in the training sample is found to be 88.3%. The model is then used for 90 set of unknown test sample images and the final labelling of stained cells and HER2 scores (as 0/1+, 2+ and 3+) are compared with the ground truth, that is expert pathologists' score from the collaborative hospital. The test sample images were also fed to ImmunoMembrane software for a comparative assessment. The results from the proposed AutoIHC-Analyzer and ImmunoMembrane software were compared with the expert pathologists' score where significant agreement using Pearson's correlation coefficient [(r = 0.9448; p < 0.001) and (r = 0.8521; p < 0.001) respectively] is observed. The results from AutoIHC-Analyzer show promising quantitative assessment of HER2 scoring.
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http://dx.doi.org/10.1111/jmi.12955DOI Listing
January 2021

Prediction of survival outcome based on clinical features and pretreatment FDG-PET/CT for HNSCC patients.

Comput Methods Programs Biomed 2020 Oct 18;195:105669. Epub 2020 Jul 18.

Department of Computer Science & Engineering, Indian Institute Of Technology Kharagpur, Kharagpur, West Bengal, 721302, India. Electronic address:

Background And Objective: In this study, we have analysed pretreatment positron-emission tomography/ computed tomography (PET/CT) images of head and neck squamous cell carcinoma (HNSCC) patients. We have used a publicly available dataset for our analysis. The clinical features of the patient, PET quantitative parameters, and textural indices from pretreatment PET-CT images are selected for the study. The main objective of the study is to use classifiers to predict the outcome for HNSCC patients and compare the performance of the model with the conventional statistical model (CoxPH).

Methods: We have applied a 40% fixed SUV threshold method for tumour delineation. Clinical features of each patient are provided in the dataset, and other features are calculated using LIFEx software. For predicting the outcome, we have implemented three classifiers - Random Forest classifier, Gradient Boosted Decision tree (GBDT) and Decision tree classifier. We have trained each model using 93 data points and test the model performance using 39 data points. The best model - GBDT is chosen based on the performance metrics.

Results: It is observed that typically three features: MTV (Metabolic tumour Volume), primary tumour site and GLCM_correlation are significant for prediction of survival outcome. For testing cohort, GBDT achieves a balanced accuracy of 88%, where conventional statistical model reported a balanced accuracy of 81.5%.

Conclusions: The proposed classifier achieves higher accuracy than the state of the art technique. Using this classifier we can estimate the HNSCC patient's outcome, and depending upon the outcome treatment policy can be selected.
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http://dx.doi.org/10.1016/j.cmpb.2020.105669DOI Listing
October 2020

Label-free detection of thalassemia and other ROS impairing diseases.

Med Biol Eng Comput 2020 Sep 17;58(9):2143-2159. Epub 2020 Jul 17.

Department of Biochemistry, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700019, India.

Pathogenesis of different diseases showed that some of them, especially thalassemia (T) and rheumatoid arthritis (RA) have an implicit association with oxidative stress and altered levels of reactive oxygen species (ROS). Introducing ROS level and the balance between ROS and antioxidants as essential metrics, an attempt was made to classify T and RA from normal individuals (treated as controls)(C) using synchronous fluorescence spectroscopy (SFS) and Raman line intensity of water. This non-invasive and label-free approach was backed up by a categorization algorithm that helped in the prediction of disease types from serum samples. The predictive system constituted principal component analysis (PCA) with four parameters, namely spectral intensity ratios of reduced nicotinamide adenine dinucleotide (NADH) to tryptophan (Trp) (NADH/Trp), kynurenine (Kyn) to tryptophan (Kyn/Trp), kynurenine to NADH (Kyn/NADH), and logarithmic changes in Raman line intensity of water (Rline), with the index headers containing the disease types. Rline has a positive correlation with both Kyn/Trp and Kyn/NADH and a negative correlation with NADH/Trp ratio, implying its direct or indirect association with oxidative stress. In addition to the classification of T, RA, and C a sub-classification of T into beta major and E-beta in their post and pre-splenectomized surgical stages could also be realized. Furthermore, receiver operating characteristic (ROC) analysis was deployed to ascertain that the misclassification error (ME) was negligible for the disease types. Graphical Abstract A schematic representation of the workflow converging into the categorical classification of disease classes.
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http://dx.doi.org/10.1007/s11517-020-02191-zDOI Listing
September 2020

De-Identification of Radiomics Data Retaining Longitudinal Temporal Information.

J Med Syst 2020 Apr 2;44(5):99. Epub 2020 Apr 2.

CSE, IIT Kharagpur, Kharagpur, India.

We propose a de-identification system which runs in a standalone mode. The system takes care of the de-identification of radiation oncology patient's clinical and annotated imaging data including RTSTRUCT, RTPLAN, and RTDOSE. The clinical data consists of diagnosis, stages, outcome, and treatment information of the patient. The imaging data could be the diagnostic, therapy planning, and verification images. Archival of the longitudinal radiation oncology verification images like cone beam CT scans along with the initial imaging and clinical data are preserved in the process. During the de-identification, the system keeps the reference of original data identity in encrypted form. These could be useful for the re-identification if necessary.
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http://dx.doi.org/10.1007/s10916-020-01563-0DOI Listing
April 2020

Next generation sequencing in lung cancer: An initial experience from India.

Curr Probl Cancer 2020 06 28;44(3):100562. Epub 2020 Feb 28.

Department of Molecular Genetics, Tata Medical Center, Kolkata, West Bengal, India. Electronic address:

Introduction: Approximately 35% of NSCLC patients in East Asia have EGFR mutations. Next-generation sequencing (NGS) provides a comprehensive mutational profile in lung cancer patients.

Material And Method: Clinicopathologic characteristics and mutational profiling data was analyzed from nonsmall cell lung carcinoma /Adenocarcinoma over a duration of 42 months (October 2014 to March 2018) using next-generation sequencing Ion Ampliseq Cancer Hotspot panel v2 (Ampliseq, Life Technologies) on the Ion torrent PGM platform.

Results: A total of 154 cases were processed during this period. The average number of mutations/case varied from one to four 72.07% (111/154), of these cases had minimum one genetic alteration. The most common mutated gene was TP53 gene (37.6%, n = 58) followed by EGFR (32.4%, n = 50), KRAS (18.18%, n = 28), ERBB2 (3.2%, n = 5), BRAF (1.94%, n = 3). EGFR positivity was more in females (43.3%) and non-smokers (52.08%) in comparison to males (26.7%) and smokers (16.1%).

Conclusion: In this paper, we have described the comprehensive mutational profiling of a large cohort of advanced lung adenocarcinoma patients from the eastern part of India. To the best of our knowledge, this is one of the largest studies from the country describing mutations in BRAF, ERBB2, TP53 genes and their clinicopathologic/histopathologic associations in lung cancers.
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http://dx.doi.org/10.1016/j.currproblcancer.2020.100562DOI Listing
June 2020

Redefining adequate margins in oral squamous cell carcinoma: outcomes from close and positive margins.

Eur Arch Otorhinolaryngol 2020 Apr 2;277(4):1155-1165. Epub 2020 Jan 2.

Department of Head and Neck Surgery, Tata Medical Center, Calcutta, West Bengal, 700160, India.

Purpose: Adequacy of surgical margins impacts outcomes in oral cancer. We sought to determine whether close and positive margins have different outcomes in patients with oral cancer.

Methods: Retrospective data from 612 patients with oral carcinoma were analyzed for the effect of margin status on locoregional recurrence-free survival (LRFS), disease-free survival (DFS) and overall survival (OS).

Results: A total of 90 cases (14.7%) had close margins and 26 patients (4.2%) had positive margins. Recurrences were documented in 173 patients (28%), of which 137 (22% of the study sample) were locoregional, and 164 patients (27%) had died. Among patients with close or positive margins, a cutoff of 1 mm optimally separated LRFS (adjusted p = 0.0190) and OS curves (adjusted p = 0.0168) whereas a cutoff of 2 mm was sufficient to significantly separate DFS curves (adjusted p = 0.0281).

Conclusions: Patients with oral carcinoma with positive margins (< 1 mm) had poorer outcomes compared to those with close margins (1-5 mm) in terms of LRFS, DFS and OS. There is a suggestion that a cutoff of < 2 mm might provide slightly more separation for DFS.
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http://dx.doi.org/10.1007/s00405-019-05779-wDOI Listing
April 2020

Clinicopathologic Determinants of Outcome in Pathologic T4a (pT4a) Squamous Cell Carcinoma of the Gingivobuccal Subsite of the Oral Cavity.

Indian J Surg Oncol 2019 Dec 27;10(4):594-599. Epub 2019 Jun 27.

1Department of Head and Neck Surgery, Tata Medical Center, Kolkata, West Bengal 700160 India.

Carcinoma of the gingivobuccal complex is one of the most common cancers in India and patients usually present in an advanced stage. There is limited data in literature regarding the factors predicting outcome in pathological T4a patients. In this study, we aimed to study the clinic-pathological factors which may influence treatment outcomes in pT4a patients. This is a retrospective study of 121 patients who underwent surgery for oral squamous cell carcinoma between August 2011 and December 2016, staged pT4a. Overall survival (OS) and disease-free survival (DFS) were analyzed for variables including age, depth of invasion, margin status, differentiation, nodal status, extranodal spread, lymphovascular and perineural spread, and adjuvant treatment. The study cohort comprised 93 males with mean age 60.28 years (S.D. 11.25). Median DFS was 21 months (range 9 to 2374 days) whereas median OS was 24.5 months (range 9 to 2374 days). On univariate analysis, lymphovascular invasion, perineural invasion, cervical nodal metastasis, and extranodal extension had a statistically significant effect on both DFS and OS. On multivariate analysis, age ( = 0.014) and adjuvant radiotherapy ( = 0.010) were the statistically significant factors affecting OS. None of the factors affected DFS on multivariate analysis. Patients staged pT4a with cervical nodal metastasis, extranodal extension, lymphovascular invasion, and perineural invasion have reduced OS and DFS. On multivariate analysis, lower age at presentation and adjuvant radiation improved patient outcome.
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http://dx.doi.org/10.1007/s13193-019-00950-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895327PMC
December 2019

Sentinel Lymph Node Biopsy After Initial Lumpectomy (SNAIL Study)-a Prospective Validation Study.

Indian J Surg Oncol 2019 Jun 18;10(2):350-356. Epub 2018 Dec 18.

1Department Of Breast Oncosurgery, Tata Medical Center, Kolkata, India.

Tertiary oncology center clinicians are commonly faced with the problem of managing patients with a diagnosis of breast cancer made after lumpectomy in the Primary Health Care (PHC) setting. There are no studies or guidelines that address the further surgical management in this group of patients regarding sentinel lymph node biopsy (SLNB) and need for breast post-operative cavity excision. Prospective observational study was planned to evaluate the feasibility of SLNB and defining the need for definitive breast surgery in patients diagnosed with breast cancer after lumpectomy in PHC. The study was carried out from January 2015 to August 2017 in Tata Medical Center, India, approved by institutional review board (EC/TMC/36/14). Seventy patients who underwent lumpectomy with a definitive histological analysis of breast cancer were included in this study. Each patient had definitive breast surgery and SLNB using subareoral blue dye injection followed by validation axillary dissection. The identification rate (IR) for SLNB was 92% (64/70). The median number of SLNs removed was 2 (IQR 1, 3). There were 2 patients with false negative results resulting in false negative rate (FNR) of 11%. Overall, SLNB procedure has the sensitivity of 89%, NPV of 96%, and accuracy was 97%. Peri-areoral incision of initial surgery was associated with low IR (84%) and high FNR (33%). Final histopathology showed residual invasive cancer in 43% and ductal carcinoma in situ in 14% of patients. Among 21 patients where initial lumpectomy histopathology margin was free of cancer, residual malignancy was found in 57% of patients. Prior excision of lumps for breast cancer does not affect the accuracy of SLNB. Peri-areoral scar may be associated with high FNR and low IR, although further studies are needed to validate this statement. Definitive breast surgery is required for all patients, irrespective of initial lumpectomy histopathological margin status.
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http://dx.doi.org/10.1007/s13193-018-0861-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527719PMC
June 2019

How do clinicians rate patient's performance status using the ECOG performance scale? A mixed-methods exploration of variability in decision-making in oncology.

Ecancermedicalscience 2019 28;13:913. Epub 2019 Mar 28.

Department of Clinical Oncology, North Wales Cancer Center, Rhyl LL18 5UJ, UK.

Background: Medical decisions made by oncology clinicians have serious implications, even when made collaboratively with the patient. Clinicians often use the Eastern Clinical Oncology Group (ECOG) performance status (PS) scores to help them make treatment-related decisions.

Methods: The current study explores the variability of the ECOG score when applied to 12 predetermined specially designed clinical case vignettes presented to a group of oncology clinicians ( = 72). The quantitative analysis included evaluation of variability of ECOG PS scores and exploration of rater and patient-related factors which may influence the final ECOG rating. In-depth interviews were conducted with oncology clinicians to ascertain factors that they felt were important while making treatment-related decisions. Basic and global themes were generated following qualitative data analysis.

Results: Quantitative results showed that there was poor agreement in ECOG rating between raters. Overall concordance with the gold standard rating ranged between 19.4% and 56.9% for the vignettes. Moreover, patients deemed to have socially desirable qualities ( < 0.004) were rated to have better PS and women patients ( < 0.004) to have worse PS. Clinicians having international work experience had increased concordance with ECOG PS rating. Qualitative results showed that 'perceived socio-economic background of the patient', 'age of the patient', 'patient's and family's preferences' and 'past treatment response' were the major themes highlighted by respondents that influenced the treatment-related decisions made by clinicians.

Conclusion: There is considerable variability in ECOG PS determined by clinicians. Decision-making in oncology is complex, multifactorial and is influenced by rater and patient-related factors.
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http://dx.doi.org/10.3332/ecancer.2019.913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467460PMC
March 2019

Radical radiotherapy or chemoradiotherapy for inoperable, locally advanced, non-small cell lung cancer: Analysis of patient profile, treatment approaches, and outcomes for 213 patients at a tertiary cancer center.

Indian J Cancer 2018 Apr-Jun;55(2):125-133

Department of Radiation Oncology, Tata Medical Center, Kolkata, West Bengal, India.

Introduction: Radical radiotherapy (RT) with curative intent, with or without chemotherapy, is the standard treatment for inoperable, locally advanced nonsmall cell lung cancer (NSCLC).

Materials And Methods: We retrospectively reviewed the data for all 288 patients who presented with inoperable, locally advanced NSCLC at our institution, between May 2011 and December 2016.

Results: RT alone or sequential chemoradiotherapy (SCRT) or concurrent chemoradiotherapy (CCRT) was used for 213 patients. Median age was 64 years (range: 27-88 years). Stage-III was the biggest stage group with 189 (88.7%) patients. Most patients with performance status (PS) 0 or 1 received CCRT, whereas most patients with PS 2 received RT alone (P < 0.001). CCRT, SCRT, and RT alone were used for 120 (56.3%), 24 (11.3%), and 69 (32.4%) patients, respectively. A third of all patients (32.4%) required either volumetric-modulated arc radiotherapy (VMAT) or tomotherapy. Median follow-up was 16 months. The median progression-free survival and median overall survival (OS) were 11 and 20 months, respectively. One-year OS and 2-year OS were 67.9% and 40.7%, respectively. Patients treated using CCRT lived significantly longer with a median survival of 28 months, compared with 13 months using SCRT and RT alone (P < 0.001). On multivariate analysis, OS was significantly affected by age, stage group, treatment approach, and response to treatment.

Conclusion: RT including CCRT is feasible, safe, and well tolerated in our patient population and results in survival benefits comparable with published literature. CCRT should be considered for all patients with inoperable, locally advanced NSCLC, who are fit and have good PS.
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http://dx.doi.org/10.4103/ijc.IJC_469_17DOI Listing
April 2019

Impact of modern radiotherapy techniques on survival outcomes for unselected patients with large volume non-small cell lung cancer.

Br J Radiol 2019 Mar 29;92(1095):20180928. Epub 2018 Nov 29.

1 Department of Radiation Oncology, Tata Medical Center, Kolkata , India.

Objective:: Intensity modulated radiotherapy (IMRT) is used, where necessary, for bulky or complex-shaped, locally advanced, non-small cell lung cancer (NSCLC). We evaluate our real-world experience with radical radiotherapy including concurrent chemoradiation (CCRT), and analyse the impact of IMRT on survival outcomes in patients with larger volume disease.

Methods:: All patients treated between May 2011 and December 2017 were included. Analyses were conducted for factors affecting survival, including large volume disease that was defined as planning target volume (PTV) > 500 cc.

Results:: In 184 patients with large volume disease, the median overall survival was 19.2 months, compared to 22 months seen with the overall cohort of 251 patients who received radical radiotherapy. PTV and using CCRT were significant predictors for survival. IMRT was used in 93 (50.5%) of 184 patients with large PTV. The patients treated using IMRT had significantly larger disease volume (median PTV = 859 vs 716 cc; p-value = 0.009) and more advanced stage (proportion of Stage IIIB: 56 vs 29%; p-value = 0.003) compared to patients treated with three-dimensional conformal radiotherapy. Yet, the outcomes with IMRT were non-inferior to those treated with 3DCRT. CCRT was used in 103 (56%) patients with large volume disease and resulted in a significantly better median survival of 24.9 months. The proportional benefit from CCRT was also greater than in the overall cohort.

Conclusion:: Despite being used for larger volume and more advanced NSCLC, inverse-planned IMRT resulted in non-inferior survival.

Advances In Knowledge:: IMRT enables the safe use of curative CCRT for large-volume, locally-advanced NSCLC.
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http://dx.doi.org/10.1259/bjr.20180928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540869PMC
March 2019

Development and validation of a decision support tool to select IMRT as radiotherapy treatment planning modality for patients with locoregionally advanced non-small cell lung cancers (NSCLC).

Br J Radiol 2019 Feb 9;92(1094):20180431. Epub 2018 Nov 9.

1 Department of Radiation Oncology, Tata Medical Center , Rajarhat, Kolkata , India.

Objective:: Radiation planning for locally-advanced non-small cell lung cancer (NSCLC) can be time-consuming and iterative. Many cases cannot be planned satisfactorily using multisegment three-dimensional conformal radiotherapy (3DCRT). We sought to develop and validate a predictive model which could estimate the probability that acceptable target volume coverage would need intensity modulated radiotherapy (IMRT).

Methods:: Variables related to the planning target volume (PTV) and topography were identified heuristically. These included the PTV, it's craniocaudal extent, the ratio of PTV to total lung volume, distance of the centroid of the PTV from the spinal canal, and the extent PTV crossed the midline. Metrics were chosen such that they could be measured objectively, quickly and reproducibly. A logistic regression model was trained and validated on 202 patients with NSCLC. A group of patients who had both complex 3DCRT and IMRT planned was then used to derive the utility of the use of such a model in the clinic based on the time taken for planning such complex 3DCRT.

Results:: Of the 202 patients, 93 received IMRT, as they had larger volumes crossing midline. The final model showed a good rank discrimination (Harrell's C-index 0.84) and low calibration error (mean absolute error of 0.014). Predictive accuracy in an external dataset was 92%. The final model was presented as a nomogram. Using this model, the dosimetrist can save a median planning time of 168 min per case.

Conclusion:: We developed and validated a data-driven, decision aid which can reproducibly determine the best planning technique for locally-advanced NSCLC.

Advances In Knowledge:: Our validated, data-driven decision aid can help the planner to determine the need for IMRT in locally advanced NSCLC saving significant planning time in the process.
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http://dx.doi.org/10.1259/bjr.20180431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404834PMC
February 2019

Quality Indicators for Sentinel Lymph Node Biopsy in Breast Cancer: Applicability and Clinical Relevance in a Non-screened Population.

Indian J Surg Oncol 2018 Sep 21;9(3):312-317. Epub 2017 Aug 21.

1Department of Breast Oncosurgery, Tata Medical Center, Kolkata, India.

Quality Indicators for Sentinel Lymph Node Biopsy in Breast Cancer: Applicability and Clinical Relevance in a Non-screened Population: sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) as standard of care for management of early breast cancer. This study assessed our SLNB program against 11 published quality indicators (QIs). All breast cancer patients who underwent SLNB in our centre from June 2013-Dec 2015 were included. Clinical, pathological and follow-up data were extracted from the institutional REDCap data system. Analysis was done with SPSS 23. Following validation, 234 patients had SLNB, always performed along with primary surgery. Identification rate was 95.3% and > 1 SLN was identified in 72% of patients. SLNB positivity was 33%, of these, 100% underwent ALND. Overall 91% of QI eligible patients underwent SLNB. No ineligible patients (T4) underwent SLNB. For the patients who had radio colloid, injection criteria were met for 100%. Pathological evaluation and reporting criteria were met for 100% of patients. There were no axillary recurrences in a median follow-up of 2 years. 7.6% patients had SLN negative on frozen section but positive on final histology. 7.2% of patients with clinical negative nodes had pN2 disease in final histopathology report after surgery. Sixty percent of patients who had completion ALND had only positive SLN. This study supports the applicability of published QI of SLNB in a non-screened cohort of early breast cancer patients. Although QI were useful, modification based on patient characteristics and resource availability may be needed. These indicators can be used as audit tools to improve the overall accuracy of the procedure.
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http://dx.doi.org/10.1007/s13193-017-0695-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154378PMC
September 2018

Resource requirements and reduction in cardiac mortality from deep inspiration breath hold (DIBH) radiation therapy for left sided breast cancer patients: A prospective service development analysis.

Pract Radiat Oncol 2018 Nov - Dec;8(6):382-387. Epub 2018 Mar 21.

Department of Surgical Oncology, Tata Medical Center, Newtown, Kolkata, West Bengal.

Introduction: Use of deep inspiration breath hold (DIBH) radiation therapy may reduce long-term cardiac mortality. The resource and time commitments associated with DIBH are impediments to its widespread adoption. We report the dosimetric benefits, workforce requirements, and potential reduction in cardiac mortality when DIBH is used for left-sided breast cancers.

Methods And Materials: Data regarding the time consumed for planning and treating 50 patients with left-sided breast cancer with DIBH and 20 patients treated with free breathing (FB) radiation therapy were compiled prospectively for all personnel (regarding person-hours [PH]). A second plan was generated for all DIBH patients in the FB planning scan, which was then compared with the DIBH plan. Mortality reduction from use of DIBH was calculated using the years of life lost resulting from ischemic heart disease for Indians and the postulated reduction in risk of major cardiac events resulting from reduced cardiac dose.

Results: The median reduction in mean heart dose between the DIBH and FB plans was 166.7 cGy (interquartile range, 62.7-257.4). An extra 6.76 PH were required when implementing DIBH as compared with FB treatments. Approximately 3.57 PH were necessary per Gy of reduction in mean heart dose. The excess years of life lost from ischemic heart disease if DIBH was not done in was 0.95 per 100 patients, which translates into a saving of 12.8 hours of life saved per PH of work required for implementing DIBH. DIBH was cost effective with cost for implementation of DIBH for all left-sided breast cancers at 2.3 times the annual per capita gross domestic product.

Conclusion: Although routine implementation of DIBH requires significant resource commitments, it seems to be worthwhile regarding the projected reductions in cardiac mortality.
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http://dx.doi.org/10.1016/j.prro.2018.03.007DOI Listing
January 2019

Antibiotic Prophylaxis for Breast Oncosurgery in a Setting With a High Prevalence of Multidrug-Resistant Bacteria: Common Sense Infection Control Measures Are More Important Than Prolonged Antibiotics.

Infect Control Hosp Epidemiol 2018 04 13;39(4):498-500. Epub 2018 Feb 13.

1Department of Breast Oncosurgery,Tata Medical Center,Kolkata,India.

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http://dx.doi.org/10.1017/ice.2017.313DOI Listing
April 2018

Phase III, Randomized, Double-Blind Study Comparing the Efficacy, Safety, and Immunogenicity of SB3 (Trastuzumab Biosimilar) and Reference Trastuzumab in Patients Treated With Neoadjuvant Therapy for Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer.

J Clin Oncol 2018 04 26;36(10):968-974. Epub 2018 Jan 26.

Xavier Pivot, University Hospital Jean Minjoz, Institut National de la Santé et de la Recherche Médicale 1098, Besançon, France; Igor Bondarenko, State Institution Dnipropetrovsk Medical, Academy of the Ministry of Health of Ukraine, Communal Institution Dnipropetrovsk City Multifield Clinical Hospital No. 4 of Dnipropetrovsk Regional Council, Dnipropetrovsk; Yuriy Vinnyk, Communal Healthcare Institution Kharkiv, Regional Clinical Oncological Center, Kharkiv; Yaroslav Shparyk, Lviv State Oncological Regional Treatment and Diagnostic Center, Lviv, Ukraine; Zbigniew Nowecki, Centrum Onkologii-Instytutim. M. Sklodowskiej Curie; Tomasz Sarosiek, Magodent, Warsaw; Marek Z. Wojtukiewicz, Comprehensive Cancer Center, Medical University, Bialystok, Poland; Mikhail Dvorkin, BHI of Omsk Region, Clinical Oncology Dispensary, Omsk; Ekaterina Trishkina, SBHI Leningrad Regional Oncology Dispensary; Vladimir Moiseyenko, SBHI Saint Petersburg Scientific and Practical Center of Specialized Methods of Medical Help; Vladimir Semiglazov, FSI Scientific and Research Institution of Oncology n.a. N.N. Petrov of Ministry of Healthcare and SD of RF, St Petersburg, Russia; Jin-Hee Ahn, Asan Medical Center; Seock-Ah Im, Seoul National University Hospital, Seoul; Sujeong Song and Jaeyun Lim, Samsung Bioepis, Incheon, Republic of Korea; Sanjoy Chatterjee, Tata Medical Centre, Kolkata, India; and Maximino Bello III, St Luke's Medical Center, Quezon City, Philippines.

Purpose This phase III study compared SB3, a trastuzumab (TRZ) biosimilar, with reference TRZ in patients with human epidermal growth factor receptor 2-positive early breast cancer in the neoadjuvant setting ( ClinicalTrials.gov identifier: NCT02149524). Patients and Methods Patients were randomly assigned to receive neoadjuvant SB3 or TRZ for eight cycles concurrently with chemotherapy (four cycles of docetaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide) followed by surgery, and then 10 cycles of adjuvant SB3 or TRZ. The primary objective was comparison of breast pathologic complete response (bpCR) rate in the per-protocol set; equivalence was declared if the 95% CI of the ratio was within 0.785 to 1.546 or the 95% CI of the difference was within ± 13%. Secondary end points included comparisons of total pathologic complete response rate, overall response rate, event-free survival, overall survival, safety, pharmacokinetics, and immunogenicity. Results Eight hundred patients were included in the per-protocol set (SB3, n = 402; TRZ, n = 398). The bpCR rates were 51.7% and 42.0% with SB3 and TRZ, respectively. The adjusted ratio of bpCR was 1.259 (95% CI, 1.085 to 1.460), which was within the predefined equivalence margins. The adjusted difference was 10.70% (95% CI, 4.13% to 17.26%), with the lower limit contained within and the upper limit outside the equivalence margin. The total pathologic complete response rates were 45.8% and 35.8% and the overall response rates were 96.3% and 91.2% with SB3 and TRZ, respectively. Overall, 96.6% and 95.2% of patients experienced one or more adverse event, 10.5% and 10.7% had a serious adverse event, and 0.7% and 0.0% had antidrug antibodies (up to cycle 9) with SB3 and TRZ, respectively. Conclusion Equivalence for efficacy was demonstrated between SB3 and TRZ on the basis of the ratio of bpCR rates. Safety and immunogenicity were comparable.
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http://dx.doi.org/10.1200/JCO.2017.74.0126DOI Listing
April 2018

Human papillomavirus in head and neck cancer in India: Current status and consensus recommendations.

South Asian J Cancer 2017 Jul-Sep;6(3):93-98

Department of Medical Oncology, Asian Institute of Oncology, Mumbai, Maharashtra, India.

Human papillomavirus (HPV) associated head and neck squamous cell cancers (HNSCC) have become increasingly common in the West, but the same cannot be said about India. These cancers have a different biology and confer a better prognosis, however, its current role in the management of patients in India is not clearly defined. At the 35 Indian Cooperative Oncology Network conference held in September 2016, a panel of radiation, surgical and medical oncologists, pathologists, and basic scientists from across the country having experience in clinical research with respect to HPV in HNSCC reviewed the available literature from India. All the ideas and facts were thereafter collated in this report. Various topics of controversy in dealing with the diagnosis and management of HPV-associated HNSCC have been highlighted in this report in context to the Indian scenario. Furthermore, the prevalence of the same and its association with tobacco and high-risk sexual behavior has been touched on. Conclusively, a set of recommendations has been proposed by the panel to guide the practicing oncologists of the country while dealing with HPV-associated HNSCC.
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http://dx.doi.org/10.4103/sajc.sajc_96_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615888PMC
October 2017

Stigma Perceived by Women Following Surgery for Breast Cancer.

Indian J Med Paediatr Oncol 2017 Apr-Jun;38(2):146-152

Department of Surgical Oncology, Tata Medical Centre, Kolkata, West Bengal, India.

Context: Women undergoing treatment for breast cancer often have psychological morbidity and body image difficulties. The risk factors for increased levels of stigma in women with breast cancer have not been adequately studied.

Aims: This study aimed at investigating the associations of high levels of stigma in women with breast cancer.

Settings And Design: This cross-sectional study was conducted in a comprehensive cancer center in India and recruited women ( = 134) undergoing surgical treatment for breast cancer.

Methods: Body image difficulties, including stigma and affective symptoms, were quantified, alongside disease- and treatment-related variables using standardized questionnaires.

Statistical Analysis Used: Univariate analysis followed by multivariate logistic regression was performed to find the risk factors of high levels of stigma related to body image.

Results: In the univariate analysis, high levels of stigma were associated with lesser educational attainment (odds ratio [OR] =2.92, confidence interval [CI] 1.25-6.8, = 0.01), breast conservation surgery (BCS) as opposed to mastectomy (OR = 4.78, CI 2.07-11.03, < 0.001), having an anxiety disorder (OR = 2.4, CI 1.09-5.33, = 0.03), and depression (OR = 3.08, CI 1.37-6.89, < 0.01). On multivariate logistic regression, with stigma as the dependent variable, being less educated (adjusted OR [AOR] 3.08, CI 1.18-8.04, = 0.02) and opting for BCS (AOR 6.12, CI 2.41-15.5, < 0.001) were associated with higher stigma.

Conclusions: Women with breast cancer should be screened for distress and stigma. Women opting for BCS may still have unmet emotional needs on completion of surgery and should have access to psychological interventions to address stigma, affective symptoms, and body image problems.
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http://dx.doi.org/10.4103/ijmpo.ijmpo_74_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582551PMC
September 2017

Near-set Based Mucin Segmentation in Histopathology Images for Detecting Mucinous Carcinoma.

J Med Syst 2017 Aug 10;41(9):144. Epub 2017 Aug 10.

School of Medical Science and Technology, IIT Kharagpur, Kharagpur, 721 302, India.

This paper introducesnear-set based segmentation method for extraction and quantification of mucin regions for detecting mucinouscarcinoma (MC which is a sub type of Invasive ductal carcinoma (IDC)). From histology point of view, the presence of mucin is one of the indicators for detection of this carcinoma. In order to detect MC, the proposed method majorly includes pre-processing by colour correction, colour transformation followed by near-set based segmentation and post-processing for delineating only mucin regions from the histological images at 40×. The segmentation step works in two phases such as Learn and Run.In pre-processing step, white balance method is used for colour correction of microscopic images (RGB format). These images are transformed into HSI (Hue, Saturation, and Intensity) colour space and H-plane is extracted in order to get better visual separation of the different histological regions (background, mucin and tissue regions). Thereafter, histogram in H-plane is optimally partitioned to find set representation for each of the regions. In Learn phase, features of typical mucin pixel and unlabeled pixels are learnt in terms of coverage of observed sets in the sample space surrounding the pixel under consideration. On the other hand, in Run phase the unlabeled pixels are clustered as mucin and non-mucin based on its indiscernibilty with ideal mucin, i.e. their feature values differ within a tolerance limit. This experiment is performed for grade-I and grade-II of MC and hence percentage of average segmentation accuracy is achieved within confidence interval of [97.36 97.70] for extracting mucin areas. In addition, computation of percentage of mucin present in a histological image is provided for understanding the alteration of such diagnostic indicator in MC detection.
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http://dx.doi.org/10.1007/s10916-017-0792-6DOI Listing
August 2017

An Advanced Deep Learning Approach for Ki-67 Stained Hotspot Detection and Proliferation Rate Scoring for Prognostic Evaluation of Breast Cancer.

Sci Rep 2017 06 12;7(1):3213. Epub 2017 Jun 12.

Tata Medical Center, New Town, Kolkata, West Bengal, India.

Being a non-histone protein, Ki-67 is one of the essential biomarkers for the immunohistochemical assessment of proliferation rate in breast cancer screening and grading. The Ki-67 signature is always sensitive to radiotherapy and chemotherapy. Due to random morphological, color and intensity variations of cell nuclei (immunopositive and immunonegative), manual/subjective assessment of Ki-67 scoring is error-prone and time-consuming. Hence, several machine learning approaches have been reported; nevertheless, none of them had worked on deep learning based hotspots detection and proliferation scoring. In this article, we suggest an advanced deep learning model for computerized recognition of candidate hotspots and subsequent proliferation rate scoring by quantifying Ki-67 appearance in breast cancer immunohistochemical images. Unlike existing Ki-67 scoring techniques, our methodology uses Gamma mixture model (GMM) with Expectation-Maximization for seed point detection and patch selection and deep learning, comprises with decision layer, for hotspots detection and proliferation scoring. Experimental results provide 93% precision, 0.88% recall and 0.91% F-score value. The model performance has also been compared with the pathologists' manual annotations and recently published articles. In future, the proposed deep learning framework will be highly reliable and beneficial to the junior and senior pathologists for fast and efficient Ki-67 scoring.
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http://dx.doi.org/10.1038/s41598-017-03405-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5468356PMC
June 2017

Discordance in Immunohistochemical Status of Breast Cancer Post Neoadjuvant Chemotherapy.

Indian J Surg Oncol 2017 Jun 10;8(2):245-246. Epub 2016 Dec 10.

Department of Breast Oncosurgery, Tata Medical Center, Kolkata, India.

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http://dx.doi.org/10.1007/s13193-016-0606-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427038PMC
June 2017

Automated characterization and counting of Ki-67 protein for breast cancer prognosis: A quantitative immunohistochemistry approach.

Comput Methods Programs Biomed 2017 Feb 9;139:149-161. Epub 2016 Nov 9.

School of Medical Science & Technology, IIT Kharagpur, Kharagpur, West Bengal, India. Electronic address:

Ki-67 protein expression plays an important role in predicting the proliferative status of tumour cells and deciding the future course of therapy in breast cancer. Immunohistochemical (IHC) determination of Ki-67 score or labelling index, by estimating the fraction of Ki67 positively stained tumour cells, is the most widely practiced method to assess tumour proliferation (Dowsett et al. 2011). Accurate manual counting of these cells (specifically nuclei) due to complex and dense distribution of cells, therefore, becomes critical and presents a major challenge to pathologists. In this paper, we suggest a hybrid clustering algorithm to quantify the proliferative index of breast cancer cells based on automated counting of Ki-67 nuclei. The proposed methodology initially pre-processes the IHC images of Ki-67 stained slides of breast cancer. The RGB images are converted to grey, L*a*b*, HSI, YCbCr, YIQ and XYZ colour space. All the stained cells are then characterized by two stage segmentation process. Fuzzy C-means quantifies all the stained cells as one cluster. The blue channel of the first stage output is given as input to k-means algorithm, which provides separate cluster for Ki-67 positive and negative cells. The count of positive and negative nuclei is used to calculate the F-measure for each colour space. A comparative study of our work with the expert opinion is studied to evaluate the error rate. The positive and negative nuclei detection results for all colour spaces are compared with the ground truth for validation and F-measure is calculated. The F-measure for L*a*b* colour space (0.8847) provides the best statistical result as compared to grey, HSI, YCbCr, YIQ and XYZ colour space. Further, a study is carried out to count nuclei manually and automatically from the proposed algorithm with an average error rate of 6.84% which is significant. The study provides an automated count of positive and negative nuclei using L*a*b*colour space and hybrid segmentation technique. Computerized evaluation of proliferation index can aid pathologist in assessing breast cancer severity. The proposed methodology, further, has the potential advantage of saving time and assisting in decision making over the present manual procedure and could evolve as an assistive pathological decision support system.
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http://dx.doi.org/10.1016/j.cmpb.2016.11.002DOI Listing
February 2017

Acute toxicity and its dosimetric correlates for high-risk prostate cancer treated with moderately hypofractionated radiotherapy.

Med Dosim 2017 Spring;42(1):18-23. Epub 2017 Jan 24.

Department of Radiation Oncology, Tata Medical Center, Kolkata, India.

Aims: To report the acute toxicity and the dosimetric correlates after moderately hypofractionated radiotherapy for localized prostate cancer.

Methods: A total of 101 patients with localized prostate cancer were treated with image-guided intensity-modulated radiation therapy. Patients were treated to 65Gy/25Fr/5 weeks (n = 18), or 60Gy/20Fr/4 weeks (n = 83). Most (82.2%) had high-risk or pelvic node-positive disease. Acute toxicity was assessed using Radiation Therapy Oncology Group (RTOG) acute morbidity scoring criteria. Dose thresholds for acute rectal and bladder toxicity were identified.

Results: The incidence of acute grade 2 GI toxicity was 20.8%, and grade 2 genitourinary (GU) toxicity was 6.9%. No Grade 3 to 4 toxicity occurred. Small bowel toxicity was uncommon (Gr 2 = 4%). The 2Gy equivalent doses (EQD2) to the rectum and bladder (α/β = 3) calculated showed that the absolute doses were more consistent predictors of acute toxicities than the relative volumes. Those with grade 2 or more GI symptoms had significantly higher V (13.2 vs 9.9cc, p = 0.007) and V (20.6 vs 15.4cc, p = 0.005). Those with grade 2 or more GU symptoms had significantly higher V (30.4 vs 18.4cc, p = 0.001) and V (44.0 vs 28.8cc, p = 0.001). The optimal cutoff value for predicting grade 2 acute proctitis, for V was 9.7cc and for V was 15.9cc. For grade 2 GU symptoms, the threshold values were 23.6cc for V and 38.1cc for V.

Conclusions: Hypofractionated radiotherapy for prostate cancer is well tolerated and associated with manageable acute side effects. The absolute dose-volume parameters of rectum and bladder predict for acute toxicities.
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http://dx.doi.org/10.1016/j.meddos.2016.10.002DOI Listing
September 2017

Progesterone Receptors, Pathological Complete Response and Early Outcome for Locally Advanced Breast Cancer - a Single Centre Study. (PPLB - 01).

Indian J Surg Oncol 2016 Dec 23;7(4):397-406. Epub 2016 Apr 23.

Department of Breast Oncosurgery, Tata Medical Centre, Kolkata, India.

Neoadjuvant chemotherapy (NACT) for locally advanced breast cancer (LABC), apart from increasing breast conservation rates, also provides an opportunity to assess tumour response to chemotherapy, with Pathological Complete Response (pCR) described as an independent prognostic factor and a surrogate marker for better outcome and survival. Our primary aim was to identify clinical and pathological factors associated with pCR following NACT in patients with LABC treated at our institution. Our secondary aim was to analyze the impact of pCR and associated factors on disease free survival (DFS) and overall survival (OS). A retrospective analysis of LABC patients treated with NACT between Jun 2011 and Dec 2013. Clinical and histological variables were analyzed for association with pCR (no invasive or in situ carcinoma in breast or axillary lymph nodes). Kaplan-Meier curves and Cox regression model was used for survival analysis. All values were twosided, and statistical significance was defined as  < 0.05. 240 patients were included. The median tumor size was 6 cm, with T4 disease in 49.8 %. 45 % of tumors were of low grade (G1 + G2) and 53.8 % of high grade (G3). Estrogen Receptor (ER) was positive in 70.8 %, progesterone receptor (PR) in 53.3 % and Her2 in 38.8 %. The preferred NACT regimen was sequential anthracycline and taxane and 88.8 % of patients received this regimen. Of 93 potential Her2 Positive patients, only 23 received trastuzumab. Overall 23.2 % patients had pCR. At median follow up of 21 months (range, 3-42), 16.3 % of patients had recurrent disease, and 6.7 % had died. High tumor grade ( = 0.04), PR negative status ( < 0.01) and trastuzumab treatment ( = 0.01) were significant predictors of pCR in univariate analysis. On multivariate analysis PR negativity (OR 3.2, 95 % CI = 1.6 to 6.04,  = 0.001) and Trastuzumab use (OR 0.24, 95 % CI = 0.1 to 0.6,  = 0.004) were significant. Patients with pCR had positive associations with survival ( < .02,OS& .02,DFS) and interestingly PR positivity had positive association with DFS ( = 0.02) in Kaplan-Meier curves. On Cox regression, PR positivity (HR = 0.3,  < 0.01) and pCR (HR = 0.2,  < 0.01) correlated with DFS, though not with early OS. for the PR positive patients were paradoxical. Though less likely to have pCR (15 %, vs 32 % if PR negative), they had better DFS ( = 0.02), and achieving pCR had no survival benefit in this group. In contrast, PR negative patients, irrespective of ER status, had a high pCR rate, and achieving pCR had survival advantage ( < 0.05,DFS&  < 0.02,OS). PR negative patients without pCR had the worst DFS ( < 0.01) among all. High grade and Trastuzumab treatment as predictors of pCR, and pCR as a surrogate marker for survival are well recognized, and are supported by our findings. In present cohort, PR negativity showed prognostic importance independent of ER status. However these results were derived from sub-group, post-hoc analysis of data from a pre-existing cohort, without 'a-priori' hypothesis for survival analysis in relation to PR. These "hypothesis generating" results need confirmation by a well-designed prospective cohort or a randomized trial.
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http://dx.doi.org/10.1007/s13193-016-0523-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097757PMC
December 2016