Publications by authors named "Animesh Saha"

12 Publications

  • Page 1 of 1

Can dosimetry affect local control and survival in patients with early-stage lung cancer treated with Stereotactic Ablative Radiotherapy (SABR)? An analysis of the UK's largest cohort of lung SABR patients.

Acta Oncol 2021 Apr 24;60(4):505-512. Epub 2021 Jan 24.

Department of Medical Physics, Leeds Teaching Hospitals, NHS trust, Leeds, UK.

Purpose/objectives: A recent study has shown that tight conformity of lung Stereotactic Ablative Radiotherapy (SABR) plans might worsen loco-regional control and can predict distant metastases. The study aims to report overall survival (OS), progression-free survival (PFS), local recurrence free survival (LRFS), and dosimetry of early-stage lung cancer patients treated with SABR and to try to explore any dosimetric predictor of outcomes.

Material And Methods: Patients treated in our institute (May 2009-August 2018) were included. Electronic medical records were reviewed for baseline characteristics, treatment details, and outcomes. Dosimetric data were extracted from Xio and Monaco software. Patients were treated according to the United Kingdom (UK) SABR consortium guidelines. Kaplan-Meier's analysis with log-rank test was used for survival analysis. The univariate and multivariable Cox regression model was used for correlating dosimetric variables and outcomes.

Results: We treated 1266 patients with median age of 75 years and 47.4% were male. Median follow up was 56 months. Median OS was 36 months with 1, 2, and 5 years OS of 84.2%, 64.5%, and 31.5%, respectively. Median for PFS and LRFS was not reached. One, 2, and 5 years PFS were 87.4%, 78.4%, and 72.5%, respectively. One, 2, and 5 years LRFS were 98.2%, 95.1%, and 92.5%, respectively. Planning target volume (PTV), dose to 99% volume of PTV (D99), and R50 (volume receiving the 50% dose/volume (PTV)) were significantly associated with OS. PTV, mean lung dose (MLD), V20 (volume of lung minus gross tumour volume (GTV) receiving 20 Gy), V12.5 (volume of lung minus GTV receiving 12.5 Gy), and dose fractionation were significantly associated with PFS. Nothing was associated with LRFS on univariate analysis. R100 of >1.1 was associated with better OS, PFS, and LRFS compared to R100 ≤ 1.1.

Conclusion: SABR achieves good clinical outcomes in patients with early-stage lung cancer; even in elderly patients with multiple comorbidities. In the largest UK early lung cancer cohort treated with SABR, we found that dosimetry correlates with clinical outcomes. Further validation of these results is needed to guide future optimisation of SABR delivery.
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April 2021

Clinical and dosimetric predictors of radiation pneumonitis in early-stage lung cancer treated with Stereotactic Ablative radiotherapy (SABR) - An analysis of UK's largest cohort of lung SABR patients.

Radiother Oncol 2021 Mar 14;156:153-159. Epub 2020 Dec 14.

Department of Medical Physics, St James's University Hospital, Leeds, UK.

Background: Stereotactic Ablative Radiotherapy (SABR) is the standard treatment for early-stage medically inoperable lung cancer. Predictors of radiation pneumonitis (RP) in patients treated with SABR are poorly defined. In this study, we investigate clinical and dosimetric parameters, which can predict symptomatic RP in early-stage lung cancer patients treated with SABR.

Materials And Methods: Patients treated with lung SABR between May 2009 and August 2018, in a single United Kingdom (UK) radiotherapy center were included. The patient's baseline characteristics, treatment details, and toxicity were retrieved from the electronic medical record. Dosimetric data was extracted from Xio and Monaco treatment planning systems. Patients were treated according to the UK SABR consortium guidelines. RP was graded retrospectively using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, based on available clinical and imaging information. Univariate and multivariate binary logistic regression was performed to determine predictive factors for grade ≥ 2 radiation pneumonitis, using Statistical Package for the Social Sciences (SPSS) statistics version 21 software. The goodness of fit was assessed using the Hosmer and Lemeshow test. The optimal diagnostic threshold was tested using the Receiver operating characteristics (ROC) curve. The chi-square test was carried out to test the different risk factors against the likelihood of developing grade ≥ 2 pneumonitis.

Results: A total of 1266 patients included in the analysis. The median age of patients was 75 years. Six hundred sixty-six patients (52.6%) were female. Median follow up was 56 months. Sixty-five percent of patients received 55 Gy in 5 fractions. Forty-three percent of patients had Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 and 16.2% had PS of 3. The Median Charlson comorbidity index was 6 (range 2-11). Median Standardized Uptake Value (SUV) max of the tumor was 6.5. Four hundred two patients (31.8%) had confirmed histological diagnosis; other patients were treated based on a radiological diagnosis. The median tumor size was 20 mm (range 4 mm-63 mm). Median Planning Target Volume (PTV) was 30.3 cc. Median values of R100, R50, and D2cm were 1.1, 5.6, 32.8 Gy. The median value of mean lung dose, V20, and V12.5 were 3.9 Gy, 5 %and 9.3% respectively. Eighty-five (6.7%) patients developed symptomatic RP (grade ≥ 2) with only 5(0.4%) developing grade 3 RP. Five percent of patients developed rib fractures but only 28% of these were symptomatic. On univariate analysis lower lobe tumor location, larger tumor size, PTV, mean lung dose, lung V20Gy, and V12.5 Gy were significantly associated with grade ≥ 2 RP. On multivariate analysis, only mean lung dose was associated with grade ≥ 2 pneumonitis. ROC curve analysis showed optimal diagnostic threshold for tumour size, PTV, mean lung dose, V20 and V12.5; are 22.5 mm ((Area Under Curve (AUC)-0.565)), 27.15 cc (AUC-0.58), 3.7 Gy (AUC-0.633), 4.6% (AUC-0.597), 9.5% (AUC-0.616). The incidence of ≥grade 2 RP was significantly high for values higher than the ROC threshold.

Conclusion: SABR treatment resulted in a very low rate of grade 3 pneumonitis. Lower lobe tumor location, larger tumor size, PTV, mean lung dose, V20, and V12.5 were found to be significant predictors of symptomatic radiation pneumonitis.
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March 2021

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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November 2020

Development of Non-alcoholic Fatty Liver Disease (NAFLD) in Young Obese Tribal Subjects of Tripura: Link between Low 25 (OH) Vitamin-D Levels and Immune Modulators.

J Assoc Physicians India 2019 Aug;67(8):52-56

Research Assistant ICMR Project, Tripura Medical College and Dr. BRAM Teaching Hospital, Agartala, Tripura.

Background: There have been many studies conducted so far on Non Alcoholic Fatty Liver Disease (NAFLD) with its many aspects including its association with 25 hydroxy Vitamin D levels and its rather complex interplay with pro-inflammatory cytokines such as Interleukin-1a (IL-1a), Interleukin-6 (IL-6) and Tumour Necrosis Factor-Alpha (TNF-α), Interleukin-17a (IL-17a) and anti-inflammatory cytokines such as Interleukin-4 (IL-4) and Interleukin-10 (IL-10). This study was designed to show the development of NAFLD in the young tribal population of Tripura and the link between 25(OH) Vitamin D and pro-inflammatory cytokines (IL-1a, IL-6, IL-17a and TNF-ɑ) and -inflammatory cytokines such as IL - 4 and IL - 10 and the development of NAFLD while at the same time throws light on the prevalence of 25(OH) Vitamin D deficiencies and the levels of pro-inflammatory cytokines in the study group.

Methods: The study is an analytical cross-sectional study with final population of 94 cases between 18 to 40 years of age fulfilling inclusion and exclusion criteria and an equal number of subjects from same tribal community age and sex matched taken as control population.

Results: There was a significant relationship between level of 25(OH) Vitamin D and fatty liver (OR: 9.46, 95% CI: 4.82 - 18.59; p < 0.001). The mean serum 25(OH) Vitamin D level in the cases was significantly higher than the controls (17.21 ng/ ml + 6.34 ng/ml vs 26.56 ng/ml + 10.63 ng/ml; p < 0.001). There was a significant difference between the mean serum levels of IL-1a (11.50 Pg/ml ± 2.75 Pg/ml vs 8.28 Pg/ml ± 2.08 Pg/ml; p < 0.001), IL-4 (0.69 Pg/ml ± 0.43 Pg/ml vs 0.84 Pg/ml ± 0.36 Pg/ml; p = 0.009), IL-6 (2.99 ± 1.11 Pg/ml vs 2.22 ± 1.08 Pg/ml; p < 0.001), IL-10 (6.50 ± 2.76 Pg/ml vs 5.23 Pg/ml ± 2.67 Pg/ml; p = 0.002), IL-17a (5.33 Pg/ml ± 2.22 Pg/ml vs 3.64 Pg/ml ± 1.99 Pg/ml; p < 0.001) and TNF-α (6.99 ± 2.81 Pg/ml vs 5.40 ± 3.08 Pg/ml; p < 0.001) of the cases and the controls Low serum 25(OH) D [OR: 0.87 (95% CI: 0.83 - 0.92), p = 0.0001], and high IL-1a [OR: 1.52 (95% CI: 1.26 - 1.84), p < 0.0001] were independently associated with the risk of NAFLD.

Conclusion: 25(OH) Vitamin D concentration are lower while that of IL-1a, IL-4, IL-6, IL-10, IL-17a and TNF-α are higher in subjects with fatty liver in comparison to those without. 25(OH) Vitamin D deficiency and high levels of serum IL-1a were independently associated with the risk of development of NAFLD.
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August 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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April 2019

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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December 2016

Correlation of clinicopathological outcomes with changes in IHC4 status after NACT in locally advanced breast cancers: do pre-NACT ER/PR status act as better prognosticators?

Breast Cancer (Dove Med Press) 2015 10;7:381-8. Epub 2015 Dec 10.

Department of Breast Surgery, Tata Medical Center, Kolkata, West Bengal, India.

Background: Following neoadjuvant chemotherapy (NACT) for breast cancer, changes in estrogen receptor (ER), progesterone receptor (PR), HER2 status, and Ki-67 index (IHC4 status) and its correlation with pathological complete response (pCR) or relapse-free survival (RFS) rates could lead to better understanding of tumor management.

Patients And Methods: Pre- and post-NACT IHC4 status and its changes were analyzed in 156 patients with breast cancer. Associations between pCR, RFS rates to IHC4 status pre- and post-NACT were investigated.

Results: pCR was found in 25.3% patients. Both ER and PR positive tumors had the lowest (14.3%) pCR compared to ER and PR negative (29%) or either ER-/PR-positive (38.6%) tumors. PR positivity was significantly associated with less likelihood of pCR (15% versus 34%). The pCR rate was low for luminal A subtype (13.68%) compared to 24.36%, 26.31%, and 33.33% for luminal B, HER2-enriched, and triple-negative subtypes, respectively. There was significant reduction in ER expression and Ki-67 index post-NACT. RFS of patients in whom the hormonal status changed from positive to negative was better compared to those of patients in whom the hormonal status changed from negative to positive.

Conclusion: Although changes in IHC4 occurred post-NACT, pre-NACT hazard ratio status prognosticated RFS better. pCR and RFS rates were lower in PR-positive tumors.
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December 2015

A randomized controlled pilot study to compare capecitabine-oxaliplatin with 5-FU-leucovorin as neoadjuvant concurrent chemoradiation in locally advanced adenocarcinoma of rectum.

J Cancer Res Ther 2015 Jan-Mar;11(1):88-93

Department of Radiotherapy, Institute of Post Graduate Medical Education and Research, Kolkata, India.

Context: Established as an adjuvant chemotherapy, CapeOX has recently been shown to have radiosensitizer property in a phase I and II studies, with appreciable downstaging and tolerable toxicities.

Aims: The study was designed to evaluate whether the capecitabine-oxaliplatin combination was superior to 5-fluorouracil (5-FU)-leucovorin as radiosensitizer for neoadjuvant chemoradiation in downstaging locally advanced rectal adenocarcinoma and to compare the toxicities between the two arms.

Settings And Design: Single institutional, double blinded, prospective, noncrossover, randomized control pilot study.

Subjects And Methods: In arm A (n = 21), patients received capecitabine (1,000 mg/m(2) daily) in twice dailydoseon days 1-14 and 25-38 and oxaliplatin (85 mg/m(2)) intravenous ( IV) over 2 h, on D1 and D29. In arm B (n = 21), patients received leucovorin (20 mg/m(2)) and 5-FU (350 mg/m(2)) from D1-5 and D29-33. Patient in both the arms received concurrent radiation (50.4 Gy in 28 #, in conventional fractionation of 1.8 Gy per fraction). Six to eight weeks after concurrent chemoradiation, patients underwent assessment and surgery with total mesorectal resection. Postoperatively, adjuvant chemotherapy with m-FOLFOX 6 of 4 months was given to all patients.

Statistical Analysis Used: Chi-square test was used to compare categorical variables between the groups.

Results: Objective response rate (ORR) in arm A was 80.95% compared to arm B which had 66.66% (P = 0.3055). Pathological complete response (pCR) rate of arm A was comparable to arm B (23.8 vs 14.28%, P value = 0.6944). Surgery with R0 resection was possible in 80.95% cases of arm A compared to 66.66% cases of arm B (P = 0.4827). Grade III toxicities were quite comparable between two treatment arms.

Conclusions: In terms of ORR, pCR rate, R0 resection, and toxicity profile; both the arms were comparable.
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January 2016

Demographic and clinical profile of patients with brain metastases: A retrospective study.

Asian J Neurosurg 2013 Jul;8(3):157-61

Department of Radiotherapy, IPGMER and SSKM Hospital, Kolkata, West Bengal, India.

Context: Brain metastases are the most common type of intracranial neoplasm, with the total number outnumbering primary brain tumors by a ratio of 10:1 and occur in about 25% of cancer patients. However, controversies exist regarding demographic and clinical profile of brain metastases.

Aims: The purpose of this study was to analyze retrospectively the demographic and clinical profile of patients with brain metastases.

Settings And Design: Retrospective, single institutional study.

Materials And Methods: A retrospective study of 72 patients with brain metastasis was carried out from November 2010 to October 2012. The data pertaining to these patients was entered in a standardized case record form. These include History; clinical examination and other investigations including computed tomography/magnetic resonance imaging scan of the brain.

Statistical Analysis: A statistical analysis was performed on the data collected using the MedCalc version 11.

Results: Brain metastases were more common in male and occur in 6(th) decade of life mostly. There was no relationship of occupation or socio-economic status with the incidence of brain metastases. Carcinoma lung was the most common primary giving rise to brain metastases followed by breast. Adenocarcinoma accounts for most common histology of the primary that give rise to metastases. Multiple metastases were more common than the single group. Supratentorial lesions were more common than infratentorial lesions. Among them, parietal lobe was the most common site of involvement.

Conclusions: The present study highlights that the incidence of brain metastasis is common in elderly population and mostly due to primary lung. Adenocarcinoma was the most common histology of primary. Majority of lesions has been observed at parietal lobe.
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July 2013

A two-dimensional polymer from the anthracene dimer and triptycene motifs.

J Am Chem Soc 2013 Sep 17;135(38):14134-41. Epub 2013 Sep 17.

Department of Chemistry, University of Nevada , Reno, Nevada 89557-0216, United States.

A two-dimensional polymer (2DP) based on the dimerization of anthraceno groups arranged in a triptycene motif is reported. A photoinduced polymerization is performed in the crystalline state and gives a lamellar 2DP via a crystal-to-crystal (but not single-crystal to single-crystal) transformation. Solvent-induced exfoliation provides monolayer sheets of the 2DP. The 2DP is considered to be a tiling, a mathematical approach that facilitates structural elucidation.
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September 2013

Extranodal Rosai-Dorfman Disease presenting as spinal extradural lesion: a case report with a review of the literature.

J Cancer Res Ther 2012 Oct-Dec;8(4):647-9

Sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai-Dorfman disease (RDD) is a rare, but well-documented entity. We report a male patient who presented with progressive paraparesis, with thoracolumbar extradural lesion (from D11 to L2 level) on magnetic resonance imaging (MRI). He underwent D12-L2 laminectomy followed by total removal of extradural spinal space-occupying lesion (SOL). Histopathological diagnosis of the lesion was RDD. Four weeks after surgery, he was treated with external beam radiotherapy, total dose: 50.4GY in 28 fractions. On three-month follow-up, he did not have any neurological deficits. There was no evidence of other extranodal or lymph node involvement. This case has been reported on account of rare presentation of this disease as spinal extradural lesion. Pertinent literature has been reviewed.
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July 2013

Facile and general preparation of multifunctional main-chain cationic polymers through application of robust, efficient, and orthogonal click chemistries.

J Am Chem Soc 2012 Oct 1;134(41):17291-7. Epub 2012 Oct 1.

Department of Materials, ETH-Zürich, CH-8093 Zürich, Switzerland.

Poly(ß-hydroxyl amine)s are prepared from readily available small molecular building blocks at ambient conditions. These macromolecules can be transformed into main-chain cationic polymers upon quaternization of the backbone amine units. The modular and mild nature of the synthesis allows for incorporation of multiple (2-4) chemically distinct reactive sites in the polymer chain. Modifications of the reactive sites afford multifunctional polymers with tunable properties. The orthogonal nature of the involved chemistries sets the synthetic pathway free from any functional group protection/deprotection requirements. This feature also allows for alteration of the modification sequence.
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October 2012