Publications by authors named "Renu Madan"

43 Publications

Impact of Immunohistochemical profiling of Glioblastoma multiforme on clinical outcomes: Real-world scenario in resource limited setting.

Clin Neurol Neurosurg 2021 Jun 4;207:106726. Epub 2021 Jun 4.

Department of Radiotherapy& Oncology, PGIMER, Chandigarh, India. Electronic address:

Objective: Intuition into the molecular pathways of glioblastoma multiforme (GBM) has changed the diagnostic, prognostic, and therapeutic approaches. We investigated the influence of various clinical and molecular prognostic factors on survival outcomes in radically treated GBM patients.

Methods: Medical records of 160 GBM patients treated between January-2012 and December-2018 with surgery followed by post-operative external beam radiotherapy (EBRT) with/without temozolomide (TMZ) were reviewed. Immunohistochemical (IHC) assays were performed for IDH1mutation, ATRX loss, TP53 overexpression and Ki-67% index. Apart from disease and treatment-related factors' influence on clinical outcomes, the impact of IHC markers in prognostication was analyzed using appropriate statistical tests.

Results: The median overall survival (OS) was 14 months. EBRT with concurrent TMZ was given to 60% of patients and 42.5% completed the standard Stupp-protocol. Significant improvements in OS was observed in patients aged ≤ 50years (2-year OS: 22.1% vs. 12.5%, p = 0.001), those who underwent gross total resection (2-year OS: 21.8% vs. 12.8%, p = 0.002), received concurrent TMZ (21.9% vs. 12.5%, p = 0.005), completed the entire Stupp-protocol (2-year OS: 23.4% vs. 6.5%, p = 0.000), and with Ki-67 index <20% (2-year OS: 23.3% vs. 11.6%, p = 0.015). On multivariate analysis, IDH1 mutation, ATRX loss, TP53 expression, and Ki-67 ≤ 20% were significant prognosticators of outcomes.

Conclusion: GBM patients treated with concurrent chemoradiation and those who completed the full Stupp-protocol experienced better survival outcomes. Molecular biology significantly impacts clinical outcomes and plays a key deterministic role in newer management strategies.
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http://dx.doi.org/10.1016/j.clineuro.2021.106726DOI Listing
June 2021

Pineal anlage tumor: A case report and clinico-pathological review.

Clin Neurol Neurosurg 2021 Jul 5;206:106629. Epub 2021 May 5.

Department of Radiotherapy and Oncology, PGIMER, Chandigarh.

Pineal anlage tumor (PAT) is an extremely rare tumor of paediatric population. It is considered as a subtype of pineoblastoma having ectomesenchymal/ rhabdomyoblastic and cartilaginous differentiation. PAT is presumed to have an aggressive behaviour with propensity for craniospinal fluid (CSF) spread due to histologically resemblance with pineoblastoma, thus requiring intensive multimodality treatment with craniospinal irradiation and chemotherapy. Here we report a case of PAT in a 35 years old lady along with clinical and pathological review. To the best of our knowledge only less than ten cases of pineal anlage tumors have been reported in the literature and index case is only second in the adult age group (rare histology in rare age group).
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http://dx.doi.org/10.1016/j.clineuro.2021.106629DOI Listing
July 2021

Expanding role of radiotherapy in adenoid cystic carcinoma of the tracheobronchial tree: a new horizon.

Tumori 2021 May 12:3008916211012461. Epub 2021 May 12.

Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Background: Primary adenoid cystic carcinomas (ACCs) of central trachea-bronchi system are rare and heterogeneous tumors. Definitive radiotherapy (RT) is the recommended treatment in surgically unresectable or incomplete resection or in the presence of severe comorbidities.

Objective: To evaluate the clinical features and outcomes of patients with ACC of trachea-bronchi treated with radiotherapy.

Methods: Retrospective medical records review was done in all patients with histologically confirmed ACC of trachea-bronchi between January 2010 and December 2019. Patient disease and treatment characteristics and toxicity data were analyzed. Overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were computed using Kaplan-Meier method (log-rank test).

Results: Nineteen patients (10 women and 9 men) were included in this analysis with median age of 40 years (range, 14-70). Of these patients, 63.2% (n = 12) presented in stage IV disease. Twelve and three patients received definitive (median dose 67.8 Gy) and adjuvant (median dose 50 Gy) RT, respectively. The median follow-up was 42.5 months (range, 4-120); 15 patients were alive and 4 were dead at that time. Local recurrence or progression was observed in 52.6% and distant metastasis found in 47.3% of patients. The 5-year OS, LRFS, and DMFS for all patients were 81.2%, 52.8%, and 39.6%, respectively. Baseline lymph node involvement showed significant impact on OS (56.3% vs 100%, = 0.011). Among patients receiving definitive RT, patients with higher RT dose (⩾66 Gy) had significantly better survival outcomes (5-year LRFS: 75% vs 16.7%, = 0.013).

Conclusion: Definitive RT is an exemplary treatment for unresectable disease. Higher dose is recommended to improve long-term outcomes.
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http://dx.doi.org/10.1177/03008916211012461DOI Listing
May 2021

Clinicopathological characteristics and outcomes in embryonal tumor with multilayered rosettes: A decade long experience from a tertiary care centre in North India.

Ann Diagn Pathol 2021 Apr 19;53:151745. Epub 2021 Apr 19.

Departments of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Background: Embryonal tumor with multilayered rosettes (ETMR) are a heterogenous group clinically, pathologically and topographically. Due to limited cases, data regarding its molecular genetics, pathology and prognostic factors is evolving. We retrospectively analysed our cohort of ETMR over last decade in order to study their clinicopathological characteristics and outcome.

Methods: Our cohort consisted of patients diagnosed with Embryonal tumor with abundant neuropil and true rosettes (ETANTR)/Ependymoblastoma (EBL)/ Medulloepithelioma (MEPL) over the past decade. Clinical details, including outcome and imaging data was retrieved. Histological analysis including immunohistochemical work-up was performed.

Results: Cohort included 15 patients with age range between 1 and 28 years and M:F ratio of 1.5:1. Supratentorial location predominated in comparison to tumors arising in posterior fossa. ETANTR and EBL patterns were equally distributed (40% each), followed by one case each of mixed pattern (EBL + ETANTR), MEPL and embryonal tumor, unclassified. All tumors readily expressed LIN 28A and INI-1 was retained. Recurrence with evidence of glial and rhabdoid differentiation was noted in a single patient 9 months following resection. Follow-up period ranged from 1 to 31 months, with overall median survival of 6.4 months. Eight patients were planned for adjuvant treatment following surgery, of which only four could complete it. All patients, except for one, succumbed to the disease.

Conclusions: ETMR have a heterogenous morphology and gathers ETANTR, EBL, MEPL within its spectrum. Following treatment, the recurrent tumor may feature glial/rhabdoid differentiation. LIN28A is expressed in all cases, however should be interpreted in context of histology. Prognosis of ETMR remains dismal despite multimodal therapy.
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http://dx.doi.org/10.1016/j.anndiagpath.2021.151745DOI Listing
April 2021

Clinical behaviour and outcome in pediatric glioblastoma: current scenario.

Radiat Oncol J 2021 Mar 30;39(1):72-77. Epub 2021 Mar 30.

Department of Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Pediatric glioblastoma (pGBM) is a rare entity accounting for only approximately 3% of all childhood brain tumors. Treatment guidelines for pGBM have been extrapolated from those in adult glioblastoma. Rarity of pGBM and underrepresentation of pediatric population in major studies precludes from defining the ideal treatment protocol for these patients. Maximum safe resection is performed in most of the cases followed by postoperative radiotherapy in children over 3 years of age. Benefit of temozolomide is unclear in these patients. Here, we present the clinicopathological details and outcome of six pGBM patients treated at our institute in 2018-2019.
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http://dx.doi.org/10.3857/roj.2020.00591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024182PMC
March 2021

Multimodality treatment for Central Nervous System Germ Cell Tumors: Disease spectrum and management strategies - A tertiary care center experience from India.

Clin Neurol Neurosurg 2021 Mar 13;202:106481. Epub 2021 Jan 13.

Department of Radiotherapy & Oncology, PGIMER, Chandigarh, India. Electronic address:

Objective: Intracranial germ cell tumors (GCTs) are relatively rare neoplasms, representing 2-3 % of paediatric brain tumors in Western countries and 8-15 % in East Asia. Here, we discuss the clinical features and treatment outcomes in patients with central nervous system (CNS) GCTs treated at our institute.

Methods: Medical records of all primary CNS GCT patients were retrieved retrospectively from 2007 to 2019. Demographic, clinical, treatment and follow up details were entered in a predesigned proforma. Overall survival (OS) and progression-free survival was computed using Kaplan-Meier method and Log-Rank test. Effect of various prognostic factors on survival outcomes was assessed by univariate and multivariate analysis.

Results: A total of 28 CNS GCT patients were included in this analysis. Median age at presentation was 17 years (range, 7-45 years) with a male to female ratio of 1.8:1. Pineal region was the commonest location, encountered in 15 patients (53.6 %). Pure germinoma was the most frequent histology observed, seen in 19 patients (67.9 %). Male gender and germinoma histology were highly associated with pineal location (p = 0.043 and p = 0.052, respectively). Fourteen patients underwent surgical intervention and nine patients underwent biopsy for diagnostic purpose or to relieve the obstructive symptoms. Only 23 patients (82.1 %) received chemotherapy. However, all patients received radiotherapy (Craniospinal irradiation/whole brain radiotherapy/whole ventricular radiotherapy/ or local radiotherapy). After a median follow-up of 53 months (range, 7-150), 23 patients (82.1 %) were alive. OS was significantly affected by histology (89 % in germinoma vs. 60 % in non-germinomatous, p = 0.054) and location (93 % in pineal region vs. 64.2 % in other location, p = 0.042). Age, gender and surgery did not have any impact on the survival outcomes.

Conclusion: CNS GCTs are relatively rare and heterogeneous neoplasms commonly seen in pineal and suprasellar locations. A combination of chemotherapy and radiotherapy had shown excellent outcomes.
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http://dx.doi.org/10.1016/j.clineuro.2021.106481DOI Listing
March 2021

Analysis of 24 cases of epithelioid glioblastoma: Experience from a tertiary centre of North India.

Ann Diagn Pathol 2021 Feb 13;50:151679. Epub 2020 Dec 13.

Department of Neurosurgery, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India.

Background: Epithelioid glioblastoma (eGB) is a recently recognized and a rare variant of glioblastoma. This study aimed to describe the clinical, histological and immunohistochemical spectrum and outcome of eGB from a tertiary care hospital in north India.

Materials And Methods: Twenty four cases of eGB diagnosed over past 10 years were reviewed with detailed morphological and immunohistochemical analysis (GFAP, EMA, Vimentin, Myogenin, INI-1, Cytokeratin, Synaptophysin, CD99, S100, MelanA, IDH1, ATRX, p16, EZH2, Ki-67, and BRAF V600E mutant antibody).

Result: The mean age was 29.9 years (3-54 years), with equal male and female patients. All had supratentorial tumor. All cases showed epithelioid cells in sheets; however, focal spindling (7 cases, 29.2%), grouping/nesting (6 cases, 25%) and papillary configuration (5 cases, 20.8%) were also noted. All showed microvascular proliferation (MVP) and all except one demonstrated areas of necrosis. INI1 was retained in all cases, while 2 showed patchy loss. EZH2 overexpression (>25%) was observed in 4 cases, while 5 cases showed loss of p16 expression. BRAF V600E mutant protein expression was seen in 12/23 (52.2%) cases. Outcome was available in 8 cases, out of which 6 (75%) experienced recurrence. The median survival was 25.5 months. Cases with tumor infiltrating lymphocytes had a better outcome.

Conclusion: eGB is a distinct variant of glioblastoma which has predilection towards younger age group. It shows high percentage of BRAF V600E mutation and a subset of it shows longer survival. Cases with presence of tumor infiltrating lymphocytes are associated with better outcome.
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http://dx.doi.org/10.1016/j.anndiagpath.2020.151679DOI Listing
February 2021

Small cell glioblastoma multiforme: a case series and clinicopathological update.

CNS Oncol 2020 12 7;9(4):CNS63. Epub 2020 Dec 7.

Department of Neurosurgery, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.

Small cell glioblastoma (scGBM) is a rare histological variant of classical glioblastoma (GBM). Presence of necrosis and microvascular proliferation is not essential for the diagnosis. It is thought to have more aggressive behavior as compared with classical GBM; however, because of its rarity standard treatment guidelines are not available. Adjuvant treatment for these cancers consists of postoperative radiotherapy with concurrent and maintenance temozolomide similar to classical GBM. Here we present a case series of five small cell glioblastoma patients along with the clinical-pathological review.
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http://dx.doi.org/10.2217/cns-2020-0016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737196PMC
December 2020

Primary mediastinal germ cell tumors: Survival outcomes and prognostic factors - 10 years experience from a tertiary care institute.

Rare Tumors 2020 18;12:2036361320972220. Epub 2020 Nov 18.

Department of Radiotherapy & Oncology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Primary Mediastinal Germ Cell Tumor (PMGCT) is a rare and heterogeneous entity. These tumors are typically diagnosed in young adults and carry a poor prognosis. We conducted this study to evaluate the role of radiotherapy on treatment outcomes and prognostic factors in PMGCT that may allow a more adapted treatment strategy to improve survival. Case records of patients who presented with PMGCT over a period of 10-years from January-2009 to December-2019 were retrospectively evaluated. Survival analyses were calculated using Kaplan-Meier (Log-rank) method. Poor prognostic factors for survival were evaluated with Multivariate analysis using Cox-regression method. A total of 46-patients data was analyzed, the majority of the patients were males (95.7%) with a median age of 25-years (range, 17-62). Non-seminomatous histology was predominant (60.9%). Sixteen-patients (34.7%) presented with complications at their initial presentation. Majority of the patients were treated with multimodality approach using chemotherapy, surgery, and/or radiotherapy. At a median follow-up of 40.8 months, the 1, 3, and 5-year overall survival (OS) was 69.6%, 52.2%, and 44.7% respectively. Patients who received radiotherapy in first-line treatment showed significant improvement in 5-year OS (72% vs 30%,  = 0.004) and disease-free survival (70% vs 24%,  = 0.007) in comparison with patients who did not receive. Multivariate analysis revealed that radiotherapy, chemotherapy, surgery, and complications at presentation were independent prognostic factors for OS. PMGCTs are aggressive neoplasms especially in patients presenting with disease-related complications. Dual modality management (radiotherapy as local therapy along with chemotherapy) had shown improvement in survival.
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http://dx.doi.org/10.1177/2036361320972220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682202PMC
November 2020

Delayed yet effective response of an endolymphatic sac tumor to radiosurgery: case report focusing on its radio-biological behavior.

Br J Neurosurg 2020 Nov 25:1-4. Epub 2020 Nov 25.

Department of Radiotherapy, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Endolymphatic sac tumors (ELST), though benign are locally invasive lesions. Owing to its vascularity, complete surgical resection is often not possible and adjuvant gamma knife radiosurgery (GKRS) is advocated to control tumor growth. These lesions do not uniformly respond to radiation therapy in the initial phase and their early radiobiological course after GKRS is less understood. We discuss a case of residual ELST where a mild increase was noted at 36 months following GKRS and then regressed completely after a decade. This report possibly has the longest follow-up revealing the true efficacy of GKRS in these tumors. ELST shows a variable response in the early years after GKRS. They may remain static, regress or increase in size. One should be aware of these patterns of early radiological responses and a long term follow up is warranted as some lesions may show radiosurgical effectiveness after a long latent period.
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http://dx.doi.org/10.1080/02688697.2020.1849553DOI Listing
November 2020

Erectile dysfunction and cancer: current perspective.

Radiat Oncol J 2020 Dec 26;38(4):217-225. Epub 2020 Aug 26.

Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Erectile dysfunction (ED) is one of the major but underreported concerns in cancer patients and survivors. It can lead to depression, lack of intimacy between the couple, and impaired quality of life. The causes of erectile dysfunction are psychological distress and endocrinal dysfunction caused by cancer itself or side effect of anticancer treatment like surgery, radiotherapy, chemotherapy and hormonal therapy. The degree of ED depends on age, pre-cancer or pre-treatment potency level, comorbidities, type of cancer and its treatment. Treatment options available for ED are various pharmacotherapies, mechanical devices, penile implants, or reconstructive surgeries. A complete evaluation of sexual functioning should be done prior to starting anticancer therapy. Management should be individualized and couple counseling should be an integral part of the anticancer treatment.
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http://dx.doi.org/10.3857/roj.2020.00332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785841PMC
December 2020

Comment on: Role of 68-Ga-PSMA-PET/CT in pelvic radiotherapy field definitions for lymph node coverage in prostate cancer patients, by Onal C et al.

Radiother Oncol 2021 02 24;155:e13-e14. Epub 2020 Sep 24.

Department of Radiotherapy and Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.

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http://dx.doi.org/10.1016/j.radonc.2020.09.031DOI Listing
February 2021

Can 3D-CRT meet the desired dose distribution to target and OARs in glioblastoma? A tertiary cancer center experience.

CNS Oncol 2020 09 18;9(3):CNS60. Epub 2020 Sep 18.

Department of Radiotherapy & Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.

The purpose of the study is to perform a dosimetric analysis of the doses received by planning target volume and organ at risks in the postoperative glioblastoma by using 3D-conformal radiotherapy to a total dose of 60 Gy in 30 fractions.   All patients received concurrent temozolomide every day, and this was followed by adjuvant temozolomide of 5 days of treatment per month. More than 98% of patients were treated with a dose of 60 Gy. Doses were analyzed for the normal whole brain, tumor volume, as well as all the organs at risk. Given the grave prognosis and the limited survival of glioblastoma despite the best treatment available, makes 3D-conformal radiotherapy an equally acceptable treatment option.
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http://dx.doi.org/10.2217/cns-2020-0010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546124PMC
September 2020

Clinical Outcomes and Prognostic Factors in Gastric Carcinoma Patients with Curative Surgery Followed by Adjuvant Treatment: Real-World Scenario.

J Gastrointest Cancer 2021 Jun;52(2):616-624

Department of Radiotherapy and Oncology, PGIMER, Chandigarh, 160012, India.

Background: A wide range of adjuvant treatment regimens exist in gastric carcinoma patients which include chemotherapy, radiotherapy, and/or both either sequential or concurrent. The study aimed to assess the benefit of adjuvant sequential chemotherapy followed by radiotherapy for operable gastric cancers and evaluate the prognostic factors associated with clinical outcomes.

Methods: Patients of stage IB-III gastric carcinoma who underwent radical surgery followed by adjuvant treatment from January 2013 to December 2016 were analyzed retrospectively. Survival was computed using Kaplan-Meier method and prognostic factors were analyzed in multivariate analysis using Cox progression hazard model. A P value < 0.05 was taken as statistically significant.

Results: A total of 108 patients were identified with a median follow-up of 31.7 months (range: 6-96). Seventy-two percent of the patients received adjuvant sequential chemoradiation (N = 77) and 28% of patients received chemotherapy alone. The median survival was 26 months (95% CI: 23.09-28.90). Overall survival (OS) rates for 1, 2, 3, 4, and 5 years were 88.9%, 57.4%, 40.7%, 28.8%, and 20.4%, respectively. Five-year OS for stage-IB, II, and III was 75%, 45%, and 8.3%, respectively (p = 0.023). Surgical margin positivity (9.5% vs. 26.9%, p = 0.042), signet-ring cell histology (6.5% vs. 25.8%, p = 0.00), and adjuvant sequential chemoradiation (p = 0.002) showed a significant impact on survival outcomes and proved as independent prognostic factors.

Conclusion: The present study demonstrated that survival in gastric carcinoma is influenced by the stage of disease and surgical margins. In locally advanced patients, radical surgery followed by sequential chemoradiation based on a doublet/triplet regimen was an independent prognostic factor for survival. Majority of patients in our set-up presented in locally advanced stage, curative resection followed by adjuvant sequential chemoradiation was an independent prognostic factor for survival.
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http://dx.doi.org/10.1007/s12029-020-00440-wDOI Listing
June 2021

Impact of volume of irradiation on survival and quality of life in glioblastoma: a prospective, phase 2, randomized comparison of RTOG and MDACC protocols.

Neurooncol Pract 2020 Jan 18;7(1):86-93. Epub 2019 Jul 18.

Department of Radiotherapy, PGIMER (Post-Graduate Institute of Medical Education and Research), Chandigarh, India.

Background: Though conformal partial-brain irradiation is the standard adjuvant treatment for glioblastoma, there is no consensus regarding the optimal volume that needs to be irradiated. European Organisation for Research and Treatment of Cancer (EORTC) and The University of Texas MD Anderson Cancer Center (MDACC) guidelines differ from the Radiation Therapy Oncology Group (RTOG) in their approach toward peritumoral edema, whereas RTOG and MDACC guidelines differ from EORTC in the concept of boost phase. A scarcity of randomized comparisons has resulted in remarkable variance in practice among institutions.

Methods: Fifty glioblastoma patients were randomized to receive adjuvant radiotherapy using RTOG or MDACC protocols. Apart from dosimetric and volumetric analysis, acute toxicities, recurrence patterns, progression-free survival (PFS), overall survival (OS), and quality of life (QoL) were compared using appropriate statistical tests.

Results: Both groups were comparable with respect to demographic characteristics. Dosimetric analysis revealed significantly lower boost-phase planning treatment volumes and V60 Gy in the MDACC arm (chi-squared, = .001 and .013, respectively). No significant differences were observed in doses with respect to organs at risk, acute toxicity, or recurrence patterns (chi-squared, > .05). On the log-rank test, median PFS (8.8 months vs 6.1 months, = .043) and OS (17 months vs 12 months, = .015) were statistically superior in the MDACC group.Age, extent of resection, and proportion of whole brain receiving prescription dose were associated with improved PFS and OS on regression analysis. QoL of patients was significantly better in the MDACC group in all domains except cognitive, as assessed with the EORTC Quality of Life Questionnaire (QLQ-C30) and Brain Cancer Module (QLQ-BN20) (general linear model, < .05).

Conclusions: Use of limited-margin MDACC protocol can potentially improve survival outcomes apart from QoL of glioblastoma patients, as compared with the RTOG protocol.
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http://dx.doi.org/10.1093/nop/npz024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104885PMC
January 2020

Head-and-neck paragangliomas: An overview of 54 cases operated at a tertiary care center.

South Asian J Cancer 2019 Oct-Dec;8(4):237-240

Department of Otorhinolaryngology, All India Institute of Medical Sciences, New Delhi, India.

Background: Head-and-neck paragangliomas (HNP's) are rare autonomic neoplasms associated with high morbidity and mortality. We aimed to study epidemiology, clinicopathological correlation, and management of HNP to assist clinicians in advocating the most appropriate therapy.

Materials And Methods: Epidemiological parameters, including age and sex distribution, clinical presentation, tumor classification, familial predisposition, multicentricity, and treatment modalities adopted, were analyzed in this retrospective analysis of 54 patients of HNP.

Results: Age ranged from 15 to 85 years, with a female preponderance. Among all HNP, carotid body tumor (CBT) (48.1%) was the most common, followed by Glomus Jugulare (24.1%). Majority of the patients presented with neck swelling associated with nerve palsies. A preoperative neurological deficit was most commonly observed with Glomus jugulotympanicum (68.4%).

Conclusion: CBT is the largest and most common paraganglioma in our study. The familial occurrence warrants meticulous screening for multifocality. Tumor location, neurovascular involvement, malignant potential, and patient factors should guide the designing of management options.
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http://dx.doi.org/10.4103/sajc.sajc_339_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852631PMC
December 2019

Hurdles in radiation planning for glioblastoma: Can delayed-contrast enhanced computed tomography be a potential solution?

Asia Pac J Clin Oncol 2019 Oct 30;15(5):e103-e108. Epub 2019 Jan 30.

Department of Radiotherapy, PGIMER, Chandigarh, India.

Objective: Conformal radiation is the standard of care in treatment of glioblastoma. Although co-registration of magnetic resonance imaging (MRI) with early contrast enhanced computed tomography (CECT) is recommended for target delineation by consensus guidelines, ground realities in developing countries often result in availability of less-than-ideal MR sequences for treatment planning. Purpose of this study is to analyze the impact of incorporation of delayed-CECT sequences for radiation planning in glioblastomas, as an adjunct or alternative to MRI.

Methods: Case records of all patients of glioblastoma treated at our center between 2011 and 2014 were retrospectively evaluated. Gross treatment volumes were delineated on T1 contrast MRI (m-GTV), early CECT (e-GTV) and delayed CECT (d-GTV); volumetric comparisons were made using repeated measures analysis of variance and pair-wise analysis.

Results: Although 96% of registered patients underwent postoperative MRI, only 38% of them had desirable sequences suitable for co-registration. Median duration between acquisition of postoperative MRI and surgery was 45 days (range, 33-60), whereas that between MRI and treatment-planning CT was 5 days (range, 1-10). Statistically significant differences (P < 0.0001) were obtained between mean volumes of e-GTV (41.20cc), d-GTV (58.09cc) and m-GTV (60.52cc). Although the mean GTV increased by 46% between early CECT and MRI, the difference was only 4% between delayed CECT and MRI.

Conclusion: Delayed CECT is superior to early CECT for co-registration with MRI for target delineation, especially when available MR sequences are less-than-ideal for treatment planning, and can be considered as the most appropriate adjunct as well as an alternative to MRI, compared to early CECT.
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http://dx.doi.org/10.1111/ajco.13111DOI Listing
October 2019

Radiation induced secondary malignancies: a review article.

Radiat Oncol J 2018 Jun 29;36(2):85-94. Epub 2018 Jun 29.

Department of Radiotherapy and Oncology, PGIMER, Chandigarh, India.

Radiation-induced second malignancies (RISM) is one of the important late side effects of radiation therapy and has an impact on optimal treatment decision-making. Many factors contribute to the development of RISM such as age at radiation, dose and volume of irradiated area, type of irradiated organ and tissue, radiation technique and individual and family history of cancer. Exact mechanism of RISM is unknown. But nowadays, it is a growing concern in oncology because of the increased number of cancer survivors and efforts are being made to prevent or decrease the incidence of RISM. The primary search for articles was carried via Google Scholar and PubMed with keywords included 'radiation induced malignancies, second malignancies, and chemotherapy induced malignancies'. Additional papers were found through references from relevant articles. In this review article, we have discussed about the pathogenesis, factors contributing to RISM, screening and prevention strategies of RISM.
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http://dx.doi.org/10.3857/roj.2018.00290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6074073PMC
June 2018

F-Fluorocholine-Positron Emission Tomography/Computerised Tomography is Useful in Localising Tc-Sesta-methoxyisobutylisonitrile-Negative Parathyroid Cyst Causing Normocalcemic Primary Hyperparathyroidism.

Eur Endocrinol 2018 Apr 18;14(1):56-58. Epub 2018 Apr 18.

Department of Pathology, Venkateshwar Hospitals, New Delhi, India.

Parathyroid cysts are extremely rare and are rarely associated with primary hyperparathyroidism (PHPT), which are difficult to localise, as they are Tc-sesta-methoxyisobutylisonitrile (sestaMIBI) negative. We report for the first time the utility of F-fluorocholinepositron emission tomography/computerised tomography (PC-PET/CT) in localising parathyroid cyst causing normocalcemic PHPT. A 76-year-old lady with progressively worsening osteoporosis from 2014-2017 (in spite of annual zolendronic acid infusions, daily calcium and vitamin-D supplementation) with persistently normal serum calcium and vitamin D, but elevated parathyroid hormone, had normal sestaMIBI scans of the neck on multiple occasions. FC-PET/CT finally revealed soft tissue uptake, suggestive of right superior parathyroid adenoma/ hyperplasia. Surgical removal of the culprit lesion resulted in resolution of hyperparathyroidism, histopathologic evaluation of which revealed a cystic lesion lined by chief cell variant parathyroid cells without any nuclear atypia, capsular or vascular invasion. FC-PET/CT is useful in localising culprit parathyroid lesions, especially when they are sestaMIBI negative. PC-PET/CT is useful in localising parathyroid hyperplasia and ectopic parathyroids, which are frequently missed by sestaMIBI. There is an urgent need for comparative studies between sestaMIBI and FC-PET/CT in PHPT. We report for the first time the usefulness of FC-PET/CT in localising sestaMIBI-negative functional parathyroid cyst causing normocalcemic PHPT.
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http://dx.doi.org/10.17925/EE.2018.14.1.56DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954597PMC
April 2018

Occult phosphaturic mesenchymal tumour of femur cortex causing oncogenic osteomalacia - diagnostic challenges and clinical outcomes.

Endokrynol Pol 2018 14;69(2):205-210. Epub 2018 Feb 14.

Department of Endocrinology Diabetology and Metabolic Disorders, Venkateshwar Hospitals, Dwarka, New Delhi.

Background: Tumor induced osteomalacia (TIO) are extremely rare paraneoplastic syndrome with less than 300 reported cases. This report highlights the pitfalls and challenges in diagnosing and localizing TIO in patients with refractory and resistant osteomalacia.

Patient And Methods: 41- year gentleman with 4-year history of musculoskeletal weakness and pathologic fractures presented in wheelchair bound incapacitated state of 1-year duration. Investigations were significant for severe hypophosphatemia, severe phosphaturia, normal serum calcium, reduced 1,25-dihydroxy vitamin-D, elevated ALP, elevated intact parathyroid hormone (iPTH), and pseudo-fractures involving pelvis and bilateral femur. Whole body MRI and 99mTc methylene diphosphonate bone-scan were also normal. Whole body FDG-PET scan involving all 4 limbs revealed a small FDG avid lesion at lateral border of lower end of left femur (SUV max 3.9), which was well characterized on 3-dimensional CT reconstruction. Plasma C-terminal fibroblast growth factor (FGF)-23 was 698 RU/ mL (normal < 150 RU/ml). Wide surgical excision of the tumor was done. Histopathology confirmed mesenchymal tumor of mixed connective tissue variant. Serum phosphorous normalized post-surgery day-1. High dose oral calcium and vitamin-D was continued. FGF-23 normalized post surgery (73RU/ml). Physical strength improved significantly and now he is able to walk independently.

Conclusion: TIO is frequently confused with normocalcemic hyperparathyroidism and vitamin-D resistant rickets/osteomalacia, which increases patient morbidity. Imaging for tumor localization should involve whole body from head to tip of digits, cause these tumors are notoriously small and frequently involve digits of hands and legs. Complete surgical removal of the localized tumor is key to good clinical outcomes.
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http://dx.doi.org/10.5603/EP.a2018.0016DOI Listing
October 2018

Role of radiotherapy in residual pineal parenchymal tumors.

Clin Neurol Neurosurg 2018 03 31;166:91-98. Epub 2018 Jan 31.

Department of Neurosurgery, PGIMER, Chandigarh, India. Electronic address:

Objectives: Surgical excision of pineal parenchymal tumors(PPT), though desirable for good long term outcome, may not always be possible. Role of adjuvant radiotherapy (RT) in residual PPT's is not well delineated. The purpose of this single institutional retrospective study is to assess the role of radiotherapy in residual PPT's.

Patients And Methods: Between 2006-2016, fourteen patients with residual PPT's were treated with adjuvant radiotherapy (12 with 3D conformal RT). Eight had pineocytomas (PC), 4 pineal parenchymal tumors with intermediate differentiation (PPID) and 2 pineoblastomas (PB). Doses of 45-54 Gy was delivered in 1.8-2 Gy per fraction. Cranio-spinal irradiation(CSI) was given to one case of PB and PPID each, with drop lesions at presentation. Patients were followed up at regular intervals.

Results: The average Planning Target Volume (PTV) was 279.4cc. Clinico-radiological response was noted in all with complete disappearance of tumor in 4 patients with PC and 2 with PPID. Delayed recurrence (36-72 months later, median 42.5 months) was seen in 3 patients with PC and early recurrence in both with PB (median 28 months). Overall median follow-up for PC and PB was 54 and 31.5 months respectively. Two patients with PC and 2 with PB expired. The median follow-up for PPID was 21.5 months with no deaths or recurrences.

Conclusions: Some PC and PPID may behave aggressively and recur or spread along neural axes requiring close follow up. Radiotherapy appears to be effective in patients with residual PC, PPID. Re-irradiation or radiosurgery may help in recurrences.
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http://dx.doi.org/10.1016/j.clineuro.2018.01.027DOI Listing
March 2018

Impact of acute hematological toxicity on treatment interruptions during cranio-spinal irradiation in medulloblastoma: a tertiary care institute experience.

J Neurooncol 2017 Sep 2;134(2):309-315. Epub 2017 Jun 2.

Department of Radiotherapy & Oncology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

To analyze treatment interruptions due to acute hematological toxicity in patients of medulloblastoma receiving cranio-spinal irradiation (CSI). Prospectively collected data from case records of 52 patients of medulloblastoma treated between 2011 and 2014 was evaluated. Blood counts were monitored twice a week during CSI. Spinal irradiation was interrupted for patients with ≥grade 2 hematological toxicity and resumed after recovery to grade 1 level (TLC >3000; platelet count >75,000). Treatment interruptions and hematological toxicity were analyzed. Median age was 11 years. All patients received adjuvant CSI of 36 Gy, followed by boost of 18 Gy to posterior fossa, at 1.8 Gy per fraction. Concurrent chemotherapy was not given. Adjuvant chemotherapy was given after CSI for high risk patients. Spinal fields were interrupted in 73.1% of patients. Cause of first interruption was leucopenia in 92.1%, thrombocytopenia in 2.6%, and both in 5.3%. Median number of fractions at first interruption was 8, with 25% of interruptions in first week. Median duration for hematological recovery after nadir was 5 days for leucopenia and 3 days for thrombocytopenia. Half of the patients had at least 2 interruptions, and 19% subsequently developed grade 3 toxicity. On multivariate analysis, significant correlation with duration of delay was observed for pre-treatment haemoglobin, number of fractions at first interruption, grade and duration of recovery of leucopenia. Acute hematological toxicity with CSI is frequently under-reported. Patients with low pre-treatment hemoglobin, early onset leucopenia, profound leucopenia and prolonged recovery times are at a higher risk of having protracted courses of irradiation. Frequent monitoring of blood counts and timely interruption of spinal fields of irradiation at grade 2 level of hematological toxicity minimizes the risk of grade 3 and grade 4 toxicity, while reducing the interruptions in irradiation of the gross tumour bed.
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http://dx.doi.org/10.1007/s11060-017-2524-7DOI Listing
September 2017

Patterns of care and survival among small cell lung cancer patients: Experience from a tertiary center in India.

J Egypt Natl Canc Inst 2017 Mar 14;29(1):47-51. Epub 2016 Nov 14.

Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India.

Background/purpose: Lung cancer is the commonest malignancy and the most common cause of cancer related mortality in males worldwide. Non-small cell lung cancer (NSCLC) is the commonest histology while small cell lung cancer (SCLC) contributes to only 15% of all cases of lung cancer. This report intended to present the patterns of care, survival outcomes and prognostic factors of SCLC treated in a tertiary care institute.

Results: A total of 85 patients of SCLC were registered in radiotherapy unit I during the period January, 2005 to December, 2012. The median age of the cohort was 56.5years (95% CI 34-72). The majority of the patients were male with a male:female ratio of 6.7:1. Sixty eight percent of the patients were smokers. Sixty percent patients presented with extensive stage disease. Radiotherapy (RT) was used in 76% of the patients while chemotherapy was used in 75% of the patients. Platinum Etoposide was the most common regimen which was used in 70% of the patients who received chemotherapy. The median progression free survival (PFS) of the entire cohort was 11.4months (95% CI 9.11-13.58months). Stage, performance status, and use of chemotherapy were found to be significant factors affecting survival outcome in patients with SCLC.

Conclusion: The pattern of care and survival outcomes in the present study parallels that of the various published retrospective reviews. Basic research and development of targeted agents may be the way forward in improving the outcome of patients with SCLC.
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http://dx.doi.org/10.1016/j.jnci.2016.10.001DOI Listing
March 2017

Primary Non-Hodgkins Lymphoma of Uterine Cervix: A Case Report of Two Patients.

J Obstet Gynaecol India 2016 Apr 25;66(2):125-7. Epub 2014 Dec 25.

Department of Radiotherapy, IRCH, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.1007/s13224-014-0647-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818829PMC
April 2016

A Rare Case of Plantar Epithelioma Cuniculatum Arising from a Wart.

Indian J Dermatol 2015 Sep-Oct;60(5):485-7

Department of Pathology, INHS Asvini, Mumbai, Maharashtra, India.

A 68-year-old man, a known case of hypertension, coronary artery disease and old cardiovascular accident with right-sided hemiplegia, came with the chief complaints of a large cauliflower like growth with pus discharge on the left heel since 15 years. The patient had sustained a penetrating injury by a thorn on the left heel region few days before the lesion appeared. Dermatological examination revealed a single verrucous lesion measuring 7 × 7 cm on the left heel region associated with discharge of foul smelling cheesy material. There was also a enlarged right inguinal lymph node which was non-tender, firm, measuring 2 cm in diameter with normal overlying skin. X-ray left ankle was done which showed some soft tissue swelling. A skin biopsy showed hyperkeratosis, acanthosis and parakeratosis. Elongated rete ridges with keratinocyte hyperplasia, forming a large mass pressing on the underlying dermis were seen. There was formation of multiple large keratin filled invaginations and crypts. No atypical cells were seen. Based on history, clinical examination and investigations, a diagnosis of epithelium cuniculatum type of verrucous squamous cell carcinoma was made. A wide excision with a flap cover was performed in consultation with the oncosurgeon and the excision sample was sent for histopathological re-examination, which confirmed the diagnosis of epithelioma cuniculatum.
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http://dx.doi.org/10.4103/0019-5154.164369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601417PMC
November 2015

Primary spinal glioblastoma treated with adjuvant radiation and temozolomide: Report of two cases.

J Cancer Res Ther 2015 Jul-Sep;11(3):654

Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India.

Primary spinal glioblastoma multiforme (GBM) is a rare entity, which is invariably associated with poor outcome. Standard treatment is surgery followed by post-operative radiotherapy. Due to paucity of cases role of chemotherapy is investigational. We intend to report two cases of primary spinal GBM treated with radiation and adjuvant temozolomide.
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http://dx.doi.org/10.4103/0973-1482.137998DOI Listing
August 2016

Microvessel density and Ki-67 labeling index in esthesioneuroblastoma: is there a prognostic role?

Ann Diagn Pathol 2015 Dec 18;19(6):391-6. Epub 2015 Jul 18.

Department of Pathology, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

Esthesioneuroblastoma (ENB) is a malignant neuroectodermal tumor. Hyams grading has an established role in its prognostication. The importance of microvessel density (MVD) and Ki-67 labeling index (Ki-67 LI) is well studied in various tumors, but the same remains understated in ENB. The aims of the study were to estimate proliferation index and MVD in ENB and to correlate them with Hyams grade. Twenty-six ENB cases diagnosed over a period of 5 years were included. Hyams grade, MVD, and Ki-67 LI were evaluated for each of them. The cases were categorized as low (Hyams grades 1 and 2) and high (Hyams grades 3 and 4) grades. Microvessel density and Ki-67 LI were correlated with grade. The treatment response was analyzed in different grades. The commonest histologic grade was 4 (42%). The mean Ki-67 LI was 2%, 8.2%, 30.8%, and 40.5% and mean MVD was 81.67/mm(2), 37/mm(2), 24/mm(2), and 25.2/mm(2) in grades 1, 2, 3, and 4, respectively. A statistically significant correlation of grade with Ki-67 LI (P < .001) and MVD (P < .007) was noted. Hyams grade in ENB correlates well with treatment response. Ki-67 LI is an important prognostic factor in ENB. We propose a cutoff of 25% for Ki-67 LI to differentiate low- vs high-grade ENB, but larger studies are needed for validation. Contrary to epithelial tumors, there is a decrease in MVD with increasing grade in ENB.
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http://dx.doi.org/10.1016/j.anndiagpath.2015.06.008DOI Listing
December 2015

Radiation Induced Cystitis and Proctitis - Prediction, Assessment and Management.

Asian Pac J Cancer Prev 2015 ;16(14):5589-94

All India Institute of Medical Sciences, New Delhi, India, E-mail :

Cystitis and proctitis are defined as inflammation of bladder and rectum respectively. Haemorrhagic cystitis is the most severe clinical manifestation of radiation and chemical cystitis. Radiation proctitis and cystitis are major complications following radiotherapy. Prevention of radiation-induced haemorrhagic cystitis has been investigated using various oral agents with minimal benefit. Bladder irrigation remains the most frequently adopted modality followed by intra-vesical instillation of alum or formalin. In intractable cases, surgical intervention is required in the form of diversion ureterostomy or cystectomy. Proctitis is more common in even low dose ranges but is self-limiting and improves on treatment interruption. However, treatment of radiation proctitis is broadly non-invasive or invasive. Non-invasive treatment consists of non-steroid anti-inflammatory drugs (NSAIDs), anti-oxidants, sucralfate, short chain fatty acids and hyperbaric oxygen. Invasive treatment consists of ablative procedures like formalin application, endoscopic YAG laser coagulation or argon plasma coagulation and surgery as a last resort.
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http://dx.doi.org/10.7314/apjcp.2015.16.14.5589DOI Listing
June 2016

Short course palliative radiotherapy in the management of choroidal metastasis: An effective technique since ages.

J Egypt Natl Canc Inst 2016 Mar 31;28(1):49-53. Epub 2015 Jul 31.

Department of Radiation Oncology, Dr. B.R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi 110029, India.

Purpose: Uveal tract is the most common site of intra-ocular metastasis. Overall, the reported prevalence of clinically evident uveal metastases in patients with cancer ranges from 2% to 9%, with the majority of the cases being due to breast cancer. We aimed at evaluating the role of palliative radiotherapy in the management of choroidal metastasis from carcinoma breast.

Materials And Methods: We describe the clinico-pathologic features, treatment and outcome of ten patients of carcinoma breast who presented to the ophthalmology department at our institution with ocular symptoms attributable to choroidal metastasis.

Results: Nine of the patients were female while one was male. All of them presented with painless progressive diminution of vision. Median duration of symptoms was 2.25 months. Five patients had associated lung metastasis while bone and brain metastases were seen in three and two patients respectively. All of them received palliative radiotherapy (RT) to the involved eye (or eye+brain) by 3D-CRT (n=7), or 2 Dimensional technique (n=2) or electron therapy (n=1). Doses prescribed were 30 Gy/10#/2 weeks (n=8); 20 Gy/5 #/1 week (n=2). Simultaneously they received hormonal therapy (n=6) or systemic chemotherapy (n=3). After a median follow up of 18 months seven patients had complete resolution and two patients had partial resolution of the metastases.

Conclusion: Short course palliative radiation therapy is an effective modality for the management of choroidal metastasis in patients of carcinoma breast. In the current report it led to formidable local control with acceptable radiation induced toxicity.
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http://dx.doi.org/10.1016/j.jnci.2015.07.003DOI Listing
March 2016

Impact of Treatment Time on Chemoradiotherapy in Locally Advanced Cervical Carcinoma.

Asian Pac J Cancer Prev 2015 ;16(12):5075-9

Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India E-mail :

Background: Adverse effects of treatment prolongation beyond 8 weeks with radiotherapy for cervical cancer have been established. Clinical data also show that cisplatin increases the biologically effective dose of radiotherapy. However, there are no data on the effect of overall treatment time in patients with locally advanced cervical cancer treated with concomitant chemo-radiotherapy (CCRT) in an Indian population. The present study concerned the feasibility of concurrent chemotherapy and interspacing brachytherapy during the course of external radiotherapy to reduce the overall treatment time and compare the normal tissue toxicity and loco- regional control with a conventional schedule.

Materials And Methods: Between January 2009 and March 2012 fifty patients registered in the Gynaecologic Oncology Clinic of Institute Rotary Cancer Hospital with locally advanced cervical cancer (FIGO stage IIB-IIIB) were enrolled. The patients were randomly allocated to treatment arms based on a computer generated random number. Arm I (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions, and weekly cisplatin 40 mg/m2. High dose rate intra-cavitary brachytherapy (HDR-ICBT) was performed after one week of completion of external beam radiotherapy (EBRT). The prescribed dose for each session was 7 Gy to point A for three insertions at one week intervals. Arm II (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions. Mention HDR-ICBT ICRT was performed after 40Gy and 7 Gy was delivered to point A for three insertions (days 23, 30, 37) at one week intervals. Cisplatin 20 mg/m2/day was administered from D1-5 and D24-28. Overall treatment time was taken from first day of EBRT to last day of HDR brachytherapy. The overall loco-regional response rate (ORR) was determined at 3 and 6 months.

Results: A total of 46 patients completed the planned treatment. The overall treatment times in arm I and arm II were 65±12 and 48±4 days, respectively (p=0.001). At three and six months of follow-up the ORR for arm I was 96% while that for arm II was 88%. No statistically significant difference was apparent between the two arms. The overall rate of grade≥3 toxicity was numerically higher in arm I (n=7) than in arm II (n=4) though statistical significance was not reached. None of the predefined prognostic factors like age, performance status, baseline haemoglobin level, tumour size, lymph node involvement, stage or histopathological subtype showed any impact on outcome.

Conclusions: In the setting of concurrent chemo- radiotherapy a shorter treatment schedule of 48 days may be feasible by interspacing brachytherapy during external irradiation. The response rates and toxicities were comparable.
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http://dx.doi.org/10.7314/apjcp.2015.16.12.5075DOI Listing
April 2016