Publications by authors named "Divya Khosla"

49 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

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

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

Synchronous splenic metastases from squamous cell carcinoma of oesophagus: a case report and review of literature.

Clin J Gastroenterol 2021 Apr 5;14(2):410-414. Epub 2021 Jan 5.

Department of Radiotherapy and Oncology, Regional Cancer Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.

Synchronous splenic metastases from oesophageal squamous cell carcinomas are extremely rare. Most of the cases of splenic metastases reported in the literature are mainly metachronous and occur usually from adenocarcinoma primary. The treatment options range from splenectomy to palliative chemotherapy with standard doses in fit individuals. However, in cases with poor performance status, the management is often the best supportive care only due to the fear of tolerance and toxicities with standard dose chemotherapy. Herein, we report a case of squamous cell carcinoma of the distal thoracic oesophagus in a poorly fit elderly male diagnosed with synchronous splenic metastases and successfully treated with palliative chemotherapy with reduced flat doses and radiotherapy with no significant toxicities.
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http://dx.doi.org/10.1007/s12328-020-01321-2DOI Listing
April 2021

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

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

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

Real world clinical outcomes of adjuvant sequential chemoradiation in patients with gallbladder carcinomas with poor performance status.

Radiat Oncol J 2019 Dec 28;38(4):262-269. Epub 2020 Dec 28.

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

Purpose: The purpose of the study is to analyze the overall survival, relapse-free survival, and relapse patterns of adjuvant sequential chemoradiation for gallbladder cancers after curative resection in patients with poor performance status.

Materials And Methods: We retrospectively reviewed clinical records of gallbladder patients with pathologic stage T2-4 or node positivity treated with sequential chemoradiation at our institute between January 2015 and January 2019. Sequential chemoradiotherapy protocol consisted of six cycles of gemcitabine 1,000 mg/m2 and oxaliplatin 100 mg/m2 administered every 2 weekly and postoperative radiation therapy (45 Gy in 25 fractions over 5 weeks) by three-dimensional conformal technique.

Results: A total of 36 patients were included. The median overall survival and relapse-free survival was 26 months (95% confidence interval [CI], 21.4-30.5) and 21 months (95% CI, 11.8-30.1), respectively. The 2-year overall and relapse-free survival rates were 55.1% (95% CI, 37.9%-72.3%) and 44.7% (95% CI, 27.5%-61.9%), respectively. Locoregional, systemic, and combined recurrence were noted in 2 (5.5%), 14 (38.8%), and 3 (8.3%) patients, respectively. On univariate analysis, tumour grading significantly influenced relapse free survival; nodal stage and overall stage demonstrated a statistically significant influence on overall survival (p < 0.05) with a trend towards significance for lymphovascular invasion. On multivariate analysis, no significant factors were found. Grade 3 and 4 haematological adverse events were observed only in 2 (5.5%) with chemotherapy. No grade 3 and 4 adverse events were observed due to radiation therapy.

Conclusion: Sequential chemoradiation is feasible and tolerable with acceptable efficacy in the adjuvant setting in patients unfit for concurrent chemoradiotherapy.
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http://dx.doi.org/10.3857/roj.2020.00626DOI Listing
December 2019

In Regard to Boulle et al.

Int J Radiat Oncol Biol Phys 2019 12;105(5):1160

Department of Radiation Therapy, All India Institute of Medical Sciences (AIIMS), New Delhi, India.

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http://dx.doi.org/10.1016/j.ijrobp.2019.08.063DOI Listing
December 2019

Ovarian Small Cell Carcinoma of Hypercalcemic Type in an Adolescent Girl.

J Obstet Gynaecol India 2019 Apr 2;69(Suppl 1):60-62. Epub 2018 Feb 2.

1Department of Radiotherapy and Oncology, Government Medical College and Hospital, Chandigarh, India.

Objective: Small cell carcinoma of ovary, hypercalcemic type is a rare malignancy with a dismal prognosis. The diagnosis is often confused with many other tumors.

Case Report: We describe a rare case of ovarian small cell carcinoma of hypercalcemic type in an adolescent. She presented with abdominal pain, awareness of mass and vomiting. She underwent exploratory laparotomy and right ovarian excision. The detailed histopathological examination including immunohistochemistry was suggestive of ovarian small cell carcinoma of hypercalcemic type. She had progressive disease on chemotherapy and ultimately died within 2 years of diagnosis. Due to rarity of this neoplasm and its aggressive nature, the optimal treatment regimen has not been established.

Conclusion: We report this case because of its rare occurrence leading to clinical and diagnostic challenges and need to explore effective treatment options to improve survival in these patients.
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http://dx.doi.org/10.1007/s13224-018-1091-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431709PMC
April 2019

Extraosseous Ewing's Sarcoma of the Parapharyngeal Space - A Rare Entity - with Review of Literature.

Iran J Otorhinolaryngol 2019 Jan;31(102):51-54

Department of Radiotherapy, Government Medical College and Hospital, Chandigarh, India.

Introduction: Extraosseous Ewing's sarcoma (EES) of the head and neck region is a rare occurrence, and Ewing's sarcoma of the parapharyngeal space is even rarer. To the best of our knowledge, only three cases of EES of the parapharyngeal space have been reported in the literature.

Case Report: We report a rare case of EES of the parapharyngeal space in an 8-year-old girl. She presented with complaints of earache, difficulty in breathing and swallowing and bleeding from the mouth. Investigations revealed a large parapharyngeal mass causing narrowing of the nasopharyngeal and oropharyngeal airway with skeletal and lung metastasis. Biopsy from the parapharyngeal mass was suggestive of malignant small round cell tumor. The patient was treated with chemotherapy and radiotherapy, but developed brain metastasis and succumbed to disease approximately 1 year after diagnosis. Herein, we describe the characteristic clinicopathological features and treatment with a comprehensive review of the literature.

Conclusion: EES in this unusual location behaves aggressively, with a high rate of recurrence and distant metastasis. Aggressive multimodal treatment comprising of multi-agent chemotherapy, surgical resection if feasible, and radiotherapy should be considered.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368983PMC
January 2019

Polymorphous Low Grade Adenocarcinoma of the Parotid in a Teenager.

Iran J Otorhinolaryngol 2017 Sep;29(94):299-302

Department of Radiotherapy, Government Medical College and Hospital, Chandigarh, India.

Introduction: Polymorphous low grade adenocarcinoma (PLGA) is a rare salivary gland neoplasm with an indolent course. It occurs primarily in the minor salivary glands but can rarely occur in the major salivary glands. It usually occurs in the fifth to seventh decades of life with female preponderance.

Case Report: A 16-year-old male presented with recurrent painless swelling in the right preauricular region and with a history of surgical intervention at the same site in the past. His histopathology report was suggestive of pleomorphic adenoma. The swelling recurred after one year of excision and a superficial parotidectomy was performed. The detailed histopathological examination was suggestive of Polymorphous low grade adenocarcinoma. In view of close margins, the patient was given adjuvant radiotherapy. Thirty-three months post-surgery, he is alive and disease-free. We describe a rare case of PLGA of the parotid gland in a teenager with its clinical characteristics, histopathological features, and treatment.

Conclusion: The occurrence of PLGA in the parotid gland is rare with only a few cases reported in literature. The diagnosis of PLGA is challenging due to morphological diversity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610380PMC
September 2017

Correlation of higher levels of soluble TNF-R1 with a shorter survival, independent of age, in recurrent glioblastoma.

J Neurooncol 2017 02 17;131(3):449-458. Epub 2016 Nov 17.

The Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Taussig Cancer Center, The Cleveland Clinic, Cleveland, OH, USA.

The circulating levels of soluble tumor necrosis factor receptor-1 (sTNF-R1) and sTNF-R2 are altered in numerous diseases, including several types of cancer. Correlations with the risk of progression in some cancers, as well as systemic manifestations of the disease and therapeutic side-effects, have been described. However, there is very little information on the levels of these soluble receptors in glioblastoma (GBM). Here, we report on an exploratory retrospective study of the levels of sTNF-Rs in the vascular circulation of patients with GBM. Banked samples were obtained from 112 GBM patients (66 untreated, newly-diagnosed patients and 46 with recurrent disease) from two institutions. The levels of sTNF-R1 in the plasma were significantly lower in patients with newly-diagnosed or recurrent GBM than apparently healthy individuals and correlated with the intensity of expression of TNF-R1 on the tumor-associated endothelial cells (ECs) in the corresponding biopsies. Elevated levels of sTNF-R1 in patients with recurrent, but not newly-diagnosed GBM, were significantly associated with a shorter survival, independent of age (p = 0.02) or steroid medication. In contrast, the levels of circulating sTNF-R2 were significantly higher in recurrent GBM than healthy individuals and there was no significant correlation with expression of TNF-R2 on the tumor-associated ECs or survival time. The results indicate that larger, prospective studies are warranted to determine the predictive value of the levels of sTNF-R1 in patients with recurrent GBM and the factors that regulate the levels of sTNF-Rs in the circulation in GBM patients.
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http://dx.doi.org/10.1007/s11060-016-2319-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352462PMC
February 2017

Multiple eccrine axillary hidrocystomas.

JAAD Case Rep 2016 May 5;2(3):257-8. Epub 2016 Jul 5.

Department of Dermatology, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.

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http://dx.doi.org/10.1016/j.jdcr.2016.05.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939421PMC
May 2016

Concurrent therapy to enhance radiotherapeutic outcomes in glioblastoma.

Authors:
Divya Khosla

Ann Transl Med 2016 Feb;4(3):54

Department of Radiotherapy and Oncology, Government Medical College & Hospital, Chandigarh 160030, India.

Glioblastoma is one of the most fatal and incurable human cancers characterized by nuclear atypia, mitotic activity, intense microvascular proliferation and necrosis. The current standard of care includes maximal safe surgical resection followed by radiation therapy (RT) with concurrent and adjuvant temozolomide (TMZ). The prognosis remains poor with median survival of 14.6 months with RT plus TMZ. Majority will have a recurrence within 2 years from diagnosis despite adequate treatment. Radiosensitizers, radiotherapy dose escalation and altered fractionation have failed to improve outcome. The molecular biology of glioblastoma is complex and poses treatment challenges. High rate of mutation, genotypic and phenotypic heterogeneity, rapid development of resistance, existence of blood-brain barrier (BBB), multiple intracellular and intercellular signalling pathways, over-expression of growth factor receptors, angiogenesis and antigenic diversity renders the tumor cells differentially susceptible to various treatment modalities. Thus, the treatment strategies require personalised or individualized approach based on the characteristics of tumor. Several targeted agents have been evaluated in clinical trials but the results have been modest despite these advancements. This review summarizes the current standard of care, results of concurrent chemoradiation trials, evolving innovative treatments that use targeted therapy with standard chemoradiation or RT alone, outcome of various recent trials and future outlook.
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http://dx.doi.org/10.3978/j.issn.2305-5839.2016.01.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740000PMC
February 2016

Adult rhabdomyosarcoma: Clinical presentation, treatment, and outcome.

J Cancer Res Ther 2015 Oct-Dec;11(4):830-4

Department of Radiotherapy and Oncology, Regional Cancer Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Objective: Rhabdomyosarcoma (RMS) in adults is a rare malignancy. The objective of our study was to determine presentation, treatment, patterns of failure, and outcome in this disease.

Materials And Methods: A retrospective analysis of 25 patients of adult (>16 years) RMS who were treated at our institute from 2000 to 2009 was carried out. Tumors were classified according to the Intergroup Rhabdomyosarcoma Study (IRS) staging. All patients were treated with multimodality treatment except for three patients who received chemotherapy as the only modality.

Results: The median age was 19 years (range, 16-68 years). The most common site was head and neck (52%) followed by extremities (24%), genitourinary (20%), and retroperitoneal RMS (4%). Three out of 25 patients presented with distant metastasis. With a median follow-up of 45 months, the 5-year overall survival (OS) rate was 45%. The 5-year local control (LC) rate was 53%. IRS grouping and complete response after primary therapy were predictors of a better survival.

Conclusions: RMS in adults have poor prognosis as compared to childhood RMS. Adult RMS should therefore be treated aggressively with multidisciplinary approach comprising of surgery, radiation, and chemotherapy to achieve cure and prolonged survival.
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http://dx.doi.org/10.4103/0973-1482.144637DOI Listing
December 2016

Survival and failure patterns in atypical and anaplastic meningiomas: A single-center experience of surgery and postoperative radiotherapy.

J Cancer Res Ther 2015 Oct-Dec;11(4):735-9

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

Introduction: Intracranial meningiomas are the second most common tumor of the CNS. The high-grade tumors are atypical and malignant meningioma comprising 5-7% and 1-3% of all meningiomas. The high-grade meningioma have an aggressive histopathological and clinical behavior.

Materials And Methods: We retrospectively reviewed 37 patients of high-grade meningioma treated in our institute from 2002 to 2011. Clinical characteristics and treatment modality in form of surgery and radiotherapy (RT) were noted. Statistical analysis was done with regards to progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis.

Results: The median age of the patients was 45.0 years. The median duration of symptoms was 6 months. Headache was the most common presenting symptom. Fourteen patients underwent complete excision, while 23 had subtotal excision. Twenty-two patients had World Health Organization (WHO) grade II histology tumors and 15 patients had grade III histology. Median RT dose delivered was 50 Gy for grade II tumors and 54 Gy for grade III tumors. Five-year PFS for grade II and III tumors was 58 and 20%, respectively. Five-year OS for grade II and III tumors was 83 and 23%, respectively.

Conclusions: High-grade meningiomas represent a rare and aggressive neoplasm. The mainstay of therapy is gross total resection (GTR) at the initial surgery. Postoperative adjuvant RT should be offered to all patients, regardless of the degree of resection achieved. Long-term follow-up is important as local recurrences and progression can develop years after the initial treatment.
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http://dx.doi.org/10.4103/0973-1482.151426DOI Listing
November 2016

Apropos of a case of cutaneous metastasis from laryngeal cancer with review of literature.

J Cancer Res Ther 2015 Jul-Sep;11(3):655

Department of Radiotherapy and Oncology, Government Medical College and Hospital, Chandigarh, India.

Cutaneous metastasis from laryngeal carcinoma is a rare occurrence. A 55-year-old male patient with supraglottic cancer was treated with concurrent chemoradiation. Eighteen months later, he presented with ulceroproliferative growth on dorsum of the right hand. Biopsy revealed metastatic squamous cell carcinoma. Further investigations revealed underlying bone destruction with lung metastasis. In view of poor general condition and widespread dissemination of disease, palliative radiotherapy was delivered to the hand of the patient. He achieved satisfactory palliation in form of pain relief, control of bleeding, and discharge. The present report serves to emphasize the importance of properly diagnosing metastatic spread to unusual sites. Such metastasis is rare and is associated with a poor prognosis. Treatment is usually aimed at providing pain relief in these patients with limited life expectancy. Hence, we present a case of extensive cutaneous metastasis from laryngeal carcinoma with review of the literature.
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http://dx.doi.org/10.4103/0973-1482.143348DOI Listing
August 2016

Long term outcome analysis of role of radiotherapy in Grade I meningiomas: A single centre experience from North India.

Int J Appl Basic Med Res 2015 May-Aug;5(2):128-32

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

Background: Intracranial meningiomas are the second most common tumor of the central nervous system. Grade I tumors are the most common variety of meningioma and have a benign course. Surgery is the mainstay of treatment. Radiotherapy (RT) decreases the local recurrence rates and progression in patients with subtotal excision (STE). The authors present our institute's experience in combined modality management of 18 successive patients of Grade I meningioma.

Materials And Methods: We retrospectively reviewed 18 patients of Grade I meningioma treated in our institute from 2003 to 2011. Clinical characteristics and treatment modality in form of surgery and RT were noted. Statistical analysis was done with regards to recurrence free survival and overall survival using Kaplan-Meier survival analysis.

Results: The median age of the patients was 52.5 years. Seven patients were males and 11 patients were females. The median duration of symptoms was 8 months. Headache was the most common presenting symptom followed by vomiting, seizures, motor weakness and visual deficits. Five patients underwent complete excision while 13 had STE. 11 patients received early RT while 5 patients received RT at recurrence. Median RT dose delivered was 50 Gy. RT had significant effect on local control especially in subtotal resections, with overall 93.75% local control rates.

Conclusions: Grade I meningiomas represent a benign neoplasm. The mainstay of therapy is gross total resection at the initial surgery. Postoperative adjuvant RT should be offered to patients with subtotal resection. Long-term follow-up is important as local recurrences and progression can develop years after the initial treatment.
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http://dx.doi.org/10.4103/2229-516X.157169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456888PMC
June 2015

Urachal carcinoma: clinicopathological features, treatment and outcome.

J Cancer Res Ther 2014 Jul-Sep;10(3):571-4

Department of Radiotherapy and Oncology, Regional Cancer Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Introduction: Urachal carcinoma is a rare malignancy of urogenital tract. The objective of this study was to assess the clinical presentation, histopathological findings, treatment and outcome of patients of urachal carcinoma at a tertiary care centre.

Materials And Methods: A retrospective analysis of six cases of urachal carcinoma diagnosed over a period of 7 years from 2005 to 2011 was carried out. All pathologic specimens were reviewed by a single pathologist. Clinical and histological features along with treatment were reviewed and patient follow-up and survival outcome was obtained.

Results: The mean age at diagnosis was 36 years. Of the six patients, five were male. The tumor was located in dome in five and dome and anterior wall in one patient. All patients underwent partial cystectomy with bilateral pelvic lymph node dissection. The Sheldon pathologic stage was stage II in 1, IIIA in 2, IVA in 3 cases. Five out of six patients received adjuvant radiotherapy. The mean follow-up period was 37 months. Three out of six were disease free at last follow-up.

Conclusions: Urachal carcinomas are rare and usually locally advanced at presentation with a high risk of distant metastases. Surgery is the primary treatment of choice. Adjuvant therapy may decrease the chances of recurrence but it needs to be elucidated by prospective trials.
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http://dx.doi.org/10.4103/0973-1482.137955DOI Listing
June 2015

Leiomyosarcoma of the vagina: A rare entity with comprehensive review of the literature.

Int J Appl Basic Med Res 2014 Jul;4(2):128-30

Department of Radiotherapy and Oncology, Regional Cancer Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Primary malignant lesions of the vagina are uncommon, and vaginal sarcomas are even rarer. We describe a rare case of stage I, high-grade leiomyosarcoma of the vagina treated with combined modality treatment. A 39-year-old female presented with vaginal mass and underwent resection. Histopathological examination revealed atypical leiomyoma of the vagina with definite risk of recurrence. Eleven months later, she presented with a recurrent vaginal mass and underwent exploratory laparotomy with total abdominal hysterectomy and bilateral salpingo-oophorectomy plus resection of recurrent tumor and partial vaginectomy. The detailed histopathological examination was suggestive of leiomyosarcoma of the vagina. The patient received adjuvant radiotherapy and chemotherapy. The patient is alive and disease-free 29 months postsurgery. Experience with vaginal leiomyosarcomas is limited. The optimal treatment methods have not yet been established because of the rarity of the tumor. We add another case of leiomyosarcoma of the vagina to the limited existing literature.
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http://dx.doi.org/10.4103/2229-516X.136806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137639PMC
July 2014

Sacro-coccygeal teratoma in adult: Two rare case reports and review of literature.

Int J Appl Basic Med Res 2014 Jul;4(2):122-4

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

The sacrococcygeal area is the most common site of extragonadal teratomas in infants, but is a challenge to make clinical as well as radiological diagnosis in adults. We herein describe two cases of sacrococcygeal teratoma (SCT) in adult. The clinical, radiological and histopathological characteristics of both the cases with their outcome are described with review of the literature. The standard care for SCTs is complete surgical resection of the tumor. The presence of malignant transformation is associated with a less favorable outcome.
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http://dx.doi.org/10.4103/2229-516X.136803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137637PMC
July 2014

Palliative approach in advanced pelvic osteosarcoma: a single centre experience of a rare disease.

Indian J Palliat Care 2014 May;20(2):112-5

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

Background: Pelvic osteosarcoma is a rare and aggressive malignant neoplasm with poor outcomes. It represents only 5% of all osteosarcomas. The authors present our institute's experience in management and outcomes of five successive patients of pelvic osteosarcoma.

Materials And Methods: We retrospectively reviewed five patients of pelvis osteosarcoma treated in our institute from September 2008 to December 2010. Clinical characteristics and treatment (CCT) modality in form of surgery and chemotherapy were noted. Statistical analysis was done with regards to progression-free survival (PFS) using Kaplan-Meier survival analysis.

Results: The median age of the patients was 16.0 years. The median duration of symptoms was 9 months. One patient had lung metastases at presentation. All patients received systemic chemotherapy. One patient underwent surgery in the form of limb sparing approach. Three patients had partial response to treatment, one had complete response, and one had progressive disease. Median duration of PFS was 7 months only.

Conclusions: Pelvic osteosarcomas are rare neoplasms with aggressive growth patterns. Survival results are poor in view of advanced stage of presentation and difficult surgical approaches. The combined modality approach is needed to improve the results.
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http://dx.doi.org/10.4103/0973-1075.132624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4129997PMC
May 2014

Dosimetric comparison of vaginal vault ovoid brachytherapy versus intensity-modulated radiation therapy plans in postoperative patients of cervical carcinoma following whole pelvic radiotherapy.

J Cancer Res Ther 2014 Jan-Mar;10(1):153-8

Department of Radiotherapy and Oncology, Regional Cancer Centre, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, India.

Introduction: Dosimetric study to compare high dose rate (HDR) vaginal vault ovoid brachytherapy plan versus intensity-modulated radiation therapy (IMRT) boost plan for doses delivered to target volume and organs at risk (OAR) in postoperative patients of cervical carcinoma following whole pelvic radiotherapy (WPRT).

Materials And Methods: Fifteen postoperative patients of cervical carcinoma suitable for vaginal ovoid brachytherapy following WPRT of 46 Gy/23 fractions/4.5 weeks were included. All were treated with brachytherapy (two sessions of 8.5 Gy each). The equivalent dose for IMRT was calculated by computing biologically effective dose of brachytherapy by linear quadratic model. Dose of brachytherapy (two sessions of 8.5 Gy) was equivalent to IMRT dose of 26 Gy/13 fractions. Doses to target volume and OAR were compared between HDR and IMRT plans.

Results: Target volume was well covered with both HDR and IMRT plans, but dose with brachytherapy was much higher (P < 0.05). Mean doses, doses to 0.1, 1, 2, and 5cc, 1/3 (rd) , 1/2, and 2/3 (rd) volume of bladder and rectum were significantly lower with HDR plans.

Conclusion: In postoperative patients of cervical carcinoma, HDR brachytherapy following WPRT appears to be better than IMRT for tumor coverage and reducing dose to critical organs.
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http://dx.doi.org/10.4103/0973-1482.131449DOI Listing
December 2014

Ovarian granulosa cell tumor: clinical features, treatment, outcome, and prognostic factors.

N Am J Med Sci 2014 Mar;6(3):133-8

Department of Radiotherapy and Oncology, Government Medical College and Hospital, Chandigarh, India.

Background: Granulosa cell tumors are rare neoplasms characterized by long natural history and favorable prognosis.

Aims: The objective of this study was to determine the clinical presentation, treatment, outcome, and prognostic factors for patients of granulosa cell tumors.

Materials And Methods: A retrospective analysis of 26 patients of granulosa cell tumor of ovary from 2002 to 2011 was carried out. The records of all patients were analyzed to determine clinical presentation, treatment, survival, and prognostic factors.

Results: The median age of the patients was 50 years (range, 17-71 years). Abdominal pain was the most common presenting symptom. The median follow-up was 71.4 months (range, 21.6-149.9 months). The estimated 5 and 10 year overall survival (OS) was 84.6 and 72.5%, respectively. Event-free survival (EFS) was 76.5 and 52.9% at 5 and 10 years, respectively. Advanced stage was significant independent poor prognostic indicator for both OS and EFS.

Conclusion: Majority of the patients with granulosa cell tumors of the ovary present in early stage. Surgery is the primary treatment modality for granulosa cell tumors. Advanced stage and presence of residual disease were associated with inferior survival, but only prospective studies can ascertain their definite role.
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http://dx.doi.org/10.4103/1947-2714.128475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978936PMC
March 2014

Primitive neuroectodermal tumor of the uterine cervix diagnosed during pregnancy: a rare case with review of literature.

J Obstet Gynaecol Res 2014 Mar;40(3):878-82

Primitive neuroectodermal tumors of the cervix are very rare. A 28-year-old pregnant woman presented with a cervical mass. The tumor was staged as IB2. The biopsy from tumor was suggestive of malignant small round cell tumor. She then underwent termination of pregnancy followed by radical hysterectomy. Based on morphologic and immunohistochemical profile, a diagnosis of peripheral primitive neuroectodermal tumor of the cervix was made. The patient received adjuvant chemotherapy and radiotherapy. The patient is alive and disease-free 33 months post-surgery. The present case highlights the importance of keeping primitive neuroectodermal tumors in the differential diagnosis of small cell neoplasms of the uterine cervix. Pregnancy should not be a barrier to early detection and treatment of this potentially aggressive tumor. The optimal treatment methods have not yet been established because of the rarity of the tumor.
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http://dx.doi.org/10.1111/jog.12238DOI Listing
March 2014

Penile metastasis from carcinoma of caecum- unusual cause of priapism: a case report and review of literature.

Indian J Surg Oncol 2012 Dec 9;3(4):299-301. Epub 2012 Aug 9.

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

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http://dx.doi.org/10.1007/s13193-012-0180-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521541PMC
December 2012

Dosimetric and clinical outcome in image-based high-dose-rate interstitial brachytherapy for anal cancer.

Brachytherapy 2014 Jul-Aug;13(4):388-93. Epub 2013 Nov 6.

Department of Radiotherapy and Oncology, Regional Cancer Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Purpose: To evaluate dosimetric and clinical outcome in patients of anal cancer treated with image-based interstitial high-dose-rate brachytherapy following chemoradiation.

Methods And Materials: Sixteen patients with anal cancer were treated with chemoradiation followed by brachytherapy boost with image-based high-dose-rate interstitial brachytherapy from January 2007 to June 2011. Two brachytherapy dose schedules were used: 21 Gy in seven fractions and 18 Gy in six fractions depending on response to chemoradiation. CT scan was done after placement of needles for confirmation of placement and treatment planning. Target volume was contoured on CT scans. Volumetric quality indices and dose parameters were calculated.

Results: The mean clinical target volume was 17.7 ± 4.98 cm(3), and the median overall tumor size was 4.2cm (3.4-5cm). The mean values of coverage index, dose homogeneity index, overdose volume index, dose non-uniformity ratio, and conformal index were 0.94, 0.83, 0.21, 0.37, and 0.88, respectively. With a median followup of 41 months (range, 20-67.2 months), preservation of the anal sphincter was achieved in 14 patients. The 1- and 2-year local control rates were 93.8% and 87.5%, respectively. Treatment was well tolerated and none of the patients developed Grade 3 or higher late toxicity.

Conclusions: The combination of external beam radiotherapy with interstitial brachytherapy increases the dose to the tumor volume and limits the volume of irradiated normal tissue, thereby decreasing late toxicity. The use of image-based treatment planning provides better dose conformality with reduced toxicity and helps to prevent a geographic miss.
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http://dx.doi.org/10.1016/j.brachy.2013.09.006DOI Listing
September 2014