Selvamani Backianathan

Nanotechnology in oncology: Characterization and in vitro release kinetics of cisplatin-loaded albumin nanoparticles: Implications in anticancer drug delivery.

Context: Nanotechnology is an empowering technology that holds promise in cancer therapeutics by increasing the ratio of tumor control probability to normal tissue complication probability. It can increase the bioavailability of the drug at the target site, reduce the frequency of administration and reach otherwise lesser-accessible sites. The present study shows the feasibility of the cisplatin-loaded albumin nanoparticle as a sustained delivery system. Aims: Cisplatin is one of the most widely used chemotherapeutic agents for the treatment of malignant disorders. Conventional cisplatin formulation given as intravenous infusion has low bioavailability to the target organ in addition to significant side-effects, like ototoxicity and nephrotoxicity. The aim of this study was to develop a protein-based nanoparticulate system for sustained release of cisplatin. Materials and Methods: Nanoparticles were prepared by the coacervaton method of microcapsulation and chemical cross-linking with glutaraldehyde. Particle size was characterized by dynamic light scattering and transmission electron microscopy. Results and Conclusions: Using the coacervation method, nanoparticles of less than 70 nm diameter were produced. Drug encapsulation measured by ultraviolet spectroscopy varied from 30% to 80% for different ratios of cisplatin and protein. In vitro release kinetics shows that the nanoparticle-based formulation has biphasic release kinetics and is capable of sustained release compared with the free drug (80% release in 45 h). The study proves the feasibility of the albumin-based cisplatin nanoparticle formulation as a sustained release vehicle of cisplatin.

Accuracy of relocation, evaluation of geometric uncertainties and clinical target volume (CTV) to planning target volume (PTV) margin in fractionated stereotactic radiotherapy for intracranial tumors using relocatable Gill‐Thomas‐Cosman (GTC) frame

The present study is aimed at determination of accuracy of relocation of Gill‐Thomas‐Cosman frame during fractionated stereotactic radiotherapy. The study aims to quantitatively determine the magnitudes of error in anteroposterior, mediolateral and craniocaudal directions, and determine the margin between clinical target volume to planning target volume based on systematic and random errors. Daily relocation error was measured using depth helmet and measuring probe. Based on the measurements, translational displacements in anteroposterior (z), mediolateral (x), and craniocaudal (y) directions were calculated. Based on the displacements in x, y and z directions, systematic and random error were calculated and three‐dimensional radial displacement vector was determined. Systematic and random errors were used to derive CTV to PTV margin. The errors were within ± 2 mm in 99.2% cases in anteroposterior direction (AP), in 99.6% cases in mediolateral direction (ML), and in 97.6% cases in craniocaudal direction (CC). In AP, ML and CC directions, systematic errors were 0.56, 0.38, 0.42 mm and random errors were 1.86, 1.36 and 0.73 mm, respectively. Mean radial displacement was 1.03 mm ± 0.34. CTV to PTV margins calculated by ICRU formula were 1.86, 1.45 and 0.93 mm; by Strooms formula they were 2.42, 1.74 and 1.35 mm; by van Herks formula they were 2.7, 1.93 and 1.56 mm (AP, ML and CC directions). Depth helmet with measuring probe provides a clinically viable way for assessing the relocation accuracy of GTC frame. The errors were within ± 2 mm in all directions. Systematic and random errors were more along the anteroposterior axes. According to the ICRU formula, a margin of 2 mm around the tumor seems to be adequate. PACS number: 87.55.‐x

Radiation-induced opticochiasmatic glioblastoma multiforme following conventional radiotherapy for Cushing's disease

Abstract We report the rare occurrence of an opticochiasmatic glioblastoma multiforme 6 years following conventional radiotherapy for Cushings disease. This article highlights the risks of collateral damage to the optic apparatus when irradiating the sellar region.

Radiation Pneumonitis After Conventional Radiotherapy For Breast Cancer: A Prospective Study

BACKGROUND Loco-regional radiotherapy is an important treatment modality in breast cancer and radiation pneumonitis (RP) is one of the early toxicities. AIM To study the occurrence, correlation of RP with patient and radiotherapy related factors and the effects on pulmonary function following conventional radiotherapy in breast cancer. SETTINGS AND DESIGN Prospective study, from a tertiary hospital in a developing country. MATERIALS AND METHODS Prospective analysis of clinical symptoms, pulmonary function and radiologic changes was done prior to and 12 weeks after adjuvant radiotherapy (n=46). Statistical analysis was done using SPSS version 10 software. RESULTS Radiological and clinical RP was seen in 45.65% (n=21) and 19.56% (n=9) respectively. RP was significantly higher with age >50 years (OR 4.4), chest wall irradiation with electrons, (electrons 83.3% vs cobalt60 32.4%, p=0.02) and supraclavicular field treatment with 6 MV photons (p= 0.011). There was significant relationship between Inferior Lung Distance (ILD) and RP (p=0.013). The fall in Total Lung Capacity (TLC) was significantly more in those with RP (p=0.02). CONCLUSION Clinical RP occurs in almost one-fifth of breast cancer patients treated with conventional radiotherapy. Chest wall irradiation with electrons, supraclavicular field irradiation with 6 MV photons, higher ILD and age >50 years was associated with increased RP. The pulmonary function parameter most affected was TLC. The factors associated with increased RP should be considered when adjuvant radiotherapy is planned to minimize its likelihood and intervene appropriately.

An Unusually Long Survival of A Patient with Glioblastoma of Spinal Cord: A Case Report

Primary glioblastoma of spinal cord are rare and are associated with poor survival especially in adults. We report a case of glioblastoma of thoracic spinal cord (D3 to D6) in an adult treated with partial resection surgery and radiation therapy with a survival of six years with good quality of life. The patient had paraplegia at presentation but improved after surgery and radiation therapy to grade 4 in both lower limbs. After 5 years, he developed new lesion in a different location of the spine (L1, L2 & L5) along with multiple lesions over entire spine and was treated with radiation therapy and a year later developed a new lesion intracranially in the posterior fossa involving cerebellopontine angle region infiltrating brainstem. He was treated with palliative radiotherapy and is on chemotherapy with Temozolomide and is still alive with ability to do activities of daily living at the time of this report. Radiation therapy provided prolonged local control with effective palliation of symptoms and good quality of life in this patient enabling to do activities of daily living.

Clinicopathological Study of Triple Negative Breast Cancers

INTRODUCTION Triple Negative Breast Cancers (TNBC) are a subset of breast cancers which are composed of different molecular subtypes. The most common is the basal like subtype, which has an adverse prognosis and limited treatment options. AIM This study was undertaken to assess the clinico-pathologic and immunohistochemical subtypes of triple negative breast cancers and assess how each of these subtypes correlate with clinical behaviour and survival outcomes. MATERIALS AND METHODS Fifty-three (22.2%) of 238 cases of primary invasive breast carcinomas diagnosed from January 2010 to June 2011 were found to be negative for immunohistochemical markers- ER, PR and HER2. These fifty three cases were included in the study and were classified into four histological subtypes proposed by Ishikawa et al. Basal markers- CK5/6, EGFR and CK14 were done on these cases and they were further classified immunohistochemically into basal and non basal subtypes. The morphological features, disease free survival and overall survival were evaluated for both basal and non basal subtypes. RESULTS Majority (96%) of TNBC cases were classified according to WHO as invasive ductal carcinoma (NOS). Type C Ishikawa histological subtype was found to be the commonest subtype in both basal and non-basal TNBC. Of 53 TNBC cases, basal immunohistochemical markers were performed on 47 cases only because of paucity of tissue. Of these 47 cases, thirty-five (74.4%) were found to be of basal like subtype and all these cases were picked up by a combination of CK5/6 and EGFR. CONCLUSION High grade morphological features, hormonal markers with additional use of basal markers can help identify the basal like subtype of TNBC, thereby predicting breast cancer survival. The combination of CK5/6 and EGFR identified all cases of basal subtype. EGFR in addition also has potential therapeutic implications. The morphological features and survival outcomes were not significantly different between basal and non-basal phenotypes.

Oral and gastrointestinal symptomatic metastases as initial presentation of lung cancer

Metastasis to the tongue, duodenum or pancreas from primary lung cancer is uncommon. Primary lung cancer presenting with symptoms related to metastases at these sites, at initial presentation is extremely rare. We report a 45-year-old man with disseminated lung malignancy who presented with dyspepsia, melena, symptoms due to anaemia and swelling in the tongue. Oral examination revealed a hard submucosal anterior tongue lesion. Biopsies from the tongue lesion and the duodenal ulcer seen on upper gastrointestinal endoscopy were suggestive of metastasis from lung primary. CT revealed lung primary with disseminated metastasis to lung, liver, adrenals, kidneys, head and body of pancreas, duodenum and intra-abdominal lymph nodes. The patient was treated with palliative chemotherapy. The unusual presentation and diagnostic details are discussed.

An Early and Rare Second Malignancy in A Treated Glioblastoma Multiforme: Is It Radiation or Temozolomide?

Glioblastoma Multiforme (GBM) is a high-grade brain tumour with the most dismal prognosis. There are very few reports on second malignancies occurring in GBM patients, as the survival has been short. Second malignancies have been reported after treatment of malignancies with radiation therapy and chemotherapy especially after 5 to 10 y of treatment. Here in, we present a very unique case where a patient succumbed to sinonasal carcinoma occurring one and half years after treatment of GBM. A 17-year-old boy was diagnosed to have GBM and underwent surgery followed by chemoradiation and adjuvant chemotherapy with Temozolamide. He presented with undifferentiated sinonasal carcinoma, in the sinonasal region outside the radiation field within two years of treatment. Here we discuss the histology and possible chances of it being a second malignancy.

Management and Outcome in Patients with Advanced Juvenile Nasopharyngeal Angiofibroma

Objective To report the management outcome in a series of patients with advanced juvenile nasopharyngeal angiofibroma (JNA). Design Retrospective study. Setting Tertiary care teaching hospital. Participants Forty‐five patients classified as Radkowski stage IIIA or IIIB who presented to us over the past 10 years. Main Outcome Measures Surgical approaches used and disease free outcomes in patients with advanced JNA. Results Surgical access for the extracranial component included open (41.9%) and expanded endonasal approaches (58.1%). Craniotomy (16.3%), endoscopy‐assisted open approach (7%), or expanded endonasal approach (20.9%) was performed to excise the skull base or intracranial component. Follow up ranged from 4 to 96 months (mean, 20.3 months). Of 35 patients who underwent imaging at the first postoperative follow up, 25 (71.4%) had negative scans. Three symptomatic patients with residual disease underwent endoscopic excision and had negative scans thereafter. Of two others who had radiation therapy, one was disease free and the other lost to follow up. Five others had stable, residual disease. Three patients (8.6%) with recurrent disease underwent surgical excision, of whom two had minimal, stable residual disease. At the last follow‐up, 27 (77.1%) patients had negative scans, and 7 (20%) had stable residual disease with one (2.9%) patient lost to follow‐up. Conclusions Advanced JNA may be successfully treated in most cases with expanded endonasal/endoscopy assisted ± craniotomy approach after appropriate preoperative evaluation. At follow‐up, only symptomatic patients or those with enlarging residue require treatment; periodic imaging surveillance is adequate for those with stable disease.

Unusual sites of metastases of carcinoma cervix

We present a case of metastatic squamous cell carcinoma cervix with solitary bone metastases to the right tibia and multiple cutaneous metastases. A woman aged 52 years with cancer of the cervix and lung metastases, after 21 months of initial diagnosis and palliative chemotherapy presented with pain in the right knee and multiple nodular skin lesions. Bone scintigraphy revealed intense increased tracer activity in the proximal and mid shaft of the right tibia. Biopsy from the tibial lesion confirmed metastatic squamous cell carcinoma. The presentation, diagnosis and management of this rare case are discussed.