Rajesh Isiah

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.

Hypofractionated palliative radiotherapy in locally advanced inoperable head and neck cancer: CMC vellore experience

Background: A novel, short duration, palliative radiotherapy schedule for inoperable head and neck cancer was evaluated in terms of palliation of cancer-related symptoms and acute toxicities. Materials and Methods: Thirty-six patients with inoperable head and neck cancer were included in the study (2010-2012). All patients received 40 Gy in 10 fractions (equivalent dose: 49.8 Gy in conventional fractionation) with 2 fractions per week. Treatment-related toxicity was assessed using Radiation Therapy Oncology Group criteria. Functional Assessment of Cancer Therapy (Head and Neck, FACT H and N) quality of life (QOL) tool was administered before starting and at the completion of radiotherapy. Mean value before and after treatment was compared (paired t-test, P = 0.05, two-tailed for significance). Results: Thirty-three patients (male: 29, female: 4, mean age: 57.8 ± 9.7 years) were included in the analysis (three patients discontinued treatment due to socioeconomic reasons). All patients had advanced inoperable head and neck cancers (27% IVA, 61% IVB, 9% IVC, TNM stage and 3% recurrent disease). Distressing pain at primary site (42%), dysphagia (18%), neck swelling (30%), and hoarseness (10%) were common presentations. Incidence of grade III mucositis and dermatitis and pain was 18%, 3%, and 24%, respectively. Planned radiotherapy without any interruptions was completed by 73% patients. QOL assessment showed improvement in social well-being (17.4 vs. 20.01, P = 0.03), but no significant change was observed in head and neck specific score (25.1 vs. 25.0, P = NS) after treatment. Reduction of pain was observed in 88% patients and 60% patients had improvement of performance status. Median overall survival of the cohort was 7 months. Conclusions: The study shows that this short duration palliative radiotherapy schedule is a clinically viable option for advanced inoperable head and neck cancer to achieve significant palliation of the main presenting symptoms like pain, dysphagia, and throat pain.

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

Role of conventional and diffusion weighted MRI in predicting treatment response after low dose radiation and chemotherapy in locally advanced carcinoma cervix.

BACKGROUND AND PURPOSE To assess the diagnostic performance of conventional and diffusion weighted (DWI) magnetic resonance imaging (MRI) in predicting response in locally advanced cervical cancer. MATERIALS AND METHODS Total 24 patients with stage IIB-IIIB squamous cell carcinoma cervix were treated with initial two cycles of paclitaxel and carboplatin and concurrent low dose radiotherapy prior to standard chemoradiation. Response was assessed clinically and radiologically after 3 weeks of initial treatment. Volumetric and functional parameters derived from conventional and diffusion weighted MRI, due to treatment were measured. RESULTS Significant reduction of GTV was noted in MRI (54 cm(3) vs. 11 cm(3), p < 0.01) and DWI (44 cm(3) vs. 6 cm(3), p < 0.01, ΔADC = 0.49 × 10(-3)mm(2)/sec, p < 0.01) after treatment. Tumor volume reduction rate (TVRR) in DWI was significantly higher in pathological good responders (p = 0.03). In this group both mean post treatment apparent diffusion coefficient (ADC) value and ΔADC were significantly higher (p = 0.01 and p = 0.03). ADC was a good predictor for pathological response (area under receiver operating characteristic curve (ROC) 0.814). CONCLUSION TVRR (DWI) and ΔADC can be used as a predictor of early pathological response. Complete response based on DWI, could be a useful predictor of long term disease control.

Mesenteric Fibromatosis Mimicking Metastasis: A Case Report and Review of Literature

Fibromatosis is a heterogeneous group of tumors arising from muscle, fascia, or aponeurosis and is characterized by proliferation of fibroblasts and myofibroblasts [1, 2]. Although benign and never known to metastasize, it has a remarkable tendency to infiltrate adjacent structures, causing obstructive symptoms or neurovascular impairment. Deep fibromatosis of the mesentery is rare and present as multicentric nodules with heterogeneous signal intensities in magnetic resonance imaging [3]. With prior history of malignancy, it may be difficult to differentiate these lesions with disease recurrence or metastasis. Fibromatosis can show variable uptake in fluro-2 deoxy-D-glucose positron emission tomography (FDG PET) scan. We report a case of mesenteric fibromatosis showing uptake in FDG PET in a patient with endometrial carcinoma.

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.

Low-dose fractionated radiation and chemotherapy prior to definitive chemoradiation in locally advanced carcinoma of the uterine cervix: Results of a prospective phase II clinical trial

BACKGROUND We investigated the feasibility of neoadjuvant low-dose radiation and chemotherapy with paclitaxel and carboplatin (LDCRT) before radical chemoradiation (CRT) and assessed the feasibility, efficacy, and response rate to such a regimen. METHODS This is a single-arm phase II trial of 24 patients, with locally advanced squamous cell carcinoma of the cervix (stage IIB-IIIB). Patients received low-dose fractionated radiotherapy, carboplatin (AUC×5) and paclitaxel (175 mg/m(2)), three weekly for two cycles followed by CRT. The primary end point was overall and disease-free survival. RESULTS Mean age of the patients at diagnosis was 50 years; Radiological complete or partial response rate was 40% and 60%, respectively, post-LDCRT. The median follow-up was 30 months (24-36 months). Both overall and progression-free survivals at 2.5 years were 84%. Grade 3/4 toxicities were 24% hematological toxicity during LDCRT and 46% during CRT (hematological: 42%, non-hematological: 4%). CONCLUSION A good response rate is achieved by low-dose radiation and chemotherapy with carboplatin and paclitaxel followed by radical CRT. This treatment regimen is feasible and effective as evidenced by the acceptable toxicity and 84% local control at 2.5 years.

Comparison of setup errors based on bony landmarks in high precision radiotherapy in head and neck cancer: Results of a prospective study

Background: Comparison of setup errors for various immobilization devices in head and neck cancer and to determine the treatment margin in high precision radiotherapy using bony landmark based matching. Materials and Methods: Total 20 patients were immobilized with BrainLAB immobilization device (BL) or thermoplastic ray cast (RC) for high precision radiotherapy. Total, systematic, and random errors in mediolateral (ML), craniocaudal (CC) and antero-posterior directions were determined and clinical target volume (CTV) to planning target volume (PTV) margin by Strooms formula was compared. Unpaired t-test was used for comparing errors. The standard deviations (systematic and random errors) in different groups were compared by variance ratio test (Levenes test) and P < 0.05 was considered significant. Results: The total error in ML direction (BL vs. RC) was 1.00 mm versus 1.39 mm (P = 0.03), systematic error 0.09 cm versus 0.197 cm and random error 0.116 cm versus 0.258 cm (F-test, P = 0.001). CTV to PTV margin was significantly lower in BL (0.26 cm vs. 0.57 cm, P < 0.05). In CC direction, BL system had lower total error (0.075 cm vs. 0.157 cm) and a significantly less systematic error (0.116 cm vs. 0.258 cm, F = 7.149, P = 0.015). CTV to PTV margin was less in BL than RC in CC direction (0.34 cm vs. 0.92 cm, P = 0.06). Conclusion: In head and neck region, when electronic portal imaging device based verification is used, for BL margins ranged from 2.6 to 3.7 mm. For RC in the PTV margin was 5.7–9.2 mm. Therefore, a margin of 3 mm for BL and 5–10 mm for RC with online correction in head and neck is adequate.