One Pot Synthesis of PEGylated Bimetallic Gold-Silver Nanoparticles for Imaging and Radiosensitization of Oral Cancers.

BACKGROUND: Radiotherapy is an important treatment modality for many types of head and neck squamous cell carcinomas. Nanomaterials comprised of high atomic number (Z) elements are novel radiosensitizers enhance radiation injury by production of free radicals and subsequent DNA damage. Gold nanoparticles are upcoming as promising radiosensitizers due to their high (Z) biocompatibility, and ease for surface engineering. Bimetallic nanoparticles have shown enhanced anticancer activity compared to monometallic nanoparticles. MATERIALS AND METHODS: PEG-coated Au-Ag alloy nanoparticles (BNPs) were synthesized using facile one pot synthesis techniques. Size of ~50±5nm measured by dynamic light scattering. Morphology, structural composition and elemental mapping were analyzed by electron microscopy and SAXS (small-angle X-ray scattering). The radiosensitization effects on KB oral cancer cells were evaluated by irradiation with 6MV X-rays on linear accelerator. Nuclear damage was imaged using confocal microscopy staining cells with Hoechst stain. Computed tomography (CT) contrast enhancement of BNPs was compared to that of the clinically used agent, Omnipaque. RESULTS: BNPs were synthesized using PEG 600 as reducing and stabilizing agent. The surface charge of well dispersed colloidal BNPs solution was -5mV. Electron microscopy reveals spherical morphology. HAADF-STEM and elemental mapping studies showed that the constituent metals were Au and Ag intermixed nanoalloy. Hydrodynamic diameter was ~50±5nm due to PEG layer and water molecules absorption. SAXS measurement confirmed BNPs size around 35nm. Raman shift of around 20 cm-1 was observed when BNPs were coated with PEG. 1H NMR showed extended involvement of - OH in synthesis. BNPs efficiently enter cytoplasm of KB cells and demonstrated potent in vitro radiosensitization with enhancement ratio ~1.5-1.7. Imaging Hoechst-stained nuclei demonstrated apoptosis in a dose-dependent manner. BNPs exhibit better CT contrast enhancement ability compared to Omnipaque. CONCLUSION: This bimetallic intermix nanoparticles could serve a dual function as radiosensitizer and CT contrast agent against oral cancers, and by extension possibly other cancers as well.

Fluorodeoxyglucose-positron emission tomography in carcinoma nasopharynx: Can we predict outcomes and tailor therapy based on postradiotherapy fluorodeoxyglucose-positron emission tomography?

BACKGROUND: Positron emission tomography-computed tomography (PET-CT) is an emerging modality for staging and response evaluation in carcinoma nasopharynx. This study was conducted to evaluate the impact of PET-CT in assessing response and outcomes in carcinoma nasopharynx. MATERIALS AND METHODS: Forty-five patients of nonmetastatic carcinoma nasopharynx who underwent PET-CT for response evaluation at 10-12 weeks posttherapy between 2004 and 2009 were evaluated. Patients were classified as responders (Group A) if there was a complete response on PET-CT or as nonresponders (Group B) if there was any uptake above the background activity. Data regarding demographics, treatment, and outcomes were collected from their records and compared across the Groups A and B. RESULTS: The median age was 41 years. 42 out of 45 (93.3%) patients had WHO Grade 2B disease (undifferentiated squamous carcinoma). 24.4%, 31.1%, 15.6, and 28.8% patients were in American Joint Committee on Cancer Stage IIb, III, Iva, and IVb. All patients were treated with neoadjuvant chemotherapy followed by concomitant chemoradiotherapy. Forty-five patients, 28 (62.2%) were classified as responders, whereas 17 (37.8%) were classified as nonresponders. There was no significant difference in the age, sex, WHO grade, and stage distribution between the groups. Compliance to treatment was comparable across both groups. The median follow-up was 25.3 months (759 days). The disease-free survival (DFS) of the group was 57.3% at 3 years. The DFS at 3 years was 87.3% and 19.7% for Group A and B, respectively (log-rank test, P < 0.001). Univariate and multivariate analysis revealed Groups to be the only significant factor predicting DFS (P value 0.002 and < 0.001, respectively). In Group B, the most common site of disease failure was distant (9, 53%). CONCLUSION: PET-CT can be used to evaluate response and as a tool to identify patients at higher risk of distant failure. Further, this could be exploited to identify patients who may need treatment intensification. This needs to be validated prospectively.

Guidelines for locoregional therapy in primary breast cancer in developing countries: The results of an expert panel at the 8(th) Annual Women's Cancer Initiative - Tata Memorial Hospital (WCI-TMH) Conference.

BACKGROUND: Limited guidelines exist for breast cancer management in developing countries. In this context, the Women's Cancer Initiative - Tata Memorial Hospital (WCI-TMH) organised its 8(th) Annual Conference to update guidelines in breast cancer. MATERIALS AND METHODS: Appropriately formulated guideline questions on each topic and subtopic in the surgical, radiation and systemic management of primary breast cancer were developed by the scientific committee and shared with the guest faculty of the Conference. Majority of the questions had multiple choice answers. The opinion of the audience, comprising academic and community oncologists, was electronically cumulated, followed by focussed presentations by eminent national and international experts on each topic. The guidelines were finally developed through an expert panel that voted on each guideline question after all talks had been delivered and audience opinion elicited. Separate panels were constituted for locoregional and systemic therapy in primary breast cancer. RESULTS: Based on the voting results of the expert panel, guidelines for locoregional therapy of breast cancer have been formulated. Voting patterns for each question are reported. CONCLUSIONS: The updated guidelines on locoregional management of primary breast cancer in the context of developing countries are presented in this article. These recommendations have been designed to allow centers in the developing world to improve the quality of care for breast cancer patients.

Impact of comorbidity on therapeutic decision-making in head and neck cancer: audit from a comprehensive cancer center in India.

BACKGROUND: Head and neck cancer has increased incidence of comorbidity due to tobacco and alcohol use. METHODS: Two hundred consecutive patients were included in this cross-sectional study. Data on clinico-demographic characteristics and comorbidity was extracted from case records. Comorbidity was assessed with Adult Comorbidity Evaluation 27 (ACE-27) and Charlson Comorbidity Index (CCI). Change in therapeutic decision-making from institutional evidence-based guidelines was classified as low, medium, or high-impact. RESULTS: Of 200 patients, 68(34%) had comorbidity while 15 had multimorbidity. No change in therapeutic decision-making was seen in 139 patients (69.5%), 61patients (30.5%) had change from institutional evidence-based guidelines. There was strong positive correlation (Spearman's correlation coefficient = 0.80; p < .001) between ACE-27 and change in therapeutic decision-making. For CCI, there was moderate positive correlation (Spearman's correlation coefficient = 0.50; p < .001). CONCLUSION: Comorbidity in patients with head and neck cancer can influence therapeutic decision-making. Prospective longitudinal rigorous collection of comorbidity data is warranted for correlation with outcomes. ACE-27 may be a clinically more meaningful tool for comorbidity assessment.

Non-Hodgkin's lymphoma: is India ready to incorporate recent advances in day to day practice?

BACKGROUND: Non Hodgkin's Lymphoma (NHL) cure rates are increasing and morbidities are decreasing, with more active pharmacological agents and technological advancements. In spite of this, India is still battling with the prejudices of an economically and educationally impoverished patient base. METHODS AND RESULTS: We analyzed NHL cases from 2000 to 2006 using data from case sheets. Of 303 cases, only 100 patients had complete workup and received some form of treatment. For 203 patients, reasons for non-compliance were: financial constraint (119), distance from center (38), inability of physician to provide guarantees of cure (13), poor prognosis/fear of recurrence (28)), preferences for alternate medicine (5). Most common investigations that could not be afforded for staging were whole body CT scans and bone marrow aspiration and biopsy. Thirteen patients were in stage III and 53 in Stage IV. The most common regimen was CHOP (Cyclophosphamide, Adriamycin, Vincristine, Prednisolone). Forty-five patients did not complete six courses of CHOP and 35 patients had significant delay. Reasons for delay were intermittent availability of cash (35), intolerable toxicities (30), absence of supportive care (21), given-up attitudes (17). Eighty-three patients suffered Grade III/IV debilitating toxicities. Overall survival at five years was 50%. CONCLUSIONS: NHL in India is no different from the developed world. However, there are disparities in survivorship and outcomes, due to un-affordability and attitudes of the patients. Therefore, we suggest the development of Community Health Insurance Schemes (CHIs), with the hospital as the nodal center to address the above mentioned issues.

Diffuse large B-cell lymphoma of the uterine cervix: a rare case managed novelly.

Non-Hodgkin's lymphoma (NHL) of the uterine cervix is exceedingly rare. The management of the disease is not standardized. A 44-year-old lady presented with a history of bleeding pervaginum and a foul-smelling discharge of 2 months' duration. A 7 x 7 growth was seen in the cervix. A biopsy revealed it to be a CD20-positive diffuse large B-cell (DLBCL)-type NHL. She was diagnosed as stage IE after staging work-up, and managed with three courses of rituximab, cyclophosphamide, vincristine, adriamycin, and prednisolone followed by external beam radiotherapy (46 Gy in 23 fractions) by 3D conformal technique. She attained a complete response, and has been in remission for 1 year 3 months.