Level of Awareness of Various Aspects of Lung Cancer Among College Teachers in India: Impact of Cancer Awareness Programmes in Prevention and Early Detection.

Lung cancer is one of the most common causes of cancer mortality among men in India and incidence is increasing, but actually, they are largely preventable diseases. In India, advanced stage at the time of presentation is responsible for high mortality and morbidity and early detection is the only way to reduce it. The purpose of this study is to know the level of awareness of various aspects of lung cancer among college teachers and impact of awareness programmes in its prevention and early detection. This assessment was part of Pink Chain Campaign-a campaign on cancer awareness. During the cancer awareness events in 2011-2013 at various women colleges in different parts in India, pre-test related to lung cancer was followed by awareness programme. Post-test using the same questionnaire was conducted at the end of interactive session, at 6 months and 1 year. A total of 872 out of 985 teachers participated in the study (overall response rate was 88.5 %). Mean age of the study population was 41.6 years (range 26-59 years). There was a significant increase in the level of knowledge regarding lung cancer at 6 months, and this was sustained at 1 year. Among teachers who were just asked yes or no question, 117 teachers (13.4 %) were smokers and 241 teachers (27.6 %) were alcoholics. Magazines and newspapers were sources for knowledge in 50-60 % of teachers, whereas approximately 30 % of teachers were educated by TV and Internet regarding various aspects of lung cancer. Post awareness at 6 months and 1 year, Pink Chain Campaign was the major source of knowledge related to lung cancer in more than 90 % of teachers by continuous and timely update on subject. Post awareness at 6 months and 1 year, there was a significant change in alcohol and smoking habits. Major reasons for not going for check-up were ignorance (83.1 %), fear (30.1 %) and lethargic attitude (29.3 %) initially, but over time, lack of time, lethargic attitude and hesitation became important factors after knowing various aspects of lung cancer. Knowledge of lung cancer was very low among teachers. Overall awareness of risk factors, sign and symptoms, screening modalities of lung cancer has improved in a year along with practices related to smoking and alcohol, but there was not much improvement in people undergoing regular check-ups. To inculcate safe practices in the lifestyle of people, awareness programmes such as the Pink Chain Campaign should be conducted more widely and frequently.

Genome-wide small noncoding RNA profiling of pediatric high-grade gliomas reveals deregulation of several miRNAs, identifies downregulation of snoRNA cluster HBII-52 and delineates H3F3A and TP53 mutant-specific miRNAs and snoRNAs.

Pediatric high-grade gliomas (HGGs) are highly malignant tumors that remain incurable and relatively understudied. The crucial role of noncoding RNAs (ncRNAs) has been reported in various cancers. However, the study on miRNAs in pediatric HGGs is scant and there is no report till date on the status of other small ncRNAs. Genome-wide microarray analysis was performed to investigate small ncRNA expression in pediatric HGG (n = 14) and compared to adult glioblastoma (GBM) signature. The validation of miRNAs and small nucleolar RNAs (snoRNAs) was done by real-time polymerase chain reaction. TP53 and H3F3A mutation-specific miRNA and snoRNA profiles were generated and analyzed. Pediatric HGGs showed upregulation of miR-17/92 and its paralog clusters (miR106b/25 and miR-106a/363), whereas majority of downregulated miRNAs belonged to miR379/656 cluster (14q32). Unsupervised hierarchical clustering identified two distinct groups. Interestingly, Group 2 with downregulated 14q32 cluster showed better overall survival. The miRNAs unique to pediatric HGG as compared to adult GBM were predicted to affect PDGFR and SMAD2/3 pathways. Similarities were seen between pediatric HGG and TP53 mutant miRNA profiles as compared to wild types. Several of H3F3A mutation-regulated genes were found to be the targets of H3F3A mutant-specific miRNAs. Remarkably, a significant downregulation of HBII-52 snoRNA cluster was found in pediatric HGGs, and was specific to H3F3A nonmutants. This is the first genome-wide profiling study on miRNAs and snoRNAs in pediatric HGGs with respect to H3F3A and TP53 mutations. The comparison of miRNA profiles of pediatric HGGs and adult GBM reiterates the overlaps and differences as also seen with their gene expression and methylation signatures.

Extracellular cytochrome c as a biomarker for monitoring therapeutic efficacy and prognosis of non-small cell lung cancer patients.

Non-small cell lung cancer has a devastating prognosis, and markers enabling a precise prediction of therapy response have long remained scarce. Better treatment monitoring would allow an individual's more effective patient adjusted therapy with lesser side effects and good clinical outcomes. In the present study, we monitored the serum cytochrome c levels pre- and post-chemotherapy of non-small cell lung cancer patients. Using highly sensitive enzyme-linked immunosorbent assay, we evaluated cytochrome c levels in serum of 100 non-small cell lung cancer and 100 healthy controls. We observed about threefold lower serum cytochrome c level in newly diagnosed non-small cell lung cancer patients than healthy individuals. Patients in advanced stages and grade 3 histological differentiation showed significantly low level of serum cytochrome c, and the lower levels were associated with worse survival outcome of non-small cell lung cancer patients. In addition, serum cytochrome c level was observed to be more than 13-fold higher after first cycle of conventional chemotherapy, wherein patients with higher level of serum cytochrome c before any therapy showed better response to chemotherapy in terms of significantly higher level of serum cytochrome c after first cycle of chemotherapy than patients with low level of serum cytochrome c at the time of diagnosis. Detection of serum cytochrome c levels at the time of diagnosis may be useful in suggesting disease severity and prognosis of the non-small cell lung cancer patients. Monitoring of serum cytochrome c might also serve as a sensitive apoptotic marker in vivo reflecting chemotherapy-induced cell death burden in patients with non-small cell lung cancer.

Association of p53 and mdm2 in the development and progression of non-small cell lung cancer.

MDM2 protein is an important regulator of the p53 pathway and has a large effect on the anti-tumorigenic activity of the p53. Presently, we aimed to analyze the possible association of p53 and mdm2 in the development and progression of non-small cell lung cancer. In addition, impact of an important gene promoter polymorphism of MDM2 (T309G, rs 2279744) on its gene expression and ultimately of the TP53 was investigated in non-small cell lung cancer patients. A case-control study using peripheral blood samples of 100 non-small cell lung cancer patients and 100 cancer free healthy controls was conducted. Expression profile of MDM2 and TP53 gene were evaluated by using quantitative real time polymerase chain reaction assay, and MDM2 promoter polymorphism were analyzed by amplification refractory mutation system polymerase chain reaction. Non-small cell lung cancer patients expressed more than 6-fold increased mdm2 and about 7-folds decreased in p53 expression levels compared to healthy controls. Higher fold change increase of mdm2 and/or decrease of p53 were associated with advanced status and poor clinical outcome of the patients. A significant increase in mdm2 of about 14-folds and decrease in p53 of about 16.5-fold were observed among patients with MDM2 (309GG) genotype vs just 2.2-fold increase in mdm2 and 1.9-fold decrease in p53 among patients with MDM2 (309TT) genotype. In conclusion, present study demonstrated that MDM2 (309 T > G) polymorphism may be one of the important factors for the increased expression mdm2, which was associated with down-regulation of p53 at messenger RNA (mRNA) level and ultimately may contribute in the poor clinical outcome of the non-small cell lung cancer patients, thus may prove as a promising target for the treatment of non-small cell lung cancer at molecular level.

Role of survivin re-expression in the development and progression of non-small cell lung cancer.

Survivin is highly expressed in fetal tissue and is completely absent in terminally differentiated cells, but its re-expression has been observed in most human tumors. Presently, we aimed to analyze the possible impact of the survivin gene (-31G > C, rs 9904341) promoter polymorphism on the expression profile of survivin gene and ultimately the role of survivin re-expression in the development and progression of non-small cell lung cancer. A case-control study of 100 non-small cell lung cancer patients and 100 cancer-free healthy controls was conducted. Survivin gene promoter polymorphism was analyzed by PCR-restriction fragment length polymorphisms (RFLP) technique, and the survivin expression profile was evaluated using quantitative real-time PCR assay. Compared to the survivin GG genotype, odd ratio of 3.2 (95 % CI 4.8-25.9, p = 0.004) was found to be associated to homozygous CC genotype with 15-fold increase of survivin gene expression in non-small cell lung cancer patients. Significant trend of increase in survivin expression was observed with the increase in severity of the disease. Patients with survivin (-31CC) genotype had significantly shorter overall survival compared to survivin (-31GG) genotype carriers. In addition, advanced disease status and significant poor overall survival were also reflected by patients with higher-fold increase in survivin gene expression. In conclusion, present study demonstrated that survivin (-31G > C) polymorphism may contribute to the risk of developing non-small cell lung cancer in Indian population. Survivin (-31CC) genotype was associated with significantly increased survivin gene expression and ultimately may contribute in the poor clinical outcome of non-small cell lung cancer patients, suggesting its possible significance in the development and progression of non-small cell lung cancer.

Intradural extra medullary hemangiopericytoma of dorsal spine.

PURPOSE: Spinal hemangiopericytoma is a rare neoplasm that behaves similar to intracranial hemangiopericytoma, with approximately 60 cases being reported in the literature of which only 10 are located in the intradural extramedullary (IDEM) location. METHODS: We report a rare case of recurrent IDEM hemangiopericytoma of dorsal spine in a 16-year-old boy treated with surgery and adjuvant radiotherapy. RESULTS: Patient is disease free at 5 years posttreatment with residual neurological deficit, but is able to carry out his activities of daily living. CONCLUSION: Gross total resection, if feasible, followed by radiotherapy is the initial treatment of choice as radiotherapy improves recurrence free survival as well as overall survival.

Malignant peripheral nerve sheath tumour of penis.

Malignant peripheral nerve sheath tumour (MPNST) is a rare variety of soft tissue sarcoma that originates from Schwann cells or pluripotent cells of neural crest origin. They have historically been difficult tumours to diagnose and treat. Surgery is the mainstay of treatment with a goal to achieve negative margins. Despite aggressive surgery and adjuvant therapy, the prognosis of patients with MPNST remains poor. MPNST arising from penis is a very rare entity; thus, it presents a diagnostic and therapeutic challenge. We present a case of penile MPNST in a 38-year-old man in the absence of neurofibromatosis treated with surgery followed by post-operative radiotherapy to a dose of 60 Gray in 30 fractions and adjuvant chemotherapy with ifosfamide and adriamycin.

Evolving multidisciplinary treatment of squamous cell carcinoma of the head and neck in India✰.

In this article, we highlight the evolution of a multimodal approach in the overall management of squamous cell carcinoma of the head and neck (SCCHN) in India; present advances in technology (newer surgical techniques), novel medical and radiotherapy (RT) approaches; review their roles for an integrated approach for treating SCCHN and discuss the current role of immunotherapy in SCCHN. For locally advanced (LA) SCCHN, the multidisciplinary approach includes surgery followed by RT, with or without chemotherapy (CT) or concurrent chemoradiotherapy. Improved surgical techniques of reconstruction and voice-preservation are being implemented. Advanced forms of high-precision conformal techniques like intensity-modulated radiotherapy are used to deliver highly conformal doses to tumors, sparing the surrounding normal tissue. Compared with RT alone, novel CT regimens and targeted therapeutic agents have the potential to improve locoregional control and survival and reduce treatment-induced toxicities. Several clinical trials have demonstrated efficacy, safety, and quality of life benefits of adding cetuximab to RT regimens in LASCCHN. Studies have also suggested a cetuximab-related laryngeal preservation benefit. At progression, platinum-based CT combined with cetuximab (a monoclonal anti-epidermal growth factor receptor antibody) is the only validated option available as the first-line therapy. Thus, an integrated multidisciplinary approach plays a key role in maximizing patient outcomes, reduction in treatment related morbidities that consequently impact quality of life of survivors.

A rare case of paraganglioma of the sella with bone metastases.

Sellar paragangliomas are very rare lesions with only 11 previous cases described in the literature. We present a further case of sellar paraganglioma. The patient is a 17-year-old man who developed headache, visual blurring, and diplopia. MRI showed a sellar lesion. Trans-nasal trans-sphenoid biopsy showed features of paraganglioma. He was treated by Stereotactic radiotherapy. Four months after treatment he developed bone metastases which was palliated by radiation, zoledronic acid, and chemotherapy. This is the first case of sellar paraganglioma showing metastases to bone.

Radiation dose escalation by percutaneous interstitial brachytherapy in locally advanced non-small cell lung cancer.

Management of locally advanced non-small cell lung cancer is associated with a poor overall survival using concurrent chemoradiotherapy. Therefore, newer approaches to treatment which enable dose escalation are warranted. Interstitial brachytherapy in lung is a new emerging concept with many distinct advantages. We report here a case of locally advanced non-small cell lung cancer with residual disease after conventional treatment. The patient was successfully treated using percutaneous interstitial brachytherapy and is disease-free at 18-month follow-up.

Biodosimetry using micronucleus assay in acute partial body therapeutic irradiation.

Biological dosimetry provides information on the absorbed dose and its distribution in the body for an early assessment of irradiation consequences in exposed individuals. In this study, an effort has been made to see the applicability of biological dosimetry using micronuclei assay for dose estimation in therapeutic irradiation of cancer patients in acute high dose partial body irradiation. Dose estimation in partial body irradiations was done on the basis of Dolphin's contaminated Poisson method, using the in vitro dose response calibration curve. The equivalent whole body dose and the dose to the irradiated part of the body were estimated to be 1.8+/-0.1 Gy and 6.4+/-0.3 Gy, respectively. The estimated percentage of irradiated blood and the fraction of cells exposed were 41.5+/-1.6% and 10.4+/-0.8%, respectively. The estimated fraction of irradiated cells was comparable with the actual volume of irradiation.

A phase II study of sequential neoadjuvant gemcitabine plus doxorubicin followed by gemcitabine plus cisplatin in patients with operable breast cancer: prediction of response using molecular profiling.

This study examined the pathological complete response (pCR) rate and safety of sequential gemcitabine-based combinations in breast cancer. We also examined gene expression profiles from tumour biopsies to identify biomarkers predictive of response. Indian women with large or locally advanced breast cancer received 4 cycles of gemcitabine 1200 mg m(-2) plus doxorubicin 60 mg m(-2) (Gem+Dox), then 4 cycles of gemcitabine 1000 mg m(-2) plus cisplatin 70 mg m(-2) (Gem+Cis), and surgery. Three alternate dosing sequences were used during cycle 1 to examine dynamic changes in molecular profiles. Of 65 women treated, 13 (24.5% of 53 patients with surgery) had a pCR and 22 (33.8%) had a complete clinical response. Patients administered Gem d1, 8 and Dox d2 in cycle 1 (20 of 65) reported more toxicities, with G3/4 neutropenic infection/febrile neutropenia (7 of 20) as the most common cycle-1 event. Four drug-related deaths occurred. In 46 of 65 patients, 10-fold cross validated supervised analyses identified gene expression patterns that predicted with >or=73% accuracy (1) clinical complete response after eight cycles, (2) overall clinical complete response, and (3) pCR. This regimen shows strong activity. Patients receiving Gem d1, 8 and Dox d2 experienced unacceptable toxicity, whereas patients on other sequences had manageable safety profiles. Gene expression patterns may predict benefit from gemcitabine-containing neoadjuvant therapy.

Excellent response to letrozole in brain metastases from breast cancer.

Breast cancer with multiple parenchymal brain metastases carries an extremely poor outcome. Cranial radiotherapy improves survival by only a few months and the role of systemic therapy is marginal and largely unexplored. We report a patient with recurrent carcinoma of breast presenting with multiple bilateral cervical nodes and brain metastases manifesting as a right hemiparesis and facial nerve palsy, who was treated with palliative whole brain irradiation and letrozole. At the follow up at 20 months, neurological function had fully recovered, and both cerebral and extracerebral lesions had completely resolved, with calcification of the cerebral lesions. This report suggests that letrozole has beneficial effects both in extracranial and intracranial disease in hormone responsive metastatic breast cancer.

Biological estimation of dose in hemi-body irradiation of cancer patients by cytogenetic analysis.

The objective of this study was to estimate equivalent whole body dose and dose to the irradiated region in hemi-body irradiation of cancer patients using chromosome aberrations and micronuclei techniques. The frequency of unstable chromosome aberrations and micronuclei was studied in peripheral blood lymphocytes of cancer patients before and after hemi-body irradiation. The mean estimated equivalent whole body dose was 3.74 +/- 0.16 Gy and 4.07 +/- 0.15 Gy from dicentrics and micronuclei frequency in lymphocytes after hemi-body irradiation. The mean dose to the irradiated region from unstable chromosome aberrations was estimated to be 6.85 +/- 0.2 Gy and 6.79 +/- 0.26 Gy using Dolphin's contaminated Poisson dispersion analysis and the Qdr method, respectively. The mean dose to the irradiated region from micronuclei frequency was 7.04 +/- 0.25 Gy by Dolphin's method. There was a slight underestimation of mean dose to the irradiated part in vivo. The percentage of irradiated blood and fraction of the cells exposed could be estimated using the contaminated Poisson method.

Can field-in-field technique replace wedge filter in radiotherapy treatment planning: a comparative analysis in various treatment sites.

The aim of the study was to show whether field-in-field (FIF) technique can be used to replace wedge filter in radiation treatment planning. The study was performed in cases where wedges are commonly used in radiotherapy treatment planning. Thirty patients with different malignancies who received radiotherapy were studied. This includes patients with malignancies of brain, head and neck, breast, upper and lower abdomen. All the patients underwent computed tomography scanning and the datasets were transferred to the treatment planning system. Initially, wedge based planning was performed to achieve the best possible dose distribution inside the target volume with multileaf collimators (Plan 1). Wedges were removed from a copy of the same plan and FIF plan was generated (Plan 2). The two plans were then evaluated and compared for mean dose, maximum dose, median dose, doses to 2% (D2) and 98% (D98) of the target volume, volume receiving greater than 107% of the prescribed dose (V > 107%), volume receiving less than 95% of the prescribed dose (V< 95%), conformality index (CI) and total monitor units. FIF gives equivalent dosimetric results as wedge based treatment planning. It is better than wedge planning in terms of maximum dose, D2, V >107% and CI for most of the sites with statistically significant reduction in monitor units. FIF results in better dose distribution in terms of homogeneity in most of the sites. It is feasible to replace wedge filter with FIF in radiotherapy treatment planning.

Prevalence of HIV in Patients with Malignancy and of Malignancy in HIV Patients in a Tertiary Care Center from North India.

BACKGROUND AND OBJECTIVES: People living with HIV/AIDS are at an increased risk of developing cancer. The goals of this study were to obtain data on the prevalence of HIV in the cancer population and vice versa at a major tertiary cancer and HIV center in North India. METHODS: This cross-sectional study was conducted over a 3-year period from July 2013 to June 2016, wherein successive HIV positive patients from an anti-retroviral therapy (ART) center were screened for malignancy. Simultaneously, successive cancer patients at the cancer center were screened for HIV. Baseline demographic details, risk factors, and laboratory investigations were obtained for all the patients. RESULTS: Among the 999 HIV-positive patients at the ART center, the prevalence of malignancy was 2% (n=20; 95% confidence interval (CI) 1.13, 2.87). Among the 998 patients with a malignancy, the prevalence of HIV infection was 0.9% (n=9; 95% CI 0.31, 1.49). Weight loss, loss of appetite, and fever were the most common symptoms in patients with HIV and cancer. Among 29 patients with HIV and cancer, AIDS-defining cancer was found in 19 patients; non-Hodgkin's lymphoma was the most common malignancy reported (n=13). INTERPRETATION AND CONCLUSION: There is a low prevalence of HIV in cancer patients as well as a low prevalence of cancer in HIV patients. AIDS-defining cancers remain much more common than non-AIDS-defining cancers. With the increased coverage of ART, it is expected that non-AIDSdefining cancers will increase, as is evident from data from more developed countries.

Comparison of contralateral breast dose for various tangential field techniques in clinical radiotherapy.

Contralateral breast (CLB) cancer is a rare but serious concern in radiotherapy. In this study, the CLB dose was measured using MOSFET dosimeter in 49 patients who underwent breast conservation surgery treated by different radiotherapy tangential field techniques, which included enhanced dynamic wedge (EDW), physical wedge, and intensity modulated radiation therapy (IMRT). The mean percent of the prescribed dose received by the contralateral areola in treatment technique using physical wedge (Cobalt), physical wedge (Linac), EDW, and IMRT were 4.27% (SD: 0.65), 3.61% (SD: 0.60), 3.38% (SD: 0.58), and 1.65% (SD: 0.24), respectively. There was a 29% CLB dose reduction at 3 cm from the medial tangential field border with IMRT compared to other wedged tangential field techniques. The study shows that the CLB dose could be reduced with IMRT or reducing or avoiding the medial wedge in conventional tangential field planning for breast cancer.

Feasibility of using MRI alone for 3D radiation treatment planning in brain tumors.

OBJECTIVE: The aim of this study was to establish whether radiation treatment planning using MRI alone could replace CT-based planning for brain tumors while retaining the dosimetric accuracy. This would help to provide a single imaging modality for both target delineation as well as treatment planning, thus saving time and resources. METHODS: Twenty-five patients with brain tumors were scanned on a spiral CT scanner and 1.5 T MRI scanner. Three treatment plans were generated for all patients. The first plan was generated using the CT scan images with inhomogeneity correction (CT + IC); the second plan used the CT scan without inhomogeneity correction (CT-IC) and the third plan was generated using the MRI scan (MRI alone). RESULTS: The maximum distortion in the MRI phantom study was less than 1 mm. There were no statistically significant differences in any of the target coverage parameters analysed in this study. Similarly, the maximum antero-posterior and lateral dimensions for the CT-based and MRI-based planning did not show any statistical difference. CONCLUSION: MRI-based treatment planning for brain lesions is feasible and gives equivalent dosimetric results compared to CT-based treatment planning.

Biodosimetry using chromosome aberrations in human lymphocytes.

In vitro dose-response calibration curves for (60)Co gamma rays have been established for unstable chromosome aberrations in human peripheral blood lymphocytes. The observed dose-response data were fitted to a linear quadratic model. The calibration curve parameters were used to estimate the equivalent whole-body dose and dose to the irradiated region in partial body irradiation of cancer patients. The derived partial body doses and fractions of lymphocytes irradiated were in agreement with those estimated from the radiotherapy regimes.

A study on contralateral breast surface dose for various tangential field techniques and the impact of set-up error on this dose.

The risk of inducing contralateral breast (CLB) cancer in patients undergoing tangential field irradiation for the treatment of breast cancer is a serious concern in radiation oncology. A bilateral breast phantom made of wax attached onto the Alderson Rando phantom was used for studying the CLB dose for techniques using physical wedges, EDWs, IMRT and open fields. The skin dose to the CLB was measured at four different points (3 cm from the medial border of the tangential field (P1), nipple (P3), axilla (P4), midpoint between P3 and P1 (P2)). The highest measured dose occurred at P1 with the 60 degrees physical wedges; it was 15.3% of the dose at isocentre. Similarly, the dose measured at P3 (nipple) with 60 degrees physical wedges was 1.90 times higher than the dose with 60 degrees EDWs. The dose at P1 for IMRT (7.8%) was almost the same as that for the open field (8.7%). The skin dose measured at the nipple was 2.1 - 10.9 % of the isocentre dose. The highest CLB doses were contributed by medial wedged fields. The dose to the CLB can be reduced by using IMRT or avoiding wedging the medial tangential fields. A set-up error in the longitudinal direction has little impact on the CLB dose. Set-up errors > 1 cm in the vertical and lateral directions have significant impact on the CLB dose.