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.

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.

Metaplastic carcinoma of breast: A case series of seven patients from a tertiary care center and review of literature.

PURPOSE: Metaplastic carcinoma of breast (MCB) is a rare histological subtype of breast carcinoma and accounts for less than 1 percent of the total breast cancer cases. Here we are reporting a series of seven patients of MCB from single institute along with review of literature. MATERIAL AND METHODS: Patients records from January 2008 to August 2014 were retrieved to search for MCB patients. A etrospective review was conducted to document the clinicopathological features, treatment and outcomes of these patients. The data was entered in a predesigned proforma document. RESULTS: Seven patients were diagnosed to have MCB during this period. Most common symptom at presentation was lump in the breast with associated discharge per nipple in one patient. On histology, there was no definite differentiation in four patients while one patient had spindle cell neoplasia, one had osteoid and chondroid neoplasia respectively. Five patients underwent modified radical mastectomy while other two patients underwent simple mastectomy. All the patients were pathologically node negative and triple negative breast cancer. Adjuvant chemo-radiotherapy was given to all patients. Median follow up was 4 years (Range 3-6 years). Three out of seven patients completed 5 years of follow up. One patient developed isolated liver metastasis six years after completion of the treatment and she lost to follow up for further treatment. CONCLUSION: Metaplastic carcinoma of breast is a rare disease entity and there are no specific treatment guidelines. The prognosis of patients in this rare sub group remains poor and multi institutional studies evaluating role of new therapies may be required to improve outcome.

Anti EGFR therapy in the treatment of non-metastatic head and neck squamous cell carcinoma: The current evidence.

Head and neck squamous cell carcinoma (HNSCC) accounts for a large oncologic burden in the developing countries. In patients with locally advanced head and neck cancer multimodality treatment is warranted. Radiation therapy with concurrent chemotherapy has long been considered the standard for patients with disease involving the oropharynx, larynx and hypopharynx. However, addition of chemotherapy to radiotherapy increases treatment related toxicity by many folds and compliance rates decrease. In this context a systemic therapy, which when used concurrent with radiation with favorable toxicity profile is of great importance for improving disease control in locally advanced HNSCC. Anti-epithelial growth factor receptor targeted therapy emerged as a potential treatment option. In recent years many trials were conducted to find the optimum treatment option with the combination of these targeted agents. The initial trials showed excellent results with minimal morbidity and led to great enthusiasm across the globe to incorporate these regimens as a standard of care. However, subsequently many trials failed to maintain such results and now there is little agreement to the initial results achieved with these drugs. Based on the current evidence we cannot recommend the replacement of cisplatin with targeted therapy in concurrent setting. It may be considered in patients with altered renal parameters, hypersensitivity or intolerance to cisplatin. The addition of targeted therapy in addition to chemotherapy in the concurrent setting can't also be recommended as the benefit is doubtful and is associated with a significant increase in toxicity.

Intracranial fibrosarcoma treated with adjuvant radiation and temozolomide: Report of a case and review of all published cases.

INTRODUCTION: Fibrosarcoma is a rare brain tumour with 33 cases reported so far. However, there is no clear consensus about the nature of the disease and treatment as well as outcome. METHODS: A MEDLINE search was carried out using MESH terms like intracranial fibrosarcoma, intraspinal fibrosarcoma, fibrosarcoma meninges and fibrosarcoma brain. A total of 22 case reports and series reporting a total of 33 cases were identified. We here also report a case treated in our institute with adjuvant radiation and concurrent and maintenance temozolomide. RESULTS: The age of presentation ranged from 2months to 75years (Median=17years). The gender ratio was found to be M:F of 1.75-1. Treatment modalities were described for 17 cases. Surgery was part of treatment in all cases while radiation was a part of treatment in 59% of cases (n=10) and chemotherapy in 29% cases (n=5). Survival data were available only for 8 cases and ranged from 1day to 8years (Median=15.5months). CONCLUSION: Fibrosarcoma is a rare disease with dismal prognosis. Surgery remains the cornerstone of therapy. Radiation confers long term disease control and survival. Chemotherapy needs to be evaluated for these tumours to improve survival.

Breast cancer prevention with anti-estrogens: review of the current evidence and future directions.

There is a potential for reducing the incidence of breast cancer by modifying or changing the reversible risk factors like dietary modifications, modifications in the sedentary life habits, etc. One of such methods which has gained popularity now is chemoprevention. Many agents have been evaluated in the chemoprevention setting in females with increased risk of breast cancers. Metformin, NSAIDS, Bisphosphonates, and statins were evaluated by various investigators with variable results. One of the agents that have been proven to be beneficial in this setting is the anti-estrogens. A major disadvantage of chemoprevention is that unlike prophylactic mastectomy it can never reduce the risk to near zero although it reduces the risk significantly. Another issue is the compliance as chemoprevention with anti-estrogens will need to be continued for 5 years while surgery is a one-time procedure. Another disadvantage is the possible side effects peculiar to each drug used which may not be a significant concern in prophylactic mastectomy group. All these factors must also be kept in mind and properly explained to the patient before starting chemoprevention using anti-estrogens. Here in this review we intend to look into the large randomized controlled trials to quantify the present status of chemoprevention with anti-estrogens.

Invasive lobular carcinoma of the male breast: A rare histology of an uncommon disease.

Male breast carcinoma is a rare malignancy comprising less than 1% of all breast cancers. It is a serious disease with most patients presenting in advanced stages. Infiltrating ductal carcinoma is the most common histology while lobular carcinoma represents less than 1% of all these tumors. We report a case of locally advanced lobular carcinoma of breast in a 60 year old male.

Adjuvant radiotherapy in the treatment of gall bladder carcinoma: What is the current evidence.

Gall bladder carcinoma (GBC) is considered the fifth most common one of the most aggressive gastro intestinal tract malignancies. Owing to their large incidence randomised controlled trials have hardly been conducted to look into their optimum treatment. Over the years surgical resection has been considered the only curative treatment of these tumors. However, the outcome still remains guarded. The predominant pattern of failure is loco-regional followed by systemic. Hence, local adjuvant radiation has been used by different institutes with concurrent and adjuvant chemotherapy. The large retrospective series with their limitations showed improved survival in patients with regional spread or tumors infiltrating the liver when treated with adjuvant radiotherapy. In the present era with modern radiation techniques and target delineation radiation may further improve upon the impact without adding to the toxicity profile. Hence, radiation in gall bladder cancer needs a relook to optimize treatment outcome of such aggressive disease.

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.

Level of awareness of lung cancer risk factors, signs, symptoms and safe practices among college teachers of different states in India: Do awareness programmes have an impact on adoption of safe practices?

UNLABELLED: Lung cancer is the one of the most common cause of cancer mortality among men in India where incidence rates are increasing although they are largely preventable diseases. In India, late presentation is generally responsible for high mortality and morbidity rates and early detection is one of the best ways to control it. The purpose of this study is to measure the level of awareness on lung cancer among women represented by a sample of college teachers in India and the impact of awareness programs in changing or adopting safer practices and the prevention and early detection of the disease. MATERIAL AND METHODS: The assessment was conducted during a Pink Chain Campaign on cancer awareness in 2011 in various women colleges in India. Pre-test related to lung cancer was followed by awareness programs. Posttest using the same questionnaire was conducted at the end of interactive session, at 1 year and 6 months. RESULTS: A total of 156 out of 182 teachers participated in the study (overall response rate was 85.7%). Mean age of the study population was 42.4 years (range- 28-59 yrs). There was a significant increase in level of knowledge regarding lung cancer at 6 months and this was sustained at 1 year. Magazines and newspapers were the primary source for information regarding risk factors, signs and symptoms of lung cancer in more than 60% of teachers whereas more than 30% teachers were educated by doctors. At post-awareness after 1 year and 6 months, there was a significant change in alcohol and smoking habits. The main reasons for not undergoing screening tests are: ignorance (50%), lethargic attitude (44.8 %) and lack of time (34.6 %). CONCLUSION: Knowledge about lung cancer was very low among teachers. Overall awareness of risk factors, signs and symptoms, and screening modalities of lung cancer have improved after 1 year along with practices related to smoking and alcohol consumption. There was a significant improvement in people undergoing regular check-up's. Improved means of communication, access to information and effective warnings about cigarette smoking are necessary to increase public awareness. To ensure the adoption of safe practices in the lifestyle of people who smoke and consume alcohol, awareness programmes such as the pink chain campaign should be conducted regularly, frequently and more widely in various areas of India.

Primary spinal glioblastoma treated with adjuvant radiation and temozolomide: Report of two cases.

Primary spinal glioblastoma multiforme (GBM) is a rare entity, which is invariably associated with poor outcome. Standard treatment is surgery followed by post-operative radiotherapy. Due to paucity of cases role of chemotherapy is investigational. We intend to report two cases of primary spinal GBM treated with radiation and adjuvant temozolomide.

Prevention of Chemotherapy-Induced Nausea and Vomiting in Cancer Patients.

The supportive care of patients receiving antineoplastic treatment has dramatically improved over the past few years and development of effective measures to prevent nausea and vomiting after chemotherapy serves as one of the most important examples of this progress. A patient who starts cancer treatment with chemotherapy lists chemotherapy-induced nausea and vomiting as among their greatest fears. Inadequately controlled emesis impairs functional activity and quality of life, increases the use of health care resources, and may occasionally compromise adherence to treatment. New insights into the pathophysiology of chemotherapy-induced nausea and vomiting, a better understanding of the risk factors for these effects, and the availability of new antiemetic agents have all contributed to substantial improvements in emetic control. This review focuses on current understanding of chemotherapy-induced nausea and vomiting and the status of pharmacological interventions for their prevention and treatment.

Radiation induced heart disease: Pathogenesis, management and review literature.

Radiation therapy (RT) is a very important part of multimodality cancer therapy. Addition of RT improves survival in many cancers, but there are some accompaniments of radiation. One of them is radiation induced heart disease (RIHD). RT for mediastinal lymphoma, breast, lung and oesophageal cancer is associated with the development of RIHD. The problem can be intensified with the addition of chemotherapy. Therapeutic modalities for RIHD are the same as in the non-irradiated population. However, surgery may be difficult in the irradiated patients. The long latent period is the reason why RIHD is not extensively studied. Survival of cancer patients has improved over past few decades, so RIHD is a growing concern especially in younger patients. In this review article, we have discussed the pathogenesis, clinical manifestation and management of RIHD along with impact of chemotherapeutic agents.

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.

Non small cell carcinoma of lung with metachronous breast metastasis and cardiac tamponade: Unusual presentation of a common cancer.

INTRODUCTION: Lung cancer is the most common cause of cancer related death worldwide. Mostly these tumors present with cough, chest pain weight loss. However, presentation as breast mass and cardiac tamponade is very rare. RESULTS: We are presenting a rare case of breast metastasis from primary lung cancer. This case presented as cardiac tamponade adding to the diagnostic dilemma. CONCLUSION: The importance of this case is to highlight molecular profiling as an applicable tool to distinguish extra-mammary metastasis that masquerade as mammary neoplasm thereby preventing unnecessary need of surgery and radiation therapy.

Holocord low grade astrocytoma--Role of radical irradiation and chemotherapy.

Spinal intradural tumors, especially those extending along the entire length of the spinal cord, termed as 'holocord' tumors are uncommon. Most of these are gliomas, with astrocytomas (low grade) predominating in children and ependymomas in adults. Other histologies, though reported, are even rarer. Management is debatable, with both surgery and radiotherapy of such extensive tumors posing challenges. We describe a case of a 14-year-old girl with holocord astrocytoma extending from cervicomedullary junction till lumbar spine, who recovered full neurological function following radical irradiation of entire spine followed by temozolomide-based chemotherapy. No grade 3/4 bone marrow morbidity was seen. Five years following treatment, she maintained normal neurological function and apparently normal pubertal and skeletal growth despite residual disease visible on imaging. Literature review of existing reports of holocord astrocytomas highlighting management and outcome is presented.

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.

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.