Population-based cancer screening programmes in low-income and middle-income countries: regional consultation of the International Cancer Screening Network in India.

The reductions in cancer morbidity and mortality afforded by population-based cancer screening programmes have led many low-income and middle-income countries to consider the implementation of national screening programmes in the public sector. Screening at the population level, when planned and organised, can greatly benefit the population, whilst disorganised screening can increase costs and reduce benefits. The International Cancer Screening Network (ICSN) was created to share lessons, experience, and evidence regarding cancer screening in countries with organised screening programmes. Organised screening programmes provide screening to an identifiable target population and use multidisciplinary delivery teams, coordinated clinical oversight committees, and regular review by a multidisciplinary evaluation board to maximise benefit to the target population. In this Series paper, we report outcomes of the first regional consultation of the ICSN held in Agartala, India (Sept 5-7, 2016), which included discussions from cancer screening programmes from Denmark, the Netherlands, USA, and Bangladesh. We outline six essential elements of population-based cancer screening programmes, and share recommendations from the meeting that policy makers might want to consider before implementation.

Impact of surgery, adjuvant treatment, and other prognostic factors in the management of anaplastic ganglioglioma.

BACKGROUND/PURPOSE: Anaplastic ganglioglioma (AGG) is a rare tumor with both glial and neuronal component accounting for less than 1% of all CNS tumors with limited information about the optimum treatment and outcome of these tumors. METHOD AND MATERIALS: We did a thorough search of the PubMed with the following MesH terms: "Ganglioglioma; Anaplastic ganglioglioma; Ganglioglioma AND treatment; and Anaplastic ganglioglioma AND survival" to find all possible publications related to AGG to perform an individual patient data analysis and derive the survival outcome and optimum treatment of these tumors. RESULTS: A total of 56 articles were retrieved pertaining to AGG with 88 patients. However, a total of 40 publications found eligible with 69 patients for individual patient data analysis. Median age for the entire cohort was 16 years (range 0.2-77 years). Surgical details were available for 64 patients. A gross total or near total resection was reported in 21 cases (32.8%), subtotal resection or debulking was reported in 25 cases (39.1%). Surgical details were available for 64 patients. A gross total or near total resection was reported in 21 cases (32.8%), and subtotal resection or debulking was reported in 25 cases (39.1%). Median overall survival (OS) was 29 months [95% CI 15.8-42.2 months] with 2- and 5-year OS 61 and 39.4% respectively. CONCLUSION: AGG is associated with a dismal. Pediatric age and a gross total resection of tumor confer a better progression-free survival and OS. Hence, surgery should remain the cornerstone of therapy. However, because of modest survival, there is enough opportunity to improve survival with addition of adjuvant radiation and chemotherapy. A whole genome sequencing and molecular characterization would help to derive the best treatment option.

Radiation induced oral mucositis: a review of current literature on prevention and management.

Oral mucositis (OM) is a major limiting acute side effect of radiotherapy for head and neck cancer. The spectrum of problems associated with mucositis includes oral pain, odynophagia, reduced oral intake, and secondary infections. Incidence of mucositis is increased with addition of concurrent chemotherapy as well as altered fractionation schedules. This leads to treatment interruption and suboptimal disease control. Hence, prevention as well as timely management of OM is necessary for optimum tumor control. We reviewed the English literature with key words "Radiation induced mucositis, Mucositis, Oral Mucositis" to find relevant articles describing incidence, pathophysiology, prophylaxis, and treatment of oral mucositis. Prevention and treatment of OM is an active area of research. Maintenance of oral hygiene is an important part in prevention of OM. A battery of agents including normal saline and alkali (soda bicarbonate) mouth washes, low level laser therapy, and benzydamine (non-steroidal analgesic and anti-inflammatory) have effectiveness in the prevention and treatment of radiation induced oral mucositis. Chlorhexidine mouth gargles are recommended for prevention of chemotherapy induced oral mucositis but is not recommended for radiotherapy associated mucositis. Treatment of co-existing infection is also important and both topical (povidone iodine) and systemic anti fungals should be used judiciously. Radiation induced oral mucositis is a common problem limiting the efficacy of radiation by increasing treatment breaks. Adequate prophylaxis and treatment may limit the severity of radiation mucositis and improve compliance to radiation which may translate in better disease control and survival.

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.

Report from a symposium on catalyzing primary and secondary prevention of cancer in India.

PURPOSE: Oral, breast, and cervical cancers are amenable to early detection and account for a third of India's cancer burden. We convened a symposium of diverse stakeholders to identify gaps in evidence, policy, and advocacy for the primary and secondary prevention of these cancers and recommendations to accelerate these efforts. METHODS: Indian and global experts from government, academia, private sector (health care, media), donor organizations, and civil society (including cancer survivors and patient advocates) presented and discussed challenges and solutions related to strategic communication and implementation of prevention, early detection, and treatment linkages. RESULTS: Innovative approaches to implementing and scaling up primary and secondary prevention were discussed using examples from India and elsewhere in the world. Participants also reflected on existing global guidelines and national cancer prevention policies and experiences. CONCLUSIONS: Symposium participants proposed implementation-focused research, advocacy, and policy/program priorities to strengthen primary and secondary prevention efforts in India to address the burden of oral, breast, and cervical cancers and improve survival.

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.

Indigenously developed multipurpose acrylic head phantom for verification of IMRT using film and gel dosimetry.

The purpose of this study was to validate the newly designed acrylic phantom for routine dosimetric purpose in radiotherapy. The phantom can be used to evaluate and compare the calculated dose and measured dose using film and gel dosimetric methods. In this study, a doughnut-shaped planning target volume (8.54 cm3) and inner organ at risk (0.353 cm3) were delineated for an IMRT test plan using the X-ray CT image of the phantom. The phantom consists of acrylic slabs which are integrated to form a human head with a hole in the middle where several dosimetric inserts can be positioned for measurement. An inverse planning with nine coplanar intensity-modulated fields was created using Pinnacle TPS. For the film analysis, EBT2 film, flatbed scanner, in-house developed MATLAB codes and ImageJ software were used. The 3D dose distribution recorded in the MAGAT gel dosimeter was read using a 1.5 T MRI scanner. Scanning parameters were CPMG pulse sequence with 8 equidistant echoes, TR = 5600, echo step = 22 ms, pixel size = 0.5 × 0.5, slice thickness = 2 mm. Using a calibration relationship between absorbed dose and spin-spin relaxation rate (R2), R2 images were converted to dose images. The dose comparison was accomplished using in-house MATLAB-based graphical user interface named "IMRT3DCMP". For gel measurement dose grid from the TPS was extracted and compared with the measured dose grid of the gel. Gamma index analysis of film measurement for the tolerance criteria of 2%/2mm, 1%/1 mm showed more than 90% voxels pass rate. Gamma index analysis of 3D gel measurement data showed more than 90% voxels pass rate for different tolerance criteria of 2%/2 mm and 1%/1 mm. Overall both 2D and 3D measurement were in close agreement with the Pinnacle TPS calculated dose. The phantom designed is cost-effective and the results are promising, but further investigation is required to validate the phantom with other 3D conformal techniques for dosimetric purpose.

Leveraging epigenetics to enhance the efficacy of cancer-testis antigen: a potential candidate for immunotherapy.

Ovarian cancer is the most lethal gynecological malignancy in women. The phenotype is characterized by delayed diagnosis, recurrence and drug resistance. Inherent immunogenicity potential, oncogenic function and expression of cancer-testis/germline antigen (CTA) in ovarian cancer render them a potential candidate for immunotherapy. Revolutionary clinical findings indicate that tumor antigen-mediated T-cell and dendritic cell-based immunotherapeutic approaches provide an excellent strategy for targeting tumors. Currently, dendritic cell vaccination for the treatment of B-cell lymphoma and CTA-based T-cell receptor transduced T-cell therapy involving MAGE-A4 and NY-ESO-1 are well documented and shown to be effective. This review highlighted the mechanical aspects of epigenetic drugs that can elicit a CTA-based humoral and cellular immune response and implicate T-cell and dendritic cell-based immunotherapeutic approaches.

Despite substantial advancements in prognosis and diagnostic approaches, epithelial ovarian cancer is still the most lethal gynecological malignancy worldwide. In addition to radiotherapy, chemotherapy, hormonal therapy, and surgery, immunotherapy in the clinical setting is promising. Tumor-restricted expression and strong immunogenic potential make cancer-testis/germline antigen (CTA) a potential candidate for efficient T-cell and dendritic cell-mediated cancer immunotherapy. The expression of CTAs is shown to be modulated by a specific epigenetic fine-tuning mechanism. However, the expression and role of CTA in epithelial ovarian cancer immunotherapy are poorly understood. Therefore, in the current work, the authors thoroughly highlight and explore the possible epigenetic mechanisms associated with CTA expression and their implication in T-cell and dendritic cell-based immunotherapy approaches to ovarian cancer. Understanding such a paradigm is essential to adopting a precision medicine approach for better therapeutic options.

Deciphering the impact of missense mutations on structure and dynamics of SMAD4 protein involved in pathogenesis of gall bladder cancer.

Gall bladder cancer (GBC) is the most common malignancy of biliary tract cancer associated with high mortality rate and poor prognosis due to lack of suitable biomarkers. In this study, we explored the structural and functional effects of different missense mutations occurs in SMAD4 that was associated with the development of GBC. We utilized in silico methods to predict the harmful effects of nonsynonymous missense mutations and monitored the stability of protein. We found that all mutations (D351N, G352E, R361C, R361H, E526Q) associated with SMAD4 were deleterious in nature resulting in the formation of deformed or unstable protein structure. Molecular dynamics simulation studies revealed how these mutations affect protein stability, structure, conformation and function. We observed, different mutants increase the compactness and rigidity of SMAD4 protein, alter secondary structure composition, decrease the surface area and protein-ligand interaction and affect its conformation. Findings of current work indicated that the analyzed mutations might affect the structure of protein and its caliber to interact with other molecules, which probably related to functional impairment of SMAD4 upon D351N, G352E, R361C, R361H, E526Q mutations and their involvement in cancer. Hence, the present study has significance of rational drug design and further increase our understanding of GBC development.Communicated by Ramaswamy H. Sarma.

Glioblastoma with Primitive Neuroectodermal Component Treated with Adjuvant Radiotherapy and Temozolomide: A Pooled Analysis of 23 Patients.

AIM: Glioblastoma (GBM) is one of the most aggressive neoplasms of the central nervous system with dismal survival. In recent years, different variants of GBM have been described in the literature. GBM with areas of neuroectodermal differentiation (GBM-PNET) is a relatively new entity in GBM. Presence of the neuroectodermal component increases the propensity of systemic dissemination as with other intracranial primitive neuroectodermal tumors (PNET). The optimal treatment for these patients remains a controversy, with authors reporting local radiotherapy to craniospinal irradiation and chemotherapy. We intend to analyze the pattern of care for GBM with neuroectodermal component. MATERIALS AND METHODS: We retrieved data of four patients with GBM-PNET treated in our institute; data were also retrieved from published series to derive treatment and outcome results. RESULTS: In this series, we report the outcome of a series of four patients of GBM-PNET treated with adjuvant radiotherapy and temozolomide. All but one patient underwent gross total resection of the tumor. Adjuvant hypofractionated radiation with concurrent and adjuvant temozolomide was used in all cases. The median follow-up was 12.9 months in the present series. One patient experienced local recurrence 18 months after the treatment. A review of published literature on GBM-PNET was done; studies with details of patient outcome were used for an independent analysis. Twenty-three patients were identified, and the pooled analysis revealed a median progression free and overall survival of 10 and 25, months respectively. Extent of surgery, local radiation vs. craniospinal irradiation, and age at presentation had no impact on the survival. CONCLUSION: GBM PNET is a new entity with only few cases reported so far. Clinical behavior and treatment outcome of these tumors are not different from conventional GBM. However, these patients are at higher risk of CSF dissemination. Hence, an individualized treatment approach is best suited.

Molecular and genomic landscapes in secondary & therapy related acute myeloid leukemia.

Acute myeloid leukemia (AML) is a complex, aggressive myeloid neoplasm characterized by frequent somatic mutations that influence different functional categories' genes, resulting in maturational arrest and clonal expansion. AML can arise de novo (dn-AML) or can be secondary AML (s-AML) refers to a leukemic process which may arise from an antecedent hematologic disorder (AHD-AML), mostly from a myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) or can be the result of an antecedent cytotoxic chemotherapy or radiation therapy (therapy-related AML, t-AML). Clinical and biological features in secondary and therapy-related AML are distinct from de novo AML. Secondary and therapy-related AML occurs mainly in the elderly population and responds worse to therapy with higher relapse rates due to resistance to cytotoxic chemotherapy. Over the last decade, advances in molecular genetics have disclosed the sub-clonal architecture of secondary and therapy-related AML. Recent investigations have revealed that cytogenetic abnormalities and underlying genetic aberrations (mutations) are likely to be significant factors dictating prognosis and critical impacts on treatment outcome. Secondary and therapy-related AML have a poorer outcome with adverse cytogenetic abnormalities and higher recurrences of unfavorable mutations compared to de novo AML. In this review, we present an overview of the clinical features of secondary and therapy-related AML and address the function of genetic mutations implicated in the pathogenesis of secondary leukemia. Detailed knowledge of the pathogenetic mechanisms gives an overview of new prognostic markers, including targetable mutations that will presumably lead to the designing and developing novel molecular targeted therapies for secondary and therapy-related AML. Despite significant advances in knowing the genetic aspect of secondary and therapy-related AML, its influence on the disease's pathophysiology, standard treatment prospects have not significantly evolved during the past three decades. Thus, we conclude this review by summarizing the modern and developing treatment strategies in secondary and therapy-related acute myeloid leukemia.

Practical Consensus Recommendations for Optimizing Risk versus Benefit of Chemotherapy in Patients with HR Positive Her2 Negative Early Breast Cancer in India.

Breast cancer is a public health challenge globally as well as in India. Improving outcome and cure requires appropriate biomarker testing to assign risk and plan treatment. Because it is documented that significant ethnic and geographical variations in biological and genetic features exist worldwide, such biomarkers need to be validated and approved by authorities in the region where these are intended to be used. The use of western guidelines, appropriate for the Caucasian population, can lead to inappropriate overtreatment or undertreatment in Asia and India. A virtual meeting of domain experts discussed the published literature, real-world practical experience, and results of opinion poll involving 185 oncologists treating breast cancer across 58 cities of India. They arrived at a practical consensus recommendation statement to guide community oncologists in the management of hormone positive (HR-positive) Her2-negative early breast cancer (EBC). India has a majority (about 50%) of breast cancer patients who are diagnosed in the premenopausal stage (less than 50 years of age). The only currently available predictive test for HR-positive Her2-negative EBC that has been validated in Indian patients is CanAssist Breast. If this test gives a score indicative of low risk (< 15.5), adjuvant chemotherapy will not increase the chance of metastasis-free survival and should not be given. This is applicable even during the ongoing COVID-19 pandemic.

South Asian Declaration-Consensus Guidelines for COVID-19 Vaccination in Cancer Patients.

We provide the South Asian Declaration, containing the consensus guidelines for coronavirus disease 2019 (COVID-19) vaccination in cancer patients.

Molecular update on biology of Wilms Tumor 1 gene and its applications in acute myeloid leukemia.

Wilms tumor gene 1 (WT1) is an important gene which is involved in growth and development of many organs. It is identified as a tumor suppressor gene in nephroblastoma. However, its role as a tumor oncogene has been highlighted by many studies in haematological as well as non haematological malignant neoplasm. The expression of WT1 on leukemic blast cells sensitised us to explore its impact on neoplastic phenomenon. WT1 is has been found both mutated as well as over expressed in different subsets of acute myeloid leukemia (AML). WT1 is a gene has been used as a biomarker for diagnosis, monitoring of minimal residual disease (MRD) and detection of relapse for molecular remission in AML. It also has potential of being a predictive molecular predictive biomarker for the treatment of leukemic cases after allogeneic transplantation. The WT1 specific expression on blast cells and its interaction with cytotoxic T cell has also been explored for its potential usage WT1 based immunotherapy. Here, we are reviewing molecular updates of WT1 gene and discuss its potential clinical applications as a predictive molecular biomarker for diagnosis, as MRD detection and as immunotherapy in AML.

A systematic review with in silico analysis on transcriptomic profile of gallbladder carcinoma.

Gallbladder cancer (GBC) is an aggressive malignancy of the biliary tract. It is asymptomatic in its early stages, and often, characterized by a poor prognosis and worse treatment response. Distribution of GBC shows both geographical as well as ethnic variations. Several studies have elucidated the differential gene expression profile between the normal gallbladder and GBCs, with varied but inconsistent results. Thus, a deep understanding of the expression profile of GBC might aid in the identification of potential biomarkers, which would further help in better disease management and appropriate therapy selection. This review summarizes studies on the transcriptomic profile of GBC with emphasis on studies pertaining to coding (mRNA) and noncoding (micro and long noncoding) RNA along with aberrant promoter methylation studies, ranging from a single gene to global gene to high throughput RNA sequencing approaches, published between 2000 to May, 2019. In addition, data mining of GBC from the available public functional genomics data repository at Gene Expression Omnibus has been done to rule out potentially important dysregulated genes in this malignancy. To the best of our knowledge, this is the first article to shed light on the RNA based gene regulatory network(s) along with bioinformatic analysis. Moreover, this review represents major research challenges and ambiguity, knowledge of which is a must for establishing molecular/ clinical biomarkers for early GBC diagnosis, management, and treatment protocols.

Indian clinical practice consensus guidelines for the management of squamous cell carcinoma of head and neck.

Head and neck cancers (HNCs) are malignant tumors of the upper aerodigestive tract and are the sixth most common cancer worldwide. In India, around 30-40% of all cancers are HNCs. Even though there are global guidelines or recommendations for the management of HNCs, these may not be appropriate for Indian scenarios. In an effort to discuss current practices, latest developments and to come to a consensus to recommend management strategies for different anatomical subsites of HNCs for Indian patients, a group of experts (medical, surgical and radiation oncologists and dentists) was formed. A review of literature from medical databases was conducted to provide the best possible evidence base, which was reviewed by experts during a consensus group meeting (January, 2019) to provide recommendations.

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.

Total skin electron irradiation treatment for mycosis fungoides with a new alternate daily treatment schedule to minimize radiation-associated toxicity: a preliminary experience.

Conventional total skin electron irradiation (TSEI) for mycosis fungoides (MF) causes radiation toxicity, requiring treatment interruptions that prolong the treatment period, making patient compliance poor. We evaluated an alternate daily treatment schedule of TSEI, using a high dose rate (HDR) to minimize radiation toxicity and shorten the treatment duration. Four patients (aged 45-73 years with MF duration of 7-22 months) were treated by TSEI using HDR. The treatment was given on 5 days/week for 2 weeks followed by treatment on alternate days to deliver a total dose of 36 Gy. All the patients completed treatment in 10 weeks and had complete remission. Radiation toxicity was much less common with this schedule, requiring no treatment interruption. All the patients were until in remission after 60-84 months of follow-up. This schedule of TSEI treatment caused minimal radiation toxicity and allowed completion of treatment over a shorter period, giving good clinical remission and prolonged disease-free survival.