Developing institutions for cancer care in low-income and middle-income countries: from cancer units to comprehensive cancer centres.

Global cancer centres operate across different sizes, scales, and ecosystems. Understanding the essential aspects of the creation, organisation, accreditation, and activities within these settings is crucial for developing an affordable, equitable, and quality cancer care, research, and education system. Robust guidelines are scarce for cancer units, cancer centres, and comprehensive cancer centres in low-income and middle-income countries. However, some robust examples of the delivery of complex cancer care in centres in emerging economies are available. Although it is impossible to create an optimal system to fit the unique needs of all countries for the delivery of cancer care, we summarise what has been published about the development and management of cancer centres in low-income and middle-income countries so far and highlight the need for clinical and political leadership.

Pattern of care and impact of prognostic factors on the outcome of head and neck extramedullary plasmacytoma: a systematic review and individual patient data analysis of 315 cases.

INTRODUCTION: Head and neck extramedullary plasmacytoma is a rare localized plasma cell neoplasm. We intended to perform this review of the published literature to assess the demographic profile, pattern of care and survival outcomes. METHODS: Two authors independently searched PubMed, Google search and Cochrane library for eligible studies from 1950 till July 1, 2016, published in English language. RESULTS: Median age of the cohort was 57 years (range 11-85). Site-wise distributions were paranasal sinuses 22.3% (70), nasal cavity 17.5% (55), nasopharynx 10.8% (34). Median size of SEMP was 3 cm (range 0.3-12 cm). Treatment distribution was radiotherapy (RT) in 52% (164), surgery (S) 19% (60), chemotherapy (C) 5% (16), S + RT 23.49% (74),CRT 1.9% (6), S + C 0.6% (2), S + RT + C 0.95% (3).Radiation was used as a modality in 78.4%(247), surgery in 44.1%(139), chemotherapy in 4.8%(15). Median radiation dose used was 45 Gy with range 20-61 Gy. Median overall survival (OS) was 40 months (range 0.5-298). Median local progression-free survival was 36 months (range 0-298). Median myeloma relapse-free survival was 36 months (range 0.5-298). Five- and 10-year OS was 78.33 and 68.61%. Five-year cause-specific survival (CSS) and 10-year CSS was 90.15 and 83.31%. Five-year LPFS was 94.78%, and 10-year LPFS was 88.43%. Five-year myeloma progression-free survival was 84.46%, and 10-year myeloma PFS was 80.44%. The factors associated with risk of local relapse were site of disease (sinonasal), secretory EMP, type of treatment received (surgery + RT > RT alone > surgery on univariate analysis). Risk factors for myeloma relapse were coexisting diseases, site of disease (sinonasal), bony erosion, size of lesion > 5 cm and type of treatment received on univariate analysis. CONCLUSION: Our study shows that combined modality S + RT is superior compared to uni-modality in preventing local recurrence. Radiation dose of 45 Gy is optimal. Nodal irradiation has no impact on local recurrence.

Patterns of care and survival outcomes in patients with an extraventricular neurocytoma: An individual patient data analysis of 201 cases.

INTRODUCTION:: Extraventricular neurocytoma is a rare neuronal tumor arising outside the ventricles. However, because of its rarity, its optimum treatment remains undefined. MATERIALS AND METHODS: We intended to perform an individual patient data analysis to examine the patterns of care and prognostic factors involved in the treatment of extraventricular neurocytomas. PubMed, SCOPUS, and Google Scholar were searched with the following MeSH terms: "Neurocytoma, Extra ventricular neurocytoma, Spinal neurocytoma AND treatment, Survival" to find all possible publications pertaining to EVN. RESULTS: From 108 publications, we retrieved 201 patients of extraventricular neurocytoma. Their median age was 30 years (range: 0.6-78 years). Sixty seven patients were in the pediatric (age ≤20 years) age group. There was a bimodal age distribution. Surgical details were available for 132 cases, and 51.5% underwent a gross total resection whereas 41.7% underwent a subtotal resection. Adjuvant radiation was used in 40% cases. For the entire cohort, the median progression free survival was 77 months (53.3-100.7). However, we could not find an impact of any of the prognostic factors on survival. CONCLUSION: An extraventricular neurocytoma is a very rare disease with varied presentations and different sites of origin. Gross total resection remains the standard of care. Adjuvant radiation may be used for salvage. However, radiation therapy after subtotal resection of an atypical neurocytoma may be administered.

Patterns of care and survival outcomes in patients with astroblastoma: an individual patient data analysis of 152 cases.

BACKGROUND: Astroblastoma (AB) is a rare tumor with significant dilemma regarding diagnostic criteria, behavior, and optimum treatment. MATERIALS AND METHODS: We searched PubMed, Google Search, and Cochrane Library for eligible studies with the following search words: astroblastoma, high-grade astroblastoma, and anaplastic astroblastoma till July 1, 2016, published in English language and collected data regarding age, sex, site of disease, pathological grade, treatment received, and survival. RESULTS: Data of 152 patients were retrieved from 63 publications. Median age was 16 years (range 0-71). Females were affected twice more frequently than male (70.3 vs. 29.7%). Tumors were most commonly located in the frontal (39%) followed by parietal lobe (26.7%). Fifty-two and 25% of the patients had headache and seizure at presentation, 76.3% of the patients underwent a gross total resection, 41 out of 89 had a high-grade tumor, and 56 patients received adjuvant radiation with a median dose of 54 Gy (range 20-72). Adjuvant chemotherapy was used in 23 patients. Temozolomide was the most common drug used in 30% of the patients. A combination of cisplatin, etoposide with vincristine, or ifosfamide was used in 17%. Median follow-up duration was 37 months (range 1-238). Median progression-free survival and OS were 36 and 184 months, respectively. Patients with a higher-grade tumor had significantly worse OS with HR 5.260 and p = 0.001. Forty patients experienced local progression. Sixty-five percent patients underwent surgery while 50% underwent radiation as salvage. CONCLUSION: AB has two distinct grades with higher-grade tumors having significantly poor survival. Maximal safe surgery followed by adjuvant radiation and temozolomide should be advocated for these tumors.

Pattern of care and impact of prognostic factors in the outcome of ameloblastic carcinoma: a systematic review and individual patient data analysis of 199 cases.

Ameloblastic carcinoma is a rare locally aggressive odontogenic neoplasm. These tumors are most commonly found to arise from mandible. Because of rarity, there is limited information about the clinical behaviour of such patients. We intended to perform this review of published literature to assess the demographic profile, pattern of care and assess survival outcomes. Two authors independently searched PubMed, Google search, and Cochrane library for eligible studies from 1950 until July 1 2016 published in English language. Data of 199 patients were retrieved from 94 publications for statistical analysis. Median age of the entire cohort was 49 years (range 7-91 years). The analysis revealed that a clear twofold higher incidence in male with male-to-female ratio was 2.4:1 (140:57). Mandible was found to be the commonest tumor location in 66.7% (n = 132) cases followed by maxilla (31.8%) (n = 64). The present analysis revealed that median PFS of 57 months (95% CI 39-120 months) with 5- and 10-year PFS was found to be 47.88 and 29.48%, respectively. Median OS for the entire cohort which was 122 months (95% CI 96-153 months) with 2- and 5-year OS for the entire cohort was 87.16 and 69.08%, respectively. In univariate analysis, patients with an R0 resection were found to have a favourable survival. In addition, patients with localized disease and younger age were found to have a better survival. Adjuvant radiation did not confer any survival advantage. The present analysis revealed excellent outcome for patients treated with an R0 resection. Older patients with high-risk factor may benefit from adjuvant radiation. Role of chemotherapy needs to be evaluated.

Molecular predictive and prognostic factors in ependymoma.

An ependymoma is an uncommon glial tumor, which arises from different parts of the neuroaxis. Considerable variation in presentation and survival in tumors in different locations after an optimum treatment indicates inherent molecular and genetic differences in tumorigenesis between them. A number of genetic aberrations have been identified to distinctly characterize different subgroups of ependymomas that include a posterior fossa tumor, a supratentorial tumor, and a pediatric tumor. These different groups have substantial genetic alterations, and also distinct demography, clinical characteristics, and prognosis. This article is intended to review the diverse molecular and genetic aberrations that may be helpful in prognostication and prediction of survival in patients suffering from an ependymoma.

Delivery of affordable and equitable cancer care in India.

The delivery of affordable and equitable cancer care is one of India's greatest public health challenges. Public expenditure on cancer in India remains below US$10 per person (compared with more than US$100 per person in high-income countries), and overall public expenditure on health care is still only slightly above 1% of gross domestic product. Out-of-pocket payments, which account for more than three-quarters of cancer expenditures in India, are one of the greatest threats to patients and families, and a cancer diagnosis is increasingly responsible for catastrophic expenditures that negatively affect not only the patient but also the welfare and education of several generations of their family. We explore the complex nature of cancer care systems across India, from state to government levels, and address the crucial issues of infrastructure, manpower shortages, and the pressing need to develop cross-state solutions to prevention and early detection of cancer, in addition to governance of the largely unregulated private sector and the cost of new technologies and drugs. We discuss the role of public insurance schemes, the need to develop new political mandates and authority to set priorities, the necessity to greatly improve the quality of care, and the drive to understand and deliver cost-effective cancer care programmes.

The growing burden of cancer in India: epidemiology and social context.

Cancer can have profound social and economic consequences for people in India, often leading to family impoverishment and societal inequity. Reported age-adjusted incidence rates for cancer are still quite low in the demographically young country. Slightly more than 1 million new cases of cancer are diagnosed every year in a population of 1.2 billion. In age-adjusted terms this represents a combined male and female incidence of about a quarter of that recorded in western Europe. However, an estimated 600,000-700,000 deaths in India were caused by cancer in 2012. In age-standardised terms this figure is close to the mortality burden seen in high-income countries. Such figures are partly indicative of low rates of early-stage detection and poor treatment outcomes. Many cancer cases in India are associated with tobacco use, infections, and other avoidable causes. Social factors, especially inequalities, are major determinants of India's cancer burden, with poorer people more likely to die from cancer before the age of 70 years than those who are more affluent. In this first of three papers, we examine the complex epidemiology of cancer, the future burden, and the dominant sociopolitical themes relating to cancer in India.

Cancer research in India: national priorities, global results.

Over the past 20 years, cancer research in India has grown in size and impact. Clinicians, scientists, and government and state policy makers in India have championed cancer research, from studies to achieve low-tech, large-scale health outcomes to some of the most advanced areas of fundamental cancer science. In this paper, we frame public policy discussions about cancer with use of an in-depth analysis of research publications from India. Cancer research in India is a complex environment that needs to balance public policy across many competing agendas. We identify major needs across these environments such as those for increased research capacity and training and protected time for clinical researchers; for more support from states and enhanced collaborative funding programmes from government; for development of national infrastructures across a range of domains (ie, clinical trials, tissue banking, registries, etc); and for a streamlined and rational regulatory environment. We also discuss improvements that should be made to translate research into improvements in cancer outcomes and public health.

A patient-based dosimetric study of intracavitary and interstitial brachytherapy in advanced stage carcinoma of the cervix.

Intracavitary brachytherapy (ICBT) and interstitial brachytherapy (IB) techniques are commonly practiced for treating carcinoma of the cervix, either alone or in combination with external beam radiotherapy. Both these brachytherapy techniques have their own advantages and limitations in terms of tumor coverage and normal tissue sparing. Limited studies have been reported comparing the dosimetric features of these two techniques, especially from a single institution. We carried out a prospective clinical dosimetric comparison between ICBT and IB for patients treated at one center to bring out the inherent dosimetric features of these to two techniques. The study was carried out on 26 patients treated with ICBT and 55 with IB using CT-based planning. Of the 55 patients treated with IB, 27 included tandem source loading (IBT) and 28 without the tandem loading (IBWT). The high-dose volumes covered by 200% and 180% isodose surfaces were considerably larger in ICBT as compared to IB, whereas the treated volume was larger in IB as compared to ICBT. The bladder and rectal doses were the highest in ICBT and IBWT, respectively. The larger treated volume in IB as compared to ICBT was mainly because patients with larger tumor volumes were generally considered for IB. The results also indicated that in interstitial brachytherapy, better rectal sparing was achieved by including the tandem for treatment delivery.

Comparison of high-dose-rate intracavitary brachytherapy dosimetry with and without anesthesia in patients with cervical carcinoma.

This study compares the dosimetry of high-dose-rate intracavitary brachytherapy (HDR-ICBT) performed with and without general anesthesia/spinal anesthesia (GA/SA) in patients with cervical carcinoma. We retrospectively retrieved the records of 138 HDR-ICBT applicator insertions performed in 46 patients: 69 performed with GA/SA (anesthesia group known as AG) in 23 patients, and 69 performed without GA/SA (nonanesthesia group known as NAG) in 23 patients. The intracavitary brachytherapy (ICBT) application was done with central tandem and two vaginal ovoids. For each ICBT plan, a high-dose-rate (HDR) dose of 7 Gy was prescribed to point A. From each plan, the doses to Point B right (B(R)), Point B left (B(L)), bladder and rectal reference points (Bladder(ref) and Rectal(ref)) were recorded and compared in the two groups. Student's t-test was applied to find out the significance of difference. The two groups were comparable in terms of demography and clinical characteristics. Mean Point BL doses in AG and NAG were 1.89 Gy (27% of Point A dose) and 1.82 Gy (26% of Point A dose), respectively. Mean Point BR doses in AG and NAG were 1.91 Gy (27% of Point A dose) and 1.85 Gy (26% of point A), respectively (p-value 0.7). The mean dose to Bladder(ref) in AG and NAG was 5.03 Gy and 4.90 Gy, respectively (p-value 0.6). The mean dose to Rectal(ref) was significantly higher in AG than NAG (5.09 Gy vs. 4.49 Gy, p-value 0.01). Although based on conventional 2D dosimetry planning, our study has demonstrated that avoiding GA/SA does not result in inferior HDR-ICBT dosimetry.

Systematic Review and Individual Patient Data Analysis of Uncommon Variants of Glioblastoma: An Analysis of 196 Cases.

Objectives: Different variant of GBM has been reported viz. Epithelioid Glioblastoma (GBM-E), Rhabdoid GBM (GBM-R), Small cell GBM (GBM-SC), Giant cell GBM (GBM-GC), GBM with neuro ectodermal differentiation (GBM-PNET) with unknown behavior. Materials: We conducted a systematic review and individual patient data analysis of these rare GBM variants. We searched PubMed, google search, and Cochrane library for eligible studies till July 1st 2016 published in English language and collected data regarding age, sex, subtype and treatment received, Progression Free Survival (PFS), Overall Survival (OS). Statistical Package for social sciences (SPSS) v16 software was used for all statistical analysis. Results: We retrieved data of 196 patients with rare GBM subtypes. Among these GBM-GC is commonest (51%), followed by GBM-R (19%), GBM-PNET (13%), GBM-SC (9%) and GBM-E (8%). Median age at diagnosis was 38, 40, 43.5, 69.5 and 18 years, respectively. Male: female ratio was 2:1 for GBM-E, and 1:3 for GBM-SC. Maximal safe resection followed by adjuvant local radiation was used for most of the patients. However, 6 patients with GBM-PNET, 3 each of GBM-E, GBM-SC received adjuvant craniospinal radiation. Out of 88 patients who received chemotherapy, 64 received Temozolomide alone or combination chemotherapy containing Temozolomide. Median PFS and OS for the entire cohort were 9 and 16 months. In univariate analysis, patient with a Gross Total Resection had significantly better PFS and OS compared to those with a Sub Total Resection [23 vs. 13 months (p-0.01)]. Median OS for GBM PNET, GBM-GC, GBM-SC, GBM-R and GBM-E were 32, 18.3, 11, 12 and 7.7 months, respectively (P = 0.001). Interestingly, 31.3%, 37.8% of patients with GBM-E, GBM-R had CSF dissemination. Conclusion: Overall cohort of rarer GBM variant has equivalent survival compared to GBM not otherwise specified. However, epithelioid and Rhabdoid GBM has worst survival and one third shows CSF dissemination.

Rosette Forming Glioneural Tumor Treated with Conformal Radiation.

Rosette forming glioneural tumors (RGNT) are a rare type of low-grade brain tumor included in 2007 in WHO classification. Given the benign nature of the disease, a complete surgical excision has been considered optimum. However, a handful of cases have reported the locally aggressive nature of RGNT. In addition, radiation may also be considered for a tumor located in areas where surgical excision is difficult. We present a similar case, where surgical risk was weighed against resection and we treated the patient with conformal radiation.

Demography, patterns of care, and survival outcomes in patients with salivary duct carcinoma: an individual patient data analysis of 857 patients.

Aim: Salivary duct carcinoma (SDC) is a rare and aggressive malignancy. The optimal treatment protocols are debated. Methodology: A systematic search and individual patient data analysis of published cases of SDC was performed. SPSS v21 was used for statistical analysis. Results: Data of 857 patients available. Median overall survival (OS) and progression-free survival (PFS) of the entire cohort 42 months and 24 months. Nodal involvement, males, primary size >5 cm, androgen receptor (AR) negativity significantly worse OS. Patients with surgery had a favorable median PFS (p = 0.000) and OS (p = 0.077). Patients with adjuvant radiation had better PFS (30 vs 18 months; p = 0.077). Conclusion: SDC has modest survival. Surgery and adjuvant radiation should be advocated for all patients. AR expression appears prognostic for survival.

Consensus guidelines on management of oral potentially malignant disorders.

Oral cancer is usually preceded by oral potentially malignant disorders (OPMDs) and early detection can downstage the disease. The majority of OPMDs are asymptomatic in early stages and can be detected on routine oral examination. Though only a proportion of OPMDs may transform to oral squamous cell carcinoma (OSCC), they may serve as a surrogate clinical lesion to identify individuals at risk of developing OSCC. Currently, there is a scarcity of scientific evidence on specific interventions and management of OPMDs and there is no consensus regarding their management. A consensus meeting with a panel of experts was convened to frame guidelines for clinical practices and recommendations for management strategies for OPMDs. A review of literature from medical databases was conducted to provide the best possible evidence and provide recommendations in management of OPMDs.

Lycopene in treatment of high-grade gliomas: a pilot study.

BACKGROUND: The therapeutic benefit of lycopene is well established for carcinoma prostate in various clinical trials and has been proposed for other malignancies including high-grade gliomas. SETTING AND DESIGN: Randomized placebo control study in the Department of Radiation Oncology of a teaching hospital. MATERIALS AND METHODS: Fifty patients with high-grade gliomas were treated with surgery followed by adjuvant radiotherapy and concomitant paclitaxel. Patients were randomized to receive either oral lycopene (Group A) 8 mg daily with radiotherapy or placebo (Group B). Pre-and post-radiotherapy plasma lycopene levels were measured using high-precision liquid chromatography. McDonald's criteria were used for response assessment. Magnetic resonance imaging (MRI) of brain and Single Photon Emission Computed Tomograph (SPECT) were done three-monthly for two visits and six-monthly thereafter. Primary endpoint was response at six months post radiotherapy. Statistical Analysis Used : The data was analyzed using SPSS Software v10.0 (SPSS corporation Chicago IL) by applying Student's t-test, ANOVA F test, Chi-square test and Karl Pearson Correlation Coefficient. RESULTS: Median age was 38 years. The commonest histology was glioblastoma multiforme (n = 32). Pre- and post-treatment plasma lycopene levels in the patients in Gropu A were 152 ng/ml and 316 ng/ml and in the patients in Group B were 93 ng/ml and 98 ng/ml (P = 0.009). There was non-significant differences in favor of lycopene between Group A and Group B with higher overall response at six months (P = 0.100), response at last follow-up (P = 0.171) and time to progression (40.83 vs. 26.74 weeks, P = 0.089)., The follow-up duration was significantly higher for Group A than Group B (66.29 vs. 38.71 weeks, P = 0.05). CONCLUSIONS: Addition of nutrition supplements such as lycopene may have potential therapeutic benefit in the adjuvant management of high-grade gliomas.

Radiation therapy in paediatric gliomas: our institutional experience.

BACKGROUND AND PURPOSE: The aim of our retrospective study was to analyze the clinical outcome of paediatric glioma patients treated with radiation therapy (RT) in our institution. MATERIAL AND METHODS: We retrieved the case records of all children with gliomas (age < 18 years) who received RT in our department between 2004 and 2007. We analyzed the information regarding patients' demography, clinical details, treatment given, RT details, and survival. The event-free survival (EFS), the period from the date of completion of RT to the date of the event, i.e. death/recurrence, was calculated with respect to age, sex, location of tumour (brainstem vs. non-brainstem), histopathology (low grade vs. high grade), extent of surgical resection, dose and duration of RT, and use of chemotherapy. RESULTS: A total of 70 children with glioma received RT during the above-mentioned period. The 3-year EFS rate for all patients was 44% and the median EFS period was 18 months. The 3-year EFS in patients who underwent surgical decompression and no surgery was 58% and 25%, respectively (p < 0.05). Patients with brainstem lesions had statistically significantly lower 3-year EFS to non-brainstem gliomas (28% vs. 56%, p < 0.01). Chemotherapy use showed no statistically significant trend towards better survival. CONCLUSIONS: RT is an effective modality of treatment in paediatric glioma patients in our setup. Early use of RT in incompletely resected low-grade gliomas is worth revisit-ing. Results of chemotherapy in high-grade glioma and brainstem gliomas are encouraging.

Impact of surgery and adjuvant treatment on the outcome of extraocular sebaceous carcinoma: a systematic review and individual patient's data analysis of 206 cases.

BACKGROUND: Extraocular sebaceous carcinoma (EOSC) is an aggressive malignancy of the sebaceous gland. Surgery is considered the cornerstone of treatment, but there is lack of clarity about extent and adjuvant treatment. METHODS: We conducted a systematic review and analysis of individual patient data of all published cases of EOSC to look into demography, pattern of care, importance of type of surgery, and other adjuvant treatment and survival outcome. A search of PubMed and Google Scholar was done with the key words sebaceous carcinoma, extraocular sebaceous carcinoma, and Muir-Torre syndrome till December 2017. The data were compiled in an Excel chart and analyzed using SPSS IBM software. RESULTS: Data of 206 patients were retrieved. Median age at presentation was 65 years (range: 11-96 years). Surgery was performed in all except 13 patients. Of these 13, eight were deemed inoperable for extensive disease, and five had metastatic disease. Median PFS and OS for the entire cohort were 84 months (95% CI: 10-158 months) and 92 months (95% CI: 59-126 months). Univariate analysis revealed significantly poor survival for patients with a metastatic disease, regional nodal metastasis, and those with Mohs micrographic or incomplete surgery. CONCLUSION: EOSC is a disease of elderly patients with good prognosis. Complete surgery with regional lymph node dissection is standard treatment. The role of adjuvant radiotherapy is debatable but can be considered in patients with incomplete surgery or high-risk factors.

Impact of adjuvant therapy on survival in patients with myoepithelial carcinoma: A systematic review and individual patient data analysis of 691 patients.

INTRODUCTION: Myoepithelial carcinoma (MEC) is an extremely rare low grade salivary gland neoplasm [1-4]. A surgical resection is considered as corner stone of therapy. Role of adjuvant therapy is not clear. METHODOLOGY: We performed systematic review and individual patient data analysis of 691 patients to look into the impact of adjuvant therapy and different prognostic variable for MEC. RESULTS: Data of 691 individual patients were retrieved from 340 publications. Median age of presentation was 56 years (Range: 0-103 years) with a trend of increasing incidence for increase in age. Major salivary glands (36.4%) were the commonest sub-site followed by minor salivary glands, skin and soft tissue, and breast. Median PFS and OS of entire cohort was 48 months (95% CI: 30-65 months) and 167 months (95% CI: 82-251 months). In univariate analysis A R0 resection was associated with significantly better PFS and OS. Median PFS and OS were significantly worse for patients with tumour size >5 cm compared to smaller tumours and for patients with a mitotic index >10/10 high power field (hpf) compared to lower mitotic index. Adjuvant radiation was found to reduce loco-regional recurrence. Adjuvant radiation and chemotherapy both were associated with negative impact on survival in univariate analysis. This negative impact on survival was lost in multivariate analysis. CONCLUSION: MEC appears to be a low grade malignancy with good survival outcome. A R0 resection should be the standard of care. Adjuvant radiation should be considered for patients with adverse risk features to improve loco-regional disease control.