Afatinib versus methotrexate as second-line treatment in Asian patients with recurrent or metastatic squamous cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 3): an open-label, randomised phase III trial.

BACKGROUND: Treatment options are limited for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) following progression after first-line platinum-based therapy, particularly in Asian countries. PATIENTS AND METHODS: In this randomised, open-label, phase III trial, we enrolled Asian patients aged ≥18 years, with histologically or cytologically confirmed recurrent/metastatic HNSCC following first-line platinum-based therapy who were not amenable for salvage surgery or radiotherapy, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0/1. Patients were randomised (2 : 1) to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m2/week), stratified by ECOG performance status and prior EGFR-targeted antibody therapy. The primary end point was progression-free survival (PFS) assessed by an independent central review committee blinded to treatment allocation. RESULTS: A total of 340 patients were randomised (228 afatinib; 112 methotrexate). After a median follow-up of 6.4 months, afatinib significantly decreased the risk of progression/death by 37% versus methotrexate (hazard ratio 0.63; 95% confidence interval 0.48-0.82; P = 0.0005; median 2.9 versus 2.6 months; landmark analysis at 12 and 24 weeks, 58% versus 41%, 21% versus 9%). Improved PFS was complemented by quality of life benefits. Objective response rate was 28% with afatinib and 13% with methotrexate. There was no significant difference in overall survival. The most common grade ≥3 drug-related adverse events were rash/acne (4% with afatinib versus 0% with methotrexate), diarrhoea (4% versus 0%), fatigue (1% versus 5%), anaemia (<1% versus 5%) and leukopenia (0% versus 5%). CONCLUSIONS: Consistent with the phase III LUX-Head & Neck 1 trial, afatinib significantly improved PFS versus methotrexate, with a manageable safety profile. These results demonstrate the efficacy and feasibility of afatinib as a second-line treatment option for certain patients with recurrent or metastatic HNSCC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01856478.

Essure(®) for management of hydrosalpinx prior to in vitro fertilisation-a systematic review and pooled analysis.

BACKGROUND: Hydrosalpinges in infertile women reduce the success of in vitro fertilisation (IVF) by 50%. Surgical management of hydrosalpinges before IVF improves outcome but these procedures are often contraindicated in women with dense pelvic adhesions. Tubal occlusion achieved by Essure(®) via hysteroscopy provides an alternative. OBJECTIVES: To conduct a systematic review on the efficacy and safety of Essure(®) in the management of hydrosalpinx before IVF. SEARCH STRATEGY: We searched MEDLINE (January 1950 to July 2013), EMBASE (January 1980 to July 2013) and Web of Science (1899 to July 2013). We also searched reference lists of relevant articles and proceedings of relevant international conferences (2000-2013). SELECTION CRITERIA: All types of studies where women with suspected infertility and presence of hydrosalpinx had hysteroscopic tubal occlusion with Essure(®) before IVF. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies and extracted data. Where necessary, study authors were contacted for further data. MAIN RESULTS: In all, 115 women in 11 studies received Essure(®) , mainly in the outpatient setting where local anaesthesia by paracervical block and/or intravenous sedation was used. Successful placement of Essure(®) was achieved in 96.5% (95% confidence interval [95% CI] 91.1-98.9%) of women and tubal occlusion in 98.1% (95% CI 93.1-99.9%). Subsequent IVF resulted in 38.6% pregnancy rate (95% CI 30.9-46.8%), 27.9% live birth rate (95% CI 21.1-35.8%) and 28.6% combined ongoing pregnancy and live birth rate (95% CI 21.7-36.6%) per embryo transfer. AUTHOR'S CONCLUSIONS: Essure(®) appears to be an effective option for management of hydrosalpinx in women before IVF although evidence from a randomised controlled clinical trial is lacking.

Patient tracking during treatment of children with cancer in India - An exploratory study.

BACKGROUND: Abandonment of treatment, a major cause of treatment failure in low- and middle-income countries like India, is particularly high during the diagnostic and initial phase of treatment. Tracking of patients during this risk period may reduce treatment abandonment rates and increase quality of care. AIM: The primary aim was to pilot the use and check the acceptability of a tool for tracking children with cancer in New Delhi during the initial part of their treatment. Secondary aim was to estimate abandonment rates among these patients. METHODS: This prospective study was carried out in two centers of North India in New Delhi and enrolled children less than 18 years diagnosed with cancer at these centers and who had registered with Cankids for social support. Parent support group (PSG) workers maintained contact with the child's family at least once a week for the first 12 weeks. Details of each contact and subsequent action were recorded in a customized book (called "You are not alone" or YANA Book). Descriptive analysis of these contacts was done in Microsoft Excel and presented in frequencies and percentages. The five-point Likert scale was used to check the acceptability of the tool among the PSG workers. RESULTS: Seven PSG workers enrolled and tracked 81 patients (73% male with a median age of 6 years). During the 12-week study period, 986 contacts were attempted and three (3.7%) patients had abandoned their treatment. All PSG workers strongly agreed that the YANA book was simple to understand and use, decreased their workload, and helped provide better assistance to patients. CONCLUSION: The tool for patient tracking was well accepted by the PSG workers and considered easy to use. We now plan to implement our model as a routine service at all the partnering hospitals in India.

Geographical and temporal distribution of cancer survival in teenagers and young adults in England.

BACKGROUND: Between 1979 and 2001, an analysis of cancer survival in young people in England, aged 13 to 24 years, showed overall improvements. However, for some diagnostic groups, little or no increases were observed. The aim of this study was to analyse the regional distribution of cancer survival in teenagers and young adults in England in order to identify patterns and potential for improvements at a regional scale. METHODS: We examined geographical and temporal patterns in relative survival in cancer patients aged 13-24 years in England during the time period 1979-2001. Cancer cases were grouped according to an internationally recognised morphology-based diagnostic scheme. RESULTS: For most diagnostic groups, there was little variation in survival between regions, except for testicular germ cell tumours (P=0.006) and colorectal carcinoma (P=0.002). For certain diagnostic groups, the temporal pattern in survival differed between regions. However, in regions that showed poor survival during the early part of the study period, greatest improvements were observed in groups such as acute lymphoid leukaemia, acute myeloid leukaemia, testicular tumours and melanoma. CONCLUSION: In conclusion, there was a reduction in the differences in survival between regions during the study period.

Chronic eosinophilic leukemia with a unique translocation.

We report a case of chronic eosinophilic leukemia in a 9 year old girl who presented with anemia, thrombocytopenia, leucocytosis (mostly dysplastic eosinophils), lymphadenopathy and hepatosplenomegaly. There was no increase in blasts but myelofibrosis was seen in the bone marrow. A previously unreported translocation 46,XX,t(1;4)(q24;q35), was found on cytogenetic analysis and involvement of the myocardium was also present. Shortly after commencing steroids, the family abandoned therapy.

Enzyme replacement therapy in 12 patients with MPS I-H/S with homozygous p.Leu490Pro mutation.

We describe a cohort of 14 Hurler-Scheie patients homozygous for the p.Leu490Pro missense mutation in the alpha-L-iduronidase gene. Now based in the UK, they are all of Pakistani/Kashmiri descent; 64% were female; 11/14 (79%) had a sibling or cousin with MPS I and the parents are consanguineous in all cases. The median age at diagnosis was 1.8 years (range from antenatal diagnosis to 16.5 years). Twelve were on ERT with recombinant human alpha-L-iduronidase (IDUA; Laronidase, Genzyme) for a median duration of 22.5 months (range 2-71 months) and median age at commencement of ERT was 8.6 years (range 0.4-23.1 years). There was clear improvement in the size of liver and spleen as well as reduction in urine glycosaminoglycans (GAGs). The mean (range) urine GAG levels in mg/mmol creatinine were 63.4 (28.9-105.6), 28.3 (10.9-41.4), 22.8 (12.1-43.1), 15.7 (9.2-24.8) and 16.3 (10.1-21.0) at commencement, 3 months post ERT, 6 months post ERT, 12 months post ERT and 24 months post ERT, respectively. Effects on growth were not clear as there does not seem to be an obvious trend of increase or decrease in height after commencement of ERT and this seems to be the case regardless of the age at which ERT was started.

A survey of nutritional practices for children with cancer in India.

BACKGROUND: Assessing nutritional status and delivering optimal nutritional care is a part of modern day treatment of children with cancer. The nutritional practices in India for these children have not been previously described. AIMS: To describe the existing nutrition assessment and management practices for children with cancer in India. METHODS: Attendees of the First International Society of Pediatric Oncology-Pediatric Oncology in Developing Countries workshop on nutrition in children with cancer organized in September 2014 at Tata Memorial Hospital, Mumbai, India were invited to complete a self-administered questionnaire related to three domains: nutritional assessment, intervention, and education. RESULTS: Hundred and eight respondents from 42 health institutions and background in the health sector participated in the survey. There was variability in nutritional assessment, practice and education. Lack of resources and time are contributory. CONCLUSIONS: This assessment of nutritional services in India provided useful information to plan development of national guidelines, policy, and delivery of services.

Burkitt lymphoma of thyroid gland in an adolescent.

Burkitt Lymphoma is a highly aggressive form of non-Hodgkin's lymphoma that in nonendemic areas has abdominal primary sites. We report a very rare case of Burkitt lymphoma of the thyroid gland presenting as a rapidly growing thyroid swelling in a 14-year-old white Caucasian British male with no preexisting thyroid or medical problems. The diagnosis was confirmed by an open wedge biopsy following a fine needle aspiration. The patient was treated according to the Children's Cancer and Leukaemia Group guidelines for BL-Group B protocol and currently is in remission.

Outcomes of hepatoblastoma in the Indian context.

A comprehensive review and critical appraisal of published and grey literature was undertaken to identify current treatment practices and outcomes of children with hepatoblastoma in India. Eight single-centre studies with 157 patients (range five to 36 patients in each study) were included. Pre-operative chemotherapy (mainly cisplatin and doxorubicin) followed by surgical resection and additional chemotherapy was the usual practice. There was no stratification of treatment by risk group in any of the studies. The median event-free survival ranged from 33-100%. The two main reasons for treatment failure were treatment-related mortality (0-50%) and progression of disease (0-30%).

Understanding refusal and abandonment in the treatment of childhood cancer.

Treatment refusal and abandonment is the principal cause of therapy failure in children with cancer in the developing world. A complex interplay of biological, socio-economic and treatment-related factors underlies this problem. Interventions are likely to succeed when they try and address all of these issues simultaneously, as exemplified by the success of twinning programs linking resource-rich and resource-limited countries. Hitherto, there has been no systematic attempt to understand and address this problem in India. Based on the knowledge gained from research in other parts of the developing world, we offer suggestions for dealing with this problem.

Epidemiology of childhood cancer in India.

There has been enormous progress in the treatment of childhood cancer in the developed world and the epidemiology in these countries is well described. Hitherto, there has been no attempt to systematically study the burden of childhood cancer in India or to understand how the occurrence and outcome of the disease varies across the country. We have reviewed the epidemiology (incidence, survival, and mortality) of childhood cancer across different population-based cancer registries in India and also compared it with data from the resource-rich countries. Incidence and mortality data were obtained from the National Cancer Registry Program Reports and the Cancer Incidence in 5 Continents publications. Further, a comprehensive review of medical literature was done for information on individual cancers as well as survival data. 1.6 to 4.8% of all cancer in India is seen in children below 15 years of age and the overall incidence of 38 to 124 per million children, per year, is lower than that in the developed world. The considerable inter-regional variation in incidence and mortality rates across India suggests a possible deficiency in ascertainment of cases and death notification, particularly in rural areas. The marked male preponderance of Hodgkin's disease, lower incidence of central nervous system tumors, and higher incidence of retinoblastoma merit further analysis.