The international scandal of defective asparaginase: A blight on children with cancer.

Acute lymphoblastic leukemia is the commonest form of cancer in children and adolescents worldwide, and asparaginase is an essential component of successful chemotherapy for this disease associated with long-term survival rates often exceeding 90% in high-income countries. Demonstrably defective preparations of asparaginase, distributed from China and India, increase the burden of morbidity and mortality, reducing attainable survival rates. This adverse outcome is enabled by inadequate regulation and oversight, especially in resource-poor settings in low- and middle-income countries where the great majority of children and adolescents with cancer live. The pediatric oncology community must rise to the challenge.

The UK's contribution to cancer control in low-income and middle-income countries.

Cancer mortality rates in low-income and middle-income countries (LMICs) are unacceptably high, requiring both collaborative global effort and in-country solutions. Experience has shown that working together in policy, clinical practice, education, training, and research leads to bidirectional benefit for LMICs and high-income countries. For over 60 years, the UK National Health Service has benefited from recruitment from LMICs, providing the UK with a rich diaspora of trained health-care professionals with links to LMICs. A grassroots drive to engage with partners in LMICs within the UK has grown from the National Health Service, UK academia, and other organisations. This drive has generated a model that rests on two structures: London Global Cancer Week and the UK Global Cancer Network, providing a high-value foundation for international discussion and collaboration. Starting with a historical perspective, this Series paper describes the UK landscape and offers a potential plan for the future UK's contribution to global cancer control. We also discuss the opportunities and challenges facing UK partnerships with LMICs in cancer control. The UK should harness the skills, insights, and political will from all partners to make real progress.

The role of twinning in sustainable care for children with cancer: A TIPPing point? SIOP PODC Working Group on Twinning, Collaboration, and Support.

With the World Health Organization (WHO) Global Initiative for Childhood Cancer, there is renewed interest in sustainable interventions to improve childhood cancer care in low-/middle-income countries (LMICs). Practitioners in LMICs have traditionally practiced "twinning," i.e., targeted international pediatric oncology partnerships (TIPPs) between one or more institutions in a high-income country (HIC) and an LMIC, to improve care for children with cancer in the latter. The International Society of Paediatric Oncology Committee for Paediatric Oncology in Developing Countries Working Group on Twinning, Collaboration, and Support reviewed guidelines from https://cancerpointe.com and the current literature, gathered input from practitioners in LMICs, and in this article discuss the role of TIPPs in the WHO initiative.

Radial artery neuro guide catheter entrapment during mechanical thrombectomy for acute ischemic stroke: Rescue brachial plexus block.

To our knowledge, radial artery catheter entrapment during mechanical thrombectomy for acute ischemic stroke using an 8 F neuro guiding catheter (.088 in ID) and successful use of a brachial plexus block has not been described in the literature. In this technical note, we describe a patient that underwent rapid and successful radial access mechanical thrombectomy for an acute right middle cerebral artery occlusion, however, during withdrawal of the Balt Ballast 0.088 inch long sheath (Balt USA, Irvine, CA, USA), radial/brachial artery entrapment was encountered. We describe a modified step-wise approach to previously published online article by Pitta et al. from 2017 SCAI communication in the management of catheter entrapment and describe the technique for ultrasound guided brachial plexus block, which helped avoid need for surgical removal.

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.

Patient Preference for Transradial Access over Transfemoral Access for Cerebrovascular Procedures.

PURPOSE: Shared decision-making, when physicians and patients collaborate and agree on health care decisions, is a key tenant of patient-centered care. Choice of access site for neurovascular procedures is rarely a shared decision point between physicians and patients. We present our initial evaluation of patient preference for radial over femoral access for cerebrovascular procedures. MATERIALS AND METHODS: IRB approved single-center, prospective, and consecutive survey of all patients undergoing transradial access for cerebrovascular imaging and intervention. Primary inclusion criteria were patients who had previously undergone a transfemoral access procedure and chose to have their second procedure via a transradial approach. All patients underwent pre-procedural neurologic and extremity exams (including Barbeau tests for radial access suitability prior to radial access), post-procedural neurological evaluation and radial access assessment post-procedure, and complete neurological and radial access-site evaluation in the neurointerventional outpatient clinic 1-2 week post-procedure. RESULTS: Twenty five consecutive patients who underwent radial access cerebrovascular procedures after previous femoral access cerebrovascular procedures (16 diagnostic angiograms and 9 interventional procedures) were included. No major complications (including hematomas, infection, or delayed radial artery occlusion) were encountered during the immediate post-procedurral period or on outpatient follow-up (average 8 days). On immediate post-procedural examination, 16% had mild bruising and 24% had mild pain at the radial access site. Of the 25 patients included in this study, 24 strongly preferred radial access over femoral access and reported that, if they needed another procedure, they would prefer radial access. CONCLUSION: There was nearly unanimous patient preference for radial over femoral access for cerebrovascular procedures in this single-center prospective analysis. There were no major complications and no incidences of delayed radial occlusion. In the current age of value-based and patient-centered medicine, the radial approach should be considered for nearly all neurovascular procedures.

The Collaborative Wilms Tumour Africa Project; baseline evaluation of Wilms tumour treatment and outcome in eight institutes in sub-Saharan Africa.

AIM: Reported survival of Wilms tumour in sub-Saharan Africa is below 50%. A published International Society of Pediatric Oncology (SIOP) Pediatric Oncology in Developing Countries (PODC) consensus adapted treatment guideline is implemented as a multi-centre prospective clinical trial at eight centres in sub-Saharan Africa. A baseline evaluation has been done to help decide on priorities to improve outcome and to assess improvements over time. METHODS: A retrospective chart review was performed of patients admitted with Wilms tumour in the three years (2011-2013) preceding the collaborative trial. Patient outcome at the end of treatment was documented for all patients diagnosed in 2011 and 2012. Outcome was classified as (1) alive, no evidence of disease; (2) alive with disease; (3) died during treatment and (4) incomplete treatment. Details on treatment facilities, staff and estimated cost of treatment are documented. RESULTS: Every year 114-130 patients are diagnosed. The mean survival at end of treatment is 39% (69/176) ranging from 11% to 61%. Incomplete treatment is the most common cause of treatment failure with 31% (54/176), ranging from 14% to 48% between centres. Twenty-six percent (46/176) of patients died during treatment, ranging from 13% to 37%. Estimated cost of treatment for parents ranged from 100 US$ to 1100 US$ and was considered an important cause of failure to complete treatment. CONCLUSION: Overall two year survival is estimated at 25%. Prevention of incomplete treatment is possible and will positively affect outcome. Sharing similar local challenges in this regional collaborative project helps to identify and implement feasible, sustainable and successful strategies.

Clinical trials to improve childhood cancer care and survival in sub-Saharan Africa.

Over 80% of children with cancer live in low and middle-income countries where survival rates are much lower than high-income countries. Challenges to successful treatment of paediatric cancers in these countries include late presentation, malnutrition, failure to complete treatment and less-intense supportive care leading to increased treatment-related mortality and the need to reduce the intensity of treatment. Clinical trials can contribute to improved care and survival by providing objective information on the number of patients treated, accuracy of diagnosis, causes of treatment failure and the efficacy of specific interventions. Clinical trials can also help to build capacity (salary support and training), improve facilities (equipment) and fund treatment or essential associated costs (social support, nutritional support and follow-up care). In this article, we discuss our experience with clinical trials in Malawi and sub-Saharan Africa with emphasis on the treatment of children with Wilms tumour.

Young people describe their prediagnosis cancer experience.

OBJECTIVE: Young people often report a protracted journey to diagnosis and frequently report perceived delays. This study was undertaken to increase understanding of the self-reported prediagnosis experiences in young people with a non-haematological cancer, as close as possible to the time of diagnosis. METHODS: Narrative interviews were conducted with 24 young people aged 16-24, 2-4 months from the diagnosis of a solid tumour. Data were analysed to identify whether prediagnosis narratives could be classified according to shared characteristics (typologies) to identify broader contextual issues concerning cancer, and cancer risk perceptions, in this age group. Case notes were also accessed to contextualize and confirm accounts. RESULTS: The main themes, which included a group narrative concerning perspectives of delay, included the impact on an individual's everyday life by symptoms; the role that significant others in young peoples' lives played in the interpretation of symptom significance; the negotiation of entry into, and experiences of, generalist health care; entry into specialist care; and the threshold points that exemplified when events shifted and a diagnosis was eventually obtained. CONCLUSIONS: The narratives reveal complex, and multidimensional explanations for delay with individual and contextual factors contributing. Insights were gained into preventable diagnostic delay; including investigations having been instigated, but not followed up. Each narrative also offered significant insights into how cancer symptoms should be considered within the context of young peoples' lives. This would help prevent signs and symptoms in this age group failing to trigger suspicion and not being treated seriously.

Comparing doctors' and nurses' accounts of how they provide emotional care for parents of children with acute lymphoblastic leukaemia.

OBJECTIVE: Despite the emphasis that communication skills training (CST) programmes place on attending to the emotional care of patients, evidence suggests that practitioners neglect this aspect of patient care. We describe and compare doctors' and nurses' accounts of managing the emotional care of parents of children with leukaemia, with the overall objective of examining how their accounts might inform training and policy. METHODS: Audio-recorded qualitative interviews with 30 doctors and nurses working in six UK paediatric oncology and haematology treatment centres were analysed interpretatively, drawing on the constant comparative method. RESULTS: Doctors' and nurses' descriptions of managing emotional care differed markedly. Doctors described reassuring parents through their ongoing clinical care of the child and by explaining the potentially curative nature of treatment. Doctors did not think they could reassure parents by eliciting and explicitly discussing parents' fears. In contrast, nurses relied on psychological skills and explicit discussion of parents' emotions to provide reassurance. Both doctors and nurses relied on each other to ensure that parents' emotional needs were met by the multidisciplinary team rather than by individual practitioners. CONCLUSION: Nurses' accounts of providing emotional care resembled the emphasis on explicit emotional talk in CST. However, doctors' accounts indicated that they provided emotional care in ways that diverged markedly from expectations in CST but that were more consistent with their biomedical and authoritative role in patient care. These findings may have implications for CST in future revisions of guidelines, but work is first needed to explore parents' perspectives on emotional care.

Brief report on pediatric oncology in Bangladesh.

Cancer in children is emerging as a significant threat to life as deaths from infections and malnutrition have begun to decrease due to concerted maternal and child health initiatives. Efforts are being made to create a comprehensive service for children with Cancer. The major challenges to be overcome are professional and public awareness, late diagnosis, perceptions of incurablity, treatment refusal and abandonment, toxic deaths and drug costs/inconsistent availability.

Subsequent publication rate of studies from India presented at the annual congresses of SIOP.

Subsequent publication as a complete manuscript is a desirable end-point for studies presented at scientific meetings. Between 2001 and 2005, 191 studies from India were presented at annual congresses of the International Society of Paediatric Oncology. Of these 24 (12.6%) were published with a median time to publication of 20 months. This subsequent publication rate is lower than previous reports of SPR for either paediatric or oncological meetings. A lower proportion of oral presentations and randomised clinical trials (RCTs) could partly explain our findings. Further research is needed to understand barriers to subsequent publication of presented data from India.

Faith and protection: the construction of hope by parents of children with leukemia and their oncologists.

BACKGROUND: Oncologists are criticized for fostering unrealistic hope in patients and families, but criticisms reflect a perspective that is oversimplified and "expert" guidance that is ambiguous or impractical. Our aim was to understand how pediatric oncologists manage parents' hope in practice and to evaluate how they address parents' needs. METHODS: Participants were 53 parents and 12 oncologists whom they consulted across six U.K. centers. We audio recorded consultations approximately 1-2, 6, and 12 months after diagnosis. Parents were interviewed after each consultation to elicit their perspectives on the consultation and clinical relationship. Transcripts of consultations and interviews were analyzed qualitatively. RESULTS: Parents needed hope in order to function effectively in the face of despair, and all wanted the oncologists to help them be hopeful. Most parents focused hope on the short term. They therefore needed oncologists to be authoritative in taking responsibility for the child's long-term survival while cushioning parents from information about longer-term uncertainties and being positive in providing information about short-term progress. A few parents who could not fully trust their oncologist were unable to hope. CONCLUSION: Oncologists' pivotal role in sustaining hope was one that parents gave them. Most parents' "faith" in the oncologist allowed them to set aside, rather than deny, their fears about survival while investing their hopes in short-term milestones. Oncologists' behavior generally matched parents' needs, contradicting common criticisms of oncologists. Nevertheless, oncologists need to identify and address the difficulty that some parents have in fully trusting the oncologist and, consequently, being hopeful.

Comparative incidence patterns and trends of gonadal and extragonadal germ cell tumors in England, 1979 to 2003.

BACKGROUND: It is believed that gonadal and extragonadal germ cell tumors (GCTs) arise from primordial germ cells and may have similar etiopathogenesis. Unlike testicular GCTs, there has been limited comprehensive population-based analysis of ovarian and extragonadal GCTs. METHODS: All malignant GCTs and all central nervous system (CNS) GCTs with benign and uncertain behavior that were registered in England in the age group 0 to 84 years from 1979 to 2003 were included in the current study. Incidence rates were calculated and adjusted to the world standard population. RESULTS: There were 33,364 GCTs (92.5% testes, 3.9% ovary, 3.2% extragonadal) in individuals aged 0 to 84 years. The CNS was the most common extragonadal site. An initial peak in incidence at ages 0 to 4 years of nongerminomas was observed at all sites except ovary. Second incidence peaks between ages 10 to 39 years that were more marked among males also were observed at all sites. The ages at these incidence peaks varied by site and were 10 to 14 years (CNS), 15 to 19 years (ovary), 25 to 29 years (other extragonadal sites), and 30 to 34 years (testes). A statistically significant increase in incidence over time was observed in germinomas (testes, CNS) and nongerminomas (testes, ovary). CONCLUSIONS: The age-incidence patterns observed suggested a common initiation of GCTs in embryonic/fetal life with variable rates of tumor progression as a result of subsequent events that may be site specific. The authors concluded that future genetic studies should consider GCTs from all sites to enable a better understanding of their etiology.

Cancer at ages 15-29 years: the contrasting incidence in India and England.

BACKGROUND: There has been a steady increase in published research from Europe and North America on the epidemiology of cancers in young people. There are limited data from the developing world. We contrast the incidence of cancer at ages 15-29 years in India and England. PROCEDURE: Malignant neoplasms in those aged 15-29 years registered during 2001-2003 in five urban population-based cancer registries (PBCRs) of India and in eight PBCRs in England were included. Site-based classification was used. Age-standardized incidence rates were expressed per 100,000 person years. RESULTS: In India, 4,864 (5.8%) of 84,450 cases and in England, 8,137 (1.2%) of 65,6752 cancer cases occurred in those aged 15-29 years. For this age group, the incidence rate for males and females in India were 12.91 and 14.19, and in England were 27.75 and 28.88, respectively. In males aged 15-29 years, the three most common cancers in India were leukemia, lymphoma, and central nervous system tumors and in England were cancers of male genital organs, lymphoma, and leukemia. Cancers of female genital organs, breast, and leukemia were most common in females in India and cancers of female genital organs, lymphoma, and melanoma in England. For cancers of mouth, stomach, and gall bladder, the incidence was higher in India. CONCLUSION: Incidence of cancer at ages 15-29 years in England is higher at most sites than in India. Variation in environmental exposures between the two countries might be an explanation. Under-ascertainment of cases and gender bias in seeking healthcare may also influence reported incidence rates in India.

The contrasting age-incidence patterns of bone tumours in teenagers and young adults: Implications for aetiology.

Bone tumours comprise 0.2% of cancers overall but 5.7% in 15-24 year olds. To explore the relationship with adolescence we have analysed age-incidence patterns of bone tumours in a large national dataset. Data on incident cases of bone tumours in 0-84 year olds in England, 1979-2003, were extracted from national cancer registration data. Incidence rates per million person-years by 5-year age-group, sex, morphology and primary site were calculated and adjusted to the world standard population. Nine thousand one hundred forty-six cases were identified giving an overall age-standardized rate of 7.19 per million person-years. The distribution by morphology was: osteosarcoma, 34.2%; chondrosarcoma, 27.2%; Ewing sarcoma, 19.3%; other, 19.4%. The distribution varied by age. Ewing sarcoma was most common in 0-9 year olds, osteosarcoma in 10-29 year olds and chondrosarcoma in 30-84 year olds. 29.2% of all tumours occurred in 0-24 year olds. Highest incidence of osteosarcoma and Ewing sarcoma in females was in 10-14 year olds. In males, peak incidence occurred at 15-19 years and exceeded that in females. Chondrosarcoma incidence steadily increased with age. The proportions of Ewing sarcomas occurring in respective bones were consistent with those of the adult skeleton by weight. In osteosarcoma tumours of long bones of lower limb were markedly over-represented in the adolescent peak, being six times more than at any other site. Variation in incidence patterns with age and site suggests pubertal bone growth to be a key factor in osteosarcoma while different biological pathways could be relevant for Ewing sarcoma.

How frequently do young people with potential cancer symptoms present in primary care?

BACKGROUND: Although uncommon in teenagers and young adults, cancer is the leading cause of non-accidental death in those aged 15-24 years. A prolonged period to cancer diagnosis in this cohort is reported and thought to be a consequence of the rarity of cancer in this age group, together with the complexity of presenting symptoms. Although diagnostic delay is perceived to be a problem for teenagers and young adults with cancer, little research has focused on their use of primary care services. AIM: To determine how often teenagers and young adults consult, their reasons for doing so, and how often potential oncological symptoms ('alert' symptoms) appear. DESIGN AND SETTING: Retrospective audit of consultations over 1 year. Three general medical practices in Scotland. METHOD: Medical records were examined for 2326 teenagers and young adults. Date of birth, sex, and free-text relating to the consultation were recorded and coded according to an agreed coding system; symptoms of potential oncological significance were coded as alert symptoms. RESULTS: A total of 1659 teenagers and young adults (71.3% of registered patients) attended their GP at least once. Females attended more frequently than males (P < 0.001), and older females more frequently than younger females (P < 0.001). Males exhibited no association between consultation frequency and age. The main reasons for consultation were pregnancy/contraception (15.8%) and infection (15.7%). Alert symptoms were uncommon, (reported in 4.0% of all consultations; 276 alert symptoms in 179 patients), and were not associated with age or sex. The most common alert symptoms were unexplained pain (34.8%), unexplained fatigue (14.5%), and lumps (13.4%). Two benign tumours were detected. CONCLUSION: A high proportion of teenagers and young adults consult their GP. Alert symptoms are uncommon and generally occur in isolation. More research is required to confirm these findings in a larger cohort and to examine how GPs respond to such alert symptoms.