A study of soft tissue sarcomas after childhood cancer in Britain

Among 16 541 3-year survivors of childhood cancer in Britain, 39 soft tissue sarcomas (STSs) occurred and 1.1 sarcomas were expected, yielding a standardised incidence ratio (SIR) of 16.1. When retinoblastomas were excluded from the cohort, the SIR for STSs was 15.9, and the cumulative risk of developing a soft tissue tumour after childhood cancer within 20 years of 3-year survival was 0.23%. In the case–control study, there was a significant excess of STSs in those patients exposed to both radiotherapy (RT) and chemotherapy, which was five times that observed among those not exposed (P=0.02). On the basis of individual radiation dosimetry, there was evidence of a strong dose–response effect with a significant increase in the risk of STS with increasing dose of RT (P<0.001). This effect remained significant in a multivariate model. The adjusted risk in patients exposed to RT doses of over 3000 cGy was over 50 times the risk in the unexposed. There was evidence of a dose–response effect with exposure to alkylating agents, the risk increasing substantially with increasing cumulative dose (P=0.05). This effect remained after adjusting for the effect of radiation exposure

AT 2016dah and AT 2017fyp: the first classical novae discovered within a tidal stream

AT2016dah and AT2017fyp are fairly typical Andromeda Galaxy (M31) classical novae. AT2016dah is an almost text book example of a 'very fast' declining, yet uncommon, Fe II'b' (broad-lined) nova, discovered during the rise to peak optical luminosity, and decaying with a smooth broken power-law light curve. AT2017fyp is classed as a 'fast' nova, unusually for M31, its early decline spectrum simultaneously shows properties of both Fe II and He/N spectral types - a 'hybrid'. Similarly, the light curve of AT2017fyp has a broken power-law decline but exhibits an extended flat-topped maximum. Both novae were followed in the UV and X-ray by the Neil Gehrels Swift Observatory, but no X-ray source was detected for either nova. The pair were followed photometrically and spectroscopically into their nebular phases. The progenitor systems were not visible in archival optical data, implying that the mass donors are main sequence stars. What makes AT2016dah and AT2017fyp particularly interesting is their position with respect to M31. The pair are close on the sky but are located far from the centre of M31, lying almost along the semi-minor axis of their host. Radial velocity measurements and simulations of the M31 nova population leads to the conclusion that both novae are members of the Andromeda Giant Stellar Stream (GSS). We find the probability of at least two M31 novae appearing coincident with the GSS by chance is ~1%. Therefore, we claim that these novae arose from the GSS progenitor, not M31 - the first confirmed novae discovered in a tidal steam

Risk of Cerebrovascular Events in 178 962 Five-Year Survivors of Cancer Diagnosed at 15 to 39 Years of Age: The TYACSS (Teenage and Young Adult Cancer Survivor Study)

Background: Survivors of teenage and young adult (TYA) cancer are at risk of cerebrovascular events, but the magnitude of and extent to which this risk varies by cancer type, decade of diagnosis, age at diagnosis and attained age remains uncertain. This is the largest ever cohort study to evaluate the risks of hospitalisation for a cerebrovascular event among long-term survivors of TYA cancer. Methods:The population-based Teenage and Young Adult Cancer Survivor Study (N=178,962) was linked to Hospital Episode Statistics data for England to investigate the risks of hospitalisation for a cerebrovascular event among 5-year survivors of cancer diagnosed when aged 15-39 years. Observed numbers of first hospitalisations for cerebrovascular events were compared to that expected from the general population using standardised hospitalisation ratios (SHR) and absolute excess risks (AER) per 10,000 person-years. Cumulative incidence was calculated with death considered a competing risk. Results: Overall, 2,782 cancer survivors were hospitalised for a cerebrovascular event—40% higher than expected (SHR=1.4, 95% confidence interval [CI]=1.3-1.4). Survivors of central nervous system (CNS) tumours (SHR=4.6, CI=4.3-5.0), head & neck tumours (SHR=2.6, CI=2.2-3.1) and leukaemia (SHR=2.5, CI=1.9-3.1) were at greatest risk. Males had a significantly higher AER than females (AER=7 versus 3), especially among head & neck tumour survivors (AER=30 versus 11). By age 60, 9%, 6% and 5% of CNS tumour, head & neck tumour, and leukaemia survivors, respectively, had been hospitalised for a cerebrovascular event. Beyond age 60, every year 0.4% of CNS tumour survivors were hospitalised for a cerebral infarction (versus 0.1% expected. Whereas at any age, every year 0.2% of head & neck tumour survivors were hospitalised for a cerebral infarction 7 (versus 0.06% expected). Conclusions: Survivors of a CNS tumour, head & neck tumour, and leukaemia are particularly at risk of hospitalisation for a cerebrovascular event. The excess risk of cerebral infarction among CNS tumour survivors increases with attained age. For head & neck tumour survivors this excess risk remains high across all ages. These groups of survivors, and in particular males, should be considered for surveillance of cerebrovascular risk factors and potential pharmacological interventions for cerebral infarction prevention

Second malignant neoplasms after a first cancer in childhood: temporal pattern of risk according to type of treatment

The variation in the risk of solid second malignant neoplasms (SMN) with time since first cancer during childhood has been previously reported. However, no study has been performed that controls for the distribution of radiation dose and the aggressiveness of past chemotherapy, which could be responsible for the observed temporal variation of the risk. The purpose of this study was to investigate the influence of the treatment on the long-term pattern of the incidence of solid SMN after a first cancer in childhood. We studied a cohort of 4400 patients from eight centres in France and the UK. Patients had to be alive 3 years or more after a first cancer treated before the age of 17 years and before the end of 1985. For each patient in the cohort, the complete clinical, chemotherapy and radiotherapy history was recorded. For each patient who had received external radiotherapy, the dose of radiation received by 151 sites of the body were estimated. After a mean follow-up of 15 years, 113 children developed a solid SMN, compared to 12.3 expected from general population rates. A similar distribution pattern was observed among the 1045 patients treated with radiotherapy alone and the 2064 patients treated with radiotherapy plus chemotherapy; the relative risk, but not the excess absolute risk, of solid SMN decreased with time after first treatment; the excess absolute risk increased during a period of at least 30 years after the first cancer. This pattern remained after controlling for chemotherapy and for the average dose of radiation to the major sites of SMN. It also remained when excluding patients with a first cancer type or an associated syndrome known to predispose to SMN. When compared with radiotherapy alone, the addition of chemotherapy increases the risk of solid SMN after a first cancer in childhood, but does not significantly modify the variation of this risk during the time after the first cancer. © 1999 Cancer Research Campaig

Offspring sex ratio and gonadal irradiation in the British Childhood Cancer Survivor Study

We investigated offspring sex ratio among 6232 offspring born to 3218 survivors of childhood cancer in relation to therapeutic irradiation, and pooled our data with those from two other large-scale studies giving a total of 9685 offspring. Exposure to high-dose gonadal irradiation was not associated with a significant alteration in offspring sex ratio compared to low doses (men: P=0.58, women: P=0.66). There was also no evidence that the ratio varied with time since cancer diagnosis when comparing survivors treated with radiotherapy vs those without (men: P=0.51; women: P=0.46). This, the largest study to date, finds no evidence that exposure to radiation affects the offspring sex ratio among survivors of childhood cancer

AT2016dah and AT2017fyp: the first classical novae discovered within a tidal stream

AT 2016dah and AT 2017fyp are fairly typical Andromeda galaxy (M 31) classical novae. AT 2016dah is an almost text book example of a 'very fast' declining, yet uncommon, Fe II'b' (broad-lined) nova, discovered during the rise to peak optical luminosity, and decaying with a smooth broken power-law light curve. AT 2017fyp is classed as a 'fast' nova, unusually for M31, its early decline spectrum simultaneously shows properties of both Fe II and He/N spectral types - a 'hybrid'. Similarly, the light curve of AT 2017fyp has a broken power-law decline but exhibits an extended flat-topped maximum. Both novae were followed in the UV and X-ray by the Neil Gehrels Swift Observatory, but no X-ray source was detected for either nova. The pair were followed photometrically and spectroscopically into their nebular phases. The progenitor systems were not visible in archival optical data, implying that the mass donors are main-sequence stars. What makes AT 2016dah and AT 2017fyp particularly interesting is their position with respect to M31. The pair are close on the sky but are located far from the centre ofM31, lying almost along the semiminor axis of their host. Radial velocity measurements and simulations of the M31 nova population leads to the conclusion that both novae are members of the Andromeda Giant Stellar Stream (GSS). We find the probability of at least two M31 novae appearing coincident with the GSS by chance is similar to 1 per cent. Therefore, we claim that these novae arose from the GSS progenitor, not M31 - the first confirmed novae discovered in a tidal steam

Treatment of severe neutropenia with high-dose pyridoxine in a patient with chronic graft versus host disease and squamous cell carcinoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>The differential diagnosis of neutropenia includes medications, infections, autoimmune diseases, and deficiencies of Vitamin B12 and folate. The association of Vitamin B6 deficiency with severe neutropenia is a rare finding.</p> <p>Case presentation</p> <p>A 51-year-old Caucasian woman presented with fever and profound neutropenia (48 neutrophils/uL). Her clinical history included non-Hodgkin lymphoma, in remission following treatment with allogeneic bone marrow transplantation, quiescent chronic graft-versus-host disease, and squamous cell carcinoma of the skin metastatic to cervical lymph nodes. Medications included atenolol, topical clobetasol, Ditropan (oxybutynin), prophylactic voriconazole, prophylactic valganciclovir, Soriatane (acitretin), and Carac (fluorouracil) cream. The bone marrow was hypocellular without metastatic cancer or myelodysplasia. Neutropenia did not respond to stopping medications that have been associated with neutropenia (valganciclovir, voriconazole and Soriatane) or treatment with antibiotics or granulocyte colony stimulating factor. Blood tests revealed absence of antineutrophil antibodies, normal folate and B12 levels, moderate zinc deficiency and severe Vitamin B6 deficiency. Replacement therapy with oral Vitamin B6 restored blood vitamin levels to the normal range and corrected the neutropenia. Her cervical adenopathy regressed clinically and became negative on scintography following Vitamin B6 therapy and normalization of the blood neutrophil count.</p> <p>Conclusion</p> <p>Severe pyridoxine deficiency can lead to neutropenia. Screening for Vitamin B6 deficiency, along with folate and Vitamin B12 levels, is recommended in patients with refractory neutropenia, especially those with possible malabsorption syndromes, or a history of chronic-graft-versus host disease. Severe neutropenia may facilitate progression of squamous cell carcinoma.</p

Risk of subsequent primary neoplasms in survivors of adolescent and young adult cancer (Teenage and Young Adult Cancer Survivor Study): a population-based, cohort study.

Background Few studies have investigated the risks of subsequent primary neoplasms after adolescent and young adult (AYA) cancer. We investigated the risks of specific subsequent primary neoplasms after each of 16 types of AYA cancer. Methods The Teenage and Young Adult Cancer Survivor Study is a population-based cohort of 200 945 survivors of cancer diagnosed when aged 15–39 years in England and Wales from Jan 1, 1971, to Dec 31, 2006. The cohort was established using cancer registrations from the Office for National Statistics and the Welsh Cancer registry. Follow-up was from 5-year survival until the first occurrence of death, emigration, or study end date (Dec 31, 2012). In this analysis, we focus on the risk of specific subsequent primary neoplasms after 16 types of AYA cancer: breast; cervical; testicular; Hodgkin lymphoma (female); Hodgkin lymphoma (male); melanoma; CNS (intracranial); colorectal; non-Hodgkin lymphoma; thyroid; soft-tissue sarcoma; ovarian; bladder; other female genital; leukaemia; and head and neck cancer. We report absolute excess risks (AERs; per 10 000 person-years) and cumulative incidence of specific types of subsequent primary neoplasm after each type of AYA cancer. Findings During the 2 631 326 person-years of follow-up (median follow-up 16·8 years, IQR 10·5–25·2), 12 321 subsequent primary neoplasms were diagnosed in 11 565 survivors, most frequently among survivors of breast cancer, cervical cancer, testicular cancer, and Hodgkin lymphoma. AERs of any subsequent primary neoplasms were 19·5 per 10 000 person-years (95% CI 17·4–21·5) in survivors of breast cancer, 10·2 (8·0–12·4) in survivors of cervical cancer, 18·9 (16·6–21·1) in survivors of testicular cancer, 55·7 (50·4–61·1) in female survivors of Hodgkin lymphoma, and 29·9 (26·3–33·6) in male survivors of Hodgkin lymphoma. The cumulative incidence of all subsequent primary neoplasms 35 years after diagnosis was 11·9% (95% CI 11·3–12·6) in survivors of breast cancer, 15·8% (14·8–16·7) in survivors of cervical cancer, 20·2% (18·9–21·5) in survivors of testicular cancer, 26·6% (24·7–28·6) in female survivors of Hodgkin lymphoma, and 16·5% (15·2–18·0) in male survivors of Hodgkin lymphoma. In patients who had survived at least 30 years from diagnosis of cervical cancer, testicular cancer, Hodgkin lymphoma in women, breast cancer, and Hodgkin lymphoma in men, we identified a small number of specific subsequent primary neoplasms that account for 82%, 61%, 58%, 45%, and 41% of the total excess number of neoplasms, respectively. Lung cancer accounted for a notable proportion of the excess number of neoplasms across all AYA groups investigated. Interpretation Our finding that a small number of specific subsequent primary neoplasms account for a large percentage of the total excess number of neoplasms in long-term survivors of cervical, breast, and testicular cancer, and Hodgkin lymphoma provides an evidence base to inform priorities for clinical long-term follow-up. The prominence of lung cancer after each of these AYA cancers indicates the need for further work aimed at preventing and reducing the burden of this cancer in future survivors of AYA cancer. Funding Cancer Research UK, National Institute for Health Research, Academy of Medical Sciences, and Children with Cancer UK

Can programme theory be used as a 'translational tool’ to optimise health service delivery in a national early years’ initiative in Scotland: a case study

Background Theory-based evaluation (TBE) approaches are heralded as supporting formative evaluation by facilitating increased use of evaluative findings to guide programme improvement. It is essential that learning from programme implementation is better used to improve delivery and to inform other initiatives, if interventions are to be as effective as they have the potential to be. Nonetheless, few studies describe formative feedback methods, or report direct instrumental use of findings resulting from TBE. This paper uses the case of Scotland’s, National Health Service, early years’, oral health improvement initiative (Childsmile) to describe the use of TBE as a framework for providing feedback on delivery to programme staff and to assess its impact on programmatic action.&lt;p&gt;&lt;/p&gt; Methods In-depth, semi-structured interviews and focus groups with key stakeholders explored perceived deviations between the Childsmile programme 'as delivered’ and its Programme Theory (PT). The data was thematically analysed using constant comparative methods. Findings were shared with key programme stakeholders and discussions around likely impact and necessary actions were facilitated by the authors. Documentary review and ongoing observations of programme meetings were undertaken to assess the extent to which learning was acted upon.&lt;p&gt;&lt;/p&gt; Results On the whole, the activities documented in Childsmile’s PT were implemented as intended. This paper purposefully focuses on those activities where variation in delivery was evident. Differences resulted from the stage of roll-out reached and the flexibility given to individual NHS boards to tailor local implementation. Some adaptations were thought to have diverged from the central features of Childsmile’s PT, to the extent that there was a risk to achieving outcomes. The methods employed prompted national service improvement action, and proposals for local action by individual NHS boards to address this.&lt;p&gt;&lt;/p&gt; Conclusions The TBE approach provided a platform, to direct attention to areas of risk within a national health initiative, and to agree which intervention components were 'core’ to its hypothesised success. The study demonstrates that PT can be used as a 'translational tool’ to facilitate instrumental use of evaluative findings to optimise implementation within a complex health improvement programme.&lt;p&gt;&lt;/p&gt