Infertility and risk of breast cancer in men: a national case-control study in England and Wales.

PURPOSE: Breast cancer is uncommon in men and its aetiology is largely unknown, reflecting the limited size of studies thus far conducted. In general, number of children fathered has been found a risk factor inconsistently, and infertility not. We therefore investigated in a case-control study, the relation of risk of breast cancer in men to infertility and number of children. PATIENTS AND METHODS: We conducted a national case-control study in England and Wales, interviewing 1998 cases incident 2005-17 and 1597 male controls, which included questions on infertility and offspring. RESULTS: Risk of breast cancer was statistically significantly associated with male-origin infertility (OR = 2.03 (95% confidence interval (CI) 1.18-3.49)) but not if a couple's infertility had been diagnosed as of origin from the female partner (OR = 0.86 (0.51-1.45)). Risk was statistically significantly raised for men who had not fathered any children (OR = 1.50 (95% CI 1.21-1.86)) compared with men who were fathers. These associations were statistically significantly present for invasive tumours but not statistically significant for in situ tumours. CONCLUSION: Our data give strong evidence that risk of breast cancer is increased for men who are infertile. The reason is not clear and needs investigation.

Risk of breast cancer in men in relation to weight change: A national case-control study in England and Wales.

Breast cancer is uncommon in men and knowledge about its causation limited. Obesity is a risk factor but there has been no investigation of whether weight change is an independent risk factor, as it is in women. In a national case-control study, 1998 men with breast cancer incident in England and Wales during 2005 to 2017 and 1597 male controls were interviewed about risk factors for breast cancer including anthropometric factors at several ages. Relative risks of breast cancer in relation to changes in body mass index (BMI) and waist/height ratios at these ages were obtained by logistic regression modelling. There were significant trends of increasing breast cancer risk with increase in BMI from age 20 to 40 (odds ratio [OR] 1.11 [95% confidence interval (CI) 1.05-1.17] per 2 kg/m2 increase in BMI; P < .001), and from age 40 to 60 (OR 1.12 [1.04-1.20]; P = .003), and with increase in self-reported adiposity compared to peers at age 11 to BMI compared with peers at age 20 (OR 1.19 [1.09-1.30]; P < .001). Increase in waist/height ratio from age 20 to 5 years before diagnosis was also highly significantly associated with risk (OR 1.13 [1.08-1.19]; P < .001). The associations with increases in BMI and waist/height ratio were significant independently of each other and of BMI or waist/height ratio at the start of the period of change analysed, and effects were similar for invasive and in situ tumours separately. Increases in BMI and abdominal obesity are each risk factors for breast cancer in men, independently of obesity per se. These associations might relate to increasing oestrogen levels with weight gain, but this needs investigation.

Genetic susceptibility to radiation-induced breast cancer after Hodgkin lymphoma.

Female Hodgkin lymphoma (HL) patients treated with chest radiotherapy (RT) have a very high risk of breast cancer. The contribution of genetic factors to this risk is unclear. We therefore examined 211 155 germline single-nucleotide polymorphisms (SNPs) for gene-radiation interaction on breast cancer risk in a case-only analysis including 327 breast cancer patients after chest RT for HL and 4671 first primary breast cancer patients. Nine SNPs showed statistically significant interaction with RT on breast cancer risk (false discovery rate, <20%), of which 1 SNP in the PVT1 oncogene attained the Bonferroni threshold for statistical significance. A polygenic risk score (PRS) composed of these SNPs (RT-interaction-PRS) and a previously published breast cancer PRS (BC-PRS) derived in the general population were evaluated in a case-control analysis comprising the 327 chest-irradiated HL patients with breast cancer and 491 chest-irradiated HL patients without breast cancer. Patients in the highest tertile of the RT-interaction-PRS had a 1.6-fold higher breast cancer risk than those in the lowest tertile. Remarkably, we observed a fourfold increased RT-induced breast cancer risk in the highest compared with the lowest decile of the BC-PRS. On a continuous scale, breast cancer risk increased 1.4-fold per standard deviation of the BC-PRS, similar to the effect size found in the general population. This study demonstrates that genetic factors influence breast cancer risk after chest RT for HL. Given the high absolute breast cancer risk in radiation-exposed women, these results can have important implications for the management of current HL survivors and future patients.

Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma.

To further our understanding of inherited susceptibility to Hodgkin lymphoma (HL), we performed a meta-analysis of 7 genome-wide association studies totaling 5325 HL cases and 22 423 control patients. We identify 5 new HL risk loci at 6p21.31 (rs649775; P = 2.11 × 10-10), 6q23.3 (rs1002658; P = 2.97 × 10-8), 11q23.1 (rs7111520; P = 1.44 × 10-11), 16p11.2 (rs6565176; P = 4.00 × 10-8), and 20q13.12 (rs2425752; P = 2.01 × 10-8). Integration of gene expression, histone modification, and in situ promoter capture Hi-C data at the 5 new and 13 known risk loci implicates dysfunction of the germinal center reaction, disrupted T-cell differentiation and function, and constitutive NF-κB activation as mechanisms of predisposition. These data provide further insights into the genetic susceptibility and biology of HL.

Radiologic features of breast cancer after mantle radiation therapy for Hodgkin disease: a study of 230 cases.

PURPOSE: To retrospectively review diagnostic mammography in women diagnosed with breast cancer who previously had mantle field radiation therapy for Hodgkin disease in England and Wales over a period of 30 years. MATERIALS AND METHODS: From a national cohort study of 5002 women treated with supradiaphragmatic radiation therapy when they were younger than 36 years (mean, 22.1 years) during 1956-2003, 392 patients developed breast cancer. With ethics committee approval and informed consent, mammograms were obtained that showed 230 tumors in 222 (56.6%) patients from 95 hospitals, and the size and appearance of each carcinoma was recorded by two breast radiologists. Comparison was made with a historical report of more than 1000 general-population breast cancers by using Pearson χ(2) test. RESULTS: Thirty-eight tumors were occult on mammograms. Mean tumor maximum diameter was 12.3 mm (n = 81) on oblique view. The quadrant distribution of the tumors was significantly different (P < .001) from the historic controls, and chest radiation therapy patients had a greater proportion of tumors in the upper outer (66.9% [107 of 160] vs 48.7% [385 of 784]) and, to a lesser extent, lower inner (10.6% [17 of 160] vs 7.8% [61 of 784]) quadrants. The dominant radiologic feature was of an irregular mass (56.8% [109 of 192]) followed by microcalcifications (25.0% [48 of 192]). CONCLUSION: This study suggests that in patients who previously underwent mantle radiation therapy for Hodgkin disease, breast cancers are more commonly seen within the upper outer quadrants than are cancers in the general population. Poorly defined masses were the most common appearance.

FGFR2 genotype and risk of radiation-associated breast cancer in Hodgkin lymphoma.

Women treated at young ages with supradiaphragmatic radiotherapy for Hodgkin lymphoma (HL) have a highly increased risk of breast cancer. For personalized advice and follow-up regimens for patients, information is needed on how the radiotherapy-related risk is affected by other breast cancer risk factors. Genome-wide association studies have identified 14 independently replicated common single nucleotide polymorphisms that influence breast cancer risk. To examine whether these variants contribute to risk of radiation-associated breast cancer in HL, we analyzed 2 independent case-control series, from the United Kingdom and The Netherlands, totaling 693 HL patients, 232 with breast cancer and 461 without. rs1219648, which annotates the FGFR2 gene, was associated with risk in both series (combined per-allele odds ratio = 1.59, 95% confidence interval: 1.26-2.02; P = .000111). These data provide evidence that genetic variation in FGFR2 influences radiation-induced breast cancer risk.

Genetic variants at chromosomes 2q35, 5p12, 6q25.1, 10q26.13, and 16q12.1 influence the risk of breast cancer in men.

Male breast cancer accounts for approximately 1% of all breast cancer. To date, risk factors for male breast cancer are poorly defined, but certain risk factors and genetic features appear common to both male and female breast cancer. Genome-wide association studies (GWAS) have recently identified common single nucleotide polymorphisms (SNPs) that influence female breast cancer risk; 12 of these have been independently replicated. To examine if these variants contribute to male breast cancer risk, we genotyped 433 male breast cancer cases and 1,569 controls. Five SNPs showed a statistically significant association with male breast cancer: rs13387042 (2q35) (odds ratio (OR)  = 1.30, p = 7.98×10⁻4), rs10941679 (5p12) (OR = 1.26, p = 0.007), rs9383938 (6q25.1) (OR = 1.39, p = 0.004), rs2981579 (FGFR2) (OR = 1.18, p = 0.03), and rs3803662 (TOX3) (OR = 1.48, p = 4.04×10⁻6). Comparing the ORs for male breast cancer with the published ORs for female breast cancer, three SNPs--rs13387042 (2q35), rs3803662 (TOX3), and rs6504950 (COX11)--showed significant differences in ORs (p<0.05) between sexes. Breast cancer is a heterogeneous disease; the relative risks associated with loci identified to date show subtype and, based on these data, gender specificity. Additional studies of well-defined patient subgroups could provide further insight into the biological basis of breast cancer development.

Multiple Hodgkin lymphoma-associated loci within the HLA region at chromosome 6p21.3.

Since an association between the human leukocyte antigen (HLA) region and Hodgkin lymphoma (HL) was first reported in 1967, many studies have reported associations between HL risk and both single nucleotide polymorphism (SNP) and classic HLA allele variation in the major histocompatibility complex. However, population stratification and the extent and complexity of linkage disequilibrium within the major histocompatibility complex have hindered efforts to fine-map causal signals. Using SNP data to impute alleles at classic HLA loci, we have conducted an integrated analysis of HL risk within the HLA region in 582 early-onset HL cases and 4736 controls. We confirm that the strongest signal of association comes from an SNP located in the class II region, rs6903608 (odds ratio [OR] = 1.79, P = 6.63 × 10(-19)), which is unlikely to be driven by association to HLA-DRB, DQA, or DQB alleles. In addition, we identify independent signals at rs2281389 (OR = 1.73, P = 6.31 × 10(-13)), a SNP that maps closely to HLA-DPB1, and the class II HLA allele DQA1*02:01 (OR = 0.56, P = 1.51 × 10(-7)). These data suggest that multiple independent loci within the HLA class II region contribute to the risk of developing early-onset HL.

Exome sequencing reveals germline NPAT mutation as a candidate risk factor for Hodgkin lymphoma.

A strong clustering of Hodgkin lymphoma in certain families has been long acknowledged. However, the genetic factors in the background of familial Hodgkin lymphoma are largely unknown. We have studied a family of 4 cousins with a rare subtype of the disease, nodular lymphocyte predominant Hodgkin lymphoma. We applied exome sequencing together with genome-wide linkage analysis to this family and identified a truncating germline mutation in nuclear protein, ataxia-telangiectasia locus (NPAT) gene, which segregated in the family. We also studied a large number of samples from other patients with Hodgkin lymphoma, and a germline variation leading to the deletion of serine 724 was found in several cases suggesting an elevated risk for the disease (odds ratio = 4.11; P = .018). NPAT is thus far the first gene implicated in nodular lymphocyte predominant Hodgkin lymphoma predisposition.

Oxygen-enhanced MRI and radiotherapy in patients with oropharyngeal squamous cell carcinoma.

Background and purpose: This study aimed to assess the role of T1 mapping and oxygen-enhanced MRI in patients undergoing radical dose radiotherapy for HPV positive oropharyngeal cancer, which has not yet been examined in an OE-MRI study. Materials and methods: Variable Flip Angle T1 maps were acquired on a 3T MRI scanner while patients (n = 12) breathed air and/or 100 % oxygen, before and after fraction 10 of the planned 30 fractions of chemoradiotherapy ('visit 1' and 'visit 2', respectively). The analysis aimed to assess to what extent (1) native R1 relates to patient outcome; (2) OE-MRI response relates to patient outcome; (3) changes in mean R1 before and after radiotherapy related to clinical outcome in patients with oropharyngeal squamous cell carcinoma. Results: Due to the radiotherapy being largely successful, the sample sizes of non-responder groups were small, and therefore it was not possible to properly assess the predictive nature of OE-MRI. The tumour R1 increased in some patients while decreasing in others, in a pattern that was overall consistent with the underlying OE-MRI theory and previously reported tumour OE-MRI responses. In addition, we discuss some practical challenges faced when integrating this technique into a clinical trial, with the aim that sharing this is helpful to researchers planning to use OE-MRI in future clinical studies. Conclusion: Altogether, these results suggest that further clinical OE-MRI studies to assess hypoxia and radiotherapy response are worth pursuing, and that there is important work to be done to improve the robustness of the OE-MRI technique in human applications in order for it to be useful as a widespread clinical technique.

Using Variable Flip Angle (VFA) and Modified Look-Locker Inversion Recovery (MOLLI) T1 mapping in clinical OE-MRI.

BACKGROUND AND PURPOSE: The imaging technique known as Oxygen-Enhanced MRI is under development as a noninvasive technique for imaging hypoxia in tumours and pulmonary diseases. While promising results have been shown in preclinical experiments, clinical studies have mentioned experiencing difficulties with patient motion, image registration, and the limitations of single-slice images compared to 3D volumes. As clinical studies begin to assess feasibility of using OE-MRI in patients, it is important for researchers to communicate about the practical challenges experienced when using OE-MRI on patients to help the technique advance. MATERIALS AND METHODS: We report on our experience with using two types of T1 mapping (MOLLI and VFA) for a recently completed OE-MRI clinical study on oropharyngeal squamous cell carcinoma. RESULTS: We report: (1) the artefacts and practical difficulties encountered in this study; (2) the difference in estimated T1 from each method used - the VFA T1 estimation was higher than the MOLLI estimation by 27% on average; (3) the standard deviation within the tumour ROIs - there was no significant difference in the standard deviation seen within the tumour ROIs from the VFA versus MOLLI; and (4) the OE-MRI response collected from either method. Lastly, we collated the MRI acquisition details from over 45 relevant manuscripts as a convenient reference for researchers planning future studies. CONCLUSION: We have reported our practical experience from an OE-MRI clinical study, with the aim that sharing this is helpful to researchers planning future studies. In this study, VFA was a more useful technique for using OE-MRI in tumours than MOLLI T1 mapping.

Obesity and Breast Cancer Risk in Men: A National Case-Control Study in England and Wales.

Background: Breast cancer is rare in men, and information on its causes is very limited from studies that have generally been small. Adult obesity has been shown as a risk factor, but more detailed anthropometric relations have not been investigated. Methods: We conducted an interview population-based case-control study of breast cancer in men in England and Wales including 1998 cases incident during 2005-2017 at ages younger than 80 years and 1597 male controls, with questions asked about a range of anthropometric variables at several ages. All tests of statistical significance were 2-sided. Results: Risk of breast cancer statistically significantly increased with increasing body mass index (BMI) at ages 20 (odds ratio [OR] = 1.07, 95% confidence interval [CI] = 1.02 to 1.12 per 2-unit change in BMI), 40 (OR = 1.11, 95% CI = 1.07 to 1.16), and 60 (OR = 1.14, 95% CI = 1.09 to 1.19) years, but there was also an indication of raised risk for the lowest BMIs. Large waist circumference 5 years before interview was more strongly associated than was BMI with risk, and each showed independent associations. Associations were similar for invasive and in situ tumors separately and stronger for HER2-positive than HER2-negative tumors. Of the tumors, 99% were estrogen receptor positive. Conclusions: Obesity at all adult ages, particularly recent abdominal obesity, is associated with raised risk of breast cancer in men, probably because of the conversion of testosterone to estrogen by aromatase in adipose tissue. The association is particularly strong for HER2-expressing tumors.

Common Susceptibility Loci for Male Breast Cancer.

BACKGROUND: The etiology of male breast cancer (MBC) is poorly understood. In particular, the extent to which the genetic basis of MBC differs from female breast cancer (FBC) is unknown. A previous genome-wide association study of MBC identified 2 predisposition loci for the disease, both of which were also associated with risk of FBC. METHODS: We performed genome-wide single nucleotide polymorphism genotyping of European ancestry MBC case subjects and controls in 3 stages. Associations between directly genotyped and imputed single nucleotide polymorphisms with MBC were assessed using fixed-effects meta-analysis of 1380 cases and 3620 controls. Replication genotyping of 810 cases and 1026 controls was used to validate variants with P values less than 1 × 10-06. Genetic correlation with FBC was evaluated using linkage disequilibrium score regression, by comprehensively examining the associations of published FBC risk loci with risk of MBC and by assessing associations between a FBC polygenic risk score and MBC. All statistical tests were 2-sided. RESULTS: The genome-wide association study identified 3 novel MBC susceptibility loci that attained genome-wide statistical significance (P < 5 × 10-08). Genetic correlation analysis revealed a strong shared genetic basis with estrogen receptor-positive FBC. Men in the top quintile of genetic risk had a fourfold increased risk of breast cancer relative to those in the bottom quintile (odds ratio = 3.86, 95% confidence interval = 3.07 to 4.87, P = 2.08 × 10-30). CONCLUSIONS: These findings advance our understanding of the genetic basis of MBC, providing support for an overlapping genetic etiology with FBC and identifying a fourfold high-risk group of susceptible men.

IRF4 polymorphism rs872071 and risk of Hodgkin lymphoma.

The reciprocal familial risk between chronic lymphocytic leukaemia (CLL) and Hodgkin lymphoma (HL) suggests genetic variants with pleiotropic effects may influence the risk of both CLL and HL. We have recently shown that the IRF4 variant rs872071 influences CLL risk. To examine if rs872071 genotype is associated with HL risk we genotyped two case-control series (totalling, 529 and 2192, respectively). This analysis provides evidence that IRF4 rs872071 influences HL risk; Odds Ratio = 1.21 (95% confidence interval: 1.05-1.39, P = 0.009) and highlights the importance of inherited variation in B-cell developmental genes in the development of HL.

Stereotactic body radiotherapy for moderately central and ultra-central oligometastatic disease: Initial outcomes.

BACKGROUND: Delivery of SBRT to central thoracic tumours within 2 cm of the proximal bronchial tree (PBT), and especially ultra-central tumours which directly abut the PBT, has been controversial due to concerns about high risk of toxicity and treatment-related death when delivering high doses close to critical mediastinal structures. We present dosimetric and clinical outcomes from a group of oligometastatic patients treated with a risk-adapted SBRT approach. METHODS: Between September 2015 and October 2018, 27 patients with 28 central thoracic oligometastases (6 moderately central, 22 ultra-central) were treated with 60 Gy in 8 fractions under online CBCT guidance. PTV dose was compromised where necessary to meet mandatory OAR constraints. Patients were followed up for toxicity and disease status. RESULTS: Mandatory OAR constraints were met in all cases; this required PTV coverage compromise in 23 cases, with V100% reduced to <70% in 11 cases. No acute or late toxicities of Grade ≥ 3 were reported. One and 2 year in-field control rates were 95.2% and 85.7% respectively, progression-free survival rates were 42.8% and 23.4% respectively, and overall survival rates were 82.7% and 69.5% respectively. No significant differences were seen in control or survival rates by extent of PTV underdosage or between moderately and ultra-central cases. CONCLUSION: It appears that compromising PTV coverage to meet OAR constraints allows safe and effective delivery of SBRT to moderately and ultra-central tumours, with low toxicity rates and high in-field control rates. This treatment can be delivered on standard linear accelerators with widely available imaging technology.

Response of FDG avid pelvic bone marrow to concurrent chemoradiation for anal cancer.

BACKGROUND AND PURPOSE: To determine if suppression of active bone marrow, as defined on FDG PETCT, is seen in on-treatment imaging of anal cancer patients receiving concurrent chemoradiation. METHODS AND MATERIALS: Scans from 26 patients participating in the ART trial (full title: Anal squamous cell carcinoma: Investigation of functional imaging during chemoRadioTherapy), a single center observational study with FDG PETCT prior to radiotherapy and at fraction 8-10 of concurrent chemoradiation were analysed. Active bone marrow was contoured in both the pelvis and un-irradiated thoracic spine. SUV and volume of active bone marrow after 8-10 fractions of treatment were compared to baseline. Dose metrics to pelvic active bone marrow were extracted and compared to reduction in SUV/active bone marrow volume and to blood count nadir using linear regression. RESULTS: Suppression of active bone marrow is seen in the pelvis by a reduction in mean SUV and volume of active bone marrow after 8-10 fractions of treatment. Suppression is not seen in un-irradiated thoracic spine. Dose metrics were associated with reduced SUV and reduced volume of active bone marrow. Volume of active bone marrow receiving <20 Gy was associated with WCC/ANC nadir. 20 Gy was identified as the most likely clinically meaningful dose threshold for toxicity. Volume of active bone marrow receiving <20 Gy correlated to WCC and ANC with an increase of 100 cc being associated with an increase of 0.4 and 0.3 respectively. CONCLUSION: The effect of concurrent chemoradiation in suppression of active bone marrow is seen in on-treatment FDG PETCT scans. Chemotherapy appears well tolerated after 2 weeks of treatment.

Oxygen-enhanced MRI MOLLI T1 mapping during chemoradiotherapy in anal squamous cell carcinoma.

BACKGROUND AND PURPOSE: Oxygen-enhanced magnetic resonance imaging (MRI) and T1-mapping was used to explore its effectiveness as a prognostic imaging biomarker for chemoradiotherapy outcome in anal squamous cell carcinoma. MATERIALS AND METHODS: T2-weighted, T1 mapping, and oxygen-enhanced T1 maps were acquired before and after 8-10 fractions of chemoradiotherapy and examined whether the oxygen-enhanced MRI response relates to clinical outcome. Patient response to treatment was assessed 3 months following completion of chemoradiotherapy. A mean T1 was extracted from manually segmented tumour regions of interest and a paired two-tailed t-test was used to compare changes across the patient population. Regions of subcutaneous fat and muscle tissue were examined as control ROIs. RESULTS: There was a significant increase in T1 of the tumour ROIs across patients following the 8-10 fractions of chemoradiotherapy (paired t-test, p < 0.001, n = 7). At baseline, prior to receiving chemoradiotherapy, there were no significant changes in T1 across patients from breathing oxygen (n = 9). In the post-chemoRT scans (8-10 fractions), there was a significant decrease in T1 of the tumour ROIs across patients when breathing 100% oxygen (paired t-test, p < 0.001, n = 8). Out of the 12 patients from which we successfully acquired a visit 1 T1-map, only 1 patient did not respond to treatment, therefore, we cannot correlate these results with clinical outcome. CONCLUSIONS: These clinical data demonstrate feasibility and potential for T1-mapping and oxygen enhanced T1-mapping to indicate perfusion or treatment response in tumours of this nature. These data show promise for future work with a larger cohort containing more non-responders, which would allow us to relate these measurements to clinical outcome.

Long-term mortality after childhood growth hormone treatment: the SAGhE cohort study.

BACKGROUND: Recombinant human growth hormone has been used for more than 30 years and its indications have increased worldwide. There is concern that this treatment might increase mortality, but published data are scarce. We present data from the entire dataset of all eight countries of the Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) consortium, with the aim of studying long-term overall and cause-specific mortality in young adult patients treated with recombinant human growth hormone during childhood and relating this to the underlying diagnosis. METHODS: This cohort study was done in eight European countries (Belgium, France, Germany, Italy, The Netherlands, Sweden, Switzerland, and the UK). Patients were classified a priori based on pre-treatment perceived mortality risk from their underlying disease and followed up for cause-specific mortality. Person-years at risk of mortality and expected rates from general population data were used to calculate standardised mortality ratios (SMRs). FINDINGS: The cohort comprised 24 232 patients treated with recombinant human growth hormone during childhood, with more than 400 000 patient-years of follow-up. In low-risk patients with isolated growth hormone deficiency or idiopathic short stature, all-cause mortality was not significantly increased (SMR 1·1, 95% CI 0·9-1·3). In children born small for gestational age, all-cause mortality was significantly increased when analysed for all countries (SMR 1·5, CI 1·1-1·9), but this result was driven by the French subcohort. In patients at moderate or high risk, mortality was increased (SMR 3·8, 3·3-4·4; and 17·1, 15·6-18·7, respectively). Mortality was not associated with mean daily or cumulative doses of recombinant human growth hormone for any of the risk groups. Cause-specific mortality from diseases of the circulatory and haematological systems was increased in all risk groups. INTERPRETATION: In this cohort, the largest, to our knowledge, with long-term follow-up of patients treated with recombinant human growth hormone during childhood, all-cause mortality was associated with underlying diagnosis. In patients with isolated growth hormone deficiency or idiopathic short stature, recombinant human growth hormone treatment was not associated with increased all-cause mortality. However, mortality from certain causes was increased, emphasising the need for further long-term surveillance. FUNDING: European Union.

Impact of abdominal compression on setup error and image matching during radical abdominal radiotherapy.

PURPOSE: To determine the impact of abdominal compression (AC) on setup error and image matching time. MATERIALS AND METHODS: This study included 72 liver, pancreas and abdominal node patients treated radically from 2016 to 2019 in a single centre. Patients received either SBRT or conventional radical fractionation (CRF). Compressed patients were supine, arms up with kneefix and AC equipment. Uncompressed patients were supine, arms up with kneefix. All patients received daily online-matched CBCTs before treatment. Initial setup error was determined for all patients. Registration error was assessed for 10 liver and 10 pancreas patients. Image matching times were determined using beam on times. Statistical tests conducted were an F-test to compare variances in setup error, Student's t-tests for setup error and average image analysis, and a Wilcoxon Mann Whitney test for imaging matching time analysis. RESULTS: Initial setup displacement was similar between compressed and uncompressed patients. Displacements > 1 cm occurred more frequently in the longitudinal direction for most patients. SBRT patients required more additional manual positioning following imaging. Mean absolute registration error in the SI direction was 5.4 mm and 3.3 mm for uncompressed and compressed pancreas patients respectively and 1.7 mm and 0.8 mm for uncompressed and compressed liver patients respectively. Compressed patients required less time for image matching and fewer images per fraction on average. Repeat imaging occurred more frequently in SBRT and uncompressed patients. CONCLUSIONS: Although abdominal compression has no significant impact on setup error, it can reduce imaging matching times resulting in improved treatment accuracy.

Risk of Meningioma in European Patients Treated With Growth Hormone in Childhood: Results From the SAGhE Cohort.

Context: There has been concern that GH treatment of children might increase meningioma risk. Results of published studies have been inconsistent and limited. Objective: To examine meningioma risks in relation to GH treatment. Design: Cohort study with follow-up via cancer registries and other registers. Setting: Population-based. Patients: A cohort of 10,403 patients treated in childhood with recombinant GH in five European countries since this treatment was first used in 1984. Expected rates from national cancer registration statistics. Main Outcome Measures: Risk of meningioma incidence. Results: During follow-up, 38 meningiomas occurred. Meningioma risk was greatly raised in the cohort overall [standardized incidence ratio (SIR) = 75.4; 95% CI: 54.9 to 103.6], as a consequence of high risk in subjects who had received radiotherapy for underlying malignancy (SIR = 658.4; 95% CI: 460.4 to 941.7). Risk was not significantly raised in patients who did not receive radiotherapy. Risk in radiotherapy-treated patients was not significantly related to mean daily dose of GH, duration of GH treatment, or cumulative dose of GH. Conclusions: Our data add to evidence of very high risk of meningioma in patients treated in childhood with GH after cranial radiotherapy, but suggest that GH may not affect radiotherapy-related risk, and that there is no material raised risk of meningioma in GH-treated patients who did not receive radiotherapy.