The risk of radiation-induced neurocognitive impairment and the impact of sparing the hippocampus during pediatric proton cranial irradiation.

BACKGROUND AND PURPOSE: Hippocampus is a central component for neurocognitive function and memory. We investigated the predicted risk of neurocognitive impairment of craniospinal irradiation (CSI) and the deliverability and effects of hippocampal sparing. The risk estimates were derived from published NTCP models. Specifically, we leveraged the estimated benefit of reduced neurocognitive impairment with the risk of reduced tumor control. MATERIAL AND METHODS: For this dose planning study, a total of 504 hippocampal sparing intensity modulated proton therapy (HS-IMPT) plans were generated for 24 pediatric patients whom had previously received CSI. Plans were evaluated with respect to target coverage and homogeneity index to target volumes, maximum and mean dose to OARs. Paired t-tests were used to compare hippocampal mean doses and normal tissue complication probability estimates. RESULTS: The median mean dose to the hippocampus could be reduced from 31.3 GyRBE to 7.3 GyRBE (p < .001), though 20% of these plans were not considered clinically acceptable as they failed one or more acceptance criterion. Reducing the median mean hippocampus dose to 10.6 GyRBE was possible with all plans considered as clinically acceptable treatment plans. By sparing the hippocampus to the lowest dose level, the risk estimation of neurocognitive impairment could be reduced from 89.6%, 62.1% and 51.1% to 41.0% (p < .001), 20.1% (p < .001) and 29.9% (p < .001) for task efficiency, organization and memory, respectively. Estimated tumor control probability was not adversely affected by HS-IMPT, ranging from 78.5 to 80.5% for all plans. CONCLUSIONS: We present estimates of potential clinical benefit in terms of neurocognitive impairment and demonstrate the possibility of considerably reducing neurocognitive adverse effects, minimally compromising target coverage locally using HS-IMPT.

Volumetric changes of the parotid gland during IMRT based on mid-treatment imaging: implications for parotid stem cell sparing strategies in head and neck cancer.

BACKGROUND: To evaluate the change in parotid glands at mid-treatment during IMRT and the association between radiation dose to the parotid gland stem cell (PGSC) region and patient-reported xerostomia for patients with head and neck cancer (HNC). MATERIAL AND METHODS: Patients who were treated from 2006-2012 at our institution with patient-reported xerostomia outcomes available at least 9 months following RT were included. PG and PGSC regions were delineated and the dose was estimated from the treatment plan dose distribution, using contours from pre- and mid-treatment CT scans. The association between radiation dose and volumetric changes was assessed using linear regression. Univariable logistic regression, logistic dose-response curves, and receiver operating characteristics (ROC) were used to examine the relationship between radiation dose and patient-reported xerostomia. RESULTS: Sixty-three patients were included, most treated with 70 Gy in 33 fractions; 34 patients had mid-treatment CT scans. Both contralateral and ipsilateral PGs had considerable volume reduction from baseline to mid-treatment (25% and 27%, respectively, both p < .001), significantly associated with mean PG dose (-0.44%/Gy, p = .008 and -0.54%/Gy, p < .001, respectively). There was a > 5 Gy difference in mean PG and PGSC dose for 8/34 patients at mid-treatment, with 6/8 (75%) reporting severe xerostomia. Xerostomia prediction based on whole PG or PGSC region dose showed similar performance (ROC AUC 0.754 and 0.749, respectively). The corresponding dose-response models also predicted similar risk of patient-reported xerostomia with mean dose to the contralateral PG (32.5%) or PGSC region (31.4%) at the 20 Gy QUANTEC-recommended sparing level. CONCLUSIONS: The radiation dose to the PGSC region did not show stronger association with patient-reported xerostomia compared to that of whole PG, possibly due to considerable anatomical changes identified at mid-treatment. This shift in the size and position of the PG warrants adaptive planning strategies to evaluate the true benefit of parotid stem cell sparing.

Organ-at-risk dose prediction using a machine learning algorithm: Clinical validation and treatment planning benefit for lung SBRT.

OBJECTIVE: To quantify the clinical performance of a machine learning (ML) algorithm for organ-at-risk (OAR) dose prediction for lung stereotactic body radiation therapy (SBRT) and estimate the treatment planning benefit from having upfront access to these dose predictions. METHODS: ML models were trained using multi-center data consisting of 209 patients previously treated with lung SBRT. Two prescription levels were investigated, 50 Gy in five fractions and 54 Gy in three fractions. Models were generated using a gradient-boosted regression tree algorithm using grid searching with fivefold cross-validation. Twenty patients not included in the training set were used to test OAR dose prediction performance, ten for each prescription. We also performed blinded re-planning based on OAR dose predictions but without access to clinically delivered plans. Differences between predicted and delivered doses were assessed by root-mean square deviation (RMSD), and statistical differences between predicted, delivered, and re-planned doses were evaluated with one-way analysis of variance (ANOVA) tests. RESULTS: ANOVA tests showed no significant differences between predicted, delivered, and replanned OAR doses (all p ≥ 0.36). The RMSD was 2.9, 3.9, 4.3, and 1.7Gy for max dose to the spinal cord, great vessels, heart, and trachea, respectively, for 50 Gy in five fractions. Average improvements of 1.0, 1.4, and 2.0 Gy were seen for spinal cord, esophagus, and trachea max doses in blinded replans compared to clinically delivered plans with 54 Gy in three fractions, and 1.8, 0.7, and 1.5 Gy, respectively, for the esophagus, heart and bronchus max doses with 50 Gy in five fractions. Target coverage was similar with an average PTV V100% of 94.7% for delivered plans compared to 97.3% for blinded re-plans for 50 Gy in five fractions, and respectively 98.4% versus 99.2% for 54 Gy in three fractions. CONCLUSION: This study validated ML-based OAR dose prediction for lung SBRT, showing potential for improved OAR dose sparing and more consistent plan quality using dose predictions for patient-specific planning guidance.

The risk of late effects following pediatric and adult radiotherapy regimens in Hodgkin lymphoma.

PURPOSE: Adolescent young adults (AYA) with Hodgkin lymphoma (HL) are treated according to either pediatric or adult protocols, however, the best strategy has yet to be established. We describe the AYA patients referred for radiotherapy and quantify the risk of radiation-induced late effects and the corresponding life years lost (LYL) following pediatric and adult regimens. METHODS: Patients ≤24 years irradiated for HL were included. For each patient, organs at risk (OARs) were contoured and dosimetric parameters were extracted. Estimated excess hazard ratios of radiation-induced late effects were calculated from dose-response models and LYL attributable to various late effects were estimated. RESULTS: In total, 77 patients were analyzed (pediatric regimen: 15; adult regimen: 62). Age, clinical stage, and the number of patients enrolled in protocols were significantly different between the groups. Pediatric patients had more advanced disease, which resulted in larger target volumes and higher doses to most OARs, despite a lower prescribed dose compared to adult regimens. LYL estimates were all higher with the pediatric regimens. Total LYL with pediatric and adult treatment regimens were 3.2 years and 2.3 years, respectively. Due to the clinical stage variation and heterogeneity in disease location, a direct comparison of the estimated risks of late effects was only exploratory. CONCLUSION: Pediatric regimens selected patients with more advanced disease to radiotherapy resulting in larger target volumes and higher doses to the OARs. Target volume rather than prescribed dose impacted OAR exposure. Consequently, the estimated risk of radiation-induced late effects and corresponding LYL was increased when compared to adult regimens.

The effects of exercise on cardiovascular disease risk factors and cardiovascular physiology in rheumatoid arthritis.

Cardiovascular disease (CVD) morbidity and mortality is highly prevalent in patients with rheumatoid arthritis (RA) with debilitating effects for the individual as well as significant healthcare impact. Current evidence demonstrates that engaging in aerobic and resistance exercise (i.e. structured physical activity) can significantly improve patient-reported and clinical index-assessed outcomes in RA. In addition to this, engagement in exercise programmes improves, in a dose-dependent manner, the risk of developing CVD as well as CVD symptoms and outcomes. The present narrative review uses evidence from systematic reviews and meta-analyses as well as controlled trials, to synthesize the current state-of-the-art on the potential effects of aerobic and resistance exercise on CVD risk factors as well as on cardiac and vascular function and structure in people with RA. Where there is a lack of evidence in RA to explain potential mechanisms, relevant studies from the general population are also discussed and linked to RA.

Human papillomavirus, radiation dose and survival of patients with anal cancer.

Purpose: To determine if anal cancer patients with HPV positive disease have different overall survival (OS) compared to those with HPV negative disease, and to elucidate differences in the association between radiation dose and OS.Patients and methods: We utilized the National Cancer Database (NCDB) registry to identify a cohort of non-metastatic anal cancer patients treated with curative intent between 2008 and 2014. Propensity score matching was used to account for potential selection bias between patients with HPV positive and negative disease. Multivariable Cox regression was used to determine the association between HPV status and OS. Kaplan-Meier methods were used to compare actuarial survival estimates.Results: We identified 5927 patients with tumor HPV status for this analysis, 3523 (59.4%) had HPV positive disease and 2404 (40.6%) had HPV negative disease. Propensity-matched analysis demonstrated that patients with HPV positive locally advanced (T3-4 or node positive) anal cancer had better OS (HR = 0.81 (95%CI: 0.68-0.96), p=.018). For patients with early stage disease (T1-2 and node negative) there was no difference in OS (HR = 1.11 (95%CI: 0.86-1.43), p=.43). In the unmatched cohort, we found a significant improvement in OS with increasing radiation dose only for patients with locally advanced, HPV negative disease (p<.001). In those patients, significant improvement in OS compared to the group receiving 30-45 Gy was seen for increasing doses up to 55-60 Gy, but not beyond 60 Gy.Conclusion: We found HPV to be a significant prognostic marker in anal tumors, especially for locally advanced disease. We further found that higher radiation dose up to 55-60 Gy was associated with better OS, but only for patients with locally advanced, HPV negative disease.

Characterizing the concept of activity pacing as a non-pharmacological intervention in rheumatology care: results of an international Delphi survey.

OBJECTIVE: To develop a consensual list of the most important aspects of activity pacing (AP) as an intervention within the context of non-pharmacological rheumatology care. METHOD: An international, multidisciplinary expert panel comprising 60 clinicians and/or healthcare providers experienced in AP across 12 different countries participated in a Delphi survey. Over four Delphi rounds, the panel identified and ranked the most important goals of AP, behaviours of AP (the actions people take to meet the goal of AP), strategies to change behaviour in AP, and contextual factors that should be acknowledged when instructing AP. Additionally, topics for future research on AP were formulated and prioritized. RESULTS: The Delphi panel prioritized 9 goals, 11 behaviours, 9 strategies to change behaviour, and 10 contextual factors of AP. These items were integrated into a consensual list containing the most important aspects of AP interventions in non-pharmacological rheumatology care. Nine topics for future research on AP with the highest ranking were included in a research agenda highlighting that future research should focus on the effectiveness of AP interventions and on appropriate outcome measures to assess its effectiveness, as selected by 64% and 82% of the panellists, respectively. CONCLUSIONS: The diversity and number of items included in the consensual list developed in the current study reflect the heterogeneity of the concept of AP. This study is an important first step in achieving more transparency and homogeneity in the concept of AP in both rheumatology daily clinical practice and research.

Effects of aerobic and muscle strengthening exercise in adults with rheumatoid arthritis: a narrative review summarising a chapter in Physical activity in the prevention and treatment of disease (FYSS 2016).

BACKGROUND: Besides pharmacological treatment, regular exercise is one of the cornerstones of care in rheumatoid arthritis (RA). In many of the earlier studies of exercise in RA, the intensity of the exercise did not reach the current recommendations or is not described in satisfactory detail. This narrative review is based on randomised controlled trials with a detailed description of the exercise type, frequency, duration and intensity. RESULTS: There is moderate-quality evidence that short-term land-based aerobic exercise of moderate to high intensity augments oxygen uptake but does not improve muscle strength. Short-term water-based aerobic exercise of moderate to high intensity augments oxygen uptake; short term land-based aerobic and muscle strengthening exercise of moderate to high intensity augments oxygen uptake and muscle strength. Long-term land-based aerobic and muscle strengthening exercise of moderate to high intensity reduces activity limitations and improves both oxygen uptake and muscle strength. CONCLUSIONS: Clinicians should recommend that patients with RA participate in various types of exercise.

The impact of involved node, involved field and mantle field radiotherapy on estimated radiation doses and risk of late effects for pediatric patients with Hodgkin lymphoma.

BACKGROUND: The use of radiotherapy (RT) is debated for pediatric patients with Hodgkin lymphoma (HL) due to the late effects of treatment. Radiation doses to the thyroid, heart, lungs, and breasts are compared with the extensive mantle field (MF), Involved Field RT(IFRT), Modified IFRT (mIFRT), and Involved Node RT (INRT) and the risk of radiation-induced cardiovascular disease, secondary cancers, and the corresponding Life Years Lost (LYL) is estimated with each technique. PROCEDURE: INRT, mIFRT, IFRT, and MF plans (20 and 30 Gy) were simulated for 10 supradiaphragmatic, clinical stage I­II classical HL patients <18 years old, total of 4 x 2 plans for each patient. The lifetime excess risks of cardiac morbidity, cardiac mortality, lung, breast, and thyroid cancer with each technique were estimated. The estimated excess risks attributable to RT were based on HL series with long-term follow-up, treating death from other causes as competing risks. The corresponding LYL were derived from the estimated excess risks. Statistical analyses were performed with repeated measures ANOVA. RESULTS: Both a reduction in field size and in prescribed radiation dose significantly lowered the estimated dose to the heart, lungs, breasts, and thyroid compared to past,extended fields, even for patients with mediastinal disease. This translated into a significantly reduced estimated risk of cardiovascular disease, secondary cancers, and LYL. CONCLUSIONS: Involved Node Radiotherapy should be considered for pediatric patients with Hodgkin lymphoma since it is estimated to substantially lower the risk of severe long-term complications.

Optimizing the radiation therapy dose prescription for pediatric medulloblastoma: minimizing the life years lost attributable to failure to control the disease and late complication risk.

BACKGROUND: A mathematical framework is presented for simultaneously quantifying and evaluating the trade-off between tumor control and late complications for risk-based radiation therapy (RT) decision-support. To demonstrate this, we estimate life years lost (LYL) attributable to tumor recurrence, late cardiac toxicity and secondary cancers for standard-risk pediatric medulloblastoma (MB) patients and compare the effect of dose re-distribution on a common scale. METHODS: Total LYL were derived, based on the LYL attributable to radiation-induced late complications and the LYL from not controlling the primary disease. We compared the estimated LYL for three different treatments in 10 patients: 1) standard 3D conformal RT; 2) proton therapy; 3) risk-adaptive photon treatment lowering the dose to part of the craniospinal (CS) target volume situated close to critical risk organs. RESULTS: Late toxicity is important, with 0.75 LYL (95% CI 0.60-7.2 years) for standard uniform 24 Gy CS irradiation. However, recurrence risk dominates the total LYL with 14.2 years (95% CI 13.4-16.6 years). Compared to standard treatment, a risk-adapted strategy prescribing 12 Gy to the spinal volume encompassing the 1st-10th thoracic vertebrae (Th1-Th10), and 36 Gy to the remaining CS volume, estimated a LYL reduction of 0.90 years (95% CI -0.18-2.41 years). Proton therapy with 36 Gy to the whole CS volume was associated with significantly fewer LYL compared to the risk-adapted photon strategies, with a mean LYL difference of 0.50 years (95% CI 0.25-2.60 years). CONCLUSIONS: Optimization of RT prescription strategies considering both late complications and the risk of recurrence, an all-cause mortality dose painting approach, was demonstrated. The risk-adapted techniques compared favorably to the standard, and although in this context, the gain is small compared to estimated uncertainty, this study demonstrates a framework for all-cause mortality risk estimation, rather than evaluates direct clinical applicability of risk-adapted strategies.

A treatment planning and delivery comparison of volumetric modulated arc therapy with or without flattening filter for gliomas, brain metastases, prostate, head/neck and early stage lung cancer.

BACKGROUND: Flattening filter-free (FFF) beams are an emerging technology that has not yet been widely implemented as standard practice in radiotherapy centers. To facilitate the clinical implementation of FFF, we attempted to elucidate the difference in plan quality and treatment delivery time compared to flattening filter beams (i.e. standard, STD) for several patient groups. We hypothesize that the treatment plan quality is comparable while the treatment delivery time of volumetric modulated arc therapy (VMAT) is considerably shorter using FFF beams, especially for stereotactic treatments. METHODS: A total of 120 patients treated for head and neck (H&N) tumors, high-grade glioma, prostate cancer, early stage lung cancer and intra-cranial metastatic disease (both single and multiple metastases) were included in the study. For each cohort, 20 consecutive patients were selected. The plans were generated using STD- and FFF-VMAT for both 6 MV and 10 MV, and were compared with respect to plan quality, monitor units and delivery time using Wilcoxon signed rank tests. RESULTS: For H&N and high-grade gliomas, there was a significant difference in homogeneity index in favor for STD-VMAT (p < 0.001). For the stereotactic sites there were no differences in plan conformity. Stereotactic FFF-VMAT plans required significantly shorter delivery time compared to STD-VMAT plans (p < 0.001) for higher dose per fraction, on average 54.5% for 6 MV and 71.4% for 10 MV. FFF-VMAT generally required a higher number of MU/Gy (p < 0.001), on average 7.0% for 6 MV and 8.4% for 10 MV. CONCLUSION: It was generally possible to produce FFF-VMAT plans with the same target dose coverage and doses to organs at risk as STD-VMAT plans. Target dose homogeneity tended to be somewhat inferior for FFF-VMAT for the larger targets investigated. For stereotactic radiotherapy, FFF-VMAT resulted in a considerable time gain while maintaining similar plan quality compared to STD beams.

Estimated risk of cardiovascular disease and secondary cancers with modern highly conformal radiotherapy for early-stage mediastinal Hodgkin lymphoma.

BACKGROUND: Hodgkin lymphoma (HL) survivors have an increased morbidity and mortality from secondary cancers and cardiovascular disease (CD). We evaluate doses with involved node radiotherapy (INRT) delivered as 3D conformal radiotherapy (3D CRT), volumetric modulated arc therapy (VMAT), or proton therapy (PT), compared with the extensive Mantle Field (MF). PATIENTS AND METHODS: For 27 patients with early-stage, mediastinal HL, treated with chemotherapy and INRT delivered as 3D CRT (30 Gy), we simulated an MF (36 Gy), INRT-VMAT and INRT-PT (30 Gy). Dose to the heart, lungs, and breasts, estimated risks of CD, lung (LC) and breast cancer (BC), and corresponding life years lost (LYL) were compared. RESULTS: 3D CRT, VMAT or PT significantly lower the dose to the heart, lungs and breasts and provide lower risk estimates compared with MF, but with substantial patient variability. The risk of CD is not significantly different for 3D CRT versus VMAT. The risk of LC and BC is highest with VMAT. For LYL, PT is the superior modern technique. CONCLUSIONS: In early-stage, mediastinal HL modern radiotherapy provides superior results compared with MF. However, there is no single best radiotherapy technique for HL-the decision should be made at the individual patient level.

Self-report and device-based physical activity measures and adherence to physical activity recommendations: a cross-sectional survey among people with inflammatory joint disease in four European countries.

OBJECTIVES: Self-monitoring of physical activity (PA) has the potential to contribute to successful behaviour change in PA interventions in different populations, including people with inflammatory joint diseases (IJDs). The objectives of this study were to describe the use and knowledge of self-report-based and device-based PA measures in people with IJDs in four European countries, and to explore if the use of such devices, sociodemographic or disease-related variables were associated with adherence to the recommendations of at least 150 min of moderate to vigorous PA per week. SETTING: Cross-sectional survey, performed in 2015-2016. PARTICIPANTS: People with IJDs in Belgium, Denmark, Ireland and Sweden. PRIMARY AND SECONDARY OUTCOME MEASURES: Use of self-report and device-based PA measures, receipt of instructions how to use PA measures, confidence in using them, adherence to PA recommendations and associated factors for adherence to PA recommendations. RESULTS: Of the 1305 respondents answering questions on PA measures, 600 (46%) reported use of any kind of self-report or device-based measures to self-monitor PA. Between country differences of 34%-58% was observed. Six per cent and four per cent received instructions from health professionals on how to use simple and complex devices, respectively. Independent associated factors of fulfilment of recommendations of PA were living in Ireland (OR=84.89, p<0.001) and Sweden (OR=1.68, p=0.017) compared with living in Denmark, not perceiving activity limitations in moderate activities (OR=1.92, p<0.001) and using a device to measure PA (OR=1.56, p<0.001). Those living in Belgium (OR=0.21, p<0.001) were less likely to fulfil recommendations of PA. CONCLUSIONS: Almost half of the participants with IJDs used self-report-based or deviced-based PA measures, although few used wearable devices regularly. The results indicate that participants meeting public PA health guidelines were engaged in self-monitoring of PA.

Hepatocellular Carcinoma in HIV-Infected Patients: Clinical Presentation and Outcomes in a Racially Diverse Urban Population.

PURPOSE: As life expectancy for HIV patients improve, hepatocellular carcinoma (HCC) has become a non-AIDS defining illness with a high impact on morbidity and mortality of HIV-infected individuals. We sought to compare outcomes in HIV- versus non-HIV-infected patients treated for HCC at a multiethnic academic medical health system. METHODS: A retrospective chart review of patients diagnosed with HCC from 1/1/2005 to 12/31/2016 was performed. Differences in characteristics among HIV and non-HIV subjects were assessed. Associations between HIV status, viral load, CD4 count, and overall survival (OS) were also assessed. RESULTS: We identified 915 subjects (842 non-HIV and 73 with HIV). HIV-infected subjects were younger, predominantly male non-Hispanic Blacks, and more likely to have HBV and HCV co-infection, and alcohol use at diagnosis compared to non-HIV counterparts. Stage, MELD score, Child-Pugh, and ECOG performance status were similar. HIV-positive patients received systemic therapy at significantly higher rates and liver transplantation for HCC at significantly lower rates than those without HIV. The actuarial 3- and 5-year overall survival (OS) for all patients was 48.3% and 39.4%. For HIV-infected subjects, 3- and 5-year OS was significantly worse at 36.8% and 28.3% compared to 49.3% and 40.4%, respectively, for non-HIV subjects (log rank p = 0.033). CONCLUSIONS: HIV-infected HCC patients have lower survival rates compared to those without HIV. Despite younger age and similar stage, MELD, and ECOG at diagnosis, HIV portends worse outcomes in patients with HCC.

Risk of Subsequent Neoplasms in Childhood Cancer Survivors After Radiation Therapy: A Comprehensive PENTEC Review.

PURPOSE: A Pediatric Normal Tissue Effects in the Clinic (PENTEC) analysis of published investigations of central nervous system (CNS) subsequent neoplasms (SNs), subsequent sarcomas, and subsequent lung cancers in childhood cancer survivors who received radiation therapy (RT) was performed to estimate the effect of RT dose on the risk of SNs and the modification of this risk by host and treatment factors. METHODS AND MATERIALS: A systematic literature review was performed to identify data published from 1975 to 2022 on SNs after prior RT in childhood cancer survivors. After abstract review, usable quantitative and qualitative data were extracted from 83 studies for CNS SNs, 118 for subsequent sarcomas, and 10 for lung SNs with 4 additional studies (3 for CNS SNs and 1 for lung SNs) later added. The incidences of SNs, RT dose, age, sex, primary cancer diagnosis, chemotherapy exposure, and latent time from primary diagnosis to SNs were extracted to assess the factors influencing risk for SNs. The excess relative ratio (ERR) for developing SNs as a function of dose was analyzed using inverse-variance weighted linear regression, and the ERR/Gy was estimated. Excess absolute risks were also calculated. RESULTS: The ERR/Gy for subsequent meningiomas was estimated at 0.44 (95% CI, 0.19-0.68); for malignant CNS neoplasms, 0.15 (95% CI, 0.11-0.18); for sarcomas, 0.045 (95% CI, 0.023-0.067); and for lung cancer, 0.068 (95% CI, 0.03-0.11). Younger age at time of primary diagnosis was associated with higher risk of subsequent meningioma and sarcoma, whereas no significant effect was observed for age at exposure for risk of malignant CNS neoplasm, and insufficient data were available regarding age for lung cancer. Females had a higher risk of subsequent meningioma (odds ratio, 1.46; 95% CI, 1.22-1.76; P < .0001) relative to males, whereas no statistically significant sex difference was seen in risk of malignant CNS neoplasms, sarcoma SNs, or lung SNs. There was an association between chemotherapy receipt (specifically alkylating agents and anthracyclines) and subsequent sarcoma risk, whereas there was no clear association between specific chemotherapeutic agents and risk of CNS SNs and lung SNs. CONCLUSIONS: This PENTEC systematic review shows a significant radiation dose-response relationship for CNS SNs, sarcomas, and lung SNs. Given the linear dose response, improved conformality around the target volume that limits the high dose volume might be a promising strategy for reducing the risk of SNs after RT. Other host- and treatment-related factors such as age and chemotherapy play a significant contributory role in the development of SNs and should be considered when estimating the risk of SNs after RT among childhood cancer survivors.

Barriers and facilitators for physical activity in rheumatic and musculoskeletal disease: a European-based survey.

Physical activity (PA) is a key strategy for improving symptoms in people with rheumatic and musculoskeletal diseases (RMDs). The aim of this study was to investigate and rank the importance of known barriers and facilitators for engaging in PA, from the perspective of people living with RMD. Five hundred thirty-three people with RMD responded to a survey (nine questions) disseminated by the People with Arthritis and Rheumatism (PARE) network of the European Alliance of Associations for Rheumatology (EULAR). The survey required participants to rank - based on their perceived importance - known PA barriers and facilitators from the literature, and specifically RMD symptoms as well as healthcare and community factors that may affect PA participation. Of the participants, 58% reported rheumatoid arthritis as their primary diagnosis, 89% were female, and 59% were between 51 and 70 years of age. Overall, participants reported fatigue (61.4%), pain (53.6%) and painful/swollen joints (50.6%) as the highest ranked barriers for engaging in PA. Conversely, less fatigue (66.8%) and pain (63.6%), and being able to do daily activities more easy (56.3%) were identified as the most important facilitators to PA. Three literature identified PA barriers, i.e., general health (78.8%), fitness (75.3%) and mental health (68.1%), were also ranked as being the most important for PA engagement. Symptoms of RMDs, such as pain and fatigue, seem to be considered the predominant barriers to PA by people with RMD; the same barriers are also the ones that they want to improve through increasing PA, suggesting a bi-directional relationship between these factors. Key Points • Symptoms of rheumatic and musculoskeletal disease (RMD) are the predominant barriers for lack of physical activity engagement. • RMD symptoms are the factors that people with RMDs want to improve when engaging in PA. • The barriers that stop people living with RMDs to do more PA are the ones that can be significantly improved through PA engagement.

Life years lost--comparing potentially fatal late complications after radiotherapy for pediatric medulloblastoma on a common scale.

BACKGROUND: The authors developed a framework for estimating and comparing the risks of various long-term complications on a common scale and applied it to 3 different techniques for craniospinal irradiation in patients with pediatric medulloblastoma. METHODS: Radiation dose-response parameters related to excess hazard ratios for secondary breast, lung, stomach, and thyroid cancer; heart failure, and myocardial infarction were derived from large published clinical series. Combined with age-specific and sex-specific hazards in the US general population, the dose-response analysis yielded excess hazards of complications for a cancer survivor as a function of attained age. After adjusting for competing risks of death, life years lost (LYL) were estimated based on excess hazard and prognosis of a complication for 3-dimensional conformal radiotherapy (3D CRT), volumetric modulated arc therapy (VMAT), and intensity-modulated proton therapy (IMPT). RESULTS: Lung cancer contributed most to the estimated LYL, followed by myocardial infarction, and stomach cancer. The estimates of breast or thyroid cancer incidence were higher than those for lung and stomach cancer incidence, but LYL were lower because of the relatively good prognosis. Estimated LYL ranged between 1.90 years for 3D CRT to 0.28 years for IMPT. In a paired comparison, IMPT was associated with significantly fewer LYL than both photon techniques. CONCLUSIONS: Estimating the risk of late complications is associated with considerable uncertainty, but including prognosis and attained age at an event to obtain the more informative LYL estimate added relatively little to this uncertainty.

Stereotactic radiosurgery with immunotherapy is associated with improved overall survival in patients with metastatic melanoma or non-small cell lung cancer: a National Cancer Database analysis.

PURPOSE: Immunotherapy is now a first-line treatment for metastatic non-small cell lung cancer (NSCLC) and melanomaQuery. It is important to understand the relationship between immunotherapy and radiation to the brain. The aim of this study was to assess the role of stereotactic radiosurgery (SRS) or WBRT in addition to immunotherapy in patients with melanoma or NSCLC metastatic to the brain. METHODS/PATIENTS: Using the National Cancer Database, 2951 patients with NSCLC and 936 patients with melanoma treated with immunotherapy were identified. Patients were classified as having received immunotherapy alone, immunotherapy with SRS, or immunotherapy with whole-brain radiation therapy (WBRT). Kaplan-Meier, multivariate Cox regression analyses, and propensity matching were performed to evaluate the impact of adding SRS to immunotherapy on overall survival (OS). Immortal survival bias was accounted for by only including patients who received radiation before immunotherapy and time zero was defined as the start of immunotherapy. RESULTS: 205(6.9%) and 75(8.0%) patients received immunotherapy with no radiation, 822(27.9%) and 326(34.8%) received SRS and immunotherapy, and 1924(65.2%) and 535(57.2%) received WBRT and immunotherapy for NSCLC and melanoma, respectively. Adding SRS to immunotherapy was associated with improved OS in multivariate analyses (NSCLC HR = 0.81, 95% CI 0.66-0.99, p = 0.044; melanoma HR = 0.63, 95% CI 0.45-0.90, p = 0.011). The addition of WBRT to immunotherapy did not improve OS in patients with melanoma nor NSCLC. CONCLUSIONS: This analysis suggests that treatment with SRS and immunotherapy is associated with improved OS compared to immunotherapy alone for patients with melanoma or NSCLC metastatic to the brain.

Case Report: Can Targeted Intraoperative Radiotherapy in Patients With Breast Cancer and Pacemakers be the New Standard of Care?

Background: Partial breast irradiation with Intra-operative radiotherapy (IORT) has become a popular management option as opposed to whole breast radiation using external beam radiotherapy for breast cancer patients. While previous studies have highlighted the use of IORT in breast cancer patients, there is a scarcity of literature on the use of IORT in those who also have ipsilateral pacemakers. Thus, the aim of our case report is to highlight the applicability of IORT in breast cancer patients who also have a pacemaker. Case Reports: Two female patients with an implanted dual-chamber pacemaker presented with a diagnosis of left-sided invasive ductal carcinoma on mammogram. Mammography of the left breast revealed a 10 mm and 7 mm spiculated mass, respectively, further confirmed with an ultrasound-guided core biopsy that was conclusive of clinical Stage I T1 N0 grade 2, ER +, PR + Her2 - invasive ductal carcinoma. They met our eligibility criteria for IORT, which is being performed as a registry trial. These patients underwent a wide excision lumpectomy along with IORT. Conclusion: Our findings underscore the successful use of targeted IORT for breast-conserving surgery in a patient with invasive ductal carcinoma and pacemaker, hence eliminating the necessity for relocating pacemaker surgeries in these patients. Furthermore, no device failure or malfunction for the pacemaker was recorded before, during, or after the surgery, demonstrating the safety of using IORT in patients with preinstalled pacemaker despite a lack of evidence on safe radiation dosage or manufacturer guidelines. Nonetheless, the effects of IORT on pacemaker < 10 cm were not studied in our patients and further clinical studies are recommended to reinforce the applicability and safe distance of IORT in breast cancer patients with pacemaker.

Fatigue in Patients With Head and Neck Cancer Treated With Radiation Therapy: A Prospective Study of Patient-Reported Outcomes and Their Association With Radiation Dose to the Cerebellum.

Purpose: Although fatigue is a known side effect in patients with head and neck cancer (HNC) receiving radiation therapy, knowledge regarding long-term fatigue and dose-response relationships to organs at risk is scarce. The aim of this prospective study was to analyze patient-reported fatigue in patients with HNC receiving radiation therapy and to explore any possible association with organ-at-risk doses. Methods and Materials: Patients with HNC referred for curative radiation therapy were eligible for inclusion in the study. To assess patient-reported fatigue, quality of life questionnaires (European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-FA12) were distributed before treatment and 1, 3, 6, 12, 24, and 60 months after the start of treatment. Mean dose (Dmean) and near maximum dose (D2%) of the cerebellum and brain stem were evaluated in relation to baseline-adjusted fatigue scores at 3 months. Results: One hundred twenty-six patients treated with intensity modulated radiation therapy between 2008 and 2010 were available for final analysis. Female sex and age <60 years were associated with higher fatigue at baseline, whereas patients also treated with chemotherapy had reduced physical and emotional fatigue at 6 months. Physical fatigue (QLQ-FA12 scale) increased from baseline up to 3 months (29 vs 59; P < .0001) but showed no difference compared with baseline from 1 to 5 years. Emotional fatigue was significantly lower at 5 years compared with baseline (14 vs 28; P < .0001). Patients with cerebellum Dmean > 3.5 Gy had higher mean physical fatigue scores at 3 months (38 vs 27; P = .036). Conclusions: Although there is a significant increase in fatigue scores for patients with HNC up to 1 year after radiation therapy, this study showed a return to baseline levels at 5 years. A possible association was found between physical fatigue and a higher mean dose to the cerebellum.