Influence of eye movement on lens dose and optic nerve target coverage during craniospinal irradiation

PURPOSE: Optic nerves are part of the craniospinal irradiation (CSI) target volume. Modern radiotherapy techniques achieve highly conformal target doses while avoiding organs-at-risk such as the lens. The magnitude of eye movement and its influence on CSI target- and avoidance volumes are unclear. We aimed to evaluate the movement-range of lenses and optic nerves and its influence on dose distribution of several planning techniques. METHODS: Ten volunteers underwent MRI scans in various gaze directions (neutral, left, right, cranial, caudal). Lenses, orbital optic nerves, optic discs and CSI target volumes were delineated. 36-Gy cranial irradiation plans were constructed on synthetic CT images in neutral gaze, with Volumetric Modulated Arc Therapy, pencil-beam scanning proton therapy, and 3D-conventional photons. Movement-amplitudes of lenses and optic discs were analyzed, and influence of gaze direction on lens and orbital optic nerve dose distribution. RESULTS: Mean eye structures’ shift from neutral position was greatest in caudal gaze; −5.8±1.2 mm (±SD) for lenses and 7.0±2.0 mm for optic discs. In 3D-conventional plans, caudal gaze decreased Mean Lens Dose (MLD). In VMAT and proton plans, eye movements mainly increased MLD and diminished D98 orbital optic nerve (D98(OON)) coverage; mean MLD increased up to 5.5 Gy [total ΔMLD range −8.1 to 10.0 Gy], and mean D98(OON) decreased up to 3.3 Gy [total ΔD98(OON) range −13.6 to 1.2 Gy]. VMAT plans optimized for optic disc Internal Target Volume and lens Planning organ-at-Risk Volume resulted in higher MLD over gaze directions. D98(OON) became ≥95% of prescribed dose over 95/100 evaluated gaze directions, while all-gaze bilateral D98(OON) significantly changed in 1 of 10 volunteers. CONCLUSION: With modern CSI techniques, eye movements result in higher lens doses and a mean detriment for orbital optic nerve dose coverage of <10% of prescribed dose

Deep learning-enabled MRI-only photon and proton therapy treatment planning for paediatric abdominal tumours

Purpose: To assess the feasibility of magnetic resonance imaging (MRI)-only treatment planning for photon and proton radiotherapy in children with abdominal tumours. Materials and methods: The study was conducted on 66 paediatric patients with Wilms' tumour or neuroblastoma (age 4 +/- 2 years) who underwent MR and computed tomography (CT) acquisition on the same day as part of the clinical protocol. MRI intensities were converted to CT Hounsfield units (HU) by means of a UNet-like neural network trained to generate synthetic CT (sCT) from T1- and T2-weighted MR images. The CT-to-sCT image similarity was evaluated by computing the mean error (ME), mean absolute error (MAE), peak signal-to-noise ratio (PSNR) and Dice similarity coefficient (DSC). Synthetic CT dosimetric accuracy was verified against CT-based dose distributions for volumetric-modulated arc therapy (VMAT) and intensity-modulated pencil-beam scanning (PBS). Relative dose differences (D-diff) in the internal target volume and organs-at-risk were computed and a three-dimensional gamma analysis (2 mm, 2%) was performed. Results: The average +/- standard deviation ME was -5 +/- 12 HU, MAE was 57 +/- 12 HU, PSNR was 30.3 +/- 1. 6 dB and DSC was 76 +/- 8% for bones and 92 +/- 9% for lungs. Average D-diff were 99% (range [85; 100]%) for VMAT and >96% (range [87; 100]%) for PBS. Conclusion: The deep learning-based model generated accurate sCT from planning T1w- and T2w-MR images. Most dosimetric differences were within clinically acceptable criteria for photon and proton radiotherapy, demonstrating the feasibility of an MRI-only workflow for paediatric patients with abdominal tumours. (C) 2020 The Authors. Published by Elsevier B.V

Review - Late toxicity of abdominal and pelvic radiotherapy for childhood cancer

As survival improves in childhood cancer, prevention of late treatment-related toxicity in survivors becomes increasingly relevant. Radiotherapy is an important contributor to late toxicity. Therefore, minimizing radiation exposure to normal tissues is an important step towards improving the long-term therapeutic window of childhood cancer treatment. Since children are growing and developing, they are particularly vulnerable to radiation exposure. This makes the 'as low as reasonably achievable (ALARA)' principle even more important. In order to guide and achieve clinically meaningful dose reductions through advanced and emerging radiation techniques, it is important to investigate age-dependent relationships between radiation exposure to healthy tissues and late radiation-induced toxicity. In this review, we provide an overview of literature on the association between radiotherapy dose and late toxicity after abdominal and pelvic irradiation in childhood cancer. With this information, we aim to aid in decision-making regarding radiotherapy for childhood cancer. (c) 2022 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology 170 (2022) 27-36 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Long-term survivors of early breast cancer treated with chemotherapy are characterized by a pro-inflammatory biomarker profile compared to matched controls

Background: Chemo- and radiotherapy for breast cancer (BC) can lead to cardiotoxicity even years after the initial treatment. The pathophysiology behind these late cardiac effects is poorly understood. Therefore, we studied a large panel of biomarkers from different pathophysiological domains in long-term BC survivors, and compared these to matched controls. Methods and results: In total 91 biomarkers were measured in 688 subjects: 342 BC survivors stratified either to treatment with chemotherapy ± radiotherapy (n = 170) or radiotherapy alone (n = 172) and matched controls. Mean age was 59 ± 9 years and 65 ± 8 years for women treated with chemotherapy ± radiotherapy and radiotherapy alone, respectively, with a mean time since treatment of 11 ± 5.5 years. No biomarkers were differentially expressed in survivors treated with radiotherapy alone vs. controls (P for all >0.1). In sharp contrast, a total of 19 biomarkers were elevated, relative to controls, in BC survivors treated with chemotherapy ± radiotherapy after correction for multiple comparisons (P <0.05 for all). Network analysis revealed upregulation of pathways relating to collagen degradation and activation of matrix metalloproteinases. Furthermore, several inflammatory biomarkers including growth differentiation factor 15, monocyte chemoattractant protein 1, chemokine (C-X-C motif) ligand 16, tumour necrosis factor super family member 13b and proprotein convertase subtilisin/kexin type 9, elevated in survivors treated with chemotherapy, showed an independent association with lower left ventricular ejection fraction. Conclusion: Breast cancer survivors treated with chemotherapy ± radiotherapy show a distinct biomarker profile associated with mild cardiac dysfunction even 10 years after treatment. These results suggest that an ongoing pro-inflammatory state and activation of matrix metalloproteinases following initial treatment with chemotherapy might play a role in the observed cardiac dysfunction in late BC survivors

The Importance of Radiation Dose to the Atherosclerotic Plaque in the Left Anterior Descending Coronary Artery for Radiation-Induced Cardiac Toxicity of Breast Cancer Patients?

IMPORTANCE: Radiation-induced acute coronary events (ACEs) may occur as treatment-related late side effect of breast cancer (BC) radiation. However, the underlying mechanisms behind this radiation-induced cardiac disease remains to be determined. OBJECTIVE: The objective of this study was to test the hypothesis that radiation dose to calcified atherosclerotic plaques in the left anterior descending coronary artery (LAD) is a better predictor for ACEs than radiation dose to the whole heart or left ventricle in BC patients treated with radiotherapy (RT). DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOMES AND MEASURES: The study cohort consisted of 910 BC patients treated with postoperative RT after breast conserving surgery. In total, 163 patients had an atherosclerotic plaque in the LAD. The endpoint was the occurrence of an ACE after treatment. For each individual patient, the mean heart dose (MHD), volume of the left ventricle receiving ≥ 5 Gy (LV-V5), mean LAD dose and mean dose to calcified atherosclerotic plaques in the LAD, if present, were acquired based on planning CT-scans. Cox-regression analysis was used to analyse the effects on the cumulative incidence of ACEs. RESULTS: The median follow-up time was 9.2 years (range: 0.1-14.3 years). In total, 38 patients (4.2%) developed an ACE during follow-up. For patients with an atherosclerotic plaque (n=163) the mean dose to the atherosclerotic plaque was the strongest predictor for ACE, even after correction for cardiovascular risk factors (HR: 1.269 (95% CI: 1.090-1.477), P=0.002). The LV-V5 was associated with ACEs in patients without atherosclerotic plaques in the LAD (n=680) (hazard ratio (HR): 1.021 (95% CI: 1.003-1.039; P=0.023). CONCLUSION AND RELEVANCE: The results of this study suggest that radiation dose to pre-existing calcified atherosclerotic plaques in the LAD is strongly associated with the development of ACEs in BC patients

Diaphragm and abdominal organ motion during radiotherapy:a comprehensive multicenter study in 189 children

Background: For accurate thoracic and abdominal radiotherapy, inter- and intrafractional geometrical uncertainties need to be considered to enable accurate margin sizes. We aim to quantify interfractional diaphragm and abdominal organ position variations, and intrafractional diaphragm motion in a large multicenter cohort of pediatric cancer patients (&lt; 18 years). We investigated the correlation of interfractional position variations and intrafractional motion with age, and with general anesthesia (GA). Methods: In 189 children (mean age 8.1; range 0.4–17.9 years) from six institutes, interfractional position variation of both hemidiaphragms, spleen, liver, left and right kidneys was quantified using a two-step registration. CBCTs were registered to the reference CT relative to the bony anatomy, followed by organ registration. We calculated the group mean, systematic and random errors (standard deviations Σ and σ, respectively) in cranial-caudal (CC), left-right and anterior-posterior directions. Intrafractional right hemidiaphragm motion was quantified using CBCTs on which the breathing amplitude, defined as the difference between end-inspiration and end-expiration peaks, was assessed (N = 79). We investigated correlations with age (Spearman’s ρ), and differences in motion between patients treated with and without GA (N = 75; all &lt; 5.5 years). Results: Interfractional group means were largest in CC direction and varied widely between patients, with largest variations in the right hemidiaphragm (range -13.0–17.5 mm). Interfractional group mean of the left kidney showed a borderline significant correlation with age (p = 0.047; ρ = 0.17). Intrafractional right hemidiaphragm motion in patients ≥ 5.5 years (mean 10.3 mm) was significantly larger compared to patients &lt; 5.5 years treated without GA (mean 8.3 mm) (p = 0.02), with smaller Σ and σ values. We found a significant correlation between breathing amplitude and age (p &lt; 0.001; ρ = 0.43). Interfractional right hemidiaphragm position variations were significantly smaller in patients &lt; 5.5 years treated with GA than without GA (p = 0.004), but intrafractional motion showed no significant difference. Conclusion: In this large multicenter cohort of children undergoing thoracic and abdominal radiotherapy, we found that interfractional position variation does not depend on age, but the use of GA in patients &lt; 5.5 years showed smaller systematic and random errors. Furthermore, our results showed that breathing amplitude increases with age. Moreover, variations between patients advocate the need for a patient-specific margin approach.</p

Correspondence between primary and secondary healthcare providers about patients with cancer; how can it be improved?

OBJECTIVE: To explore the correspondence between primary and secondary healthcare providers about patients with lung, breast or colorectal cancer.DESIGN: Qualitative research.METHOD: We collected the medical files of 50 patients with lung, breast or colorectal cancer by purposive sampling and selected the correspondence-related items from them. These concerned referral letters from primary to secondary caregivers and letters from specialists. A qualitative content analysis of these documents was performed. In addition, 4 general practitioners, 4 oncologists and 1 nurse specialist were interviewed.RESULTS: We analysed 50 referral letters and 369 letters from specialists. Content could be divided into 6 main themes in the referral letters, and it was noticeable that highly relevant information regarding the past medical history was often mixed with less relevant information. The same was true for the medication list and case history to a certain extent. We could distinguish 9 themes in the letters from specialists. All the letters from specialists did include information about the current treatment, but information about treatment intent (curative or palliative) or alternative treatment options was rarely available. Interviews with the healthcare providers confirmed these findings.CONCLUSION: The study findings indicate that referral letters and specialist correspondence are not sufficiently tailored to the needs of the recipient.</p

Assessment of Bone Lesions with F-18-FDG PET Compared with Tc-99m Bone Scintigraphy Leads to Clinically Relevant Differences in Metastatic Breast Cancer Management

It is unknown whether assessment of potential bone lesions in metastatic breast cancer (MBC) by F-18-FDG PET instead of Tc-99m bone scintigraphy (BS) supports clinically relevant changes in MBC management. Therefore, we retrospectively compared management recommendations based on bone lesion assessment by (18)FFDG PET plus contrast-enhanced CT (ceCT) or BS plus ceCT, for patients with newly diagnosed MBC. Methods: Baseline ceCT, BS, and F-18-FDG PET for all patients included in the IMPACT-MBC study (NCT01957332) at the University Medical Center Groningen were reviewed for bone lesions. If bone lesions were found by any imaging modality, virtual MBC management recommendations were made by a multidisciplinary expert panel, based on either F-18-FDG PET plus ceCT or BS plus ceCT. The panel had access to standard clinicopathologic information and baseline imaging findings outside the skeleton. Clinically relevant management differences between the 2 recommendations were defined either as different treatment intent (curative, noncurative, or unable to determine) or as different systemic or local treatment. If no bone lesions were found by any imaging modality, the patients were included in the analyses without expert review. Results: In total, 3,473 unequivocal bone lesions were identified in 10(2) evaluated patients (39% by ceCT, 26% by BS, and 87% by F-18-FDG PET). Additional bone lesions on F-18-FDG PET plus ceCT compared with BS plus ceCT led to change in MBC management recommendations in 16% of patients (95% CI, 10%-24%). BS also changed management compared with F-18-FDG PET in 1 patient (1%; 95% CI, 0%-5%). In 26% (95% CI, 19%-36%) of patients, an additional F-18-FDG PET exam was requested, because BS provided insufficient information. Conclusion: In this exploratory analysis of newly diagnosed MBC patients, F-18-FDG PET versus BS to assess bone lesions resulted in clinically relevant management differences in 16% of patients. BS delivered insufficient information in over one fourth of patients, resulting in an additional request for F-18-FDG PET. On the basis of these data, F-18-FDG PET should be considered a primary imaging modality for assessment of bone lesions in newly diagnosed MBC

Health-related quality of life of early-stage breast cancer patients after different radiotherapy regimens

PURPOSE: To evaluate and compare health-related quality of life (HRQL) of women with early-stage breast cancer (BC) treated with different radiotherapy (RT) regimens. METHODS: Data were collected from five prospective cohorts of BC patients treated with breast-conserving surgery and different RT regimens: intraoperative RT (IORT, 1 × 23.3 Gy; n = 267), external beam accelerated partial breast irradiation (EB-APBI, 10 × 3.85 Gy; n = 206), hypofractionated whole breast irradiation(hypo-WBI, 16 × 2.67 Gy; n = 375), hypo-WBI + boost(hypo-WBI-B, 21–26 × 2.67 Gy; n = 189), and simultaneous WBI + boost(WBI-B, 28 × 2.3 Gy; n = 475). Women ≥ 60 years with invasive/in situ carcinoma ≤ 30 mm, cN0 and pN0-1a were included. Validated EORTC QLQ-C30/BR23 questionnaires were used to asses HRQL. Multivariable linear regression models adjusted for confounding (age, comorbidity, pT, locoregional treatment, systemic therapy) were used to compare the impact of the RT regimens on HRQL at 12 and 24 months. Differences in HRQL over time (3–24 months) were evaluated using linear mixed models. RESULTS: There were no significant differences in HRQL at 12 months between groups except for breast symptoms which were better after IORT and EB-APBI compared to hypo-WBI at 12 months (p < 0.001). Over time, breast symptoms, fatigue, global health status and role functioning were significantly better after IORT and EB-APBI than hypo-WBI. At 24 months, HRQL was comparable in all groups. CONCLUSION: In women with early-stage breast cancer, the radiotherapy regimen did not substantially influence long-term HRQL with the exception of breast symptoms. Breast symptoms are more common after WBI than after IORT or EB-APBI and improve slowly until no significant difference remains at 2 years posttreatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10549-021-06314-4