Introduction: Patients with cancer receiving radio- or chemotherapy undergo many immunological stressors. Chronic regular exercise has been shown to positively influence the immune system in several populations, while exercise overload may have negative effects. Exercise is currently recommended for all patients with cancer. However, knowledge regarding the effects of exercise on immune markers in patients undergoing chemo- or radiotherapy is limited. The aim of this study is to systematically review the effects of moderate- and high-intensity exercise interventions in patients with cancer during chemotherapy or radiotherapy on immune markers. Methods: For this review, a search was performed in PubMed and EMBASE, until March 2023. Methodological quality was assessed with the PEDro tool and best-evidence syntheses were performed both per immune marker and for the inflammatory profile. Results: Methodological quality of the 15 included articles was rated fair to good. The majority of markers were unaltered, but observed effects included a suppressive effect of exercise during radiotherapy on some proinflammatory markers, a preserving effect of exercise during chemotherapy on NK cell degranulation and cytotoxicity, a protective effect on the decrease in thrombocytes during chemotherapy, and a positive effect of exercise during chemotherapy on IgA. Conclusion: Although exercise only influenced a few markers, the results are promising. Exercise did not negatively influence immune markers, and some were positively affected since suppressed inflammation might have positive clinical implications. For future research, consensus is needed regarding a set of markers that are most responsive to exercise. Next, differential effects of training types and intensities on these markers should be further investigated, as well as their clinical implications.
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Background and purpose: Automatic approaches are widely implemented to automate dose optimization in radiotherapy treatment planning. This study systematically investigates how to configure automatic planning in order to create the best possible plans. Materials and methods: Automatic plans were generated using protocol based automatic iterative optimization. Starting from a simple automation protocol which consisted of the constraints for targets and organs at risk (OAR), the performance of the automatic approach was evaluated in terms of target coverage, OAR sparing, conformity, beam complexity, and plan quality. More complex protocols were systematically explored to improve the quality of the automatic plans. The protocols could be improved by adding a dose goal on the outer 2 mm of the PTV, by setting goals on strategically chosen subparts of OARs, by adding goals for conformity, and by limiting the leaf motion. For prostate plans, development of an automated post-optimization procedure was required to achieve precise control over the dose distribution. Automatic and manually optimized plans were compared for 20 head and neck (H&N), 20 prostate, and 20 rectum cancer patients. Results: Based on simple automation protocols, the automatic optimizer was not always able to generate adequate treatment plans. For the improved final configurations for the three sites, the dose was lower in automatic plans compared to the manual plans in 12 out of 13 considered OARs. In blind tests, the automatic plans were preferred in 80% of cases. Conclusions: With adequate, advanced, protocols the automatic planning approach is able to create high-quality treatment plans.
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Abstract gepubliseerd in Elsevier: For patients with intermediate- and high risk prostate cancer, treated with high dose radiotherapy, the CTV generally involves the prostate and (part of) the seminal vesicles (SV) [1,2]. Fiducial markers locate the prostate reliably during radiotherapy [3]. However the SV may move independent from the corpus of the prostate [4–6]. As this should be incorporated in the PTV margin [4,6–8], this may lead to a larger irradiated rectum volume and more gastro-intestinal toxicity [9]. Several studies have shown that rectal and bladder filling are of influence on prostate and SV mobility [10–13]. Using a dietary protocol or applying rectal gas removal could somewhat decrease the prostate and SV mobility [14,15], however, these methods are not very patient friendly. In this study we hypothesize that the vesicles become more rigidly attached to the prostate in case of tumour infiltration. This would imply that in case of extensive infiltration, the prostate and vesicles move as a rigid body and are thus adequately localized by marker-based Image Guided Radiotherapy (IGRT). The aim of this study was to assess the impact of tumour invasion in the SV on their mobility.
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Abstract: Plan adaptation during the course of (chemo)radiotherapy of H&N cancer requires repeat CT scanning to capture anatomy changes such as parotid gland shrinkage. Hydration, applied to prevent nephrotoxicity from cisplatin, could temporarily alter the hydrogen balance and hence the captured anatomy. The aim of this study was to determine geometric changes of parotid glands as function of hydration during chemoradiotherapy compared to a control group treated with radiotherapy only.
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Purpose/Objective: Most dose-escalation trials in glioblastoma patients integrate the escalated dose throughout the standard course by targeting a specific subvolume. We hypothesize that anatomical changes during irradiation may affect the dose coverage of this subvolume for both proton- and photon-based radiotherapy. Material and Methods: For 24 glioblastoma patients a photon- and proton-based dose escalation treatment plan (of 75 Gy/30 fr) was simulated on the dedicated radiotherapy planning MRI obtained before treatment. The escalated dose was planned to cover the resection cavity and/or contrast enhancing lesion on the T1w post-gadolinium MRI sequence. To analyze the effect of anatomical changes during treatment, we evaluated on an additional MRI that was obtained during treatment the changes of the dose distribution on this specific high dose region. Results: The median time between the planning MRI and additional MRI was 26 days (range 16–37 days). The median time between the planning MRI and start of radiotherapy was relatively short (7 days, range 3–11 days). In 3 patients (12.5%) changes were observed which resulted in a substantial deterioration of both the photon and proton treatment plans. All these patients underwent a subtotal resection, and a decrease in dose coverage of more than 5% and 10% was observed for the photon- and proton-based treatment plans, respectively. Conclusion: Our study showed that only for a limited number of patients anatomical changes during photon or proton based radiotherapy resulted in a potentially clinically relevant underdosage in the subvolume. Therefore, volume changes during treatment are unlikely to be responsible for the negative outcome of dose-escalation studies.
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Abstract Background: The benefit of MR-only workflow compared to current CT-based workflow for prostate radiotherapy is reduction of systematic errors in the radiotherapy chain by 2–3 mm. Nowadays, MRI is used for target delineation while CT is needed for position verification. In MR-only workflows, MRI based synthetic CT (sCT) replaces CT. Intraprostatic fiducial markers (FMs) are used as a surrogate for the position of the prostate improving targeting. However, FMs are not visible on sCT. Therefore, a semi-automatic method for burning-in FMs on sCT was developed. Accuracy of MR-only workflow using semi-automatically burned-in FMs was assessed and compared to CT/MR workflow. Methods: Thirty-one prostate cancer patients receiving radiotherapy, underwent an additional MR sequence (mDIXON) to create an sCT for MR-only workflow simulation. Three sources of accuracy in the CT/MR- and MR-only workflow were investigated. To compare image registrations for target delineation, the inter-observer error (IOE) of FM-based CT-to-MR image registrations and soft-tissue-based MR-to-MR image registrations were determined on twenty patients. Secondly, the inter-observer variation of the resulting FM positions was determined on twenty patients. Thirdly, on 26 patients CBCTs were retrospectively registered on sCT with burned-in FMs and compared to CT-CBCT registrations. Results: Image registration for target delineation shows a three times smaller IOE for MR-only workflow compared to CT/MR workflow. All observers agreed in correctly identifying all FMs for 18 out of 20 patients (90%). The IOE in CC direction of the center of mass (COM) position of the markers was within the CT slice thickness (2.5 mm), the IOE in AP and RL direction were below 1.0 mm and 1.5 mm, respectively. Registrations for IGRT position verification in MR-only workflow compared to CT/MR workflow were equivalent in RL-, CC- and AP-direction, except for a significant difference for random error in rotation. Conclusions: MR-only workflow using sCT with burned-in FMs is an improvement compared to the current CT/ MR workflow, with a three times smaller inter observer error in CT-MR registration and comparable CBCT registration results between CT and sCT reference scans. Trial registry Medical Research Involving Human Subjects Act (WMO) does apply to this study and was approved by the Medical Ethics review Committee of the Academic Medical Center. Registration number: NL65414.018.18. Date of registration: 21–08-2018.
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Op verzoek van Jelle Scheurleer: Purpose: To investigate the accuracy of dose calculation on cone beam CT (CBCT) data sets after HU-RED calibration and validation in phantom studies and clinical patients. Material and methods: Calibration of HU-RED curves for kV-CBCT were generated for three clinical protocols (H&N, thorax and pelvis) by using a Gammex RMI phantom with human tissue equivalent inserts and additional perspex blocks to account for patient scatter. Two calibration curves per clinical protocol were defined, one for the Varian Truebeam 2.0 and another for the OBI systems (Varian, Palo Ato). Differences in HU values with respect to the CT-calibration curve were evaluated for all the inserts. Four radiotherapy plans (breast, prostate, H&N and lung) were produced on an anthropomorphic phantom (Alderson) to evaluate dose differences on the kV-CBCT with the new calibration curves with respect to the CT based dose calculation. Dose differences were evaluated according to the D2%, D98% and Dmean metrics extracted from the DVHs of the plans and - evaluation (2%, 1mm) on the three planes at the isocenter for all plans. Clinical evaluation was performed on 5 patients and dose differences were evaluated as in the phantom study.
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BACKGROUND AND PURPOSE: Radiotherapy of the head and neck is challenged by the relatively large number of organs-at-risk close to the tumor. Biologically-oriented objective functions (OF) could optimally distribute the dose among the organs-at-risk. We aimed to explore OFs based on multivariable normal tissue complication probability (NTCP) models for grade 2-4 dysphagia (DYS) and tube feeding dependence (TFD).MATERIALS AND METHODS: One hundred head and neck cancer patients were studied. Additional to the clinical plan, two more plans (an OFDYS and OFTFD-plan) were optimized per patient. The NTCP models included up to four dose-volume parameters and other non-dosimetric factors. A fully automatic plan optimization framework was used to optimize the OFNTCP-based plans.RESULTS: All OFNTCP-based plans were reviewed and classified as clinically acceptable. On average, the Δdose and ΔNTCP were small comparing the OFDYS-plan, OFTFD-plan, and clinical plan. For 5% of patients NTCPTFD reduced >5% using OFTFD-based planning compared to the OFDYS-plans.CONCLUSIONS: Plan optimization using NTCPDYS- and NTCPTFD-based objective functions resulted in clinically acceptable plans. For patients with considerable risk factors of TFD, the OFTFD steered the optimizer to dose distributions which directly led to slightly lower predicted NTCPTFD values as compared to the other studied plans.
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OBJECTIVES: Patients with head and neck cancer (HNC) frequently encounter weight loss with multiple negative outcomes as a consequence. Adequate treatment is best achieved by early identification of patients at risk for critical weight loss. The objective of this study was to detect predictive factors for critical weight loss in patients with HNC receiving (chemo)radiotherapy ((C)RT).MATERIALS AND METHODS: In this cohort study, 910 patients with HNC were included receiving RT (±surgery/concurrent chemotherapy) with curative intent. Body weight was measured at the start and end of (C)RT. Logistic regression and classification and regression tree (CART) analyses were used to analyse predictive factors for critical weight loss (defined as >5%) during (C)RT. Possible predictors included gender, age, WHO performance status, tumour location, TNM classification, treatment modality, RT technique (three-dimensional conformal RT (3D-RT) vs intensity-modulated RT (IMRT)), total dose on the primary tumour and RT on the elective or macroscopic lymph nodes.RESULTS: At the end of (C)RT, mean weight loss was 5.1±4.9%. Fifty percent of patients had critical weight loss during (C)RT. The main predictors for critical weight loss during (C)RT by both logistic and CART analyses were RT on the lymph nodes, higher RT dose on the primary tumour, receiving 3D-RT instead of IMRT, and younger age.CONCLUSION: Critical weight loss during (C)RT was prevalent in half of HNC patients. To predict critical weight loss, a practical prediction tree for adequate nutritional advice was developed, including the risk factors RT to the neck, higher RT dose, 3D-RT, and younger age.
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To validate the model-based 3D dose calculation performed by theCOMPASS system, and to evaluate the use of the combination ofmodel-based and measurement-based 3D dose determination forclinical QA purposes.
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