[Protontherapy : principles, advantages, limitations, indications, perspectives...and some Belgian peculiarities]. / La protonthérapie : principes, avantages, limitations, indications, perspectives...et quelques histoires belges.

Most radiotherapy treatments are nowadays delivered with linear accelerators producing photons. This robust radiation technique improved outstandingly during the last three decades, allowing treatments for most tumoural indications with an exquisite accuracy, a formidable effectiveness, a low toxicity, and a very low cost for the society. Therefore, the reasons for using and developing the more expensive hadron therapy and more particularly proton therapy may seem futile. In the current article targeting the general practitioners readership, we look at the principles of this innovative technique, its inherent advantages and limitations, the current and future indications, the challenges and perspectives for the future. We conclude with an overview of the Belgian landscape in terms of installation, operation, access and reimbursement procedures.

L'essentiel des traitements de radiothérapie sont délivrés à l'aide d'accélérateurs linéaires produisant des photons. La technique est robuste et a connu une évolution fulgurante ces trois dernières décennies, apportant une efficacité redoutable et une extrême précision dans de nombreuses indications tumorales, avec les avantages d'un risque de toxicité réduit et d'un coût sociétal extrêmement faible. Dès lors, quel intérêt y aurait-il à utiliser et développer des traitements de radiothérapie par hadrons, et plus particulièrement par protons, sachant que les coûts d'installation et de production sont, au bas mot, décuplés par rapport aux photons ? Dans cet article destiné en première intention aux praticiens de santé généralistes, nous abordons les principes de fonctionnement, les avantages et limitations inhérents à la technique, les indications actuelles et celles qui se profilent, les défis et perspectives à venir. Nous terminons, enfin, par un tour d'horizon du paysage belge en termes d'installation, de fonctionnement, d'accès et de modalités de remboursement.

Clinical implications of dose to functional lung volumes in the trimodality treatment of esophageal cancer.

BACKGROUND: Trimodality treatment, i.e., neoadjuvant chemoradiotherapy (nCRT) followed by surgery, for locally advanced esophageal cancer (EC) improves overall survival but also increases the risk of postoperative pulmonary complications. Here, we tried to identify a relation between dose to functional lung volumes (FLV) as determined by 4D-CT scans in EC patients and treatment-related lung toxicity. MATERIALS AND METHODS: All patients with EC undergoing trimodality treatment between 2017 and 2022 in UZ Leuven and scanned with 4D-CT-simulation were selected. FLVs were determined based on Jacobian determinants of deformable image registration between maximum inspiration and expiration phases. Dose/volume parameters of the anatomical lung volume (ALV) and FLV were compared between patients with versus without postoperative pulmonary complications. Results of pre- and post-nCRT pulmonary function tests (PFTs) were collected and compared in relation to radiation dose. RESULTS: Twelve out of 51 EC patients developed postoperative pulmonary complications. ALV was smaller while FLV10Gy and FLV20Gy were larger in patients with complications (respectively 3141 ± 858mL vs 3601 ± 635mL, p = 0.025; 360 ± 216mL vs 264 ± 139mL, p = 0.038; 166 ± 106mL vs 118 ± 63mL, p = 0.030). No differences in ALV dose-volume parameters were detected. Baseline FEV1 and TLC were significantly lower in patients with complications (respectively 90 ± 17%pred vs 102 ± 20%pred, p = 0.033 and 93 ± 17%pred vs 110 ± 13%pred, p = 0.001), though no other PFTs were significantly different between both groups. DLCO was the only PFT that had a meaningful decrease after nCRT (85 ± 17%pred vs 68 ± 15%pred, p < 0.001) but was not related to dose to ALV/FLV. CONCLUSION: Small ALV and increasing FLV exposed to intermediate (10 to 20 Gy) dose are associated to postoperative pulmonary complications. Changes of DLCO occur during nCRT but do not seem to be related to radiation dose to ALV or FLV. This information could attribute towards toxicity risk prediction and reduction strategies for EC.

Potential Molecular Mechanisms behind the Ultra-High Dose Rate "FLASH" Effect.

FLASH radiotherapy, or the delivery of a dose at an ultra-high dose rate (>40 Gy/s), has recently emerged as a promising tool to enhance the therapeutic index in cancer treatment. The remarkable sparing of normal tissues and equivalent tumor control by FLASH irradiation compared to conventional dose rate irradiation­the FLASH effect­has already been demonstrated in several preclinical models and even in a first patient with T-cell cutaneous lymphoma. However, the biological mechanisms responsible for the differential effect produced by FLASH irradiation in normal and cancer cells remain to be elucidated. This is of great importance because a good understanding of the underlying radiobiological mechanisms and characterization of the specific beam parameters is required for a successful clinical translation of FLASH radiotherapy. In this review, we summarize the FLASH investigations performed so far and critically evaluate the current hypotheses explaining the FLASH effect, including oxygen depletion, the production of reactive oxygen species, and an altered immune response. We also propose a new theory that assumes an important role of mitochondria in mediating the normal tissue and tumor response to FLASH dose rates.

Optimal 68Ga-PSMA and 18F-PSMA PET window levelling for gross tumour volume delineation in primary prostate cancer.

PURPOSE: This study proposes optimal tracer-specific threshold-based window levels for PSMA PET-based intraprostatic gross tumour volume (GTV) contouring to reduce interobserver delineation variability. METHODS: Nine 68Ga-PSMA-11 and nine 18F-PSMA-1007 PET scans including GTV delineations of four expert teams (GTVmanual) and a majority-voted GTV (GTVmajority) were assessed with respect to a registered histopathological GTV (GTVhisto) as the gold standard reference. The standard uptake values (SUVs) per voxel were converted to a percentage (SUV%) relative to the SUVmax. The statistically optimised SUV% threshold (SOST) was defined as those that maximises accuracy for threshold-based contouring. A leave-one-out cross-validation receiver operating characteristic (ROC) curve analysis was performed to determine the SOST for each tracer. The SOST analysis was performed twice, first using the GTVhisto contour as training structure (GTVSOST-H) and second using the GTVmajority contour as training structure (GTVSOST-MA) to correct for any limited misregistration. The accuracy of both GTVSOST-H and GTVSOST-MA was calculated relative to GTVhisto in the 'leave-one-out' patient of each fold and compared with the accuracy of GTVmanual. RESULTS: ROC curve analysis for 68Ga-PSMA-11 PET revealed a median threshold of 25 SUV% (range, 22-27 SUV%) and 41 SUV% (40-43 SUV%) for GTVSOST-H and GTVSOST-MA, respectively. For 18F-PSMA-1007 PET, a median threshold of 42 SUV% (39-45 SUV%) for GTVSOST-H and 44 SUV% (42-45 SUV%) for GTVSOST-MA was found. A significant pairwise difference was observed when comparing the accuracy of the GTVSOST-H contours with the median accuracy of the GTVmanual contours (median, - 2.5%; IQR, - 26.5-0.2%; p = 0.020), whereas no significant pairwise difference was found for the GTVSOST-MA contours (median, - 0.3%; IQR, - 4.4-0.6%; p = 0.199). CONCLUSIONS: Threshold-based contouring using GTVmajority-trained SOSTs achieves an accuracy comparable with manual contours in delineating GTVhisto. The median SOSTs of 41 SUV% for 68Ga-PSMA-11 PET and 44 SUV% for 18F-PSMA-1007 PET form a base for tracer-specific window levelling. TRIAL REGISTRATION: Clinicaltrials.gov ; NCT03327675; 31-10-2017.

Development and External Validation of a Multiparametric Magnetic Resonance Imaging and International Society of Urological Pathology Based Add-On Prediction Tool to Identify Prostate Cancer Candidates for Pelvic Lymph Node Dissection.

PURPOSE: We sought to expand current prediction tools for lymph node invasion in patients with prostate cancer using current state-of-the-art available tumor information, including multiparametric magnetic resonance imaging based tumor stage and detailed biopsy information. MATERIALS AND METHODS: We selected patients with prostate cancer for study who had available registered information on ISUP (International Society of Urological Pathology) based biopsy grading and multiparametric magnetic resonance imaging, and who had undergone radical prostatectomy with extended pelvic lymph node dissection. We developed a lymph node invasion prediction tool in 420 patients and externally validated it in 187. A concordance index was estimated to quantify the discriminative performance of the model. RESULTS: In the development cohort a median of 21 lymph nodes were removed per patient and 71 patients (16.9%) were diagnosed with lymph node invasion. Statistically significant predictors of lymph node invasion were the initial prostate specific antigen value, multiparametric magnetic resonance imaging based T stage, maximum tumor length in 1 core in mm and ISUP grade group corresponding to the maximum tumor involvement in 1 core. The predictive accuracy of this lymph node invasion prediction tool was 79.7% after fivefold internal cross validation and 72.5% after external validation. CONCLUSIONS: We report a contemporary, externally validated prediction tool for lymph node invasion in patients with prostate cancer. This prediction tool is a response to the paradigm shift from systematic to targeted biopsies by incorporating additional core specific biopsy information instead of the percent of positive cores. This new tool will also overcome stage migration, which is a potential risk when multiparametric magnetic resonance imaging information is used in digital rectal examination based nomograms.

Variation in adjuvant and early salvage radiotherapy after robot-assisted radical prostatectomy for prostate cancer: a population-based cohort study.

Purpose: The primary aim of the study was to assess the association between having a radiotherapy (RT) department on-site at the surgical centre and the performed postoperative treatment strategy for prostate cancer (PCa) patients. According to the current international guidelines, adjuvant radiotherapy (ART) or a regular prostate-specific antigen (PSA)-based follow-up with (early) salvage radiotherapy ((e)SRT) if needed is recommended in case of adverse pathological characteristics.Material and methods: Prospective data on consecutive robot-assisted radical prostatectomy (RARP) patients in Belgium from 2009 to 2016 were identified in the Belgian Robotic-Assisted-Laparoscopic-Prostatectomy (Be-RALP) database. Multivariable regression was used to evaluate patient- and facility-related factors associated with postoperative radiation treatment.Results: 2072 patients undergoing a RARP, suffering at least one of the following adverse pathological features, i.e., extracapsular extension (ECE), seminal vesicle invasion (SVI) or positive section margins (PSM), and with registered follow-up until 24 months were enrolled. After RARP, ART was applied to 9.1% and (e)SRT to 12.6% of the patients. Multivariable analysis demonstrated that patients were more likely to receive ART or (e)SRT if they were operated in a hospital with a RT department on-site (odds ratio, ART: 1.49 [1.07-2.07]; (e)SRT: 1.55 [1.16-2.06]). Furthermore, the presence of higher tumour category (T-category) and/or PSM on final pathology was associated with a higher chance of getting ART and (e)SRT (p < .01).Conclusion: Variations in ART and (e)SRT are not only driven by patient-related characteristics. In our nationwide cohort, the availability of a RT department on-site at the surgical centre was found to be an independent predictor for ART and (e)SRT, with a 1.5 times higher odds of receiving postoperative RT during the first 24 months after surgery.

Improved repeatability of dynamic contrast-enhanced MRI using the complex MRI signal to derive arterial input functions: a test-retest study in prostate cancer patients.

PURPOSE: The arterial input function (AIF) is a major source of uncertainty in tracer kinetic (TK) analysis of dynamic contrast-enhanced (DCE)-MRI data. The aim of this study was to investigate the repeatability of AIFs extracted from the complex signal and of the resulting TK parameters in prostate cancer patients. METHODS: Twenty-two patients with biopsy-proven prostate cancer underwent a 3T MRI exam twice. DCE-MRI data were acquired with a 3D spoiled gradient echo sequence. AIFs were extracted from the magnitude of the signal (AIFMAGN ), phase (AIFPHASE ), and complex signal (AIFCOMPLEX ). The Tofts model was applied to extract Ktrans , kep and ve . Repeatability of AIF curve characteristics and TK parameters was assessed with the within-subject coefficient of variation (wCV). RESULTS: The wCV for peak height and full width at half maximum for AIFCOMPLEX (7% and 8%) indicated an improved repeatability compared to AIFMAGN (12% and 12%) and AIFPHASE (12% and 7%). This translated in lower wCV values for Ktrans (11%) with AIFCOMPLEX in comparison to AIFMAGN (24%) and AIFPHASE (15%). For kep , the wCV was 16% with AIFMAGN , 13% with AIFPHASE , and 13% with AIFCOMPLEX . CONCLUSION: Repeatability of AIFPHASE and AIFCOMPLEX is higher than for AIFMAGN , resulting in a better repeatability of TK parameters. Thus, use of either AIFPHASE or AIFCOMPLEX improves the robustness of quantitative analysis of DCE-MRI in prostate cancer.

Patched 1 Expression Correlates with Biochemical Relapse in High-Risk Prostate Cancer Patients.

There is an unmet clinical need for adequate biomarkers to aid risk stratification and management of prostate cancer (PCa) patients. Even within the high-risk PCa category, not all patients will invariably have a poor prognosis, and improved stratification of this heterogeneous group is needed. In this context, components of the hedgehog (Hh) pathway may have promise as biomarkers, because the available evidence suggests increased Hh pathway activity may confer a poorer outcome in advanced and castrate-resistant PCa. In this study, potential associations between Hh pathway protein expression and clinicopathological factors, including time to biochemical recurrence (BCR), were investigated using a tissue microarray constructed from benign and malignant prostate samples from 75 predominantly high-risk PCa patients who underwent radical prostatectomy. Hh signaling activity was found to differ between benign and malignant prostate tissue, with a greater amount of active Hh signaling present in malignant than benign prostate epithelium. High expression of Patched 1 in malignant prostate epithelium was found to be an independent predictor of BCR in high-risk PCa patients. Glioma-associated oncogene 1 may potentially represent a clinically useful biomarker of an aggressive tumor phenotype. Evaluation of Hh signaling activity in PCa patients may be useful for risk stratification, and epithelial Patched 1 expression, in particular, may be a prognostic marker for BCR in high-risk PCa patients.

Tissue microarray analysis indicates hedgehog signaling as a potential prognostic factor in intermediate-risk prostate cancer.

BACKGROUND: Prostate cancer (PCa) is a heterogeneous disease with a variable natural history, genetics, and treatment outcome. The Hedgehog (Hh) signaling pathway is increasingly recognized as being potentially important for the development and progression of PCa. In this retrospective study, we compared the activation status of the Hh signaling pathway between benign and tumor tissue, and evaluated the clinical significance of Hh signaling in PCa. METHODS: In this tissue microarray (TMA) study, the protein expression of several Hh signaling components and Hh target proteins, along with microvessel density, were compared between benign (n = 64) and malignant (n = 170) prostate tissue, and correlated with PCa clinicopathological characteristics and biochemical recurrence (BCR). RESULTS: The Hh signaling pathway appeared to be more active in PCa than in benign prostate tissue, as demonstrated by lower expression of the negative regulators PTCH1 and GLI3 in the tumor tissue compared to benign. In addition, high epithelial GLI2 expression correlated with higher pathological Gleason score. Overall, higher epithelial GLI3 expression in the tumor was shown to be an independent marker of a favorable prognosis. CONCLUSION: Hh signaling activation might reflect aggressive tumoral behavior, since high epithelial GLI2 expression positively correlates with a higher pathological Gleason score. Moreover, higher epithelial GLI3 expression is an independent marker of a more favorable prognosis.

The Effect of Metformin and GANT61 Combinations on the Radiosensitivity of Prostate Cancer Cells.

The anti-diabetes drug metformin has been shown to have anti-neoplastic effects in several tumor models through its effects on energy metabolism and protein synthesis. Recent studies show that metformin also targets Hedgehog (Hh) signaling, a developmental pathway re-activated in several tumor types, including prostate cancer (PCa). Furthermore, we and others have shown that Hh signaling is an important target for radiosensitization. Here, we evaluated the combination of metformin and the Hh inhibitor GANT61 (GLI-ANTagonist 61) with or without ionizing radiation in three PCa cell lines (PC3, DU145, 22Rv1). The effect on proliferation, radiosensitivity, apoptosis, cell cycle distribution, reactive oxygen species production, DNA repair, gene and protein expression was investigated. Furthermore, this treatment combination was also assessed in vivo. Metformin was shown to interact with Hh signaling by inhibiting the effector protein glioma-associated oncogene homolog 1 (GLI1) in PCa cells both in vitro and in vivo. The combination of metformin and GANT61 significantly inhibited PCa cell growth in vitro and enhanced the radiation response of 22Rv1 cells compared to either single agent. Nevertheless, neither the growth inhibitory effect nor the radiosensitization effect of the combination treatment observed in vitro was seen in vivo. Although the interaction between metformin and Hh signaling seems to be promising from a therapeutic point of view in vitro, more research is needed when implementing this combination strategy in vivo.

In vitro and in vivo evaluation of the radiosensitizing effect of a selective FGFR inhibitor (JNJ-42756493) for rectal cancer.

BACKGROUND: We examined the anti-tumor effect and radiosensitizing potential of a small molecule inhibitor of fibroblast growth factor receptor (FGFR) in colorectal cancer (CRC) in vitro and in vivo. METHODS: Effects of in vitro drug treatment on cell survival, proliferation, FGFR signaling, cell cycle distribution, apoptosis and radiosensitivity were assessed using various CRC cell lines with FGFR wild type (Caco2 and HCA7) and FGFR2 amplification (HCT116, NCI-H716). In vivo tumor responses to FGFR inhibition with and without radiation therapy were evaluated by growth delay assays in two colorectal xenograft mouse models (NMRI nu/nu mice injected with NCI-H716 or CaCo2 cells). Mechanistic studies were conducted using Western blot analysis, immunohistochemistry and qPCR. RESULTS: In the tested cell lines, the FGFR inhibitor (JNJ-42756493) was effective in vitro and in vivo in CRC tumors with highest expression of FGFR2 (NCI-H716). In vitro, cell proliferation in this line was decreased, associated with increased apoptotic death and decreased cell survival. In vivo, growth of NCI-H716 tumors was delayed by 5 days by drug treatment alone, although when drug delivery was stopped the relative tumor volume increased compared to control. The FGFR inhibitor did not radiosensitize NCI-H716 tumors either in vitro or in vivo. CONCLUSIONS: Among tested CRC cell lines, the growth inhibitory activity of this FGFR inhibitor was evident in cell lines with high constitutive FGFR2 expression, suggesting that FGFR addiction may provide a window for therapeutic intervention, though caution is advised. Preclinical study with NCI-H716 and Caco2 tumor demonstrated that continued presence of drug could be essential for tumor growth control, especially in cells with aberrant FGFR expression. In the tested set-up, the inhibitor showed no radiosensitizing effect.

Reliability of sentinel node procedure for lymph node staging in prostate cancer patients at high risk for lymph node involvement.

AIM: To investigate the reliability of a sentinel node (SN) procedure for nodal staging in prostate cancer (PCa) patients at high risk for lymph node (LN) involvement. MATERIAL AND METHODS: Seventy-four patients with localized prostate adenocarcinoma, who were clinically node-negative and had a risk of LN involvement of ≥ 10% (Partin tables), were prospectively enrolled. Upon intraprostatic 99mTc-nanocolloid injection, they underwent planar scintigraphy and SPECT imaging. Surgical removal of the SN, located by means of a gamma probe, was completed with a superextended LN dissection (seLND) as a reference and followed by radical prostatectomy. RESULTS: In total, 470 SN (median 6, IQR 3-9) were scintigraphically detected of which 371 (median 4, IQR 2-6) were located by gamma probe and selectively removed during surgery (79%). Histopathology confirmed LN metastases in 37 patients (50%) having 106 affected LN in total (median number per patient 2, IQR 1-4). Twenty-eight patients were node positive (N+) based on the analysis of the resected SN. However, the seLND that was performed as a reference revealed nine additional N+ patients resulting in a sensitivity of 76% (28/37). In total, 15 of 37 patients (41%) had metastases in SN only and could have been spared seLND to remove all affected nodes. CONCLUSION: We found a relatively low sensitivity when addressing the SN procedure for nodal staging in PCa patients at high risk for LN involvement. Importantly, only less than half of the N+ patients could have been spared a seLND to remove all affected lymphoid tissue.

Multiparametric MRI for prostate cancer localization in correlation to whole-mount histopathology.

PURPOSE: To prospectively evaluate multiparametric magnetic resonance imaging (MRI) for accurate localization of intraprostatic tumor nodules, with whole-mount histopathology as the gold standard. MATERIALS AND METHODS: Seventy-five patients with biopsy-proven, intermediate, and high-risk prostate cancer underwent preoperative T2-weighted (T2w), dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) MRI at 1.5T. Localization of suspicious lesions was recorded for each of 24 standardized regions of interest on the different MR images and correlated with the pathologic findings. Generalized estimating equations (GEE) were used to estimate the sensitivity, specificity, accuracy, positive, and negative predictive value for every MRI modality, as well as to evaluate the influence of Gleason score and pT-stage. Tumor volume measurements on histopathological specimens were correlated with those on the different MR modalities (Pearson correlation). RESULTS: DW MRI had the highest sensitivity for tumor localization (31.1% vs. 27.4% vs. 44.5% for T2w, DCE, and DW MRI, respectively; P < 0.005), with more aggressive or more advanced tumors being more easily detected with this imaging modality. Significantly higher sensitivity values were obtained for the combination of T2w, DCE, and DW MRI (58.8%) as compared to each modality alone or any combination of two modalities (P < 0.0001). Tumor volume can most accurately be assessed by means of DW MRI (r = 0.75; P < 0.0001). CONCLUSION: Combining T2w, DCE, and DW imaging significantly improves prostate cancer localization.

Identification and characterization of nodal metastases in prostate cancer patients at high risk for lymph node involvement.

AIM: To investigate whether blood-based markers could be used to identify prostate cancer (PCa) patients harboring lymph node (LN) metastases. In addition, E-cadherin expression was studied within the concept of epithelial mesenchymal plasticity. MATERIAL AND METHODS: Seventy-five patients with clinically localized PCa who underwent a superextended lymphadenectomy followed by radical prostatectomy (RP) were included in this study. Preoperative plasma/serum levels of endoglin, transforming growth factor-ß1 (TGF-ß1), osteopontin, vascular endothelial growth factor (VEGF), vascular cell adhesion molecule-1 (VCAM-1), and E-cadherin were measured using commercially available enzyme immunoassays in 47/75 patients and correlated with clinicopathological parameters. E-cadherin expression in the diagnostic biopsies (n = 63), RP specimens (n = 75) and LN metastases (n = 106) was examined by immunohistochemical analysis. RESULTS: Occult LN metastases were present in almost half of the patients (37/75), with a total of 106 affected LN. Preoperative levels of endoglin, TGF-ß1, osteopontin, VEGF, VCAM-1 nor E-cadherin were significantly associated with LN status. Only a positive correlation between plasma endoglin and serum prostate-specific antigen was found (Spearman's r = 0.44; p = 0.002). The majority of biopsies (91.9%) and RP specimens (79.7%) showed strong E-cadherin expression, while in the LN this was found to be much weaker (28.9%). While the staining pattern in the isolated tumor cells (ITC) and micrometastases was mainly homogenous, the macrometastases showed a much more heterogeneous pattern (χ², p < 0.0001). CONCLUSION: In this study, none of the blood-based markers tested could be used for nodal staging in PCa, nor could E-cadherin expression in the tissue. However, the difference in E-cadherin expression pattern between the ITC/micrometastases and the macrometastases may point to another biological behavior. The specific staining pattern seen in the macrometastases could indicate an ongoing mesenchymal epithelial transition, presumed to be a mechanism for metastatic colonization. As the latter is the rate-limiting step in the metastatic process, evaluation of the E-cadherin expression pattern could have potential therapeutic implications.

Hedgehog signaling in prostate cancer and its therapeutic implication.

Activation of Hedgehog (Hh) signaling is implicated in the development and progression of several tumor types, including prostate cancer, which is still the most common non-skin malignancy and the third leading cause of cancer-related mortality in men in industrialized countries worldwide. Several studies have indicated that the Hh pathway plays a crucial role in the development as well as in the progression of this disease to more aggressive and even therapy-resistant disease states. Moreover, preclinical data have shown that inhibition of Hh signaling has the potential to reduce prostate cancer invasiveness and metastatic potential. Clinical trials investigating the benefit of Hh inhibitors in patients with prostate cancer have recently been initiated. However, acquired drug resistance has already been observed in other tumor types after long-term Hh inhibition. Therefore, combining Hh inhibitors with ionizing radiation, chemotherapy or other molecular targeted agents could represent an alternative therapeutic strategy. In this review, we will highlight the role of Hh signaling in the development and progression of prostate cancer and summarize the different therapeutic applications of Hedgehog inhibition.

The use of electronic Patient Reported Outcomes in follow-up after palliative radiotherapy: A survey study in Belgium.

Objective: Electronic Patient-Reported Outcome Measures (ePROMs) could be used to monitor patients' symptoms after treatment. However, ePROM implementation in clinical practice has been challenging, especially in (palliative) radiation oncology. The aim of this study was to explore the opinions of healthcare providers (HCP) active in radiation oncology in Belgium on the use of ePROMs for symptom follow-up after palliative radiotherapy. Methods: An anonymous online survey was conducted with different HCP in radiation oncology in Belgium. Participants were recruited through several professional organizations with approximately 390 members actively working in the field of radiation oncology. The survey used was a self-developed questionnaire, based on existing literature on implementation of (e)PROMs in cancer care, our previous research on this topic as well as our personal experience in the field of oncology and palliative care. Results: Of the 128 respondents, 26% had experience with ePROMs in clinical practice. Eighty-four percent considered ePROMs beneficial for patients' health and symptom knowledge, symptom self-management and active participation in care. ePROMs could help HCP to focus on detection of relevant symptoms and improve their management. Almost 75% were willing to implement and use ePROMs. Assigning ePROM introduction and follow-up to a dedicated person, such as a nurse navigator, was suggested to promote ePROM implementation and use in clinical practice. Conclusion: Despite limited experience with ePROMs in clinical care for palliative radiotherapy patients, the majority of respondents is willing to implement and use ePROMs for this particular patient population. Innovation: This is one of the first studies specifically focusing on experiences and opinions of HCP in radiation oncology on the use of ePROMs for symptom follow-up in palliative radiotherapy. HCP should be actively involved in implementation of ePROMs after palliative radiotherapy, to translate their vision of their ideals in practice.

"Scan-(pre)Plan-Treat" Workflow for Bone Metastases Using the Ethos Therapy System: A Single-Center, In Silico Experience.

Purpose: To report on the accuracy of automated delineation, treatment plan quality, and duration of an in-silico "scan-(pre)plan-treat" (SPT) workflow for vertebral bone metastases using a 1 × 8 Gy regimen. Method and Materials: The cloud-based emulator system of the Ethos therapy system was used to adapt an organ-at-risk-sparing preplan created on the diagnostic CT to the anatomy-of-the-day using the cone beam CT made before treatment. Results: SPT using the Ethos emulator system resulted in relatively good coverage of the PTV and acceptable dose to the OAR. Delivery time and plan homogeneity was the best for 7-field IMRT plan template. Conclusions: A SPT workflow formula results in a highly conformal treatment delivery while maintaining an acceptable timeframe for the patient on the treatment couch.

From once-weekly to semi-weekly whole prostate gland stereotactic radiotherapy with focal boosting: Primary endpoint analysis of the multicenter phase II hypo-FLAME 2.0 trial.

BACKGROUND AND PURPOSE: The hypo-FLAME trial showed that once-weekly (QW) focal boosted prostate stereotactic body radiotherapy (SBRT) is associated with acceptable acute genitourinary (GU) and gastrointestinal (GI) toxicity. Currently, we investigated the safety of reducing the overall treatment time (OTT) of focal boosted prostate SBRT from 29 to 15 days. MATERIAL AND METHODS: Patients with intermediate- and high-risk prostate cancer were treated with SBRT delivering 35 Gy in 5 fractions to the whole prostate gland with an iso-toxic boost up to 50 Gy to the intraprostatic lesion(s) in a semi-weekly (BIW) schedule. The primary endpoint was radiation-induced acute toxicity (CTCAE v5.0). Changes in quality of life (QoL) were examined in terms of proportions achieving a minimal clinically important change (MCIC). Finally, acute toxicity and QoL scores of the BIW schedule were compared with the results of the prior QW hypo-FLAME schedule (n = 100). RESULTS: Between August 2020 and February 2022, 124 patients were enrolled and treated BIW. No grade ≥3 GU or GI toxicity was observed. The 90-days cumulative incidence of grade 2 GU and GI toxicity rates were 47.5% and 7.4%, respectively. Patients treated QW scored significant less grade 2 GU toxicity (34.0%, p = 0.01). No significant differences in acute GI toxicity were observed. Furthermore, patients treated QW had a superior acute bowel and urinary QoL. CONCLUSION: Semi-weekly prostate SBRT with iso-toxic focal boosting is associated with acceptable acute GU and GI toxicity. Based on the comparison between the QW and BIW schedule, patients should be counselled regarding the short-term advantages of a more protracted schedule. Registration number ClinicalTrials.gov: NCT04045717.

Using ePROMs for follow-up after palliative radiotherapy: An exploratory study with patients and health care providers.

OBJECTIVES: Patients treated with palliative radiotherapy may experience symptoms decreasing their quality of life. Electronic patient-reported outcome measures (ePROMs) could provide an opportunity to follow-up patients after treatment. METHODS: A mixed-method study was performed using self-constructed questionnaires, focus groups and interviews with patients and health care professionals (HCP). A qualitative approach was used to code the data. RESULTS: Forty-two patients, 21 radiation-oncologists, 15 general practitioners (GPs) and 24 home-care nurses completed a questionnaire. Ten patients, 6 radiation-oncologists, 14 GPs and 5 nurses were interviewed or participated in a focus group. Although patients and HCP are satisfied with current care, they believe ePROMs could improve follow-up, communication, continuity of care and self-management of symptoms. An easy to use, versatile ePROM platform seems to be important for successful implementation. Self-care tips and contact information should be added to relevant ePROM-questions, on both physical and psychological symptoms. CONCLUSION: Patients and HCP agree that ePROMs could improve systematical clinical follow-up after palliative radiotherapy, with self-management support being the primary objective of such a system. Practice implications ePROMs after palliative radiotherapy seem feasible, the exact patient population that could benefit the most will need to be explored further; as the palliative population is very diverse.