European Society of Radiotherapy and Oncology (ESTRO) strategy 2024-2026: Growth and diversification in a rapidly changing world.

In 2019, the European Society of Radiotherapy and Oncology (ESTRO) published its 2030 Vision "Radiation Oncology, Optimal Health, For All, Together". However, in 2020, the global pandemic, coinciding with the Society's 40th anniversary, had long-term consequences on global behaviours and on the financial environment for scientific associations worldwide. In 2022, ESTRO conducted a survey among its members, revealing their strong appreciation for networking opportunities and the creation of high-quality interdisciplinary scientific content. In response to the survey findings and to address the evolving landscape following the COVID pandemic, ESTRO initiated a strategic review process to respond to, and refocus on, the opportunities and challenges ahead. This paper, marking a turning point in ESTRO's strategy for achieving its Vision 2030 in a post-pandemic era, describes the 2022-23 strategic review process, discussions, and consequent recommendations. The comprehensive strategic review process involved: (i) pre-meeting preparations with surveys and strategic documents; (ii) a carefully themed three-day retreat in Brussels incorporating a blend of plenary sessions, workshops focusing on ESTRO's role, value creation and capture, strategic objectives; and (iii) a post-retreat phase including qualitative analysis and development of action plans. The strategic review emphasized the need for adaptive tactics for scientific associations to remain current and productive in the face of changing global conditions. The development of key strategic goals for the years 2024-2026 focused on improving research impact, strengthening and diversifying ESTRO's educational offerings and fostering proactive and mutually beneficial partnerships. The Board approved these objectives, alongside prioritising digital innovation, financial sustainability, and community engagement for ESTRO's continued growth and development. In essence, ESTRO aims to advocate, empower, expand, and diversify its community, with the overarching goal of enhancing cancer care for patients in Europe, and beyond.

Optimizing patient selection for stereotactic ablative radiotherapy in patients with locally advanced pancreatic cancer after initial chemotherapy - a single center prospective cohort.

Background: The role of stereotactic ablative radiation therapy (SABR) as local treatment option after chemotherapy for locally advanced pancreatic cancer (LAPC) is evolving. However adequate patient selection criteria for SABR in patients with LAPC are lacking. Methods: A prospective institutional database collected data of patients with LAPC treated with chemotherapy, mainly FOLFIRINOX, followed by SABR, which was delivered using magnetic resonance guided radiotherapy, 40 Gy in 5 fractions within two weeks. Primary endpoint was overall survival (OS). Cox regression analyses were performed to identify predictors for OS. Results: Overall, 74 patients were included, median age 66 years, 45.9% had a KPS score of ≥90. Median OS was 19.6 months from diagnosis and 12.1 months from start of SABR. Local control was 90% at one year. Multivariable Cox regression analyses identified KPS ≥90, age <70, and absence of pain prior to SABR as independent favorable predictors for OS. The rate of grade ≥3 fatigue and late gastro-intestinal toxicity was 2.7%. Conclusions: SABR is a well-tolerated treatment in patients with unresectable LAPC following chemotherapy, with better outcomes when applied in patients with higher performance score, age <70 years and absence of pain. Future randomized trials will have to confirm these findings.

Single-Fraction Stereotactic Ablative Body Radiotherapy to the Lung - The Knockout Punch.

This overview summarises the current evidence on efficacy and safety of single-fraction stereotactic ablative body radiotherapy (SABR) for primary lung cancers and lung metastases, in comparison with the more widely adapted multi-fraction SABR regimens. A literature search using the Medline database through PubMed was carried out using the following key words: ('stereotactic' or 'sabr' or 'sbrt'), ('radiotherapy' or 'radiation therapy'), ('lung' or 'thorax' or 'thoracic' or 'chest'), ('cancer' or 'metasta-' or 'oligometasta-'), alongside: (i) ('single-fraction' or 'single-dose') to identify trials and cohort studies with single-fraction SABR to lung malignant tumours and (ii) ('fraction' or 'schedule') limiting the search to 'clinical trial' and 'randomized controlled trial' to ensure thorough capture of lung SABR trials comparing different fractionations. The review discusses the radiobiological, technical and organ at risk considerations of single-fraction SABR to the lung.

Treatment of brain metastases in small cell lung cancer: Decision-making amongst a multidisciplinary panel of European experts.

BACKGROUND: Brain metastases (BM) are common in patients with small cell lung cancer (SCLC). In recent years, the role of whole brain radiotherapy (WBRT) for brain metastases in lung cancer is being reevaluated, especially in the context of new systemic treatments available for SCLC. With this analysis, we investigate decision-making in SCLC patients with BM among European experts in medical oncology and radiation oncology. METHODS: We analyzed decision-making from 13 medical oncologists (selected by IASLC) and 13 radiation oncologists (selected by ESTRO) specialized in SCLC. Management strategies of individual experts were converted into decision trees and analyzed for consensus. RESULTS AND CONCLUSION: In asymptomatic patients, chemotherapy alone is the most commonly recommended first line treatment. In asymptomatic patients with limited volume of brain metastases, a higher preference for chemotherapy without WBRT among medical oncologists compared to radiation oncologists was observed. For symptomatic patients, WBRT followed by chemotherapy was recommended most commonly. For limited extent of BM in symptomatic patients, some experts chose stereotactic radiotherapy as an alternative to WBRT. Significant variation in clinical decision-making was observed among European SCLC experts for the first line treatment of patients with SCLC and BM.

The clinical introduction of MR-guided radiation therapy from a RTT perspective.

The latest development in radiation oncology departments towards high precision and adaptive radiation therapy is the clinical introduction of magnetic resonance image guided radiation therapy (MRgRT). Early 2016, patient treatment using MRgRT was started at Amsterdam UMC, location VU University Medical Center. Introducing this novel technique in clinical practice requires thorough preparation with regard to important topics, such as MR-safety and training, equipping the treatment vault and console room, development of MRgRT workflow and logistical issues. Certainly when MRgRT is combined with daily plan adaptation, this indicates adjusting existing workflows and protocols. The MRgRT workflow requires a multidisciplinary process, and while each discipline has had its own tasks and responsibilities, with growing clinical experience there has been a shift towards RTT responsibilities. In this overview we discuss preclinical training and preparation for the implementation of (adaptive) MRgRT, with a particular focus on the perspective of RTTs. Although the reviewed logistics are partly the result of the decision to perform daily plan re-optimization, our experience can be extrapolated to implementation of alternative approaches for MRgRT.

Stereotactic ablative radiotherapy (SABR) for early-stage central lung tumors: New insights and approaches.

The use of stereotactic ablative radiotherapy (SABR) for central lung tumors is increasing. Centrally located lung tumors can be subdivided into two categories, namely the 'moderately central' tumors where the planning target volume is located within 2 cm of the proximal bronchial tree, and the 'ultracentral' tumors where a planning target volume (PTV) overlaps the trachea or main stem bronchi. The toxicity of SABR appears acceptable when 'moderately central' tumors are treated using techniques that comply with organs at risk tolerance doses used for prospective trials and in recent publications. A high toxicity is seen when ultracentral tumors are treated using SABR, and conventional radiotherapy appears more appropriate in such tumors as the true normal organ tolerance doses remain unknown. When ultracentral tumors are treated with non-SABR hypofractionated radiotherapy, a homogenous dose distribution in the planning target volume and limitation of both normal organ maximum point doses and volumes receiving high doses seems to be needed.

Esophagus toxicity after stereotactic and hypofractionated radiotherapy for central lung tumors: Normal tissue complication probability modeling.

PURPOSE: To correlate esophagus toxicity and dose-volume histogram (DVH) parameters in order to assess risks, and derive a Normal Tissue Complication Probability (NTCP) model. METHODS AND MATERIALS: Patients with a central lung tumor from 2 centers, who underwent stereotactic or hypofractionated radiotherapy (≤12 fractions), were analyzed. Doses were recalculated to an equivalent dose of 2 Gy with an α/ß ratio of 10 (EQD210). The esophagus was manually delineated and DVH-parameters (Dmax,EQD2, D1cc,EQD2, D2cc,EQD2, D5cc,EQD2) were analyzed and used for NTCP modeling based on logistic regression analysis. RESULTS: Two-hundred-and-thirty-one patients with 252 tumors were eligible. No acute or late grade 3-5 esophageal toxicity was reported. Acute grade 1-2 esophagus toxicity was recorded in 38 patients (17%). All DVH-parameters were significantly higher in patients with toxicity. NTCP models showed a 50% probability of acute grade 1-2 toxicity at a Dmax of 67 Gy EQD210 and D1cc of 42 Gy EQD210. No difference in overall survival was observed between patients with and without toxicity (p = 0.428). CONCLUSION: As no grade 3-5 esophageal toxicity was observed in our cohort, a Dmax of 56 Gy EQD210 and a D5cc of 35.5 Gy EQD210 could be delivered without high risks of severe toxicity. The NTCP models of this study might be used as practical guidelines for the treatment of central lung tumors with stereotactic radiotherapy.

Normal Tissue Complication Probability Modeling of Pulmonary Toxicity After Stereotactic and Hypofractionated Radiation Therapy for Central Lung Tumors.

PURPOSE: To evaluate clinical pulmonary and radiographic bronchial toxicity after stereotactic ablative radiation therapy and hypofractionated radiation therapy for central lung tumors, and perform normal tissue complication probability modeling and multivariable analyses to identify predictors for toxicity. METHODS AND MATERIALS: A pooled analysis was performed of patients with a central lung tumor treated using ≤12 fractions at 2 centers between 2006 and 2015. Airways were manually contoured on planning computed tomography scans, and doses were recalculated to an equivalent dose of 2 Gy per fraction with an α/ß ratio of 3. Grade ≥3 (≥G3) clinical pulmonary toxicity was evaluated by 2 or more physicians. Radiographic toxicity was defined as a stenosis or an occlusion with or without atelectasis using follow-up computed tomography scans. Logistic regression analyses were used for statistical analyses. RESULTS: A total of 585 bronchial structures were studied in 195 patients who were mainly treated using 5 or 8 fractions (60%). Median patient survival was 27.9 months (95% confidence interval 22.3-33.6 months). Clinical ≥G3 toxicity was observed in 24 patients (12%) and radiographic bronchial toxicity in 55 patients (28%), both mainly manifesting ≤12 months after treatment. All analyzed dosimetric parameters correlated with clinical and lobar bronchial radiographic toxicity, with V130Gy,EQD having the highest odds ratio. Normal tissue complication probability modeling showed a volume dependency for the development of both clinical and radiographic toxicity. On multivariate analyses, significant predictors for ≥G3 toxicity were a planning target volume overlapping the trachea or main stem bronchus (P = .005), chronic obstructive pulmonary disease (P = .034), and the total V130Gy,EQD (P = .012). Radiographic bronchial toxicity did not significantly correlate with clinical toxicity (P = .663). CONCLUSIONS: We identified patient and dosimetric factors associated with clinical and radiographic toxicity after high-dose radiation therapy for central lung tumors. Additional data from prospective studies are needed to validate these findings.

Incidence of High-Risk Radiologic Features in Patients Without Local Recurrence After Stereotactic Ablative Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer.

PURPOSE: To investigate, in the setting of stereotactic ablative radiation therapy (SABR) for early-stage non-small cell lung cancer, the incidence and patterns of change in high-risk radiologic features (HRFs) in patients known to have no local recurrence. METHODS AND MATERIALS: Computed tomography (CT) scans of patients treated using volumetric modulated arc therapy SABR between 2008 and 2013 were eligible if follow-up scans were available for 2 years and no local recurrences were diagnosed. All scans were reviewed at a workstation using an add-on tool for ClearCanvas (Synaptive Medical). Five clinicians who were blinded to clinical outcomes scored the presence of HRFs: enlarging opacity (EO), sequential enlarging opacity, enlarging opacity after 12 months (EO12), bulging margin, loss of linear margins, cranio-caudal growth, and loss of air bronchogram. After each review, clinicians recommended follow-up procedures based on published recommendations. RESULTS: A total of 88 patients (747 CT scans) were evaluated. The HRFs most frequently recorded by ≥3 observers on at least 1 follow-up scan were EO (64.8%), EO12 (50.0%), and sequential enlarging opacity (13.6%). Fifty-six patients developed EO within the first year after SABR, and of these, 46 also developed subsequent EO (EO12). In 76 patients who developed EO after 1 year of follow-up, 30 had not manifested EO previously. Three or more HRFs have been associated with recurrences, and this was observed on CT scan in 22.7% of patients. In their routine care, 6 patients had undergone a positron emission tomography scan because of a suspected local recurrence, and 4 underwent an attempt at biopsy. CONCLUSIONS: More than 50% of patients without a local recurrence after SABR develop HRFs. Because ≥3 HRFs were present in nearly 25% of patients, further refinement of follow-up recommendations are necessary.

Fast and robust online adaptive planning in stereotactic MR-guided adaptive radiation therapy (SMART) for pancreatic cancer.

BACKGROUND AND PURPOSE: To implement a robust and fast stereotactic MR-guided adaptive radiation therapy (SMART) online strategy in locally advanced pancreatic cancer (LAPC). MATERIAL AND METHODS: SMART strategy for plan adaptation was implemented with the MRIdian system (ViewRay Inc.). At each fraction, OAR (re-)contouring is done within a distance of 3cm from the PTV surface. Online plan re-optimization is based on robust prediction of OAR dose and optimization objectives, obtained by building an artificial neural network (ANN). Proposed limited re-contouring strategy for plan adaptation (SMART3CM) is evaluated by comparing 50 previously delivered fractions against a standard (re-)planning method using full-scale OAR (re-)contouring (FULLOAR). Plan quality was assessed using PTV coverage (V95%, Dmean, D1cc) and institutional OAR constraints (e.g. V33Gy). RESULTS: SMART3CM required a significant lower number of optimizations than FULLOAR (4 vs 18 on average) to generate a plan meeting all objectives and institutional OAR constraints. PTV coverage with both strategies was identical (mean V95%=89%). Adaptive plans with SMART3CM exhibited significant lower intermediate and high doses to all OARs than FULLOAR, which also failed in 36% of the cases to adhere to the V33Gy dose constraint. CONCLUSIONS: SMART3CM approach for LAPC allows good OAR sparing and adequate target coverage while requiring only limited online (re-)contouring from clinicians.

The Current Role of Radiotherapy in the Treatment of Small Cell Lung Cancer.

Radiotherapy has been shown to play a key role in the management of small cell lung cancer. There are well-established data in the literature for the use of concurrent chemoradiotherapy for stage I-III disease, although key questions remain over the timing of radiation, the optimal dose/fractionation and particularly once versus twice daily treatment, the use of elective nodal irradiation and drug combinations. Data for the use of thoracic radiation in stage IV disease, after chemotherapy, have recently become available and are leading to a change in practice. Prophylactic cranial irradiation has been shown to be of use in both stage I-III and stage IV disease, although uncertainties surround its use in the elderly population and the use of brain imaging before treatment. This overview will address the current available evidence and focus on areas for future research.

[Radiotherapy in Europe]. / Radiotherapie in Europa.

Radiotherapy plays an important part in the curing of cancer patients and is an effective treatment for tumour-related symptoms. However, in many countries the level of access to this treatment modality is unacceptably low due to shortage of infrastructure, modern apparatus and trained staff. In Europe it is mainly the Eastern European countries that are behind in the provision of and accessibility to radiotherapy. Worldwide investment to narrow the gap would put an end to these undesirable differences. In addition, these investments would deliver economic benefits, especially in low-to-middle income countries. In this article, on the basis of a number of recently published reports, we discuss the differences that exist in the geographical spread of radiotherapy departments and the availability of apparatus within Europe. In conclusion we also take a short look at the Dutch situation.

Individual patient information to select patients for different radiation techniques.

BACKGROUND AND PURPOSE: Proton therapy is an emerging technique in radiotherapy which results in less dose to the normal tissues with similar target dose than photon therapy, the current standard. Patient-level simulation models support better decision making on which patients would benefit most. MATERIALS AND METHODS: A simulation model was developed tracking individual patients' status regarding the primary tumour and multiple complications. As a proof of principle, the model was populated based on information from a cohort of 1013 head and neck cancer patients. Dose-volume parameters for photon and proton radiation treatment plans were then fed into the model to compare outcomes in terms of length and quality of life and select patients that would benefit most. RESULTS: The illustrative model could adequately replicate the outcomes of photon therapy in the cohort. Improvements from proton therapy varied considerably between patients. The model projects medium-term outcomes for specific individuals and determines the benefits of applying proton rather than photon therapy. CONCLUSIONS: While the model needs to be fed with more and especially recent data before being fully ready for use in clinical practice, it could already distinguish between patients with high and low potential benefits from proton therapy. Benefits are highest for patients with both good prognosis and high expected damage to adjacent organs. The model allows for selecting such patients a priori based on patient relevant outcomes.

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk.

The clinical applications of stereotactic body radiotherapy or stereotactic ablative radiotherapy (SABR) for the treatment of primary and metastatic tumours of different organ sites have been expanding rapidly in the recent decade. SABR requires advanced technology in radiotherapy planning and image guidance to deliver a highly conformal ablative dose precisely to targets (or tumours) in the body. Although this treatment modality has shown promising results with regard to tumour control, some serious complications have been observed and reported. In order to achieve a favourable therapeutic ratio, strategies to mitigate the risk of complications must be in place. This overview will summarise the reported serious complications caused by SABR and strategies to mitigate the risk will be discussed.

Stage I-II non-small-cell lung cancer treated using either stereotactic ablative radiotherapy (SABR) or lobectomy by video-assisted thoracoscopic surgery (VATS): outcomes of a propensity score-matched analysis.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) lobectomy and stereotactic ablative radiotherapy (SABR) are both used for early-stage non-small-cell lung cancer. We carried out a propensity score-matched analysis to compare locoregional control (LRC). PATIENTS AND METHODS: VATS lobectomy data from six hospitals were retrospectively accessed; SABR data were obtained from a single institution database. Patients were matched using propensity scores based on cTNM stage, age, gender, Charlson comorbidity score, lung function and performance score. Eighty-six VATS and 527 SABR patients were matched blinded to outcome (1:1 ratio, caliper distance 0.025). Locoregional failure was defined as recurrence in/adjacent to the planning target volume/surgical margins, ipsilateral hilum or mediastinum. Recurrences were either biopsy-confirmed or had to be PET-positive and reviewed by a tumor board. RESULTS: The matched cohort consisted of 64 SABR and 64 VATS patients with the median follow-up of 30 and 16 months, respectively. Post-SABR LRC rates were superior at 1 and 3 years (96.8% and 93.3% versus 86.9% and 82.6%, respectively, P = 0.04). Distant recurrences and overall survival (OS) were not significantly different. CONCLUSION: This retrospective analysis found a superior LRC after SABR compared with VATS lobectomy, but OS did not differ. Our findings support the need to compare both treatments in a randomized, controlled trial.

The predictive value of 3D time-of-flight MR angiography in assessment of brain arteriovenous malformation obliteration after radiosurgery.

BACKGROUND AND PURPOSE: The purpose of radiosurgery of bAVMs is complete angiographic obliteration of its nidus. We assessed the diagnostic accuracy of 1.5T T2-weighted MR imaging and TOF-MRA images for detecting nidus obliteration after radiosurgery. MATERIALS AND METHODS: The pre- and postradiosurgery MR images and DSA images from 120 patients who were radiosurgically treated for a bAVM were re-evaluated by 2 observers for patency of the nidus (preradiosurgery) and obliteration (postradiosurgery: final follow-up MR imaging), by using a 3-point scale of confidence. Consensus reading of the DSA after radiosurgery was considered the criterion standard for obliteration. Sensitivity, specificity, PPVs, and NPVs, and overall diagnostic performance by using ROC were determined. RESULTS: Mean bAVM volume during radiosurgery was 3.4 mL (95% CI, 2.6-4.3 mL). Sixty-six patients (55%) had undergone previous endovascular embolization. The mean intervals between radiosurgery and follow-up MR imaging and for DSA, respectively, were 35.6 months (95% CI, 32.3-38.9 months) and 42.1 months (95% CI, 40.3-44.0 months). With ROC, an area under curve of 0.81-0.83 was found. PPVs of final follow-up MR-imaging for definitive obliteration varied between 0.89 [corrected] and 0.95. NPV was 0.52 [corrected] . An average false-positive rate, meaning overestimation of nidus obliteration of 0.10 [corrected] and an average false-negative rate, meaning underestimation of nidus obliteration of 0.42 [corrected] were found. CONCLUSIONS: MRA is insufficient to diagnose obliteration in the follow-up of bAVMs after radiosurgery. A remaining nidus diameter <10 mm seems to be the major limiting factor for reliable assessment of obliteration. We highly recommend follow-up DSA for definitive diagnosis of complete obliteration.

Postoperative elective nodal irradiation for squamous cell carcinoma of the head and neck: outcome and prognostic factors for regional recurrence.

BACKGROUND: This study describes the results of elective irradiation in the N0 neck and tries to identify prognostic factors for regional recurrence. MATERIALS AND METHODS: Between 1985 and 2000, 785 cN0 or pN0 necks were treated with elective nodal irradiation in 619 head and neck squamous cell carcinoma patients. RESULTS: Regional control at 3 years was 94% in the cN0 (nondissected) neck compared with 97% in the pN0 (dissected) neck and 90% in the ipsilateral compared with 96% in the contralateral neck (P = 0.08 and P = 0.006, respectively). Regional control in the ipsilateral cN0 neck was 78% compared with 96% in the contralateral cN0 neck. Surgical margin of the primary tumor was an additional prognostic factor in all N0 and pN0 necks. CONCLUSIONS: Neck control rates in electively irradiated N0 necks were excellent. Regional control was worse in the cN0 neck compared with the pN0 neck and in the ipsilateral neck compared with the contralateral side. Additionally, in case of positive surgical margins of the primary tumor, elective nodal irradiation should be applied, even in case of a pN0 neck.

Absence of the MGMT protein as well as methylation of the MGMT promoter predict the sensitivity for temozolomide.

BACKGROUND: The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) can cause resistance to the alkylating drug temozolomide (TMZ). The purpose of this study was to determine the relationship between the MGMT status, determined by means of several techniques and methods, and the cytotoxic response to TMZ in 11 glioblastoma multiforme (GBM) cell lines and 5 human tumour cell lines of other origins. METHODS: Cell survival was analysed by clonogenic assay. The MGMT protein levels were assessed by western blot analysis. The MGMT promoter methylation levels were determined using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and quantitative real-time methylation-specific PCR (qMSP). On the basis of the results of these techniques, six GBM cell lines were selected and subjected to bisulphite sequencing. RESULTS: The MGMT protein was detected in all TMZ-resistant cell lines, whereas no MGMT protein could be detected in cell lines that were TMZ sensitive. The MS-MLPA results were able to predict TMZ sensitivity in 9 out of 16 cell lines (56%). The qMSP results matched well with TMZ sensitivity in 11 out of 12 (92%) glioma cell lines. In addition, methylation as detected by bisulphite sequencing seemed to be predictive of TMZ sensitivity in all six cell lines analysed (100%). CONCLUSION: The MGMT protein expression more than MGMT promoter methylation status predicts the response to TMZ in human tumour cell lines.

Radiotherapy for extensive stage small cell lung cancer.

Small cell lung cancer is an aggressive form of lung cancer with a poor prognosis. Most patients present with extensive stage of the disease. To reduce the high risk of brain metastases, prophylactic cranial irradiation has been shown to be very effective. Prophylactic cranial irradiation should now routinely be used for all patients who have responded to chemotherapy. Thoracic radiotherapy is often reserved for palliation. However, the high incidence of residual disease after chemotherapy and the reported beneficial effect of radiotherapy in a single study has led to two clinical trials which will soon open and address the question whether thoracic radiotherapy also has a role in responding patients with extensive stage small cell lung cancer.