Individualized early death and long-term survival prediction after stereotactic radiosurgery for brain metastases of non-small cell lung cancer:Two externally validated nomograms

Introduction Commonly used clinical models for survival prediction after stereotactic radiosurgery (SRS) for brain metastases (BMs) are limited by the lack of individual risk scores and disproportionate prognostic groups. In this study, two nomograms were developed to overcome these limitations. Methods 495 patients with BMs of NSCLC treated with SRS for a limited number of BMs in four Dutch radiation oncology centers were identified and divided in a training cohort (n = 214, patients treated in one hospital) and an external validation cohort n = 281, patients treated in three other hospitals). Using the training cohort, nomograms were developed for prediction of early death (<3 months) and long-term survival (>12 months) with prognostic factors for survival. Accuracy of prediction was defined as the area under the curve (AUC) by receiver operating characteristics analysis for prediction of early death and long term survival. The accuracy of the nomograms was also tested in the external validation cohort. Results Prognostic factors for survival were: WHO performance status, presence of extracranial metastases, age, GTV largest BM, and gender. Number of brain metastases and primary tumor control were not prognostic factors for survival. In the external validation cohort, the nomogram predicted early death statistically significantly better (p < 0.05) than the unfavorable groups of the RPA, DS-GPA, GGS, SIR, and Rades 2015 (AUC = 0.70 versus range AUCs = 0.51–0.60 respectively). With an AUC of 0.67, the other nomogram predicted 1 year survival statistically significantly better (p < 0.05) than the favorable groups of four models (range AUCs = 0.57–0.61), except for the SIR (AUC = 0.64, p = 0.34). The models are available on www.predictcancer.org. Conclusion The nomograms predicted early death and long-term survival more accurately than commonly used prognostic scores after SRS for a limited number of BMs of NSCLC. Moreover these nomograms enable individualized probability assessment and are easy into use in routine clinical practice

The EPTN consensus-based atlas for CT- and MR-based contouring in neuro-oncology

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

High-precision stereotactic irradiation for focal drug-resistant epilepsy versus standard treatment: a randomized waitlist-controlled trial (the PRECISION trial)

Introduction: The standard treatment for patients with focal drug-resistant epilepsy (DRE) who are not eligible for open brain surgery is the continuation of anti-seizure medication (ASM) and neuromodulation. This treatment does not cure epilepsy but only decreases severity. The PRECISION trial offers a non-invasive, possibly curative intervention for these patients, which consist of a single stereotactic radiotherapy (SRT) treatment. Previous studies have shown promising results of SRT in this patient population. Nevertheless, this intervention is not yet available and reimbursed in the Netherlands. We hypothesize that: SRT is a superior treatment option compared to palliative standard of care, for patients with focal DRE, not eligible for open surgery, resulting in a higher reduction of seizure frequency (with 50% of the patients reaching a 75% seizure frequency reduction at 2 years follow-up). Methods: In this waitlist-controlled phase 3 clinical trial, participants are randomly assigned in a 1:1 ratio to either receive SRT as the intervention, while the standard treatments consist of ASM continuation and neuromodulation. After 2-year follow-up, patients randomized for the standard treatment (waitlist-control group) are offered SRT. Patients aged ≥ 18 years with focal DRE and a pretreatment defined epileptogenic zone (EZ) not eligible for open surgery will be included. The intervention is a LINAC-based single fraction (24 Gy) SRT treatment. The target volume is defined as the epileptogenic zone (EZ) on all (non) invasive examinations. The seizure frequency will be monitored on a daily basis using an electronic diary and an automatic seizure detection system during the night. Potential side effects are evaluated using advanced MRI, cognitive evaluation, Common Toxicity Criteria, and patient-reported outcome questionnaires. In addition, the cost-effectiveness of the SRT treatment will be evaluated. Discussion: This is the first randomized trial comparing SRT with standard of care in patients with DRE, non-eligible for open surgery. The primary objective is to determine whether SRT significantly reduces the seizure frequency 2 years after treatment. The results of this trial can influence the current clinical practice and medical cost reimbursement in the Netherlands for patients with focal DRE who are not eligible for open surgery, providing a non-invasive curative treatment option. Trial registration: Clinicaltrials.gov Identifier: NCT05182437. Registered on September 27, 2021

Considerations for shoot-through FLASH proton therapy

Purpose. To discuss several pertinent issues related to shoot-through FLASH proton therapy based on an illustrative case. Methods. We argue that with the advent of FLASH proton radiotherapy and due to the issues associated with conventional proton radiotherapy regarding the uncertainties of positioning of the Bragg peaks, the difficulties of in vivo verification of the dose distribution, the use of treatment margins and the uncertainties surrounding linear energy transfer (LET) and relative biological effectiveness (RBE), a special mode of shoot-through FLASH proton radiotherapy should be investigated. In shoot-through FLASH, the proton beams have sufficient energy to reach the distal exit side of the patient. Due to the FLASH sparing effect of normal tissues at both the proximal and distal side of tumors, radiotherapy plans can be developed that meet current planning constraints and issues regarding RBE can be avoided. Results. A preliminary proton plan for a neurological tumor in close proximity to various organs at risk (OAR) with strict dose constraints was studied. A plan with four beams mostly met the constraints for the OAR, using a treatment planning system that was not optimized for this novel treatment modality. When new treatment planning algorithms would be developed for shoot-through FLASH, constraints would be easier to meet. The shoot-through FLASH plan led to a significant effective dose reduction in large parts of the healthy tissue. The plan had no uncertainties associated to Bragg peak positioning, needed in principle no large proximal or distal margins and LET increases near the Bragg peak became irrelevant. Conclusion. Shoot-through FLASH proton radiotherapy may be an interesting treatment modality to explore further. It would remove some of the current sources of uncertainty in proton radiotherapy. An additional advantage could be that portal dosimetry may be possible with beams penetrating the patient and impinging on a distally placed imaging detector, potentially leading to a practical treatment verification method. With current proton accelerator technology, trials could be conducted for neurological, head&neck and thoracic cancers. For abdominal and pelvic cancer a higher proton energy would be required

Difficult medical encounters in oncology: What physicians need. An exploratory study

Objective: The objective of this study was to assess how often-medical oncology professionals encounter difficult consultations and if they desire support in the form of training. Methods: In February 2022, a survey on difficult medical encounters in oncology, training and demographics was set up. The survey was sent to 390 medical oncology professionals part of the OncoZON network of the Southeast region of the Netherlands. Results: Medical oncology professionals perceive a medical encounter as difficult when there is a dominant family member (n = 27), insufficient time (n = 24), or no agreement between medical professional and patient (n = 22). Patients involved in these encounters are most often characterized with low health literacy (n = 12) or aggressive behavior (n = 10). The inability to comprehend difficult medical information or perceived difficult behavior complicates encounters. Of the medical oncology professionals, 27–44% preferred a training as a physical group meeting (24%) or an individual virtual meeting (19%). Conclusion: Medical oncology professionals consider dominant or aggressive behavior and the inability to comprehend medical information by patients during consultations as difficult encounters for which they would appreciate support. Innovation: Our results highlight concrete medical encounters in need of specific education programs within daily oncology practice