Patient autonomy and shared decision-making in the context of clinical trial participation.

AIMS: This study aimed to explore how incorporating shared decision-making (SDM) can address recruitment challenges in clinical trials. Specifically, it examines how SDM can align the trial process with patient preferences, enhance patient autonomy and increase active patient participation. Additionally, it identifies potential conflicts between SDM and certain clinical trial aspects, such as randomization or blinding, and proposes solutions to mitigate these issues. MATERIALS AND METHODS: We conducted a comprehensive review of existing literature on patient recruitment challenges in clinical trials and the role of SDM in addressing these challenges. We analysed case studies and trial reports to identify common obstacles and assess the effectiveness of SDM in improving patient accrual. Additionally, we evaluated three proposed solutions: adequate trial design, communication skill training and patient decision aids. RESULTS: Our review indicates that incorporating SDM can significantly enhance patient recruitment by promoting patient autonomy and engagement. SDM encourages physicians to adopt a more open and informative approach, which aligns the trial process with patient preferences and reduces psychological barriers such as fear and mental stress. However, implementing SDM can conflict with elements such as randomization and blinding, potentially complicating trial design and execution. DISCUSSION: The desire for patient autonomy and active engagement through SDM may clash with traditional clinical trial methodologies. To address these conflicts, we propose three solutions: redesigning trials to better accommodate SDM principles, providing communication skill training for physicians and developing patient decision aids. By focussing on patient wishes and emotions, these solutions can integrate SDM into clinical trials effectively. CONCLUSION: Shared decision-making provides a framework that can promote patient recruitment and trial participation by enhancing patient autonomy and engagement. With proper implementation of trial design modifications, communication skill training and patient decision aids, SDM can support rather than hinder clinical trial execution, ultimately contributing to the advancement of evidence-based medicine.

Localized and Locally Advanced Prostate Cancer: Treatment Options.

BACKGROUND: There are many treatment options for localized and locally advanced prostate cancer with radiotherapy and surgery representing the main local therapeutic strategies. SUMMARY: Depending on the risk of disease recurrence, we can stratify patients into low-, intermediate- and high-risk groups, which will guide patients' treatment. For low-risk patients, active surveillance is an option. Brachytherapy is also an option for low- and intermediate-risk patients and can be used as a boost following external beam radiotherapy for high-risk patients. For intermediate- and high-risk patients, radical prostatectomy and radiotherapy should be considered. Moreover, in addition to radiotherapy, concomitant androgen deprivation therapy may be needed. Finally, after radical prostatectomy and depending on pathological, biological and clinical factors, radiotherapy ± androgen deprivation therapy can be proposed as an adjuvant or salvage treatment. Key Messages: With radiotherapy and surgery being well-established treatment options for localized prostate cancer patients with equally good overall survival rates, priority must be given to patients' choice concerning the logistics and the toxicity profile of each option.

Creation of clinical algorithms for decision-making in oncology: an example with dose prescription in radiation oncology.

In oncology, decision-making in individual situations is often very complex. To deal with such complexity, people tend to reduce it by relying on their initial intuition. The downside of this intuitive, subjective way of decision-making is that it is prone to cognitive and emotional biases such as overestimating the quality of its judgements or being influenced by one's current mood. Hence, clinical predictions based on intuition often turn out to be wrong and to be outperformed by statistical predictions. Structuring and objectivizing oncological decision-making may thus overcome some of these issues and have advantages such as avoidance of unwarranted clinical practice variance or error-prevention. Even for uncertain situations with limited medical evidence available or controversies about the best treatment option, structured decision-making approaches like clinical algorithms could outperform intuitive decision-making. However, the idea of such algorithms is not to prescribe the clinician which decision to make nor to abolish medical judgement, but to support physicians in making decisions in a systematic and structured manner. An example for a use-case scenario where such an approach may be feasible is the selection of treatment dose in radiation oncology. In this paper, we will describe how a clinical algorithm for selection of a fractionation scheme for palliative irradiation of bone metastases can be created. We explain which steps in the creation process of a clinical algorithm for supporting decision-making need to be  performed and which challenges and limitations have to be considered.

Decision Making Criteria in Oncology.

Decision making is one of the most complex skills required of an oncologist and is affected by a broad range of parameters. For example, the wide variety of treatment options, with various outcomes, side-effects and costs present challenges in selecting the most appropriate treatment. Many treatment choices are affected by limited scientific evidence, availability of therapies or patient-specific factors. In the decision making process, standardized approaches can be useful, but a multitude of criteria are relevant to this process. Thus, the aim of this review is to summarize common types of decision criteria used in oncology by focusing on 3 main categories: criteria associated with the decision maker (both patient and doctor), decision specific criteria, and the often-overlooked contextual factors. Our review aims to highlight the broad range of decision criteria in use, as well as variations in their interpretation.

Insular Decision Criteria in Clinical Practice: Analysis of Decision-Making in Oncology.

BACKGROUND: Medical decision-making is complex and involves a variety of decision criteria, many of which are universally recognised. However, decision-making analyses have demonstrated that certain decision criteria are not used uniformly among clinicians. AIM: We describe decision criteria, which for various contexts are only used by a minority of decision makers. For these, we introduce and define the term "insular criteria". METHODS: 19 studies analysing clinical decision-making based on decision trees were included in our study. All studies were screened for decision-making criteria that were mentioned by less than three local decision makers in studies involving 8-26 participants. RESULTS: 14 out of the 19 included studies reported insular criteria. We identified 42 individual insular criteria. They could be intuitively allocated to seven major groups, these were: comorbidities, treatment, patients' characteristics/preferences, caretaker, scores, laboratory and tumour properties/staging. CONCLUSION: Insular criteria are commonly used in clinical decision-making, yet, the individual decision makers may not be aware of them. With this analysis, we demonstrate the existence of insular criteria and their variety. In daily practice and clinical studies, awareness of insular criteria is important.

Salvage radiotherapy for macroscopic local recurrences after radical prostatectomy : A national survey on patterns of practice.

INTRODUCTION: Although salvage radiotherapy (SRT) for PSA recurrence after radical prostatectomy provides better oncological outcomes when delivered early, in the absence of detectable disease many patients are treated for macroscopic locally recurrent tumors. Due to limited data from prospective studies, we hypothesized an important variability in the SRT management of these patients. Our aim was to investigate current practice patterns of SRT for local macroscopic recurrence after radical prostatectomy. MATERIAL AND METHODS: A total of 14 Swiss radiation oncology centers were asked to complete a survey on treatment specifications for macroscopic locally recurrent disease including information on pretherapeutic diagnostic procedures, dose prescription, radiation delivery techniques and androgen deprivation therapy (ADT). Treatment recommendations on ADT were analyzed using the objective consensus methodology. RESULTS: The majority of centers recommended pretreatment magnetic resonance imaging (MRI) of the pelvis and choline positron emission tomography (PET). The median prescribed dose to the prostate bed was 66 Gy (range 65-72 Gy) with a boost to the macroscopic lesion used by 79% of the centers with a median total dose of 72 Gy (range 70-80 Gy). Intensity-modulated rotational techniques were used by all centers and daily cone beam computed tomography (CT) was recommended by 43%. The use of concomitant ADT for any macroscopic recurrence was recommended by 43% of the centers while the remaining centers recommended it only for high-risk disease, which was not consistently defined. CONCLUSION: We observed a high variability of treatment paradigms when SRT is indicated for macroscopic local recurrences after prostatectomy. These data reflect the need for more standardized approaches and ultimately further research in this field.

Predictive and prognostic value of tumor volume and its changes during radical radiotherapy of stage III non-small cell lung cancer : A systematic review.

PURPOSE: Lung cancer remains the leading cause of cancer-related mortality worldwide. Stage III non-small cell lung cancer (NSCLC) includes heterogeneous presentation of the disease including lymph node involvement and large tumour volumes with infiltration of the mediastinum, heart or spine. In the treatment of stage III NSCLC an interdisciplinary approach including radiotherapy is considered standard of care with acceptable toxicity and improved clinical outcome concerning local control. Furthermore, gross tumour volume (GTV) changes during definitive radiotherapy would allow for adaptive replanning which offers normal tissue sparing and dose escalation. METHODS: A literature review was conducted to describe the predictive value of GTV changes during definitive radiotherapy especially focussing on overall survival. The literature search was conducted in a two-step review process using PubMed®/Medline® with the key words "stage III non-small cell lung cancer" and "radiotherapy" and "tumour volume" and "prognostic factors". RESULTS: After final consideration 17, 14 and 9 studies with a total of 2516, 784 and 639 patients on predictive impact of GTV, GTV changes and its impact on overall survival, respectively, for definitive radiotherapy for stage III NSCLC were included in this review. Initial GTV is an important prognostic factor for overall survival in several studies, but the time of evaluation and the value of histology need to be further investigated. GTV changes during RT differ widely, optimal timing for re-evaluation of GTV and their predictive value for prognosis needs to be clarified. The prognostic value of GTV changes is unclear due to varying study qualities, re-evaluation time and conflicting results. CONCLUSION: The main findings were that the clinical impact of GTV changes during definitive radiotherapy is still unclear due to heterogeneous study designs with varying quality. Several potential confounding variables were found and need to be considered for future studies to evaluate GTV changes during definitive radiotherapy with respect to treatment outcome.

Surgical management of urolithiasis - a systematic analysis of available guidelines.

BACKGROUND: Several societies around the world issue guidelines incorporating the latest evidence. However, even the most commonly cited guidelines of the European Association of Urology (EAU) and the American Urological Association (AUA) leave the clinician with several treatment options and differ on specific points. We aimed to identify discrepancies and areas of consensus between guidelines to give novel insights into areas where low consensus between the guideline panels exists, and therefore where more evidence might increase consensus. METHODS: The webpages of the 61 members of the Societé Internationale d'Urologie were analysed to identify all listed or linked guidelines. Decision trees for the surgical management of urolithiasis were derived, and a comparative analysis was performed to determine consensus and discrepancies. RESULTS: Five national and one international guideline (EAU) on surgical stone treatment were available for analysis. While 7 national urological societies refer to the AUA guidelines and 11 to the EAU guidelines, 43 neither publish their own guidelines nor refer to others. Comparative analysis revealed a high degree of consensus for most renal and ureteral stone scenarios. Nevertheless, we also identified a variety of discrepancies between the different guidelines, the largest being the approach to the treatment of proximal ureteral calculi and larger renal calculi. CONCLUSIONS: Six guidelines with recommendations for the surgical treatment of urolithiasis to support urologists in decision-making were available for inclusion in our analysis. While there is a high grade of consensus for most stone scenarios, we also detected some discrepancies between different guidelines. These are, however, controversial situations where adequate evidence to assist with decision-making has yet to be elicited by further research.

Neutrophil-lymphocyte ratio complements volumetric staging as prognostic factor in patients treated with definitive radiotherapy for oropharyngeal cancer.

BACKGROUND: Volumetric tumor staging has been shown as superior prognostic tool compared to the conventional TNM system in patients undergoing definitive intensity-modulated radiotherapy (IMRT) for head and neck cancer. Recently, clinical immunoscores such as the neutrophil-lymphocyte ratio (NLR) have been investigated as prognostic markers in several tumor entities. The aim of this study was to assess the combined prognostic value of NLR and tumor volume in patients treated with IMRT for oropharyngeal cancer (OC). METHODS: Data on all consecutive patients treated for locally advanced or inoperable OC with IMRT from 2002-2011 was prospectively collected. Tumor volume was assessed based on the total gross tumor volume (tGTV) calculated by the treatment planning system volume algorithm. The NLR was collected by a retrospective analysis of differential blood count before initiation of therapy. RESULTS: Overall, 187 eligible patients were treated with a median IMRT dose of 69.6 Gy. Three-year recurrence-free survival (RFS) for low, intermediate, high and very high tumor volume groups was 88%, 74%, 62% and 25%, respectively (p = 0.007). Patients with elevated NLR (>4.68) showed a significantly decreased 3-year RFS of 44% vs. 81% (p < 0.001) and 3-year OS of 56% vs. 84% (p < 0.001). The NLR remained a significant prognostic factor for RFS and OS when tested among tumor volume groups. Univariate and multivariate regression analysis confirmed both tumor volume and NLR as independent prognostic factors. The NLR offered further statistically significant prognostic differentiation of the small/intermediate/large tumor volume groups. CONCLUSION: The NLR remains an independent prognostic factor for patients with OC undergoing radiotherapy independent of the tumor volume.

Applied Swarm-based medicine: collecting decision trees for patterns of algorithms analysis.

BACKGROUND: The objective consensus methodology has recently been applied in consensus finding in several studies on medical decision-making among clinical experts or guidelines. The main advantages of this method are an automated analysis and comparison of treatment algorithms of the participating centers which can be performed anonymously. METHODS: Based on the experience from completed consensus analyses, the main steps for the successful implementation of the objective consensus methodology were identified and discussed among the main investigators. RESULTS: The following steps for the successful collection and conversion of decision trees were identified and defined in detail: problem definition, population selection, draft input collection, tree conversion, criteria adaptation, problem re-evaluation, results distribution and refinement, tree finalisation, and analysis. CONCLUSION: This manuscript provides information on the main steps for successful collection of decision trees and summarizes important aspects at each point of the analysis.

Treatment of melanoma brain metastases.

PURPOSE OF REVIEW: Melanoma has a tendency to metastasize to the brain. The development of brain metastasis is observed in all mutational subgroups. Overall, they are associated with poor prognosis. They are also associated with pain, neurological deterioration and thus, have a major impact on patients' quality of life. Historically, effective palliation by systemic therapy has been rare. The availability of new therapeutic agents, however, heralds a significant improvement in management options for these patients. RECENT FINDINGS: The development of targeted therapies and immune activating checkpoint inhibitors with durable benefit has led to a treatment paradigm change. Several clinical studies in patients with metastatic melanoma have demonstrated improved survival compared to chemotherapy. Many of these studies however excluded patients with brain involvement. Antitumor activity in brain metastasis has now been observed with some agents; further positive data are emerging. Surgery and stereotactic radiotherapy are also used for local control of oligometastatic disease. We discuss the usefulness of the available systemic treatments for management of brain metastases and how these are integrated with local treatments to enable optimal palliation. SUMMARY: Advances in the treatment of melanoma are providing significant palliative benefit for patients with brain metastases. Further investigations are needed to determine optimal treatment combinations and sequences.

Stereotactic body radiotherapy for renal cell cancer and pancreatic cancer : Literature review and practice recommendations of the DEGRO Working Group on Stereotactic Radiotherapy.

PURPOSE: This report of the Working Group on Stereotactic Radiotherapy of the German Society of Radiation Oncology (DEGRO) aims to provide a literature review and practice recommendations for stereotactic body radiotherapy (SBRT) of primary renal cell cancer and primary pancreatic cancer. METHODS: A literature search on SBRT for both renal cancer and pancreatic cancer was performed with focus on prospective trials and technical aspects for clinical implementation. RESULTS: Data on renal and pancreatic SBRT are limited, but show promising rates of local control for both treatment sites. For pancreatic cancer, fractionated SBRT should be preferred to single-dose treatment to reduce the risk of gastrointestinal toxicity. Motion-compensation strategies and image guidance are paramount for safe SBRT delivery in both tumor entities. CONCLUSION: SBRT for renal cancer and pancreatic cancer have been successfully evaluated in phase I and phase II trials. Pancreatic SBRT should be practiced carefully and only within prospective protocols due to the risk of severe gastrointestinal toxicity. SBRT for primary renal cell cancer appears a viable option for medically inoperable patients but future research needs to better define patient selection criteria and the detailed practice of SBRT.

Consensus and differences in primary radiotherapy for localized and locally advanced prostate cancer in Switzerland: A survey on patterns of practice.

INTRODUCTION: External beam radiotherapy (EBRT), with or without androgen deprivation therapy (ADT), is an established treatment option for nonmetastatic prostate cancer. Despite high-level evidence from several randomized trials, risk group stratification and treatment recommendations vary due to contradictory or inconclusive data, particularly with regard to EBRT dose prescription and ADT duration. Our aim was to investigate current patterns of practice in primary EBRT for prostate cancer in Switzerland. MATERIALS AND METHODS: Treatment recommendations on EBRT and ADT for localized and locally advanced prostate cancer were collected from 23 Swiss radiation oncology centers. Written recommendations were converted into center-specific decision trees, and analyzed for consensus and differences using a dedicated software tool. Additionally, specific radiotherapy planning and delivery techniques from the participating centers were assessed. RESULTS: The most commonly prescribed radiation dose was 78 Gy (range 70-80 Gy) across all risk groups. ADT was recommended for intermediate-risk patients for 6 months in over 80 % of the centers, and for high-risk patients for 2 or 3 years in over 90 % of centers. For recommendations on combined EBRT and ADT treatment, consensus levels did not exceed 39 % in any clinical scenario. Arc-based intensity-modulated radiotherapy (IMRT) is implemented for routine prostate cancer radiotherapy by 96 % of the centers. CONCLUSION: Among Swiss radiation oncology centers, considerable ranges of radiotherapy dose and ADT duration are routinely offered for localized and locally advanced prostate cancer. In the vast majority of cases, doses and durations are within the range of those described in current evidence-based guidelines.

Cationic versus neutral microbubbles for ultrasound-mediated gene delivery in cancer.

PURPOSE: To test whether plasmid-binding cationic microbubbles (MBs) enhance ultrasound-mediated gene delivery efficiency relative to control neutral MBs in cell culture and in vivo tumors in mice. MATERIALS AND METHODS: Animal studies were approved by the institutional animal care committee. Cationic and neutral MBs were characterized in terms of size, charge, circulation time, and DNA binding. Click beetle luciferase (CBLuc) reporter plasmids were mixed with cationic or neutral MBs. The ability of cationic MBs to protect bound plasmids from nuclease degradation was tested by means of a deoxyribonuclease (DNase) protection assay. Relative efficiencies of ultrasound-mediated transfection (ultrasound parameters: 1 MHz, 1 W/cm(2), 20% duty cycle, 1 minute) of CBLuc to endothelial cells by using cationic, neutral, or no MBs were compared in cell culture. Ultrasound-mediated gene delivery to mouse hind limb tumors was performed in vivo (n = 24) with insonation (1 MHz, 2 W/cm(2), 50% duty cycle, 5 minutes) after intravenous administration of CBLuc with cationic, neutral, or no MBs. Tumor luciferase activity was assessed by means of serial in vivo bioluminescence imaging and ex vivo analysis. Results were compared by using analysis of variance. RESULTS: Cationic MBs (+15.8 mV; DNA binding capacity, 0.03 pg per MB) partially protected bound DNA from DNase degradation. Mean CBLuc expression of treated endothelial cells in culture was 20-fold higher with cationic than with neutral MBs (219.0 relative light units [RLUs]/µg protein ± 92.5 [standard deviation] vs 10.9 RLUs/µg protein ± 2.7, P = .001) and was significantly higher (P < .001) than that in the no MB and no ultrasound control groups. Serial in vivo bioluminescence of mouse tumors was significantly higher with cationic than with neutral MBs ([5.9 ± 2.2] to [9.3 ± 5.2] vs [2.4 ± 0.8] to [2.9 ± 1.1] × 10(4) photons/sec/cm(2)/steradian, P < .0001) and versus no MB and no ultrasound controls (P < .0001). Results of ex vivo analysis confirmed these results (ρ = 0.88, P < .0001). CONCLUSION: Plasmid-binding cationic MBs enhance ultrasound-mediated gene delivery efficiency relative to neutral MBs in both cell culture and mouse hind limb tumors.

Patterns of care for relapsed oesophageal cancer after initial curative trimodality therapy: Long-term follow-up of the SAKK 75/08 trial.

BACKGROUND: Recurrent oesophageal cancer after the initial curative multimodality treatment is a disease condition with a poor prognosis. There is limited evidence on recurrence patterns and on the optimal therapeutic approach. METHODS: We analysed the pattern of disease recurrence and subsequent therapies in patients with recurrent oesophageal cancer based on prospectively collected data within a predefined subproject of the randomised phase 3 trial Swiss Group for Clinical Cancer Research (SAKK) 75/08. RESULTS: Among 300 patients included in the SAKK 75/08 trial, tumour recurrence was observed in 103 patients with a median follow-up of 5.8 years. Locoregional recurrence only was found in 26.2% of the patients, 21.4% of patients had both distant and locoregional recurrence and 52.4% of patients had distant recurrence only. Fifty-nine patients (58%) received at least one line of systemic therapy at recurrence, most commonly oxaliplatin-based combination therapies for adenocarcinoma and single-agent chemotherapy for squamous cell carcinoma. Local therapies, most commonly palliative radiotherapy, were used in 49 patients (48%). Six patients underwent a second curative resection or radiochemotherapy. We found no significant overall survival difference for isolated locoregional recurrence versus distant recurrence (15.1 versus 8.7 months, p = 0.167). In a multivariable Cox regression model, time from oesophagectomy to recurrence and the number of recurrence sites as well as the use of systemic therapy or a second curative local therapy significantly correlated with overall survival. CONCLUSIONS: Recurrent oesophageal cancer remains a disease with a poor prognosis and requires multidisciplinary management. A second curative approach for localised disease recurrence may be an option for highly selected patients.

Radiotherapy or Surgery? Comparative, Qualitative Assessment of Online Patient Education Materials on Prostate Cancer.

As multiple different treatment options are available for prostate cancer (PCa) and YouTube is commonly used as a source for medical information, we performed a systematic and comparative assessment of available videos guiding patients on their choice for the optimal treatment. An independent search for surgical therapy or radiotherapy of PCa on YouTube was performed and the 40 most viewed videos of both groups were analyzed. The validated DISCERN questionnaire and PEMAT were utilized to evaluate their quality and misinformation. The median overall quality of the videos was found to be low for surgery videos, while radiotherapy videos results reached a moderate quality. The median PEMAT understandability score was 60% (range 0-100%) for radiotherapy and 75% (range 40-100) for surgery videos. The radiotherapy videos contained less misinformation and were judged to be of higher quality. Summarized, the majority of the provided videos offer insufficient quality of content and are potentially subject to commercial bias without reports on possible conflict of interest. Thus, most of available videos on YouTube informing PCa patients about possible treatment methods are not suited for a balanced patient education or as a basis for the patient's decision.

A cost-effectiveness analysis of pembrolizumab with or without chemotherapy for the treatment of patients with metastatic, non-squamous non-small cell lung cancer and high PD-L1 expression in Switzerland.

INTRODUCTION: Pembrolizumab monotherapy or in combination with chemotherapy are two new treatment options for patients with metastatic non-squamous non-small cell lung cancer (NSCLC) and high (≥ 50%) programmed death ligand 1 (PD-L1) expression. We conducted a cost-effectiveness analysis for Switzerland comparing these two options but also pembrolizumab to chemotherapy. METHODS: We constructed a 3-state Markov model with a time horizon of 10 years. Parametric functions were fitted to Kaplan-Meier overall survival (OS) and progression-free survival (PFS) using 2-year follow-up data from the KN-024 and KN-189 registration trials. We included estimated costs for further treatment lines and costs for best supportive care. Costs were assessed from the Swiss healthcare payer perspective. We used published utility values. RESULTS: Combination therapy resulted in an expected gain of 0.17 quality-adjusted life years (QALYs) per patient and incremental costs of Swiss Francs (CHF) 81,085 as compared to pembrolizumab. These estimates led to an incremental cost-effectiveness ratio (ICER) of CHF 475,299/QALY. Pembrolizumab in comparison to chemotherapy was estimated to generate mean incremental QALYs of 0.83 and incremental costs of CHF 56,585, resulting in an ICER of CHF 68,580/QALY. Results were most sensitive to changes in costs of 1L pembrolizumab and combination therapy, together with changes in PFS. In the probabilistic sensitivity analysis, we estimated combination therapy was cost-effective in 4.9% of the simulations and pembrolizumab monotherapy in 82.9%, assuming a willingness-to-pay threshold of CHF 100,000 per QALY gained. CONCLUSIONS: Pembrolizumab is likely to be cost-effective from the Swiss healthcare payer perspective, whereas pembrolizumab plus chemotherapy is not.

Radiotherapy for lentigo maligna and lentigo maligna melanoma - a systematic review.

Lentigo maligna (LM) is the most common subtype of in situ melanoma und occurs frequently in the sun-exposed head and neck region in elderly patients. The therapeutic "gold standard" is surgical excision, as there is the risk of progression to invasive (lentigo maligna) melanoma (LMM). However, surgery is not feasible in certain patients due to age, comorbidities or patient preference. Radiotherapy using Grenz rays or superficial X-rays has been established as non-invasive alternative for the treatment of LM and LMM. We performed a systematic literature search of MEDLINE and Embase databases in September 2019 and identified 14 patient series using radiotherapy for LM or LMM. No prospective trials were found. The 14 studies reported a total of 1243 lesions (1075 LM and 168 LMM) treated with radiotherapy. Local recurrence rates ranged from 0 to 31% and were comparable to surgical series in most of the reports on radiotherapy. Superficial radiotherapy was prescribed in 5-23 fractions with a total dose of 35-57 Gy. Grenz ray therapy was prescribed in 42-160 Gy in 3-13 fractions with single doses up to 20 Gy. Cosmetic results were reported as "good" to "excellent" for the majority of patients.In conclusion, the available low-level evidence suggests that radiotherapy may be a safe and effective treatment for LM and LMM. Data from prospective trials such as the phase 3 RADICAL trial are needed to confirm these promising findings and to compare radiotherapy to other non-surgical therapies and to surgery.

Cost effectiveness of pembrolizumab vs chemotherapy as first-line treatment for metastatic NSCLC that expresses high levels of PD-L1 in Switzerland.

AIM: The study aim was to evaluate the cost effectiveness of pembrolizumab monotherapy compared with chemotherapy as a first-line treatment for previously untreated metastatic non-small cell lung cancer (NSCLC) with programmed death ligand-1 (PD-L1) tumour proportion score (TPS) ≥50%, from a Swiss payer perspective. Cost effectiveness of pembrolizumab for this indication has not previously been evaluated in Switzerland. METHODS: We conducted an analysis using a partitioned survival model with a cycle length of one week, base-case time horizon of 20 years and discount rate of 3% for cost and health outcomes. KEYNOTE-024 randomised controlled trial data for pembrolizumab monotherapy compared with chemotherapy was used as a basis for projecting time-on-treatment, progression-free survival and overall survival, over a 20-year period. For overall survival and progression-free survival, we used Kaplan-Meier probabilities for a brief initial period of the model, followed by parametric curves that had the best fit with subsequent trial data. Quality-adjusted life years (QALYs) were calculated based on the EuroQol 5-dimensional 3-level (EQ-5D-3L) questionnaire administered to trial patients. Costs (in CHF, year 2018) of drug acquisition/administration, adverse events and disease management were included. RESULTS: For the base-case, pembrolizumab monotherapy resulted in mean incremental costs of CHF 77,060 (pembrolizumab CHF 223,324, chemotherapy CHF 146,264) and mean incremental QALYs of 1.34 (pembrolizumab 3.05, chemotherapy 1.71), leading to an incremental cost-effectiveness ratio of CHF 57,402 per QALY gained. Cost-effectiveness results were most sensitive to overall survival and relatively insensitive to other parameters varied. In probabilistic sensitivity analysis, the probability of cost effectiveness of pembrolizumab, with an assumption of a willingness-to-pay threshold of CHF 100,000 per QALY gained, was 88%. CONCLUSION: Pembrolizumab is likely to be cost effective for treating Swiss patients with previously untreated metastatic NSCLC expressing PD-L1 TPS ≥50%. (This economic evaluation was based on the KEYNOTE-024 trial. The trial identifier is NCT02142738.).