Explainable artificial intelligence (XAI) has experienced a vast increase in recognition over the last few years. While the technical developments are manifold, less focus has been placed on the clinical applicability and usability of systems. Moreover, not much attention has been given to XAI systems that can handle multimodal and longitudinal data, which we postulate are important features in many clinical workflows. In this study, we review, from a clinical perspective, the current state of XAI for multimodal and longitudinal datasets and highlight the challenges thereof. Additionally, we propose the XAI orchestrator, an instance that aims to help clinicians with the synopsis of multimodal and longitudinal data, the resulting AI predictions, and the corresponding explainability output. We propose several desirable properties of the XAI orchestrator, such as being adaptive, hierarchical, interactive, and uncertainty-aware.

A high neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation and together with the platelet-to-lymphocyte ratio (PLR) is associated with worse outcomes in several solid tumors. We investigated the prognostic value of NLR and PLR in patients with head and neck squamous cell carcinoma (HNSCC) treated with primary or adjuvant (chemo)radiotherapy ((C)RT). A retrospective chart review of consecutive patients with HNSCC was performed. Neutrophil-to-lymphocyte ratio and PLR were computed using complete blood counts (CBCs) performed within 10 days before treatment start. The prognostic role of NLR and PLR was evaluated with univariable and multivariable Cox regression analyses adjusting for disease-specific prognostic factors. NLR and PLR were assessed as log-transformed continuous variables (log NLR and log PLR). Endpoints of interest were overall survival (OS), locoregional recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and acute toxicity. We analyzed 186 patients treated from 2007 to 2010. Primary sites were oropharynx (45%), oral cavity (28%), hypopharynx (14%), and larynx (13%). Median follow-up was 49 months. Higher NLR was associated with OS (adjusted HR per 1 unit higher log NLR = 1.81 (1.16–2.81), p = 0.012), whereas no association could be shown with LRFS (HR = 1.49 (0,83-2,68), p = 0.182), DRFS (HR = 1.38 (0.65–3.22), p = 0.4), or acute toxicity grade ≥ 2. PLR was not associated with outcome, nor with toxicity. Our data suggest that in HNSCC patients treated with primary or adjuvant (C)RT, NLR is an independent predictor of mortality, but not disease-specific outcomes or toxicity. Neutrophil-to-lymphocyte ratio is a readily available biomarker that could improve pre-treatment prognostication and may be used for risk-stratification.

The functional outcome after the treatment of laryngeal cancer is tightly related to the quality of life of affected patients. The aim of this study is to describe the long-term morbidity and functional outcomes associated with the different treatment modalities for laryngeal cancer. Retrospective chart review of 477 patients undergoing curatively intended treatment for laryngeal cancer at our tertiary referral center from 2001 to 2014: Details on patient and disease characteristics, diagnostics and treatment related functional outcomes were analyzed. With a median follow-up of 51 months, the crude rate of functional larynx preservation was 74.6%. Radiotherapy +/− chemotherapy was the dominant treatment modality (n = 359–75.3%), whereas 24.7% (n = 118) underwent primary surgery, with 58.5% (69) receiving adjuvant treatment. The 5-year laryngectomy-free survival was 57% (95% CI, 48–66%) after surgery vs. 69% (95% CI, 64–75%) after chemoradiotherapy (p < 0.01). In stage III-IVB, these rates were 26% (95% CI, 16–39%) vs. 47% (95% CI, 36–59%), respectively (p < 0.01). Aspiration occurred in 7%, tracheostomy was necessary in 19.8% and feeding tube placement in 25.4%. Feeding tube and tracheostomy necessity was higher in the initially surgically treated group. Primary surgery (HR: 1.67, 95% CI: 1.19–2.32; p < 0.01), stage III-IVB (HR: 4.07, 95% CI: 2.97–5.60; p < 0.01) and tumor recurrence (HR: 3.83, 95% CI: 2.79–5.28; p < 0.01) remained as adverse factors for laryngectomy-free survival. Preserving the laryngeal function after cancer treatment is challenging. Advanced tumor stages, primary surgery and recurrence are related to a poor functional outcome. Therefore, the criteria for initial decision-making needs to be further refined.

Evaluation of dose escalated salvage radiotherapy (SRT) in patients after radical prostatectomy (RP) who had never received antihormonal therapy. To investigate prognostic factors of the outcome of SRT and to analyze which patient subsets benefit most from dose escalation. Between 2002 and 2008, 76 patients were treated in three different dose-groups: an earlier cohort treated with 66 Gy irrespective of pre-RT-characteristics and two later cohorts treated with 70 Gy or 75 Gy depending on pre-RT-characteristics. Biochemical-relapse-free-survival (bRFS), clinical-relapse-free-survival (cRFS) and late toxicity were evaluated. Four-year bRFS and cRFS were 62.5% and 85%. Gleason score 66 Gy. While > 70 Gy did not improve the overall results, 4-year bRFS for patients with manifest local recurrence in the high-dose group was still comparable to those without manifest local recurrences. No grade 4 and minimal grade 3 gastrointestinal and urinary toxicity were observed. Dose-escalated SRT achieves high biochemical control. The data strongly support the application of at least 70 Gy rather than 66 Gy. They do not prove positive effects of doses >70 Gy but do not disprove them as these doses were only applied to an unfavorable patients selection.

Aim: The optimal management for early recurrent prostate cancer following radical prostatectomy (RP) in patients with negative prostate-specific membrane antigen positron-emission tomography (PSMA-PET) scan is an ongoing subject of debate. The aim of this study was to evaluate the outcome of salvage radiotherapy (SRT) in patients with biochemical recurrence with negative PSMA PET finding. Methods: This retrospective, multicenter (11 centers, 5 countries) analysis included patients who underwent SRT following biochemical recurrence (BR) of PC after RP without evidence of disease on PSMA-PET staging. Biochemical recurrence-free survival (bRFS), metastatic-free survival (MFS) and overall survival (OS) were assessed using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predefined predictors of survival outcomes. Results: Three hundred patients were included, 253 (84.3%) received SRT to the prostate bed only, 46 (15.3%) additional elective pelvic nodal irradiation, respectively. Only 41 patients (13.7%) received concomitant androgen deprivation therapy (ADT). Median follow-up after SRT was 33 months (IQR: 20–46 months). Three-year bRFS, MFS, and OS following SRT were 73.9%, 87.8%, and 99.1%, respectively. Three-year bRFS was 77.5% and 48.3% for patients with PSA levels before PSMA-PET ≤ 0.5 ng/ml and > 0.5 ng/ml, respectively. Using univariate analysis, the International Society of Urological Pathology (ISUP) grade > 2 (p = 0.006), metastatic pelvic lymph nodes at surgery (p = 0.032), seminal vesicle involvement (p < 0.001), pre-SRT PSA level of > 0.5 ng/ml (p = 0.004), and lack of concomitant ADT (p = 0.023) were significantly associated with worse bRFS. On multivariate Cox proportional hazards, seminal vesicle infiltration (p = 0.007), ISUP score >2 (p = 0.048), and pre SRT PSA level > 0.5 ng/ml (p = 0.013) remained significantly associated with worse bRFS. Conclusion: Favorable bRFS after SRT in patients with BR and negative PSMA-PET following RP was achieved. These data support the usage of early SRT for patients with negative PSMA-PET findings.

Introduction: Enzalutamide, a second-generation androgen receptor inhibitor, is indicated for the treatment of metastatic disease, as well as in the treatment of non-metastatic castration resistant prostate cancer (PCa). This systematic review aims to determine outcomes and toxicity in patients with non-metastatic castration sensitive prostate cancer (nmCSPC) treated with enzalutamide in the primary or salvage settings. Method: We performed a systematic review focusing on the role of Enzalutamide in the treatment of nmCSPC, using the PubMed/Medline database. Articles focusing on androgen receptor inhibitors in nmCSPC were included, while articles discussing exclusively metastatic or castration-resistant PCa were excluded. Results: The initial search retrieved 401 articles, of which 15 underwent a thorough assessment for relevance. Ultimately, 12 studies with pertinent outcomes were meticulously examined. Among these, seven studies were dedicated to the investigation of enzalutamide in the primary setting, while the remaining five publications specifically addressed its use in salvage settings. Regardless of the treatment setting, our data revealed two distinct therapeutic strategies. The first advocates for the substitution of enzalutamide for androgen deprivation therapy (ADT), based on the premise of achieving equivalent, if not superior, oncological outcomes while minimizing treatment-related toxicity. The second, adopting a more conventional approach, entails augmenting the effectiveness of ADT by incorporating enzalutamide. Conclusion: Enzalutamide has considerable potential as a therapeutic strategy for nmCSPC, either used alone or in combination with ADT in the primary or in the salvage settings. The use of enzalutamide instead of ADT is an appealing strategy. However, more trials will be required to further understand the efficacy and side-effect profile of enzalutamide monotherapy.