Post-operative KEloids iRradiation (POKER): does the surgery/high-dose interventional radiotherapy association make a winning hand?

PURPOSE: To report the results involving post-operative interventional radiotherapy (POIRT) in a homogenous cohort of patients affected by keloid and treated at a single institution with the same fractionation schedule. PATIENTS AND METHODS: Inclusion criteria were: surgery with a histopathological diagnosis of keloid, subsequent high-dose rate interventional radiotherapy (HDR-IRT)-12 Gy in 4 fractions (3 Gy/fr) twice a day-and follow-up period ≥ 24 months. RESULTS: One-hundred and two patients and a total of 135 keloids were eligible for the analyses. Median follow-up was 64 [IQR: 25-103] months. Thirty-six (26.7%) recurrences were observed, 12-months and 36-months cumulative incidence of recurrence were 20.7% (95% CI 12.2-28.5) and 23.8% (95% CI 14.9-31.7) respectively. History of spontaneous keloids (HR = 7.00, 95% CI 2.79-17.6, p < 0.001), spontaneous cheloid as keloid cause (HR = 6.97, 95% CI 2.05-23.7, p = 0.002) and sternal (HR = 10.6, 95% CI 3.08-36.8, p < 0.001), ear (HR = 6.03, 95% CI 1.71-21.3, p = 0.005) or limb (HR = 18.8, 95% CI 5.14-68.7, p < 0.001) keloid sites were significantly associated to a higher risk of recurrence. CONCLUSIONS: The findings support the use of surgery and POIRT as an effective strategy for controlling keloid relapses. Further studies should focus on determining the optimal Biologically Effective Dose and on establishing a scoring system for patient selection.

Adjuvant radiotherapy in node positive prostate cancer patients: a debate still on. when, for whom?

OBJECTIVE: To evaluate the impact of adjuvant radiotherapy (aRT) in patients with prostate cancer (PCa) found to have pathological positive lymph nodes (pN1s) after radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND) with regard to distant recurrence-free survival (RFS), according to both main tumour pathological characteristics and number of positive lymph nodes. Biochemical RFS, local RFS, overall survival (OS) and acute and late toxicity were assessed as secondary endpoints. PATIENTS AND METHODS: A retrospective cohort of 187 consecutive patients with pN1 PCa were treated with aRT at the IEO, European Institute of Oncology IRCCS, Milan, Italy. aRT on the tumour bed and pelvis was administered within 6 months of RP. Androgen deprivation therapy was administered according to the guidelines. Univariate and multivariate Cox regression analyses predicting biochemical RFS, local RFS, distant RFS and OS rates were performed to assess whether the number of pN1s represented an independent prognostic factor. The Youden index was computed to find the optimal threshold for the number of pN1s able to discriminate between patients with or without biochemical and clinical relapse. RESULTS: At 5 years, local RFS, distant RFS, biochemical RFS and OS were 68%, 71%, 56% and 94%, respectively. The median follow-up was 49 months. The number of pN1s was significantly associated with biochemical RFS, local RFS and distant RFS. The best threshold for discriminating between patients with or without biochemical and clinical relapse was five pN1s. In multivariate analyses, the number of pN1s was confirmed to be an independent predictor of biochemical RFS, local RFS and distant RFS, but not of OS. Multivariate analyses also showed an increased risk of biochemical relapse for increasing values of initial prostate-specific antigen and for patients with tumour vascular invasion. Local and distant RFS were also inversely correlated with significantly reduced risk for International Society of Urological Pathology grade group <3 (group 1 or 2 compared to group 3). CONCLUSIONS: Our data confirmed the encouraging outcomes of patients with pN1 PCa treated with adjuvant treatments and the key role represented by the number of pN1s in predicting biochemical RFS, clinical RFS and distant RFS. Large prospective cohort studies and randomized clinical trials are needed to confirm these results and to identify the subgroup of patients with pN1 PCa who would most benefit from aRT.

Blood- and Imaging-Derived Biomarkers for Oncological Outcome Modelling in Oropharyngeal Cancer: Exploring the Low-Hanging Fruit.

AIMS: To assess whether CT-based radiomics and blood-derived biomarkers could improve the prediction of overall survival (OS) and locoregional progression-free survival (LRPFS) in patients with oropharyngeal cancer (OPC) treated with curative-intent RT. METHODS: Consecutive OPC patients with primary tumors treated between 2005 and 2021 were included. Analyzed clinical variables included gender, age, smoking history, staging, subsite, HPV status, and blood parameters (baseline hemoglobin levels, neutrophils, monocytes, and platelets, and derived measurements). Radiomic features were extracted from the gross tumor volumes (GTVs) of the primary tumor using pyradiomics. Outcomes of interest were LRPFS and OS. Following feature selection, a radiomic score (RS) was calculated for each patient. Significant variables, along with age and gender, were included in multivariable analysis, and models were retained if statistically significant. The models' performance was compared by the C-index. RESULTS: One hundred and five patients, predominately male (71%), were included in the analysis. The median age was 59 (IQR: 52-66) years, and stage IVA was the most represented (70%). HPV status was positive in 63 patients, negative in 7, and missing in 35 patients. The median OS follow-up was 6.3 (IQR: 5.5-7.9) years. A statistically significant association between low Hb levels and poorer LRPFS in the HPV-positive subgroup (p = 0.038) was identified. The calculation of the RS successfully stratified patients according to both OS (log-rank p < 0.0001) and LRPFS (log-rank p = 0.0002). The C-index of the clinical and radiomic model resulted in 0.82 [CI: 0.80-0.84] for OS and 0.77 [CI: 0.75-0.79] for LRPFS. CONCLUSIONS: Our results show that radiomics could provide clinically significant informative content in this scenario. The best performances were obtained by combining clinical and quantitative imaging variables, thus suggesting the potential of integrative modeling for outcome predictions in this setting of patients.

Stereotactic Radiotherapy Ablation and Atrial Fibrillation: Technical Issues and Clinical Expectations Derived From a Systematic Review.

Aim: The purpose of this study is to collect available evidence on the feasibility and efficacy of stereotactic arrhythmia radio ablation (STAR), including both photon radiotherapy (XRT) and particle beam therapy (PBT), in the treatment of atrial fibrillation (AF), and to provide cardiologists and radiation oncologists with a practical overview on this topic. Methods: Three hundred and thirty-five articles were identified up to November 2021 according to preferred reporting items for systematic reviews and meta-analyses criteria; preclinical and clinical studies were included without data restrictions or language limitations. Selected works were analyzed for comparing target selection, treatment plan details, and the accelerator employed, addressing workup modalities, acute and long-term side-effects, and efficacy, defined either by the presence of scar or by the absence of AF recurrence. Results: Twenty-one works published between 2010 and 2021 were included. Seventeen studies concerned XRT, three PBT, and one involved both. Nine studies (1 in silico and 8 in vivo; doses ranging from 15 to 40 Gy) comprised a total of 59 animals, 12 (8 in silico, 4 in vivo; doses ranging from 16 to 50 Gy) focused on humans, with 9 patients undergoing STAR: average follow-up duration was 5 and 6 months, respectively. Data analysis supported efficacy of the treatment in the preclinical setting, whereas in the context of clinical studies the main favorable finding consisted in the detection of electrical scar in 4/4 patients undergoing specific evaluation; the minimum dose for efficacy was 25 Gy in both humans and animals. No acute complication was recorded; severe side-effects related to the long-term were observed only for very high STAR doses in 2 animals. Significant variability was evidenced among studies in the definition of target volume and doses, and in the management of respiratory and cardiac target motion. Conclusion: STAR is an innovative non-invasive procedure already applied for experimental treatment of ventricular arrhythmias. Particular attention must be paid to safety, rather than efficacy of STAR, given the benign nature of AF. Uncertainties persist, mainly regarding the definition of the treatment plan and the role of the target motion. In this setting, more information about the toxicity profile of this new approach is compulsory before applying STAR to AF in clinical practice.

Retrospective application of Program to Access and Review Trending iNformation and Evaluate coRrelation to Symptoms in patients with Heart Failure criteria for the remote management of patients with cardiac resynchronisation therapy.

Aim The Program to Access and Review Trending iNformation and Evaluate coRrelation to Symptoms in patients with Heart Failure (PARTNERS HF) trial elaborated a multiparametric model for prediction of acute decompensation in advanced heart failure patients, based on periodical in office data download from cardiac resynchronisation devices. In this study, we evaluated the ability of the PARTNERS HF criteria to detect initial decompensation in a population of moderate heart failure patients under remote monitoring. Methods We retrospectively applied the PARTNERS HF criteria to 1860 transmissions from 104 patients (median follow up 21 months; range 1-67 months), who were enrolled in our programme of telemedicine after cardiac resynchronisation therapy. We tested the ability of a score based on these criteria to predict any acute clinical decompensation occurring in the 15 days following a transmission. Results In 441 cases, acute heart failure was diagnosed after the index transmission. The area under the curve (AUC) of the score for the diagnosis of acute decompensation was 0.752 (confidence interval (CI) 95% 0.728-0.777). The best score cut-off was consistent with the results of PARTNERS HF: with a score ≥2, sensitivity was 75% and specificity 68%. The odds ratio for events was 6.24 (CI 95% 4.90-7.95; p < 0.001). Conclusions When retrospectively applied to remote monitoring transmissions and arranged in a score, PARTNERS HF criteria could identify HF patients who subsequently developed acute decompensation. These results warrant prospective studies applying PARTNERS HF criteria to remote monitoring.