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Background: This study aimed to develop a predictive model for acute gastrointestinal (GI) and genitourinary (GU) toxicity in prostate cancer patients treated with salvage radiotherapy (SRT) post-prostatectomy, using machine learning techniques to identify key prognostic factors. Methods: A multicenter retrospective study analyzed 454 patients treated with SRT from three Italian radiotherapy centers. Acute toxicity was assessed using Radiation Therapy Oncology Group criteria. Predictors of grade ≥ 2 toxicity were identified through Least Absolute Shrinkage and Selection Operator (LASSO) regression and Classification and Regression Tree (CART) modeling. The analyzed variables included surgical technique, clinical target volume (CTV) to planning target volume (PTV) margins, extent of lymphadenectomy, radiotherapy technique, and androgen-deprivation therapy (ADT). Results: No patients experienced grade ≥ 4 toxicity, and grade 3 toxicity was below 1% for both GI and GU events. The primary determinant of acute toxicity was the surgical technique. Open prostatectomy was associated with significantly higher grade ≥ 2 GI (41.8%) and GU (35.9%) toxicity compared to laparoscopic/robotic approaches (18.9% and 12.2%, respectively). A CTV-to-PTV margin ≥ 10 mm further increased toxicity, particularly when combined with extensive lymphadenectomy. SRT technique and ADT were additional predictors in some subgroups. Conclusions: SRT demonstrated excellent tolerability. Surgical technique, CTV-to-PTV margin, and treatment parameters were key predictors of toxicity. These findings emphasize the need for personalized treatment strategies integrating surgical and radiotherapy factors to minimize toxicity and optimize outcomes in prostate cancer patients.

In a recent multicenter analysis of 454 patients undergoing post-prostatectomy salvage radiotherapy, the open surgical approach, as opposed to minimally invasive surgery, emerged, unexpectedly, as the strongest predictor of acute gastrointestinal and genitourinary toxicity. Patients treated with laparoscopic or robotic prostatectomy experienced significantly lower rates of ≥grade 2 toxicity compared to those who had undergone open retropubic surgery, irrespective of total dose, treatment margins, or radiation delivery platform. This finding, which to our knowledge has not been previously reported, raises the hypothesis that surgical technique leaves a lasting biological imprint on irradiated tissues. Drawing on current knowledge in radiobiology, cytokine signaling, wound healing, and pelvic dosimetry, we explore potential mechanisms by which open surgery may create a more hypoxic, inflamed, and fibrotic microenvironment, thereby amplifying radiation damage. We further discuss how target volume margins may biologically interact with this tissue state to increase normal tissue exposure. This Perspective aims to provide a conceptual framework for understanding this unexpected association, highlighting its clinical relevance for individualizing margins, counselling high-risk patients, and designing future studies at the interface of surgery and radiation oncology. This paper does not introduce additional patients or statistical models; instead, it offers an in-depth clinical and mechanistic interpretation of previously published ICAROS findings.

Palliative radiotherapy (PRT) is central to symptom control in advanced cancer, yet referrals are often late, and patients and clinicians frequently hold misconceptions about intent, benefits, and logistics. Patient education may address these gaps, but the PRT-specific evidence base has not been consolidated. We conducted a narrative review following SANRA guidance. We searched PubMed, Scopus, and the Cochrane Library for English-language studies from 1 January 2000 to 18 July 2025. Eligible articles evaluated structured patient-education interventions or characterized education or communication content, information needs, or decision processes among adults referred to or receiving PRT. Two reviewers independently screened and extracted data. Owing to heterogeneity of designs and endpoints, we performed a narrative synthesis without meta-analysis. Six studies met criteria: two randomized controlled trials, two prospective pre–post studies, one qualitative interview study, and one observational communication study, conducted in the Netherlands, the United States, Canada, and Hong Kong. Education at referral or consultation improved knowledge, reduced decisional uncertainty, and increased readiness to proceed with PRT. Education integrated with treatment improved symptom outcomes, including higher rates of pain control at 12 weeks and faster time to pain control when a nurse-led pain-education program accompanied PRT for painful bone metastases, and improvements in dyspnea, fatigue, anxiety, and function in advanced lung cancer. Observational and qualitative work showed low patient question-asking and persistent curative expectations; overall quality of life generally did not change. Although the evidence is limited and heterogeneous, targeted, standardized education appears to improve decision quality and selected symptoms in PRT pathways. Pragmatic multi-site trials and implementation studies are needed to define content, timing, personnel, and delivery models that are scalable in routine care.

Background: Previous studies have often reported a link between advanced age and inadequate cancer pain management. Given Italy’s demographic profile as the country with the oldest population in Europe, it offers an ideal setting to explore whether this association remains valid today. Aim: This study aimed primarily to assess the influence of advanced age on the adequacy of pain management among patients receiving treatment in Italian radiotherapy (RT) departments, and secondarily, to identify age-specific determinants of analgesic undertreatment. Methods: In this prospective, multicenter study, we enrolled 2104 consecutive patients attending 13 RT centers between October and November 2019. Pain intensity was evaluated using the numeric rating scale (NRS), and patients reporting scores ≥ 1 (n = 1353) were included in the analysis. Pain management adequacy was assessed using the Pain Management Index (PMI), with negative values indicating undertreatment. A two-step statistical approach was employed: variable selection via Least Absolute Shrinkage and Selection Operator regression, followed by Classification and Regression Tree analysis to identify key predictors. Separate analyses were performed for the overall population, older adults (≥65 years), and younger adults (18–64 years). Results: Overall, 42% of patients were undertreated (PMI < 0), without significant differences between older (41.0%) and younger patients (43.1%). However, factors contributing to undertreatment varied according to age. For the entire cohort, non-cancer pain was associated with substantially higher rates of undertreatment (74.3%) compared to cancer-related pain (34.2%). Among cancer patients, those receiving curative RT had poorer pain control (49.4%) than those receiving palliative RT (28.8%). In older patients, geographic location strongly influenced pain management, with higher rates of undertreatment in central and southern Italy compared to the north (e.g., palliative RT: 64.0% vs. 15.4%, respectively). Conversely, younger patients showed no geographical differences; instead, timing of assessment (beginning vs. end of RT) influenced outcomes, with improved PMI values towards the end of treatment. Conclusions: Unlike previous studies, advanced age itself was not associated with inadequate analgesia. However, the determinants of inadequate pain management differed significantly by age: geographic disparities were predominant among older patients, while assessment timing influenced outcomes for younger patients. Further longitudinal research and targeted interventions are needed to address these age-dependent challenges.

Introduction Biliary tract cancers (BTC) are rare and aggressive neoplasms. The current management of locally advanced or unresectable BTC is primarily based on chemotherapy (CHT) alone, linked to a median overall survival (OS) of approximately 12 months. However, international guidelines still consider concurrent chemoradiation (CRT) as an alternative treatment option. This study aims to review the current evidence on “modern” CRT for primary or recurrent unresectable BTC. Materials and Methods A comprehensive search was conducted on PubMed, Scopus, and Cochrane Library to identify relevant papers. Prospective or retrospective trials reporting outcomes after concurrent CRT of unresectable non‐metastatic, primary, or recurrent BTC were included. Only English‐written papers published between January 2010 and June 2022 were considered. Results Seventeen papers, comprising a total of 1961 patients, were included in the analysis. Among them, 11 papers focused solely on patients with primary unresectable BTC, while two papers included patients with isolated local recurrences and four papers encompassed both settings. In terms of tumor location, 12 papers included patients with intrahepatic, extrahepatic, and hilar BTC, as well as gallbladder cancer. The median CRT dose delivered was 50.4 Gy (range: 45.0–72.6 Gy) using conventional fractionation. Concurrent CHT primarily consisted of 5‐Fluorouracil or Gemcitabine. The pooled rates of 1‐year progression‐free survival (PFS) and OS were 40.9% and 56.2%, respectively. The median 1‐ and 2‐year OS rates were 63.1% and 29.4%, respectively. Grade ≥3 acute gastrointestinal toxicity ranged from 5.6% to 22.2% (median: 10.9%), while grade ≥3 hematological toxicity ranged from 1.6% to 50.0% (median: 21.7%). Conclusion Concurrent CRT is a viable alternative to standard CHT in patients with locally advanced BTC, offering comparable OS and PFS rates, along with an acceptable toxicity profile. However, prospective trials are needed to validate and further explore these findings. This is a systematic review of the current evidence on “modern” chemoradiation for primary or recurrent unresectable biliary tract cancers. We have critically compared chemoradiation outcomes with those of other treatment options, seeking to determine whether specific chemoradiation modalities provide distinct advantages in terms of treatment efficacy and patient safety. This analysis is pivotal for informing future treatment guidelines and optimizing patient care in this challenging clinical area.

Background/Aim: Radium-223 dichloride (223RaCl2) represents a therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) patients dealing with symptomatic bone metastases. The identification of baseline variables potentially affecting the life-prolonging role of 223RaCl2 is still ongoing. Bone scan index (BSI) defines the total load of bone metastatic disease detected on a bone scan (BS) and is expressed as a percentage value of the whole bone mass. The aim of this multicenter study was to assess the impact of baseline BSI on overall survival (OS) in mCRPC patients treated with 223RaCl2. For this purpose, the DASciS software developed by the Sapienza University of Rome for BSI calculation was shared between six Italian Nuclear Medicine Units. Methods: 370 pre-treatment BS were analyzed through the DASciS software. Other clinical variables relevant to OS analysis were taken into account for the statistical analysis. Results: Of a total of 370 patients, 326 subjects had died at the time of our retrospective analysis. The median OS time from the first cycle of 223RaCl2 to the date of death from any cause or last contact was 13 months (95%CI 12–14 months). The mean BSI value resulted in 2.98% ± 2.42. The center-adjusted univariate analysis showed that baseline BSI was significantly associated with OS as an independent risk factor (HR 1.137, 95%CI: 1.052–1.230, p = 0.001), meaning that patients with higher BSI values had worse OS. When adjusting for other measures on multivariate analysis, in addition to Gleason score and baseline values of Hb, tALP, and PSA, baseline BSI was confirmed to be a statistically significant parameter (HR 1.054, 95%CI: 1.040–1.068, p < 0.001). Conclusions: Baseline BSI significantly predicts OS in mCRPC treated with 223RaCl2. The DASciS software was revealed to be a valuable tool for BSI calculation, showing rapid processing time and requiring no more than a single demonstrative training for each participating center.

Background: The primary objective of this study was to assess the adequacy of analgesic care in radiotherapy (RT) patients, with a secondary objective to identify predictive variables associated with pain management adequacy using a modern statistical approach, integrating the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and the Classification and Regression Tree (CART) analysis. Methods: This observational, multicenter cohort study involved 1387 patients reporting pain or taking analgesic drugs from 13 RT departments in Italy. The Pain Management Index (PMI) served as the measure for pain control adequacy, with a PMI score < 0 indicating suboptimal management. Patient demographics, clinical status, and treatment-related factors were examined to discern the predictors of pain management adequacy. Results: Among the analyzed cohort, 46.1% reported inadequately managed pain. Non-cancer pain origin, breast cancer diagnosis, higher ECOG Performance Status scores, younger patient age, early assessment phase, and curative treatment intent emerged as significant determinants of negative PMI from the LASSO analysis. Notably, pain management was observed to improve as RT progressed, with a greater discrepancy between cancer (33.2% with PMI < 0) and non-cancer pain (73.1% with PMI < 0). Breast cancer patients under 70 years of age with non-cancer pain had the highest rate of negative PMI at 86.5%, highlighting a potential deficiency in managing benign pain in younger patients. Conclusions: The study underscores the dynamic nature of pain management during RT, suggesting improvements over the treatment course yet revealing specific challenges in non-cancer pain management, particularly among younger breast cancer patients. The use of advanced statistical techniques for analysis stresses the importance of a multifaceted approach to pain management, one that incorporates both cancer and non-cancer pain considerations to ensure a holistic and improved quality of oncological care.

Aim: The frequent inadequacy of pain management in cancer patients is well known. Moreover, the quality of analgesic treatment in patients treated with radiotherapy (RT) has only been rarely assessed. In order to study the latter topic, we conducted a multicenter, observational and prospective study based on the Pain Management Index (PMI) in RT Italian departments. Methods: We collected data on age, gender, tumor site and stage, performance status, treatment aim, and pain (type: CP—cancer pain, NCP—non-cancer pain, MP—mixed pain; intensity: NRS: Numeric Rating Scale). Furthermore, we analyzed the impact on PMI on these parameters, and we defined a pain score with values from 0 (NRS: 0, no pain) to 3 (NRS: 7–10: intense pain) and an analgesic score from 0 (pain medication not taken) to 3 (strong opioids). By subtracting the pain score from the analgesic score, we obtained the PMI value, considering cases with values < 0 as inadequate analgesic prescriptions. The Ethics Committees of the participating centers approved the study (ARISE-1 study). Results: Two thousand one hundred four non-selected outpatients with cancer and aged 18 years or older were enrolled in 13 RT departments. RT had curative and palliative intent in 62.4% and 37.6% patients, respectively. Tumor stage was non-metastatic in 57.3% and metastatic in 42.7% of subjects, respectively. Pain affected 1417 patients (CP: 49.5%, NCP: 32.0%; MP: 18.5%). PMI was < 0 in 45.0% of patients with pain. At multivariable analysis, inadequate pain management was significantly correlated with curative RT aim, ECOG performance status = 1 (versus both ECOG-PS3 and ECOG- PS4), breast cancer, non-cancer pain, and Central and South Italy RT Departments (versus Northern Italy).Conclusions: Pain management was less adequate in patients with more favorable clinical condition and stage. Educational and organizational strategies are needed in RT departments to reduce the non-negligible percentage of patients with inadequate analgesic therapy.

Background: Pain is a prevalent symptom among cancer patients, and its management is crucial for improving their quality of life. However, pain management in cancer patients referred to radiotherapy (RT) departments is often inadequate, and limited research has been conducted on this specific population. This study aimed to assess the adequacy and effectiveness of pain management when patients are referred for RT. Moreover, we explored potential predictors of adequate pain management. Methods: This observational, prospective, multicenter cohort study included cancer patients aged 18 years or older who were referred to RT departments. A pain management assessment was conducted using the Pain Management Index (PMI), calculated by subtracting the pain score from the analgesic score (PMI < 0 indicated inadequate pain management). Univariate and multivariate analyses were performed to identify predictors of adequate pain management. Results: A total of 1042 cancer outpatients were included in the study. The analysis revealed that 42.9% of patients with pain did not receive adequate pain management based on PMI values. Among patients with pain or taking analgesics and referred to palliative or curative RT, 72% and 75% had inadequate or ineffective analgesic therapy, respectively. The odds of receiving adequate pain management (PMI ≥ 0) were higher in patients undergoing palliative RT (OR 2.52; p < 0.001), with worse ECOG-PS scores of 2, 3 and 4 (OR 1.63, 2.23, 5.31, respectively; p: 0.017, 0.002, 0.009, respectively) compared to a score of 1 for those with cancer-related pain (OR 0.38; p < 0.001), and treated in northern Italy compared to central and southern of Italy (OR 0.25, 0.42, respectively; p < 0.001). Conclusions: In this study, a substantial proportion of cancer patients referred to RT departments did not receive adequate pain management. Educational and organizational strategies are necessary to address the inadequate pain management observed in this population. Moreover, increasing the attention paid to non-cancer pain and an earlier referral of patients for palliative RT in the course of the disease may improve pain response and treatment outcomes.