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Despite the recent advanced developments in radiation therapy planning, treatment planning for head-neck and pelvic cancers remains challenging due to large concave target volumes, multiple dose prescriptions and numerous organs at risk close to targets. Inter-institutional studies highlighted that plan quality strongly depends on planner experience and skills. Automated optimization of planning procedure may improve plan quality and best practice. We performed a comprehensive dosimetric and clinical evaluation of the Pinnacle 3 AutoPlanning engine, comparing automatically generated plans (AP) with the historically clinically accepted manually-generated ones (MP). Thirty-six patients (12 for each of the following anatomical sites: head-neck, high-risk prostate and endometrial cancer) were re-planned with the AutoPlanning engine. Planning and optimization workflow was developed to automatically generate “dual-arc” VMAT plans with simultaneously integrated boost. Various dose and dose-volume parameters were used to build three metrics able to supply a global Plan Quality Index evaluation in terms of dose conformity indexes, targets coverage and sparing of critical organs. All plans were scored in a blinded clinical evaluation by two senior radiation oncologists. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 1500 2D-array. Autoplanning was able to produce high-quality clinically acceptable plans in all cases. The main benefit of Autoplanning strategy was the improvement of overall treatment quality due to significant increased dose conformity and reduction of integral dose by 6–10%, keeping similar targets coverage. Overall planning time was reduced to 60–80 minutes, about a third of time needed for manual planning. In 94% of clinical evaluations, the AP plans scored equal or better to MP plans. Despite the increased fluence modulation, dose measurements reported an optimal agreement with dose calculations with a γ-pass-rate greater than 95% for 3%(global)-2 mm criteria. Autoplanning engine is an effective device enabling the generation of VMAT high quality treatment plans according to institutional specific planning protocols.

The purpose of the present multicentric study was to review stereotactic body radiotherapy (SBRT) with or without chemotherapy (CHT) experience in locally advanced pancreatic cancer (LAPC). Endpoints were overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS). Several parameters' impact on these outcomes was assessed. Fifty-six patients with LAPC undergoing SBRT+/-CHT were included. SBRT median BED was 48.0 Gy (range=28.0-78.7). Survival curves were calculated by Kaplan-Meier method. A Cox regression model was fitted. At a median follow-up of 15.0 months, 2-year OS, LC, DMFS were: 33.8% 55.4%, and 22.9%, respectively. Patients treated with BED ≥48 Gy showed improved OS (p=0.020) and LC (p=0.024). At multivariate analysis, BED ≥48 Gy was significantly associated to both higher OS (p=0.042) and LC (p=0.045), while post-SBRT CHT improved DMFS (p=0.003). SBRT proved to be tolerable and effective in LAPC. Moreover, BED ≥48 Gy was significantly correlated with improved OS and LC.

OBJECTIVEThe aim of this study was to investigate the impact of SUVmax fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) measured in the primary tumor, pelvic and para-aortic node with disease-free survival (DFS) and overall survival (OS) in patients with locally advanced cervical cancer. METHODS AND MATERIALSA total of 92 patients with histological diagnosis of locally advanced cervical cancer are treated with radiochemotherapy plus brachytherapy boost from January 2008 to April 2014 in our Institution. A pretreatment FDG-PET/CT for staging and radiotherapy planning was performed, and the value of SUVmax measured in primary tumor and positive nodes was related to DFS and OS. RESULTSUnivariate analysis showed that DFS is related to FDG-PET/CT positive para-aortic nodes (P = 0.01), International Federation of Gynecology and Obstetrics (FIGO) stage of disease (P = 0.01), and primary tumor SUVmax (P = 0.02), and OS is related to positive para-aortic nodes (P = 0.01) and primary tumor SUVmax (P = 0.02).In multivariate analysis, DFS is modified by FDG-PET/CT positive para-aortic lymph nodes, stage and high T SUVmax (P = 0.02; P = 0.003; P = 0.04), but the only worse prognostic factor of OS is the high SUVmax in the primary tumor (P = 0.01). CONCLUSIONSWe found that T SUVmax, stage, and para-aortic lymph node status assessed by FDG-PET were independent prognostic factors of DFS, whereas only T SUVmax correlated with OS.

This narrative review explores the potential role of electrochemotherapy (ECT) in treating anorectal tumors, focusing on its effectiveness, feasibility, and associated toxicities. ECT, which combines chemotherapy with the application of an electric field to enhance drug uptake by tumor cells, has shown promise as a local treatment, particularly in cases where conventional therapies such as radiotherapy have been exhausted or are unsuitable. The review, conducted according to SANRA guidelines, included 18 studies, on ECT in anorectal tumors, ranging from preclinical trials in dogs to case reports and clinical studies in humans. The findings indicate that ECT can achieve high tumor overall response rates (70-100%) with minimal side effects, offering benefits such as tumor reduction and preserved organ function. These results highlight the potential of ECT to provide not only tumor reduction but also the preservation of vital organ function with a relatively low toxicity profile. However, further comparative research is necessary to substantiate its role as a standard therapeutic option. Moreover, the evidence is limited by significant heterogeneity across studies, small sample sizes, and a lack of comparative research with other local treatments like radiotherapy and cryosurgery. Consequently, while ECT appears to be a promising option, particularly for palliative care or in a neoadjuvant setting, it cannot yet be recommended as a standard treatment. Future research should focus on larger, more robust studies with standardized outcomes and explore the potential synergy between ECT and other therapies to establish its place in the treatment of anorectal tumors.

To retrospectively evaluate the outcome of patients with unresectable biliary cholangiocarcinoma (CC) treated with radiotherapy (RT) plus/minus chemotherapy (CHT). Data of patients with intrahepatic CC (ICC), Klatskin's tumor (KT), distal extrahepatic CC (ECC), and gallbladder cancer (GBC) diagnosed from 1991 to 2017 were retrospectively analyzed. The treatment was mainly based on RT plus concurrent CHT +/- brachytherapy (BRT) boost. The Kaplan-Meier method was used to calculate survival curves that were compared using the log-rank test. Seventy-six patients were included in this analysis (males: 59%; females: 41%; median age: 66.5 years). A minority of patients (7.9%) were treated for disease recurrence after surgery. According to TNM, 78.5% of patients had T stage >3 and 77.6% of patients were treated with concurrent CHT-RT while 22.3% received RT followed by sequential CHT. Median RT dose was 50 Gy (range: 16-75 Gy) delivered with conventional fractionation. CHT was based on Gemcitabine or 5-fluorouracil. BRT was prescribed to 51.3% of patient with a median dose of 14 Gy. Reported Grade ≥3 acute GI and hematological toxicity were 13.2% and 8.1%, respectively. No other severe acute toxicities were reported. One- and 2-year overall survival (OS) were 58.1% and 25.8%, respectively (median: 13.5 months), while 1- and 2-year progression-free survival (PFS) were 43.4% and 9.4%, respectively. None of the following variables had a significant impact on OS and PFS: BRT boost, tumor site, concurrent CHT, and the drugs used in concurrent CHT. In contrast, patients receiving RT with 2D technique showed a PFS significantly higher compared to patients treated with the 3D technique (median: 15.5 vs. 8.5 months; p=0.02). Combined modality treatment (RT+CHT±BRT) in unresectable biliary cancer was associated with acceptable toxicity and OS comparable to the actual standard treatment (CHT). The significantly improved PFS in patients undergoing 2D-RT raises doubts regarding the adequacy of target delineation in these neoplasms.

ObjectiveThis retrospective, multicenter study analyzes the efficacy and safety of stereotactic body radiotherapy in a large cohort of patients with oligometastatic/persistent/recurrent cervical cancer.MethodsA standardized data collection from several radiotherapy centers that treated patients by stereotactic body radiotherapy between March 2006 and February 2021 was set up. Clinical and stereotactic body radiotherapy parameters were collected. Objective response rate was defined as a composite of complete and partial response, while clinical benefit included objective response rate plus stable disease. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Common Terminology Criteria for Adverse Events scales were used to grade toxicities. The primary endpoints were the rate of complete response to stereotactic body radiotherapy, and the 2 year actuarial local control rate on a ‘per lesion’ basis. The secondary end points were progression-free survival and overall survival, as well as toxicity.ResultsA total of 83 patients with oligometastatic/persistent/recurrent cervical cancer bearing 125 lesions treated by stereotactic body radiotherapy at 15 different centers were selected for analysis. Of the sites of metastatic disease, lymph node metastases were most common (55.2%), followed by parenchyma lesions (44.8%). Median total dose was 35 Gy (range 10–60), in five fractions (range 1–10), with a median dose/fraction of 7 Gy (range 4–26). Complete, partial, and stable response were found in 73 (58.4%), 29 (23.2%), and 16 (12.8%) lesions, respectively, reaching 94.4% of the clinical benefit rate. Forty-six (55.4%) patients had a complete response. Patients achieving complete response on a ‘per lesion’ basis experienced a 2 year actuarial local control rate of 89.0% versus 22.1% in lesions not achieving complete response (p<0.001). The 2 year actuarial progression-free survival rate was 42.5% in patients with complete response versus 7.8% in patients with partial response or stable or progressive disease (p=0.001). The 2 year actuarial overall survival rate was 68.9% in patients with complete response versus 44.3% in patients with partial response or stable or progressive disease (p=0.015). Fifteen patients (18.1%) had mild acute toxicity, totaling 29 side events. Late toxicity was documented in four patients (4.8%) totaling seven adverse events.ConclusionOur analysis confirmed the efficacy of stereotactic body radiotherapy in oligometastatic/persistent/recurrent cervical cancer patients. The low toxicity profile encourages the wider use of stereotactic body radiotherapy in this setting.

Purpose DESTROY—4 ( D OSE- E SCALATION STUDY OF ST EREOTACTIC BODY R ADIATI O N THERAP Y ) was a Phase I trial aimed to evaluate the safety and the feasibility of escalating doses of stereotactic body radiation therapy (SBRT) on MRI-defined Dominant Intraprostatic Lesion (DIL) in low- and intermediate-risk pCa patients using a simultaneous integrated boost-volumetric arc therapy (SIB-VMAT) technique. Methods Eligible patients included those with low- and intermediate-risk prostate carcinoma (NCCN risk classes) and an International Prostatic Symptoms Score (IPSS) ≤ 15. No restriction about DIL and prostate volumes was set. Pretreatment preparation required an enema and the placement of intraprostatic gold fiducials. SBRT was delivered in five consecutive daily fractions. For the first three patients, the DIL radiation dose was set at 8 Gy per fraction up to a total dose of 40 Gy (PTV1) and was gradually increased in succeeding cohorts to total doses of 42.5 Gy, 45.0 Gy, 47.5 Gy, and finally, 50.0 Gy, while keeping the prescription of 35 Gy/7 Gy per fraction for the entire prostate gland. Dose-limiting toxicity (DLT) was defined as grade 3 or worse gastrointestinal (GI) or genitourinary (GU) toxicity occurring within 90 days of follow-up (Common Terminology Criteria of Adverse Events scale 4.0). Patients completed quality-of-life questionnaires at defined intervals. Results Twenty-four patients with a median age of 75 (range, 58–89) years were enrolled. The median follow-up was 26.3 months (8.9–84 months). 66.7% of patients were classified as intermediate-risk groups, while the others were low-risk groups, according to the NCCN guidelines. Enrolled patients were treated as follows: 8 patients (40 Gy), 5 patients (42.5 Gy), 4 patients (45 Gy), 4 patients (47.5 Gy), and 3 patients (50 Gy). No severe acute toxicities were observed. G1 and G2 acute GU toxicities occurred in 4 (16%) and 3 patients (12.5%), respectively. Two patients (8.3%) and 3 patients (12.5%) experienced G1 and G2 GI toxicities, respectively. Since no DLTs were observed, 50 Gy in five fractions was considered the MTD. The median nadir PSA was 0.20 ng/mL. A slight improvement in QoL values was registered after the treatment. Conclusion This trial confirms the feasibility and safety of a total SIB-VMAT dose of 35 Gy on the whole gland and 50 Gy on DIL in 5 fractions daily administered in a well-selected low- and intermediate-risk prostate carcinoma population. A phase II study is ongoing to confirm the tolerability of the schedule and assess the efficacy.

Background: Bone metastases (BMs) are a common complication in patients with cancer, often leading to significant pain that adversely affects quality of life, necessitating effective pain management strategies. This study aims to evaluate the effectiveness of pain management in patients with BMs undergoing palliative radiotherapy and to identify determinants of pain management adequacy. Methods: We conducted an observational analysis of 560 patients from the Palliative Radiotherapy and Inflammation Study (PRAIS) trial across several European centers, focusing on the Pain Management Index (PMI) for assessing pain management adequacy. Key predictors examined included Karnofsky Performance Status (KPS), treatment setting, primary tumor type, and site of BMs. Results: Our findings indicate that 19.0% of patients experienced inadequate pain management (PMI < 0). Specifically, patients with KPS ⩾ 90 had a notably lower rate of adequate analgesic therapy (59.3%) compared with those with a KPS < 90 (85.0%). Among outpatients, 23.7% reported inadequate pain management, contrasted with a significantly lower inadequacy rate (3.8%) in palliative care or hospice settings. In addition, in outpatients, pain management adequacy varied with the primary tumor type, showing improved outcomes for patients with lung cancer (89.2%) versus other primary tumors (79.1%). Moreover, in non-outpatients, pain management was less effective for patients receiving radiotherapy on pelvic BMs (89.5%) compared with other sites (95.7%). Conclusion: Although overall rates of inadequate pain management were lower than seen in previous studies, significant variability exists based on patient health status, care setting, primary tumor type, and site of BMs. These results underscore the need for personalized pain management approaches and highlight specific areas for improvement in outpatient settings and among patients with generally good health but significant pain from BMs.

Aims This review aims to synthesize the existing literature on palliative radiotherapy (RT) delivered in two daily fractions for patients with advanced cancer, focusing on its impact on symptom alleviation, treatment tolerance, and the implications for clinical practice and future research. Methods An international team conducted this narrative review, adhering to SANRA guidelines. Studies published in English on palliative RT delivered in two daily fractions were selected without date restrictions. The literature search, using a combination of specific key terms, led to a comprehensive examination of relevant studies. Data on study objectives, treatment approaches, palliative effectiveness, and toxicity were extracted and qualitatively analyzed. Results The review included 29 publications, showing consistent efficacy in symptom reduction (63.0%–100% palliative response rate) and general tolerability across various cancer types. These studies highlighted the potential radiobiological advantages and practicality of accelerated multi-fractionated regimens, which provide rapid tumor response with reduced late toxicity risks. Furthermore, the logistical benefits of such treatments, including shorter hospital stays and minimized travel requirements, were noted as particularly valuable during challenging times such as recent pandemics. Conclusions The evidence supports the integration of evidence-based, accelerated-hypofractionated RT into palliative care strategies, ensuring effective symptom management with minimal patient burden. Future research should focus on comparative studies on single versus multiple-cycle treatments, optimal intervals between treatment cycles, and the integration of advanced RT techniques.

Preserving cognitive functions is a priority for most patients with brain metastases. Knowing the mechanisms of hyperglutamatergic neurotoxicity and the role of some hippocampal areas in cognitive decline (CD) led to testing both the antiglutamatergic pharmacological prophylaxis and hippocampal-sparing whole-brain radiotherapy (WBRT) techniques. These studies showed a relative reduction in CD four to six months after WBRT. However, the failure to achieve statistical significance in one study that tested memantine alone (RTOG 0614) led to widespread skepticism about this drug in the WBRT setting. Moreover, interest grew in the reasons for the strong patient dropout rates in the first few months after WBRT and for early CD onset. In fact, the latter can only partially be explained by subclinical tumor progression. An emerging interpretation of the (not only) cognitive impairment during and immediately after WBRT is the dysfunction of the limbic and hypothalamic system with its immune and hormonal consequences. This new understanding of WBRT-induced toxicity may represent the basis for further innovative trials. These studies should aim to: (i) evaluate in greater detail the cognitive effects and, more generally, the quality of life impairment during and immediately after WBRT; (ii) study the mechanisms producing these early effects; (iii) test in clinical studies, the modern and advanced WBRT techniques based on both hippocampal-sparing and hypothalamic-pituitary-sparing, currently evaluated only in planning studies; (iv) test new timings of antiglutamatergic drugs administration aimed at preventing not only late toxicity but also acute effects.