Antonella Bianculli

In post-prostatectomy prostate cancer, combining androgen deprivation therapy (ADT) with salvage radiotherapy (SRT) significantly improves clinical outcomes, though the absolute benefit varies based on baseline PSA, pathological risk, and treatment design. This review synthesizes findings from key randomized trials and contemporary meta-analyses—including RTOG 9601, SPPORT, GETUG-AFU 16, GETUG-AFU 22, and RADICALS-HD—evaluating the integration and duration of ADT with postoperative irradiation. While systemic therapy consistently enhances biochemical and clinical progression-free survival, a universal overall survival benefit remains uncertain or limited to high-risk cohorts with elevated pre-treatment PSA values. Concurrently, data from the prospective phase II OLIGOPELVIS (GETUG P07) and PEACE V-STORM trials are redefining the standard of care for pelvic nodal oligorecurrent disease detected via next-generation imaging (NGI). Transitioning away from exclusive lifelong ADT or isolated focal metastasis-directed therapy, emerging evidence strongly supports a multimodal paradigm: combining prostate bed RT, whole-pelvis elective nodal irradiation, and a high-dose boost to PET-positive nodes, complemented by a short course of systemic therapy. Ultimately, this narrative review provides clinicians with evidence-based guidance on integrating ADT to maximize regional disease control and delay systemic progression, while successfully sparing the majority of patients from the toxicities of continuous ADT.

Background and purpose Ultra-hypofractionated whole-breast radiotherapy (UHF-RT; 26 Gy/5fx) shortens treatment duration and mitigates travel burdens compared to moderate hypofractionation (MHF-RT; 40.5 Gy/15fx) for breast cancer (BC) patients at IRCCS CROB in Basilicata, Italy. This study quantified visit reductions, analyzed radiobiological advantages, and assessed treatment fidelity in a resource-constrained, geographically challenging region. Materials and methods We analyzed 204 consecutive BC patients receiving adjuvant UHF-RT (2022–2025), evaluating travel distance, time, vehicle access, and demographics. K-means clustering (k=4) identified logistical risk profiles, comparing resource utilization and radiobiological metrics against MHF-RT using an effective BED framework incorporating treatment-break rates by a population-level effective BED and Treatment Fidelity model. Results In this cohort, K-means clustering stratified the cohort into four distinct profiles: Autonomous Regional Commuters (36.3%), Ultra-Range Travelers (29.9%), Proximal Fragility (19.6%), and Isolated High-Risk (14.2%). Moving from 15 to 5 fractions achieved a 66.7% reduction in clinical visits and a 3.76-fold increase in daily biological dose intensity (11.96 vs. 3.18 Gy/day). Transitioning from 15 to 5 fractions achieved an absolute 66.7% reduction in clinical visits. UHF-RT delivered a 3.76-fold increase in daily biological dose intensity (11.96 Gy/day vs. 3.18 Gy/day). UHF-RT delivered a 3.76-fold increase in daily biological dose intensity (11.96 Gy/day vs. 3.18 Gy/day). Incorporating real-world interruptions, population-level tumor treatment fidelity (≥ 95% of planned BED) was higher under UHF-RT compared to MHF-RT (97.3% vs. 95.2%), ensuring full radiobiological delivery across the logistically vulnerable population. Conclusions In geographically fragmented settings, UHF-RT reduces hospital visits, preserves treatment fidelity, and mitigates travel toxicity for appropriate BC patients.

Breast-conserving surgery followed by adjuvant whole-breast irradiation (WBI) remains the standard of care for patients with early-stage breast cancer. In this setting, irradiation of the tumor bed with an additional boost dose has historically been used to reduce the risk of ipsilateral breast tumor recurrence (IBTR). Major randomized trials established that boost irradiation improved local control, particularly in younger patients, but did not confer a consistent overall survival (OS) benefit and was associated with increased late toxicity, like fibrosis, and poorer cosmetic outcomes as well. More recent evidence, including systematic reviews and contemporary consensus recommendations, suggests that boost irradiation may be safely omitted in selected low-risk patients, especially when the estimated absolute reduction in 10-year local recurrence is less than 3%. At the same time, the routine use of boost irradiation has been challenged by modern systemic therapy treatments questioning if boost could be really omitted in this set. Further advances in radiation techniques are redefining the scheduling and timing of boost administration, shifting from a conventional fractionation to hypofractionation and from the sequential (SEB) to simultaneous delivery with simultaneous integrated boost (SIB). In light of increasingly minimally invasive surgery and a de-escalation RT policy, unresolved clinical issues still remain about the management of positive or close margins and the role of boost irradiation in ductal carcinoma in situ. This narrative review summarizes the biological rationale, historical trial evidence, and recent literature addressing these evolving scenarios. Current evidence supports a more individualized approach to boost prescription based on recurrence risk, patient age, tumor biology, margin status, treatment techniques (surgery and radiotherapy), and patient preference.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor clinical outcomes and limited responsiveness to conventional treatments. Beyond delayed diagnosis, its high mortality is linked to limited treatment choices and resistance to chemotherapy. Neoplastic cells characterized by stem-like features and epithelial–mesenchymal transition (EMT) activation are crucial drivers of drug resistance and metastatic progression. Consequently, targeting these cellular programs could represent a promising therapeutic strategy for PDAC. N-acetyl-L-aspartic acid (NAA) is an endogenous metabolite, mainly localized in the central nervous system, where it facilitates acetate storage for lipid metabolism. Previous studies established its antineoplastic effect in neuroblastoma, promoting a more differentiated phenotype of cancer cells. Here we investigated the effects of NAA on BxPC-3 pancreatic cancer cells using both 2D and 3D models. NAA treatment induced a dose-dependent reduction in cell proliferation and led to a significant downregulation of stemness-associated surface markers, with concomitant upregulation of E-cadherin. Furthermore, NAA significantly enhanced cellular radiosensitization with a reduction in caveolin-1 and increased efficacy of gemcitabine in PDAC cells. Collectively, these results confirmed the anticancer activity of NAA and provide a rationale for further investigation of its synergistic effects with radiotherapy to yield better PDAC treatments.

In post-prostatectomy prostate cancer, combining androgen deprivation therapy (ADT) with salvage radiotherapy (SRT) significantly improves clinical outcomes, though the absolute benefit varies based on baseline PSA, pathological risk, and treatment design. This review synthesizes findings from key randomized trials and contemporary meta-analyses including RTOG 9601, SPPORT, GETUG-AFU 16, GETUG-AFU 22, and RADICALS-HD evaluating the integration and duration of ADT with postoperative irradiation. While systemic therapy consistently enhances biochemical and clinical progression-free survival, a universal overall survival benefit remains uncertain or limited to high-risk cohorts with elevated pre-treatment PSA values. Concurrently, data from the prospective phase II trials OLIGOPELVIS (GETUG P07) and PEACE V - STORM are redefining the standard of care for pelvic nodal oligorecurrent disease detected via next-generation imaging (NGI). Transitioning away from exclusive lifelong ADT or isolated focal metastasis-directed therapy, emerging evidence strongly supports a multimodal paradigm: combining prostate bed RT, whole-pelvis elective nodal irradiation, and a high-dose boost to PET-positive nodes, complemented by a short course of systemic therapy. This narrative review provides readers with effective indication to use adjuvant HT according recent literature evidences to maximizes regional disease control and delays systemic progression, while successfully sparing the majority of patients from the toxicities of continuous androgen deprivation.

Breast-conserving surgery followed by adjuvant whole-breast irradiation ( WBI) remains the standard of care for patients with early-stage breast cancer. In this setting, irradiation of the tumor bed with an additional boost dose has historically been used to reduce the risk of ipsilateral breast tumor recurrence (IBTR). The major randomized trials established that boost irradiation improves local control, particularly in younger patients, but does not confer a consistent overall survival (OS) benefit and is associated with increased late toxicity, like fibrosis and poorer cosmetic outcomes as well. More recent evidence, including systematic reviews and contemporary consensus recommendations, suggests that boost irradiation may be safely omitted in selected low-risk patients, especially when the estimated absolute reduction in 10-year local recurrence is is less than 3%. At the same time, the routine use of boost irradiation has been challenged by modern systemic therapy treatments questioning if boost could be really omitted in this set. Further advances in radiation techniques are redefining the scheduling and timing of boost administration, shifting from a conventional fractionation to hypofractionation, and from the sequential (SEB) to the simultaneous delivery with simultaneous integrated boost (SIB). In light of increasingly minimally invasive surgery and de-escalation RT policy, unresolved clinical issues still remains about the management of positive or close margins and the role of boost irradiation in ductal carcinoma in situ. This narrative review summarizes the biological rationale, historical trial evidence, and recent literature addressing these evolving scenarios. Current evidence supports a more individualized approach to boost prescription based on recurrence risk, patient age, tumor biology, margin status, treatment techniques(surgery and radiotherapy), and patient preference.

Whole breast radiotherapy in adjuvant breast cancer (BC) treatment has been commonly delivered in supine positioning for more than 50 years. Its widespread use is related to the broad availability of simple and common breast board immobilization devices, which exploit the natural recumbent position of the body with arms above the head, the good match with linac tables and well-established set up procedures. However, in scenarios like painful arm discomfort in patients with post-surgery arm or arthritic limitation, unfavorable chest geometry like pectus excavatum (PE), large and pendulous breasts in obese women and cardiac morbidity in left sided BC, supine position seems very uncomfortable for patients and troublesome for radiation oncologists. The question is how to proceed when supine IMRT or DIBH are ineffective strategies? Alternative positions have been analyzed over the past twenty years, starting with a lot of trials testing prone positioning variants with and without DIBH, lateral decubitus or upright standing radiotherapy. A better recognition of new treatment position options in BC adjuvant therapy may provide more opportunities for personalized radiotherapy in this population, to ensure they receive an appropriate, safe and comfortable treatment.

Whole breast radiotherapy in adjuvant breast cancer (BC) treatment is commonly delivered in supine positioning since more than 50 years ago. Its widespread use is related to the broad availability of simply and common breast board immobilization devices which exploit the natural recumbent position of the body with arms above the head, the good match with linac tables and well established set up procedures. However, several criticisms have been raised over time in case of scenarios like painful arm discomfort in patients with post-surgery arm or arthritic limitation, unfavorable chest geometry like pectus excavatum, large and pendulous breasts in obese women, cardiac morbidity in left sided BC. In these scenarios supine position seems very uncomfortable for patients and troublesome for radiation oncologists. Heart dosimetry in pectus excavatum (PE) and left sided breasts, breast size and shape matter when DIBH is not allowed. In fact, not all patients are suitable DIBH candidates because of the limiting factors like obesity or pulmonary morbidities. Thus, adjuvant whole breast radiotherapy in supine positioning could be very critical. Alternative positions have been analyzed in these last twenty years starting from a lot of trials testing prone positioning variants with and without DIBH, lateral decubitus or up-right standing radiotherapy. Customized immobilization devices have been developed to make these alternative positions more comfortable and consistent with beams angles arrangements and modern RT delivery avoiding collisions with the device or the Linac. To standardize the target delineation in these positions, customized guidelines have been also provided and recently several atlas-based segmentation processes have been provided to reduce bias by incorporating an interobserver quality analysis. Researches and a better recognition of new treatment position options in BC adjuvant therapy may provide more opportunities for a personalized radiotherapy mainly in that population not suitable for supine RT, to ensure them an appropriate, safe and comfortable treatment.

Over the past two decades, interest in prone-position whole breast irradiation (WBI) as an effective and practical alternative to supine treatment has been growing a lot. Although solid scientific data has provided evidence of substantial dosimetric benefit with decreased toxicity, there is still conflict in the radiotherapy community over whether to adopt prone-position WBI as a valid alternative to supine radiotherapy (RT) in routine clinical practice. A large number of prone trials have been conducted to assess and address concerns related to prone treatment in large and pendulous breasts and in left and right breast cancer (BC), nodal irradiation, and its reproducibility with deep inspiration breath hold (DIBH) delivery with photons or protons. Appropriate atlases have been defined to improve prone nodal irradiation. Additionally, more comfortable customized immobilization couches have been constructed to permit IMRT beams and VMAT arrangements with modern LINACs. Although our search in literature databases shows a growing body of evidence from the past two decades on this issue, prone WBI is still underused. Given the paradox of the advances and benefits of this positioning and the lack of drive in the radiotherapy community towards its clinical implementation, the purpose of this comprehensive review is to evaluate the true advantages of this position in real life and contextualize it in scenarios like large breasts, left-sided breast cancer, and nodal irradiation to encourage its implementation in clinical practice.