Background: To date, in breast cancer (BC) treatment, adjuvant chemotherapy (A-CT) has preceded adjuvant radiotherapy (A-RT). In the last twenty years, the adjuvant treatment of BC has quickly evolved due to better knowledge of its molecular biology, genetic profile, and α/β ratio of 3/4 Gy for tumor and normal tissue radiosensitivity. Thus, new schedules with hypofractionated radiotherapy have been tested, and a third generation of A-CT has been introduced, raising the question of whether it is time to rethink the sequencing between these two approaches. Methods: In the last 20 years, many attempts have been made worldwide to optimize the best sequencing strategy between these two approaches in terms of sequential CT-RT and RT-CT and concomitant and sandwich modalities using drugs and schedules. This paper presents a comprehensive review of the state of the art, analyzing all the available studies to assess the sequencing between A-CT and A-RT with different generations of chemotherapy schedules. Results: More than 8000 patients from 30 studies treated with adjuvant chemotherapy and whole breast radiotherapy who were enrolled in randomized, retrospective, and prospective studies were analyzed. Sequential, concomitant, and sandwich modalities of chemotherapy with conventional or hypofractionated RT schedules from the most important studies were included. The most used sequence was adjuvant chemotherapy followed by conventional or hypofractionated radiotherapy. In the concomitant approach, i.v. CMF has been the most important adopted schedule, while the concomitant use of anthracyclines and taxanes with conventional or hypofractionated radiotherapy has been found to be more toxic. One study analyzed the benefit in terms of reducing adjuvant treatment time with upfront hypofractionated radiotherapy and third-generation chemotherapy. Conclusions: At present, the best sequencing strategy has not yet been defined. This comprehensive review is a journey among the most important randomized, retrospective, and prospective studies that highlights the past, current, and novel time sequencing proposals between A-CT and A-RT to assess the state of the art and provide useful information for future adjuvant approaches in breast cancer treatment.

Up to now in breast cancer (BC) treatment, adjuvant chemotherapy (A-CT) precedes adjuvant radiotherapy (A-RT). It’s beyond question that A-RT improves local control while A-CT improves the Disease Free Survival (DFS) due to the reduction of metastatic distant recurrences. Taken togheter these two approaches impact favourably on the reduction of breast cancer mortality. In the last twenty years, the adjuvant treatment of BC has evolved quickly due to a better knowledge of its molecular biology , genetic prohile and its α/β ratio 3 / 4 Gy for the tumor and normal tissues radiosensitivity. Thus new schedules with hypofractionated radiotherapy have been tested and third generation of A-CT have been introduced leading to a better survival rate but a further delay in A-RT starting, raising the question to rethink the sequencing between these two approaches. However the sequencing timing between these two approaches still remains unchanged with A-CT before A-RT as the standard of care. Many attempts have been provided in order to optimize this sequencing. This comprehensive review is a journey among randomised, retrospective and prospective studies which highlights the past, the current and the novelties on timing sequencing proposals between these two modalities to assess the state of art. Sequential, concomitant and sandwitch modalities of chemotherapy with conventional or hypofractionated RT schedules from the most important studies will be analysed in this review.

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.

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.

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.

Background: In this study, we retrospectively analyzed clinical and toxicity outcomes of 67 prostate cancer (PCa) patients undergoing moderately hypofractionated radiotherapy (RT) after prostatectomy, with adjuvant or salvage intent. Methods: Irradiation was delivered by volumetric modulated arc therapy. The median follow-up was 48 months. The 3- and 5-year biochemical relapse-free survival rates were 80% and 69%. The RT schedule consisted of a median total dose of 67.5 Gy with a median number of 25 fractions and a median fraction dose of 2.7 Gy to the prostate bed (PB) and 60% of patients simultaneously received whole pelvis irradiation (WP; fraction dose: 1.8 Gy, median total dose of 46.8 Gy). Results: The rate of acute toxicity was 54% for gastrointestinal (GI) and 36% for genitourinary (GU). No grade 3 acute toxicity was observed. Late toxicity was as follows: G1, G2, and G3 GI events in 25.5%, 3.6%, and 1.8% of the cases, respectively; G1, G2, and G3 GU events in 37.1%, 11.1%, and 7.4%, respectively. The toxicity-free survival (TFS) curves showed a different trend for acute and late toxicity. TFS was significantly associated with RT volume, except for acute GI toxicity. Specifically, the concomitant irradiation of PB and WP appeared to be a significant risk factor for late GI and GU toxicity (p = 0.029 and p = 0.012, respectively). Conclusions: At the 48-month median timepoint considered by our study, postoperative hypofractionated RT achieved promising results in terms of clinical outcomes with acceptable toxicity. Only the irradiated volume seems to be an important predictor for toxicity.