ARTO trial was a phase II randomized trial suggesting the benefit of a concomitant treatment strategy including Abiraterone acetate plus predisone (AAP) and stereotactic body radiotherapy (SBRT) in oligometastatic castrate resistant prostate cancer (omCRPC). The object of the current analysis is to explore whether the benefit provided by SBRT to AAP is maintained at later stages of disease after oligoprogression Patients enrolled in ARTO trial in whom a first progression event was reported were divided in two groups according to the treatment approach received, regardless of the initial randomization. After first progression event, Patients in Group A received SBRT on oligoprogressive disease, while patients in group B received second line systemic treatment. Palliative RT was not considered for the purpose of this analysis. Progression-Free survival (PFS) 1 and 2 were defined as time between AAP start and first progression event and time between first and second progression event, death or last follow up, (whichever came first), respectively. Cox regression analysis was performed to compare PFS1 + PFS2 in patients in group A vs Group B. Kaplan–Meier analysis was performed to compare overall survival between the two groups Median PFS1 + PFS2 was 45.9 months vs. not reached in group A (n = 43) vs Group B (n = 20), respectively (HR 0.63, 95

Background: Oligometastatic disease in head and neck squamous cell carcinoma (HNSCC) is a rare setting. Local ablative therapies are the most adopted strategies although no evidence-based recommendations are currently published. We report on long-term clinical outcomes of a cohort of HNSCC patients treated with stereotactic body radiotherapy (SBRT) for lung-only oligometastatic disease. Material and Methods: Eligible patients had 1-5 lung metastases. The oligometastatic pattern was classified as "de novo" or "induced oligoprogressive". We evaluated time to progression (TTP) as the time from the last day of SBRT to disease progression or death from any cause. Predictive factors of better clinical outcome and survival analysis were performed. Results: A cohort of 50 patients (52 metastases) was retrospectively evaluated. The median age was 68 years and 45 patients had an ECOG PS 0-1. Oropharynx cancer was the primary tumor subsite in 20 patients and HPV positive status was reported in 13 patients. "De novo" oligometastatic pattern was observed for the majority of patients. After a median follow up of 24,5 months, median TTP and overall survival (OS) from the end of SBRT were 17 months and 46 months, respectively. The 2-years LC rates was 86 %. At univariate analysis, patients aged > 70 years reported a better TTP (0.03). Conclusion: Our findings suggested that SBRT may improve clinical outcome prolonging time to progression in a properly selected cohort of HNSCC patients with lung-only oligometastatic disease. Distant metastases from HPV-related primary HNSCC should be tested for p16/HPV status.

Background Moderate hypofractionated radiotherapy is a treatment option for the cure of localized prostate cancer (PCa) patients based on the results of randomized prospective trials, but there is a clinical concern about the relatively short length of follow-up, and real-world results on outcome and toxicity based on cutting-edge techniques are lacking. The objective of this study is to present the long-term results of a large multicentric series. Materials and methods We retrospectively evaluated 1325 PCa patients treated with daily volumetric image-guided hypofractionated radiotherapy between 2007 and 2020 in 16 Centers. For survival endpoints, we used Kaplan–Meier survival curves and fitted univariate and multivariable Cox’s proportional hazards regression models to study the association between the clinical variables and each survival type. Results At the end of the follow-up, 11 patients died from PCa. The 15-year values of cancer-specific survival (CSS) and biochemical relapse-free survival (b-RFS) were 98.5% (95%CI 97.3–99.6%) and 85.5% (95%CI 81.9–89.4%), respectively. The multivariate analysis showed that baseline PSA, Gleason score, and the use of androgen deprivation therapy were significant variables for all the outcomes. Acute gastrointestinal (GI) and genitourinary (GU) toxicities of grade ≥ 2 were 7.0% and 16.98%, respectively. The 15-year late grade ≥ 2 GI and GU toxicities were 5% (95%CI 4–6%) and 6% (95%CI 4–8%), respectively. Conclusion Real-world long-term results of this multicentric study on cutting-edge techniques for the cure of localized PCa demonstrated an excellent biochemical-free survival rate of 85.5% at 15 years, and very low rates of ≥ G3 late GU and GI toxicity (1.6% and 0.9% respectively), strengthening the results of the available published trials.

TPS235 Background: TITAN trial showed that apalutamide + ADT improved OS in patients with metastatic hormone sensitive prostate cancer (mHSPC), both in low and high-volume disease. On the other hand, SABR-COMET trial suggested that stereotactic body radiotherapy (SBRT) improved outcomes in oligometastatic patients if compared to systemic therapy alone. Recently, one trial suggested that SBRT may offer significant benefit in terms of biochemical response and progression free survival within oligometastatic castrate resistant prostate cancer patients undergoing first line abiraterone acetate treatment (ARTO trial, NCT03449719). However, there are no data specifically assessing the benefit offered by SBRT in oligometastatic mHSPC treated with apalutamide. PERSIAN trial is aimed to test the hypothesis that metastases directed SBRT will improve outcomes in select subgroups of pts with oligometastatic mHSPC treated with apalutamide + ADT. Moreover, we implemented baseline blood sample tests at enrollment/randomization, to evaluate the status of PIK3CA/AKT1/PTEN and BRCA1/BRCA2 mutations, and to investigate the predictive value of these alterations on treatment response. Furthermore, oncometabolites expression will be evaluated through metabolomic analysis before and after start of SBRT. Methods: PERSIAN trial is a prospective phase II randomized superiority study. All patients are affected by metachronous oligometastatic HSPC defined as presence of < 5 non-visceral metastatic lesions. Patients with de novo metastatic disease are excluded from the trial. Patients will be randomized to receive standard systemic treatment alone with apalutamide + ADT (Arm A: Control) or the same systemic treatment combined with SBRT on all sites of metastatic spread (Arm B: Treatment). This trial design will allow us to evaluate the benefit of SBRT in a selected cohort of patients with identical systemic treatments. Primary endpoint of the trial is the rate of patients with complete biochemical response (PSA < 0.2 ng/ml) 6 months after apalutamide + ADT start. Assuming a rate of complete biochemical response of 61% in the control arm, a sample size of 180 patients will have 80% statistical power to detect an absolute benefit of 19% in the treatment group, with alpha 0.05. Secondary endpoints are: time to PSA progression, radiologic progression free survival, frequency of treatment severe adverse events, overall and cancer specific survival, quality of life (measured with EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires). Enrollment started in March 2023, 31 patients have been enrolled to date. Clinical trial information: NCT05717660 .

INTRODUCTION:Post-mastectomy radiotherapy (PMRT) improves local control rates and survival in patients with adverse prognostic features. The dose coverage to target volumes is critical to yield maximum benefit to treated patients, increasing local control and reducing risk of toxicity. This study aims to assess patterns of breast cancer relapse in patients treated with mastectomy, breast reconstruction and PMRT. METHODS:Breast cancer patients treated with PMRT between 1992 and 2017 were retrospectively reviewed. Clinical and pathological characteristics of patients were collected. Recurrences were defined as "in field," "marginal" or "out of field." Survival analyses were performed in relation to progression-free survival (PFS) and overall survival (OS). Correlation between baseline features was explored. RESULTS:Data of 140 patients are collected. After a median follow-up time of 72 months, median PFS and OS of 63 and 74 months were detected, respectively. Neoadjuvant chemotherapy, lympho-vascular space invasion (LVI) and size of primary tumor were all significantly associated with worst PFS and OS. Ten patients developed local recurrence: 30% "in field," 30% marginal recurrences, 20% "out of field" and 20% both "in field" and "out of field." No recurrence was detected under the expander, 80% above the device and 20% patients relapsed on IMN chain. The mean distant relapse-free survival was 39 months. Overall, 39 of 140 patients developed distant metastases. CONCLUSIONS:The onset of local-regional relapses occurred mainly above the expander/prosthesis, underlying the importance of inclusion of the subcutaneous tissues within the target volume. In order to refine new contouring recommendations for PMRT and breast reconstruction, future prospective studies are needed.

OPINION article Front. Oncol., 09 January 2024Sec. Head and Neck Cancer Volume 13 - 2023 | https://doi.org/10.3389/fonc.2023.1240913

Abstract Background Trastuzumab deruxtecan (T-DXd) currently represents the standard of care for the treatment of patients with metastatic HER2-positive (HER2+) breast cancer (BC) after disease progression in the first line, which includes taxanes and trastuzumab. This recommendation is based on the results of the DESTINY-Breast03 trial, which demonstrated improved efficacy compared to trastuzumab emtansine (T-DM1). Radiation therapy (RT) is frequently required in the metastatic setting, either for palliative purposes or with ablative intent in cases of oligometastatic or oligoprogressive disease. The aim of our study is to evaluate the safety of using T-DXd and concomitant radiation therapy (RT) in a consecutive series of HER2+ BC patients. Methods We conducted a retrospective evaluation of patients diagnosed with metastatic HER2+ BC who initiated treatment with T-DXd between May 2021 and May 2023 at our institution, with or without receiving RT. We collected clinical data pertaining to the diagnosis of metastatic disease, T-DXd treatment, acute toxicities, survival data, and biological characteristics of both the primary tumor and metastases. The primary objective of this study was to assess the association between RT and any adverse events greater than grade (G) 2. Results We retrospectively evaluated data from 30 consecutive patients who were treated with T-DXd, with or without RT. Among these patients, ten received RT either immediately before (within a month) or during T-DXd treatment, while the remaining 20 did not. The median age of the patients was 72 years (range 34-88), and the median follow-up period was 9 months. Thirteen patients received T-DXd as the fourth or subsequent line of systemic anti-HER2 treatment, eight patients received it as the third line, and seven patients received it as the second line. Two patients, who experienced early metastatic disease relapse (< 6 months after completion of adjuvant anti-HER2 therapy), received T-DXd as their first-line treatment. The median prescribed total dose of RT was 34 Gy (range 20-48), with a median number of fractions of 4 (range 2-10). The median equivalent dose in 2 Gy fractions (EQD2) was 64 Gy (range 23.3-104), and the median biologically effective dose (BED) was 76 Gy (range 28-125). The most commonly treated sites were bone (70% of cases), followed by brain (20%) and liver (10%). A chi-square test of independence was conducted to examine the relationship between the administration of RT and the development of toxicity exceeding G2. However, this analysis did not reveal a significant relationship (p = .27). Regarding the specific toxicities of interest associated with T-DXd, three cases of grade 3 fatigue were reported in the group that did not receive RT, while one case was observed in the RT group. Overall, only one case of grade 3 nausea was reported, and it occurred in the group that did not receive RT. G2 interstitial lung disease, which led to discontinuation of T-DXd, was observed in one case in the RT group and one case in the no-RT group. Conclusions Our initial data is promising regarding the potential safety of this combination, as it indicates that concurrent RT did not lead to an increase in severe acute toxicity. However, larger series of data are required to validate and confirm these findings. Citation Format: Luca Visani, Carlotta Becherini, Niccolo' Bertini, Ilaria Bonaparte, Luca Burchini, Carolina Orsatti, Marianna Valzano, Marco Banini, Viola Salvestrini, Erika Scoccimarro, Vieri Scotti, Isacco Desideri, Giulio Francolini, Lorenzo Orzalesi, Marco Bernini, Cinzia Tommasi, Jacopo Nori, Simonetta Bianchi, Icro Meattini, Lorenzo Livi. Safety and efficacy of trastuzumab deruxtecan and concomitant radiation therapy in patients with metastatic HER2-positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-22-06.

The therapeutic landscape of metastatic prostate cancer has undergone a profound revolution in recent years. In addition to the introduction of novel molecules in the clinics, the field has witnessed a tremendous development of functional imaging modalities adding new biological insights which can ultimately inform tailored treatment strategies, including local therapies. The evolution and rise of Stereotactic Body Radiotherapy (SBRT) have been particularly notable in patients with oligometastatic disease, where it has been demonstrated to be a safe and effective treatment strategy yielding favorable results in terms of disease control and improved oncological outcomes. The possibility of debulking all sites of disease, matched with the ambition of potentially extending this treatment paradigm to polymetastatic patients in the not-too-distant future, makes Biology-guided Radiotherapy (BgRT) an attractive paradigm which can be used in conjunction with systemic therapy in the management of patients with metastatic prostate cancer.

Cisplatin-based chemoradiotherapy (CRT) is standard treatment for head and neck squamous cell carcinoma (HNSCC). However, IMRT may increase chemotherapy-induced nausea and vomiting (CINV). The purpose of this study is to investigate the effect of fosaprepitant in preventing CINV. An infusion of 150 mg fosaprepitant was given through a 30 min. We assessed acute toxicity using CTCAE v.4 and the incidence of CINV using the FLIE questionnaire. The evaluation of CINV was done at the second and fifth weeks of CRT and 1 week after the end. The EORTC QLQ-HN 43 questionnaire was administered before treatment beginning (baseline), at second (T1) and fifth (T2) weeks. A dosimetric analysis was performed on dorsal nucleus of vagus (DVC) and area postrema (AP). Between March and November 2020, 24 patients were enrolled. No correlation was found between nausea and DVC mean dose (p = 0.573), and AP mean dose (p = 0.869). Based on the FLIE questionnaire, patients reported a mean score of 30.5 for nausea and 30 for vomiting during week 2 and 29.8 for nausea and 29.2 for vomiting during week 5. After treatment ended, the mean scores were 27.4 for nausea and 27.7 for vomiting. All patients completed the EORTC QLQ-HN 43. Significantly higher scores at T2 assessment than baseline were observed. The use of fosaprepitant in preventing CINV reduced incidence of moderate to severe nausea and vomiting. No correlation has been found between nausea and median dose to DVC and AP.