Pattern of recurrence after stereotactic body radiotherapy for para-aortic oligo-recurrent prostate cancer, a multicentric analysis.

BACKGROUND: M1a disease represents an intermediate status between loco-regional relapse and bone metastatic disease. Metastasis directed therapy (MDT), through stereotactic body RT (SBRT) may be offered to patients, aiming to exclusively treat sites of macroscopic relapse and avoiding wide prophylactic treatment volumes. This appears as a viable treatment, especially after the rise of PSMA tailored treatment approaches. MATERIALS AND METHODS: Data about patients treated in two different institutions were retrieved from a prospectively collected dataset. All included patients were affected by oligo-recurrent M1a disease after definitive RT or radical prostatectomy, defined as ≤ 3 nodal lesions situated above aortic bifurcation and below renal arteries. Both castration resistant PCa (CRPC) and castration sensitive (CSPC) PCa patients were included. All imaging methods were allowed to detect recurrence (CT scan, Choline or PSMA PET/CT).All sites of recurrences were treated with SBRT. RESULTS: Median PFS was 10 months (95% CI 8-17). Twelve patients died, with a median OS of 114 months (95% CI 85-114). Out of the 83 recurrences, 2 (2.4%), 11 (13.25%), 36 (43.37%) and 15 (18%) patients had respectively prostate bed only, pelvic nodal, para-aortic or distant relapse. Furthermore, 19 (22.9%) patients experienced a biochemical only relapse with negative imaging at re-staging. DISCUSSION: MDT conferred a remarkable PFS outcome in a mixed cohort of CSPC and CRPC patients with m1a disease, with an optimal safety profile. Prospective trials are needed in order to compare MDT and ENRT for these patients, allowing to select the best treatment option.

Anal squamous cell carcinoma: Impact of radiochemotherapy evolution over years and an explorative analysis of MRI prediction of tumor response in a mono-institutional series of 131 patients.

Introduction: Radiochemotherapy (RCHT) for the treatment of anal squamous cell carcinoma (ASCC) has evolved dramatically, also thanks to intensity-modulated RT (IMRT) and 3D image guidance (3D IGRT). Despite most patients presenting fair outcomes, unmet needs still exist. Predictors of poor tumor response are lacking; acute toxicity remains challenging; and local relapse remains the main pattern of failure. Patients and methods: Between 2010 and 2020, ASCC stages I-III treated with 3D conformal radiotherapy or IMRT and CDDP-5FU or Mytomicine-5FU CHT were identified. Image guidance accepted included 2D IGRT or 3D IGRT. The study endpoints included freedom from locoregional recurrence (FFLR), colostomy free survival (CFS), freedom from distant metastasis (FFDM), overall survival (OS), and acute and late toxicity as measured by common terminology criteria for adverse events (CTCAE) version 5.0. An exploratory analysis was performed to identify possible radiomic predictors of tumor response. Feature extraction and data analysis were performed in Python™, while other statistics were performed using SPSS® v.26.0 software (IBM®). Results: A total of 131 patients were identified. After a median FU of 52 months, 83 patients (63.4%) were alive. A total of 35 patients (26.7%) experienced locoregional failure, while 31 patients (23.7%) relapsed with distant metastasis. Five year FFLR, CFS, DMFS and PS resulted 72.3%, 80.1%, 74.5% and 64.6%. In multivariate analysis, 2D IGRT was associated with poorer FFLR, OS, and CFS (HR 4.5, 4.1, and 5.6, respectively); 3DcRT was associated with poorer OS and CFS (HR 3.1 and 6.6, respectively). IMRT reduced severe acute gastro-intestinal (GI) and severe skin acute toxicity in comparison with 3DcRT. In the exploratory analysis, the risk of relapse depended on a combination of three parameters: Total Energy, Gray Level Size Zone Matrix's Large Area High Gray Level Emphasis (GLSZM's LAHGLE), and GTV volume. Conclusions: Advances in radiotherapy have independently improved the prognosis of ASCC patients over years while decreasing acute GI and skin toxicity. IMRT and daily 3D image guidance may be considered standard of care in the management of ASCC. A combination of three pre-treatment MRI parameters such as low signal intensity (SI), high GLSZM's LAHGLE, and GTV volume could be integrated in risk stratification to identify candidates for RT dose-escalation to be enrolled in clinical trials.

Early results of PRO-EPI: PROspective multicenter observational study on elective pelvic nodes irradiation in patients with intermediate/high/very high-risk non-metastatic prostate cancer submitted to radical, adjuvant, or salvage radiotherapy with or without concomitant androgen deprivation therapy.

Simple Summary: Although radiotherapy plays a fundamental role in the management of intermediate/high/very high-risk non-metastatic prostatic cancer (IHR-nmPca), there is still no consensus on the optimal treatment strategy in this setting. Remarkably, the role of elective nodal irradiation (ENI) is still highly controversial. The PROspective multicenter observational study on Elective Pelvic nodes Irradiation (PRO-EPI) was designed to provide "real life" data regarding the patterns of care for IHR-nmPca. Forty-three Italian Radiation Oncology centers participated in the PROspective multicenter observational study on Elective Pelvic nodes Irradiation (PRO-EPI) project, with 1029 patients enrolled. In this preliminary analysis, we longitudinally evaluated the impact of Elective Nodal Irradiation (ENI) and radiotherapy features on toxicity and quality of life (QoL). Six months follow-up data were available for 913 patients and 12 months data for 762 patients. Elective Nodal Irradiation was given to 506 patients (48.9%). Volumetric Intensity-Modulated Radiation Therapy (IMRT) was adopted in more than 77% of patients and Image-Guided Radiation Therapy (IGRT) in 84.4%. Androgen deprivation therapy (ADT) was administered to the majority of patients (68.3%), and it was associated to ENI in 408 cases (81.1%). Toxicity was mostly mild and reversible and IGRT resulted in a significant reduction of rectal toxicity, although a non-significant trend toward increased urinary toxicity was observed. No statistically significant differences in QoL and toxicity were seen in patients treated with or without ENI. The adoption of IGRT is widespread and increasing and could reduce treatment toxicity. ENI is not yet the standard treatment, but it is performed in a growing fraction of cases and not resulting into an increase in toxicity or in a deterioration of QoL. Further analyses are needed to clarify the long-term toxicity profile and the impact of ENI on survival.

'Le Roi est mort, vive le Roi': New Roles of Radiotherapy in the Treatment of Lymphomas in Combination With Immunotherapy.

BACKGROUND: immunotherapy (IT), including checkpoint inhibitors (CIs) and Chimeric Antigen Receptor T cell therapy (CAR-T) revolutionized the treatment of relapsing or refractory (r/r) lymphoma. Several preliminary experiences evaluated concomitant administration of radiotherapy and IT. METHODS: we performed a systematic review of current literature as of March 30, 2020. A total of 1090 records was retrieved, 42 articles were selected on the basis of title and abstract and, after the removal of analyses with no original data or insufficient clinical information, 28 papers were included in the review. RESULTS: previous studies were mostly represented by case reports/series or small cohorts. Nonetheless, combination of radiotherapy and CIs or CAR-T led to promising outcomes, resulting in extremely high rates of complete response and improving progression free and overall survival compared with data from recent clinical trials. Combination of RT and CIs had a fair toxicity profile with no reports of severe side effects. Within the limits of the small cohorts retrieved, RT seems a superior option compared with systemic treatment as a 'bridge' to CAR-T and could as well reduce severe complications rates. Radiotherapy could elicit immune response against lymphoma, as demonstrated by multiple cases of abscopal effect and its inclusion in anti-neoplastic vaccines protocols. CONCLUSION: The results of this review warrant the evaluation of combination of RT and immunotherapy in larger and preferably prospective and randomized cohorts to confirm these preliminary impressive outcomes. The optimal dose, fractionation and timing of RT still have to be clarified.

Stereotactic prostate radiotherapy with or without androgen deprivation therapy, study protocol for a phase III, multi-institutional randomized-controlled trial.

Objective: The therapeutic landscape for localized prostate cancer (PC) is evolving. Stereotactic radiotherapy (SRT) has been reported to be at least not inferior to standard radiotherapy, but the effect of androgen deprivation therapy (ADT) in this setting is still unknown and its use is left to clinical judgment. There is therefore the need to clarify the role of ADT in association with SRT, which is the aim of the present study. Methods: We present a study protocol for a randomized, multi-institutional, Phase III clinical trial, designed to study SRT in unfavorable intermediate and a subclass of high-risk localized PC. Patients (pts) will be randomized 1:1 to SRT + ADT or SRT alone. SRT will consists in 36.25 Gy in 5 fractions, ADT will be a single administration of Triptorelin 22.5 mg concurrent to SRT. Primary end point will be biochemical disease-free survival. Secondary end points will be disease-free survival, freedom from local recurrence, freedom from regional recurrence, freedom from distant metastasis and overall survival (OS); quality of life QoL and patient reported outcomes will be an exploratory end point and will be scored with EPIC-26, EORTC PR 25, IPSS, IIEF questionnaires in SRT + ADT and SRT alone arms. Moreover, clinician reported acute and late toxicity, assessed with CTCAE v. 5.0 scales will be safety end points. Results: Sample size is estimated of 310 pts. For acute toxicity and quality of life results are awaited after 6 months since last patient in, whereas, for efficacy end points and late toxicity mature results will be available 3-5 years after last patient in. Conclusion: Evidence is insufficient to guide decision making concerning ADT administration in the new scenario of prostate ultra-hypofractionation. Hence, the need to investigate the ADT role in SRT specific setting. Advances in knowledge: The stereotactic prostate radiotherapy with or without ADT trial (SPA Trial) has been designed to establish a new standard of care for SRT in localized unfavorable intermediate and a subclass of localized high risk PC.