Long term update on toxicity and survival of a phase II trial of linac-based stereotactic body radiation therapy for low-intermediate risk prostate cancer.

BACKGROUND: In 2016 we published a phase II study exploring safety and efficacy of Stereotactic Body Radiation Therapy (SBRT) delivered with Volumetric Modulated Arc Therapy (VMAT) and Flattening Filter Free (FFF) beams techniques in prostate cancer (PC) patients. We present herein the updated results on late toxicity and long-term survival. METHODS: Patients enrolled in the study had a biopsy-confirmed localized PC and the features of a low- or intermediate-risk disease (National Comprehensive Network Criteria). The radiotherapy (RT) schedule consisted of 35 Gy delivered in five fractions every other day. Toxicities were registered according to the common toxicity adverse events v4.0. Biochemical recurrence was defined as an increase of prostate specific antigen after nadir, confirmed at least once. Local recurrence (LR) and distant metastases were detected either with Choline- or PSMA-PET/CT scans. Kaplan-Meier curves for Biochemical Recurrence-Free Survival (BFS), Local Control (LC), Distant Metastasis Free Survival (DMFS) and Cancer Specific Survival, were calculated by using MedCalc. RESULTS: Ninety patients were submitted to SBRT between February 2012 and March 2015. Fifty-eight patients (64.5%) had a Gleason Score of 6, while 32 (35.5%) had a Gleason Score of 7. A late grade 1 Genito-Urinary toxicity was observed in 54.5% of patients while a grade 2 in 3.3%. A late Gastro-intestinal grade 1 toxicity was reported in 18.9% of patients, while a grade 2 in 2.2%. Erectile dysfunction was reported by 13% of patients No heavier toxicities were observed. At a median follow-up of 102 months, 5- and 8-year BFS were 93.0% and 84.4% respectively, 5- and 8-year LC were 95.2% and 87.0% respectively, 5- and 8-year DMFS were 95.3% and 88.4%, respectively. CONCLUSIONS: This long-term update confirms that SBRT is a valid therapeutic strategy for low-intermediate risk PC. RT with VMAT and FFF warrants optimal results in terms of toxicity and disease control.

Radiomics-based prognosis classification for high-risk prostate cancer treated with radiotherapy.

OBJECTIVE: The present study aimed to investigate if CT-based radiomics features could correlate to the risk of metastatic progression in high-risk prostate cancer patients treated with radical RT and long-term androgen deprivation therapy (ADT). MATERIALS AND METHODS: A total of 157 patients were investigated and radiomics features extracted from the contrast-free treatment planning CT series. Three volumes were segmented: the prostate gland only (CTV_p), the prostate gland with seminal vesicles (CTV_psv), and the seminal vesicles only (CTV_sv). The patients were split into two subgroups of 100 and 57 patients for training and validation. Five clinical and 62 radiomics features were included in the analysis. Considering metastases-free survival (MFS) as an endpoint, the predictive model was used to identify the subgroups with favorable or unfavorable prognoses (separated by a threshold selected according to the Youden method). Pure clinical, pure radiomic, and combined predictive models were investigated. RESULTS: With a median follow-up of 30.7 months, the MFS at 1 and 3 years was 97.2% ± 1.5 and 92.1% ± 2.0, respectively. Univariate analysis identified seven potential predictors for MFS in the CTV_p group, 11 in the CTV_psv group, and 9 in the CTV_sv group. After elastic net reduction, these were 4 predictors for MFS in the CTV_p group (positive lymph nodes, Gleason score, H_Skewness, and NGLDM_Contrast), 5 in the CTV_psv group (positive lymph nodes, Gleason score, H_Skewnesss, Shape_Surface, and NGLDM_Contrast), and 6 in the CTV_sv group (positive lymph nodes, Gleason score, H_Kurtosis, GLCM_Correlation, GLRLM_LRHGE, and GLZLM_SZLGE). The patients' group of the training and validation cohorts were stratified into favorable and unfavorable prognosis subgroups. For the combined model, for CTV_p, the mean MFS was 134 ± 14.5 vs. 96.9 ± 22.2 months for the favorable and unfavorable subgroups, respectively, and 136.5 ± 14.6 vs. 70.5 ± 4.3 months for CTV_psv and 150.0 ± 4.2 vs. 91.1 ± 8.6 months for CTV_sv, respectively. CONCLUSION: Radiomic features were able to predict the risk of metastatic progression in high-risk prostate cancer. Combining the radiomic features and clinical characteristics can classify high-risk patients into favorable and unfavorable prognostic groups.

Moderate hypofractionated radiotherapy for post-operative treatment of prostate cancer: long-term outcome and pattern of toxicity.

OBJECTIVE: Postoperative radiotherapy (RT) is an established treatment for prostate cancer (PC). Though hypofractionation is commonly used for radical treatments, open issues still remain in the postoperative setting due to the lack of long-term data. Aim of this study was to evaluate long-term results of postoperative moderately hypofractionated RT (MHRT). METHODS: We conducted a retrospective analysis including PC patients treated with prostatectomy and postoperative MHRT delivered with volumetric modulated arc therapy (VMAT). Endpoints of the analysis included biochemical relapse-free survival (BRFS), distant metastases free-survival (DMFS), overall survival (OS), and pattern of acute and late toxicity. RESULTS: 181 patients were included. Pathological stage was classified as pT3a in 33.6% and pT3b in 30%. Median PSA value before RT was 0.23 ng/ml and median RT total dose was 70 Gy (65-74.2 Gy) in 25/28 fractions. With a median follow-up of 54.5 months, rates of BRFS at 3 and 5 years were 80.7 and 72.3%. ISUP grade group (HR 1.44, p = 0.015), pathological T stage (HR 2.03; p = 0.009), and pre-RT PSA >0.2 ng/ml (HR 2.64; p = 0.015) were correlated with BRFS. Three and 5­year DMFS were 87.4 and 80.8%. ISUP grade group (HR 1.50; p = 0.011) and pre-RT PSA (HR 5.34; p = 0.001) were correlated with DMFS. Five (2.7%) and 3 (1.6%) patients reported late grade 3 GU and GI toxicity, respectively. CONCLUSION: Our results confirm the long-term safety and efficacy of postoperative MHRT for PC. ADVANCES IN KNOWLEDGE: The present paper demonstrates the long-term safety and efficacy of MHRT for postoperative prostate cancer. Reduction of treatment time in long-course radiotherapy has advantages in terms of both patients' quality of life and departmental organization.

Dosimetric impact of volumetric modulated arc therapy for nasopharyngeal cancer treatment.

BACKGROUND: The purpose of the study was to evaluate the toxicity and outcome of nasopharyngeal carcinoma patients treated using 3-dimensional conformal radiotherapy (3DCRT) or volumetric modulated arc therapy (VMAT) technique. MATERIALS AND METHODS: 68 patients treated between 2006 and 2018 were retrospectively analysed. Since 2009 patients received 3DCRT with 50/70 Gy to the elective/boost volumes in 35 fractions; from then, VMAT with simultaneous integrated boost (SIB) with 54.45/69.96 Gy in 33, or 54/66 Gy in 30 fractions. Induction chemotherapy was administered in 74% of the patients, concomitant cisplatinum in 87%. Acute and late toxicity data, progression-free survival PSF and overall survival OS, and toxicity correlations with dose metrics were reported. RESULTS: With a median follow-up of 64 months, complete remission at the last evaluation was in 68% of the patients, while 28% and 9% had locoregional relapse and distant disease, respectively. The 5- and 10-year progression free survival (PFS) rates were 62.7 ± 6.5% and 53.2 ± 8.7%, respectively. The 5- and 10-year OS rates were 78.9 ± 5.5% and 61.4 ± 9.2%, respectively. At the multivariate Cox analysis TNM stage (p = 0.02) and concomitant chemotherapy (p = 0.01) resulted significant for PFS, concomitant chemotherapy (p = 0.04) for OS.Improvements in acute toxicity were presented for VMAT patients due to its ability to spare OARs. Odds ratio (OR) for acute salivary toxicity, between VMAT and 3DCRT, was 4.67 (p = 0.02). Dosimetrically, salivary toxicity correlated with mean parotid dose (p = 0.05), dysphagia with laryngeal (p = 0.04) and mean oral cavity (p = 0.06) doses, when dose-volume histograms (DVHs) are corrected for fractionation. CONCLUSION: This study is a proof of a significant benefit of the VMAT technique compared with 3DCRT in terms of side effects in nasopharynx patients, and adds dosimetric correlations.

Linac-based stereotactic body radiation therapy for low and intermediate-risk prostate cancer : Long-term results and factors predictive for outcome and toxicity.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is considered an effective and safe treatment in patients with low- and intermediate-risk prostate cancer (PC). However, due to a lack of long-term follow-up and late toxicity data, this treatment is not universally accepted. The present study aimed to evaluate outcome and early and late toxicity in a cohort of patients with low- and intermediate-risk PC treated prospectively with linear accelerator (linac)-based SBRT. PATIENTS AND METHODS: Patients with low- or intermediate-risk (NCCN criteria) PC were included. All patients received linac-based SBRT to 35 Gy in 5 fractions delivered on alternate days. Endpoints were toxicity, biochemical relapse-free survival (BRFS), metastatic progression-free survival (mPFS), and overall survival (OS). RESULTS: From 2012 to 2018, 178 patients were treated. Median baseline prostate-specific antigen (iPSA) was 6.37 ng/ml (range 1.78-20). Previous transurethral resection of the prostate (TURP) was present in 23 (12.9%) patients. Median follow-up was 58.9 months (range 9.7-89.9). BRFS rates at 1, 3, and 5 years were 98.3 (95% confidence interval, CI, 94.7-99.4%), 94.4 (95%CI 89.4-97), and 91.6% (95%CI 85.4-95.2), respectively. In univariate analysis, performance status (PS), iPSA, and nadir PSA (nPSA) were correlated with BRFS. In multivariable analysis iPSA and nPSA remained significant. BRFS rates at 5 years were 94.9% (95%CI 86.8-98) for International Society of Urological Pathology (ISUP) grade group 1, 93.2% (95%CI 80.5-97.7) for ISUP group 2, and 74.8% (95%CI 47.1-89.5) for ISUP group 3. At 1, 3, and 5 years, mPFS rates were 98.8 (95%CI 95.5-99.7), 96.2 (95%CI 91.9-98.3), and 92.9% (95%CI 87.2-96.2), respectively; OS rates were 100, 97.2 (95%CI 92.9-98.9), and 95.1% (95%CI 90-97.6), respectively. One (0.56%) case of grade 3 acute genitourinary (GU), one case of acute gastrointestinal (GI), and one case of grade 3 late GU toxicity were observed. GI toxicity positively correlated with prostate volume. CONCLUSION: At long-term follow-up, linac-based SBRT continues to be a valid option for the management localized PC. Biochemical control remains high at 5 years, albeit with some concerns regarding the optimal schedule for unfavorable intermediate-risk PC. Considering the excellent prognosis, patient selection is crucial for prevention of severe late toxicity.

Trends in combined radio-chemotherapy for locally advanced rectal cancer: a survey among radiation oncology centers of Sicily region on behalf of AIRO.

AIM: To conduct a survey among Sicilian centers of radiation oncology belonging to Associazione Italiana di Radioterapia ed Oncologia Clinica (AIRO), to record the different methods of integration of radio-chemotherapy both in neoadjuvant and adjuvant settings, to evaluate surgical procedures in relation to the sphincter preservation and to report the different toxicity profiles of the treatment strategies. METHODS: A questionnaire was sent at the end of 2017 to all the radiation oncology centers of Sicily region in order to collect the data from individual centers and the treatment characteristics retrospectively over the previous 5 years, from 2012 to 2016. The required data were collected from 13 centers out of 17 which, in relation to the single catchment areas, correspond to approximately 85% of the Sicilian population. The requested data concerned the type of integrated treatment (neoadjuvant vs adjuvant vs radical), combination with chemotherapy (induction, concomitant, adjuvant), type of surgical intervention (sphincter-saving vs abdomino-perineal resection), disease stage, schedule and radiotherapy technique adopted, as well as toxicity detected over the treatment period. RESULTS: A total of 784 pts (M/F: 509/275) were treated between 2012 and 2016, with a median age of 67 years (range 25-92). The majority of patients was treated in the neoadjuvant phase (62% of the total) compared to the adjuvant phase (31%) and to those treated radically (7%). Twenty-five percent of patients did not receive combination chemotherapy mainly for cardiovascular problems. Chemotherapy used concomitantly to radiotherapy was single-agent capecitabine (73% of patients) or 5-fluorouracil (27%). The use of chemotherapy alone before concomitant treatment is more common for patients treated in the adjuvant phase (64% of this subgroup), while 14% of patients treated in the neoadjuvant phase received induction chemotherapy before the concomitant phase; in both cases of chemotherapy alone, the majority of patients (91%) received oxaliplatin-based protocols (FOLFOX/XELOX/CAPOX). Few patients (3%) received chemotherapy alone after the concomitant phase. Information on the surgical treatment received is available for 88% of the sample. Of these, 93% received a surgical treatment. The overall rate of sphincter-saving surgery (anterior resection) was 72%, but the contribution of neoadjuvant treatment allowed to reach a rate of 83% in this subgroup (against 65% found in the subgroup of patients treated in adjuvant phase). Traditional radiotherapy schedule (45-50 Gy in 25-28 fractions) was used in 90% of patients, of which an intensified treatment in neoadjuvant phase (45 Gy + boost of 9-10 Gy) was used in 11% of patients. A short-course regimen (25 Gy in 5 fraction) in neoadjuvant setting was opted rarely (7%). Three-dimensional conformal technique was preferred over intensity-modulated ones (73% vs 27%). Toxicity was mainly of grade I-II CTCAE (skin 23%, gastrointestinal 39%, genitourinary 14%) compared to grade III (gastrointestinal 4%, genitourinary and hematological < 1%). Interestingly, the toxicity rates were significantly higher in the adjuvant group compared to the neoadjuvant (GI: 58% vs 31%, GU: 21% vs 10%). CONCLUSION: The present survey shows that in the Sicily region integrated therapies for rectal cancer have allowed a neoadjuvant approach in the majority of patients, thus resulting in a greater use of sphincter conservative surgery. The toxicity has also been reported to be significantly less in this treatment setting.

Toxicity profile and Patient-Reported outcomes following salvage Stereotactic Ablative Radiation Therapy to the prostate Bed: The POPART multicentric prospective study.

Background: While SBRT to the prostate has become a valuable option as a radical treatment, limited data support its use in the postoperative setting. Here, we report the updated results of the multicentric Post-Prostatectomy Ablative Radiation Therapy (POPART) trial, investigating possible predictors of toxicities and patient-reported outcomes. Methods: Patients with PSA levels between 0.1-2.0 ng/mL after radical prostatectomy received Linac-based SBRT to the prostate bed in five fractions every other day for a total dose of 32.5 Gy (EQD21.5 = 74.3 Gy). Late toxicity was assessed using CTCAE v.5 scale, while EPIC-CP, ICIQ-SF, IIEF 5 questionnaires and PSA levels measured quality of life and biochemical control. Pre- and post-treatment scores were compared using a paired t-test, with MID established at > 0.5 pooled SD from the baseline. A logistic regression analysis was performed to evaluate potential associations between specific patient/tumor/treatment factors and outcome deterioration. Results: From April 2021 to April 2023 a total of 50 pts were enrolled and treated. Median follow-up was 12.2 (3-27) months. No late ≥ G2 GI or GU toxicity was registered. Late G1 urinary and rectal toxicities occurred in 46 % and 4 % of patients, respectively. Among 47 patients completing all EPIC-CP domains, four (9 %) showed worsened QoL, and eleven (26 %) developed erectile dysfunction correlating with PTV D2% (P = 0.032). At Multivariate analysis bladder wall D10cc independently correlated with late G1 GU toxicity (P = 0.034). Median post-treatment PSA nadir was 0.04 ng/mL (0.00 - 0.84). At the last follow-up, six patients presented with biochemical failure, including two nodal relapses. Conclusions: Our findings show that post-prostatectomy SBRT did not result in increased toxicity nor a significant decline in QoL measures, thus showing that it can be safely extended to the postoperative setting. Long-term follow-up and randomized comparisons with different RT schedules are needed to validate this approach.

Enhancing Radiotherapy Workflow for Head and Neck Cancer with Artificial Intelligence: A Systematic Review.

BACKGROUND: Head and neck cancer (HNC) is characterized by complex-shaped tumors and numerous organs at risk (OARs), inducing challenging radiotherapy (RT) planning, optimization, and delivery. In this review, we provided a thorough description of the applications of artificial intelligence (AI) tools in the HNC RT process. METHODS: The PubMed database was queried, and a total of 168 articles (2016-2022) were screened by a group of experts in radiation oncology. The group selected 62 articles, which were subdivided into three categories, representing the whole RT workflow: (i) target and OAR contouring, (ii) planning, and (iii) delivery. RESULTS: The majority of the selected studies focused on the OARs segmentation process. Overall, the performance of AI models was evaluated using standard metrics, while limited research was found on how the introduction of AI could impact clinical outcomes. Additionally, papers usually lacked information about the confidence level associated with the predictions made by the AI models. CONCLUSIONS: AI represents a promising tool to automate the RT workflow for the complex field of HNC treatment. To ensure that the development of AI technologies in RT is effectively aligned with clinical needs, we suggest conducting future studies within interdisciplinary groups, including clinicians and computer scientists.

The impact of stereotactic ablative radiotherapy on oligoprogressive metastases from renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) represents 80-90% of all kidney tumors and about 15-25% of patients will develop distant metastases. Systemic therapy represents the standard of care for metastatic patients, but stereotactic ablative radiotherapy (SABR) may play a relevant role in the oligoprogressive setting, defined as the progression of few metastases during an ongoing systemic therapy on a background of otherwise stable disease. Aim of the present study was to analyze the outcome of RCC patients treated with SABR on oligoprogressive metastases. MATERIALS AND METHODS: In this monocenter study, we analyzed patients affected by RCC treated with SABR on a maximum of 5 cranial or extracranial oligoprogressive sites of disease. Endpoints were overall survival (OS), progression-free survival (PFS), and toxicity. RESULTS: We included 74 oligoprogressions (26 intracranial and 48 extracranial) and 57 SABR treatments in 44 patients. Most common concomitant treatments were sunitinib (28, 49.1%), pazopanib (12, 21.0%) and nivolumab (11, 19.3%). Median follow-up was 19.0 months, and 1- and 2-year OS rates were 79.2% and 57.3%, respectively. Repeated SABR was a positive predictive factor for OS (p = 0.034). Median PFS was 9.8 months, with 1- and 2-year rates of 43.2% and 25.8%. At multivariable analysis, disease-free interval (p = 0.022) and number of treated metastases (p = 0.007) were significant for PFS. About 80% of patients continued the ongoing systemic therapy 1- and 2-years after SABR with no grade 3 or 4 toxicities. CONCLUSIONS: we confirmed the efficacy and safety of SABR for oligoprogression from RCC, with the potential to ablate resistant metastases and to prolong the ongoing systemic therapy.

Adaptive Volumetric-Modulated Arc Radiation Therapy for Head and Neck Cancer: Evaluation of Benefit on Target Coverage and Sparing of Organs at Risk.

BACKGROUND: Radiotherapy is essential in the management of head-neck cancer. During the course of radiotherapy, patients may develop significant anatomical changes. Re-planning with adaptive radiotherapy may ensure adequate dose coverage and sparing of organs at risk. We investigated the consequences of adaptive radiotherapy on head-neck cancer patients treated with volumetric-modulated arc radiation therapy compared to simulated non-adaptive plans: Materials and methods: We included in this retrospective dosimetric analysis 56 patients treated with adaptive radiotherapy. The primary aim of the study was to analyze the dosimetric differences with and without an adaptive approach for targets and organs at risk, particularly the spinal cord, parotid glands, oral cavity and larynx. The original plan (OPLAN) was compared to the adaptive plan (APLAN) and to a simulated non-adaptive dosimetric plan (DPLAN). RESULTS: The non-adaptive DPLAN, when compared to OPLAN, showed an increased dose to all organs at risk. Spinal cord D2 increased from 27.91 (21.06-31.76) Gy to 31.39 (27.66-38.79) Gy (p = 0.00). V15, V30 and V45 of the DPLAN vs. the OPLAN increased by 20.6% (p = 0.00), 14.78% (p = 0.00) and 15.55% (p = 0.00) for right parotid; and 16.25% (p = 0.00), 18.7% (p = 0.00) and 20.19% (p = 0.00) for left parotid. A difference of 36.95% was observed in the oral cavity V40 (p = 0.00). Dose coverage was significantly reduced for both CTV (97.90% vs. 99.96%; p = 0.00) and PTV (94.70% vs. 98.72%; p = 0.00). The APLAN compared to the OPLAN had similar values for all organs at risk. CONCLUSIONS: The adaptive strategy with re-planning is able to avoid an increase in dose to organs at risk and better target coverage in head-neck cancer patients, with potential benefits in terms of side effects and disease control.

Multimodal Treatments for Brain Metastases from Renal Cell Carcinoma: Results of a Multicentric Retrospective Study.

The aim of this study was to evaluate the clinical outcomes of a large series of brain metastatic renal cell carcinoma (BMRCC) patients treated in three Italian centers. METHODS: A total of 120 BMRCC patients with a total of 176 lesions treated were evaluated. Patients received surgery plus postoperative HSRS, single-fraction SRS, or hypofractionated SRS (HSRS). Local control (LC), brain distant failure (BDF), overall survival (OS), toxicities, and prognostic factors were assessed. RESULTS: The median follow-up time was 77 months (range 16-235 months). Surgery plus HSRS was performed in 23 (19.2%) cases, along with SRS in 82 (68.3%) and HSRS in 15 (12.5%). Seventy-seven (64.2%) patients received systemic therapy. The main total dose and fractionation used were 20-24 Gy in single fraction or 32-30 Gy in 4-5 daily fractions. Median LC time and 6 month and 1, 2 and 3 year LC rates were nr, 100%, 95.7% ± 1.8%, 93.4% ± 2.4%, and 93.4% ± 2.4%. Median BDF time and 6 month and 1, 2 and 3 year BDF rates were n.r., 11.9% ± 3.1%, 25.1% ± 4.5%, 38.7% ± 5.5%, and 44.4% ± 6.3%, respectively. Median OS time and 6 month and 1, 2 and 3 year OS rates were 16 months (95% CI: 12-22), 80% ± 3.6%, 58.3% ± 4.5%, 30.9% ± 4.3%, and 16.9% ± 3.6, respectively. No severe neurological toxicities occurred. Patients with a favorable/intermediate IMDC score, a higher RCC-GPA score, an early occurrence of BMs from primary diagnosis, absence of EC metastases, and a combined local treatment (surgery plus adjuvant HSRS) had a better outcome. CONCLUSIONS: SRS/HSRS is proven to be an effective local treatment for BMRCC. A careful evaluation of prognostic factors is a valid step to manage the optimal therapeutic strategy for BMRCC patients.

Predictive value of clinical and radiomic features for radiation therapy response in patients with lymph node-positive head and neck cancer.

BACKGROUND: Prediction of survival and radiation therapy response is challenging in head and neck cancer with metastatic lymph nodes (LNs). Here we developed novel radiomics- and clinical-based predictive models. METHODS: Volumes of interest of LNs were employed for radiomic features extraction. Radiomic and clinical features were investigated for their predictive value relatively to locoregional failure (LRF), progression-free survival (PFS), and overall survival (OS) and used to build multivariate models. RESULTS: Hundred and six subjects were suitable for final analysis. Univariate analysis identified two radiomic features significantly predictive for LRF, and five radiomic features plus two clinical features significantly predictive for both PFS and OS. The area under the curve of receiver operating characteristic curve combining clinical and radiomic predictors for PFS and OS resulted 0.71 (95%CI: 0.60-0.83) and 0.77 (95%CI: 0.64-0.89). CONCLUSIONS: Radiomic and clinical features resulted to be independent predictive factors, but external independent validation is mandatory to support these findings.

Oligoprogressive castration-resistant prostate cancer treated with metastases-directed stereotactic body radiation therapy: predictive factors for patients' selection.

Oligoprogression is defined as limited metastatic clone resistant to on-going systemic treatment that grows in a background of stable or responding systemic disease. Aim of the present study was to analyze oligoprogressive prostate cancer (PC) patients treated with stereotactic body radiation therapy (SBRT) during systemic treatment to identify predictive factors and improve patients' selection. We included PC patients treated with SBRT on a maximum of 3 sites of oligoprogression during systemic therapy. Endpoints were freedom from polymetastatic progression (FPP), local control (LC), distant progression free survival (DPFS), overall survival (OS), and next systemic therapy free survival (NEST-FS). Fifty-three patients were treated on 85 oligoprogressive metastases. Lymph nodes were the most common sites (56.47%), followed by bone (39.29%). Median follow-up was 24.9 months. Rates of FPP at 1- and 2-year were 80.1% and 68.9%, respectively. Median time to polymetastatic progression was 33.7 months. Disease free interval (p = 0.004), site of metastases (p = 0.011), and type of systemic therapy (p = 0.003) were significant for FPP. Switch or intensification of systemic therapy after SBRT was observed in 29 (54.72%) patients with a median NEST-FS of 15.2 months. LC at 1- and 2-year was 94.0% and 92.0%, with PSA doubling time resulted to be significantly associated (p = 0.047). Median DPFS was 8.93 months and median OS was 50.6 months. In conclusion, we confirmed the efficacy of SBRT for oligoprogression from PC, with the potential to prolong the on-going systemic therapy and interrupt the metastatic cascade.

Stereotactic Radiotherapy after Incomplete Transarterial (Chemo-) Embolization (TAE\TACE) versus Exclusive TAE or TACE for Treatment of Inoperable HCC: A Phase III Trial (NCT02323360).

Background: Hepatocellular carcinoma (HCC) is the most frequent liver malignancy and a leading cause of cancer death in the world. In unresectable HCC patients, transcatheter arterial (chemo-) embolization (TAE/TACE) has shown a disease response in 15-55% of cases. Though multiple TAE/TACE courses can be administered in principle, Stereotactic Body Radiotherapy (SBRT) has emerged as an alternative option in the case of local relapse following multiple TAE/TACE courses. Methods: This is a single-center, prospective, randomized, controlled, parallel-group superiority trial of SBRT versus standard TAE/TACE for the curative treatment of the intermediate stage of HCC after an incomplete response following TAE/TACE (NCT02323360). The primary endpoint is 1-year local control (LC): 18 events were needed to assess a 45% difference (HR: 0.18) in favor of SBRT. The secondary endpoints are 1-year Progression-Free Survival (PFS), Distant Recurrence-Free Survival (DRFS), Overall Survival (OS) and the incidence of acute and late complications. Results: At the time of the final analysis, 40 patients were enrolled, 19 (49%) in the TAE/TACE arm and 21 (51%) in the SBRT arm. The trial was prematurely closed due to slow accrual. The 1- and 2-year LC rates were 57% and 36%. The use of SBRT resulted in superior LC as compared to TAE/TACE rechallenge (median not reached versus 8 months, p = 0.0002). PFS was 29% and 16% at 1 and 2 years, respectively. OS was 86% and 62% at 1 year and 2 years, respectively. In the TAE arm, PFS was 13% and 6% at 1 and 2 years, respectively. In the SBRT arm, at 1 and 2 years, PFS was 37% and 21%, respectively. OS at 1 and 2 years was 75% and 64% in the SBRT arm and 95% and 57% in the TACE arm, respectively. No grade >3 toxicity was recorded. Conclusions: SBRT is an effective treatment option in patients affected by inoperable HCC experiencing an incomplete response following ≥1 cycle of TAE/TAC.

Charlson comorbidity index and G8 in older old adult(≥80 years) hepatocellular carcinoma patients treated with stereotactic body radiotherapy.

INTRODUCTION: Hepatocellular Carcinoma (HCC) is characterized, in Western countries, by higher incidence and mortality rates in the older adult population. In frail patients, limited therapeutic resources are available due to limited expected benefit concerning the risk of treatment-related toxicity. The aim of our study is to evaluate the role of Stereotactic Body Radiotherapy (SBRT) in the clinical management of older old adults (age ≥ 80 years) HCC patients and to identify predictors of efficacy and toxicity. MATERIAL AND METHODS: Clinical and treatment-related data of older old adults HCC patients treated with SBRT at our institution were retrospectively reviewed. Statistical analysis was carried out to identify variables correlated with impaired outcome and toxicity. RESULTS: Forty-two patients were included, accounting for 63 treated tumors. Median age was 85 (range 80-91) years. Median Charlson Comorbidity Index (CCI) and G8 scores were 10 (range 7-16) and 11 (range 8-14), respectively. SBRT was administered to a median BED10 of 103 Gy10. Median follow-up interval was 11 (range 3-40) months. Two years Local Control (LC), Progression-Free Survival (PFS), and Overall Survival (OS) were 93%, 31%, and 43%, respectively. Acute toxicity occurred in 28% (n = 13) of treatments. A G8 score > 10 was associated with improved survival (p = 0.045), while a CCI ≥10 was correlated with increased acute toxicity (p = 0.021). CONCLUSIONS: SBRT is a safe and effective option in older old adults HCC patients. A comprehensive geriatric assessment (CGA) is advised before treatment decisions to select optimal candidates for SBRT.

Stereotactic body radiotherapy in hepatocellular carcinoma: patient selection and predictors of outcome and toxicity.

INTRODUCTION: Stereotactic Body Radiotherapy (SBRT) emerged as a valuable option in early to advanced-stage Hepatocellular Carcinoma (HCC) as defined by Barcelona Clinic Liver Cancer (BCLC) system. The aim of our study is to evaluate SBRT in HCC patients and to identify predictors of outcome and toxicity. MATERIALS AND METHODS: A retrospective review of HCC patients treated at our Institution between November 2011 and December 2018 was carried out. SBRT was delivered in 3-10 fractions to a median Biologically Effective Dose (BED10) of 103 Gy10. RESULTS: SBRT was performed in 128 patients to 217 HCC localizations, accounting for 142 treatment courses. BCLC stage was A, B, C in, respectively, 40 (31%), 72 (56%) and 16 (13%) patients. Local Control (LC), Progression Free Survival (PFS) and Overall Survival (OS) at 2 years were, respectively: 78%, 15% and 58%. LC was influenced by BED10 > 120 Gy10 (Hazard Ratio, HR: 0.08, 95% CI 0.01-0.59; p = 0.013) and size ≥ 3 cm (HR: 2.71, 95% CI 1.10-6.66; p = 0.03). BCLC stage was correlated to PFS (median 14 vs 12 vs 5 months, p = 0.012). In BCLC stage A-B disease (n = 112), LC was associated with improved survival (median 30 months vs not reached, p = 0.036). Acute and late toxicity rate was 26% (n = 37) and 8% (n = 11). Patients with BCLC B-C stage disease showed increased acute toxicity (HR: 2.9, 95% CI 1.10-7.65; p = 0.032). CONCLUSION: Delivery of ablative doses > 120 Gy10 and tumor size are determinants of LC. Prolonged PFS and improved OS can be obtained in BCLC A-B patients. Grade 3 liver dysfunction is infrequent.

Assessing the role of Stereotactic Body Radiation Therapy in a large cohort of patients with lymph node oligometastases: Does it affect systemic treatment's intensification?

BACKGROUND AND PURPOSE: Lymph nodes (LN) are common site of oligometastases and stereotactic body radiation therapy (SBRT) represents an effective ablative treatment. Aim of this study was to analyze a large cohort of nodal oligometastases treated with SBRT to identify impact on systemic therapy intensification, pattern of recurrence, and predictive factors. MATERIALS AND METHODS: We included patients with a maximum of 5 oligometastases. Concomitant treatments were allowed. Patients were treated with Volumetric Modulated Arc Therapy (VMAT) and end points were local control of treated metastases (LC), locoregional nodal control (LRNC), distant nodal control (DNC), distant metastases free survival (DMFS), overall survival (OS) and freedom from treatment intensification (FFTI). RESULTS: 418 LN were treated in 278 patients with 327 SBRT treatments. Patients were more commonly affected by colorectal (20.9%) and prostate cancer (17.99%). Most represented schedule was 45 Gy in 6 fractions, with a median BED10 of 78.75 Gy. After median follow-up of 15.1 months, LC at 1 and 2 years were 87.2% and 76.8%, respectively. Prostate primary tumor, small volume, oligorecurrence, and BED10 ≥75 Gy were associated with higher LC. One and 2 years FFTI were 82.8% and 74.5%; in patients reporting intensification of systemic therapy, median time was 8.43 months, while for patients who repeated SBRT, median FFTI was 14.6 months. Rates of LRNC at 1 and 2 years were 70.9% and 57.6%, and DNC were 82.0% and 77.9%. CONCLUSION: With the present analysis, we confirmed on a large cohort the benefit from SBRT on lymph node oligometastases in multidisciplinary management. Combination of SBRT with new systemic therapies, including immunotherapy and targeted therapy, should be investigated to reduce the risk of progression out of the field of irradiation.

Phase II trial of high dose stereotactic body radiation therapy for lymph node oligometastases.

Lymph nodes are common sites of oligometastases for several primaries. Stereotactic body radiation therapy (SBRT) represents an effective treatment but no consensus exists regarding dose and fractionation. Aim of this trial was to evaluate safety and efficacy of high-dose SBRT. We included patients with 1 to 3 lymph node metastases. Primary end-point was safety, while secondary end-points were in-field local control (LC), out-field lymph nodal progression free survival (LPFS), distant metastasis free survival (DMFS), progression free survival (PFS) and overall survival (OS). 64 lesions in 52 patients were treated from 2015 to 2019. Most common primary tumor was genitourinary cancer (75%), in particular prostate cancer (65.4%). With a median follow-up of 24.4 months (range 3-49), treatment was very well tolerated, with only 4 (7.7%) patients reporting acute side effects, all classified as grade 1, in the form of pain, fatigue, nocturia and dysuria. No toxicity ≥ grade 2 were reported. Rates of LC at 1, 2 and 3 years were 97.9%, 82.1% and 82.1%. Male sex (HR 0.12, p value 0.014) was associated with improved LC. LPFS at 1, 2 and 3 years were 69.6%, 49.6% and 46.1%, respectively, and DMFS was 81.74%, 67.5% and 58.5%, respectively. Presence of lesions in other organs was correlated with inferior DMFS (HR 3.82, p = 0.042). PFS at 1, 2 and 3 years were 67.4%, 42.4% and 31.86%, respectively. OS at 1, 2 and 3 years were 97.3%, 94.2%, 84%, respectively and significantly correlated with in-field recurrence (HR 8.72, p = 0.000). Our prospective trial confirms safety and efficacy of SBRT in the management of lymph node metastases. Registered Clinical trial NCT02570399.