Study protocol and preliminary results from a mono-centric cohort within a trial testing stereotactic body radiotherapy and abiraterone (ARTO-NCT03449719).

BACKGROUND: ARTO trial was designed to evaluate the difference in terms of outcomes between patients affected by oligo metastatic castrate resistant prostate cancer (mCRPC) treated with Abiraterone acetate and randomized to receive or not SBRT on all sites of disease. Here, we present a preliminary analysis conducted on patients enrolled at promoting institution. OBJECTIVE: To present a preliminary overview about population features, clinical outcomes, adverse events, quality of life and explorative translational research. DESIGN, SETTING, AND PARTICIPANTS: ARTO (NCT03449719) is a phase II trial including patients affected by oligo mCRPC, randomized to receive standard of care (GnRH agonist or antagonist plus abiraterone acetate 1000 mg and oral prednisone 10 mg daily) with or without SBRT on all metastatic sites of disease. All subjects have < 3 bone or nodal metastases. All patients are treated in I line mCRPC setting, no previous lines of treatment for mCRPC are allowed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data about a mono-centric cohort of 42 patients enrolled are presented in the current analysis, with focus on baseline population features, PSA drop at 3 months, biochemical response, and quality of life outcomes. Descriptive statistics regarding translational research are also presented. RESULTS AND LIMITATION: Significant difference in terms of PSA drop at three months was not detected (p = 0.68). Biochemical response (PSA reduction > 50%) was reported in 73.7 versus 76.5% of patients in control vs SBRT arm, respectively (p = 0.84). All patients are alive. Progression occurred in 1 versus 0 patients in the control versus SBRT arm, respectively. After 3 months, an average decrease of 13 points in terms of Global Health Score was reported for the overall population. However, complete recovery was noticed at 6 months. Circulating tumor cells detection rate was 40%. CONCLUSIONS: SBRT + Abiraterone treatment was safe and well tolerated, non-significant trend in terms of PSA drop and biochemical response at 3 months was detected in SBRT arm. Interestingly, CTCs detection in this selected cohort of oligo-mCRPC was lower if compared to historical data of unselected mCRPC patients.

Durvalumab with cetuximab and radiotherapy for locally advanced squamous cell carcinoma of the head and neck: A phase 1/2 trial.

BACKGROUND AND PURPOSE: To report on the anti-tumor activity of a novel combination in high-risk locally advanced head and neck squamous cell carcinoma. MATERIALS AND METHODS: At a fixed dose of 1500 mg every 28 days, anti PD-L1 Durvalumab was given concomitantly to Radiotherapy and Cetuximab starting from the first week of combined treatment, followed by adjuvant Durvalumab to a maximum of 6 months after completion of radiation. The primary endpoint of the study was 2-year progression-free survival (PFS). A safety run-in was planned. Due to regulatory issues which prevented from opening multiple centers, COVID-19 pandemic and withdrawal of Durvalumab from supporting company, the study was prematurely terminated in April 2021. RESULTS: Between July 2019 and August 2020, 9 patients were enrolled in the study. All tumors had a PD-L1 Combined Positive Score > 1. Optimal drug exposure was observed, with mean relative dose intensity of 85.5% and 87.5% for Cetuximab and Durvalumab, respectively. No radiation breaks were necessary. A grade 4 mucositis lasting for 14 days corresponded to the only dose limiting toxicity we reported. At a median follow-up of 11.5 months (IQR 7.7-16.7) all surviving patients (6 out of 9) are disease-free, with 1 and 2-year PFS rates of 77.7% and 58.3%, respectively. A selective sparing of node levels in the elective volume was performed in all cases, yielding a cumulative mean dose of 37.6 Gy (SD 8.4). CONCLUSION: Albeit limited by the small sample size, our preliminary observation of anti-tumor activity and tolerability of Durvalumab in addition to Cetuximab and radiation may warrant further investigations.

Acupuncture for radiation-induced toxicity in head and neck squamous cell carcinoma: a systematic review based on PICO criteria.

PURPOSE: In head and neck squamous cell carcinoma (HNSCC), the potential mitigating effect of complementary medicine interventions such as acupuncture for radiation-induced toxicity is unknown. This study aimed to assess the impact of acupuncture on the incidence and degree of severity of common radiation-induced side effects. METHODS: In accordance with pre-specified PICO criteria, a systematic review was performed. Two electronic databases (Medline and Embase) were searched over a 10-year time frame (01/01/10 to 30/09/20). Patients undergoing a curatively intended, radiation-based treatment for histologically confirmed squamous cell carcinoma of the nasopharynx, oropharynx, larynx, hypopharynx and oral cavity represented the target population of our study. Accurate information on the acupuncture methodology was reported. All included articles were evaluated to identify any potential source of bias RESULTS: Five papers were included in our qualitative analysis, for a total of 633 subjects. Compliance to per-protocol defined schedule of acupuncture sessions was high, ranging from 82 to 95.9%. Most patients (70.6%) were randomly allocated to receive acupuncture for its potential preventive effect on xerostomia. The large heterogeneity in study settings and clinical outcomes prevented from performing a cumulative quantitative analysis, thus no definitive recommendations can be provided. CONCLUSIONS: Although shown to be feasible and safe, no firm evidence currently supports the use of acupuncture for the routine management of radiation-induced toxicity in HNSCC.

Radiotherapy in prostate cancer after kidney transplant in 6 cases.

BACKGROUND: Patients who received a kidney transplant (KT) are described in literature as a group with a higher incidence of malignant neoplasms compared to the general population. Cancer development after KT has become a major issue, as a remarkable percentage of patients are diagnosed with cancer. Treatment of prostate cancer (PCa) in renal transplant recipients (RTRs) is a challenging issue that has been discussed by many authors over the years, but evidence is sparse and often includes conflicting reports. Among the therapeutic options for PCa in these patients, prostate irradiation represents a valuable alternative to surgery or other systemic therapies, as RTRs are often ineligible for these treatments. OBJECTIVE: To report six cases treated at our institution between 1998 and 2017 and discuss the available literature. METHODS: Patients' characteristics were reported along with biochemical status at diagnosis, type of immunosuppressive treatment, radiation therapy technique, and dose to transplanted kidney. RESULTS: Overall, prostate irradiation was delivered respecting the dose constraints and patients showed good tolerance with no reports of acute or late transplanted kidney injury. CONCLUSIONS: Our experience confirms that prostate radiotherapy for RTRs is feasible and effective and represents a valid option that should be considered by the multidisciplinary team.

Pre-pectoral breast reconstruction: early and long-term safety evaluation of 146 unselected cases of the early pre-pectoral era of a single-institution, including cases with previous breast irradiation and post-mastectomy radiation therapy.

We re-evaluated acute and early-late toxicity-related factors among pre-pectoral immediate tissue expander/implant (TE/I) breast reconstruction (BR) unselected, first-era, cases, including previous breast radiation treatment and post-mastectomy radiation therapy (PMRT). A retrospective analysis of 146 (117 therapeutic and 29 prophylactic) pre-pectoral reconstructions, between 2012 and 2016, considered patient-related (age, body mass index [BMI], smoke-history, comorbidity, BRCA mutation), and treatment-related characteristics (previous irradiation, axillary surgery, PMRT, pre- and postoperative chemotherapy, endocrine therapy, and target-therapy). Safety was evaluated as acute and early-late complications, and TE/I failures. At multivariate analysis of the 146 cases (117 patients submitted to BR) a significant factor related to acute toxicity was: BMI ≥ 25 (31.3% [≥ 25] vs 8.8% [< 25]; OR 4.44, 95% CI 1.56-12.6; p = 0.003), while previous breast surgery on ipsilateral side presented a borderline significance (31.6% [previous surgery] vs 7.4% [no previous surgery]; OR 3.74, 95% CI 0.97-14.40; p = 0.055). Factors significantly related to TE/I failure were: current or previous smoking exposition (13.8% [smokers] vs 2.6% [non-smokers]; OR 7.32, 95% CI 1.37-39.08; p = 0.02) and preoperative chemotherapy (18.8% [yes] vs 3.5% [no]; OR 8.16, 95% CI 1.29-51.63; p = 0.026). At 4-year median follow-up, 3 deaths, 5 locoregional recurrences, and 14 distant metastases occurred. Immediate pre-pectoral BR is safe and effective, with low rates of acute and early-late complications. BMI and previous breast surgery were related to higher complications but not failure; smoking and preoperative chemotherapy were related to TE/I explant. Previous RT and PMRT were related neither to early-late toxicity nor failure.

Dose-escalated pelvic radiotherapy for prostate cancer in definitive or postoperative setting.

PURPOSE: Given the absence of standardized planning approach for clinically node-positive (cN1) prostate cancer (PCa), we collected data about the use of prophylactic pelvic irradiation and nodal boost. The aim of the present series is to retrospectively assess clinical outcomes after this approach to compare different multimodal treatment strategies in this scenario. METHODS: Data from clinical records of patients affected by cN1 PCa and treated in six different Italian institutes with prophylactic pelvic irradiation and boost on pathologic pelvic lymph nodes detected with CT, MRI or choline PET/CT were retrospectively reviewed and collected. Clinical outcomes in terms of overall survival (OS) and biochemical relapse-free survival (b-RFS) were explored. The correlation between outcomes and baseline features (International Society of Urological Pathology-ISUP pattern, total dose to positive pelvic nodes ≤ / > 60 Gy, sequential or simultaneous integrated boost (SIB) administration and definitive vs postoperative treatment) was explored. RESULTS: ISUP pattern < 2 was a significant predictor of improved b-RFS (HR = 0.3, 95% CI 0.1220-0.7647, P = 0.0113), while total dose < 60 Gy to positive pelvic nodes was associated with worse b-RFS (HR = 3.59, 95% CI 1.3245-9.741, P = 0.01). Conversely, treatment setting (postoperative vs definitive) and treatment delivery technique (SIB vs sequential boost) were not associated with significant differences in terms of b-RFS (HR = 0.85, 95% CI 0.338-2.169, P = 0.743, and HR = 2.39, 95% CI 0.93-6.111, P = 0.067, respectively). CONCLUSION: Results from the current analysis are in keeping with data from literature showing that pelvic irradiation and boost on positive nodes are effective approaches. Upfront surgical approach was not associated with better clinical outcomes.

Stereotactic Body Radiotherapy in Oligomestatic/Oligoprogressive Sarcoma: Safety and Effectiveness Beyond Intrinsic Radiosensitivity.

BACKGROUND: Metastatic soft tissue sarcoma (STS) patients may benefit from local ablative treatments due to modest efficacy of systemic chemotherapy. However, use of stereotactic body radiotherapy (SBRT) is controversial because of presumed radioresistance of STS. METHODS: Patients treated with SBRT for oligometastatic and oligoprogressive metastatic STS were retrospectively reviewed to assess results in terms of local control (LC), disease-free survival (DFS), and overall survival (OS). Incidence and grade of adverse events were reported. Statistical analysis was performed to identify variables correlated with outcome and toxicity. RESULTS: Forty patients were treated with SBRT to a median biologic effective dose (BED) of 105 (66-305) Gy5 to 77 metastases. Two-year LC, DFS, and OS were 67%, 23%, and 40%. Improved LC was shown in patients receiving a BED >150 Gy5 (hazard ratio [HR], 3.9; 95% confidence interval [CI], 1.6-9.7; P = 0.028). A delay >24 months between primary tumor diagnosis and onset of metastases was associated with improved DFS (HR, 0.46; 95% CI, 0.22-0.96; P = 0.01) and OS (HR, 0.48; 95% CI, 0.23-0.99; P = 0.03). No toxicity grade ≥3 was observed. CONCLUSIONS: Stereotactic body radiotherapy is effective in metastatic STS with a benign toxicity profile. A BED >150 Gy5 is required to maximize tumor control rates. Metastatic relapse >24 months after diagnosis is correlated to improved survival.

Impact of COVID-19 on workload burden of a complex radiotherapy facility.

BACKGROUND AND PURPOSE: COVID-19 constitutes a worldwide threat, prompting Italian Government to implement specific measures on March 8, 2020, to protect patients and health workers from disease transmission. The impact of preventive measures on daily activity of a radiotherapy facility may hamper the ability to fulfill normal workload burden. Thus, we assessed the number of delivered treatments in a specific observation period after the adoption of preventive measures (since March 11 to April 24, 2020) and compared it with the corresponding period of the year 2019. MATERIALS AND METHODS: Overall number of delivered fractions was related to actual time of platform daily activity and reported as a ratio between number of delivered fractions and activity hours (Fr/Hrs). Fr/Hrs were calculated and compared for two different periods of time, March 11-April 24, 2019 (Fr/Hrs1), and March 11-April 24, 2020 (Fr/Hrs2). RESULTS: Fr/Hrs1 and Fr/Hrs2 were 2.66 and 2.54 for year 2019 and 2020, respectively, for a Fr/Hrsratio of 1.07 (95% CI 1.03-1.12, p = 0.0005). Fr/Hrs1 was significantly higher than Fr/Hrs2 for SliR and PreciseR, with Fr/Hrsratio of 1.92 (95% CI 1.66-2.23, p < 0.0001) and 1.11 (95% CI 1.03-1.2, p = 0.003), respectively. No significant difference was reported for SynergyR and CyberknifeR with Fr/Hrsratio of 0.99 (95% CI 0.91-1.08, p = 0.8) and 0.9 (95% CI 0.77-1.06, p = 0.2), respectively. Fr/Hrs1 was significantly lower than Fr/Hrs2 for TomotherapyR, with Fr/Hrsratio of 0.88 (95% CI 0.8-0.96, p = 0.007). CONCLUSION: Preventive measures did not influence workload burden performed. Automation in treatment delivery seems to compensate effectively for health workers number reduction.

Thermal Ablation versus SBRT in liver tumours: pros and cons.

Non-surgical locally ablative treatments for primary liver cancer and liver metastases represent an effective therapeutic choice when surgery cannot be performed or is not indicated. Thermal ablative employing electric currents or electromagnetic fields have historically played an important role in this setting. Radiotherapy, in the last decades, due to a series of important technological development, has become an attractive option for the treatment of liver tumours, especially with the introduction of Stereotactic Body Radiotherapy. Published literature so far evidenced both for radiotherapy and thermal ablative techniques a benefit in terms of local control and other oncological outcomes; however, no direct prospective comparison between the two techniques have been published so far. The aim of this review is to summarize the technical and clinical implications of these treatment modalities and to identify criteria to allocate patients to one or another option in consideration of the expected efficacy. The main features and critical aspects of both thermoablative techniques and external beam radiation will also be covered in the present paper.

Artificial Intelligence in radiotherapy: state of the art and future directions.

Recent advances in computing capability allowed the development of sophisticated predictive models to assess complex relationships within observational data, described as Artificial Intelligence. Medicine is one of the several fields of application and Radiation oncology could benefit from these approaches, particularly in patients' medical records, imaging, baseline pathology, planning or instrumental data. Artificial Intelligence systems could simplify many steps of the complex workflow of radiotherapy such as segmentation, planning or delivery. However, Artificial Intelligence could be considered as a "black box" in which human operator may only understand input and output predictions and its application to the clinical practice remains a challenge. The low transparency of the overall system is questionable from manifold points of view (ethical included). Given the complexity of this issue, we collected the basic definitions to help the clinician to understand current literature, and overviewed experiences regarding implementation of AI within radiotherapy clinical workflow, aiming to describe this field from the clinician perspective.

Outcome and prognostic factors for older patients undergoing radiosurgery for brain metastases.

PURPOSE: Older patients with brain metastases (BM) are often excluded from clinical trials. The aim of our study was to investigate the outcomes following Gamma Knife radiosurgery (GKRS) in young old (65-74 years) and very old (≥75 years) patients with BM. METHODS: Between October 2012 and October 2018, we treated 89 patients aged ≥65 years with GKRS. Patients were divided in two group: young old (YO) and very old (VO) patients. At baseline G8, Graded Prognostic Assessment (DS-GPA) and Basic Score for Brain Metastases (BSBM) were assessed for all patients. Survival analysis was estimated using the Kaplan-Meier (KM) method. Cox regression model was used to investigate the influence of significant factors on KM. RESULTS: Median age at the time of GKRS was 72.2 years (range 65-87). A mean of 2.52 lesions were treated per patient (range 1-14). Median overall survival (OS) for YO and VO patients was 14.2 and 15.7 months, respectively. At univariate analysis, there were no significant differences in OS between the two age groups. A high BSBM (p ≤ .0001) and a high DS-GPA score (p = .0069) were associated with longer survival. A low DS-GPA score was the most powerful independent factor for predicting short survival (HR 1.76, 95% CI 1.25-2.46, p = .001) at multivariate analysis. CONCLUSION: GKRS is a safe approach to treat BM in elderly patients. DS-GPA score represents an important prognostic factor for survival in elderly patients undergoing GKRS.