Stereotactic body radiotherapy (SIB-VMAT technique) to dominant intraprostatic lesion (DIL) for localized prostate cancer: a dose-escalation trial (DESTROY-4).

PURPOSE: DESTROY-4 (DOSE-ESCALATION STUDY OF STEREOTACTIC BODY RADIATION THERAPY) was a Phase I trial aimed to evaluate the safety and the feasibility of escalating doses of stereotactic body radiation therapy (SBRT) on MRI-defined Dominant Intraprostatic Lesion (DIL) in low- and intermediate-risk pCa patients using a simultaneous integrated boost-volumetric arc therapy (SIB-VMAT) technique. METHODS: Eligible patients included those with low- and intermediate-risk prostate carcinoma (NCCN risk classes) and an International Prostatic Symptoms Score (IPSS) ≤ 15. No restriction about DIL and prostate volumes was set. Pretreatment preparation required an enema and the placement of intraprostatic gold fiducials. SBRT was delivered in five consecutive daily fractions. For the first three patients, the DIL radiation dose was set at 8 Gy per fraction up to a total dose of 40 Gy (PTV1) and was gradually increased in succeeding cohorts to total doses of 42.5 Gy, 45.0 Gy, 47.5 Gy, and finally, 50.0 Gy, while keeping the prescription of 35 Gy/7 Gy per fraction for the entire prostate gland. Dose-limiting toxicity (DLT) was defined as grade 3 or worse gastrointestinal (GI) or genitourinary (GU) toxicity occurring within 90 days of follow-up (Common Terminology Criteria of Adverse Events scale 4.0). Patients completed quality-of-life questionnaires at defined intervals. RESULTS: Twenty-four patients with a median age of 75 (range, 58-89) years were enrolled. The median follow-up was 26.3 months (8.9-84 months). 66.7% of patients were classified as intermediate-risk groups, while the others were low-risk groups, according to the NCCN guidelines. Enrolled patients were treated as follows: 8 patients (40 Gy), 5 patients (42.5 Gy), 4 patients (45 Gy), 4 patients (47.5 Gy), and 3 patients (50 Gy). No severe acute toxicities were observed. G1 and G2 acute GU toxicities occurred in 4 (16%) and 3 patients (12.5%), respectively. Two patients (8.3%) and 3 patients (12.5%) experienced G1 and G2 GI toxicities, respectively. Since no DLTs were observed, 50 Gy in five fractions was considered the MTD. The median nadir PSA was 0.20 ng/mL. A slight improvement in QoL values was registered after the treatment. CONCLUSION: This trial confirms the feasibility and safety of a total SIB-VMAT dose of 35 Gy on the whole gland and 50 Gy on DIL in 5 fractions daily administered in a well-selected low- and intermediate-risk prostate carcinoma population. A phase II study is ongoing to confirm the tolerability of the schedule and assess the efficacy.

Role of Chemoradiation in the Adjuvant Treatment of Radically Resected Pancreatic Cancer Patients: A Mono-Institutional Retrospective Analysis.

INTRODUCTION: Pancreatic cancer (PC) represents an unfavorable prognosis condition, even in patients with resectable disease. The aim of this series was to investigate the role of treatment intensification with adjuvant chemoradiation (CRT) in radically resected PC patients. METHODS: Data from PC patients who underwent radical surgery, adjuvant chemotherapy (CT), and CRT throughout a 20-year period were retrospectively collected. Actuarial local control (LC) and the overall survival (OS) were the primary endpoints, with disease-free survival and metastasis-free survival (MFS) representing secondary endpoints. RESULTS: The analysis included 108 PC patients treated with adjuvant CRT and CT from January 2000 to August 2019. Median age was 66 years (range: 40-83), and all patients underwent radical surgical resection with adjuvant CT (88, 81.5%) plus concomitant CRT (101, 93.5%) or radiotherapy alone (7, 6.5%). The median dose delivered to the tumor bed was 50.4 Gy (range: 45-50.6 Gy), while median dose to regional lymphatic drainage stations was 39.6 Gy (range 39.6-45 Gy). Concomitant CT was a gemcitabine-based regimen in the vast majority of patients (87, 80.6%). Median follow-up time was 21 months; the 2- and 5-year LC rates were 75.8% and 59.1%, respectively. Perineural invasion at pathological assessment was found significantly associated with LC (p = 0.028). Median OS was 40 months with 2- and 5-year OS rates of 73.9% and 41.6%, respectively. CONCLUSIONS: The outcomes of this series suggest to investigate the possible impact of adding adjuvant CRT to CT in PC patients. Timing and combination of modern CRT with new systemic therapies need to be further investigated to personalize therapy and optimize clinical advantages.

Skin toxicity following radiotherapy in patients with breast carcinoma: is anthocyanin supplementation beneficial?

BACKGROUND: The EU-supported ATHENA project stems from a previous study suggesting that moderate wine consumption reduced the side-effects of radiotherapy (RT) in breast cancer patients, an effect possibly due to non-alcoholic anthocyanin fractions of wine. OBJECTIVE: To evaluate the role of anthocyanins on RT skin side effects in breast cancer patients. METHODS: Randomized, controlled, double-blind clinical trial. Patients were assigned to an intensity modulated radiation therapy (IMRT) either for three or five weeks, then randomized to receive three times a day a water-soluble anthocyanin (125 mg)-rich extract of corn cob or a placebo. Supplementation started one week before till the end of RT. Skin characteristics were detected by a standardized, non-invasive Cutometer® dual-MPA580, providing quantitative indices of skin maximal distensibility (R0), elasticity (R2, R5, R7) and viscoelasticity (R6); a Mexameter® MX18 probe evaluated the skin erythema (Er) and melanin (M). Measures were performed before (T0), at the end of RT and of supplementation (T1), and 1, 6 and 12 months after RT (T2-T4). Acute and late skin toxicity were scored according to the RTOG/EORTG scale. Selected biomarkers were measured at T0 and T1. RESULTS: 193 patients previously assigned to 3- or 5-week RT schedules were randomized to either anthocyanin (97) or placebo (96) supplementation. RT induced changes in skin parameters: R0, R2, R5 and R7 decreased, while R6 increased; the changes in R0 and R6 continued in the same direction up to one year, while the others recovered towards basal values; Er and M peaked at T1 and T2, respectively, and returned to basal values at T4. Comparable skin changes were apparent in anthocyanin and placebo groups. A moderate RT-induced increase in total and HDL cholesterol and triglycerides was prevented by anthocyanins. CONCLUSIONS: Anthocyanin supplementation did not prevent RT-induced local skin toxicity. The supplementation was well tolerated and safe.

Importance of the correct assessment of bone fractures in the clinical management of metastatic castration-resistant prostate cancer treated with radium-223: A case report.

Patients who undergo radium-223 treatment for metastatic castration-resistant prostate cancer (mCRPC) generally have a long history of androgen deprivation therapy and/or steroid therapy, which leads to bone loss and causes osteoporosis. Notably, Osteoporosis in combination with metastatic bone disease increases the risk of bone fracture. An 84-year-old man with multi-metastatic bone CRPC underwent six administrations of intravenous radium-223, which induced a good biochemical and clinical response. However, two months following the treatment, the patient reported acute pain localized to the lumbar spine mimicking bone progression disease and presented with stable prostate-specific antigen levels. A prostate-specific membrane antigen-positron emission tomography scan showed no tracer uptake in that site, whereas a magnetic resonance imaging scan and subsequent vertebral biopsy confirmed the absence of cancer progression and showed the presence of vertebral crushing of L4-L5, which was probably due to an osteoporotic process. The patient had never received bisphosphonate therapy and refused it during α-emitting therapy with radium-223. The osteoporotic process, in association with metastatic bone disease, more easily leads to bone fractures that have an important impact on performance status, quality of life and prognosis quoad vitam in patients with advanced prostate cancer. Use of bisphosphonates or anti-RANKL antibody appears to be effective in improving bone mineral density. Notably, patients with multi-metastatic bone disease who undergo radium-223 therapy should be treated in conjunction with anti-osteoporotic therapy (bisphosphonates or anti-RANKL antibody) and adequate calcium and vitamin D supplementation. Early recognition and differentiation of osteoporotic processes when determining the progression of cancer-associated bone disease is crucial in evaluating the response to radium-223 therapy and, consequently, for further therapeutic decision making.

Preoperative chemoradiation and intra-operative radiotherapy for pancreatic carcinoma.

AIMS AND BACKGROUND: In recent years, preoperative chemoradiation has received growing interest for the treatment of locally advanced pancreatic cancer. In an attempt to improve resectability and disease control, we used preoperative radiation therapy and concomitant 5-fluorouracil in a combined modality therapy protocol. The aim of the study was to evaluate definitive results in terms of toxicity, response and clinical outcome. MATERIAL AND METHODS: Twenty-eight patients with unresectable (cT4, 19 patients) or resectable (cT3, 9 patients) nonmetastatic pancreatic tumors received radiotherapy (39.6 Gy) plus 5-fluorouracil (continuous infusion, days 1-4 at 1000 mg/m(2)/day). After 4 weeks, patients were evaluated for surgical resection. In 9 resected patients, electron-beam intra-operative radiotherapy (10 Gy) was given before reconstruction. Thereafter, in resected patients, adjuvant chemotherapy was prescribed. RESULTS: During chemoradiation, 1 patient (3.6%) developed grade 3 acute gastrointestinal toxicity and 2 patients (7.1%) developed grade 3 hematological toxicity. Three of 19 patients with unresectable tumors had tumor downstaging (15.8%). Two patients showed partial response (response rate, 7.1%; 95% CI, 0.2-25.3) and 4 patients (14.3%) had minimal tumor response. Four patients (14.3%) showed progressive disease after chemoradiation. One postoperative death was recorded. The median survival time was 11.3 months (20.5 and 9.0 months in resected and unresected patients, respectively). Only one local failure was recorded in 8 patients resected with negative margins. CONCLUSIONS: Although the response rate is still low, our preliminary results suggest that preoperative 5-fluorouracil chemoradiation is well tolerated and may result in tumor downstaging. Delivery of intra-operative radiotherapy seems to be associated with a low rate of local recurrences.