G. Siepe

Volumetric modulated arc therapy for treatment of solid tumors: current insights

Aim This article discusses the current use of volumetric modulated arc therapy (VMAT) techniques in clinical practice and reviews the available data from clinical outcome studies in different clinical settings. An overview of available literature about clinical outcomes with VMAT stereotactic/radiosurgical treatment is also reported. Materials and methods All published manuscripts reporting the use of VMAT in a clinical setting from 2009 to November 2016 were identified. The search was carried out in December 2016 using the National Library of Medicine (PubMed/Medline). The following words were searched: “volumetric arc therapy”[All Fields] OR “vmat”[All Fields] OR “rapidarc”[All Fields], AND “radiotherapy”[All Fields] AND “Clinical Trial”[All Fields]. Results Overall, 37 studies (21 prospective and 16 retrospective) fulfilling inclusion criteria and thus included in the review evaluated 2,029 patients treated with VMAT; of these patients, ~30.8% had genitourinary (GU) tumors (81% prostate, 19% endometrial), 26.2% head-and-neck cancer (H&NC), 13.9% oligometastases, 11.2% had anorectal cancer, 10.6% thoracic neoplasms (81% breast, 19% lung), and 7.0% brain metastases (BMs). Six different clinical scenarios for VMAT use were identified: 1) BMs, 2) H&NC, 3) thoracic neoplasms, 4) GU cancer, 5) anorectal tumor, and 6) stereotactic body radiation therapy (SBRT) performed by VMAT technique in the oligometastatic patient setting. Conclusion The literature addressing the clinical appropriateness of VMAT is scarce. Current literature suggests that VMAT, especially when used as simultaneous integrated boost or SBRT strategy, is an effective safe modality for all cancer types.

68Ga-PSMA-11 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy and PSA <0.5 ng/ml. Efficacy and impact on treatment strategy

PurposeThe primary aim of this retrospective, single-centre analysis was to assess the performance of 68Ga-PSMA-11 PET/CT in prostate cancer (PCa) patients in early PSA failure after radical prostatectomy (RP). The secondary aim was to assess the potential impact of 68Ga-PSMA-11 PET/CT on treatment strategy.Methods68Ga-PSMA-11 PET/CT is performed in our institution within an investigational new drug (IND) trial in PCa patients with biochemical recurrence (BCR). The records of all patients enrolled between March 2016 and July 2017 were evaluated. These records were retrospectively analysed according to the following inclusion criteria: (a) RP as primary therapy, (b) proven BCR, ©) PSA levels in the range 0.2–0.5xa0ng/ml at the time of the 68Ga-PSMA-11 PET/CT investigation, and (d) no salvage radiotherapy (S-RT) performed after recurrence. The performance of 68Ga-PSMA-11 PET/CT was evaluated in terms of detection rate on a per-patient and a per-region basis (local vs. distant lesions). We further performed an intention-to-treat (ITT) analysis. The patient cohort was grouped into three subpopulations, blinded to the 68Ga-PSMA-11 PET/CT results, according to the patients’ characteristics and different patterns of treatment: (1) S-RT (with or without systemic treatment), (2) stereotactic body radiotherapy (SBRT) (with or without systemic treatment), and (3) systemic treatment. The treatment strategy was re-evaluated for each patient taking into consideration the 68Ga-PSMA-11 PET/CT images.ResultsWe enrolled 119 PCa patients (mean age 66xa0years, range 44–78xa0years) with a mean PSA level at the time of 68Ga-PSMA-11 PET/CT of 0.34xa0ng/ml (median 0.32xa0ng/ml, SD ±0.09, range 0.20–0.50xa0ng/ml). 68Ga-PSMA-1 1 PET/CT was positive in 41 of the 119 patients, resulting in an overall detection rate of 34.4%. 68Ga-PSMA-11 uptake was observed in the prostate bed (3 patients, 2.5%), in the pelvic lymph nodes (21, 17.6%), in the retroperitoneal lymph nodes (4, 3.4%) and in the skeleton (21, 17.6%). Regarding ITT, 81 patients (68.1%) were considered possible candidates for S-RT only in the prostate bed and none of the patients (0%) for SBRT. According to the 68Ga-PSMA-11 PET/CT results, the intended treatment was changed in 36 patients (30.2%). According to the PET/CT results, S-RT was recommended in 70 patients (58.8%), only to the prostate bed in 58 (48.7%) and SBRT in 29 (24.4%). The intended RT planning was modified in 36 (87.8%) of 41 patients with a positive 68Ga-PSMA-11 PET/CT result.ConclusionIn our patient series with PSA levels <0.5xa0ng/ml, 68Ga-PSMA-11 PET/CT had a detection rate of 34.4%. In the ITT analysis, 30.2% of patients had a change in the intended treatment. These data support the hypothesis that 68Ga-PSMA-11 PET/CT is a useful procedure in the management of PCa patients showing early recurrence after RP, and should be implemented in routine clinical practice.

Tailored postoperative treatment of prostate cancer: final results of a phase I/II trial

BackgroudThe European Organization for Research and Treatment of Cancer (EORTC) trial 22,911 reported 74% 5-year biochemical disease-free survival (bDFS) in patients with prostate carcinoma treated with radical prostatectomy (RP) followed by postoperative radiotherapy (RT). This study aimed to improve these outcomes by using a combined-intensified-modulated-adjuvant treatment, including RT and hormone therapy (HT) after RP.Materials and methodsThis phase I/II trial treatment was designed to improve 5-year bDFS from ~u200975 to 90%. Patients were consecutively enrolled using the following inclusion criteria: ageu2009<u200980 years, histological diagnosis of prostate adenocarcinoma without known metastases, stage pT2-4N0-1, and Eastern Cooperative Oncology Group performance status of 0–2. All patients had at least one of these pathologic features: capsular perforation, positive surgical margins, seminal vesicle invasion, and pelvic lymph nodes involvement. A minimum dose of 64.8u2009Gy to the tumor bed was delivered in all patients. Depending on tumor characteristics at diagnosis, patients received a higher dose (70.2u2009Gy; 85.4%) and/or prophylactic pelvic lymph nodes irradiation (57.7%) and/or HT (69.1%). Biochemical relapse was defined as two consecutive rising prostate-specific antigen (PSA) valuesu2009>u20090.2u2009ng/ml.ResultsA total of 123 patients were enrolled in the study and completed the scheduled treatment. Median preoperative and postoperative PSA were: 8.8 and 0.06u2009ng/mL, respectively. The percentages of patients with pathologically involved nodes and positive resection margins were: 14.6% and 58.5%, respectively. With a median follow-up of 67 months (range: 37–120 months), the actuarial 5-year bDFS, local control, metastasis-free survival, and overall survival (OS) were: 92.9%, 98.7%, 96.1%, and 95.1%, respectively.ConclusionA higher 5-year bDFS (92.9%) was recorded comparedxa0to studies based on standard adjuvant RT, even though patients with nodal disease and detectable postoperative PSA were enrolled. Clinical end points, as long-term disease-free survival and OS, will require further assessments. (ClinicalTrials.gov: NCT03169933)

Radiotherapy in palliation of thoracic tumors: a phase I–II study (SHARON project)

The main clinical goal for patients with advanced or metastatic thoracic cancer is palliation of tumor-related symptoms and improvement of quality of life. The aim of this phase I–II trial was to define the maximum tolerated dose (MTD) of a short-course of palliative radiotherapy (RT) and to evaluate its efficacy in terms of palliative response. A phase I trial was planned with escalating dose increments. Total doses ranged from 16 to 20xa0Gy delivered (BID) in two consecutive days. Dose limiting toxicity was defined as any acute grade ≥u20093 toxicity based on the RTOG scale. MTD was used in the phase II trial to evaluate the efficacy of this regimen using a two stage Simon’s design. Fifty-four patients were enrolled. The upper dose level of 20xa0Gy was defined as the MTD. In patients treated with this dose, the overall palliative response rate was 96.5% (CI 0.95: 81.3–99.9%). Complete pain relief rate was 50.0%. Median survival without symptomatic progression was 3xa0months. The tested short course accelerated regimen was well tolerated and effective in the palliative setting of metastatic or locally advanced chest cancer. A phase III trial is ongoing to validate this RT schedule.Trial registration: NCT03465553.