External beam radiotherapy for unresectable hepatocellular carcinoma, an international multicenter phase I trial, SAKK 77/07 and SASL 26

Abstract Purpose To assess feasibility and safety of conventionally fractionated radiotherapy (cfRT) in patients with hepatocellular carcinoma (HCC). Methods Patients with histologically confirmed stage cT1-4, cN0-1 HCC and Child-Pugh Score (CPS) A or B disease were included in a phase I multicenter trial. Metastatic HCC were allowed if \u226590% of total tumor volume was located within the liver. Patients were enrolled onto five dose-escalation levels (54\u201370Gy in 2Gy fractions) based on a modified 3 + 3 design, with cohorts of five patients instead of three patients in dose levels 4 and 5. Primary trial endpoint was dose-limiting toxicity (DLT), as specifically defined for 17 clinical and nine laboratory parameters as grade \u22653 or \u22654 toxicity (CTCAE vs. 3). The threshold to declare a dose level as maximum tolerated dose (MTD) was defined as a DLT rate of \u226416.7% in dose levels 1\u20133, and \u226410% in dose levels 4\u20135. Best objective response of target liver lesions and adverse events (AE\u2019s) were assessed as secondary endpoints. Results The trial was terminated early in DL 3 due to low accrual. Nineteen patients were recruited. Fifteen patients were evaluable for the primary and 18 for the secondary endpoints. Maximum tolerated dose was not reached. One patient in dose level 1, and one patient in dose level 2 experienced DLT (lipase > 5xULN, and neutrophils <500/\u3bcL respectively). However, dose level 3 (62Gy) was completed, with no DLTs in 3 patients. Overall, 56% of patients had a partial response and 28% showed stable disease according to RECIST. No signs of radiation induced liver disease (RILD). Two patients in dose level 3 experienced lymphocytopenia grade 4, with no clinical impact. Conclusion Conventionally fractionated radiotherapy of 58Gy to even large HCC was safe for patients with CPS A and B. 62Gy was delivered to three patients without any sign of clinically relevant increased toxicity. The maximum tolerated dose could not be determined. Trial registration ClinicalTrials.gov ..

Adherence to contouring and treatment planning requirements within a multicentric trial -results of the quality assurance of the SAKK 09/10 trial.

PURPOSE To evaluate the results of the radiation therapy (RT) quality assurance (QA) program of the phase III randomized "XXXX-Anonymized for Review" trial in biochemically recurrent prostate cancer (PC) patients after prostatectomy. METHODS AND MATERIALS Within the "XXXX-Anonymized for Review" trial testing 64Gy versus 70Gy salvage RT, a central collection of treatment plans were performed, which were thoroughly reviewed by a dedicated medical physicist and radiation oncologist. Adherence to the treatment protocol and specifically to the European Organization for the Research and Treatment of Cancer (EORTC) guidelines for target volume definition (classified as deviation observed yes vs. no) and its potential correlation with acute and late toxicity (Common Terminology Criteria for Adverse Events (CTCAE) v4.0) and freedom from biochemical progression (FFBP) were investigated. RESULTS The treatment plans of 344 patients treated between February 2011 and April 2014 depicted important deviations to the EORTC guidelines and to the recommendations per trial protocol. For example, in up to half of the cases, the delineated structures deviated from the protocol (e.g., prostate bed (PB) in 48.8%, rectal wall (RW) in 41%). In addition, variations in clinical (CTV) - and planning target volume (PTV) occurred frequently (e.g., CTV and PTV deviations in up to 42.4% and 25.9%, respectively). The detected deviations showed a significant association with a lower risk of grade ≥ 2 gastrointestinal (GI) acute toxicity when CTV not overlapped RW vs. CTV overlapping RW, (OR 0.43; CI [0.22, 0.85]; p= 0.014), and a higher rate of grade ≥ 2 late genitourinary (GU) toxicity in case of the CTV overlapped with RW, (OR 2.58; CI [1.17, 5.72]; p= 0.019). A marginally significant lower risk of grade ≥ 2 late GU toxicity in patients when PB not overlapping RW versus overlapping RW was observed (OR 0.51; CI [0.25, 1.03]; p= 0.06). In addition, a marginally significant decrease of FFBP in patients with PTV not including surgical clips as potential markers of the limits of the prostate bed, (HR 1.44; CI [0.96, 2.17]; p= 0.07) was observed. CONCLUSIONS Despite a thorough QA program, the central review of a phase-III trial showed limited adherence to treatment protocol recommendations which was associated with a higher risk of toxicity by means of acute or late GI or GU toxicity and showed a trend towards worse FFBP. Data from this QA review may help refine future QA programs and prostate bed delineation guidelines

Adherence to Contouring and Treatment Planning Requirements Within a Multicentric Trial: Results of the Quality Assurance of the SAKK 09/10 trial

PURPOSE To evaluate the results of the radiation therapy (RT) quality assurance (QA) program of the phase 3 randomized SAKK 09/10 trial in patients with biochemically recurrent prostate cancer after prostatectomy. METHODS AND MATERIALS Within the Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK) 09/10 trial testing 64-Gy versus 70-Gy salvage RT, a central collection of treatment plans was performed and thoroughly reviewed by a dedicated medical physicist and radiation oncologist. Adherence to the treatment protocol and specifically to the European Organization for the Research and Treatment of Cancer (EORTC) guidelines for target volume definition (classified as deviation observed yes vs no) and its potential correlation with acute and late toxicity (Common Terminology Criteria for Adverse Events version 4.0) and freedom from biochemical progression (FFBP) were investigated. RESULTS The treatment plans for 344 patients treated between February 2011 and April 2014 depicted important deviations from the EORTC guidelines and the recommendations per trial protocol. For example, in up to half of the cases, the delineated structures deviated from the protocol (eg, prostate bed in 48.8%, rectal wall [RW] in 41%). In addition, variations in clinical target volume (CTV) and planning target volume (PTV) occurred frequently (eg, CTV and PTV deviations in up to 42.4% and 25.9%, respectively). The detected deviations showed a significant association with a lower risk of grade ≥2 gastrointestinal acute toxicity when the CTV did not overlap the RW versus when the CTV overlapped the RW (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.22-0.85; P = .014), and a higher rate of grade ≥2 late genitourinary (GU) toxicity when the CTV overlapped the RW (OR, 2.58; 95% CI, 1.17-5.72; P = .019). A marginally significant lower risk of grade ≥2 late GU toxicity was observed when the prostate bed did not overlap versus did overlap the RW (OR, 0.51; 95% CI, 0.25-1.03; P = .06). In addition, a marginally significant decrease in FFBP was observed in patients with PTV not including surgical clips as potential markers of the limits of the prostate bed (hazard ratio, 1.44; 95% CI, 0.96-2.17; P = .07). CONCLUSIONS Despite a thorough QA program, the central review of a phase 3 trial showed limited adherence to treatment protocol recommendations, which was associated with a higher risk of toxicity by means of acute or late gastrointestinal or GU toxicity and showed a trend toward worse FFBP. Data from this QA review might help to refine future QA programs and prostate bed delineation guidelines

Search for unstable sequential neutral and charged heavy leptons in e(+)e(-) annihilation at root s=130 and 136 GeV

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