Description: Publication date: Available online 28 December 2016 Source: Radiotherapy and Oncology Author(s): George Hruby, Thomas Eade, Andrew Kneebone, Louise Emmett, Lesley Guo, Bao Ho, Ed Hsiao, Geoff Schembri, Julia Hunter, Carol Kwong Background and purpose We investigated the role of 68 Ga-PSMA-PET (PSMA) to determine the location of disease recurrence in those with a rising PSA following definitive external beam radiation treatment (EBRT). Materials and methods 538 men were treated with image guided EBRT to a dose of 78 or 82 Gy between 2007 and 2014. Patients at least 24 months post EBRT with biochemical failure (nadir + 2) underwent PSMA scanning. Local recurrence (LR) was defined as increased uptake within the prostate or seminal vesicles. Distant disease included lymph node (LN), bone or visceral metastases. Results 419 men formed the study cohort. Median follow-up was 50 months, 70 patients (17%) had biochemical failure (BF), 13 of whom have died. Of the 57 survivors, 5 had metastases detected on conventional scans; 2 were lost to follow up. 48 men (of 50 candidates) underwent PSMA; in all cases, the PSMA was unequivocally positive. Of the 48 positive scans, 25 patients (52%) failed beyond the prostate – 5 in bones, 16 LN, 3 in both, and 1 in the lungs. Fifteen men (31%) failed within the gland and in either LN (11), bones (3), or both (1). Eight (17%) had an isolated LR, which represents 2% of patients managed with definitive EBRT and followed for at least 2 years. Conclusions PSMA was positive in all patients with BF. Site of failure following dose-escalated EBRT was generally distant. Isolated LR (on PSMA) occurred in only 8 of 419 patients post-EBRT.

Description: Publication date: Available online 26 December 2016 Source: Radiotherapy and Oncology Author(s): Dae Yong Kim, Joong-Won Park, Tae Hyun Kim, Bo Hyun Kim, Sung Ho Moon, Sang Soo Kim, Sang Myung Woo, Young-Hwan Koh, Woo Jin Lee, Chang-Min Kim Purpose To evaluate clinical effectiveness and safety of simultaneous integrated boost-proton beam therapy (SIB-PBT) in hepatocellular carcinoma (HCC) patients with tumour vascular thrombosis (TVT). Material and methods Forty-one HCC patients with TVT underwent SIB-PBT using three dose-fractionation schemes: if gross tumour volume 〈1 cm ( n = 27), 1–1.9 cm ( n = 7), and ⩾2 cm ( n = 7) from gastrointestinal structures, 50 GyE (EQD2, 62.5 GyE 10 ), 60 Gy (EQD2, 80 GyE 10 ), 66 Gy (EQD2, 91.3 GyE 10 ), respectively, in 10 fractions was prescribed to planning target volume 1 (PTV1), and 30 GyE (EQD2, 32.5 GyE 10 ) in 10 fractions was prescribed to PTV2. Results Overall, treatment was well tolerated, with no grade toxicity ⩾3. Median overall survival (OS) was 34.4 months and 2-year local progression-free survival (LPFS), relapse free survival (RFS), and OS rates were 88.1%, 25%, and 51.1%, respectively. Patients treated with EQD2 of ⩾80 GyE 10 tended to show better TVT response (92.8% vs. 55.5%, p = 0.002) 2-year LPFS (92.9% vs. 82.5%, p = 0.463), RFS (28.8% vs. 19%, p = 0.545), and OS (58.4% vs. 46.8%, p = 0.428) rates than those with EQD2 of 〈80 GyE 10 . Multivariate analysis showed that TVT response and Child Pugh classification were independent prognostic factors for OS. Conclusions SIB-PBT is feasible and promising for HCC patients with TVT.

Description: Publication date: Available online 24 December 2016 Source: Radiotherapy and Oncology Author(s): Antoine Schernberg, Alexandre Escande, Eleonor Rivin Del Campo, Michel Ducreux, France Nguyen, Diane Goere, Cyrus Chargari, Eric Deutsch Objective Leukocytosis and neutrophilia could be the tip of the iceberg in the inflammatory tumor microenvironment. We aimed to validate their prognostic significance in a cohort of patients treated with definitive chemoradiation for anal squamous cell carcinoma (SCC). Materials & methods Clinical records from all consecutive patients treated in a single institution between 2006 and 2016 with curative-intent radiotherapy were retrospectively analyzed. Leukocytosis and neutrophilia, defined as leukocyte or neutrophil count over 10,000 and 7500/mm 3 , respectively, were studied in terms of overall survival (OS), progression (PFS), locoregional (LFS) and distant (DFS)-free survival. Results We identified 103 non-metastatic HIV-negative patients, with concurrent chemotherapy use in 78%. Twelve and 8% displayed baseline leukocytosis and neutrophilia, respectively. Estimated 3-year OS and PFS were 88% and 67%, respectively. In univariate analysis, both leukocytosis and neutrophilia were strongly associated with inferior OS, PFS, LFS and DFS ( p 〈 0.01). In multivariate analysis, leukocytosis and neutrophilia remained strongly associated with patient outcome ( p 〈 0.01), independently from tumor T and N-stage. Anemia was an independent predictor of worse OS and PFS, while chemoradiation overall treatment time below 50 days improved PFS. Conclusion Leukocytosis and neutrophilia are strong prognostic factors for OS, PFS, LFS and DFS in anal cancer treated with chemoradiation. These biomarkers could help identify patients with higher risk of tumor relapse that require treatment intensification.

Description: Publication date: Available online 22 December 2016 Source: Radiotherapy and Oncology Author(s): Fredrik Qvarnström, Martin Simonsson, Jan Nyman, Ingegerd Hermansson, Majlis Book, Karl-Axel Johansson, Ingela Turesson Background and purpose Previously we reported that hyper-radiosensitivity (HRS) was evidenced by quantifying DNA double strand break (DSB) foci in epidermis biopsies collected after delivering radiotherapeutic one and five dose fractions. The aim of this study was to determine whether HRS was preserved throughout a 7-week radiotherapy treatment, and also to examine the rate of foci decline and foci persistence between dose fractions. Materials and methods 42 patients with prostate cancer received 7-week fractionated radiotherapy treatment (RT) with daily dose fractions of 0.05–1.10 Gy to the skin. Before RT, and at several times throughout treatment, skin biopsies ( n = 452) were collected at 30 min, and 2, 3, 24, and 72 h after dose fractions. DSB-foci markers, γH2AX and 53BP1, were labelled in epidermal keratinocytes with immunofluorescence and immunohistochemical staining. Foci were counted both with digital image analysis and manually. Results HRS in keratinocytes was evidenced by the dose–response relationships of DSB foci, observed throughout the treatment course, independent of sampling time and quantification method. Foci observed at 24 h after dose fractions indicated considerable DSB persistence. Accordingly, foci significantly accumulated after 5 consecutive dose fractions. For doses below 0.3 Gy, persistent foci could be observed even at 72 h after damage induction. A comparison of γH2AX and 53BP1 quantifications in double-stained biopsies showed similar HRS dose–response relationships. Conclusions These results represented the first evidence of preserved HRS, assessed by γH2AX- and 53BP1-labelled DSB foci, throughout a 7-week treatment course with daily repeated subtherapeutic dose fractions.

Description: Publication date: Available online 21 December 2016 Source: Radiotherapy and Oncology Author(s): Jan Nyman, Andreas Hallqvist

Description: Publication date: Available online 21 December 2016 Source: Radiotherapy and Oncology Author(s): Lorraine Shack, Shuang Lu, Lee-Anne Weeks, Peter Craighead, Marc Kerba Purpose Determining the appropriate rate of radiotherapy (RT) utilization is important for health care planning and resource allocation. The difference between the observed and the appropriate RT rate is influenced by the choice of a criterion based benchmarking (CBB) or evidence-based estimates (EBEST) measure. Our primary objective was to determine the utilization of radiotherapy for cancers of the breast (B), cervix (C), lung (L), prostate (P) and rectum (R) in Alberta (AB) Canada and to compare the observed RT rates to estimates of need derived from the criterion based benchmarking (CBB) and evidence-based estimates (EBEST). Materials and methods All incident cases of B,C,L,P and R cancers diagnosed in AB during 2004-8 (prior to the decentralization of provincial RT capacity) were identified from the Alberta Cancer Registry. Patients receiving RT within one year (RT-1y) of diagnosis were identified and the proportion receiving RT-1y was then calculated. Factors associated with RT utilization were analysed by region. Estimates of the need for RT were derived from CBB and EBEST methods in the literature. Results A total of n = 68,164 cancer cases were identified from the ACR. RT-1y rates (95% C.I.) were B: 51.5% (50.1–52.9), C: 48.9% (43.8–54.0), L: 37.1% (35.4–38.8), P: 26.9% (25.1–28.7) and R: 39.3% (36.5–42.1). Observed rates of RT in AB were lower than estimates derived using the CBB and EBEST estimates. Shortfalls varied across cancer sites according to whether a CBB or EBEST estimate was used ranging from a low of -0.3% in cancer of the cervix to a high of 30.3% in rectal cancer. Conclusions RT shortfalls exist in the utilization of RT in AB, Canada despite centralized cancer care and a publically funded health care system. Decisions to address shortfalls need to be mindful of how model selection can impact on findings.

Description: Publication date: Available online 21 December 2016 Source: Radiotherapy and Oncology Author(s): Matthew M. Harkenrider, William Adams, Alec M. Block, Stephanie Kliethermes, William Small, Surbhi Grover Background/purpose To perform a large analysis of Stage I endometrioid-type endometrial cancer patients to determine the impact of adjuvant radiotherapy (ART) on survival. Material/methods 132,976 FIGO Stage I endometrioid-type endometrial cancer patients treated surgically were identified within the National Cancer Database (NCDB) comprising Commission on Cancer facilities in the United States. Patients were categorized as observation (OBS) or ART (vaginal brachytherapy, external beam radiotherapy, or both). Univariable generalized linear mixed effects models were used to estimate the odds of receiving ART, and a multivariable frailty survival model was used to estimate the instantaneous hazard of death for those receiving OBS versus ART. Due to the presence of a significant interaction, these estimates were stratified by PORTEC-based low, low-intermediate, high-intermediate, and high risk groups. Results 104,645 (79%) underwent OBS while 28,331 (21%) received ART. Of those receiving ART, 12,913 (46%) received VBT alone, 12,857 (45%) received EBRT alone, and 2561 (9%) received EBRT + VBT. On univariable analysis, increasing stage/myometrial invasion, higher grade, older age, presence of lymphovascular space invasion, and larger tumor size predicted poorer survival (all p 〈 0.01). On multivariable analysis, patients at high-intermediate risk and high risk experienced improved survival with ART with a hazard ratio of 0.796 (95% CI: 0.731–0.867; p 〈 0.001) and 0.783 (95% CI: 0.693–0.885; p 〈 0.001), respectively. There was no survival benefit for ART among patients at low or low-intermediate risk. Conclusions In Stage I high-intermediate and high risk endometrioid-type endometrial cancer patients, ART significantly improves overall survival.

Description: Publication date: Available online 21 December 2016 Source: Radiotherapy and Oncology Author(s): Judith van Loon, Aniek J.G. Even, Hugo J.W.L. Aerts, Michel Öllers, Frank Hoebers, Wouter van Elmpt, Ludwig Dubois, Anne-Marie C. Dingemans, Roy I. Lalisang, Pascal Kempers, Boudewijn Brans, Véronique Winnepenninckx, Ernst-Jan Speel, Eric Thunnissen, Kim M. Smits, Ronald Boellaard, Danielle J. Vugts, Dirk De Ruysscher, Philippe Lambin Background and purpose PET imaging of cetuximab uptake may help selecting cancer patients with the highest chance of benefit. The aim of this phase I trial was to determine the safety of the tracer 89 Zr-cetuximab and to assess tumour uptake. Methods Two dose schedules were used; two consecutive doses of 60 MBq 89 Zr-cetuximab or a single dose of 120 MBq, both preceded by 400 mg/m 2 of unlabelled cetuximab. Toxicity (CTCAE 3.0) was scored twice weekly. PET-CT scans were acquired on days 4, 5 and 6 (step 1) or 5, 6, 7 (step 2). Because tumour uptake could not be assessed satisfactorily, a third step was added including EGFR overexpressing tumours. Results Nine patients were included (6 NSCLC; 3 HNC). No additional toxicity was associated with administration of 89 Zr-cetuximab compared to standard cetuximab. A tumour to blood ratio (TBR) > 1 was observed in all but one patient, with a maximum of 4.56. TBR was not different between dose schedules. There was a trend for higher TBR at intervals > 5 days after injection. Conclusions Both presented 89 Zr-cetuximab administration schedules are safe. The recommended dose for future trials is 60 MBq, with a minimum time interval for scanning of 6 days.

Description: Publication date: Available online 20 December 2016 Source: Radiotherapy and Oncology Author(s): Filippo Alongi, Umberto Tebano, Rosario Mazzola

Description: Publication date: December 2016 Source: Radiotherapy and Oncology, Volume 121, Issue 3