Domenico Gabriele

Beyond D'Amico risk classes for predicting recurrence after external beam radiotherapy for prostate cancer: the Candiolo classifier

BackgroundThe aim of this work is to develop an algorithm to predict recurrence in prostate cancer patients treated with radical radiotherapy, getting up to a prognostic power higher than traditional D’Amico risk classification.MethodsTwo thousand four hundred ninety-three men belonging to the EUREKA-2 retrospective multi-centric database on prostate cancer and treated with external-beam radiotherapy as primary treatment comprised the study population. A Cox regression time to PSA failure analysis was performed in univariate and multivariate settings, evaluating the predictive ability of age, pre-treatment PSA, clinical-radiological staging, Gleason score and percentage of positive cores at biopsy (%PC). The accuracy of this model was checked with bootstrapping statistics. Subgroups for all the variables’ combinations were combined to classify patients into five different “Candiolo” risk-classes for biochemical Progression Free Survival (bPFS); thereafter, they were also applied to clinical PFS (cPFS), systemic PFS (sPFS) and Prostate Cancer Specific Survival (PCSS), and compared to D’Amico risk grouping performances.ResultsThe Candiolo classifier splits patients in 5 risk-groups with the following 10-years bPFS, cPFS, sPFS and PCSS: for very-low-risk 90 %, 94 %, 100 % and 100 %; for low-risk 74 %, 88 %, 94 % and 98 %; for intermediate-risk 60 %, 82 %, 91 % and 92 %; for high-risk 43 %, 55 %, 80 % and 89 % and for very-high-risk 14 %, 38 %, 56 % and 70 %. Our classifier outperforms D’Amico risk classes for all the end-points evaluated, with concordance indexes of 71.5 %, 75.5 %, 80 % and 80.5 % versus 63 %, 65.5 %, 69.5 % and 69 %, respectively.ConclusionsOur classification tool, combining five clinical and easily available parameters, seems to better stratify patients in predicting prostate cancer recurrence after radiotherapy compared to the traditional D’Amico risk classes.

Quality indicators in the intensity modulated/image-guided radiotherapy era

PURPOSE To propose new Quality Indicators (QIs) for the Intensity Modulated(IMRT)/Image-Guided(IGRT) Radiotherapy techniques. MATERIALS AND METHODS Two structure, 10 process and 2 outcome QIs were elaborated. A working group including Radiation Oncologist, Medical Physicist and Radiation Technologists was made up. A preliminary set of indicators was selected on the basis of evidenced critical issues; the criteria to identify more relevant and specific QIs for IMRT/IGRT were defined; structure, process and outcome QIs were defined. The elaborated indicators were tested in four Italian Radiotherapy Centers. RESULTS Fourteen indicators were proposed. Seven indicators were completely new while a new standard is proposed for four indicators based on Validation Centers (VC) data. No change was reported for 3 indicators. The indicators were applied in the four VC. The VC considered were able to respect all indicators except indicator 2 for one Center. DISCUSSION AND CONCLUSION QIs may provide useful measures of workload and service performances.

A two population model of cancer growth with fixed capacity

Cancer is not a homogenous tissue, but a very complex mix of different cell populations; moreover, a delicate equilibrium exists between these components of a tumour mass. In this work we address prostate cancer although the methods presented can be generalized to most tumour types. The aim of our work is to model the behaviour of the different cell populations within the tumour and simulate changes which occur during natural evolution and treatments.

Dose to organs at risk in the upper abdomen in patients treated with extended fields by helical tomotherapy: a dosimetric and clinical preliminary study

BackgroundThe aim of this work was to determine the technical feasibility and safety of extended-field radiotherapy (EF), performed by Helical TomoTherapy, in patients with positive pelvic and/or para-aortic nodes. Dosimetric data were collected and acute and sub-acute toxicities of the upper abdominal organs at risk (OAR) were evaluated.MethodsTwenty-nine patients suitable for EF irradiation for local disease and/or nodal disease in the pelvic or para-aortic area were treated. The prescription dose was 50.4/54 Gy (1.7-1.8 Gy/fraction) for prophylactic lymph nodes (N-) and 60–70.5 Gy (2–2.35 Gy/fraction) for clinically evident gross disease (N+). Modulation factor (MF), pitch and field width (FW) were chosen to optimize dose distribution and treatment duration. Dose values of PTVs and OAR were analysed. The length of the treatment field, the N + and N- volumes, and treatment duration were reported. To evaluate the safety of treatment, haematological, hepatic, renal and pancreatic functions were assessed before, during and after treatment. The median follow-up time was 17.6 months (range: 6–22 months).ResultsThe treatment was well tolerated and all patients but one completed treatment without interruption. Four of the 29 patients experienced G3 haematological acute toxicity (13.8%), but no patient experienced sub-acute grade G3 toxicity. Ten patients experienced G1 and three G2 acute gastrointestinal toxicity (nausea). No sub-acute gastrointestinal or renal toxicity was observed. Only one (3.7%) patient had a persistent slight increase of pancreatic enzymes and two (7.4%) patients a slight increase of hepatic enzymes six months after radiotherapy (G1 toxicity).ConclusionsWith our treatment design and dose regimen, we found that EF treatment by TomoTherapy could be safely and effectively delivered with minimal acute and sub-acute toxicities in the upper abdomen area.

Adjuvant helical IMRT by tomotherapy for bulky adrenocortical carcinoma operated with positive margins: a case report.

Background Adrenocortical carcinoma (ACC) is a rare tumor in the adult. The main therapy is surgery but in some cases radiotherapy may be needed to control the disease locally. Methods A patient with a surgically removed bulky ACC and pathologic finding of a positive margin was treated at our center by adjuvant mitotane and radiotherapy using an intensity-modulated radiation therapy (IMRT)/image-guided radiotherapy (IGRT) technique by tomotherapy. Dose prescriptions were 63 Gy on the surgical bed and 50.4 Gy on the lymphatic drainage in 28 sessions. Patient compliance was good with no evidence of acute or late toxicities. Results Thirty months after radiotherapy, the patient is alive without evidence of disease checked by 18F-fluorodeoxyglucose positron emission tomography/computed tomography and without any complication. Conclusions In patients with adverse prognostic features, the delivery of adequate adjuvant radiotherapy doses with IMRT and daily IGRT is feasible and safe and could result in an improved outcome for patients with ACC.

PO-0751: Predicting recurrence after 3DC Radiotherapy for prostate cancer: proposal for a new classifier

IEO Milan, Radiotherapy, Milan, Italy Novara HUniv Avogadro, Radiotherapy, Novara, Italy Candiolo Cancer Centre FPO-IRCCS, Department of Radiotherapy, Candiolo Turin, Italy Asti Hospital, Radiotherapy, Asti, Italy Biella Hospital, Radiotherapy, Biella, Italy Ivrea Hospital, Radiotherapy, Ivrea, Italy Verbania Hospital, Radiotherapy, Verbania, Italy Como Hospital, Radiotherapy, Como, Italy Pisa Univ Hospital, Radiotherapy, Pisa, Italy Physiology Turin Univeristy, Neuroscience, Turin, Italy

A Simple PSA-Based Computational Approach Predicts the Timing of Cancer Relapse in Prostatectomized Patients

Recurrences of prostate cancer affect approximately one quarter of patients who have undergone radical prostatectomy. Reliable factors to predict time to relapse in specific individuals are lacking. Here, we present a mathematical model that evaluates a biologically sensible parameter (α) that can be estimated by the available follow-up data, in particular by the PSA series. This parameter is robust and highly predictive for the time to relapse, also after administration of adjuvant androgen deprivation therapies. We present a practical computational method based on the collection of only four postsurgical PSA values. This study offers a simple tool to predict prostate cancer relapse. Cancer Res; 76(17); 4941-7. ©2016 AACR.

MP53-09 A SIMPLER MODIFIED GLEASON SCORE PERFORMS SLIGHTLY BETTER THAN THE STANDARD ONE

INTRODUCTION AND OBJECTIVES: To compare the predictive ability of standard Gleason Score (GS) to a modified one, summing up primary Gleason and the worst score found at the pathologic examination following radical prostatectomy. METHODS: We selected 3490 patients eligible for the study from our database of 3538 radical prostatectomysed cases, collected in the EUREKA-1 multicentric retrospective study on prostate cancer, part of the CHIC European project. We compared the predictive power of standard GS, made up of primary plus second most frequent score at the final pathologic exam after radical prostatectomy, to a simpler one, summing up primary Gleason and the worst score found in the sample (if primary and worst score are the same you have simply to double the score value). The event evaluated was biochemical relapse. Data were analysed with Cox proportional hazard regression model for survival analysis and related Concordance Index (CI). The subgroup of 2707 patients with a follow-up (FU) longer than 30 months was further studied through ROC Area Under the Curve (AUC) analysis. RESULTS: Primary plus worst GS performs slightly better than primary plus secondary GS (CI 1⁄4 0.6587 versus CI 1⁄4 0.6475). In addition, with modified GS it’s possible to split patients into four instead of three risk categories with statistical significance (GS 6, 7, 8 and 9-10 versus 6, 7 and 8-9-10 all together because of a P respectively < 0.001 versus P 1⁄4 0.45 comparing GS 8 and GS 9-10 groups) (Figures 1 and 2). This finding is confirmed by the sub-analysis of patients with a FU longer than 30 months showing a higher ROC AUC of 0.6636 for modified GS versus 0.6523 for the standard one (P 0.0114). CONCLUSIONS: A GS summing up the most frequent score and the worst one performs slightly better than the traditional GS in a huge retrospective cohort of patients. Besides, this modified GS has the advantage of being simpler and quicker during the pathologist’s routine (e.g. no need to report a tertiary higher grade GS), increasing the reliability of pathology reports. SourceofFunding:EuropeanUnionprojectCHIC,Computational Horizons In Cancer, grant agreement number 600841.

Data collection for models validation: Application to prostate cancer — Clinical aspects

In the general framework of the European ICT Project CHIC, focused on the building of a common repository for data and models in the field of human cancer, we are collecting clinical, serological and pathological data about prostate cancer for prognostic and growth modeling purposes. Two ongoing retrospective observational studies, named EUREKA-1 and EUREKA-2, focused on patients treated respectively by Radical Prostatectomy (RP) or Radical Radiotherapy (RRT) as primary treatment are presented.

Technical and clinical description of a case of extensive anogenital Paget’s disease associated with anal cancer treated by tomotherapy

In this paper we describe a case of extramammary Pagets disease associated with anal cancer, which was successfully treated by intensity-modulated radiotherapy using tomotherapy with a simultaneous integrated boost and daily image guidance. The main pitfall in this report is the relatively short follow-up (1 year), which means that the evaluated data is promising but not conclusive. Considering the rarity and wide extension of our patients Pagets disease in the anogenital region, and the lack of literature reports about curative radiotherapy in this particular setting, this case report may be considered the first related to extensive extramammary Pagets disease treated by tomotherapy.