T. Rancati

Predictors of Health-related Quality of Life and Adjustment to Prostate Cancer During Active Surveillance

BACKGROUNDnActive surveillance (AS) is emerging as an alternative approach to limit the risk of overtreatment and impairment of quality of life (QoL) in patients with low-risk localised prostate cancer. Although most patients report high levels of QoL, some men may be distressed by the idea of living with untreated cancer.nnnOBJECTIVEnTo identify factors associated with poor QoL during AS.nnnDESIGN, SETTING, AND PARTICIPANTSnBetween September 2007 and March 2012, 103 patients participated in the Prostate Cancer Research International Active Surveillance (PRIAS) QoL study. Mental health (Symptom Checklist-90), demographic, clinical, and decisional data were assessed at entrance in AS. Health-related QoL (HRQoL) Functional Assessment of Cancer Therapy-Prostate version and Mini-Mental Adjustment to Cancer outcomes were assessed after 10 mo of AS.nnnOUTCOME MEASUREMENTS AND STATISTICAL ANALYSISnMultivariate logistic regression models were used to identify predictors of low (<25th percentile) HRQoL, adjustment to cancer, and a global QoL index at 10 mo after enrollment.nnnRESULTS AND LIMITATIONSnThe mean age of the study patients was 67 yr (standard deviation: ±7 yr). Lack of partner (odds ratio [OR]: 0.08; p=0.009) and impaired mental health (OR: 1.2, p=0.1) were associated with low HRQoL (p=0.006; area under the curve [AUC]: 0.72). The maladaptive adjustment to cancer (p=0.047; AUC: 0.60) could be predicted by recent diagnosis (OR: 3.3; p=0.072). Poor global QoL (overall p=0.02; AUC: 0.85) was predicted by impaired mental health (OR: 1.16; p=0.070) and time from diagnosis to enrollment in AS <5 mo (OR: 5.52; p=0.009). Influence of different physicians on the choice of AS (OR: 0.17; p=0.044), presence of a partner (OR: 0.22; p=0.065), and diagnostic biopsy with >18 core specimens (OR: 0.89; p=0.029) were predictors of better QoL. Limitations of this study were the small sample size and the lack of a control group.nnnCONCLUSIONSnFactors predicting poor QoL were lack of a partner, impaired mental health, recent diagnosis, influence of clinicians and lower number of core samples taken at diagnostic biopsy. Educational support from physicians and emotional/social support should be promoted in some cases to prevent poor QoL.

Long term rectal function after high-dose prostatecancer radiotherapy: Results from a prospective cohort study

PURPOSEnTo prospectively evaluate long-term late rectal bleeding (lrb) and faecal incontinence (linc) after high-dose radiotherapy (RT) for prostate cancer in the AIROPROS 0102 population, and to assess clinical/dosimetric risk factors.nnnMATERIALS AND METHODSnQuestionnaires of 515 patients with G0 baseline incontinence and bleeding scores (follow-up ≥6 years) were analysed. Correlations between lrb/linc and many clinical and dosimetric parameters were investigated by univariate and multivariate logistic analyses. The correlation between lrb/linc and symptoms during the first 3 years after RT was also investigated.nnnRESULTSnOf 515 patients lrb G1, G2 and G3 was found in 32 (6.1%), 2 (0.4%) and 3 (0.6%) patients while linc G1, G2 and G3 was detected in 50 (9.7%), 3 (0.6%) and 3 (0.6%), respectively. The prevalence of G2-G3 lrb events was significantly reduced compared to the first 3-years (1% vs 2.7%, p=0.016) ≥G1 lrb was significantly associated with V75 Gy (OR=1.07). In multivariate analysis, ≥G1 linc was associated with V40 Gy (OR=1.015), use of antihypertensive medication (OR=0.38), abdominal surgery before RT (OR=4.7), haemorrhoids (OR=2.6), and G2-G3 acute faecal incontinence (OR=4.4), a nomogram to predict the risk of long-term ≥G1 linc was proposed. Importantly, the prevalence of ≥G1 linc was significantly correlated with the mean incontinence score during the first 3 years after RT (OR=16.3).nnnCONCLUSIONSnLong-term (median: 7 years) rectal symptoms are prevalently mild and strongly correlated with moderate/severe events occurring in the first 3 years after RT. Linc was associated with several risk factors.

Bladder spatial-dose descriptors correlate with acute urinary toxicity after radiation therapy for prostate cancer

PURPOSEnTo assess bladder spatial-dose parameters predicting acute urinary toxicity after radiotherapy for prostate cancer (PCa) through a pixel-wise method for analysis of bladder dose-surface maps (DSMs).nnnMATERIALS & METHODSnThe final cohort of a multi-institutional study, consisting of 539 patients with PCa treated with conventionally (CONV:1.8-2Gy/fr) or moderately hypo-fractionated radiotherapy (HYPO:2.2-2.7Gy/fr) was considered. Urinary toxicity was evaluated through the International Prostate Symptoms Score (IPSS) administered before and after radiotherapy. IPSS increases ⩾10 and 15 points at the end of radiotherapy (ΔIPSS⩾10 and ΔIPSS⩾15) were chosen as endpoints. Average DSMs (corrected into 2Gy-equivalent doses) of patients with/without toxicity were compared through a pixel-wise method. This allowed the extraction of selected spatial descriptors discriminating between patients with/without toxicity. Previously logistic models based on dose-surface histograms (DSH) were considered and replaced with DSM descriptors. Discrimination power, calibration and log-likelihood were considered to evaluate the impact of the inclusion of spatial descriptors.nnnRESULTSnData of 375/539 patients were available. ΔIPSS⩾10 was recorded in 76/375 (20%) patients, while 30/375 (8%) experienced ΔIPSS⩾15. The posterior dose at 12mm from the bladder base (roughly corresponding to the trigone region) resulted significantly associated to toxicity in the whole/HYPO populations. The cranial extension of the 75Gy isodose along the bladder central axis was the best DSM-based predictor in CONV patients. Multi-variable models including DSM descriptors showed better discrimination (AUC=0.66-0.77) when compared to DSH-based models (AUC=0.58-0.71) and higher log-likelihoods.nnnCONCLUSIONnDSMs are correlated with the risk of acute GU toxicity. The incorporation of spatial descriptors improves discrimination and log-likelihood of multi-variable models including dosimetric and clinical parameters.

EP-1764: development and validation of a tool to evaluate prostate motion due to patient’s breathing

Purpose or Objective: An electromagnetic (ELM) system (Calypso, Varian Medical System, Palo Alto, CA, USA) based on sub-millimeter high frequency localization of three transponders permanently implanted in the prostate, was recently introduced for continuous real-time tracking of the tumor. Several studies of the tracks acquired over thousands of patients were reported in literature and allowed to give a detailed insight of intra-fraction prostate motion. Aim of this work was to develop and validate a tool to selectively filter the signal produced by the ELM transponders and to apply it for the evaluation of the amplitude of prostate motion only due to patient’s breathing.

PV-0377: Inter-fraction bladder variations in RT of prostate cancer: impact on dose surface maps

ESTRO 35 2016 _____________________________________________________________________________________________________ Purpose or Objective: Contrast enhancement and respiration management are widely used during image acquisition for radiotherapy treatment planning of liver tumors along with respiration management at the treatment unit. However, neither respiration management nor intravenous contrast is commonly used during cone-beam CT (CBCT) image acquisition for alignment prior to radiotherapy. In this study, the authors investigate the potential gains of injecting an iodinated contrast agent in combination with respiration management during CBCT acquisition for liver tumor radiotherapy.

PO-0875: Multivariable models for urinary symptoms at 6-24 months after radical RT of prostate cancer

Conclusion: The delivery of a voxel by voxel iso-effective plan, if different RBE models are employed, is not feasible; it is however possible to minimize differences in dose deposited in the target. Dose prescription is a clinical task which ultimately depends only on the radiation oncologist clinical decision; in this study we made an attempt to avoid systematic errors which could potentially compromise tumor control. Initial clinical data on local control of adenoid cystic carcinoma treated in our facility confirms the validity of this approach.

Development and validation of a software to evaluate breathing-induced prostate motion tracked with implanted electromagnetic transponders

Introduction A system (Calypso, Varian Medical Systems) based on the localization of electromagnetic transponders (ELM-TRNs) permanently implanted in the prostate allows real-time tracking during radiotherapy treatments. Purpose Development and validation of a dedicated software for ELM-TRNs signal analysis to quantify the amplitude of the intra-fraction prostate motion induced by patient’s breathing, both in supine and prone position. Materials and methods For each treatment session, the software automatically identifies the breathing frequency on the power density spectrum of the recorded signal and creates a bandpass filter around this frequency. The obtained filter is then applied to selectively compute the breathing-induced harmonic excursion of the prostate around its nominal position. The software was validated with a moving phantom (QUASAR, Modus Medical Devices), provided with home-made inserts containing three ELM-TRNs. Harmonic motions along the three main directions were tracked at several known frequencies and amplitudes. The calculated frequencies and amplitudes were compared to the expected ones. The software was then applied to signals of patients who underwent radiotherapy treatments in supine or prone position. Results The software automatically computed the correct frequencies and amplitudes within a 0.6% and a 110xa0μm uncertainty, respectively, without any significant difference among the three main directions. The software was demonstrated to properly work on signals acquired both with supine and prone patients. Conclusion A software to quantify prostate motion due to patient’s breathing was successfully developed, in-phantom validated and applied to supine and prone patients, highlighting significant motion differences between the two setups. Disclosure None. Work partially funded by AIRC-(IG-14300).

PO-0702: Change over time of IPSS in two prostate cancer cohorts: radical radiotherapy vs active surveillance

Purpose/Objective: To update a Hypofractionated Tomotherapy Treatment (HTT) feasibility-study, by evaluation of toxicity and outcome, in lymph nodal relapse of patients (pts) already treated for prostate cancer. The role of 11CCholine PET/CT in detecting prostate cancer recurrence and as a guide for Tomotherapy treatment was also evaluated. Materials and Methods: From January 2005 to August 2012, 49 prostate cancer pts with biochemical recurrence and evidence of lymph nodal relapse at 11CCholine PET/CT scan (PET/CT0) were treated with moderately hypofractionated Tomotherapy. All pts had undergone previous prostatectomy, radical radiation therapy (RT) or prostatectomy + RT and all were currently receiving systemic therapy. One patient was treated 3 times, two patients twice: the total number of therapies was 53. In 49/53 cases PET/CT0 detected metastases (LNMs) at para-aortic and/or pelvic level, in 4 cases at the mediastinal level. Pelvic and/or lombo-aortic lymph nodes were treated to 51.8Gy/28 fractions and PET/CT0 positive lymph nodes were treated with higher dose using a simultaneous integrated boost. A Mega-Voltage CT scan (MVCT) was performed before each fraction to allow correct patient repositioning in order to reduce PTV margin and side effects to surrounding tissues. The doses ranged from 42 Gy in 6 fractions to 74.2 Gy in 28 fractions. To evaluate treatment efficacy, PSA serum measurement (PSA1) (all pts) and 11CCholine PET/CT(PET/CT1) (n=19) were performed after treatment and compared to basal evaluations. Results: In 17/49 pts (53 therapies) 6 genito-urinary [GU] and 11 upper-gastro intestinal [uGE] G1 acute toxicities were recorded. Only 5 G2 uGE and 2 G2 GU were observed. 3 pts had G1 rectum toxicity and 3 pts G1 erythema. No G3-G4 acute side effects were registered. Among the 41 pts with follow-up longer than 3 months, 5 had G1 late toxicity (1uGE and 4GU), 3 presented G2GU toxicity, one G2 rectal toxicity and 3 G3 GU toxicity. With a median follow-up of 24 months (range: 0-88)37/41 pts had a significant reduction of PSA value after HTT. Of the 19 pts with PET/CT1 evaluation, 14 had Complete Metabolic Response and 2 Partial Metabolic Response. During followup, only 3 of the 41 evaluable pts had progression in the irradiated area and 7 in other sites. One died of tumour progression. Half of the patients in complete remission maintained good PSA control even after suspending their medical treatment. Mean Overall survival was 31.73 months; Overall Survival at 36 months was 85.7%, PFS at 36 months was 32.8%. Conclusions: These preliminary data show that HTT 11CCholine PET/CT-guided with IGRT for precise repositioning is safe and effective in lymph nodal relapse of prostate cancer pts and could be a valid alternative to chemotherapy. Although further evaluations are necessary, the good rate of local control suggests that HTT treatment guided by 11CCholine PET/CT images maybe reasonably proposed in these patients.