- Email: [email protected]
Prognostic impact of nodal relapse in definitive prostate-only irradiation
S192
Abstracts
2179 POSTER Use of diffusion weighted-MRI (DW-MRI) as a prognostic biomarker of survival and time to cystectomy in muscle invasive bladder cancer (MIBC) following organ conserving treatment S. Hafeez1 , M.D. Koh1 , A. Sohaib2 , R. Huddart1 . 1 The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Radiotherapy and Imaging, London, United Kingdom; 2 The Royal Marsden NHS Foundation Trust, Radiotherapy and Imaging, London, United Kingdom Background: Neo-adjuvant chemotherapy (nCT) has known survival benefit in the treatment of MIBC and identifies responders who may then benefit from radical radiotherapy. Conventionally response assessment is with cystoscopy. DW-MRI quantifies water molecule motion within tissue using the apparent diffusion coefficient (ADC). As an imaging biomarker it has been related to treatment response in solid tumours. Its use as a prognostic marker in bladder cancer remains novel. Method: 48 patients with confirmed MIBC suitable for nCT were recruited prospectively to an ethics approved protocol. DW-MRI was performed on a 1.5T system using b-values 0, 50, 100, 250, 500 and 750 s/mm2 prior to and on completion of nCT. Tumour was drawn on the 750 s/mm2 images and transferred onto the corresponding ADC map to record mean values. Absolute change in ADC (DADC) was calculated as the difference between post treatment and baseline ADC. Following final DW-MRI patients proceeded to cystoscopy + biopsy. ROC curve analysis was used to identify threshold (AUC >0.6, p < 005) predictive of response with the highest specificity. Significant AUC cut points were used to dichotomise the patient population to determine potential relationship with overall survival (OS) and time to cystectomy. Comparison between the curves was made with logrank test. Results: 38 patients achieved response following nCT and 10 patients had poor reposnse as assessed at cystoscopy + biopsy. Mean DADC of 0.18×10−3 mm2 /s was identified as predicting neo-adjuvant chemotherapy response with sensitivity/specificity/positive predictive value/negative predictive value of 71.1%/80.0%/93.1%/42.1% respectively. Mean %DADC of 18.0% was identified with sensitivity/specificity/positive predictive value/ negative predictive value of 57.9%/90.0%/95.7%/36.0%. After median follow-up of 31 months (95% CI 20−55 months), median OS and time to cystectomy was 25 months (95% CI 16.4–34.9) and 27 months (95% CI 20.2–59.4) respectively. Significant improvement in OS for patients receiving nCT was seen in those achieving mean DADCb100 >0.19×10×10−3 mm2 /s (HR 2.87, 95% CI 1.14–7.23; p = 0.015), mean %DADCb100 >18.1% (HR 4.90, 95% CI 1.10–6.52; p = 0.027). Significant improvement in time to cystectomy was seen in those achieving mean DADC >0.18×10×10−3 mm2 /s (HR 2.67, 95% CI 1.07– 6.61; p = 0.002). Conclusion: DW-MRI may provide prognostic information in bladder cancer but further validation is needed. No conflict of interest. 2180 POSTER Understanding prostate cancer biology using metabolomics and proteomics approaches: potentials in the improvement of the diagnosis, prognosis and identification of new therapeutic targets J. Felgueiras1 , J. Vieira Silva1 , A. Nunes1 , A. Patr´ıcio2 , S. Pelech3 , M. Fardilha1 . 1 University of Aveiro- 3810–193 Aveiro- Portugal, Department of Medical Sciences and Institute for Biomedicine − iBiMED, Aveiro, Portugal; 2 Hospital Infante D. Pedro E.P.E., Urology Service, Aveiro, Portugal; 3 Kinexus Bioinformatics Corporation, Department of Medicine- University of British Columbia, Vancouver, Canada Background: Prostate cancer (PCa) remains a major health problem in men worldwide. The treatment of the disease is still a challenge for Urologists, as well as the establishment of a clear prognosis, which is compromised by the lack of sensitivity and specificity of the currently available markers. Therefore, it is imperative to unravel PCa biology to enable the identification of key molecular events and molecules that aid PCa diagnosis, prognosis and the discovery of new therapeutic targets. In this study we aimed to identify metabolic and proteomic alterations that enable the distinction between prostate benign and malignant tissues. Materials and Methods: Biopsies from prostate tumours and adjacent benign tissue from the central zone of the gland were obtained from eight patients. Prostate specific antigen (PSA) blood levels, prostate carcinoma stage (TNM) and Gleason score were determined in all patients. Each sample was then divided and analysed using two approaches: infrared spectroscopy and an antibody microarray, which allowed the analysis of expression and phosphorylation state of 800 signalling proteins. The list of differentially expressed/regulated proteins between normal and tumour
Poster Session, Sunday 29 January 2017 conditions was then subjected to an extensive bioinformatics analysis to integrate all data and complement with already existing studies. Results: Principal component analysis of spectroscopic signals derived from PCa biopsies and adjacent benign tissues revealed different spectra for each condition. Dysregulations in lipid metabolism, lower amounts of polysaccharides and glycogen, as well as increased content of nucleic acids and protein phosphorylation were the most relevant alterations observed in PCa tissues. Moreover, 40 proteins were identified as differentially expressed between the two conditions and 13 proteins revealed alterations in their phosphorylation levels. The identification of known PCa-related proteins reinforce the fidelity of the screen. The analysis of protein-protein interaction networks and ontologies showed the disruption of cell singling events during prostate carcinogenesis. Conclusions: Metabolomics and proteomics approaches can provide vast information about carcinogenic processes. The integration of different ‘omics’ approaches are increasingly important when moving to a personalised medicine era, which requires the understanding of a disease as a whole system. Here, we show that applying two distinct approaches to the same set of samples it is possible to retrieve a lot of complementar information, increasing not only the knowledge on prostate carcinogenesis, but also allowing the identification of key molecular alterations that may aid an accurate diagnosis/prognosis or the development of new therapies. No conflict of interest. 2180A POSTER High-throughput mutational analysis of urothelial bladder carcinoma T. Nedjadi1 , A. Dallol2 , A. Al-Amari3 , A. Al-Sayyad4 , J. Al-Maghrabi5 . 1 King Abdullah International Medical Research Center, King Abdulaziz Medical City, Jeddah, Saudi Arabia; 2 Center of Innovation in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 3 King Faisal Specialist Hospital, Urology, Jeddah, Saudi Arabia; 4 King Abdulaziz University, Urology, Jeddah, Saudi Arabia; 5 King Abdulaziz University, Pathology, Jeddah, Saudi Arabia Background: Bladder cancer (BC) is a devastating disease characterized by high recurrence rates and elevated progression rate to invasive phenotype. Recent data indicates that BC heterogeneity may contribute to cancer progression and to false-positive biomarker identification. This heterogeneity is mirrored in the genomic features of BC. Typically, identifying genetic aberrations, especially mutational hotspots, will inevitably contribute in biomarkers discovery and influence future therapeutic intervention. Methods: formalin-fixed paraffin-embedded tissues (FFPE) from 96 patients with urothelial bladder cancer were included in the study. Highthroughput mutational analysis was performed using Cancer Hotspots Panel (CHP) v2 on the Ion Torrent™ platform. Kaplan–Meier curve was used to evaluate the relationship between genes mutations and cancerspecific survival; p values were calculated using the log rank test. Results: Our data indicated that BC patients harbour frequent mutations in TP53 (84%), PIK3CA (55%), KDR (40%), FGFR3 (39%), KIT (22%), APC (19%), PTEN (19%), CDKN2A (14%), ATM (12%) and SKP2 (11%). Lower frequency mutations have also been reported for the rest of the gene panel. Interestingly, only FGFR3 mutations were significantly associated with poor disease-specific survival (p = 0.018). Conclusion: The current study was able to validate known mutations in bladder cancer and to identify other genes that are mutated at high frequency in BC patients from the Kingdom of Saudi Arabia. In addition, other, novel mutations were also identified that may prove clinically useful following validation. No conflict of interest. 2184 POSTER Prognostic impact of nodal relapse in definitive prostate-only irradiation M. Loi1 , B. Detti1 , G. Simontacchi1 , I. Desideri1 , P. Bonomo1 , D. Greto1 , M. Mangoni1 , I. Meattini1 , C. Becherini1 , C. Muntoni1 , L. Trombetta1 , L. Livi1 . 1 Universita degli Studi di Firenze, Radiation Therapy Department, Firenze, Italy Background: Nodal pelvic irradiation (WPI) in prostate cancer patients has been extensively investigated with the aim of preventing metastatic spread of cancer cells through lymphatic drainages in prostate cancer patients eligible for definitive radiotherapy (RT); on the other hand, due to uncertain clinical benefit and increased toxicity, its use has substantially declined in the last decades in favour of prostate-only irradiation (PI). The aim of our study is to assess the predictive features and patterns of nodal relapse, and their impact on outcome, in localized prostate cancer patients treated by definitive PI with or without neoadjuvant/adjuvant androgen deprivation therapy (ADT).
Poster Session, Sunday 29 January 2017 Material and Methods: Data from 207 consecutive patients treated at our Institution from 2006 to 2011 were examined. Clinical (age, stage, grade, risk class according to D’Amico and Roach equation) and treatmentrelated (ADT, RT dose, PSA nadir following PI) variables were collected. Biochemical Relapse-Free Survival (BRFS), Pelvic Nodal RecurrenceFree Survival (NRFS), Distant Metastasis-Free Survival (DMFS), Disease Specific Survival (DSS) and Overall survival (OS) were calculated by Kaplan Meyer method. Univariate and multivariate analysis of prognostic variables was performed respectively by log-rank test and Cox model. Results: Patients were stratified in low (45, 21.7%), intermediate (39, 18.8%) and high risk group (123, 59.5%) according to D’Amico criteria; median age was 73 (56−83) years. All patients received PI delivering a median dose of 80 Gy (74−80 Gy). Monthly ADT was administrated to 131 (63.3%) patients, for a median duration of 12 (2−36) months. Median follow-up was 70.9 (27.4–115.8) months; 5-years BRFS, NRFS, DMFS, DSS and OS were respectively 88.9%, 98.5%, 95.2%, 95.2% and 93.7%. On multivariate analysis, independent negative predictors of BRFS were Gleason Score (GS) 7 (HR: 3.09) and PSA nadir >0.08 (HR: 5.08). DMFS and DSS were unfavorably correlated with GS 7 (HR 6.56 and 12.3, respectively). No predictive factor was identified for OS. NRFS was not associated with any clinical variable, while occurrence of nodal relapse was not correlated to impaired outcome. Conclusions: Tumor biology (GS 7) and biological response to treatment (PSA nadir >0.08) are independent predictors of biochemical failure, while metastatic relapse and disease-related mortality are correlated only with GS at diagnosis. Isolated pelvic nodal relapse seldom occurred in our cohort treated by PI independently from risk group and did not correlate with impaired outcome, suggesting the lack of theoretical benefit of a prophylactic nodal irradiation: this finding raise the interest for locoregional treatment like stereotactic body radiation therapy in the event of nodal recurrence. No conflict of interest.
2185 POSTER The impact of hormone therapy on setup errors during external beam radiation therapy for prostate cancer C. Onal1 , Y. Dolek1 , Y. Ozdemir1 . 1 Baskent University, Dept. of Radiation Oncology, ADANA, Turkey Background: To determine if setup errors during external beam radiation therapy (RT) for prostate cancer are influenced by the combination of androgen deprivation treatment (ADT) and RT. Materials and Methods: We retrospectively analyzed data from 175 patients treated for prostate cancer [concurrent ADT plus RT, 33 patients (19%); neoadjuvant and concurrent ADT plus RT, 91 patients (52%); RT only, 51 patients (29%)]. Required couch shifts without rotations were recorded for each CBCT, and corresponding alignment shifts were recorded as left-right (x), superior-inferior (y), and anterior-posterior (z). The nonparametric Mann–Whitney test was used to compare shifts by group. Pearson correlation coefficient was used to measure correlation in couch shifts between groups. Prostate shift means and standard deviations were calculated and pooled to obtain mean or group systematic error (M), standard deviation of systematic error (S), and SD of random error (s). Results: From 175 patients included in this study, a total of 2330 CBCT images were retrospectively evaluated. The median number of CBCT studies analyzed per patient was 15 (range: 8−19). The median duration of neoadjuvant ADT delivered before RT was 3.2 months (range: 2.8−4.1 months). The magnitude of the prostate shifts in the x-direction measured in the first five days was significantly larger in the NC group compared to the N (p = 0.001) and C (p = 0.03) groups. No significant differences were observed in prostate shifts in any direction for all groups. Shifts on CBCT were all less than setup margins. The prostate volumes in the NC, C, and N groups were 31.6±16.1 cc, 47.0±23.2 cc, and 46.1±23.2 cc, respectively. The prostate volumes measured on planning CT were significantly smaller in the NC group compared to the C group (p = 0.003) and the N group (p < 0001). Prostate shifts in the x- and y-directions were not significantly correlated with prostate volume (r = 0.04, p = 0.7 for x-direction; r = 0.03, p = 0.7 for y-direction). A significant positive correlation was observed between prostate volume and average prostate shift in the z-direction (r = 0.19, p = 0.04). Although patients receiving neoadjuvant ADT before RT had significantly smaller prostates, the use of neoadjuvant ADT had no significant impact on prostate shifts in the x-, y-, and z-directions. Significant positive correlation was observed between prostate volume and z-direction prostate shift (r = 0.19, p = 0.04), regardless of ADT group, but not between volume and x- or y-direction shifts (r = 0.04, p = 0.7; r = 0.03, p = 0.7). Random and systematic errors for all patient cohorts and ADT groups were similar.
Abstracts
S193
Conclusion: Hormone therapy given concurrently with RT was not found to significantly impact setup errors. Prostate volume was significantly correlated with shifts in the anterior-posterior direction only. No conflict of interest. 2186 POSTER Predictive factors of late-onset rectal mucosal changes after radiotherapy of prostate cancer E. Ippolito1 , R. Frakulli2 , G. Macchia3 , F. Deodato3 , A. Guido2 , L. Giaccherini2 , A. Farioli4 , A. Arcelli2 , D. Cuicchi4 , L. Frazzoni4 , S. Cilla5 , M. Buwenge2 , G. Mantini6 , A.R. Alitto6 , M. Nuzzo3 , V. Valentini6 , M. Ingrosso7 , A.G. Morganti2 , L. Fuccio4 . 1 Campus Bio-Medico University, Radiotherapy Department, Rome, Italy; 2 S. Orsola-Malpighi Hospital-University of Bologna, Radiation Oncology Unit- Department of Experimental- Diagnostic and Specialty Medicine − DIMES, Bologna, Italy; 3 Fondazione di Ricerca e Cura “Giovanni Paolo II”, Radiation Oncology Unit, Campobasso, Italy; 4 S. Orsola-Malpighi Hospital-University of Bologna, Department of Medical and Surgical Sciences DIMEC, Bologna, Italy; 5 Fondazione di Ricerca e Cura “Giovanni Paolo II”, Medical Physic Unit, Campobasso, Italy; 6 Policlinico Universitario “A. Gemelli”- Universita` Cattolica del Sacro Cuore, Radiation Oncology Department, Rome, Italy; 7 Fondazione di Ricerca e Cura “Giovanni Paolo II”, Endoscopy Unit, Campobasso, Italy Background: Vienna rectoscopy score (VRS) assessed one year after radiotherapy is a surrogate end-point of late rectal toxicity. The aim of this study was to investigate the association between treatment-related factors and 1-year VRS. Material and Methods: We performed a retrospective analysis of prospectively collected data. Patients with prostate adenocarcinoma treated with curative or adjuvant radiotherapy (RT) underwent endoscopy one year after RT. Correlations between VRS 2 and treatment parameters were investigated by univariate and multivariate logistic analyses. Results: One hundred-ninety patients (mean age: 69; range:43−81) were considered eligible for the study. At the univariate analysis, patients treated with hypofractionation, radiosurgery boost and an EQD2 dose (a/b 3) >75 Gy had a significantly higher incidence of VRS >2 (p 0.001) after 1-year of follow-up. At the multivariate analysis, radiosurgery boost was an independent risk factor of developing rectal mucosal lesions (VRS 2), yielding an OR of 4.14 (95% CI 1.2–13.8), while pelvic surgery was inversely associated with VRS >2 (OR: 0.39; 95% CI: 0.17–0.94). Conclusions: Hypofractionation followed byradiosurgery boost significantly increased the risk of developing late-onset rectal mucosal changes. Therefore, special care and preventive treatment strategies are needed when using this boost technique after hypofractionated RT. No conflict of interest. 2187 POSTER SHARP hypofractionated stereotactic radiotherapy is low and intermediate-risk prostate carcinoma patients − PSA outcome M. Rucinska1 , K. Osowiecka2 , S. Nawrocki3 . 1 University of Warmia and Mazury in Olsztyn, Department of Oncology and Department of Radiation Oncology of Independent Public Health Care Facility of the Ministry of the Interior with Warmia and Mazury Oncology Centre in Olsztyn, Olsztyn, Poland; 2 Independent Public Health Care Facility of the Ministry of the Interior with Warmia and Mazury Oncology Centre in Olsztyn, Department of Radiation Oncology, Olsztyn, Poland; 3 Medical University of Silesia, Department of Oncology and Radiotherapy, Katowice, Poland Background: Prostate cancer is one of the most common solid tumors in men worldwide. For patients with early-stage prostate cancer radical prostatectomy or radiotherapy is the standard approaches. Stereotactic body radiation therapy (SBRT) is a new radiotherapy method. The objective of the study was to report tumor control of prostate cancer patients treated with SBRT. Materials and Methods: A single institution prospective clinical study was done among previously untreated, histologically confirmed localized prostate cancer patients. The patients received 33.5 Gy in 5 fractions (SHARP regimen). The prostate-specific antigen (PSA) levels were obtained before treatment and every three months. Results: There were included 68 men to the analysis (age 55−83 years), Gleason score 3−8 (mean and median, 6). Pretreatment PSA level for all patients was 4−20 ng/mL (mean, 10.9 ng/mL; median, 10 ng/mL), a median PSA level for patients who did not receive androgen deprivation therapy was 7.53 ng/mL (mean, 8.55 ng/mL). All patients completed the treatment. The average and median follow-up was 39 months. No patients died during the observation period. Four years after the end of radiotherapy, the
Abstracts
2179 POSTER Use of diffusion weighted-MRI (DW-MRI) as a prognostic biomarker of survival and time to cystectomy in muscle invasive bladder cancer (MIBC) following organ conserving treatment S. Hafeez1 , M.D. Koh1 , A. Sohaib2 , R. Huddart1 . 1 The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Radiotherapy and Imaging, London, United Kingdom; 2 The Royal Marsden NHS Foundation Trust, Radiotherapy and Imaging, London, United Kingdom Background: Neo-adjuvant chemotherapy (nCT) has known survival benefit in the treatment of MIBC and identifies responders who may then benefit from radical radiotherapy. Conventionally response assessment is with cystoscopy. DW-MRI quantifies water molecule motion within tissue using the apparent diffusion coefficient (ADC). As an imaging biomarker it has been related to treatment response in solid tumours. Its use as a prognostic marker in bladder cancer remains novel. Method: 48 patients with confirmed MIBC suitable for nCT were recruited prospectively to an ethics approved protocol. DW-MRI was performed on a 1.5T system using b-values 0, 50, 100, 250, 500 and 750 s/mm2 prior to and on completion of nCT. Tumour was drawn on the 750 s/mm2 images and transferred onto the corresponding ADC map to record mean values. Absolute change in ADC (DADC) was calculated as the difference between post treatment and baseline ADC. Following final DW-MRI patients proceeded to cystoscopy + biopsy. ROC curve analysis was used to identify threshold (AUC >0.6, p < 005) predictive of response with the highest specificity. Significant AUC cut points were used to dichotomise the patient population to determine potential relationship with overall survival (OS) and time to cystectomy. Comparison between the curves was made with logrank test. Results: 38 patients achieved response following nCT and 10 patients had poor reposnse as assessed at cystoscopy + biopsy. Mean DADC of 0.18×10−3 mm2 /s was identified as predicting neo-adjuvant chemotherapy response with sensitivity/specificity/positive predictive value/negative predictive value of 71.1%/80.0%/93.1%/42.1% respectively. Mean %DADC of 18.0% was identified with sensitivity/specificity/positive predictive value/ negative predictive value of 57.9%/90.0%/95.7%/36.0%. After median follow-up of 31 months (95% CI 20−55 months), median OS and time to cystectomy was 25 months (95% CI 16.4–34.9) and 27 months (95% CI 20.2–59.4) respectively. Significant improvement in OS for patients receiving nCT was seen in those achieving mean DADCb100 >0.19×10×10−3 mm2 /s (HR 2.87, 95% CI 1.14–7.23; p = 0.015), mean %DADCb100 >18.1% (HR 4.90, 95% CI 1.10–6.52; p = 0.027). Significant improvement in time to cystectomy was seen in those achieving mean DADC >0.18×10×10−3 mm2 /s (HR 2.67, 95% CI 1.07– 6.61; p = 0.002). Conclusion: DW-MRI may provide prognostic information in bladder cancer but further validation is needed. No conflict of interest. 2180 POSTER Understanding prostate cancer biology using metabolomics and proteomics approaches: potentials in the improvement of the diagnosis, prognosis and identification of new therapeutic targets J. Felgueiras1 , J. Vieira Silva1 , A. Nunes1 , A. Patr´ıcio2 , S. Pelech3 , M. Fardilha1 . 1 University of Aveiro- 3810–193 Aveiro- Portugal, Department of Medical Sciences and Institute for Biomedicine − iBiMED, Aveiro, Portugal; 2 Hospital Infante D. Pedro E.P.E., Urology Service, Aveiro, Portugal; 3 Kinexus Bioinformatics Corporation, Department of Medicine- University of British Columbia, Vancouver, Canada Background: Prostate cancer (PCa) remains a major health problem in men worldwide. The treatment of the disease is still a challenge for Urologists, as well as the establishment of a clear prognosis, which is compromised by the lack of sensitivity and specificity of the currently available markers. Therefore, it is imperative to unravel PCa biology to enable the identification of key molecular events and molecules that aid PCa diagnosis, prognosis and the discovery of new therapeutic targets. In this study we aimed to identify metabolic and proteomic alterations that enable the distinction between prostate benign and malignant tissues. Materials and Methods: Biopsies from prostate tumours and adjacent benign tissue from the central zone of the gland were obtained from eight patients. Prostate specific antigen (PSA) blood levels, prostate carcinoma stage (TNM) and Gleason score were determined in all patients. Each sample was then divided and analysed using two approaches: infrared spectroscopy and an antibody microarray, which allowed the analysis of expression and phosphorylation state of 800 signalling proteins. The list of differentially expressed/regulated proteins between normal and tumour
Poster Session, Sunday 29 January 2017 conditions was then subjected to an extensive bioinformatics analysis to integrate all data and complement with already existing studies. Results: Principal component analysis of spectroscopic signals derived from PCa biopsies and adjacent benign tissues revealed different spectra for each condition. Dysregulations in lipid metabolism, lower amounts of polysaccharides and glycogen, as well as increased content of nucleic acids and protein phosphorylation were the most relevant alterations observed in PCa tissues. Moreover, 40 proteins were identified as differentially expressed between the two conditions and 13 proteins revealed alterations in their phosphorylation levels. The identification of known PCa-related proteins reinforce the fidelity of the screen. The analysis of protein-protein interaction networks and ontologies showed the disruption of cell singling events during prostate carcinogenesis. Conclusions: Metabolomics and proteomics approaches can provide vast information about carcinogenic processes. The integration of different ‘omics’ approaches are increasingly important when moving to a personalised medicine era, which requires the understanding of a disease as a whole system. Here, we show that applying two distinct approaches to the same set of samples it is possible to retrieve a lot of complementar information, increasing not only the knowledge on prostate carcinogenesis, but also allowing the identification of key molecular alterations that may aid an accurate diagnosis/prognosis or the development of new therapies. No conflict of interest. 2180A POSTER High-throughput mutational analysis of urothelial bladder carcinoma T. Nedjadi1 , A. Dallol2 , A. Al-Amari3 , A. Al-Sayyad4 , J. Al-Maghrabi5 . 1 King Abdullah International Medical Research Center, King Abdulaziz Medical City, Jeddah, Saudi Arabia; 2 Center of Innovation in Personalized Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 3 King Faisal Specialist Hospital, Urology, Jeddah, Saudi Arabia; 4 King Abdulaziz University, Urology, Jeddah, Saudi Arabia; 5 King Abdulaziz University, Pathology, Jeddah, Saudi Arabia Background: Bladder cancer (BC) is a devastating disease characterized by high recurrence rates and elevated progression rate to invasive phenotype. Recent data indicates that BC heterogeneity may contribute to cancer progression and to false-positive biomarker identification. This heterogeneity is mirrored in the genomic features of BC. Typically, identifying genetic aberrations, especially mutational hotspots, will inevitably contribute in biomarkers discovery and influence future therapeutic intervention. Methods: formalin-fixed paraffin-embedded tissues (FFPE) from 96 patients with urothelial bladder cancer were included in the study. Highthroughput mutational analysis was performed using Cancer Hotspots Panel (CHP) v2 on the Ion Torrent™ platform. Kaplan–Meier curve was used to evaluate the relationship between genes mutations and cancerspecific survival; p values were calculated using the log rank test. Results: Our data indicated that BC patients harbour frequent mutations in TP53 (84%), PIK3CA (55%), KDR (40%), FGFR3 (39%), KIT (22%), APC (19%), PTEN (19%), CDKN2A (14%), ATM (12%) and SKP2 (11%). Lower frequency mutations have also been reported for the rest of the gene panel. Interestingly, only FGFR3 mutations were significantly associated with poor disease-specific survival (p = 0.018). Conclusion: The current study was able to validate known mutations in bladder cancer and to identify other genes that are mutated at high frequency in BC patients from the Kingdom of Saudi Arabia. In addition, other, novel mutations were also identified that may prove clinically useful following validation. No conflict of interest. 2184 POSTER Prognostic impact of nodal relapse in definitive prostate-only irradiation M. Loi1 , B. Detti1 , G. Simontacchi1 , I. Desideri1 , P. Bonomo1 , D. Greto1 , M. Mangoni1 , I. Meattini1 , C. Becherini1 , C. Muntoni1 , L. Trombetta1 , L. Livi1 . 1 Universita degli Studi di Firenze, Radiation Therapy Department, Firenze, Italy Background: Nodal pelvic irradiation (WPI) in prostate cancer patients has been extensively investigated with the aim of preventing metastatic spread of cancer cells through lymphatic drainages in prostate cancer patients eligible for definitive radiotherapy (RT); on the other hand, due to uncertain clinical benefit and increased toxicity, its use has substantially declined in the last decades in favour of prostate-only irradiation (PI). The aim of our study is to assess the predictive features and patterns of nodal relapse, and their impact on outcome, in localized prostate cancer patients treated by definitive PI with or without neoadjuvant/adjuvant androgen deprivation therapy (ADT).
Poster Session, Sunday 29 January 2017 Material and Methods: Data from 207 consecutive patients treated at our Institution from 2006 to 2011 were examined. Clinical (age, stage, grade, risk class according to D’Amico and Roach equation) and treatmentrelated (ADT, RT dose, PSA nadir following PI) variables were collected. Biochemical Relapse-Free Survival (BRFS), Pelvic Nodal RecurrenceFree Survival (NRFS), Distant Metastasis-Free Survival (DMFS), Disease Specific Survival (DSS) and Overall survival (OS) were calculated by Kaplan Meyer method. Univariate and multivariate analysis of prognostic variables was performed respectively by log-rank test and Cox model. Results: Patients were stratified in low (45, 21.7%), intermediate (39, 18.8%) and high risk group (123, 59.5%) according to D’Amico criteria; median age was 73 (56−83) years. All patients received PI delivering a median dose of 80 Gy (74−80 Gy). Monthly ADT was administrated to 131 (63.3%) patients, for a median duration of 12 (2−36) months. Median follow-up was 70.9 (27.4–115.8) months; 5-years BRFS, NRFS, DMFS, DSS and OS were respectively 88.9%, 98.5%, 95.2%, 95.2% and 93.7%. On multivariate analysis, independent negative predictors of BRFS were Gleason Score (GS) 7 (HR: 3.09) and PSA nadir >0.08 (HR: 5.08). DMFS and DSS were unfavorably correlated with GS 7 (HR 6.56 and 12.3, respectively). No predictive factor was identified for OS. NRFS was not associated with any clinical variable, while occurrence of nodal relapse was not correlated to impaired outcome. Conclusions: Tumor biology (GS 7) and biological response to treatment (PSA nadir >0.08) are independent predictors of biochemical failure, while metastatic relapse and disease-related mortality are correlated only with GS at diagnosis. Isolated pelvic nodal relapse seldom occurred in our cohort treated by PI independently from risk group and did not correlate with impaired outcome, suggesting the lack of theoretical benefit of a prophylactic nodal irradiation: this finding raise the interest for locoregional treatment like stereotactic body radiation therapy in the event of nodal recurrence. No conflict of interest.
2185 POSTER The impact of hormone therapy on setup errors during external beam radiation therapy for prostate cancer C. Onal1 , Y. Dolek1 , Y. Ozdemir1 . 1 Baskent University, Dept. of Radiation Oncology, ADANA, Turkey Background: To determine if setup errors during external beam radiation therapy (RT) for prostate cancer are influenced by the combination of androgen deprivation treatment (ADT) and RT. Materials and Methods: We retrospectively analyzed data from 175 patients treated for prostate cancer [concurrent ADT plus RT, 33 patients (19%); neoadjuvant and concurrent ADT plus RT, 91 patients (52%); RT only, 51 patients (29%)]. Required couch shifts without rotations were recorded for each CBCT, and corresponding alignment shifts were recorded as left-right (x), superior-inferior (y), and anterior-posterior (z). The nonparametric Mann–Whitney test was used to compare shifts by group. Pearson correlation coefficient was used to measure correlation in couch shifts between groups. Prostate shift means and standard deviations were calculated and pooled to obtain mean or group systematic error (M), standard deviation of systematic error (S), and SD of random error (s). Results: From 175 patients included in this study, a total of 2330 CBCT images were retrospectively evaluated. The median number of CBCT studies analyzed per patient was 15 (range: 8−19). The median duration of neoadjuvant ADT delivered before RT was 3.2 months (range: 2.8−4.1 months). The magnitude of the prostate shifts in the x-direction measured in the first five days was significantly larger in the NC group compared to the N (p = 0.001) and C (p = 0.03) groups. No significant differences were observed in prostate shifts in any direction for all groups. Shifts on CBCT were all less than setup margins. The prostate volumes in the NC, C, and N groups were 31.6±16.1 cc, 47.0±23.2 cc, and 46.1±23.2 cc, respectively. The prostate volumes measured on planning CT were significantly smaller in the NC group compared to the C group (p = 0.003) and the N group (p < 0001). Prostate shifts in the x- and y-directions were not significantly correlated with prostate volume (r = 0.04, p = 0.7 for x-direction; r = 0.03, p = 0.7 for y-direction). A significant positive correlation was observed between prostate volume and average prostate shift in the z-direction (r = 0.19, p = 0.04). Although patients receiving neoadjuvant ADT before RT had significantly smaller prostates, the use of neoadjuvant ADT had no significant impact on prostate shifts in the x-, y-, and z-directions. Significant positive correlation was observed between prostate volume and z-direction prostate shift (r = 0.19, p = 0.04), regardless of ADT group, but not between volume and x- or y-direction shifts (r = 0.04, p = 0.7; r = 0.03, p = 0.7). Random and systematic errors for all patient cohorts and ADT groups were similar.
Abstracts
S193
Conclusion: Hormone therapy given concurrently with RT was not found to significantly impact setup errors. Prostate volume was significantly correlated with shifts in the anterior-posterior direction only. No conflict of interest. 2186 POSTER Predictive factors of late-onset rectal mucosal changes after radiotherapy of prostate cancer E. Ippolito1 , R. Frakulli2 , G. Macchia3 , F. Deodato3 , A. Guido2 , L. Giaccherini2 , A. Farioli4 , A. Arcelli2 , D. Cuicchi4 , L. Frazzoni4 , S. Cilla5 , M. Buwenge2 , G. Mantini6 , A.R. Alitto6 , M. Nuzzo3 , V. Valentini6 , M. Ingrosso7 , A.G. Morganti2 , L. Fuccio4 . 1 Campus Bio-Medico University, Radiotherapy Department, Rome, Italy; 2 S. Orsola-Malpighi Hospital-University of Bologna, Radiation Oncology Unit- Department of Experimental- Diagnostic and Specialty Medicine − DIMES, Bologna, Italy; 3 Fondazione di Ricerca e Cura “Giovanni Paolo II”, Radiation Oncology Unit, Campobasso, Italy; 4 S. Orsola-Malpighi Hospital-University of Bologna, Department of Medical and Surgical Sciences DIMEC, Bologna, Italy; 5 Fondazione di Ricerca e Cura “Giovanni Paolo II”, Medical Physic Unit, Campobasso, Italy; 6 Policlinico Universitario “A. Gemelli”- Universita` Cattolica del Sacro Cuore, Radiation Oncology Department, Rome, Italy; 7 Fondazione di Ricerca e Cura “Giovanni Paolo II”, Endoscopy Unit, Campobasso, Italy Background: Vienna rectoscopy score (VRS) assessed one year after radiotherapy is a surrogate end-point of late rectal toxicity. The aim of this study was to investigate the association between treatment-related factors and 1-year VRS. Material and Methods: We performed a retrospective analysis of prospectively collected data. Patients with prostate adenocarcinoma treated with curative or adjuvant radiotherapy (RT) underwent endoscopy one year after RT. Correlations between VRS 2 and treatment parameters were investigated by univariate and multivariate logistic analyses. Results: One hundred-ninety patients (mean age: 69; range:43−81) were considered eligible for the study. At the univariate analysis, patients treated with hypofractionation, radiosurgery boost and an EQD2 dose (a/b 3) >75 Gy had a significantly higher incidence of VRS >2 (p 0.001) after 1-year of follow-up. At the multivariate analysis, radiosurgery boost was an independent risk factor of developing rectal mucosal lesions (VRS 2), yielding an OR of 4.14 (95% CI 1.2–13.8), while pelvic surgery was inversely associated with VRS >2 (OR: 0.39; 95% CI: 0.17–0.94). Conclusions: Hypofractionation followed byradiosurgery boost significantly increased the risk of developing late-onset rectal mucosal changes. Therefore, special care and preventive treatment strategies are needed when using this boost technique after hypofractionated RT. No conflict of interest. 2187 POSTER SHARP hypofractionated stereotactic radiotherapy is low and intermediate-risk prostate carcinoma patients − PSA outcome M. Rucinska1 , K. Osowiecka2 , S. Nawrocki3 . 1 University of Warmia and Mazury in Olsztyn, Department of Oncology and Department of Radiation Oncology of Independent Public Health Care Facility of the Ministry of the Interior with Warmia and Mazury Oncology Centre in Olsztyn, Olsztyn, Poland; 2 Independent Public Health Care Facility of the Ministry of the Interior with Warmia and Mazury Oncology Centre in Olsztyn, Department of Radiation Oncology, Olsztyn, Poland; 3 Medical University of Silesia, Department of Oncology and Radiotherapy, Katowice, Poland Background: Prostate cancer is one of the most common solid tumors in men worldwide. For patients with early-stage prostate cancer radical prostatectomy or radiotherapy is the standard approaches. Stereotactic body radiation therapy (SBRT) is a new radiotherapy method. The objective of the study was to report tumor control of prostate cancer patients treated with SBRT. Materials and Methods: A single institution prospective clinical study was done among previously untreated, histologically confirmed localized prostate cancer patients. The patients received 33.5 Gy in 5 fractions (SHARP regimen). The prostate-specific antigen (PSA) levels were obtained before treatment and every three months. Results: There were included 68 men to the analysis (age 55−83 years), Gleason score 3−8 (mean and median, 6). Pretreatment PSA level for all patients was 4−20 ng/mL (mean, 10.9 ng/mL; median, 10 ng/mL), a median PSA level for patients who did not receive androgen deprivation therapy was 7.53 ng/mL (mean, 8.55 ng/mL). All patients completed the treatment. The average and median follow-up was 39 months. No patients died during the observation period. Four years after the end of radiotherapy, the