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Genitüriner Sistem Tümörleri

This study compares the effectiveness of different treatment options in salvage prostate radiotherapy, specifically short-term androgen deprivation therapy (STAD) alone or with pelvic lymph node treatment (PLNRT). It explores the impact of these treatments on prostate-specific antigen (PSA) levels and relapse rates, as well as their potential to reduce metastasis and improve overall survival. The findings of the NRG Oncology/RTOG 0534 SPPORT trial will be presented.

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Genitüriner Sistem Tümörleri

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  1. Genitüriner Sistem Tümörleri Dr. Cem Önal Başkent Üniversitesi Tıp Fakültesi Adana Dr Turgut Noyan Uygulama ve Araştırma Merkezi Radyasyon Onkolojisi AD

  2. ASTRO 2018 – Genitourinary Cancer Salvage prostat RT’ sinde hangi tedavi seçeneği daha iyi? Short Term Androgen Deprivation Therapy Without or With Pelvic Lymph Node Treatment Added to Prostate Bed Only Salvage Radiotherapy: The NRG Oncology/RTOG 0534 SPPORT Trial

  3. Short Term Androgen Deprivation Therapy Without or With Pelvic Lymph Node Treatment Added to Prostate Bed Only Salvage Radiotherapy: The NRG Oncology/RTOG 0534 SPPORT Trial A Pollack, TG Karrison, AG Balogh, D Low, DW Bruner, JS Wefel, LG Gomella, E Vigneault, JM Michalski, S Angyalfi, H Lukka, SL Faria, G Rodrigues, MC Beauchemin, SA Seaward, AM Allen, DC Monitto, W Seiferheld, and HM Sandler ASTRO 2018

  4. Background Salvage prostat yatağı RT sonrası (PBRT) BF  %30-40/5 -10 yıl Kısa süreli neoadj + eş zamanlı ADT (STAD) definitif RT’de etkili  kurtarma PBRT ?? Pelvik lenfatik RT (PLNRT) etkinliği faz III çalışmada henüz gösterilemiş.

  5. Hipotez Prostatektomi sonrası PSA artışında PBRT’ye STAD PLNRT + STAD relapsı azaltmaya etkisi var mı? 1734 hasta

  6. NRG/RTOG 0534/SPPORT Trial Design A Phase III Trial of Short Term Androgen Deprivation with Pelvic Lymph Node or Prostate Bed Only Radiotherapy (SPPORT) in Prostate Cancer Patients with a Rising PSA after Radical Prostatectomy

  7. Primer sonlanım = FFP Herhangi birinin görülmesi PSA ≥ Nadir+2 ng/mL Klinik progresyon Lokal, rejyonel, ve uzak metastaz Ölüm (herhangi bir sebep)

  8. Radiotherapy Median prostate bed dose of 68 Gy

  9. Patient Characteristics: SVI Median Age=64y; Caucasian 83%; Non-Hispanic 91%

  10. Patient Characteristics: pStage Median Age 64 yr; Caucasian 83%; Non-Hispanic 91%

  11. Patient Characteristics: Margins Median Age=64y; Caucasian 83%; Non-Hispanic 91%

  12. Patient Characteristics: GLSC ~68% GLSC 7

  13. Patient Characteristics: Nodes

  14. Patient Characteristics: PSA

  15. FFP for First 1191 Eligible Patients -  Interim Analysis Population Minimum potential FU 5 yr; Median FU 6.4 yr 5 yr Rate Comparison Arm 3 vs Arm 1: p<0.0001 Arm 2 vs Arm 1: p=0.0001 Arm 3 vs Arm 2: p=0.0063 Arm 3 Arm 2 Arm 1 DMC Recommendation Report findings for all three arms Arm & 5 yr Rate Arm 1: PBRT Alone; 71% Arm 2: PBRT + STAD; 83% Arm 3: PLNRT+PBRT+STAD; 89%

  16. FFP: All Eligible Patients Arm 3 5 yr Rate Comparison Arm 3 vs Arm 1: p<0.0001 Arm 2 vs Arm 1: p<0.0001 Arm 3 vs Arm 2: p=0.0039 Arm 2 Arm 1 HRs and 97.5% CIs 3 vs 1: 0.45 (0.34-0.61) 2 vs 1: 0.62 (0.47-0.82) 3 vs 2: 0.71 (0.52-0.98) Arm & 5 yr Rate Arm 1: PBRT Alone; 71% Arm 2: PBRT + STAD; 81% Arm 3: PLNRT+PBRT+STAD; 87%

  17. FFP: Pre-RT PSA <0.34 (Median) 3&2 • 5 yr Rate Comparison • Arm 3 vs Arm 1: p=0.0001 • Arm 2 vs Arm 1: p=0.0002 • Arm 3 vs Arm 2: p=0.49 1 PSA <0.34 de ADT’ye pelvik RT eklenmesinin katkısı yok HRs and 97.5% CIs 3 vs 1: 0.51 (0.32-0.81) 2 vs 1: 0.54 (0.33-0.87) 3 vs 2: 0.93 (0.55-1.60) Arm 1: PBRT Alone Arm 2: PBRT + STAD Arm 3: PLNRT+PBRT+STAD

  18. FFP: Pre-RT PSA ≥0.34 Arm 3 Arm 3 • 5 yr Rate Comparison • Arm 3 vs Arm 1: p<0.0001 • Arm 2 vs Arm 1: p=0.0029 • Arm 3 vs Arm 2: p=0.0017 Arm 2 Arm 2 PSA >0.34 de ADT’ye pelvik RT etkili!!! Arm 1 Arm 1 HRs and 97.5% CIs 3 vs 1: 0.40 (0.27-0.59) 2 vs 1: 0.61 (0.44-0.86) 3 vs 2: 0.65 (0.44-0.97) Arm 1: PBRT Alone Arm 2: PBRT + STAD Arm 3: PLNRT+PBRT+STAD

  19. Freedom from Distant Metastasis: All Eligible Pts No statistically significant differences in OS 3 • 5 yr Rate Comparison • Arm 3 vs Arm 1: p=0.014 • Arm 2 vs Arm 1: p=0.05 • Arm 3 vs Arm 2: p=0.28 1 & 2 Metastasis seen in 108 Pts HRs and 97.5% CIs 3 vs 1: 0.52 (0.30-0.92) 2 vs 1: 0.81 (0.49-1.33) 3 vs 2: 0.64 (0.36-1.14) Arm and 5 year Rate Arm 1: PBRT Alone; 91.7% Arm 2: PBRT + STAD; 94.4% Arm 3: PLNRT+PBRT+STAD; 95.2%

  20. Özet FFP etkiler PLNRT+ PBRT+STAD > PBRT PBRT+STAD>PBRT PLNRT+PBRT+STAD>PBRT FFP nadir+2 progresyon ile ilişkili Uzak metastaz süresi daha erken  takip devam ediyor Özellikle akut toksisitelerde farklılık var Tek başına PBRT yeterli değil

  21. Özet Pelvik lenfatik RT’nin etkinliği gösteren en güçlü level I kanıt Uzak metatsaz etkinliği?  izlem devam ediyor PSA cut-off ?? Hangi PSA değerinden sonra PLNRT gerekli PLRT kararında PET’in yeri? Role of PET in PLNRT decisions? Definitif RT de PLNRT’nin etkinliği  NRG 0924

  22. Hangi hastaya hangi tedavi yapılmalı?? • PSA cut-off değeri • Evrelere göre tedavi • Hastaların büyük kısmı lokal ileri evre değil • SVI  %14.8, pT2  %54.3, GS≤7  %68, PSA ≤0.5%79.3 • Bu hasta grubunda pelvik nodal ışınlama ve ADT gerekli mi? • Uzak metastaz  gruplar arasında fark yok • Yüksek riskli prostat kanserinde STAD yeterli mi?

  23. ASTRO 2018 – Genitourinary Cancer İntermdiate risk prostat kanserinde ERT+BRT tek başına BRT’ye göre hasta konforunu etkiliyor mu? Patient Reported Outcomes of NRG Oncology/RTOG 0232: A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy with Brachytherapy Alone in Intermediate Risk Prostate Cancer

  24. Patient Reported Outcomes of NRG Oncology/RTOG 0232: A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy with Brachytherapy Alone in Intermediate Risk Prostate Cancer Deborah W. Bruner, RN, PhD, FAAN 1, Jennifer Moughan, MS 2, Bradley R. Prestidge, MD, MS 3, Martin G. Sanda, MD 1, William Bice, PhD 4, Jeff Michalski, MD 5, Geoffrey Ibbott, PhD 6, Mahul Amin, MD 7, Charles Catton, MD 8, ViroonDonavanik, MD, FACR 9, Hiram Gay, MD 5, David Brachman, MD 10, Steven J. Frank, MD 6, Patrick D. Maguire, MD 11, Seth A. Rosenthal, MD 12, Ursula Matulonis, MD 13, Amir Sadeghi, PhD 14, Kathryn A. Winter, MS 2, Howard M. Sandler, MD, MS 15 1 Emory University/Winship Cancer Center; 2 NRG Oncology Statistics and Data Management Center; 3Bons Secours Cancer Institute 4 John Muir Health; 5 Washington University – Siteman Cancer Center; 6 University of Texas MD Anderson Cancer Center; 7 University of Tennessee Health Science Center; 8 University Health Network - Princess Margaret Hospital; 9 Christiana Care Health Services, Inc. CCOP; 10 Arizona Oncology Services Foundation; 11 New Hanover Regional Medical Center/Zimmer Cancer Center; 12 Sutter Cancer Research Consortium; 13 Dana-Farber/Cancer Care LAPS; 14 Banner MD Anderson Cancer Center; 15 Cedars-Sinai Medical Center

  25. Study Objectives • ERT + perineal BRT veya tek başına BRT ile tedavi edilen intermediate-risk prostat kanserli hastalarda ‘health related quality of life’(HRQoL) karşılaştırılması • Toksisite • Cinsel fonksiyon • Maliyet

  26. RTOG 0232: Study Schema

  27. Eligibility Criteria • Histologically confirmed prostate adenocarcinoma, stages T1c-T2b (AJCC 6th Edition) • Zubrod Performance Scale 0-1 • One of the following combinations of factors: • Gleason score 2-6, and prostate-specific antigen ≥10 but < 20 • Gleason score 7, and prostate-specific antigen < 10 • Prostate volume < 60 cc • No prior ADT (beginning < 2 months or > 6 months prior to registration) • International Prostate Symptom Score (IPSS) < 16 • No distant metastases (M0) or clinically or radiographically suspicious nodes

  28. Primary Results Freedom From Progression Overall Survival İntermediate risk prostat kanserli hastalarda ERT + transperineal BRT tek başına transperineal BRT ye göre üstün değildir

  29. Expanded Prostate Index Composite (EPIC) • Likert scale ile ölçülüyor • 0 – 100 arası değerler • Yükseh değer daha iyi • EPIC 4 kısımdan oluşuyor: • barsak • üriner (inkontinans veirritative/obstructive) • seksüel • hormonal • Her kısımın en az %80’i doldurulmuş olmalı • Baseline, 4, 12, 24, 36, 48, ve 60. ay

  30. EPIC Question Framing Frequency/Function: Over the past 4 weeks, how often have you leaked urine? Bother: How big a problem, if any, has each of the following been for you during the last 4 weeks?

  31. EPIC Items

  32. RTOG 0232 Accrual Summary • 530/579 (92%) eligible pts on study had baseline EPIC: • 255 (89%) on EBRT + PB arm • 275 (94%) on PB arm *Not completed or not received

  33. Baseline and 24 Month EPIC Scores by Treatment Arm

  34. PRO RESULTS Δ = 4 month EPIC Scores - Baseline EPIC Scores -Δ change score indicates a decline in HRQOL at 4 mos

  35. PRO RESULTS Δ = 24 month EPIC Scores - Baseline EPIC Scores -Δ change score indicates a decline in HRQOL at 24 mos

  36. Adverse Events 55% vs. 39%; p=0.0001 28% vs. 26%; p=0.73 13% vs. 7%; p=0.03 8% vs. 8%; p=0.82 Acute: toxicities ≤ 180 days from RT start [CTC v2.0 ] Late: toxicities > 180 days from RT start [RTOG/EORTC Late RT Morbidity Scoring Scheme]

  37. Sonuç • ERT+PBRT ile tedavi edilen hastalarda üriner, barsak ve seksüel HRQoL skorları tek başına PBRT ile tedavi edilenlere göre daha düşük bulunmuştur. • ERT+PBRT’nin PBRT’ye göre PFS avantajının olmaması, PBRT sonrası HRQoL ve toksisite oranlarının daha düşük olması nedeniyle, intermediate-risk prostat kanserinde PBRT tercih edilebilir bir tedavi seçeneği olarak kabul edilmektedir.

  38. ‘Patient reported outcome’ sonuçları  Güvenilirliği?? • Intermediate-risk prostat kanserinde ERT sonrası BRT boost gereklilirliği tartışmalı • Raporlanan akut toksisite sonuçlarında istatistiksel fark yok, ancak PRO’da ERT+BRT kolunda akut dönemde üriner sistem EPIC skoru daha yüksek ???

  39. ASTRO 2018 – Genitourinary Cancer Prostat kanserinde ırksal androjen reseptör aktivitesi ve radyosensitivite farkı var mı? Androgen receptor activity and radiotherapeutic sensitivity in African-American men with prostate cancer: A large scale gene expression analysis and meta-analysis of RTOG trials

  40. Androgen receptor activity and radiotherapeutic sensitivity in African-American men with prostate cancer: A large scale gene expression analysis and meta-analysis of RTOG trials Daniel Spratt, MD Associate Professor Vice Chair, Research Department of Radiation Oncology University of Michigan DE Spratt, RT Dess, HE Hartman, BA Mahal, WC Jackson, M Alshalalfa, N Fishbane, ZS Zumsteg, WU Shipley, TM Pisansky, M Roach III, SG Zhao, C Speers, E Davicioni, M Schipper, PL Nguyen, EM Schaeffer, FY Feng, HM Sandler

  41. Prostate Cancer Disparities New cases (per 100,000) Prostate cancer deaths (per 100,000) 1.7 fold more likely to be diagnosed with prostate cancer 2.2 fold more likely to die from prostate cancer Resulted in the perception that black race is an independent prognostic factor associated with worse prostate cancer outcomes https://seer.cancer.gov/

  42. Non-biological factors (proven drivers) Drivers of Prostate Cancer Disparities: Black Death from Prostate Cancer White Access Screening Insurance Time Adjust for non-biological factors Death from Prostate Cancer Primary Care Nutrition @DrSpratticus Time

  43. Non-biological factors (proven drivers) Biologic factors (potential drivers) Drivers of Prostate Cancer Disparities: Access Screening Insurance Genetics Primary Care Nutrition

  44. Hipotez: Zenci ve beyazlar arasındaki biyolojik değişiklikler prostat kanseri etkinliğini etkilebilir @DrSpratticus

  45. Methods Prospective GRID Sample size 17,003 Total 1,953 Black Prostatectomy Tissue sample FFPE Tissue type 44,000 Number of genes captured @DrSpratticus

  46. Bulgular • Zencilerde daha fazla düşük AR-aktif tümörler görülmüş • Gen ekpresyon mekanizmaları daha farklı • Zencilerde DNA tamir mekanizmaları daha az • Zencilerin tümörleri daha radyosensitif

  47. Together, this data suggests that black men may have improved outcomes compared to white men when treated with radiotherapy. @DrSpratticus

  48. How Do You Validate this Clinically? Perform a randomized trial Can’t randomize one’s race 1. 2. Assess in RCTs comparing surgery to radiation and determine if an interaction of race and treatment modality exist Unlikely to be possible -ProtecT enrolled <1% black men (<5 black men per arm) @DrSpratticus Perform analyses in radiotherapy RCTs the outcomes by race 3.

  49. Methods Sample size Total 5,854 Black 1,129 (19%) 92-02, 94-08 94-13, 99-10 Trials Included Black White Risk Group 11% 12% Low 45% 39% Intermediate 44% 49% High @DrSpratticus

  50. Black Men Have SignificantlyLowerBiochemical Recurrence Biochemical Recurrence Probability HR 0.81 (0.73, 0.90) P = 0.0002 @DrSpratticus

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