radiotherapy-pancreatic cancer
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This document discusses pancreatic cancer and its treatment. It begins by stating that pancreatic cancer is most commonly diagnosed as locally advanced or metastatic. It then discusses the role of surgery, chemotherapy, and radiation therapy in the treatment of pancreatic cancer. It notes that the majority of surgically treated patients will have a recurrence, with a median survival of 15-20 months. The value of adjuvant and neoadjuvant therapy is debated. The document summarizes several clinical trials investigating chemotherapy and chemoradiation as adjuvant treatment after surgery. It also discusses neoadjuvant therapy and its potential advantages over adjuvant therapy. Emerging strategies discussed include induction chemotherapy followed by localized chemoradiation or second line therapy. The document concludes by describing modern radiation
![(Staley’s Ταξινόμηση, 1996) [1]
Εντοπισμένος/Εξαιρέσιμος 15--20 μήνες 5-20%
Τοπικά Προχωρημένος 6-10 μήνες 0%
Μεταστατικός 3-6 μήνες 0%
] Staley CA, et al. Pancreas 1996; 12:373-80.
5-ετης (%)Μέση Επιβίωση](https://image.slidesharecdn.com/teliko-141114154628-conversion-gate02/85/radiotherapy-pancreatic-cancer-8-320.jpg)
radiotherapy-pancreatic cancer
- 1. ΞΕΝΟΦΩΝ ΒΑΚΑΛΗΣ ΑΚΤΙΝΟΘΕΡΑΠΕΥΤΗΣ – ΟΓΚΟΛΟΓΟΣ ΙΑΤΡΙΚΟ ΚΕΝΤΡΟ ΑΘΗΝΩΝ ΚΑΡΚΙΝΟΣ ΠΑΓΚΡΕΑΤΟΣ Η θέση του Ακτινοθεραπευτή Ογκολόγου
- 2. Δηλώνω ότι δεν έχω (προσωπικά ή ως μέλος εργασιακής/ερευνητικής ομάδας) ή μέλος της οικογένειάς μου οποιοδήποτε οικονομικό ή άλλου είδους όφελος από τις εταιρείες/επιχειρήσεις που διοργανώνουν /χρηματοδοτούν την άνω εκδήλωση
- 3. Five-year Relative Survival (%)* during Three Time Periods By Cancer Site *5-year relative survival rates based on follow up of patients through 2003. †Recent changes in classification of ovarian cancer have affected 1996-2002 survival rates. Source: Surveillance, Epidemiology, and End Results Program, 1975-2003, Division of Cancer Control and Population Sciences, National Cancer Institute, 2006. Site 1975-1977 1984-1986 1996-2002 •All sites 50 53 66 •Breast (female) 75 79 89 •Colon 51 59 65 •Leukemia 35 42 49 •Lung and bronchus 13 13 16 •Melanoma 82 86 92 •Non-Hodgkin lymphoma 48 53 63 •Ovary 37 40 45 •Pancreas 2 3 5 •Prostate 69 76 100 •Rectum 49 57 66 •Urinary bladder 73 78 82 †
- 7. ΚΑΡΚΙΝΟΣ ΠΑΓΚΡΕΑΤΟΣ • Έκταση της νόσου κατά τη διάγνωση: – ΕΞΑΙΡΕΣΙΜΟΣ 20% – ΤΟΠΙΚΑ ΠΡΟΧΩΡΗΜΕΝΟΣ ΑΝΕΓΧΕΙΡΗΤΟΣ 40% – ΜΕΤΑΣΤΑΤΙΚΟΣ 40%
- 8. (Staley’s Ταξινόμηση, 1996) [1] Εντοπισμένος/Εξαιρέσιμος 15--20 μήνες 5-20% Τοπικά Προχωρημένος 6-10 μήνες 0% Μεταστατικός 3-6 μήνες 0% ] Staley CA, et al. Pancreas 1996; 12:373-80. 5-ετης (%)Μέση Επιβίωση
- 10. ΚΑΡΚΙΝΟΣ ΠΑΓΚΡΕΑΤΟΣ ΘΕΡΑΠΕΙΑ • η πλειοψηφία αυτών που υποβάλλονται σε χειρουργική εξαίρεση υποτροπιάζουν, μέση επιβίωση : 15-20 μήνες) - 2% ιώνται με την εγχείρηση • η αξία της μετεγχειρητικής (“adjuvant”) ή προεγχειρητικής (“neoadjuvant”) θεραπείας αποτελεί θέμα αμφισβήτησης.
- 11. Patterns of Failure after Surgery After surgery • local relapse rate of 50 – 86% and •distant recurrence rate of 40 – 90%
- 12. Select between Observation Chemotherapy Chemoradiation Radiotherapy Anything else to improve the patient’s outcome? 15 $1 MILLION 14 $500.000 13 $250.000 12 $100.000 11 $50.000 10 $25.000 9 $16.000 8 $8.000 7 $4.000 6 $2.000 5 $1.000 4 $500 3 $300 2 $200 1 $100
- 13. Study (Year) Number of Patients Enrolled Patients with R1 Resection (%) Treatment Assignment Median Survival Months Treatment Assignment Median Survival Months p value GITSG (1985) 49 0 5-FU-based Chemoradiation 21.0 Observation 10.9 0.035 EORTC 40891 (1999) 114* 21 5-FU-based Chemoradiation 17.1 Observation 12.6 0.09 ESPAC-1 (2004) 289 18 5-FU/Leucovorin Chemotherapy 20.1 No Chemotherapy 15.5 0.009 5-FU-based Chemoradiation 15.9 No Chemoradiation 17.9 0.05 RTOG 9704 (2006) 388 (Head lesions) 34 Unknown in 25% Gemcitabine then 5-FU/EBRT then Gemcitabine 20.5 5-FU then 5-FU/EBRT then 5-FU 16.9 0.09 CONKO 001 (2007) 368 19 Gemcitabine 22.8 Observation 20.2 0.005 DFS = 13.4 DFS = 6.9 < 0.001 Randomized Trials of Adjuvant Therapy
- 14. Entry Criteria Quality Assurance of Radiation Therapy Performed RTOG 9704 / US Intergroup Phase III Postop Adjuvant Study *First Phase III Adjuvant Pancreas Trial to Do So
- 15. trial RTOG 97-04 – RT QA
- 16. EORTC-40013-22012/FFCD-9203/GERCOR phase II study Καλύτερη η ΧΗΜΕΙΟ ή ΧΗΜΕΙΟΑΚΤΙΝΟΘΕΡΑΠΕΙΑ;
- 18. Post-operative 5-FU-based Chemoradiation (CXRT) for resected pancreatic cancer non-randomized trials Institution Time Period # Patients Median survival CXRT Median survival No CXRT P- value Mayo Clinic 1975- 2005 466 (R0) 25.2 Mo 19.2 Mo 0.001 Johns Hopkins Hospital 1993- 2005 616 (R0 + R1) 21.4 Mo 14.4 Mo <0.001 Herman JM et al. JCO, 2008 Corsini MM et al. JCO, 2008
- 20. Resected Pancreas Cancer N= 952 Gemcitabine + Erlotinib x 4 Ongoing trial phase III - Adjuvant therapy US Intergroup/RTOG 0848 Gemcitabine x 4 cycles Stratification ₋ R0 vs R1 resection; T stage; N(+) vs N(-) Primary Endpoint: Overall Survival +/- Erlotinib, +/- RT Secondary Endpoints: DFS +/- Erlotinib, +/- RT, toxicity Tissue acquistion/ correlative science R A N D O M I Z E 2nd Randomization +/- ChemoRT
- 22. RTOG contouring guidelines for adjuvant RT for pancreas CTV must include:
- 24. Author - Country Number of Patients Margin + Resection Rate Median Survival Independent Prognostic Factor Winter-U.S. 1175 42% 14 m Yes Richter-Germany 194 37% 12 m Yes Kuhlmann- Netherlands 160 50% NS Yes Takai-Japan 89 47% 8 m Yes Margin + Resections are Frequent and Associated with Poor Prognosis
- 25. Accurate Pathology and Multimodality Therapy Pancreaticoduodenectomy: Ductal Adenocarcinoma M D Anderson (N = 360) Variable No. Pts Med Sur p value Overall 360 25 N0 174 32 .002 N1 186 22 R0 300 28 .03 R1 60 22 Maj Comp No 263 27 .01 Yes 93 22 R0 17 mo R1 11 mo ESPAC-1 Ann Surg 2001 Raut, Ann Surg 2007;246:52-60 Local Failure (All pts): 8%
- 26. Preoperative Therapy R1 Resection YES 13% NO 19% The Importance of Neoadjuvant Therapy Pancreaticoduodenectomy: Ductal Adenocarcinoma M D Anderson (N = 360) Raut, Ann Surg 2007;246:52-60 Local Failure (All pts): 8%
- 27. ΠΛΕΟΝΕΚΤΗΜΑΤΑ NEOADJUVANT • Μικρότερος χρόνος θεραπείας (62 vs. 99 ημ)-υπερκλ • Αυξημένη ακτινοευαισθησία-καλύτερη οξυγόνωση • Δεν αναβάλλεται ή δεν καθυστερεί η προγρ. Θεραπεία • Χαμηλότερο ποσοστό + ορίων εκτομής – υποσταδιοπ. • Αποφυγή εγχείρησης σε ασθ. με επιθετική νόσο (26%) • Μείωση περιτοναϊκών εμφυτεύσεων • Λιγότερες παρενέργειες V adjuvant Spitz et al, 1977 Hoffman et al, ECOG study, 1988 Pisters et al, 1998
- 28. Neoadjuvant therapy • No randomized studies comparing to adjuvant • Small, Phase II, mostly single instituiton • 5-fu and Gemcitabine chemoradiation have been studied • Neoadjuvant chemoradiation can be given safely without excess surgical morbidity
- 30. Treatment phase Break ~ 6 wks CTX gem combo Staging CT Restaging Dropout Borderline Resectable PC MDACC Treatment Approach Restaging Dropout Chemo-XRT OR Classification as Borderline Katz MHG, et al. J Am Coll Surg. 2008;206(5):833-46
- 31. The first United States national trial of neoadjuvant therapy for potentially resectable pancreatic cancer (ACOSOG Z5041) is open, and eligible patients should be encouraged to enroll. Gemcitabine-Erlotinib Surgery Gemcitabine-Erlotinib No Radiotherapy
- 34. Emerging Strategies for Locally advanced pancreatic cancer Induction Chemotherapy Restage Localized ChemoXRT Metastatic 2nd Line Rx or Best Supportive Care Maintenance
- 35. 2 modern randomized trials
- 42. only 32 % received RT per protocol more complete analysis
- 44. Radiation Therapy External Beam Radiation Therapy (EBRT) is currently used. 3D Conformal Radiation (3-4 Fields) Intensity Modulated Radiation Therapy (IMRT) (3-10 fields) Volumetric modulated arc therapy (VMAT) Tomotherapy Stereotactic Body Radiation Therapy (SBRT) (multiple fields) Intraoperative radiation therapy (IORT) brachy or electrons
- 46. ELECTIVE NODAL IRRADIATION the use of radiation therapy for elective treatment of regional lymph nodes is controversial for pancreatic cancer.
- 47. IMRT vs 3-D Yovino et al. (2011) IMRT significantly reduced the incidence of Grade 3-4 nausea and vomiting (0% vs. 11%) and diarrhea (3% vs. 18%). IMRT in the recently activated EORTC/US Intergroup/RTOG 0848 adjuvant pancreas trial & RTOG 1201 for LAPC
- 49. IMRT: Duodenal Sparing SBRT: Duodenal Sparing
- 51. CYBERKNIFE
- 55. Locally Advanced Pancreatic Cancer (Gemcitabine, up to 1 Cycle allowed)* 2 week break >2 week break SBRT 6.6 Gy x 5 Mon-Fri Gemcitabine Chemotherapy (3 wks on, 1 wk off) Until toxicity or progression Primary endpoint: Late GI Toxicity > 4 months Secondary: Tumor Progression Free Survival N=60 Trial open at Stanford and Johns Hopkins. Memorial Sloan Kettering Pending. Phase II Multi-Institutional Study of Stereotactic Body Radiation Therapy for Unresectable Panceatic Cancer