1. CK RS for non-resectable pancreatic tumors
Laura Fariselli
Besta-Milano
CDI- Milano
Cristina Baiocchi
San Bortolo Hospital - Vicenza
European Protocol Development Committee Meeting (EPDC)
MILANO

2. PANCREATIC Cancer Tenth cause of cancer mortality in Europe
In 2000: 74,000 new cases in Europa
Survival:
at 1 year: 15.9 %
at 3 years: 5.4%
at 3 years: 4.1%
Average survival for patients in stage I: months

3. PANCREATIC Cancer
5-25% of the patients with pancreatic cancer is resectable at the time of the diagnose.
Most of pancreatic patients receive chemotherapy, alone or in conjunction with radiation theraphy

4. LOCAL ADVANCED PANCREATIC Cancer
Randomized chemotherapy studies have shown a significant improvement of the average survival in those patients treated with external radiotherapy combined with 5-FU bolus, in comparison to the bypass surgical resection alone, to chemotherapy alone or radiotherapy alone

5. LOCAL ADVANCED PANCREATIC Cancer
In USA and in Europa the combined treatment Chemotherapy – Radiotherapy is the therapeutic gold standard:
50.4 Gy in 28 stages +
5-FU or Gemcitabine

6. LOCAL ADVANCED PANCREATIC Cancer
Chemotherapy:
New cytotoxic agents
Radiotherapy:
dose escalation / conformational RT

7. LOCAL ADVANCED PANCREATIC Cancer
Terjanian et al
ASCO in 2000 a non-invasive stereotactic technique to irradiate a ipofractionated, high dose to the pancreas
Koong et al., 2004
Phase I study: CyberKnife stereotactic radiation therapy in single stage
Koong et al., 2005
Phase II study: CyberKnife stereotactic radiation therapy as a boost after ERT + CT
Chang et al, 2007
SBRT is effective for local control with acceptable toxicity. Distant metastases account for the vast majority of disease-related mortality.
Schellenberg et al, 2008
Evaluation of the efficacy od stereotactic radiation therapy with CyberKnife single session

8. Koong et al, 2005

9. Schellenberg et al, 2008

10. CyberKnife radiosurgery for the treatment of non resectable pancreatic tumor
Dr. Laura Fariselli, MD, Chief Director, U.O. Radioterapia, I. Besta, Milano and Project Director, CyberKnife Program, Milano
Dr. Rosabianca Guglielmi, Chief Director, U.O. Radioterapia, USSL 6 - San Bortolo H. Vicenza 
Dr. Cristina Baiocchi, MD, U.O. Radioterapia USSL 6 - San Bortolo H. Vicenza
Dr. Giancarlo Beltramo, MD, Cyberknife Center- Centro Diagnostico Italiano Milano
Dr. Lorenzo Brait PhD, Cyberknife Center- Centro Diagnostico Italiano Milano
Dr. Livia Corinna Bianchi, MD, U.P. CyberKnife, Centro Diagnostico Italiano, Milano
Dr. Francesca Brovelli, MD, U.P. Imaging, Centro Diagnostico Italiano, Milano
Dr. Maurizio Meregalli, MD, U.O. Oncologia Medica, S. Carlo H., Milano
Dr. Marco Possanzini, MD, U.P. CyberKnife, Centro Diagnostico Italiano, Milano
Dr. Paolo Scalchi, PhD, U.O. Fisica sanitaria, USSL 6 - San Bortolo H. Vicenza

11. Cyberknife radiosurgery for the treatment of non resectable pancreatic tumor
Eligibility
Gender: male and female patients with primary non operable pancreatic tumor or with locally advanced pancreatic tumor without metastatic lesion. Histology will be performed for all patients to confirm diagnosis and stage of pancreatic cancer
Age: ≥ 18 years old
Patient deemed not operable for clinical or surgical reasons or who refused surgery
Stage: stage I pancreatic tumor (T1 and T2 N0)
stage II (T3 N0) without duodenum and/or biliary tree involvement
stage III (only T4 N0) with minimal peri-pancreatic blood vessel infiltration
Maximum diameter of tumor ≤ 6 cm measured on CT-Scan
Local recurrence after radical surgery
KPS ≥ 70
Life expectancy > 3 months
Minimal peri-pancreatic blood vessel infiltration
Written informed consent

12. Cyberknife radiosurgery for the treatment of non resectable pancreatic tumor
Required Sample Size
Four patients for each step of dose escalation will be enrolled. The patients will be assessed within one month of treatment for acute toxicity. Escalation to the next dose level will be performed 1 month after delivery of the last treatment regimen at the earliest. Late toxicity will also be assessed.

13. Cyberknife radiosurgery for the treatment of non resectable pancreatic tumor
Primary Objectives of this protocol are:
to assess acute radiation toxicity. Acute toxicity is the toxicity observed during treatment and up to 1 month after treatment
to provide local control in patients with primary pancreatic tumor or locally advanced pancreatic tumors with no-metastatic lesions

14. Cyberknife radiosurgery for the treatment of non resectable pancreatic tumor
Secondary Objective of this protocol are:
to increase the overall survival rate
to increase quality of life in this population of patients
to assess early delayed (1 month to 6 month) and late radiation toxicity (after 6 months)

15. Prescription doses (dose escalation): Curative effect (Ø ≥3 cm)
Cyberknife radiosurgery for the treatment of non resectable pancreatic tumor
Prescription doses (dose escalation):
Curative effect (Ø ≥3 cm)
24 Gy in 3 fractions
32 Gy in 4 fractions
40 Gy in 4 fractions

16. Maximum acceptable dose for OARs
Cyberknife radiosurgery for the treatment of non resectable pancreatic tumor
Maximum acceptable dose for OARs
Spinal cord: 6 Gy per fraction (Max 18 Gy)
Liver: 12 Gy (in 30% of volume), 7,5 Gy (in 50% of volume), less than 700 cc ≤ 15 Gy
Kidneys: ≤ 15 Gy ( in 35% of volume)
Duodenum: 9-10 Gy per fraction (Max Gy in 5% of volume)
Stomach: 9 Gy per fraction (Max 27 Gy in 5% of volume)

17. Pancreatic cancer

18. Pancreatic cancer

19. CK RS for non-resectable pancreatic tumors
SRS is an alternative method of treating patients not suitable for surgery
It’s necessary to have data about toxicity and acceptable dose for OARs in controlled protocol
In Milan the CK protocol has been approved by Ethic Committee; in Vicenza we are waiting the consent.