Phase ǀ Study on Pancreatic Cancer Treated by CyberKnife
Condition: Pancreatic Tumor
MeSH terms: Pancreatic Neoplasms
Study type: Interventional

Summary: 
      The maximum tolerated dose on locally advanced unresectable pancreatic tumor treated with
      CyberKnife SBRT will be evaluated.
    

Detailed description: 
      Pancreatic cancer is the fourth-leading cause of cancer-related death in the world. It is
      characterized by metastatic spread and local failure and seldom detected in its earlier
      stages. For locally advanced stage pancreatic cancer, the complete surgical removal is hard
      to achieve.

      Stereotactic body radiotherapy (SBRT) with CyberKnife for unresectable pancreatic tumor is a
      relatively new treatment option made available because of significant improvements in
      diagnostic imaging and radiation delivery techniques. Different from the conventional
      radiotherapy, radiation dose is delivered in fewer fractions and higher fractional doses in
      SBRT. Gurka (1) reported that 14 patients received SBRT with prescription dose of 25 Gy in
      five fractions with biologically equivalent doses (BED) of α/β=10 in correspondence to
      37.5Gy. Grade 1 to 2 gastrointestinal toxicity (no grade 3 or 4 radiation-related toxicities)
      was observed two weeks after treatment. Two patients had a partial response, and 12 patients
      were with stable diseases. In the previous dose escalation study, a single fraction up to15
      Gy, 20 Gy, 25 Gy which is an equivalent BED10 to 37.5 Gy, 60 Gy, 87.5 Gy respectively is
      recommended by Koong AC (2) and his team. Even though the local control rate is 100%, the
      follow up is short and the sample size of 15 patients is relatively small. Moreover, the late
      toxicity is not investigated. And with single fraction scheme, higher late gastrointestinal
      (GI) toxicities were reported (2,3,4). In the meanwhile, investigators (5, 6) from South
      Korea examined that a Dmax of 35Gy and 38Gy in 3 fractions (BED10 to 75.8Gy and 86.1Gy) of
      SBRT correlated with a 5% and 10% rate of grade 3 of gastroduodenal toxicity for abdominal
      malignant tumor, respectively.

      Chuong (7) used 5 fractions to potentially decrease the risk of late normal tissue injury
      compared with 1 to 3 fractions commonly used in other institutions. Assuming α/β=3, the BED3
      delivered to normal tissue in this study (using a mean 36.4 Gy in 5 fractions to the high
      dose PTV) was 125 Gy, which is lower than the mean BED3 from other series, the corresponding
      values from Boston and Stanford were 153.7 Gy (mean, 32.96 Gy in 3 fractions) and 233.3 Gy
      (mean, 25Gy in 1 fraction), respectively (8, 9). And a relatively lower incidence of grade ≥3
      late adverse effects (5.3% VS 9%) was observed.

      Since the treatment modality and dose are still under exploratory stage, we propose to
      conduct a Phase I study determining the maximum tolerated dose of CyberKnife SBRT on dose
      escalation for the treatment of locally advanced pancreatic tumor based on a 5 fractions
      treatment regimen. A prescription dose of 35-47.5 Gy in five fractions was chosen, with an
      equivalent to the traditional dose of 2 Gy in 25-39 fractions of BED10. And this is assumed
      to be the safe and effective dose for unresectable pancreatic cancer patients.

      Study Procedure:

      CyberKnife SBRT body fixation (vacuum-bag) will be used in immobilizing the body, the arms
      and the legs.

        -  Patients will undergo a plain CT as well as an enhanced pancreatic parenchymal CT for
           radiation treatment planning and target delineation.

        -  SBRT will be delivered on CyberKnife with Synchrony Respiratory Tracking system. The
           tumor will be tracked with implanted fiducial markers by Fiducial Tracking System.
           Treatment will be delivered in 5 fractions within 1 to 2 weeks at the discretion of the
           investigator.

        -  A body fixation (vacuum-bag) will be used in immobilizing the body, the arms (both arms
           are along the body) and the legs.
    

Intervention name(s): CyberKnife
Intervention type(s): Device
Intervention description(s): Radiation Therapy
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Stereotactic Body Radiotherapy (SBRT); CyberKnife; Dose Escalation