Patient case: 48-year-old male with Pancreatic cancer. Genetic variant: CDK6 Amplification. Other conditions: None.

Clinical trial: Safety and Efficacy Study of Five-fraction Stereotactic Body Radiation Therapy to Locally Advanced Pancreatic Cancer

Summary: The safety and efficacy of five-fraction stereotactic body radiation therapy treating locally advanced pancreatic cancer

Detailed description: Although the incidence rate of pancreatic cancer is not as high as that of other gastrointestinal carcinoma in China, the cancer mortalities of males and females ranked the sixth and seventh respectively in 2013, with a surprising low 5-year survival rate (<5%). Only 15%-20% patients are suitable for surgeries among those first diagnosed with pancreatic cancer and the 5-year survival rate of patients with R0 resection is still less than 20%.
  Therefore, better efficacy cannot be achieved via surgery alone, which results in promotion of adjuvant chemoradiotherapy. In America, it has been accepted as a standard treatment contributing to the improved overall survival rates compared with surgery alone. Benefits of the treatment have also been proved in European studies. However, adjuvant chemoradiotherapy is not indicated for 21%-35% patients due to its high postoperative complication rates and worse recovery. Additionally, postoperative chemoradiotherapy would delay the initial time of intensified chemotherapy, along with the difficulty in target volume delineation and low tolerance doses of organs at risk.
  As a result, great emphasis has been placed on neoadjuvant chemoradiotherapy, with predominant features in accurate target volume delineation, low complication rates of organs at risk, low tumor load before surgeries and prevention of the delay of postoperative treatment. Therefore, the inappropriate locally advanced pancreatic cancer patients (30%-80%) for surgeries can be operated via neoadjuvant chemoradiotherapy. Nevertheless, long durations of conventional radiotherapy results in delay of the thereafter treatment.
  Compared with conventional radiation, a single-fraction dose and total dose of target volume can be increased in stereotactic body radiation therapy (SBRT). In addition, doses of organs at risk would be reduced, thus effectively improving local control rates and reducing radiation related toxicity. Shorter course of SBRT also enhance patients' compliance and render the initial of other treatment on schedule possible. Pollom et al. demonstrated that no significant differences were found in six-month and one-year overall survival rates between single-fraction SBRT and multi-fraction SBRT. However, potential trends indicated prolonged overall survivals in patients receiving multifractions. Moreover, the incidence of gastrointestinal toxicity is higher in single-fraction SBRT due to higher doses. Therefore, multi-fraction SBRT is more common in pancreatic cancer treatment. To the best of our knowledge, there are few studies on pancreatic cancer SBRT treatment, and these studies are retrospective with small patient population. Therefore, the investigators propose to conduct a phase II study: five-fraction SBRT as the initial treatment for locally advanced pancreatic cancer. Whether patients would receive thereafter treatment, including chemotherapy of surgeries, depends on their medical conditions.
  Study Procedure:
  1. 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.
  2. 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.
  3. A body fixation (vacuum-bag) will be used in immobilizing the body, the arms (both arms are along the body) and the legs.
  4. The total doses depend on patients' medical conditions, ranging from 32.5Gy-45Gy/5Fx.

Eligibility: Inclusion Criteria:
  1. Locally advanced pancreatic cancer proved by CT or MRI and biopsy
  2. Without any other treatment before SBRT
  3. A life expectancy of >3months
  4. KPS≥70
  5. Age of 18-75 years old
  6. Blood routine examination: Absolute neutrophil count (ANC) ≥ 1.5 ×109 cells/L, leukocyte count≥ 3.5 ×109 cells/L, platelets ≥ 70×109 cells/L, hemoglobin ≥ 8.0 g/dl
  7. Liver and kidney function tests: Albumin > 2.5 g/dL, total bilirubin < 3 mg/dL, creatinine < 2.0 mg/dL, AST<2.5 × ULN(Upper Limit of Normal)(0-64U/L), ALT<2.5 × ULN(0-64U/L)
  8. INR < 2 (0.9-1.1)
  9. Ability of the research subject or authorized legal representative to understand and the willingness to sign a written informed consent document.
  Exclusion Criteria:
  1. Prior surgery, chemotherapy or radiation for the pancreatic cancer
  2. Evidences of metastatic disease such as nodal or distant metastases by abdomen CT and chest CT or FDG PET-CT
  3. Contraindication to receiving radiotherapy
  4. KPS<70
  5. Age<18 or >75
  6. Abnormal results of blood routine examinations and liver and kidney tests
  7. Patients with active inflammatory bowel diseases or peptic ulcer
  8. Gastrointestinal bleeding or perforation within 6 months
  9. Heart failure: NYHA III-IV
  10. Women who are pregnant
  11. Participation in another clinical treatment trial while on study
  12. Patients in whom fiducial implantation was not possible
  13. Inability of the research subject or authorized legal representative to understand and the willingness to sign a written informed consent document.

Relevance to patient case: not relevant