Proton and Carbon Ion Radiotherapy for Locally Advanced Pancreatic Cancer

The proton dose of 50.4GyE in 28 fractions was delivered to clinical target volume (CTV), and carbon ion as a boost dose to gross tumor volume (GTV) escalated from 12GyE to 18GyE with 3GyE per fraction in 3 dose levels. The dose limiting toxicity (DLT) was defined as CTCAE grade 3 or higher of non-hematological toxicity (G3). The acute and late toxicities, overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS) and distant metastasis-free survival (DMFS) were the endpoints.

Inclusion criteria

• The histologically or cytologically confirmed, or the clinically diagnosed by clinical diagnosis criterion proposed by Pancreatic Cancer Committee of Chinese Anti-Cancer Association [15], which was based on evidences of (1). Typical symptoms of abdominal and/or back pain; (2). CA19-9 increased over the normal up limit; (3). A pancreatic mass shown on CT or MRI; and (4). SUV of PET-CT in mass increased compared to that in normal pancreas;
• Unresectable LAPC defined by the criteria of (NCCN) guidelines (Version 1. 2013), or refusal to surgery;
• Gastrointestinal tract (GI) not invaded;
• ECOG Performance Status 0-1 within 30 days prior to registration;
• Age of ≥ 18 years old;
• Enough hematological function (white blood cell count ≥ 3.0×109/L; platelets ≥50×109/L; hemoglobin ≥ 90 g/L);
• Enough liver and kidney functions (creatinine <110gmol/L; urea nitrogen <7.1mmol/L; bilirubin < 1.5 x ULN, ALT and AST ≤ 2.5 x ULN);
• No evidence of distant metastases, based upon PET, CT, or MRI images of the chest, abdomen and pelvis within 30 days prior to registration;
• Informed consent form obtained.

Exclusion criteria

• No pathological evidence of malignant tumor;
• ECOG>=2；
• Liver, kidney and bone marrow function are poor and not adequate for treatment;
• Side effect of previous treatment is not covered yet, eg. The interval between TACE and other anti-tumor therapy is less than one month;
• Prior radiation therapy to the abdomen or radioactive particle implantation;
• cardiac pacemaker or other metal implantation whose function may be disturbed by high energy beam or which affect the dose in target volume;
• Dose constrain of normal liver, digested system and other OAR could not reach the expecting safe dose constrain;
• The patient could not get benefit from proton or heavy ion radiotherapy in physician's opinion;
• Comitant diseases or affecters which could affect the proton or heavy ion radiotherapy;
• Pregnancy（blood or urine β-HCG certified）or lactation;
• Drug or alcohol abused;
• HIV positive, including received anti-retrovirus treatment; chronic hepatitis B virus replication stage; hepatitis C active stage; syphilis active stage;
• HBV positive, hepatitis B virus replication stage, need to be treated with anti-virus treatment, but could not receive anti-virus treatment because of comitant disease;
• Psychiatric history, possibly affecting the completion of treatment;
• patients with serious complications that might affect radiotherapy， including 1）unstable angina pectoris requiring hospitalization in the last 6 months，congestive heart failure，myocardial infarction； 2）acute bacterial or systemic fungal infections； 3）exacerbation of chronic obstructive pulmonary disease ( COPD) or other respiratory system disease requiring hospitalization 4）hepatic function insufficiency or renal function insufficiency 5） immunosuppressed patients
• patients with connective tissue disease such as active scleroderma or lupus and so on, which is contraindication for radiotherapy
• patients can't understand treatment goal or unwilling/unable to sign up inform consent form；
• no civil capability or limited civil capacity.