• Staging using modern contrast-enhanced abdominal CT and/or MRI with thin cuts through the pancreas must be done prior to initiation of RT
• Prior to initiation of RT, ERCP with stent placement must be considered
• Initiation of RT in PC patients may be used in the following:
  • Neoadjuvant therapy for resectable/borderline resectable tumors
  • Adjuvant therapy for resectable tumors
  • Definitive treatment for locally advanced tumors
  • Palliative treatment for non-metastatic and metastatic disease
  • Treatment for recurrent disease
• Goals of RT include:
  • Sterilization of blood vessel margins
  • Increase the likelihood of a margin-negative resection
  • Provide adequate local control to prevent or delay progression of local disease and minimize the risk of RT exposure to surrounding organs at risk
  • Palliate pain and bleeding or relieve obstructive symptoms in patients with disease progression or locally recurrent disease
• Chemoradiation therapy is an option for subsequent treatment of patients with locally advanced tumors if primary site is the sole site of progression or in select patients with recurrent disease in combination with systemic therapy
  • Preferred recommended regimens include continuous infusion 5-FU + concurrent RT or Capecitabine + concurrent RT
  • Other recommended regimen includes Gemcitabine + concurrent RT

Neoadjuvant Therapy for Resectable or Borderline Resectable Tumors

• Increases the likelihood of margin-negative resection
• Must be conducted only in a clinical trial when used as neoadjuvant therapy in patients with resectable tumors
• At least 2-6 cycles of neoadjuvant chemotherapy are recommended prior to initiating RT and subsequent chemoradiation may be an option after neoadjuvant chemotherapy
  • RT must be delivered after 2-6 months of systemic chemotherapy in patients with borderline resectable PC
• Resection must be done within a few weeks after RT for resectable cases and 4-8 weeks after RT for borderline resectable tumors to allow sterilization of the margin and allow for downstaging
• Recommended doses in chemoradiation:
  • 45-54 Gy in 1.8-2.0 Gy fractions
    • Recommended to be given as a postoperative treatment with high-energy protons >4 MV to the tumor bed, surgical anastomoses and adjacent lymph node regions
    • A follow-up dose of 5-15 Gy to the tumor bed is recommended after standard dose
  • 36 Gy in 2.4 Gy fractions

• Doses of >54 Gy may be given for patients with higher stages or if clinically appropriate
• Stereotactic body RT (SBRT) may be an option for patients with smaller borderline resectable tumors located ≥1 cm from gastrointestinal mucosal margin and without evidence of nodal involvement

Adjuvant Therapy for Resectable Tumors

• Adjuvant radiation therapy with concurrent fluoropyrimidine therapy is not routinely recommended if surgical margin is negative
• May be given after resection in patients with high risk for local recurrence which are patients with positive resection margins and/or lymph nodes
• May be an option after resection in patients without previous neoadjuvant chemotherapy and no evidence of recurrent or metastatic disease and given in combination with chemotherapy
• Recommended dose in chemoradiation:
  • 45-50.4 Gy in 1.8-2.0 Gy fractions (25-28 fractions) to the tumor bed, surgical anastomoses and adjacent lymph node basin
    • An additional dose of 5-9 Gy to the tumor bed and anastomoses may be given after the standard dose if clinically appropriate
  • Chemoradiation must be delivered 4-6 months after systemic chemotherapy

Definitive Treatment for Locally Advanced Tumor

• Goal is to prevent or delay local progression which can lead to pain and/or local obstructive symptoms, and help facilitate R0 resection in patients who are considered for surgery
• Treatment options include:
  • Chemoradiation, SBRT or hypofractionated RT in select patients who are not suitable for combination therapy
    • Chemoradiation or SBRT are treatment options for disease progression in patients with locally advanced disease provided patient is with good performance status, has not received chemoradiation or SBRT previously, and the primary site is the sole site of progression
    • Fluoropyrimidine-based chemoradiation is preferred over Gemcitabine-based chemoradiation
  • Induction chemotherapy followed by chemoradiation or SBRT in patients with locally advanced tumors and good performance status without systemic metastases
    • Recommended in patients with highly unlikely resectable tumors, suspicious metastases or who may not be able to tolerate chemoradiation
• Recommended dose in chemoradiation is 45-54 Gy in 1.8-2.0 Gy fractions
• Reported doses in SBRT include doses of 3 fractions for a total dose of 30-45 Gy or 5 fractions for a total dose of 25-50 Gy
• Hypofractionated RT include doses of 15 fractions for a total of 67.5 Gy or 25 fractions for a total dose of 75 Gy delivered in a protracted course

Palliative RT for Non-metastatic and Metastatic Disease

• Goal is to relieve pain and bleeding and/or alleviate local obstructive symptoms
• Treatment option for elderly patients with non-metastatic disease or patients with non-metastatic disease who are not suitable for definitive treatment because of poor performance status or comorbidities
• Short-course RT may be considered in patients with locally advanced PC who are highly symptomatic (eg abdominal pain, worsening jaundice, GI bleeding)
• Short-course RT may be an option for patients with metastatic sites causing pain (eg osseous pain)
• RT to the primary tumor and small margin may be an option for patients with metastatic disease requiring local palliation for bleeding, obstruction or pain unresponsive to analgesics
• Palliative RT with or without chemotherapy may be an option for patients with severe tumor-associated abdominal pain
• Specific dose of palliative RT depends on burden of metastatic disease, normal tissue tolerance and expected survival and is typically given in a dose of 25-36 Gy in 2.4-5 Gy fractions

Stereotactic Body RT (SBRT)

• Mode of RT wherein increasing dose is aimed at the gross tumor sparing radiation to surrounding healthy tissue
• Provided better median overall survival compared to patients treated with conventional fractionated RT
• Use is limited to clinical trials