Daily Online Adaptation Versus Localization for MRI-Guided SBRT for Unresectable Primary or Oligometastatic Abdominal Malignancies
Condition: Pancreatic Cancer; Pancreas Cancer; Cancer of the Pancreas; Hepatocellular Carcinoma
MeSH terms: Pancreatic Neoplasms
Intervention: Online, adaptive MR-guided SBRT; Online, non-adaptive MR-guided SBRT; European Organization for Research and Treatment of Cancer (EORTC) QLQ-30
Intervention description: Patients randomized to the online-adaptive treatment planning arm will have all tumor volumes and critical structures within 3 axial slices of the PTV re-contoured on the MR-localization image of the day. The estimated delivered dose should be calculated using the software on the console. An adapted radiation therapy plan should be generated; Patients will not have online-adaptive treatment planning; 30 questions
28 questions about various health issues with answers ranging from 1=Not At All to 4 = Very Much
1 question asking about overall health with answers ranging from 1=very poor to 7 excellent
1 question asking about overall quality of life with answers ranging from 1=very poor to 7=excellent
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      In light of this new technology and preliminary findings of low toxicity of online, adaptive,
      magnetic resonance (M)-guided stereotactic radiation on a single arm prospective study, the
      investigators propose to compare this technique to online MR-guided stereotactic body
      radiation therapy (SBRT) without adaptation. Online plan adaptation increases treatment times
      for patients and comprises an increased burden on technical and clinical staff. Although
      preliminary trial results are encouraging, it remains unclear if the dosimetric benefits of
      online-adaptive planning studies will translate to measurable improvements in clinical
      outcomes that merit its routine use. In our preliminary study, plan adaptation was most often
      required when tumors were adjacent to the gastrointestinal tract (the esophagus to the
      sigmoid colon), as those structures were most commonly the dose-limiting structures and were
      noted to change in location on a day-to-day basis. For these reasons, abdominal disease sites
      have historically highlighted the limitations of SBRT. Specifically, the investigators will
      enroll patients with oligometastatic or unresectable primary disease of the non-liver abdomen
      to a randomized, prospective trial.

      Patients will be randomized to one of two treatment arms, in which they will receive either
      online-adaptive, MRI-guided SBRT or non-adaptive MRI-guided SBRT. Both patient groups will
      undergo MRI simulation and MRI treatment localization with online MR monitoring and/or
      gating. All patients will be treated in five fractions over one to two weeks. By adhering to
      strict normal tissue constraints, the investigators expect toxicity to be within the current
      standard of care for the non-adaptive arm, with reduction in toxicity in the arm of patients
      who undergo adaptation based on daily anatomic changes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Oligometastatic disease or unresectable primary abdominal malignancy with
             biopsy-proven primary disease histology of solid tumor categorization. Patients with a
             diagnosis of hepatocellular carcinoma do not require a biopsy.

          -  No more than three progressive sites of disease, with at least one of the disease
             sites to be deemed suitable for treatment with MRI-guided, online adaptive SBRT to the
             non-liver abdomen as per radiation oncology evaluation.

          -  Must be treated per protocol to lesion(s) of a single abdominal site that can
             reasonably be encompassed within a single treatment field. Treatment of additional
             site(s) outside of the abdomen while the patient is on trial is acceptable.

          -  The treated lesion must be within 2 cm of the abdominal gastrointestinal tract
             (abdominal esophagus to sigmoid colon) on the basis of cross sectional imaging study
             such as computed tomography (CT), positron emission tomography (PET)/CT, or MRI.

          -  Must be deemed medically fit for SBRT by the treating physician.

          -  At least 18 years of age.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Must have completed any systemic therapy at least one week prior to planned start of
             SBRT (two weeks preferred), and must have no plans to initiate systemic therapy for at
             least one week following end of SBRT (two weeks preferred).

          -  Women of childbearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control, abstinence) prior to study entry and for
             the duration of study participation. Should a woman become pregnant or suspect she is
             pregnant while participating in this study, she must inform her treating physician
             immediately.

          -  Able to understand and willing to sign an Institutional Review Board (IRB) approved,
             written informed consent document (or that of legally authorized representative, if
             applicable).

        Exclusion Criteria:

          -  Primary disease of hematologic origin, lymphoma, or small cell cancer.

          -  Past history of external beam radiotherapy within the projected treatment field of any
             of the disease sites to be treated by MRI-guided, online adaptive SBRT.

          -  Currently receiving any other investigational agents.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
             arrhythmia.

          -  Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 14
             days of study entry.

          -  Medical contraindication to undergoing MR imaging.