University of Pennsylvania Health System

Clinical Briefings™: Clinical Reports from Penn Medicine

Wednesday, September 26, 2012

Proton Radiotherapy for the Treatment of Upper Gastrointestinal and Biliary Malignancies


Radiation oncologists at Penn Medicine are investigating the use of proton radiotherapy to treat upper gastrointestinal malignancies, including cancers of the pancreas, stomach, duodenum and bile ducts (extrahepatic cholangiocarcinoma).

Definitive treatment of these tumors usually includes some combination of surgical resection, radiotherapy and chemotherapy. After surgery, upper GI malignancies (including cholangiocarcinoma) are often treated with combined chemoradiation with continuous infusion 5-FU, which acts as a radiation sensitizer and to address systemic micrometastases.

Chemoradiation is a standard of care for unresected pancreatic cancer and is used as a preoperative treatment for locally advanced disease in some patients. In these settings, the combination of radiation to the stomach and bowel results in significant acute gastrointestinal toxicity, often made more severe by concurrent 5-FU and chemotherapy itself. The acute toxicity of treatment makes it difficult to deliver radiation to the abdomen, and patients often require treatment breaks or discontinuation of therapy.

These factors can compromise the efficacy of treatment. In the current study at Penn [ClinicalTrials.gov Identifier: NCT01449864], proton therapy with concurrent continuous infusion 5-FU or oral capecitabine chemotherapy will be administered for the treatment of upper gastrointestinal and biliary malignancies in the neo-adjuvant and adjuvant setting.

There are dosimetric data and Phase I clinical data to suggest that proton radiotherapy for pancreatic cancer is feasible and tolerable and may help reduce normal tissue toxicity. Based on these findings, it is expected that proton radiotherapy will lead to reduced normal tissue toxicity when given with concurrent chemotherapy, which will ultimately make chemoradiation more tolerable and potentially enable radiation dose escalation or the addition of other chemotherapeutic agents to 5-FU or oral capecitabine.

Clinical Study


Proton Radiotherapy for Upper Gastrointestinal Malignancies

Objectives: This is a study of concomitant proton radiotherapy and chemotherapy for patients with upper gastrointestinal and extra-hepatic biliary malignancies. The primary objectives of this study are feasibility and acute toxicity. The study will be deemed infeasible if >10% of patients:

• Cannot be given treatment because anatomy is such that a dosimetrically satisfactory treatment plan cannot be devised (i.e., 95% of target volume covered by 95% of the dose)

• Are unable to tolerate more than 25% of treatments using proton radiotherapy. (This can be for any reason, including the inability to set the patient up within acceptable limits of tolerance, or the patient is unable to tolerate treatment position or immobilization for the duration of treatment. Any treatments that cannot be delivered with protons will be delivered using photons, so that the patient receives the prescribed tumor dose. Up to 25% of treatments can be delivered using photons). Toxicity will be deemed unacceptable if greater than 60% of patients experience Grade 3 or higher acute non-hematologic toxicity from proton beam therapy and continuous infusion 5-FU or oral capecitabine chemotherapy in patients with upper GI/biliary malignancies.

The secondary objectives of the study include:
• An assessment of the late complications from proton beam therapy and continuous infusion 5-FU or oral capecitabine in patients with upper GI and biliary malignancies;

• A comparison of the dose distribution to tumor and surrounding normal structures using Dose Volume Histograms (DVHs) generated from the proton plan used to treat the patient and the photon plan generated for comparison purposes; and

• A determination of the rates of local control and overall and progression-free survival among patients treated with proton therapy and continuous infusion 5-FU or oral capecitabine for upper GI and biliary malignancies.

Methods: Patients will be stratified by treatment site into two major strata: 1) pancreatic-like tumors (including pancreatic, biliary, and duodenal adenocarcinomas) and 2) gastric-like tumors (including gastric and GE junction adenocarcinomas), based upon the different acute toxicity profiles. This study will be conducted in two phases. In the first phase, feasibility will be established using the primary objectives (above). The second phase (open registration) will begin no earlier than 90 days after the last patient in each stratum of the initial phase has started radiation treatment, and once feasibility has been verified. The secondary objectives will serve as the objectives for the second phase of the study.

Principle Investigator: John Plastaras, MD, PhD
Contact: 215.662.2812, or admin@ctsrmc.org.

Faculty Team

Among the largest and most respected programs in the world, Penn Radiation Oncology offers a variety of innovative treatment options to patients with cancer. In addition, as a national leader in basic science, translational research and clinical trials, Penn Radiation Oncology offers patients access to the latest treatment options––including proton therapy––before they are widely available elsewhere in the region.

Performing Clinical Research in Gastrointestinal Proton Therapy at Penn Medicine


Edgar Ben-Josef, MD
Vice Chair of Translational Research
Professor of Radiation Oncology

Stefan Both, PhD
Assistant Professor of Radiation Oncology,
Director of Translational Physics Research

Bruce Giantonio, MD
Professor of Medicine

Stephen M.Hahn, MD
Henry K. Pancoast Professor of Radiation Oncology

James M. Metz, MD
Clinical Director
Professor of Radiation Oncology

Peter O’Dwyer, MD
Professor of Medicine

John P. Plastaras MD, PhD
Clinical Research Director
Assistant Professor of Radiation Oncology

Ursina Teitelbaum, MD
Clinical Assistant Professor of Medicine

Zelig A. Tochner MD
Professor of Radiation Oncology

Paul S. Wissel, MD

Access

Penn Radiation Oncology
Perelman Center for Advanced Medicine
Concourse Level
3400 Civic Center Boulevard
Philadelphia, PA 19104

Roberts Proton Therapy Center
Perelman Center for Advanced Medicine
Concourse Level
3400 Civic Center Boulevard
Philadelphia, PA 19104

Consultations also available at:
Abramson Cancer Center
Penn Presbyterian Medical Center
Medical Arts Building, Suite 103A
Philadelphia, PA 19104

Clinical Research at the Roberts Proton Therapy Center

The Roberts Proton Therapy Center has the advantage of being part of a world class academic medical center, Penn Medicine, and an NCI-designated Comprehensive Cancer Center, Penn’s Abramson Cancer Center. In addition to its primary mission of improving the treatment of cancer,
however, the Roberts Proton Therapy Center at Penn Medicine has the purpose of expanding, defining and clarifying the therapeutic uses for proton therapy through clinical research.

Recent clinical protocols have sought to increase and enhance the effectiveness of proton therapy and to determine which cancers should be treated with proton versus conventional radiation. In addition to abdominal cancers, the conditions currently being investigated at the Roberts Proton Therapy Center include cancers of the prostate, breast and lung. For more information, visit:
http://www.pennmedicine.org/Roberts-Proton.

Download a pdf of this Clinical Briefing.


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