Proton Radiotherapy for Recurrent Cancers

Radiation oncologists at Penn Medicine are conducting a clinical trial to determine the feasibility of proton radiotherapy (PRT) as a modality for the treatment of previously radiated patients with histologically confirmed, non-CNS solid malignancies and tumor recurrence in or near prior radiation fields. The study (ClinicalTrials.gov Identifier: NCT01126476) includes five cohorts: recurrent cancers of the head and neck, thorax, abdomen, pelvis and extremities.

The challenge when considering curative or aggressive local control of previously irradiated recurrent tumors is that photon beam radiotherapy (including intensity-modulated  radiation therapy or IMRT), carries significant risk for organs at risk from the cumulative effects of radiation.

Unlike photon beam radiotherapy, protons deposit the bulk of their energy only at the end of their path. Thus, proton radiotherapy may offer potential dosimetric and clinical advantages compared to photon radiation in patients experiencing recurrent cancers.

The first phase of the current study at Penn studies the feasibility of re-irradiation in each of the cohorts. In cohorts where feasibility has been verified, patients can then be enrolled in the second registration phase of the study. The study evaluates patients for both acute and late toxicity.

For more information about this study, contact: John Plastaras, MD, PhD at 215-615-3714 or admin@ctsrmc.org.

The initial findings from a prospective dosimetric analysis of PRT versus IMRT in pelvic tumors were presented at the 53rd annual meeting of the American Society for Therapeutic Radiology and Oncology in October 2011.


Prospective Trial of Proton Re-Irradiation of Recurrent Pelvic Tumors: Dosimetric Analysis*

Objectives: To provide an initial dosimetric analysis of PRT versus IMRT in pelvic tumors and an acute adverse effects profile for these patients. The primary endpoints were feasibility and acute toxicity.

Methods: All patients (N=10) were adults with solid tumor recurrences in or near prior radiation fields treated at least three months prior to entering the study. Malignancies included rectal adenocarcinoma, sarcoma and cervical carcinoma. Patients were further stratified by treatment volume as either low volume CTV (<250 cc, n=6) or high volume CTV (>250 cc, n=4). Fifty percent of patients received concurrent chemotherapy as 5-FU-based treatment (N=4) or cisplatin (N=1). IMRT plans were generated for backup purposes, and were optimized to deliver the same biologically equivalent dose as the PRT plans. IMRT and PRT plans were compared.

Results: Early findings suggest that in the prospective setting, PRT for the re-irradiation of recurrent pelvic malignancies reduces dose to many critical OARs when compared with intensity-modulated radiotherapy (IMRT) including bowel dose.

 *Abigail Berman Milby MD, Stefan Both PhD, Tiffany Sharkoski BA, James M. Metz MD,
   Smith Apisarnthanarax MD, Zelig Tochner MD, John P. Plastaras MD, PhD. Department of
   Radiation Oncology, University of Pennsylvania, Philadelphia, PA.


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.

Performing Clinical Research in Proton Therapy for Recurrent Cancers at Penn Medicine

Curtiland Deville, MD
Assistant Professor of Radiation Oncology

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

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

Ramesh Rengan, MD, PhD
Assistant Professor of Radiation Oncology

Zelig A. Tochner, MD
Professor of Radiation Oncology

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

Abramson Cancer Center
Penn Presbyterian Medical Center
Medical Arts Building, Suite 103A
51 N 39th Street
Philadelphia, PA 19104


Download a pdf of this Clinical Briefing.

Clinical Trials Examine Proton Therapy for Resected Non-Small Cell Lung Cancer

Radiation oncologists at Penn Medicine are conducting clinical trials to better understand the full potential and capabilities of proton therapy for the treatment of patients with non-small cell lung cancer (NSCLC).

While research has shown that the biologic effect on exposed tissues is essentially the same for standard radiotherapy and proton therapy (PT), the distinction between the two with regard to radiation exposure in the critical organs of cancer patients remains largely unresolved.

To address this issue, researchers at the Roberts Proton Therapy Center at Penn Medicine recently compared passive scattering proton therapy (PSPT) and intensity modulated proton therapy (IMPT) to intensity modulated photon beam radiotherapy (IMRT) in patients with completely resected
non-small cell lung cancer (NSCLC).

Proton Beam versus IMRT for Post-Operative Radiotherapy in Completely Resected IIIA Non-Small Cell Lung Cancer

Objectives: The aim of this study was to determine whether proton therapy provides relative dosimetric sparing of critical organs at risk (OARs) during the post-operative period. IMRT has been shown to reduce lung, heart and esophagus dose over 3D-conformal radiotherapy in the definitive treatment of advanced stage NSCLC and other thoracic malignancies. However, the detrimental effects of post-operative radiotherapy on OARs is thought to negate potential improvements in outcome in these patients.

Methods: The computed tomography treatment planning scans of patients with completely-resected IIIA NSCLC treated with IMRT post-operative radiotherapy were used for this study. The following critical normal structures were delineated on each planning CT scan: body, spinal cord, heart, esophagus, contralateral lung, ipsilateral lung, and total lung minus the planning target volume. The IMRT, PSPT, and IMPT plans were analyzed for dosimetric endpoints. The proton plans were constructed with two or three beams. IMRT plans were optimized to deliver 50.4 Gy all in 1.8 Gy fractions. The proton plans were optimized to deliver the same biologically equivalent dose as was originally delivered in the IMRT plans. Dose volume histograms were analyzed for all OARs.

Results: The decrease in dose to all OARs with IMPT was large and statistically significant compared with IMRT and PSPT (Fig. 1). PSPT reduced the volume of lung receiving a higher dose, but increased the low-dose lung bath. Reductions by IMPT were seen in dosimetric parameters to normal lung predictive of radiation pneumonitis and to heart doses predictive of morbidity and mortality. This reduction may correlate with a decrease in the incidence of this dose limiting toxicity and thus improve the therapeutic ratio.

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 Proton Therapy at Penn Medicine

Michelle Alonso-Basanta, MD, PhD
Assistant Professor of Radiation Oncology

Justin E. Bekelman, MD
Assistant Professor of Radiation Oncology

John Christodouleas, MD, MPH
Assistant Professor of Radiation Oncology

Curtiland Deville Jr., MD
Assistant Professor of Radiation Oncology

Stephen M. Hahn, MD
Chair, Department of Radiation Oncology
Professor of Radiation Oncology

Ramesh Rengan, MD, PhD
Chief, Thoracic Service
Assistant Professor of Radiation Oncology

Zelig A. Tochner, MD
Vice Chair of Proton Therapy
Professor of Radiation Oncology

Neha Vapiwala, MD
Chief, Genitourinary Service
Assistant Professor of Radiation Oncology

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

Proton Therapy Research at Penn
Penn researchers are advancing and refining proton therapy (PT) for patients with cancer and other serious diseases. Current clinical trials seek to determine which cancers are most appropriately treated with proton therapy and ways in which PT may best be combined with standard chemotherapy and radiotherapy to improve surgical outcomes and reduce radiation exposure. Penn Radiation Oncology research programs are funded by the National Institutes of Health (NIH). For a full list of currently enrolling clinical trials in proton therapy, visit this site.

Download a pdf of this Clinical Briefing.

Advances in Enteral Feeding at Penn Medicine

From the Penn GI News, Fall 2011

Gastroenterologists at Penn Medicine are partnering with a variety of specialists throughout the health system to introduce new enteral feeding tube (ETF) techniques and devices for patients with conditions that prevent normal swallowing and feeding. The indications for ETF include impaired swallowing as a result of brain injury or trauma, gastrointestinal obstruction, pancreatitis, motility disorders and cystic fibrosis and other hypercatabolic states, including burn injuries and Crohn’s disease.

In these critically ill patients, enteral feeding has been shown to complement nutrition by modulating the metabolic reaction to stress and enhancing the immunological function of the bowel. Moreover, ETF is superior to total parenteral nutrition (TPN) in cost and adverse events (catheter and blood infections and venous thromboses).

“Enteral nutrition is an important facet of health care in patients with digestive and related disorders at Penn,” explains Gregory Ginsberg, MD, director of endoscopy at Penn and current president of the American Society for Gastrointestinal Endoscopy. “Enteral feeding employs the functional gut and as such preserves aspects of gut flora and function. This facilitates retention of the immunological function of the gut and is associated with decreased risk for bacterial translocation and lowered infection risk.”

Endoscopic means of enteral access to facilitate nutritional support can assume many forms. Short-term nutritional support is typically accomplished via nasoenteric feeding tubes (NETs). Longer-term feeding arrangements generally involve percutaneous endoscopic gastrostomy (PEG) tubes or direct-percutaneous endoscopic jejunal (DPEJ) tubes, a specialty of gastroenterologists at Penn Medicine.

Used when the proximal-most portion of the digestive tract must be bypassed and feeding must be delivered beyond the ligament of Treitz, the DPEJ technique is technically challenging, Dr. Ginsberg says.

“We’ve worked to develop tools and techniques to best ensure success in selected patients. In preclinical work, for example, we incorporate magnetic attraction forces to help localize and transiently fix the small intestine to the anterior abdominal wall to facilitate the placement of DPEJ tubes.”

Appropriate indications for the DPEJ procedure include post-operative anatomy, pancreatitis and entero-respiratory reflux.

Low-profile PEG Button Tubes Improve Enteral Feedings for Young Patients
Penn gastroenterologists have recently introduced low-profile percutaneous endoscopic gastrostomy (PEG) button tubes designed for single-step application in young patients and those with pre-existing tubes.
“The concern with conventional PEG tubes is that they can come loose as a result of forces placed on the exterior tubing,” says Octavia Pickett-Blakely, MD, MHS. “The button design places the bolster at the abdominal wall, which decreases the risk of pull-out and irritation at the wound site in young, active patients.”
In studies of pediatric patients, those with low-profile PEG tubes were likely to have fewer tube dislodgments and briefer hospital stays than patients with standard PEG tubes.


Download a pdf of the Penn GI News for Fall 2011.