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Tissue exposure to proton therapy compared to conventional photon radiation therapy
Fig. 1: Less normal tissue is exposed to radiation with proton therapy compared to conventional photon radiation therapy in patients with seminoma.

Researchers at Penn Radiation Oncology are now treating patients with stage I, IIA, IIB and relapsed testicular seminoma with proton therapy.

Testicular cancers are the most common solid malignancies in men aged 20 to 35 years. The majority of these tumors (60%) are pure seminoma. Approximately 80% of patients diagnosed with seminoma have stage I disease.

Almost all patients with stage I seminoma are cured. For those patients who require adjuvant radiation following radical inguinal orchiectomy, conventional photon external beam radiotherapy has been directed to the lymph nodes of the para-aortic and pelvic regions. However, photon radiotherapy exposes normal tissues to radiation with well known treatment-related adverse effects, including fatigue and nausea.

Furthermore, in patients with testicular cancers, radiation-associated second malignancies (non-germ cell malignancies after 10 to 35 years) are a major concern. Second primary cancers are a leading cause of death among testicular cancer survivors, in part because the majority of patients with testicular cancers are young (15-25 years) when treated.

To address these concerns for patients with seminoma, reductions in radiation dosing and fields and newer therapies, including carboplatin and surveillance, have emerged. Because proton therapy spares normal tissues distal to the target lesion, it also has been proposed as an alternative to conventional radiotherapy for seminoma.

Recently, researchers at Penn Radiation Oncology performed an institutional review board-approved Phase II, multi-center clinical trial [1] to compare photon and proton radiotherapy for the treatment of Stage I, IIA, IIB and relapsed seminoma and determine predicted rates of excess secondary malignancies for both treatment modalities.

Predicted rates of secondary malignancies from proton versus photon radiation therapy for stage I seminoma

Methods and Material: Computed tomography images from 10 consecutive patients with stage I seminoma were used to quantify dosimetric differences between photon and proton therapies. Structures reported to be at increased risk for secondary malignancies and in-field critical structures were contoured. Reported models of organ-specific radiation-induced cancer incidence rates based on organ equivalent dose were used to determine the excess absolute risk of secondary malignancies. Calculated values were compared with tumor registry reports of excess secondary malignancies among testicular cancer survivors.

Results: Photon and proton plans provided comparable target volume coverage. Proton plans delivered significantly lower mean doses to all examined normal tissues, except for the kidneys. The greatest absolute reduction in mean dose was observed for the stomach (119 cGy for proton plans vs. 768 cGy for photon plans; p<0.0001). Significantly more excess secondary cancers per 10,000 patients/year were predicted for photon radiation than for proton radiation to the stomach (4.11; 95% confidence interval [CI], 3.22–5.01), large bowel (0.81; 95% CI, 0.39–1.01), and bladder (0.03; 95% CI, 0.01–0.58), while no difference was demonstrated for radiation to the pancreas (0.02; 95% CI, –0.01–0.06).

Conclusions: For patients with stage I seminoma, proton radiation therapy reduced the predicted secondary cancer risk compared with photon therapy. We predict a reduction of one additional secondary cancer for every 50 patients with a life expectancy of 40 years from the time of radiation treatment with protons instead of photons. Proton radiation therapy also allowed significant sparing of most critical structures examined (Figure 1) and warrants further study for patients with seminoma to decrease radiation-induced toxicity.

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

Published on: June 13, 2016

Penn Faculty Team

Justin E. Bekelman, MD

Chief, Genitourinary Service, Radiation Oncology

Director, Penn Center for Cancer Care Innovation (PC3I)

Director, Strategic Initiatives, Radiation Oncology

Associate Professor of Radiation Oncology at the Hospital of the University of Pennsylvania

Associate Professor of Medical Ethics and Health Policy

John P. Christodouleas, MD

Service Line Liaison, Genitourinary Service, Radiation Oncology

Adjunct Assistant Professor of Radiation Oncology

Thomas J. Guzzo, MD, MPH

Associate Program Director, Penn Urology Residency

Chief, Division of Urology, University of Pennsylvania Health System

Associate Professor of Urology in Surgery at the Hospital of the University of Pennsylvania

Katherine L. Nathanson, MD

Deputy Director, Abramson Cancer Center

Professor of Genetics

Pearl Basser Professor for BRCA-Related Research at the Abramson Cancer Center of the University of Pennsylvania

Neha Vapiwala, MD

Associate Dean of Admissions, Perelman School of Medicine

Co-Chief, Genitourinary Service, Radiation Oncology

Vice Chair, Education, Radiation Oncology

Associate Professor of Radiation Oncology at the Hospital of the University of Pennsylvania

David J. Vaughn, MD

Vice Chief for Clinical Affairs, Hematology/Oncology

GU Medical Oncology Professor

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