title: Predicted rates of secondary malignancies from proton versus photon radiation therapy for stage I seminoma.
abstract: OBJECTIVE
  Photon radiotherapy has been the standard adjuvant treatment for stage I seminoma. Single-dose carboplatin therapy and observation have emerged as alternative options due to concerns for acute toxicities and secondary malignancies from radiation. In this institutional review board-approved study, we compared photon and proton radiotherapy for stage I seminoma and the predicted rates of excess secondary malignancies for both treatment modalities.
  
  
  METHODS
  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 and warrants further study for patients with seminoma, to decrease radiation-induced toxicity.
authors.affiliation: Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA. csimone@alumni.upenn.edu
authors.forename: Charles B
authors.initials: CB
authors.lastname: Simone
authors.forename: Kevin
authors.initials: K
authors.lastname: Kramer
authors.forename: William P
authors.initials: WP
authors.lastname: O'Meara
authors.forename: Justin E
authors.initials: JE
authors.lastname: Bekelman
authors.forename: Arnaud
authors.initials: A
authors.lastname: Belard
authors.forename: James
authors.initials: J
authors.lastname: McDonough
authors.forename: John
authors.initials: J
authors.lastname: O'Connell
mesh_terms: D000328:Adult; D006801:Humans; D007420:Intestine, Large / Q000000981:diagnostic imaging / Q000528:radiation effects; D008017:Life Expectancy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000209:etiology*; D058958:Organs at Risk / Q000000981:diagnostic imaging / Q000528:radiation effects; D010179:Pancreas / Q000000981:diagnostic imaging / Q000528:radiation effects; D017785:Photons / Q000009:adverse effects* / Q000627:therapeutic use*; D061766:Proton Therapy; D011522:Protons / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D018239:Seminoma / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D013270:Stomach / Q000000981:diagnostic imaging / Q000528:radiation effects; D013736:Testicular Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D014057:Tomography, X-Ray Computed; D001743:Urinary Bladder / Q000000981:diagnostic imaging / Q000528:radiation effects; D055815:Young Adult
chemical_list: D011522:Protons