Proton beam therapy for locally advanced Sinonasal squamous cell carcinoma

Reporter: J. Taylor Whaley, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 14, 2011

Presenter: Marco Cianchetti, M.D., Annie W. Chan, M.D., Minh T. Truong, M.D., Judy G. Adams, C.M.D., Paul M. Busse, M.D., Norbert J. Liebsch, M.D., and Jing J. Wang, M.P.H.
Presenter's Affiliation: Department of Radiation Oncology, Harvard Cancer Center


  • Sinonasal carcinomas are tumors found within the nasal cavity and paranasal sinus.
  • The most common histology for sinonasal carcinomas is overwhelmingly squamous cell carcinoma.
  • Paranasal sinus cancer is relatively rare, with only 2000 people diagnosed each year in the United States.
  • The typical age range at the time of diagnosis is middle age to elderly individuals.
  • Historically, the majority of patients with sinonasal carcinoma have been treated with surgical resection and post-operative radiation therapy; however, radical surgery can be morbid, leaving patients with severe deformations. With recent advances in chemotherapy and radiation techniques, concurrent chemoradiation is increasingly used in the definitive setting.
  • Due to the lack of exit radiation associated with proton therapy, significant dosimetric advantages can be seen compared to patients who were historically treated with photon therapy.
  • The purpose of this study was to evaluate outcomes in patients with sinonasal squamous cell carcinoma treated with proton beam therapy.

Materials and Methods

  • Between 1991 and 2008, 62 patients were treated with proton beam therapy for locally advanced sinonasal squamous cell carcinoma.
  • 43 patients were treated in the post-operative setting while 19 patients were treated in the definitive setting.
  • 53% of patients in the surgical group had T4b disease and 95% of patients in the definitive radiation group had T4b disease.
  • 33% of the post-operative patients received concurrent chemotherapy and 53% in the definitive radiation group received concurrent chemotherapy.
  • Median total doses to the primary site were 70 Gy (RBE) and 76 Gy (RBE) for the post-operative group and definitive group, respectively.
  • Doses and volume of regional nodes varied based on laterality of tumor and nodal status. 70% of patients had regional lymphatics treated with proton radiotherapy.
  • Median follow up was 28 months for all patients, 25 months for patients treated with definitive protons, and 45 months for post-operative patients.


  • Median age of patients at the time of treatment was 52 years old in the definitive setting and 59 years old in the post-operative setting.
  • There was no significant difference in Karnofsky Performance Status at the time of treatment.
  • In the definitive proton therapy group, 58% had sphenoid sinus tumors and 42% had paranasal sinus tumors. In the adjuvant group, 12% had sphenoid sinus primary tumors and 88% had paranasal sinus tumors.
  • Treatment outcomes data can be found in the table below:


Definitive Proton Therapy

Adjuvant Proton Therapy

Local Control



Regional Control



Freedom for Distant Metastases



Overal Survivial



Disease Specific Survival



  • The most common site of failure was distant failure. There was no significant difference found in any outcome parameter between the adjuvant and definitive setting.
  • No treatment was stopped secondary to excess toxicity and no grade 5 toxicity was recorded.
  • In the definitive proton group, 7% had grade 2 and 7% had grade 3 toxicity. In the adjuvant group, 30% had grade 2 toxicity and 22% had grade 3 toxicity. In the post-operative group, 17% had cutaneous fistula formation at the site of surgery.
  • The orbital preservation rates were 81% in the adjuvant group and 100% in the definitive group (p = 0.09).

Author’s Conclusions

  • In patients with locally advanced sinonasal squamous cell carcinoma, definitive proton beam radiation +/- concurrent chemotherapy results in similar outcomes to that achieved in the adjuvant setting after surgical resection.
  • Acute toxicity in this cohort of patients treated with definitive proton therapy to a mean dose of 76 Gy was slightly less than that seen with radical surgical resection followed by adjuvant radiation.
  • Further follow up is required to fully evaluate the local, regional, and distant control as well as potential late side effects of proton therapy.

Clinical Implications

  • The authors present their experience with proton radiotherapy for sinonasal squamous cell carcinoma. The presentation is certainly a valuable contribution to the standing body of literature.
  • Due to the small number of cases of sinonasal carcinoma diagnosed in the United States annually, prospective trials are difficult to perform. The majority of literature involves retrospective reports from single institutions, similar to the report presented here.
  • However, as seen in this cohort of patients, definitive radiation with proton therapy may offer patients similar outcomes without radical surgery. The acute toxicity was acceptable and slightly less than that seen in the adjuvant group.
  • Due to the rapidly evolving techniques surrounding proton therapy, this very difficult and debilitating disease could be effectively treated with fewer side effects than previously seen.
  • Information on late effects and long term outcomes associated with this treatment remains unavailable and will certainly contribute to the literature when longer follow-up permits analysis of quality of life and disease control following definitive proton beam radiotherapy.