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Proton Therapy of Nasal Cavity and Paranasal Sinus Tumors: The UFPTI Experience

Reviewer: Eric Shinohara MD, MSCI
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 14 de octubre del 2009

Presenter: Dr. R. Malyapa
Presenter's Affiliation: University of Florida Proton Therapy Institute, Jacksonville, Florida, USA
Type of Session: Scientific

Background

• Compared with 3D conformal radiation therapy, a number of studies have suggested that IMRT is able to attenuate treatment-related toxicity in patients with nasopharyngeal cancer (NPX) or cancers of the sinuses.
• However, despite the greater conformality that can be achieved with IMRT, critical dose limiting structures such as the brainstem, optic chiasm and optic nerves can still receive significant doses, leading to severe toxicities and impeding the delivery of adequate dose. Tumors which involve the base of skull can be particularly challenging.
• Protons have a better physical dose distribution compared with photon-based therapy, and have an RBE that is close to that of photons.
• The improved dose distribution with protons may allow greater sparing of critical structures .
• This study examined the use of hyperfractionated proton therapy in the treatment of tumors of the NPX and the sinuses.

Materials and Methods

• Patients were accrued at the University of Florida starting in January of 2007. Patients with tumors of the NPX or paranasal sinuses that involved the base of skull were eligible for this study.
• Radiation:
  • All patients had a planning CT with co-registration with a diagnostic MRI.
  • Patching was used to optimize proton delivery to provide optimal target coverage while maximizing sparing of critical normal structures.
  • Patients were treated to a total dose of between 69.6 and 74.4 CGE in 1.2 CGE fractions using bid dosing
    • Doses of between 68.4-69.6 CGE were used for patients with negative postoperative margins.
    • A dose of 74.4 CGE was used for patients with close or positive margins or for those patients with perineural invasion.
    • The low neck was treated with a matching photon field.
    • Some patients were treated with a mix of IMRT and protons to the primary.
    • Orthogonal kV imaging was used with a setup accuracy of approximately 1 mm for each fraction.
• Chemotherapy
  • Patients were treated with Cisplatin 30 mg/m2 weekly

Results

• From January 2007 to June 2009 a total of 26 patients were enrolled.
• Median age of the patients was 49 years old (range 30-81).
• 23/26 patients had surgery, 12 with positive margins and three with biopsy only .
• Histologies included in the present study:
  • adenocarcinoma .
  • adenoid cystic.
  • esthesioneuroblastoma.
  • mucosal melanoma.
  • poorly differentiated carcinoma.
  • sino-nasal undifferentiated carcinoma carcinoma.
• Disease sites included (number of patients):
  • sinonasal (10)
  • maxillary (6)
  • ethmoid (8)
  • frontal (1)
  • sphenoid (1)
• Stage (number of patients):
  • T1 (1)
  • T2 (1)
  • T3 (6)
  • T4 (14)
• Median follow up was 12.5 months (range 4-25 months).
• Recurrences
  • Two patients had an infield recurrence.
  • One patient had a meningeal recurrence.
  • Three patients developed distant disease.
• Toxicity:
  • One patient had a medial retinopathy that occurred in an area that was within the treatment volume.
  • All patients developed a brisk skin reaction after 4 weeks of treatment.
  • Otherwise treatment was generally well tolerated

Author's Conclusions

• Patients who underwent resection had better outcomes compared with patients who were treated with radiation alone .
• The results from this study suggest that tumors of the base of skull may benefit from high dose, hyperfractionated proton therapy.

Clinical/Scientific Implications

Treatment of tumors of the NPX and surrounding sinuses remains challenging. Although there have been better results with NPX tumors, in tumors in certain locations and with certain histologies, outcomes remain suboptimal. Proton therapy may allow for less dose to be delivered to critical normal structures and could potentially allow for dose escalation, which may improve local control. This study suggests that proton therapy using a patch technique is feasible and may be effective. There are several challenges to delivering proton therapy to the NPX and surrounding sinuses. Changes in the density of the sinuses due to collection of fluids may change the protons’ range and dose distribution. There is also the potential for greater skin reactions due to higher skin doses if only a few proton beams are used. However, in the present study, it appears that toxicity was tolerable. Longer follow up is needed to confirm local control rates and survival and further studies should be performed to confirm tumor coverage, perhaps using PET dosimetry. Protons may ultimate play a major role in the treatment of tumors which involve the base of skull either as the primary treatment or as a boost after photon-based therapy.