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Can Nanoparticle Technology Improve Side Effects after Irradiation of the Head and Neck?
I. J. Radiation Oncology d Biology d Physics
S450
2551
Volume 78, Number 3, Supplement, 2010
Proton Therapy of Nasal Cavity and Paranasal Sinuses: The UFPTI Experience
R. S. Malyapa, D. Yeung, C. McKenzie, W. M. Mendenhall, Z. Li, N. P. Mendenhall University of Florida Proton Therapy Institute, Jacksonville, FL Purpose/Objective(s): Thirty-eight patients with tumors of the nasal cavity and paranasal sinuses with skull base extension have completed treatment with proton therapy at UFPTI since January of 2007. The disease characteristics, treatment planning and delivery techniques, and follow-up results are presented. Materials/Methods: Of the 38 patients, 35 had prior surgery, 17 with positive margins. Three patients had biopsy only. Histology included poorly differentiated carcinoma, sino-nasal undifferentiated carcinoma, adenocarcinoma, adenoid cystic carcinoma, esthesioneuroblastoma, mucosal melanoma and spindle-cell carcinoma. Proton treatment targets and critical structures were delineated from co-registered simulation CT images and diagnostic MR images. The geometric relations between target volumes and critical structures were examined to select optimal proton beam parameters. Proton-specific through- and patch-fields, as well as match fields were used for these patients to achieve target-conforming and critical organ-sparing concave dose distributions. Prescribed doses ranged from 68.4 CGE to 69.6 CGE for post-op negative margins, to 74.4 CGE for positive margins or presence of gross unresectable tumor. A 1.2 CGE twice-a-day fractionation scheme, separated by at least 6 hours on the same day, was used in all patients. Proton treatments were delivered with orthogonal kV x-ray imaging guidance, to achieve 1 mm setup accuracy, for each fraction. Results: Patient follow-ups ranged from 1 to 29 months, with a mean of 13.1 months. All patients completed their prescribed treatment and tolerated the treatment well. Brisk skin reactions developed in all patients, and resolved within 4 weeks after completion of treatment. Follow-up imaging studies and biopsy revealed in-field recurrent disease in two patients at 9 and 10 months, progressive meningeal seeding in one patient within two months after completion and distant visceral and bony metastasis in three patients between 6 and 12 months after completion. Medial retinopathy occurred within the treated volume in one patient at 11 months after completion of treatment without negative impact on visual acuity. Conclusions: Our experience suggests that patients with tumors involving the nasal cavity and paranasal sinuses with extension to the skull base will benefit from high-dose conformal proton therapy treatments. Author Disclosure: R.S. Malyapa, None; D. Yeung, None; C. McKenzie, None; W.M. Mendenhall, None; Z. Li, None; N.P. Mendenhall, None.
2552
Can Nanoparticle Technology Improve Side Effects after Irradiation of the Head and Neck?
R. Manon, R. Madero-Visbal, J. Colon, B. Alvarado, M. Wason, C. Baker M.D. Anderson Cancer Center-Orlando, Orlando, FL Purpose/Objective(s): A Pilot Study was conducted to evaluate the ability of cerium oxide nanoparticles (CeO2) to improve toxicity in athymic mice treated with radiation. Materials/Methods: The head and neck region of athymic nude mice was treated with radiation therapy (RT) using a IC160 X-ray irradiation system (Kimtron Inc., Woodbury, Connecticut, USA). Animals were anesthetized and placed supine under the radiation focal spot. RT was given with an AP portal using a 160 kV X-ray unit. There were three cohorts with respect to RT (N = 30 per cohort); A) received no radiation exposure; B) received a single dose of 17.5 Gy; and C) received 30 Gy/6 fractions. Further, in each cohort, animals were randomized into three groups (N = 10 per group): 1) intraperitoneal (i.p.) injection of saline; 2) i.p. injection of 15 nM CeO2; and 3) i.p. injection of 15 mM CeO2. Two independent double-blinded researchers graded radiation-induced dermatitis and hyperpigmentation at 1, 4, and 12 weeks after RT according to CTC v. 3.0 criteria. Ninety days after radiation, all mice were anesthetized and stimulated salivary flow was measured after subcutaneous pilocarpine injection (2mg/kg of B.W.) . The animals were then sacrificed, salivary gland specimens were fixed, and cell death was evaluated via TUNEL analysis. Results: Sialometry demonstrated improved salivary production in all CeO2 groups compared to controls not receiving CeO2 (mean salivary flow 204 vs. 115 mL/10min p = .0002). Grade 3 dermatitis was more prevalent in the fractionated vs. the single fraction cohort. In the fractionated cohort, the incidence of grade 3 dermatitis 1 week after radiation was decreased in the 15 mM CeO2 group compared to the non-CeO2 controls (10% vs. 100% incidence of Grade 3 dermatitis, respectively). A similar effect in reduction of grade 3 dermatitis was seen in the 15 mM CeO2 group when compared to non-CeO2 controls in both radiation cohorts for all time points evaluated. This effect was not appreciated in the 15 nM CeO2 group. There was a decrease in skin hyperpigmentation at 12 weeks in the 15 mM CeO2 group compared to the 15 nM CeO2 and non-CeO2 groups (50, 70, and 90% grade 2, respectively). No Grade V toxicities were noted in the 15 mM CeO2 group of mice. TUNEL analysis demonstrated a dose dependent decrease in cell death inversely proportional to CeO2 concentration. There were no adverse effects noted in the groups of mice receiving CeO2 without radiation. Conclusions: CeO2 may have a protective effect on salivary gland cells of athymic mice, which is associated with improved saliva production after RT. Observations also suggest a reduction in Grade 3 radiation-induced dermatitis and skin hyperpigmentation. The use of CeO2 as a radioprotectant appears to be a feasible concept that will be tested in a larger cohort of mice using a 15 mM concentration of CeO2. Author Disclosure: R. Manon, None; R. Madero-Visbal, None; J. Colon, None; B. Alvarado, None; M. Wason, None; C. Baker, None.
2553
Phase I Study of Oral S-1 and Concurrent Radiotherapy in Patients with Head and Neck Cancer
K. Nakata, M. Someya, M. Takagi, J. Hayashi, K. Miura, K. Sakata, M. Hareyama Sapporo Medical University, Sapporo 060-8556, Japan Purpose/Objective(s): S-1 is a novel orally administered drug invented in Japan, which is a combination of tegafur, 5-chloro-2,4dihydroxypyridine (gimeracil) and potassium oxonate (oteracil) in a 1:0.4:1 molar concentration ratio. Concurrent radiotherapy
S450
2551
Volume 78, Number 3, Supplement, 2010
Proton Therapy of Nasal Cavity and Paranasal Sinuses: The UFPTI Experience
R. S. Malyapa, D. Yeung, C. McKenzie, W. M. Mendenhall, Z. Li, N. P. Mendenhall University of Florida Proton Therapy Institute, Jacksonville, FL Purpose/Objective(s): Thirty-eight patients with tumors of the nasal cavity and paranasal sinuses with skull base extension have completed treatment with proton therapy at UFPTI since January of 2007. The disease characteristics, treatment planning and delivery techniques, and follow-up results are presented. Materials/Methods: Of the 38 patients, 35 had prior surgery, 17 with positive margins. Three patients had biopsy only. Histology included poorly differentiated carcinoma, sino-nasal undifferentiated carcinoma, adenocarcinoma, adenoid cystic carcinoma, esthesioneuroblastoma, mucosal melanoma and spindle-cell carcinoma. Proton treatment targets and critical structures were delineated from co-registered simulation CT images and diagnostic MR images. The geometric relations between target volumes and critical structures were examined to select optimal proton beam parameters. Proton-specific through- and patch-fields, as well as match fields were used for these patients to achieve target-conforming and critical organ-sparing concave dose distributions. Prescribed doses ranged from 68.4 CGE to 69.6 CGE for post-op negative margins, to 74.4 CGE for positive margins or presence of gross unresectable tumor. A 1.2 CGE twice-a-day fractionation scheme, separated by at least 6 hours on the same day, was used in all patients. Proton treatments were delivered with orthogonal kV x-ray imaging guidance, to achieve 1 mm setup accuracy, for each fraction. Results: Patient follow-ups ranged from 1 to 29 months, with a mean of 13.1 months. All patients completed their prescribed treatment and tolerated the treatment well. Brisk skin reactions developed in all patients, and resolved within 4 weeks after completion of treatment. Follow-up imaging studies and biopsy revealed in-field recurrent disease in two patients at 9 and 10 months, progressive meningeal seeding in one patient within two months after completion and distant visceral and bony metastasis in three patients between 6 and 12 months after completion. Medial retinopathy occurred within the treated volume in one patient at 11 months after completion of treatment without negative impact on visual acuity. Conclusions: Our experience suggests that patients with tumors involving the nasal cavity and paranasal sinuses with extension to the skull base will benefit from high-dose conformal proton therapy treatments. Author Disclosure: R.S. Malyapa, None; D. Yeung, None; C. McKenzie, None; W.M. Mendenhall, None; Z. Li, None; N.P. Mendenhall, None.
2552
Can Nanoparticle Technology Improve Side Effects after Irradiation of the Head and Neck?
R. Manon, R. Madero-Visbal, J. Colon, B. Alvarado, M. Wason, C. Baker M.D. Anderson Cancer Center-Orlando, Orlando, FL Purpose/Objective(s): A Pilot Study was conducted to evaluate the ability of cerium oxide nanoparticles (CeO2) to improve toxicity in athymic mice treated with radiation. Materials/Methods: The head and neck region of athymic nude mice was treated with radiation therapy (RT) using a IC160 X-ray irradiation system (Kimtron Inc., Woodbury, Connecticut, USA). Animals were anesthetized and placed supine under the radiation focal spot. RT was given with an AP portal using a 160 kV X-ray unit. There were three cohorts with respect to RT (N = 30 per cohort); A) received no radiation exposure; B) received a single dose of 17.5 Gy; and C) received 30 Gy/6 fractions. Further, in each cohort, animals were randomized into three groups (N = 10 per group): 1) intraperitoneal (i.p.) injection of saline; 2) i.p. injection of 15 nM CeO2; and 3) i.p. injection of 15 mM CeO2. Two independent double-blinded researchers graded radiation-induced dermatitis and hyperpigmentation at 1, 4, and 12 weeks after RT according to CTC v. 3.0 criteria. Ninety days after radiation, all mice were anesthetized and stimulated salivary flow was measured after subcutaneous pilocarpine injection (2mg/kg of B.W.) . The animals were then sacrificed, salivary gland specimens were fixed, and cell death was evaluated via TUNEL analysis. Results: Sialometry demonstrated improved salivary production in all CeO2 groups compared to controls not receiving CeO2 (mean salivary flow 204 vs. 115 mL/10min p = .0002). Grade 3 dermatitis was more prevalent in the fractionated vs. the single fraction cohort. In the fractionated cohort, the incidence of grade 3 dermatitis 1 week after radiation was decreased in the 15 mM CeO2 group compared to the non-CeO2 controls (10% vs. 100% incidence of Grade 3 dermatitis, respectively). A similar effect in reduction of grade 3 dermatitis was seen in the 15 mM CeO2 group when compared to non-CeO2 controls in both radiation cohorts for all time points evaluated. This effect was not appreciated in the 15 nM CeO2 group. There was a decrease in skin hyperpigmentation at 12 weeks in the 15 mM CeO2 group compared to the 15 nM CeO2 and non-CeO2 groups (50, 70, and 90% grade 2, respectively). No Grade V toxicities were noted in the 15 mM CeO2 group of mice. TUNEL analysis demonstrated a dose dependent decrease in cell death inversely proportional to CeO2 concentration. There were no adverse effects noted in the groups of mice receiving CeO2 without radiation. Conclusions: CeO2 may have a protective effect on salivary gland cells of athymic mice, which is associated with improved saliva production after RT. Observations also suggest a reduction in Grade 3 radiation-induced dermatitis and skin hyperpigmentation. The use of CeO2 as a radioprotectant appears to be a feasible concept that will be tested in a larger cohort of mice using a 15 mM concentration of CeO2. Author Disclosure: R. Manon, None; R. Madero-Visbal, None; J. Colon, None; B. Alvarado, None; M. Wason, None; C. Baker, None.
2553
Phase I Study of Oral S-1 and Concurrent Radiotherapy in Patients with Head and Neck Cancer
K. Nakata, M. Someya, M. Takagi, J. Hayashi, K. Miura, K. Sakata, M. Hareyama Sapporo Medical University, Sapporo 060-8556, Japan Purpose/Objective(s): S-1 is a novel orally administered drug invented in Japan, which is a combination of tegafur, 5-chloro-2,4dihydroxypyridine (gimeracil) and potassium oxonate (oteracil) in a 1:0.4:1 molar concentration ratio. Concurrent radiotherapy