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I. J. Radiation Oncology

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● Biology ● Physics

Volume 66, Number 3, Supplement, 2006

Induction Chemotherapy followed by Chemoradiotherapy in the Treatment of Locally Advanced Tonsillar Squamous Cell Carcinoma

J. D. Kochanski, J. K. Salama, L. K. Mell, K. Stenson, E. Cohen, M. List, M. Witt, A. Dekker, E. Vokes, D. J. Haraf University of Chicago Hospitals, Chicago, IL Purpose/Objective(s): To report our experience with the treatment of Tonsillar Squamous Cell Carcinoma (SCCA) using induction chemotherapy followed by concurrent chemoradiation (CRT). Materials/Methods: From 1/1999 - 6/2002, 49 patients with locally advanced Stage IV tonsillar SCCA were treated with 2 cycles of induction carboplatin (area under the curve 2) and paclitaxel (135mg/m2) followed by concurrent paclitaxel, infusional 5-fluorouracil, hydroxyurea, delivered with 1.5 Gy BID radiation on an alternating week schedule. The median dose to gross tumor was 72 Gy (R 0 Gy -75.5 Gy). Only four patients received less then 60Gy. All patients underwent CT based planning. Neck dissections were planned on all patients with ⬎ N2a disease. Results: The median follow-up for all patients was 37 months (R 2- 73 months) and for living patients 43 months (R 12–73 months) . The breakdown by T and N stage was as follows: T stage: 7 T1, 9 T2, 9 T3, 16 T4. Nodal stage: 1 No, 4 N1, 7 N2A, 15 N2b, 6 N2c, and 8 N3. There was one local failure and no regional failures. There were four patients who failed distantly. The 2 and 3 year overall survival was 80.2% (95% CI: 66.0,89.0) and 72.3% (CI 56.9,82.9). Two and 3 year progression-free survival was 77.2% (CI: 62.7,86.7%) and 72.5% (CI: 57.4,83.1) respectively. The 2 year and 3 year cause-specific survival was 92.1% (CI: 78.1,97.1) and 87.8% (CI: 72.9,94.8). The crude local failure rate was 2% (1/49). Local regional progression free survival at 2 and 3 years was 78.1% (CI: 73.6,87.4) and 72.3% (CI: 57.0,82.9) respectively. Eighty-four percent of patients were tracheostomy free at 6 months while 82% of patients did not experience grade 3 or higher chronic toxicity. Conclusions: Our results demonstrate the effectiveness of induction chemotherapy and CRT delivered on an alternating week schedule for locally advanced tonsillar SCCA. Author Disclosure: J.D. Kochanski, None; J.K. Salama, None; L.K. Mell, None; K. Stenson, None; E. Cohen, None; M. List, None; M. Witt, None; A. Dekker, None; E. Vokes, None; D.J. Haraf, None.

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Utility of FDG-PET Scans in Staging and Prediction of Outcome in Head and Neck Cancer

S. Chaudhry, M. Natwa, J. Lavarino, P. Anne, W. Keane, C. Intenzo, M. Machtay Thomas Jefferson University Hospital, Philadelphia, PA Purpose/Objective(s): We retrospectively report our institutional experience with the utility of pre- and post- treatment (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) scanning in head and neck carcinomas (HNC). Materials/Methods: From 2003 through 2004, 54 patients with HNC underwent a pre-treatment PET scan at the time of diagnosis; of these patients, 47 underwent a post-treatment PET scan. Treatment consisted of definitive radiotherapy with or without surgery and/or chemotherapy. Initial PET scan findings and post-treatment PET response were correlated with clinical outcome. Qualitative interpretation and Standardized Uptake Value (SUV) determination was made by a single nuclear medicine physician (MN) who was blinded to clinical outcomes. Results: Median followup is 23 months. There were 7 patients (13%) in whom PET identified previously unsuspected distant metastases (confirmed with further imaging, biopsy, and/or clinical followup). The median primary tumor SUV for patients without distant metastases was 6.4 (range 1–24). Patients with a pre-treatment SUV below 6.4 had improved survival compared with patients whose SUV was ⬎ 6.4 (p⫽0.03); crude survival was 85% versus 58%. Post-treatment PET scans showed complete response (CR) in 23 of 47 patients (49%); however, CR did not correlate with survival or patterns of failure (p⫽NS). Conclusions: FDG-PET identifies distant metastases in an appreciable proportion of patients with newly diagnosed HNC. Pre-treatment PET SUV of ⬎ 6.4 (the median value in this series) was associated with poor outcome. In this relatively small series, there was no association between outcomes and CR by post-treatment PET. This work was supported in part by a grant from the Commonwealth of Pennsylvania (PA Tobacco Grant). Author Disclosure: S. Chaudhry, None; M. Natwa, None; J. Lavarino, None; P. Anne, None; W. Keane, None; C. Intenzo, None; M. Machtay, None.

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Long Term Results of Regional Control in Stage III-IV Node Positive Patients With Squamous Cell Carcinoma of the Head And Neck Using Hyperfractionated Radiation Therapy and Intraarterial Chemotherapy (HYPERRADPLAT)

S. M. Arnold1, G. W. Warren2, J. Valentino2, Y. Brill2, W. Regine3, P. Spring4, C. Given2, M. Mohiuddin5, J. L. Huhn2, M. Kudrimoti2 1 Markey Cancer Center, Lexington, KY, 2University of Kentucky, Lexington, KY, 3University of Maryland, Baltimore, MD, 4 University of Arkansas, Little Rock, AR, 5Geisinger Medical System, Wilkes Barre, PA Purpose/Objective(s): We have reported on results with hyperfractionated radiation therapy and high dose intra-arterial chemotherapy (HYPERRADPLAT) in Stage III/IV squamous cell cancer of the head and neck (SCCHN). It is often thought that the intraarterial chemotherapy to the bulk of the tumor may compromise regional and distant control. Herein we report long term control rates in node positive Stage III/IV H/N cancer. Materials/Methods: 50 patients with Stage III/IV SCCHN by virtue of bulky T2 and higher primary tumors were treated with hyperfractionated radiation therapy and high dose intraarterial cisplatin (150 mg/m2). Intraarterial injection occurred when patients reached 60 Gy coinciding with the start of the boost phase of therapy. Gross disease was treated to 76.6 – 81.6 Gy in 1.2 Gy BID fractions and low risk disease was treated to 60 Gy. Systemic effects of chemotherapy were neutralized with thiosulfate injection. Patients were monitored by a multidisciplinary head and neck cancer treatment team. Tumor response, cause specific survival (CSS), overall survival (OS), and toxicity were assessed for all patients according to NCI CCT criteria.

Proceedings of the 48th Annual ASTRO Meeting

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Results: Of 50 node positive patients, 12 patients had N1, 4 had N2A, 6 had N2B, 15 had N2C, and 13 had N3 disease. Tumors of the oropharynx were noted in 27 patients, 9-oral cavity, 8-hypoppharynx, and 6-other. Tumor stage included T2 (4%), T3 (10%), T4 (86%). Neck dissection was planned in 40% of patients. The remainder were treated to a full dose of radiation therapy (76.6 – 81.6 Gy) and neck dissection was performed in all patients (16%) without complete response at 8 weeks for patients with partial nodal response (overall neck dissection performed in 56%). Complete response at the primary site was observed in 90% of patients with 82% of patients achieving complete nodal response (42% pathologic response and 40% clinical response). Three-year CSS was 58% and OS was 44%. Overall recurrence was noted in 48% of patients with distant failure in 24% and a median time to recurrence of 10 months (range 3– 45 months). Locoregional control was maintained in 70% of patients with nodal failure in 6% of patients (all in areas of low risk disease treated with a lower dose of radiation). Median weight loss during treatment was 9% of initial body weight. Grade 3 mucositis was noted in 78% of patients and 4% of patients developed Grade 4 mucosal toxicity. Conclusions: Despite concern regarding regional nodal control with HYPERRADPLAT, results demonstrate significant organ preservation and regional control rates consistent or superior to rates reported in the literature using systemic chemoradiotherapy regimens. The incidence of distant metastases is similar to those reported in the literature for patients treated with systemic chemotherapy. Author Disclosure: S.M. Arnold, None; G.W. Warren, None; J. Valentino, None; Y. Brill, None; W. Regine, None; P. Spring, None; C. Given, None; M. Mohiuddin, None; J.L. Huhn, None; M. Kudrimoti, None.

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Retrospective and Prospective Studies of the Severity of Oral Mucositis (OM) in Intensity Modulated Radiation Therapy (IMRT) Compared to Conventional Radiation Therapy in Head and Neck Cancer (HNC) Patients

L. S. Elting1, J. Isitt2, B. A. Murphy3, A. S. Garden1, C. K. Gwede4, A. Trotti4, R. F. Meredith5, J. B. Epstein6, T. Mayne2, Q. T. Le7, et al. 1

UT MD Anderson Cancer Center, Houston, TX, 2Amgen, Inc, Thousand Oaks, CA, 3Vanderbilt University, Nashville, TN, Moffitt Cancer Center, Tampa, FL, 5University of Alabama, Birmingham, AL, 6University of Illinois, Chicago, IL, 7 Stanford University, Stanford, CA 4

Purpose/Objective(s): IMRT represents an important innovation in treatment of solid tumors. There is little research on IMRT’s impact on oral mucositis. We report the results from one retrospective and one prospective study of head and neck cancer patients receiving IMRT or conventional radiation therapy, with or without chemotherapy. Materials/Methods: Study 1: Medical records of 160 consecutive, newly diagnosed patients with cancers of the oral cavity and oropharynx were reviewed for demographic, clinical and treatment information, including clinically scored OM (NCICTC: 0⫽none to 4⫽alimentation not possible). Study 2: At 6 centers in the United States, 75 newly diagnosed patients with cancers of the oral cavity and oropharynx were assessed 5 times over 6 weeks for severity and impact of OM, using patient-reported mouth and throat soreness (MTS) score (0⫽no soreness to 4⫽extreme soreness) from the oral mucositis weekly questionnaire (OMWQ-HN). Results: The 2 study populations were remarkably similar. Study 1: 78% male; mean age ⫽ 55 years (95% CI⫽53–57 yrs); 48% received IMRT; 49% received RT plus chemotherapy. Study 2: 81% male; mean age ⫽ 59 years (95% CI⫽57– 61 yrs); 45% received IMRT; 66% received RT plus chemotherapy. The risks of grade 3– 4 OM were similar to the risks of grade 3– 4 soreness, irrespective of treatment regimen. Conclusions: Regardless of treatment regimen, the majority of HNC patients who received radiotherapy developed severe OM. There is an unmet need for prevention and treatment of OM in patients receiving radiation therapy, both with and without chemotherapy.

Percentage of patients developing severe OM (grade 3 or 4 or MTS score 3 or 4) With Chemotherapy

Study 1 % OM grade 3-4 Study 2 % MTS score 3-4

Without Chemotherapy

IMRT Value (95% CI)

Conventional RT Value (95% CI)

IMRT Value (95% CI)

Conventional RT Value (95% CI)

n⫽29 69% (49 - 85)

n⫽50 84% (71 - 93)

n⫽47 70% (55 - 83)

n⫽34 76% (59 - 89)

n⫽24 74% (52 - 90)

n⫽26 84% (64 - 96)

n⫽10 60% (26 - 88)

n⫽15 87% (60 - 98)

Author Disclosure: L.S. Elting, Amgen, Inc, C. Other Research Support; MGI Pharma, C. Other Research Support; J. Isitt, Amgen, Inc., A. Employment; B.A. Murphy, None; A.S. Garden, None; C.K. Gwede, None; A. Trotti, None; R.F. Meredith, None; J.B. Epstein, None; T. Mayne, Amgen, Inc, A. Employment; Q.T. Le, Amgen, Inc., B. Research Grant.