prospective phase ii trial of concomitant boost radiotherapy for stage ii nasopharyngeal carcinoma

1
metastasize. However the local response to fast neutrons is similar to other salivary gland histologies including adenoid cystic and mucoepidermoid carcinoma. Author Disclosure: K.R. Saroja, None; A.J. Lennox, None; J.M. Sixta, None. 2478 Biological Evaluation of a Dose Response in the Oral Cavity of Patients Undergoing Head and Neck Radiotherapy S. Narayan 1 , M. Coleman 2 , J. Lehman 1 , G. Loredo 1 , C. Yang 1 , J. Purdy 1 , S. Vijayakumar 1 , A. Vaughan 1 , 2 1 University of California at Davis, Sacramento, CA, 2 Lawrence Livermore National Laboratory, Livermore, CA Purpose/Objective(s): In vivo dose verification and correlation of dose with biological changes within humans remains an active area of investigation with implications for radiation safety and treatment. In a collaborative effort between Lawrence Livermore National Laboratory and the University of California Davis Medical Center we developed RNA transcript assays for dose analysis within the oral cavity of head and neck cancers patients treated with radiation therapy. Materials/Methods: Nine males and 3 females undergoing therapy for head and neck cancer were enrolled on a prospective pro- tocol approved by our institutional review board. Median age was 61 (range 23–79). For buccal sampling four points were chosen in separate quadrants of the patient’s oral cavity adjacent to identifiable landmarks along the buccal mucosa. Each patient under- went buccal sampling prior to and 24 h following the first radiation treatment at the four selected points using a cytobrush to remove surface cells–preserved in RNAlater for transcript analysis using QPCR. Results: Maximum and average radiation doses received by the sampled sites of a single patient ranged from 0.32 to 2.04 Gy and 0.65 to 2.07 Gy, respectively. A point dose maximum of 2.07 Gy (Ptn. 6) and a widest range 0.05–1.1 Gy (Ptn. 1) were observed for individual sampling points. Calculated dose distributions were compared to dose at each sample point using MOSFET dosimeters. A total of 16 transcripts were selected for analysis based on microarray studies in cell lines that identified robust ionizing radiation- induced responses. QPCR analysis was focused on only 6 of the patients for which at least one of the four samples received a dose .1 Gy. The QPCR method was able to detect all 16 transcripts tested within each patient and in general showed elevated levels post irradiation. However, there was substantial variation in sample transcript both within the same patient as well as between patients. Tran- scripts such as ASTN2, PCNA, TNFRSF6, GADD45A and CDKNIA showed the most robust irradiation response across the 6 patients. Conclusions: This study demonstrated the feasibility of the rapid and well tolerated collection of buccal cavity cells form patients both before and after single fraction irradiation. Further, statistically significant increases in transcripts were readily detected in samples taken from irradiated patients. Further refinements to sample collection and processing will be required in order to detect a dose response in an individual patient covering the range of doses received within the buccal cavity after single fraction irradi- ation. Nevertheless the system as described offers a well tolerated biological indicator of the effects of repetitive radiation exposure to patients receiving therapeutic irradiation to the Head and Neck. This work was performed under the auspices of the US DOE by the University of California, LLNL under Contract No. W-7405- Eng-48 with funding from the DOE Low Dose Radiation Research Program. Author Disclosure: S. Narayan, None; M. Coleman, None; J. Lehman, None; G. Loredo, None; C. Yang, None; J. Purdy, None; S. Vijayakumar, None; A. Vaughan, None. 2479 Prospective Phase II Trial of Concomitant Boost Radiotherapy for Stage II Nasopharyngeal Carcinoma J. J. Lu National University Hospital, Singapore, Singapore Purpose/Objective(s): Stage II nasopharyngeal carcinoma (NPC) treated with conventionally fractionated radiotherapy results in suboptimal outcome. This report aims to document the outcome of Stage II NPC patients treated with external beam radiotherapy delivered using an accelerated concomitant boost (C-Boost) schedule. Materials/Methods: Forty-seven 1997 AJCC Stage II NPC patients were enrolled and analyzed in this prospective phase II clin- ical trial. The primary tumor and clinically involved nodes received a total dose of 72 Gy in 42 fractions. C-Boost for gross disease consisted of 18 Gy in 12 fractions commencing on day 19, and delivered at least 6 hours after the first dose. Patients were assessed for response, survival and toxicity. Results: With a median follow-up of 30 months, 4 patients developed local recurrence only, 2 had persistent neck nodal disease or recurrence, and 1 with both locoregional recurrences. Distant metastases were seen in 5 patients, with or without locoregional re- currence. A total of 5 patients succumbed from nasopharyngeal cancer: four from effects of distant metastases and 1 from progres- sive local disease. The 3-year local, regional, and overall survival rates were 87.1%, 92%, and 85.9%, respectively. All patients experienced some degree of acute and/or late toxicity. Moderate to severe late toxicities (grade 3 and 4) were observed in 17% of cases. Conclusions: This C-Boost radiotherapy regimen administers a higher biologically effective dose compared with conventional radiation schedules, and substantially improves the overall survival rate for patients diagnosed with stage II nasopharyngeal carcinoma. Author Disclosure: J.J. Lu, None. 2480 A Phase II Study of Intensity Modulated Radiation Therapy (IMRT) Combined Chemotherapy in Local Advanced Nasopharyngeal Carcinoma (NPC) G. Zhu, Y. Wu, H. Ying, X. He, C. Hu Cancer Hospital of Fudan University, Shanghai, China Purpose/Objective(s): The aim of this prospective study is to analysis the preliminary clinical results of intensity modulated radiation therapy (IMRT) with combined chemotherapy for patients with advanced nasopharyngeal carcinoma. Proceedings of the 49th Annual ASTRO Meeting S467

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Page 1: Prospective Phase II Trial of Concomitant Boost Radiotherapy for Stage II Nasopharyngeal Carcinoma

Proceedings of the 49th Annual ASTRO Meeting S467

metastasize. However the local response to fast neutrons is similar to other salivary gland histologies including adenoid cystic andmucoepidermoid carcinoma.

Author Disclosure: K.R. Saroja, None; A.J. Lennox, None; J.M. Sixta, None.

2478 Biological Evaluation of a Dose Response in the Oral Cavity of Patients Undergoing Head and Neck

Radiotherapy

S. Narayan1, M. Coleman2, J. Lehman1, G. Loredo1, C. Yang1, J. Purdy1, S. Vijayakumar1, A. Vaughan1,2

1University of California at Davis, Sacramento, CA, 2Lawrence Livermore National Laboratory, Livermore, CA

Purpose/Objective(s): In vivo dose verification and correlation of dose with biological changes within humans remains an activearea of investigation with implications for radiation safety and treatment. In a collaborative effort between Lawrence LivermoreNational Laboratory and the University of California Davis Medical Center we developed RNA transcript assays for dose analysiswithin the oral cavity of head and neck cancers patients treated with radiation therapy.

Materials/Methods: Nine males and 3 females undergoing therapy for head and neck cancer were enrolled on a prospective pro-tocol approved by our institutional review board. Median age was 61 (range 23–79). For buccal sampling four points were chosenin separate quadrants of the patient’s oral cavity adjacent to identifiable landmarks along the buccal mucosa. Each patient under-went buccal sampling prior to and 24 h following the first radiation treatment at the four selected points using a cytobrush to removesurface cells–preserved in RNAlater for transcript analysis using QPCR.

Results: Maximum and average radiation doses received by the sampled sites of a single patient ranged from 0.32 to 2.04 Gy and0.65 to 2.07 Gy, respectively. A point dose maximum of 2.07 Gy (Ptn. 6) and a widest range 0.05–1.1 Gy (Ptn. 1) were observed forindividual sampling points. Calculated dose distributions were compared to dose at each sample point using MOSFET dosimeters. Atotal of 16 transcripts were selected for analysis based on microarray studies in cell lines that identified robust ionizing radiation-induced responses. QPCR analysis was focused on only 6 of the patients for which at least one of the four samples received a dose.1 Gy. The QPCR method was able to detect all 16 transcripts tested within each patient and in general showed elevated levels postirradiation. However, there was substantial variation in sample transcript both within the same patient as well as between patients. Tran-scripts such as ASTN2, PCNA, TNFRSF6, GADD45A and CDKNIA showed the most robust irradiation response across the 6 patients.

Conclusions: This study demonstrated the feasibility of the rapid and well tolerated collection of buccal cavity cells form patientsboth before and after single fraction irradiation. Further, statistically significant increases in transcripts were readily detected insamples taken from irradiated patients. Further refinements to sample collection and processing will be required in order to detecta dose response in an individual patient covering the range of doses received within the buccal cavity after single fraction irradi-ation. Nevertheless the system as described offers a well tolerated biological indicator of the effects of repetitive radiation exposureto patients receiving therapeutic irradiation to the Head and Neck.

This work was performed under the auspices of the US DOE by the University of California, LLNL under Contract No. W-7405-Eng-48 with funding from the DOE Low Dose Radiation Research Program.

Author Disclosure: S. Narayan, None; M. Coleman, None; J. Lehman, None; G. Loredo, None; C. Yang, None; J. Purdy, None;S. Vijayakumar, None; A. Vaughan, None.

2479 Prospective Phase II Trial of Concomitant Boost Radiotherapy for Stage II Nasopharyngeal Carcinoma

J. J. Lu

National University Hospital, Singapore, Singapore

Purpose/Objective(s): Stage II nasopharyngeal carcinoma (NPC) treated with conventionally fractionated radiotherapy results insuboptimal outcome. This report aims to document the outcome of Stage II NPC patients treated with external beam radiotherapydelivered using an accelerated concomitant boost (C-Boost) schedule.

Materials/Methods: Forty-seven 1997 AJCC Stage II NPC patients were enrolled and analyzed in this prospective phase II clin-ical trial. The primary tumor and clinically involved nodes received a total dose of 72 Gy in 42 fractions. C-Boost for gross diseaseconsisted of 18 Gy in 12 fractions commencing on day 19, and delivered at least 6 hours after the first dose. Patients were assessedfor response, survival and toxicity.

Results: With a median follow-up of 30 months, 4 patients developed local recurrence only, 2 had persistent neck nodal disease orrecurrence, and 1 with both locoregional recurrences. Distant metastases were seen in 5 patients, with or without locoregional re-currence. A total of 5 patients succumbed from nasopharyngeal cancer: four from effects of distant metastases and 1 from progres-sive local disease. The 3-year local, regional, and overall survival rates were 87.1%, 92%, and 85.9%, respectively.

All patients experienced some degree of acute and/or late toxicity. Moderate to severe late toxicities (grade 3 and 4) wereobserved in 17% of cases.

Conclusions: This C-Boost radiotherapy regimen administers a higher biologically effective dose compared with conventionalradiation schedules, and substantially improves the overall survival rate for patients diagnosed with stage II nasopharyngealcarcinoma.

Author Disclosure: J.J. Lu, None.

2480 A Phase II Study of Intensity Modulated Radiation Therapy (IMRT) Combined Chemotherapy in Local

Advanced Nasopharyngeal Carcinoma (NPC)

G. Zhu, Y. Wu, H. Ying, X. He, C. Hu

Cancer Hospital of Fudan University, Shanghai, China

Purpose/Objective(s): The aim of this prospective study is to analysis the preliminary clinical results of intensity modulatedradiation therapy (IMRT) with combined chemotherapy for patients with advanced nasopharyngeal carcinoma.