- Email: [email protected]
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I. J. Radiation Oncology
2429
● Biology ● Physics
Volume 66, Number 3, Supplement, 2006
The Prognostic Significance of EGFR Expression in African American Patients With Squamous Cell Carcinomas of the Head and Neck
K. M. Settle, R. Taylor, J. Papadimitriou, N. Carter-Monroe, N. Murali, J. Wolf, K. Cullen, M. Suntharalingam University of Maryland School of Medicine, Baltimore, MD Purpose/Objective(s): To determine the prognostic significance of EGFR expression in African American (AA) patients (pts) who received concurrent chemoradiation for locally advanced SCC H&N. Materials/Methods: We performed a retrospective analysis of 103 patients with Stage III/IV SCC H&N, who were treated at the University of Maryland between 1997 and 2003. All patients received daily RT, to a total dose of 70.2Gy (1.8Gy/day), concurrently with weekly Carboplatin (100mg/m2) and Paclitaxel (45mg/m2). This initial analysis revealed a significantly worse outcome for AA pts in terms of median survival, disease recurrence, and distant failure. Based on these findings, a correlative pathological study was performed on 20 AA pts tissue specimens to determine the impact of EGFR expression on outcome. A total of 20 paraffin tissue sections were stained for antibody against EGFR using the Ventana Benchmark system. The stained slides were then analyzed using ChromaVision Automated Cellular Imaging System. Image capture technology was used to quantify EGFR staining positivity based on color, color purity, and intensity. Staining Intensity (SI) was reported in terms of staining intensity (SI) on a scale of 0 to 97. The ACIS score (SC) of 0 to 4⫹ was documented in order to reflect IHC positivity by visual inspection. Results: The initial cohort of 103 patients (58% Caucasian and 42% AA) was similar with respect to age, gender, clinical stage, and tumor site. The median survival (MS) for the entire group was 30 months. AA pts had a higher rate of disease recurrence compared to CAU pts, 57% versus 37% (p⫽0.05). In addition, AA pts had a higher rate of distant failure, 27% versus 12% (p ⫽0.06). On multivariate analysis, factors which predicted for recurrence included race (p⫽0.02) and stage of disease (p⫽0.05). Among the 20 AA tissue samples, all stained IHC positive for EGFR. Average SC staining based on tumor differentiation is as follows: Well to moderately differentiated SC⫽ 3.2; moderately differentiated SC ⫽2.9; moderately to poorly differentiated SC⫽ 2.8; and poorly differentiated SC⫽ 2.4. The median SI for the entire cohort was 67.5. Pts who’s SI ranged above the median, had a MS of 34 months and 2 year and 5 year OS 60% and 32%, respectively. Pts who’s SI ranged below the median, had a MS of 71 months and a 2 year and 5 year OS of 75% and 60%, respectively. Conclusions: This preliminary analysis of IHC staining among AA pts suggests that EGFR expression may play a role in predicting response to concurrent chemoradiation. Further analysis of existing patient data will be necessary to validate these initial findings. Continued exploration of potential differences in cell surface receptor expression is critical as we continue to integrate biologic therapies into current chemoradiation strategies. Author Disclosure: K.M. Settle, None; R. Taylor, None; J. Papadimitriou, None; N. Carter-Monroe, None; N. Murali, None; J. Wolf, None; K. Cullen, None; M. Suntharalingam, BMS, Imclone, Aventis, Roche, MedImmune, B. Research Grant; BMS, Imclone, MedImmune, D. Speakers Bureau/Honoraria; BMS, Imclone, MedImmune, F. Consultant/Advisory Board.
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Prospective Phase II Trial of Concomitant Boost Radiotherapy for Stage II Nasopharyngeal Carcinoma
1
J. J. Lu , L. Kong2,3, K. Loh1, T. P. Shakespeare1, A. Thiagarajan1, K. Tan1 1 3
National University Hospital, Singapore, Singapore, 2Cancer Hospital of Fudan University, Shanghai, China, National University Hospital, Singapore, Singapore
Background: The long-term local control rates for Stage II nasopharyngeal carcinoma (NPC) after conventional radiation therapy is approximately 70%. Radiation therapy using accelerated concomitant boost schedule has been proven to be efficacious in treating locally advanced head and neck cancers. Purpose/Objective(s): The aim of this trial is to study the outcome of Stage II NPC patients treated with external beam radiotherapy delivered using a concomitant boost schedule. Materials/Methods: Forty-two patients with pathologically confirmed Stage II (1997 AJCC Classification) undifferentiated nasopharyngeal carcinoma were enrolled and analyzed in this prospective phase II trial. The primary tumor and clinically involved nodes received a total dose of 72 Gy in 42 fractions. Concomitant boost radiation for gross disease consisted of 18 Gy in 12 fractions commencing on day 19 and was delivered at least 6 hours after the first daily dose of 1.8 Gy. All patients were assessed for response, survival, and toxicity. Results: With a median follow-up of 28 months, 5 patients developed pathologically confirmed local recurrence, necessitating IMRT or surgery, 2 developed neck recurrence and were treated with neck dissection or chemotherapy, and 3 were treated with systemic chemotherapy for their distant relapses. One patient who had persistent neck lymphadenopathy and declined further treatment developed and died of distant metastasis. In addition, 3 patients died of distant metastasis only, and 1 patient died from bleeding secondary to nasopharyngectomy for local recurrence. The 2-year local control, regional control, and overall survival rates were 92.5%, 95.1%, and 90.7%, respectively; and those of three years were 82.4%, 89.5%, and 83.0 %, respectively. All patients experienced some degree of acute and/or late toxicity. Grade 3 trismus, soft tissue fibrosis, hearing loss, and cranial nerve palsy were seen in 1, 1, 3, and 1 patients, respectively. No patient had grade 4 or 5 toxicity after their definitive radiotherapy. The toxicity profile was comparable to that seen following standard fractionation. Acute or late toxicities directly attributable to concomitant boost radiation were not observed. Conclusions: This concomitant boost radiation regimen administers a substantially higher biologically effective dose compared with conventional radiation schedules. This radiation schedule may produce improved local and regional control rates without significant acute and/or late toxicities. Author Disclosure: J.J. Lu, None; L. Kong, None; K. Loh, None; T.P. Shakespeare, None; A. Thiagarajan, None; K. Tan, None.
I. J. Radiation Oncology
2429
● Biology ● Physics
Volume 66, Number 3, Supplement, 2006
The Prognostic Significance of EGFR Expression in African American Patients With Squamous Cell Carcinomas of the Head and Neck
K. M. Settle, R. Taylor, J. Papadimitriou, N. Carter-Monroe, N. Murali, J. Wolf, K. Cullen, M. Suntharalingam University of Maryland School of Medicine, Baltimore, MD Purpose/Objective(s): To determine the prognostic significance of EGFR expression in African American (AA) patients (pts) who received concurrent chemoradiation for locally advanced SCC H&N. Materials/Methods: We performed a retrospective analysis of 103 patients with Stage III/IV SCC H&N, who were treated at the University of Maryland between 1997 and 2003. All patients received daily RT, to a total dose of 70.2Gy (1.8Gy/day), concurrently with weekly Carboplatin (100mg/m2) and Paclitaxel (45mg/m2). This initial analysis revealed a significantly worse outcome for AA pts in terms of median survival, disease recurrence, and distant failure. Based on these findings, a correlative pathological study was performed on 20 AA pts tissue specimens to determine the impact of EGFR expression on outcome. A total of 20 paraffin tissue sections were stained for antibody against EGFR using the Ventana Benchmark system. The stained slides were then analyzed using ChromaVision Automated Cellular Imaging System. Image capture technology was used to quantify EGFR staining positivity based on color, color purity, and intensity. Staining Intensity (SI) was reported in terms of staining intensity (SI) on a scale of 0 to 97. The ACIS score (SC) of 0 to 4⫹ was documented in order to reflect IHC positivity by visual inspection. Results: The initial cohort of 103 patients (58% Caucasian and 42% AA) was similar with respect to age, gender, clinical stage, and tumor site. The median survival (MS) for the entire group was 30 months. AA pts had a higher rate of disease recurrence compared to CAU pts, 57% versus 37% (p⫽0.05). In addition, AA pts had a higher rate of distant failure, 27% versus 12% (p ⫽0.06). On multivariate analysis, factors which predicted for recurrence included race (p⫽0.02) and stage of disease (p⫽0.05). Among the 20 AA tissue samples, all stained IHC positive for EGFR. Average SC staining based on tumor differentiation is as follows: Well to moderately differentiated SC⫽ 3.2; moderately differentiated SC ⫽2.9; moderately to poorly differentiated SC⫽ 2.8; and poorly differentiated SC⫽ 2.4. The median SI for the entire cohort was 67.5. Pts who’s SI ranged above the median, had a MS of 34 months and 2 year and 5 year OS 60% and 32%, respectively. Pts who’s SI ranged below the median, had a MS of 71 months and a 2 year and 5 year OS of 75% and 60%, respectively. Conclusions: This preliminary analysis of IHC staining among AA pts suggests that EGFR expression may play a role in predicting response to concurrent chemoradiation. Further analysis of existing patient data will be necessary to validate these initial findings. Continued exploration of potential differences in cell surface receptor expression is critical as we continue to integrate biologic therapies into current chemoradiation strategies. Author Disclosure: K.M. Settle, None; R. Taylor, None; J. Papadimitriou, None; N. Carter-Monroe, None; N. Murali, None; J. Wolf, None; K. Cullen, None; M. Suntharalingam, BMS, Imclone, Aventis, Roche, MedImmune, B. Research Grant; BMS, Imclone, MedImmune, D. Speakers Bureau/Honoraria; BMS, Imclone, MedImmune, F. Consultant/Advisory Board.
2430
Prospective Phase II Trial of Concomitant Boost Radiotherapy for Stage II Nasopharyngeal Carcinoma
1
J. J. Lu , L. Kong2,3, K. Loh1, T. P. Shakespeare1, A. Thiagarajan1, K. Tan1 1 3
National University Hospital, Singapore, Singapore, 2Cancer Hospital of Fudan University, Shanghai, China, National University Hospital, Singapore, Singapore
Background: The long-term local control rates for Stage II nasopharyngeal carcinoma (NPC) after conventional radiation therapy is approximately 70%. Radiation therapy using accelerated concomitant boost schedule has been proven to be efficacious in treating locally advanced head and neck cancers. Purpose/Objective(s): The aim of this trial is to study the outcome of Stage II NPC patients treated with external beam radiotherapy delivered using a concomitant boost schedule. Materials/Methods: Forty-two patients with pathologically confirmed Stage II (1997 AJCC Classification) undifferentiated nasopharyngeal carcinoma were enrolled and analyzed in this prospective phase II trial. The primary tumor and clinically involved nodes received a total dose of 72 Gy in 42 fractions. Concomitant boost radiation for gross disease consisted of 18 Gy in 12 fractions commencing on day 19 and was delivered at least 6 hours after the first daily dose of 1.8 Gy. All patients were assessed for response, survival, and toxicity. Results: With a median follow-up of 28 months, 5 patients developed pathologically confirmed local recurrence, necessitating IMRT or surgery, 2 developed neck recurrence and were treated with neck dissection or chemotherapy, and 3 were treated with systemic chemotherapy for their distant relapses. One patient who had persistent neck lymphadenopathy and declined further treatment developed and died of distant metastasis. In addition, 3 patients died of distant metastasis only, and 1 patient died from bleeding secondary to nasopharyngectomy for local recurrence. The 2-year local control, regional control, and overall survival rates were 92.5%, 95.1%, and 90.7%, respectively; and those of three years were 82.4%, 89.5%, and 83.0 %, respectively. All patients experienced some degree of acute and/or late toxicity. Grade 3 trismus, soft tissue fibrosis, hearing loss, and cranial nerve palsy were seen in 1, 1, 3, and 1 patients, respectively. No patient had grade 4 or 5 toxicity after their definitive radiotherapy. The toxicity profile was comparable to that seen following standard fractionation. Acute or late toxicities directly attributable to concomitant boost radiation were not observed. Conclusions: This concomitant boost radiation regimen administers a substantially higher biologically effective dose compared with conventional radiation schedules. This radiation schedule may produce improved local and regional control rates without significant acute and/or late toxicities. Author Disclosure: J.J. Lu, None; L. Kong, None; K. Loh, None; T.P. Shakespeare, None; A. Thiagarajan, None; K. Tan, None.