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Concurrent Chemoradiotherapy with S-1 (TS-1) as First-Line Treatment for Oropharyngeal Cancer
I. J. Radiation Oncology d Biology d Physics
S410
Volume 75, Number 3, Supplement, 2009
patient variables included smoking history, alcohol abuse, gender, age, primary site, tumor stage, and nodal status. We also examined tumor expression of p16 by immunohistochemistry and EGFR mutation in exons encoding the hot-spot regions in the tyrosine kinase domain of EGFR (exons 18, 19, 20 and 21) by PCR-Invader assay. These markers were assessed for association with HPV infection and clinical outcome. Results: Twelve of 45 biopsies (27%) were positive for high-risk HPV and 17 (38%) expressed p16. p16 expression was significantly associated with HPV positivity (p \ .0001). No EGFR mutation was found in these 45 biopsies. No patient variable was significantly associated with HPV infection, but younger age, nonsmoking status, and no alcohol abuse tend to associate with HPV positivity. After a median follow-up of 31.7 months, patients with HPV-positive tumors had improved disease-specific survival (2-year disease-specific survival for HPV-positive and HPV-negative was 91% and 59%, respectively, p = .045, log–rank test). Patients with HPV-positive tumors had a trend of better response to IC and therefore, 9 of these patients (75%) were treated with organ-sparing treatment. Conclusions: Similar to patients from western ethnicity, HPV infection is implicated in the development of Japanese OSCC. Although the numbers in this study are small, tumor HPV infection is associated with therapeutic response and survival in OSCC patients. IC followed by CCRT is an effective treatment for OSCC, especially in patients with HPV-positive tumors, for the goal of organ preservation. Author Disclosure: Y. Ota, None; T. Soejima, None; K. Tsujino, None; O. Fujii, None; S. Iwae, None; T. Sudo, None; C. Ohbayashi, None; R. Sasaki, None.
2509
Concurrent Chemoradiotherapy with S-1 (TS-1) as First-Line Treatment for Oropharyngeal Cancer
K. Ohnishi, Y. Shioyama, S. Nomoto, S. Ohga, T. Nonoshita, T. Yoshitake, K. Atsumi, K. Terashima, H. Hirata, H. Honda Kyushu University Hospital, Fukuoka, Japan Purpose/Objective(s): S-1 is an oral anticancer agent that combines tegafur, a metabolically activated prodrug of 5-fluorouracil, with 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. S-1 alone has been shown high response rate in the late Phase II trial in patients with advanced or recurrent head and neck cancer. The purpose of this study is to review the clinical outcomes of S-1 with concurrent radiotherapy for patients with oropharyngeal cancer. Materials/Methods: Between 2002 and 2007, 43 patients with oropharyngeal cancer treated with S-1 with definitive radiotherapy concurrently at our institution were reviewed. There were 38 men and 5 women with a median age of 60 years (range, 37–81 years). Forty patients (93%) had squamous cell histology. The primary sites were the tonsil in 29 patients, the posterior wall in 6, the soft palate in 5, and the base of tongue in 3. The clinical stage was Stage I in 4 (9%) patients, Stage II in 6 (14%), Stage III in 8, and Stage IV in 25 (58%). S-1 was administered orally twice daily for 4 consecutive weeks followed by 2-weeks drug withdrawal. The initial dose of S-1 was 80mg/m2/day according to the package insert in Japan. All patients were treated using three-dimensional conformal radiotherapy, with a median total dose of 65.4 Gy (range, 60.0–71.0 Gy). Clinical outcomes and major acute toxicities including mucositis and hematological toxicities were analyzed based on medical records and clinical follow-up. Results: With a median follow-up time of 32 months, the 3-year estimates of local-regional control, distant metastases-free survival, disease-free survival and overall survival for all patients were 69%, 80%, 60% and 74%, respectively. Of the 43 patients, 16 patients with early disease (T1–2 and N0–1) had no local-regional recurrences. Of the remaining 27 patients with advanced disease (T1–2 and N2–3 or T3–4 and any N), 6 patients showed local recurrence and 9 patients developed regional recurrence. Local-regional control rate at 3 years according to the Stage were 100% for patients with Stage I and II, 75% for Stage III, and 52% for Stage IV. The acute mucositis was Grade 1 in 4 patients (9%), Grade 2 in 25 (58%), and Grade 3 in 14 (33%). The rate of Grade 3 and higher hematological toxicities was 16%. No other severe toxicities were observed. Conclusions: Concurrent chemoradiotherapy with S-1 was considered to be effective, especially for early disease. Treatment-related toxicities were acceptable and the incidence of myelotoxicity was low. Further study must be performed to compare with other chemotherapy regimens. Author Disclosure: K. Ohnishi, None; Y. Shioyama, None; S. Nomoto, None; S. Ohga, None; T. Nonoshita, None; T. Yoshitake, None; K. Atsumi, None; K. Terashima, None; H. Hirata, None; H. Honda, None.
2510
Outcomes after Intensity-modulated Radiation Therapy for Larynx-sparing Treatment of Hypopharynx Carcinoma
A. C. Cupino, P. A. Levine, J. F. Reibel, C. Y. Thomas, M. J. Jameson, P. W. Read University of Virginia Health System, Charlottesville, VA Purpose/Objective(s): To examine the use of intensity-modulated radiation therapy (IMRT) in the definitive treatment of patients with squamous cell carcinoma of the hypopharynx. Materials/Methods: Retrospective analysis of 18 patients with hypopharyngeal squamous cell carcinoma treated with definitive chemoradiation between August, 2002 and April, 2008. T-Stage as follows: T1 = 4, T2 = 7, T3 = 2, and T4 = 5. The gross disease PTV was prescribed 70 Gy in 35 fractions, and the sub-clinical disease was prescribed 50 Gy in 25 fractions. Induction chemotherapy consisted of platinum with capecitabine or a taxane. Patients having at least a partial response received cisplatin or carboplatin concurrently with radiation. Results: Median follow-up was 2.5 years. Actuarial functional larynx survival (no local disease recurrence, no tracheostomy, and no percutaneous endoscopic gastrostomy (PEG) tube), freedom from distant metastases, disease free survival, and overall survival at 3 years is 57%, 82%, 55%, and 63%, respectively. Four patients (22%) required gastrostomy (PEG) tube during radiation therapy. Two patients (11%) required PEG tube longer than one year: one due to a second malignancy, and due to incomplete therapy. Only one patient (6%) required salvage laryngectomy. Four patients (22%) experienced Grade 2 late toxicity: dysphagia (2), xerostomia (1), or throat pain (1). No Grade 3 or higher late toxicity was noted. Synchronous or metachronous cancers were found in four patients (22%).
S410
Volume 75, Number 3, Supplement, 2009
patient variables included smoking history, alcohol abuse, gender, age, primary site, tumor stage, and nodal status. We also examined tumor expression of p16 by immunohistochemistry and EGFR mutation in exons encoding the hot-spot regions in the tyrosine kinase domain of EGFR (exons 18, 19, 20 and 21) by PCR-Invader assay. These markers were assessed for association with HPV infection and clinical outcome. Results: Twelve of 45 biopsies (27%) were positive for high-risk HPV and 17 (38%) expressed p16. p16 expression was significantly associated with HPV positivity (p \ .0001). No EGFR mutation was found in these 45 biopsies. No patient variable was significantly associated with HPV infection, but younger age, nonsmoking status, and no alcohol abuse tend to associate with HPV positivity. After a median follow-up of 31.7 months, patients with HPV-positive tumors had improved disease-specific survival (2-year disease-specific survival for HPV-positive and HPV-negative was 91% and 59%, respectively, p = .045, log–rank test). Patients with HPV-positive tumors had a trend of better response to IC and therefore, 9 of these patients (75%) were treated with organ-sparing treatment. Conclusions: Similar to patients from western ethnicity, HPV infection is implicated in the development of Japanese OSCC. Although the numbers in this study are small, tumor HPV infection is associated with therapeutic response and survival in OSCC patients. IC followed by CCRT is an effective treatment for OSCC, especially in patients with HPV-positive tumors, for the goal of organ preservation. Author Disclosure: Y. Ota, None; T. Soejima, None; K. Tsujino, None; O. Fujii, None; S. Iwae, None; T. Sudo, None; C. Ohbayashi, None; R. Sasaki, None.
2509
Concurrent Chemoradiotherapy with S-1 (TS-1) as First-Line Treatment for Oropharyngeal Cancer
K. Ohnishi, Y. Shioyama, S. Nomoto, S. Ohga, T. Nonoshita, T. Yoshitake, K. Atsumi, K. Terashima, H. Hirata, H. Honda Kyushu University Hospital, Fukuoka, Japan Purpose/Objective(s): S-1 is an oral anticancer agent that combines tegafur, a metabolically activated prodrug of 5-fluorouracil, with 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. S-1 alone has been shown high response rate in the late Phase II trial in patients with advanced or recurrent head and neck cancer. The purpose of this study is to review the clinical outcomes of S-1 with concurrent radiotherapy for patients with oropharyngeal cancer. Materials/Methods: Between 2002 and 2007, 43 patients with oropharyngeal cancer treated with S-1 with definitive radiotherapy concurrently at our institution were reviewed. There were 38 men and 5 women with a median age of 60 years (range, 37–81 years). Forty patients (93%) had squamous cell histology. The primary sites were the tonsil in 29 patients, the posterior wall in 6, the soft palate in 5, and the base of tongue in 3. The clinical stage was Stage I in 4 (9%) patients, Stage II in 6 (14%), Stage III in 8, and Stage IV in 25 (58%). S-1 was administered orally twice daily for 4 consecutive weeks followed by 2-weeks drug withdrawal. The initial dose of S-1 was 80mg/m2/day according to the package insert in Japan. All patients were treated using three-dimensional conformal radiotherapy, with a median total dose of 65.4 Gy (range, 60.0–71.0 Gy). Clinical outcomes and major acute toxicities including mucositis and hematological toxicities were analyzed based on medical records and clinical follow-up. Results: With a median follow-up time of 32 months, the 3-year estimates of local-regional control, distant metastases-free survival, disease-free survival and overall survival for all patients were 69%, 80%, 60% and 74%, respectively. Of the 43 patients, 16 patients with early disease (T1–2 and N0–1) had no local-regional recurrences. Of the remaining 27 patients with advanced disease (T1–2 and N2–3 or T3–4 and any N), 6 patients showed local recurrence and 9 patients developed regional recurrence. Local-regional control rate at 3 years according to the Stage were 100% for patients with Stage I and II, 75% for Stage III, and 52% for Stage IV. The acute mucositis was Grade 1 in 4 patients (9%), Grade 2 in 25 (58%), and Grade 3 in 14 (33%). The rate of Grade 3 and higher hematological toxicities was 16%. No other severe toxicities were observed. Conclusions: Concurrent chemoradiotherapy with S-1 was considered to be effective, especially for early disease. Treatment-related toxicities were acceptable and the incidence of myelotoxicity was low. Further study must be performed to compare with other chemotherapy regimens. Author Disclosure: K. Ohnishi, None; Y. Shioyama, None; S. Nomoto, None; S. Ohga, None; T. Nonoshita, None; T. Yoshitake, None; K. Atsumi, None; K. Terashima, None; H. Hirata, None; H. Honda, None.
2510
Outcomes after Intensity-modulated Radiation Therapy for Larynx-sparing Treatment of Hypopharynx Carcinoma
A. C. Cupino, P. A. Levine, J. F. Reibel, C. Y. Thomas, M. J. Jameson, P. W. Read University of Virginia Health System, Charlottesville, VA Purpose/Objective(s): To examine the use of intensity-modulated radiation therapy (IMRT) in the definitive treatment of patients with squamous cell carcinoma of the hypopharynx. Materials/Methods: Retrospective analysis of 18 patients with hypopharyngeal squamous cell carcinoma treated with definitive chemoradiation between August, 2002 and April, 2008. T-Stage as follows: T1 = 4, T2 = 7, T3 = 2, and T4 = 5. The gross disease PTV was prescribed 70 Gy in 35 fractions, and the sub-clinical disease was prescribed 50 Gy in 25 fractions. Induction chemotherapy consisted of platinum with capecitabine or a taxane. Patients having at least a partial response received cisplatin or carboplatin concurrently with radiation. Results: Median follow-up was 2.5 years. Actuarial functional larynx survival (no local disease recurrence, no tracheostomy, and no percutaneous endoscopic gastrostomy (PEG) tube), freedom from distant metastases, disease free survival, and overall survival at 3 years is 57%, 82%, 55%, and 63%, respectively. Four patients (22%) required gastrostomy (PEG) tube during radiation therapy. Two patients (11%) required PEG tube longer than one year: one due to a second malignancy, and due to incomplete therapy. Only one patient (6%) required salvage laryngectomy. Four patients (22%) experienced Grade 2 late toxicity: dysphagia (2), xerostomia (1), or throat pain (1). No Grade 3 or higher late toxicity was noted. Synchronous or metachronous cancers were found in four patients (22%).