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Comparison of intra-arterial cisplatin and radiation therapy (RT) to other radiation therapy oncology group (RTOG) regimens using standard or accelerated RT with or without concurrent chemotherapy in patients with stage IV-T4 head and neck cancer
Proceedings of the 46th Annual ASTRO Meeting
2265
Is a Planned Neck Dissection Necessary After Chemoradiotherapy in Head and Neck Cancer Patients with Advanced Nodal Stage
S. G. Soltys,1 A. Suen,1 W. Fee,3 H. Pinto,2 R. Sivanandan,3 R. Goode,3 D. Goffinet,1 Q. Le1 Radiation Oncology, Stanford University Medical Center, Stanford, CA, 2Medical Oncology, Stanford University Medical Center, Stanford, CA, 3Otolaryngology-Head and Neck Surgery, Stanford University Medical Center, Stanford, CA 1
Purpose/Objective: The use of planned neck dissection (ND) in patients with advanced nodal disease in head and neck squamous cell carcinoma (HNSCC) after treatment with chemoradiotherapy is controversial. The purpose of this study is to clarify the role for neck dissection in patients treated with combined chemoradiotherapy (CRT) on 2 similar organ preservation protocols at our institution. Materials/Methods: The records of 90 patients with N2-N3 neck nodes who were treated between 1991 and 2001 at Stanford University on two organ preservation CRT protocols (OSP2 and OSP3) were reviewed. All patients received 2 cycles of cisplatin and 5-Fluorouracil (5-FU) induction chemotherapy, followed by concurrent CRT with similar chemotherapeutic agents. Patients on OSP3 were randomized to receive either CRT alone versus CRT and Tirapazamine for 8 doses. Radiotherapy was delivered at conventional fractionation at 2 Gy/fraction to a total dose of 66 –70 Gy to the gross target volume. Patients with persistent neck nodes either clinically or radiographically at a planned evaluation at 50 Gy proceeded to a neck dissection following completion of CRT. Patients treated on the OSP3 protocol (n ⫽ 54) also received a single dose of 5 Gy delivered via 9 –16 MeV electrons to the largest nodal mass prior to treatment for the comet study. The median follow up was 3.6 years. Results: Overall, 63% (n ⫽ 57) of the patients attained a clinical complete response (cCR) in the neck; of these, 8 patients had a ND and all 8 had a pathologic complete response (pCR). Of the remaining 49 cCR patients whose necks were observed, 13 relapsed and 2 had a neck relapse without a recurrence at the primary site (1 with an isolated neck recurrence, 1 with a neck and distant failure). Of the 33 patients (37%) with ⬍ cCR in the neck, 2 had progressive disease and died. The remaining 31 patients had NDs with a pCR rate of 52% (n ⫽ 16). Outcomes of the 3 groups: (1) cCR, (2) ⬍ cCR/pCR and (3) ⬍ cCR/⬍ pCR are summarized in table 1. The cCR rates were similar for the 2 OSP protocols (61% and 65%). There was a trend for higher pCR rate patients who underwent ND in OSP3 group (58% vs. 42%, p ⫽ 0.3, 2 Test) Conclusions: Based on our experience, in patients with N2-N3 neck nodes who have achieved a clinical and radiographic cCR in the neck following CRT, planned ND benefited only 4% (2/49) and is therefore not routinely recommended. Patients with a ⬍cCR should proceed to ND. Patients with pathologically persistent tumors in the neck on ND specimens have poor prognosis and will need more aggressive therapy.
2266
Comparison of Intra-Arterial Cisplatin and Radiation Therapy (RT) to Other Radiation Therapy Oncology Group (RTOG) Regimens Using Standard or Accelerated RT With or Without Concurrent Chemotherapy in Patients with Stage IV-T4 Head and Neck Cancer
P. Kumar,1 J. Harris,2 A. S. Garden,3 K. Fu,4 K. T. Robbins,5 T. Pajak,2 K.K. Ang3 Radiation Oncology, University of Southern California, Los Angeles, CA, 2Radiation Therapy Oncology Group, Philadelphia, PA, 3Radiation Oncology, MD Anderson Cancer Center, Houston, TX, 4Radiation Oncology, University of California, San Francisco, San Francisco, CA, 5Head and Neck Surgery, Southern Illinois University, Springfield, IL 1
Purpose/Objective: We compared overall survival (OS) and local regional control (LRC) in patients with stage IV-T4 disease originating from the oral cavity, oropharynx or hypopharynx among four RTOG head and neck cancer trials using RT with or without concurrent chemotherapy. Materials/Methods: The treatment regimens of the four RTOG protocols were as follows: 1. RTOG 8117--standard fractionated (SFX) RT [66.0-73.8 Gy] and 3 cycles of concurrent intravenous cisplatin (100 mg/m2 given on days 1, 22 and 43); 2. RTOG 9003 -- SFX RT (70 Gy in 7 weeks) alone [Arm 1], or accelerated fractionated (fx) RT with concomitant boost (AFX-C) [72 Gy in 42 fxs over 6 weeks] [Arm 4]; 3. RTOG 9703 -- concurrent SFX RT (70 Gy/7 weeks) with intravenous daily cisplatin (10 mg/m2) and 5-FU (400 mg/m2 daily continuous infusion during last 2 weeks of RT) [Arm 1], concurrent SFX RT (70 Gy/13 weeks given every other week) alternating with every other week of intravenous 5-FU (800 mg/m2/d x 5 days)/Hydroxyurea (HU) [1 gm po bid x 6 days] [Arm 2], or concurrent SFX RT (70 Gy/7 weeks) with weekly intravenous cisplatin (20 mg/m2) and Taxol (30 mg/m2) [Arm 3]; and 4. RTOG 9615 --intra-arterial (IA) weekly cisplatin (100 mg/m2) x 4 weeks with SFX RT (70 Gy/7 weeks) [RADPLAT therapy]. Results: The estimated 2 year local regional control rates and overall survival are noted in Table 1. Using a Cox proportional hazards model stratified by RPA class, RADPLAT therapy reduced death rates by more than 50% when compared to Protocols 9003 and 8117, and by 21% when compared to arm 1 of Protocol 9703; there was virtually no reduction in death rates when compared to arms 2 and 3 of Protocol 9703 (0.8% and 1.8%, respectively). Conclusions: RADPLAT therapy significantly improves local regional tumor control rates when compared to RT alone (SFX or AFX-C) or intravenous daily cisplatin/5-FU combined with concurrent SFX RT. Overall survival is also significantly improved by RADPLAT therapy as compared to RT alone (SFX or AFX-C) or intravenous cisplatin (given every 3 weeks as a single agent or daily with 5-FU) and concomitant SFX RT. Additionally, local regional tumor control and overall survival
S495
S496
I. J. Radiation Oncology
● Biology ● Physics
Volume 60, Number 1, Supplement, 2004
using RADPLAT therapy appear comparable to contemporary concurrent chemoradiation regimens. Further testing in a phase III randomized trial comparing RADPLAT therapy to intravenous chemotherapy and RT is warranted in order to validate our findings.
2267
Nasopharyngeal Carcinoma Staging by FDG PET
1
J. Chang, S. Chan,1 T. Yen,1 C. Liao,1 C. Lin,1 S. Ng1 Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
1
Purpose/Objective: To evaluate the value of FDG PET in staging nasopharyngeal carcinoma (NPC) Materials/Methods: Ninety five consecutive patients diagnosed with NPC in one year period underwent dual phase FDG PET in addition to conventional workup (CWU) including bone scan, chest x-ray, liver echo, blood chemistry and complete blood count. Any inconsistent findings between CWU and FDG PET were further evaluated with biopsies and/or additional imaging studies. Eighty one patients without distant metastases had repeat studies at 3– 4 months after initial radical treatment to evaluate response to treatment and look for previously undetected lesions. Results: Eighty-five patients with primary and 10 with recurrent NPC were enrolled. Of 14 patients with distant metastasis, all 14 had lesions detected by FDG PET, CWU detected the metastases in only 4. Two patients had a false positive MRI for neck node metastasis, whereas the FDG PET was accurate. FDG PET resulted in 10 patients having their stage increased and one whose stage decreased, changes that affected the choice of treatment. Four patients without distant metastases on initial work-up were found to have new lesions on FDG PET 3 to 4 months after initial treatment. Patient with N3 disease had a significantly higher incidence of distant metastases on FDG PET. However, the false positive rate for distant metastases on FDG PET was 38%. Conclusions: FDG PET stages N and M disease in NPC more accurately than does CWU. FDG PET is more sensitive than CWU for detecting distant metastases, but it is also less specific. FDG PET could substitute for bone scan, liver echo and chest X-ray in the routine staging.
2268
M.D. Anderson Consensus Guidelines for Head and Neck Target Volume Determination and Delineation
K. C. Chao,1 W. H. Morrison,1 K. K. Ang,1 D. I. Rosenthal,1 A. Ahamad,1 S. Apisarnthanarax,1 R. Weber,2 A. S. Garden1 Department of Radiation Oncology, UT M.D. Anderson Cancer center, Houston, TX, 2Head and Neck Surgery, M.D. Anderson Cancer Center, Houston, TX
1
Purpose/Objective: Target volume determination and delineation of various head and neck tumor sub-sites and presentations are evolving. We present multidisciplinary consensus guidelines of nodal clinical target volume (CTV) for head and neck intensity-modulated radiation therapy (IMRT). Materials/Methods: A collaborative multi-disciplinary effort was initiated to develop guidelines for inclusion of neck nodal regions in the CTVs for specific tumor sites and clinical presentations. Recommendations were derived by integrating patterns of lymphatic metastasis and locoregional failure gathered from published data with clinical discretion of the study participants. Three CTVs were defined. The CTV1 encompasses the primary gross tumor volume (pGTV) or enlarged pathologic lymph nodes (nGTV) and receives a full dose. The CTV2 encompasses the high-risk regions adjacent to CTV1 but not directly involved by tumor but judged to be at high-risk for tumor spread and receives an intermediate dose. The CTV3 includes the uninvolved cervical lymph nodes to receive elective nodal radiation dose (prophylactically treated neck). Results: A consensus was reached for clinically node negative (N0) and positive (N⫹) necks. For N0 necks, the CTV1 encompasses the pGTV for all sites. Adjacent nodal regions to CTV1 were deemed unnecessary for N0 necks, and no target volume was specified for CTV2. Furthermore, early stage (T1-2 N0) maxillary sinus and glottic tumors are to be treated only with CTV1. Contralateral nodes were included in the CTV3 for all tumors, except for maxillary sinus, early buccal/retromolar trigone (RMT), and early tonsil cancers. However, contralateral nodes may be optionally included in the CTV3 for more advanced primary tumors or midline tumor. Retropharyngeal lymph nodes were considered to be at risk for all tumors, except for early buccal/RMT tumors. Recommendations for N⫹ were designed to be simple and were congruent for all sub-sites. Both the nodal and primary gross tumor volumes are encompassed in CTV1 for all tumors with N⫹ necks. We propose to include nodal regions immediately adjacent to CTV1 (on average 3 cm distance except toward the skin surface, air, or bone) in CTV2.
2265
Is a Planned Neck Dissection Necessary After Chemoradiotherapy in Head and Neck Cancer Patients with Advanced Nodal Stage
S. G. Soltys,1 A. Suen,1 W. Fee,3 H. Pinto,2 R. Sivanandan,3 R. Goode,3 D. Goffinet,1 Q. Le1 Radiation Oncology, Stanford University Medical Center, Stanford, CA, 2Medical Oncology, Stanford University Medical Center, Stanford, CA, 3Otolaryngology-Head and Neck Surgery, Stanford University Medical Center, Stanford, CA 1
Purpose/Objective: The use of planned neck dissection (ND) in patients with advanced nodal disease in head and neck squamous cell carcinoma (HNSCC) after treatment with chemoradiotherapy is controversial. The purpose of this study is to clarify the role for neck dissection in patients treated with combined chemoradiotherapy (CRT) on 2 similar organ preservation protocols at our institution. Materials/Methods: The records of 90 patients with N2-N3 neck nodes who were treated between 1991 and 2001 at Stanford University on two organ preservation CRT protocols (OSP2 and OSP3) were reviewed. All patients received 2 cycles of cisplatin and 5-Fluorouracil (5-FU) induction chemotherapy, followed by concurrent CRT with similar chemotherapeutic agents. Patients on OSP3 were randomized to receive either CRT alone versus CRT and Tirapazamine for 8 doses. Radiotherapy was delivered at conventional fractionation at 2 Gy/fraction to a total dose of 66 –70 Gy to the gross target volume. Patients with persistent neck nodes either clinically or radiographically at a planned evaluation at 50 Gy proceeded to a neck dissection following completion of CRT. Patients treated on the OSP3 protocol (n ⫽ 54) also received a single dose of 5 Gy delivered via 9 –16 MeV electrons to the largest nodal mass prior to treatment for the comet study. The median follow up was 3.6 years. Results: Overall, 63% (n ⫽ 57) of the patients attained a clinical complete response (cCR) in the neck; of these, 8 patients had a ND and all 8 had a pathologic complete response (pCR). Of the remaining 49 cCR patients whose necks were observed, 13 relapsed and 2 had a neck relapse without a recurrence at the primary site (1 with an isolated neck recurrence, 1 with a neck and distant failure). Of the 33 patients (37%) with ⬍ cCR in the neck, 2 had progressive disease and died. The remaining 31 patients had NDs with a pCR rate of 52% (n ⫽ 16). Outcomes of the 3 groups: (1) cCR, (2) ⬍ cCR/pCR and (3) ⬍ cCR/⬍ pCR are summarized in table 1. The cCR rates were similar for the 2 OSP protocols (61% and 65%). There was a trend for higher pCR rate patients who underwent ND in OSP3 group (58% vs. 42%, p ⫽ 0.3, 2 Test) Conclusions: Based on our experience, in patients with N2-N3 neck nodes who have achieved a clinical and radiographic cCR in the neck following CRT, planned ND benefited only 4% (2/49) and is therefore not routinely recommended. Patients with a ⬍cCR should proceed to ND. Patients with pathologically persistent tumors in the neck on ND specimens have poor prognosis and will need more aggressive therapy.
2266
Comparison of Intra-Arterial Cisplatin and Radiation Therapy (RT) to Other Radiation Therapy Oncology Group (RTOG) Regimens Using Standard or Accelerated RT With or Without Concurrent Chemotherapy in Patients with Stage IV-T4 Head and Neck Cancer
P. Kumar,1 J. Harris,2 A. S. Garden,3 K. Fu,4 K. T. Robbins,5 T. Pajak,2 K.K. Ang3 Radiation Oncology, University of Southern California, Los Angeles, CA, 2Radiation Therapy Oncology Group, Philadelphia, PA, 3Radiation Oncology, MD Anderson Cancer Center, Houston, TX, 4Radiation Oncology, University of California, San Francisco, San Francisco, CA, 5Head and Neck Surgery, Southern Illinois University, Springfield, IL 1
Purpose/Objective: We compared overall survival (OS) and local regional control (LRC) in patients with stage IV-T4 disease originating from the oral cavity, oropharynx or hypopharynx among four RTOG head and neck cancer trials using RT with or without concurrent chemotherapy. Materials/Methods: The treatment regimens of the four RTOG protocols were as follows: 1. RTOG 8117--standard fractionated (SFX) RT [66.0-73.8 Gy] and 3 cycles of concurrent intravenous cisplatin (100 mg/m2 given on days 1, 22 and 43); 2. RTOG 9003 -- SFX RT (70 Gy in 7 weeks) alone [Arm 1], or accelerated fractionated (fx) RT with concomitant boost (AFX-C) [72 Gy in 42 fxs over 6 weeks] [Arm 4]; 3. RTOG 9703 -- concurrent SFX RT (70 Gy/7 weeks) with intravenous daily cisplatin (10 mg/m2) and 5-FU (400 mg/m2 daily continuous infusion during last 2 weeks of RT) [Arm 1], concurrent SFX RT (70 Gy/13 weeks given every other week) alternating with every other week of intravenous 5-FU (800 mg/m2/d x 5 days)/Hydroxyurea (HU) [1 gm po bid x 6 days] [Arm 2], or concurrent SFX RT (70 Gy/7 weeks) with weekly intravenous cisplatin (20 mg/m2) and Taxol (30 mg/m2) [Arm 3]; and 4. RTOG 9615 --intra-arterial (IA) weekly cisplatin (100 mg/m2) x 4 weeks with SFX RT (70 Gy/7 weeks) [RADPLAT therapy]. Results: The estimated 2 year local regional control rates and overall survival are noted in Table 1. Using a Cox proportional hazards model stratified by RPA class, RADPLAT therapy reduced death rates by more than 50% when compared to Protocols 9003 and 8117, and by 21% when compared to arm 1 of Protocol 9703; there was virtually no reduction in death rates when compared to arms 2 and 3 of Protocol 9703 (0.8% and 1.8%, respectively). Conclusions: RADPLAT therapy significantly improves local regional tumor control rates when compared to RT alone (SFX or AFX-C) or intravenous daily cisplatin/5-FU combined with concurrent SFX RT. Overall survival is also significantly improved by RADPLAT therapy as compared to RT alone (SFX or AFX-C) or intravenous cisplatin (given every 3 weeks as a single agent or daily with 5-FU) and concomitant SFX RT. Additionally, local regional tumor control and overall survival
S495
S496
I. J. Radiation Oncology
● Biology ● Physics
Volume 60, Number 1, Supplement, 2004
using RADPLAT therapy appear comparable to contemporary concurrent chemoradiation regimens. Further testing in a phase III randomized trial comparing RADPLAT therapy to intravenous chemotherapy and RT is warranted in order to validate our findings.
2267
Nasopharyngeal Carcinoma Staging by FDG PET
1
J. Chang, S. Chan,1 T. Yen,1 C. Liao,1 C. Lin,1 S. Ng1 Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
1
Purpose/Objective: To evaluate the value of FDG PET in staging nasopharyngeal carcinoma (NPC) Materials/Methods: Ninety five consecutive patients diagnosed with NPC in one year period underwent dual phase FDG PET in addition to conventional workup (CWU) including bone scan, chest x-ray, liver echo, blood chemistry and complete blood count. Any inconsistent findings between CWU and FDG PET were further evaluated with biopsies and/or additional imaging studies. Eighty one patients without distant metastases had repeat studies at 3– 4 months after initial radical treatment to evaluate response to treatment and look for previously undetected lesions. Results: Eighty-five patients with primary and 10 with recurrent NPC were enrolled. Of 14 patients with distant metastasis, all 14 had lesions detected by FDG PET, CWU detected the metastases in only 4. Two patients had a false positive MRI for neck node metastasis, whereas the FDG PET was accurate. FDG PET resulted in 10 patients having their stage increased and one whose stage decreased, changes that affected the choice of treatment. Four patients without distant metastases on initial work-up were found to have new lesions on FDG PET 3 to 4 months after initial treatment. Patient with N3 disease had a significantly higher incidence of distant metastases on FDG PET. However, the false positive rate for distant metastases on FDG PET was 38%. Conclusions: FDG PET stages N and M disease in NPC more accurately than does CWU. FDG PET is more sensitive than CWU for detecting distant metastases, but it is also less specific. FDG PET could substitute for bone scan, liver echo and chest X-ray in the routine staging.
2268
M.D. Anderson Consensus Guidelines for Head and Neck Target Volume Determination and Delineation
K. C. Chao,1 W. H. Morrison,1 K. K. Ang,1 D. I. Rosenthal,1 A. Ahamad,1 S. Apisarnthanarax,1 R. Weber,2 A. S. Garden1 Department of Radiation Oncology, UT M.D. Anderson Cancer center, Houston, TX, 2Head and Neck Surgery, M.D. Anderson Cancer Center, Houston, TX
1
Purpose/Objective: Target volume determination and delineation of various head and neck tumor sub-sites and presentations are evolving. We present multidisciplinary consensus guidelines of nodal clinical target volume (CTV) for head and neck intensity-modulated radiation therapy (IMRT). Materials/Methods: A collaborative multi-disciplinary effort was initiated to develop guidelines for inclusion of neck nodal regions in the CTVs for specific tumor sites and clinical presentations. Recommendations were derived by integrating patterns of lymphatic metastasis and locoregional failure gathered from published data with clinical discretion of the study participants. Three CTVs were defined. The CTV1 encompasses the primary gross tumor volume (pGTV) or enlarged pathologic lymph nodes (nGTV) and receives a full dose. The CTV2 encompasses the high-risk regions adjacent to CTV1 but not directly involved by tumor but judged to be at high-risk for tumor spread and receives an intermediate dose. The CTV3 includes the uninvolved cervical lymph nodes to receive elective nodal radiation dose (prophylactically treated neck). Results: A consensus was reached for clinically node negative (N0) and positive (N⫹) necks. For N0 necks, the CTV1 encompasses the pGTV for all sites. Adjacent nodal regions to CTV1 were deemed unnecessary for N0 necks, and no target volume was specified for CTV2. Furthermore, early stage (T1-2 N0) maxillary sinus and glottic tumors are to be treated only with CTV1. Contralateral nodes were included in the CTV3 for all tumors, except for maxillary sinus, early buccal/retromolar trigone (RMT), and early tonsil cancers. However, contralateral nodes may be optionally included in the CTV3 for more advanced primary tumors or midline tumor. Retropharyngeal lymph nodes were considered to be at risk for all tumors, except for early buccal/RMT tumors. Recommendations for N⫹ were designed to be simple and were congruent for all sub-sites. Both the nodal and primary gross tumor volumes are encompassed in CTV1 for all tumors with N⫹ necks. We propose to include nodal regions immediately adjacent to CTV1 (on average 3 cm distance except toward the skin surface, air, or bone) in CTV2.