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Intensity Modulated Radiation Therapy (IMRT) for the Treatment of Oropharyngeal Carcinoma (OPC): Effect of Tumor Volume on Clinical Outcomes
Proceedings of the 52nd Annual ASTRO Meeting combined HDR-IORT with gross total resection and adjuvant chemoradiation as our paradigm for salvage treatment of previously irradiated head and neck cancer pts. Author Disclosure: K. Hu, EUSA, B. Research Grant; Eli-Lilly, Bristol Myers Squibb, D. Speakers Bureau/Honoraria; M. Scala, None; M. Rao, None; N. Shah, None; M. Urken, None; M. Persky, None; A. Jacobson, None; T. Tran, None; E. Furhang, None; L.B. Harrison, None.
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Intensity Modulated Radiation Therapy for Esthesioneuroblastoma: Clinical Outcomes and Toxicities
1
N. Kased , I. H. El-Sayed1, V. K. Weinberg1, M. J. Kaplan2, M. W. McDermott1, J. L. Nakamura1, J. M. Quivey1, S. S. Yom1 1
University of California, San Francisco, San Francisco, CA, 2Stanford University, Palo Alto, CA
Purpose/Objective(s): Esthesioneuroblastoma (ENB) is an uncommon tumor arising from the olfactory epithelium of the upper nasal cavity. Both surgical resection and delivery of postoperative radiation therapy are challenging due to the tumor’s proximity to orbital and intracranial contents. We hypothesize that postoperative intensity-modulated radiation therapy (IMRT) confers a greater ability to treat the entirety of the tumor bed and may result in improved oncologic outcomes. Materials/Methods: We retrospectively reviewed the records of all ENB patients treated with IMRT at the University of California San Francisco (UCSF) between 1998 and 2009. Freedom from locoregional disease progression (LRDP), progression-free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier product limit method measured from diagnosis date. Toxicities were scored according to the RTOG acute and late morbidity scoring system. Results: Seventeen patients with histologically-confirmed ENB were identified. Two patients treated for recurrent disease were excluded from analysis. The average age was 50 years (range, 22-63). One patient was Kadish stage A, three were B, and 11 were C. Of the 15 surgical procedures, 7 had microscopically positive margins and 4 had gross residual disease. One patient received neoadjuvant chemotherapy, 7 received concurrent chemotherapy, and 4 received adjuvant chemotherapy. The median prescribed dose to the gross tumor volume or clinical target volume (if tumor was grossly resected), was 66 Gy (56.7-70Gy) with 2-2.2 Gy daily fractionation. Median follow-up was 44.5 months (7.4-117.3). The 5-year estimates of freedom from LRDP, PFS, and OS were 91, 83 and 81%. One patient developed local recurrence within the irradiation field at 25 months and died 15 months later. Another patient developed local recurrence at 72 months and was successfully salvaged with surgical resection and stereotactic radiosurgery. No regional or distant recurrences were observed. All patients developed mild acute grade 1 to 2 toxicities. Four patients had acute grade 3 infections including meningitis (1), neutropenic sepsis (1), sinusitis requiring surgery (1), and brain abscess (1). Late complications were comprised of 2 patients who developed grade 3 brain abscesses requiring surgery. There were no other late grade 3 or 4 toxicities. Conclusions: In newly-diagnosed patients with ENB, maximal surgical resection followed by IMRT offers high rates of locoregional control, PFS and OS. Treatment-related morbidity remains a concern. Author Disclosure: N. Kased, None; I.H. El-Sayed, None; V.K. Weinberg, None; M.J. Kaplan, None; M.W. McDermott, None; J.L. Nakamura, None; J.M. Quivey, None; S.S. Yom, None.
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Intensity Modulated Radiation Therapy (IMRT) for the Treatment of Oropharyngeal Carcinoma (OPC): Effect of Tumor Volume on Clinical Outcomes
B. Lok1,2, J. Setton1, J. Romanyshyn1, N. Caria1, S. Wolden1, M. Fury1, E. Sherman1, R. Wong1, D. Pfister1, N. Lee1 1
Memorial Sloan-Kettering Cancer Center, New York, NY, 2New York University School of Medicine, New York, NY
Purpose/Objective(s): To analyze the effect of primary gross tumor volume (pGTV) and nodal gross tumor volume (nGTV) on treatment outcomes in patients treated with definitive IMRT for OPC. Materials/Methods: Between 9/98 and 4/09, 442 patients with squamous cell carcinoma of the oropharynx were treated with IMRT with curative intent at our center. Three-hundred seventy-two patients had restorable treatment plans. Thirty patients were treated postoperatively and excluded from the study. Of the 342 patients analyzed, 325 received chemotherapy, including 311 who received concurrent chemotherapy, of which the majority was platinum-based. The T stage was T1 in 82 patients (24%), T2 in 147 (43%), T3 in 62 (18%) and T4 in 51 patients (15%). The N stage was N0 in 25 patients (7%), N1 in 72 (21%), N2 in 237 (69%), and N3 (2%) in 8 patients. The mean prescription dose to the planning target volume of the primary and nodal gross tumor was 70 Gy at 2.12 Gy per fraction while subclinical disease received between 54-59.4 Gy at 1.64-1.8 Gy per fraction. The local control (LC), regional control (RC), distant metastasis-free (DMF), and overall survival (OS) rates were calculated using the Kaplan-Meier method. The pGTV and nGTV were calculated using the original clinical treatment plans. Eight patients had pre-radiotherapy nodal excisions and were excluded from the nGTV analysis but were included in the pGTV analysis. Univariate Cox proportional hazards models were used to evaluate the correlation between tumor volumes and treatment outcomes. Results: Twenty-eight locoregional failures were observed; 10 patients failed locally only, 8 patients failed regionally only, and 10 patients had both local and regional failures. Thirty-eight patients developed distant metastasis (DM) as the first site of failure with subsequent locoregional failure in 6 of these patients. Median follow-up among surviving patients was 34 months (range, 5-67). The 3-year LC, RC, DMF and OS rates were 93.7%, 94.2%, 86.6%, and 84.9%, respectively. The mean GTV was 45.40 cm3 (range, 4.10 to 1000.73 cm3), and the mean nGTV was 31.80 cm3 (range, 0.00 to 442.05 cm3), where N0 patients were assigned a nGTV of 0 cm3. The pGTV was predictive of OS (p = 0.017) but not of LF (p = 0.22), RF (p = 0.45) or DM (p = 0.25). The nGTV was predictive of OS (p = 0.015), RF (p = 0.001) and DM (p = \ 0.0001), but not LF (p = 0.085). Conclusions: In this cohort of patients with OPC treated with IMRT, the pGTV and nGTV were predictors of OS. The nGTV was predictive of regional failure and distant metastasis. Contrary to previous reports, pGTV was not predictive of local failure, likely due to the ability of IMRT to target the pGTV accurately without underdosing portions of the pGTV. Author Disclosure: B. Lok, None; J. Setton, None; J. Romanyshyn, None; N. Caria, None; S. Wolden, None; M. Fury, None; E. Sherman, None; R. Wong, None; D. Pfister, None; N. Lee, None.
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2545
Intensity Modulated Radiation Therapy for Esthesioneuroblastoma: Clinical Outcomes and Toxicities
1
N. Kased , I. H. El-Sayed1, V. K. Weinberg1, M. J. Kaplan2, M. W. McDermott1, J. L. Nakamura1, J. M. Quivey1, S. S. Yom1 1
University of California, San Francisco, San Francisco, CA, 2Stanford University, Palo Alto, CA
Purpose/Objective(s): Esthesioneuroblastoma (ENB) is an uncommon tumor arising from the olfactory epithelium of the upper nasal cavity. Both surgical resection and delivery of postoperative radiation therapy are challenging due to the tumor’s proximity to orbital and intracranial contents. We hypothesize that postoperative intensity-modulated radiation therapy (IMRT) confers a greater ability to treat the entirety of the tumor bed and may result in improved oncologic outcomes. Materials/Methods: We retrospectively reviewed the records of all ENB patients treated with IMRT at the University of California San Francisco (UCSF) between 1998 and 2009. Freedom from locoregional disease progression (LRDP), progression-free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier product limit method measured from diagnosis date. Toxicities were scored according to the RTOG acute and late morbidity scoring system. Results: Seventeen patients with histologically-confirmed ENB were identified. Two patients treated for recurrent disease were excluded from analysis. The average age was 50 years (range, 22-63). One patient was Kadish stage A, three were B, and 11 were C. Of the 15 surgical procedures, 7 had microscopically positive margins and 4 had gross residual disease. One patient received neoadjuvant chemotherapy, 7 received concurrent chemotherapy, and 4 received adjuvant chemotherapy. The median prescribed dose to the gross tumor volume or clinical target volume (if tumor was grossly resected), was 66 Gy (56.7-70Gy) with 2-2.2 Gy daily fractionation. Median follow-up was 44.5 months (7.4-117.3). The 5-year estimates of freedom from LRDP, PFS, and OS were 91, 83 and 81%. One patient developed local recurrence within the irradiation field at 25 months and died 15 months later. Another patient developed local recurrence at 72 months and was successfully salvaged with surgical resection and stereotactic radiosurgery. No regional or distant recurrences were observed. All patients developed mild acute grade 1 to 2 toxicities. Four patients had acute grade 3 infections including meningitis (1), neutropenic sepsis (1), sinusitis requiring surgery (1), and brain abscess (1). Late complications were comprised of 2 patients who developed grade 3 brain abscesses requiring surgery. There were no other late grade 3 or 4 toxicities. Conclusions: In newly-diagnosed patients with ENB, maximal surgical resection followed by IMRT offers high rates of locoregional control, PFS and OS. Treatment-related morbidity remains a concern. Author Disclosure: N. Kased, None; I.H. El-Sayed, None; V.K. Weinberg, None; M.J. Kaplan, None; M.W. McDermott, None; J.L. Nakamura, None; J.M. Quivey, None; S.S. Yom, None.
2546
Intensity Modulated Radiation Therapy (IMRT) for the Treatment of Oropharyngeal Carcinoma (OPC): Effect of Tumor Volume on Clinical Outcomes
B. Lok1,2, J. Setton1, J. Romanyshyn1, N. Caria1, S. Wolden1, M. Fury1, E. Sherman1, R. Wong1, D. Pfister1, N. Lee1 1
Memorial Sloan-Kettering Cancer Center, New York, NY, 2New York University School of Medicine, New York, NY
Purpose/Objective(s): To analyze the effect of primary gross tumor volume (pGTV) and nodal gross tumor volume (nGTV) on treatment outcomes in patients treated with definitive IMRT for OPC. Materials/Methods: Between 9/98 and 4/09, 442 patients with squamous cell carcinoma of the oropharynx were treated with IMRT with curative intent at our center. Three-hundred seventy-two patients had restorable treatment plans. Thirty patients were treated postoperatively and excluded from the study. Of the 342 patients analyzed, 325 received chemotherapy, including 311 who received concurrent chemotherapy, of which the majority was platinum-based. The T stage was T1 in 82 patients (24%), T2 in 147 (43%), T3 in 62 (18%) and T4 in 51 patients (15%). The N stage was N0 in 25 patients (7%), N1 in 72 (21%), N2 in 237 (69%), and N3 (2%) in 8 patients. The mean prescription dose to the planning target volume of the primary and nodal gross tumor was 70 Gy at 2.12 Gy per fraction while subclinical disease received between 54-59.4 Gy at 1.64-1.8 Gy per fraction. The local control (LC), regional control (RC), distant metastasis-free (DMF), and overall survival (OS) rates were calculated using the Kaplan-Meier method. The pGTV and nGTV were calculated using the original clinical treatment plans. Eight patients had pre-radiotherapy nodal excisions and were excluded from the nGTV analysis but were included in the pGTV analysis. Univariate Cox proportional hazards models were used to evaluate the correlation between tumor volumes and treatment outcomes. Results: Twenty-eight locoregional failures were observed; 10 patients failed locally only, 8 patients failed regionally only, and 10 patients had both local and regional failures. Thirty-eight patients developed distant metastasis (DM) as the first site of failure with subsequent locoregional failure in 6 of these patients. Median follow-up among surviving patients was 34 months (range, 5-67). The 3-year LC, RC, DMF and OS rates were 93.7%, 94.2%, 86.6%, and 84.9%, respectively. The mean GTV was 45.40 cm3 (range, 4.10 to 1000.73 cm3), and the mean nGTV was 31.80 cm3 (range, 0.00 to 442.05 cm3), where N0 patients were assigned a nGTV of 0 cm3. The pGTV was predictive of OS (p = 0.017) but not of LF (p = 0.22), RF (p = 0.45) or DM (p = 0.25). The nGTV was predictive of OS (p = 0.015), RF (p = 0.001) and DM (p = \ 0.0001), but not LF (p = 0.085). Conclusions: In this cohort of patients with OPC treated with IMRT, the pGTV and nGTV were predictors of OS. The nGTV was predictive of regional failure and distant metastasis. Contrary to previous reports, pGTV was not predictive of local failure, likely due to the ability of IMRT to target the pGTV accurately without underdosing portions of the pGTV. Author Disclosure: B. Lok, None; J. Setton, None; J. Romanyshyn, None; N. Caria, None; S. Wolden, None; M. Fury, None; E. Sherman, None; R. Wong, None; D. Pfister, None; N. Lee, None.
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