- Email: [email protected]
High-dose-rate Intraoperative Radiation Therapy for the Salvage Treatment of Head and Neck Cancer
I. J. Radiation Oncology d Biology d Physics
S446
Volume 78, Number 3, Supplement, 2010
17 cases with T3 or T4, ADC and dose showed significant associations with local failure (p \ 0.01). In multivariate analysis, ADC alone showed significance (p \ 0.05). Conclusions: The results suggest that pretreatment ADC as well as T stage is a potential indicator of local failure in HNSCC treated with chemoradiotherapy or radiotherapy. Author Disclosure: M. Hatakenaka, None; K. Nakamura, None; H. Yabuuchi, None; Y. Shioyama, None; Y. Matsuo, None; K. Ohnishi, None; S. Sunami, None; T. Kamitani, None; T. Yoshiura, None; H. Honda, None.
2543
Reirradiation in Head and Neck Cancer: Balance between Efficacy and Toxicity
F. Hoebers, S. Moor, W. Heemsbergen, M. Lopez, M. Tesselaar, M. Klop, C. Rasch The Netherlands Cancer Institute, Amsterdam 1066 CX, Netherlands Purpose/Objective(s): To analyze the effectiveness of reirradiation (re-RT) for head and neck (H&N) cancer in and to document rates of complications following re-RT. Materials/Methods: A retrospective data analysis was performed of patients that underwent re-RT to the H&N area with curative intent (.= 50 Gy) to overlapping areas, previously treated with RT. Between 1998 and 2009, 58 patients were identified. Histology was squamous cell carcinoma in 88% of cases. The indication for re-RT was a second primary tumor (36%) or recurrent disease (64%). Re-RT was given as primary definitive treatment in 53%, whereas 47% of cases underwent postoperative Re-RT because of high risk pathology features. Median cumulative RT dose was 119 Gy. Median interval between first RT and re-RT was 3.0 years (0.3 - 43). Concurrent chemotherapy was administered with re-RT (CRT) in 57% of patients. Toxicity was graded according to CTCv3.0. Serious toxicity was defined as .= grade 3. Event-free survival (EFS) was defined as survival without recurrence and without serious toxicity. Univariate survival analysis was performed to identify factors associated with outcome. Results: Mean follow-up among surviving patients was 64 months (range 9-140). Locoregional control (LRC) was 50% at 2 and 5 years. Two and 5 year overall survival (OS) was 42% and 34%, respectively. The following factors were associated with improved OS: postoperative re-RT (as opposed to primary re-RT, HR 0.43, p = 0.016), treatment with RT only (as opposed to CRT, HR 0.24, p \ 0.001) and interval . 3 years between first RT and re-RT (HR 0.44, p = 0.015). For patients treated with postoperative re-RT and definitive re-RT, the 5-year OS was 49% and 20 %, resp. Patients treated with CRT had a 5-year OS of 13% compared to 62% for patients treated with RT alone. Most frequent serious toxicity was osteoradionecrosis (15%), stenosis of the pharynx (18%), vascular toxicity (TIA, CVA, carotid blow-out, 17%). Three cases of treatment related death were recorded. Serious (late) toxicity .= grade 3 was observed in 20 of 47 evaluable patients (43%). The 2 and 5 year Serious Toxicity Free interval was 59% and 55%, resp. Associated with increased risk of serious toxicity were CRT (HR 2.86, p = 0.032) and higher re-RT dose (HR 1.11, p = 0.036). EFS rates at 2 and 5 years were 34% and 31%. Conclusions: Re-RT in H&N cancer is associated with poor survival rates of 13-20% in patients with inoperable disease treated with primary (chemo-) re-RT. For this subgroup however, no other (curative) options are available. Long-term disease control and survival can be achieved in patients that receive re-RT as adjunct to surgical resection. Rates of serious toxicity (.= grade 3) after re-RT are high, with approximately 45% incidence at 5 years. About 1 in three patients survived re-RT without recurrence and severe complications. Author Disclosure: F. Hoebers, None; S. Moor, None; W. Heemsbergen, None; M. Lopez, None; M. Tesselaar, None; M. Klop, None; C. Rasch, None.
2544
High-dose-rate Intraoperative Radiation Therapy for the Salvage Treatment of Head and Neck Cancer
K. Hu, M. Scala, M. Rao, N. Shah, M. Urken, M. Persky, A. Jacobson, T. Tran, E. Furhang, L. B. Harrison Beth Israel Medical Center, New York, NY Purpose/Objective(s): High dose-rate intraoperative radiation therapy (HDR-IORT) offers an important opportunity to salvage recurrent patients (pts) and dose-escalate therapy in initially treated pts. We report the largest experience combining HDRIORT with radical resection to treat previously irradiated head and neck cancer pts. Materials/Methods: From 1/01-2/10, 90 pts with primary (n = 13) or recurrent (n = 77) head and neck cancer were treated with HDR-IORT to 101 sites after gross total resection to a median dose 12Gy (10-17.5 Gy) using the Harrison-Anderson-Mick applicator. Eleven of the 90 pts received HDR-IORT to two separate sites. Pt characteristics were as follows: median age: 60yr, (5-88yr); Males: 68%. Sites of treatment were the neck 54%, face 13%; parapharyngeal space 11%; parotid 7%; nasal cavity/paranasal sinus 7%; skull base 4% and other 4%. Histology was as follows: squamous cell carcinoma 82%; salivary gland 12%; sarcoma 4%; skin 1%; esthesioneuroblastoma 1%. The median time of HDR-IORT delivery was 15min (5-44 min) to a median area of 24cm2 (2-204cm2) at a depth of 1cm from the source. Gross total resection was obtained in all pts with positive margins in 51% and negative margins in 49%. Flap reconstruction was performed in 65%. About ˇ1/4 received additional EBRT to median dose of 45Gy (31-69Gy). Results: No intraoperative complications related to HDR-IORT ensued in any of the pts. Perioperatively, 3 flaps required revision. Complications included osteoradionecrosis (n = 1), soft tissue necrosis (n = 1) and carotid blowout (n = 1). Among the 67 pts available for detailed follow-up at a median time of 11 mo, the Kaplan-Meier estimate of 1 year OS was 66%, DFS 51%, in-field failure (IFF) 35%, out-of-field failure (OFF) 22% and distant metastasis (DM) 31% for all pts. Margin status impacted on IFF (1yr 14% vs. 44%, p = 0.0138) and DFS (66% vs. 39%, p = 0.059) in pts with negative versus positive margins, respectively, but not OS (1yr 76% vs. 58% p = 0.46), OFF (1yr 22% vs. 21%p = 0.35) or DM (35% vs. 31% p = 0.90), respectively. When stratified by HDRIORT dose and margin status, 1yr IFF among negative margin pts was 21% vs. 11% (p = 0.75) in those receiving #12Gy vs. . 12Gy, respectively; for positive margin pts, 1 yr IFF was 45% vs. 45% (p = 0.81), respectively. Conclusions: HDR-IORT is a safe and effective modality in conjunction with radical resection and flap reconstruction in pts with recurrent or primary head and neck cancer. Margin status is the most important predictor of in-field control and DFS. OFF and DM remains significant and highlights the need for comprehensive treatment in this challenging group of pts. To that end, we have
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.
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.
S447
S446
Volume 78, Number 3, Supplement, 2010
17 cases with T3 or T4, ADC and dose showed significant associations with local failure (p \ 0.01). In multivariate analysis, ADC alone showed significance (p \ 0.05). Conclusions: The results suggest that pretreatment ADC as well as T stage is a potential indicator of local failure in HNSCC treated with chemoradiotherapy or radiotherapy. Author Disclosure: M. Hatakenaka, None; K. Nakamura, None; H. Yabuuchi, None; Y. Shioyama, None; Y. Matsuo, None; K. Ohnishi, None; S. Sunami, None; T. Kamitani, None; T. Yoshiura, None; H. Honda, None.
2543
Reirradiation in Head and Neck Cancer: Balance between Efficacy and Toxicity
F. Hoebers, S. Moor, W. Heemsbergen, M. Lopez, M. Tesselaar, M. Klop, C. Rasch The Netherlands Cancer Institute, Amsterdam 1066 CX, Netherlands Purpose/Objective(s): To analyze the effectiveness of reirradiation (re-RT) for head and neck (H&N) cancer in and to document rates of complications following re-RT. Materials/Methods: A retrospective data analysis was performed of patients that underwent re-RT to the H&N area with curative intent (.= 50 Gy) to overlapping areas, previously treated with RT. Between 1998 and 2009, 58 patients were identified. Histology was squamous cell carcinoma in 88% of cases. The indication for re-RT was a second primary tumor (36%) or recurrent disease (64%). Re-RT was given as primary definitive treatment in 53%, whereas 47% of cases underwent postoperative Re-RT because of high risk pathology features. Median cumulative RT dose was 119 Gy. Median interval between first RT and re-RT was 3.0 years (0.3 - 43). Concurrent chemotherapy was administered with re-RT (CRT) in 57% of patients. Toxicity was graded according to CTCv3.0. Serious toxicity was defined as .= grade 3. Event-free survival (EFS) was defined as survival without recurrence and without serious toxicity. Univariate survival analysis was performed to identify factors associated with outcome. Results: Mean follow-up among surviving patients was 64 months (range 9-140). Locoregional control (LRC) was 50% at 2 and 5 years. Two and 5 year overall survival (OS) was 42% and 34%, respectively. The following factors were associated with improved OS: postoperative re-RT (as opposed to primary re-RT, HR 0.43, p = 0.016), treatment with RT only (as opposed to CRT, HR 0.24, p \ 0.001) and interval . 3 years between first RT and re-RT (HR 0.44, p = 0.015). For patients treated with postoperative re-RT and definitive re-RT, the 5-year OS was 49% and 20 %, resp. Patients treated with CRT had a 5-year OS of 13% compared to 62% for patients treated with RT alone. Most frequent serious toxicity was osteoradionecrosis (15%), stenosis of the pharynx (18%), vascular toxicity (TIA, CVA, carotid blow-out, 17%). Three cases of treatment related death were recorded. Serious (late) toxicity .= grade 3 was observed in 20 of 47 evaluable patients (43%). The 2 and 5 year Serious Toxicity Free interval was 59% and 55%, resp. Associated with increased risk of serious toxicity were CRT (HR 2.86, p = 0.032) and higher re-RT dose (HR 1.11, p = 0.036). EFS rates at 2 and 5 years were 34% and 31%. Conclusions: Re-RT in H&N cancer is associated with poor survival rates of 13-20% in patients with inoperable disease treated with primary (chemo-) re-RT. For this subgroup however, no other (curative) options are available. Long-term disease control and survival can be achieved in patients that receive re-RT as adjunct to surgical resection. Rates of serious toxicity (.= grade 3) after re-RT are high, with approximately 45% incidence at 5 years. About 1 in three patients survived re-RT without recurrence and severe complications. Author Disclosure: F. Hoebers, None; S. Moor, None; W. Heemsbergen, None; M. Lopez, None; M. Tesselaar, None; M. Klop, None; C. Rasch, None.
2544
High-dose-rate Intraoperative Radiation Therapy for the Salvage Treatment of Head and Neck Cancer
K. Hu, M. Scala, M. Rao, N. Shah, M. Urken, M. Persky, A. Jacobson, T. Tran, E. Furhang, L. B. Harrison Beth Israel Medical Center, New York, NY Purpose/Objective(s): High dose-rate intraoperative radiation therapy (HDR-IORT) offers an important opportunity to salvage recurrent patients (pts) and dose-escalate therapy in initially treated pts. We report the largest experience combining HDRIORT with radical resection to treat previously irradiated head and neck cancer pts. Materials/Methods: From 1/01-2/10, 90 pts with primary (n = 13) or recurrent (n = 77) head and neck cancer were treated with HDR-IORT to 101 sites after gross total resection to a median dose 12Gy (10-17.5 Gy) using the Harrison-Anderson-Mick applicator. Eleven of the 90 pts received HDR-IORT to two separate sites. Pt characteristics were as follows: median age: 60yr, (5-88yr); Males: 68%. Sites of treatment were the neck 54%, face 13%; parapharyngeal space 11%; parotid 7%; nasal cavity/paranasal sinus 7%; skull base 4% and other 4%. Histology was as follows: squamous cell carcinoma 82%; salivary gland 12%; sarcoma 4%; skin 1%; esthesioneuroblastoma 1%. The median time of HDR-IORT delivery was 15min (5-44 min) to a median area of 24cm2 (2-204cm2) at a depth of 1cm from the source. Gross total resection was obtained in all pts with positive margins in 51% and negative margins in 49%. Flap reconstruction was performed in 65%. About ˇ1/4 received additional EBRT to median dose of 45Gy (31-69Gy). Results: No intraoperative complications related to HDR-IORT ensued in any of the pts. Perioperatively, 3 flaps required revision. Complications included osteoradionecrosis (n = 1), soft tissue necrosis (n = 1) and carotid blowout (n = 1). Among the 67 pts available for detailed follow-up at a median time of 11 mo, the Kaplan-Meier estimate of 1 year OS was 66%, DFS 51%, in-field failure (IFF) 35%, out-of-field failure (OFF) 22% and distant metastasis (DM) 31% for all pts. Margin status impacted on IFF (1yr 14% vs. 44%, p = 0.0138) and DFS (66% vs. 39%, p = 0.059) in pts with negative versus positive margins, respectively, but not OS (1yr 76% vs. 58% p = 0.46), OFF (1yr 22% vs. 21%p = 0.35) or DM (35% vs. 31% p = 0.90), respectively. When stratified by HDRIORT dose and margin status, 1yr IFF among negative margin pts was 21% vs. 11% (p = 0.75) in those receiving #12Gy vs. . 12Gy, respectively; for positive margin pts, 1 yr IFF was 45% vs. 45% (p = 0.81), respectively. Conclusions: HDR-IORT is a safe and effective modality in conjunction with radical resection and flap reconstruction in pts with recurrent or primary head and neck cancer. Margin status is the most important predictor of in-field control and DFS. OFF and DM remains significant and highlights the need for comprehensive treatment in this challenging group of pts. To that end, we have
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.
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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