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Patterns of Regional Nodal Failure Following Intensity Modulated Radiation Therapy for Head and Neck Squamous Cell Carcinoma
E338
International Journal of Radiation Oncology Biology Physics
2829
IIB-IVB nasopharyngeal carcinoma were treated with RT and concurrent and adjuvant chemotherapy. Pure tone audiometry for air (AC) and bone conduction (BC) was performed before RT and 12 to 24 months following completion of CRT. The threshold for both AC and BC was measured at 0.25 to 4 kHz, as these frequencies reflect average range of conversational speech. For each frequency, increase in BC threshold indicated sensorineural HL (SNHL), and increase in air-bone gap indicated conductive HL (CHL). DVH was obtained for the right and left middle ear (malleus, incus, stapes, tympanic membrane), Eustachian tube (ET), vestibulocochlear nerve (CNVIII), and cochlea. The relationship between radiation dose to these structures and the onset of SNHL or CHL was evaluated using linear regression analysis. Patient-reported hearing function was assessed prior to and 12-24 months after RT using various quality-of-life domains within the EORTC QLQ H&N35 questionnaire. Results: Between 2006 and 2011, 24 patients were enrolled on the trial; 21 patients with complete follow up data were eligible for this analysis. Median age at diagnosis was 49 years (range 25 - 68). The stage distribution was as follows: 1 stage IIB, 17 stage III, 4 stage IVA, and 2 stage IVB. Patients received 70 Gy of RT, and all but one received 3 cycles of concurrent bolus cisplatin. Each patient received 2-3 cycles of adjuvant cisplatin (n Z 6) or carboplatin (n Z 15) with concurrent 5-FU. Fiftyseven percent of patients reported subjective hearing decline at 12 -24 months following completion of therapy (7 unilateral, 5 bilateral). For each hearing-related question on the EORTC QLQ questionnaire, an average 17% of patients showed a decline in self-reported outcomes. On pure-tone audiometry, V60 of CNVIII was associated with low-frequency SNHL. For every 1% increase in V60 of CNVIII, there was an average 0.27 and 0.37 dB increase in threshold for BC at 0.5 (P Z 0.02), and 1.0 (P Z 0.008) kHz, respectively. Dmax of ET was associated with CHL at 1.0 kHz. For every 1 Gy increase in max dose to ET, there was an average 6.14 dB increase in air-bone gap at 1.0 kHz (P Z 0.001). Conclusion: We have shown that low frequency sensorineural hearing loss is associated with V60 of CNVIII and conductive hearing loss with Dmax of ET. Delineation and avoidance of these structures are prudent. Author Disclosure: S.A. Patel: None. A.A. Aizer: None. E. Weyman: None. H. Lu: None. B.Y. Yeap: None. P.M. Busse: None. A.W. Chan: None.
Patterns of Regional Nodal Failure Following Intensity Modulated Radiation Therapy for Head and Neck Squamous Cell Carcinoma J.E. Leeman,1 J.G. Li,2 P. Venigalla,1 Z.S. Zumsteg,3 P.B. Romesser,1 N. Katabi,1 S. McBride,1 C.J. Tsai,1 D.S. Higginson,1 E.J. Sherman,1 B.R. Roman,1 N. Riaz,4 and N. Lee1; 1Memorial Sloan Kettering Cancer Center, New York, NY, 2Jiangxi Cancer Hospital, Nanchang, China, 3 Cedars-Sinai Medical Center, Los Angeles, CA, 4Memorial SloanKettering Cancer Center, New York, NY Purpose/Objective(s): Intensity modulated radiation therapy (IMRT) plays an integral role in treatment of squamous cell carcinoma of the head and neck (HNSCC) by allowing precise targeting of tumor and at-risk nodal regions. However, practices of elective nodal coverage vary significantly. Herein, we present patterns of regional nodal failure in a large cohort of HNSCC patients treated with IMRT with extended clinical follow-up. Materials/Methods: We reviewed outcomes from 1062 consecutive HNSCC patients treated with IMRT including 734 with oropharyngeal carcinoma (OPC), 155 with oral cavity carcinoma (OCC), 126 with laryngeal carcinoma (LRX) and 47 with hypopharyngeal carcinoma (HPX) between 2001 and 2013. HPV/p16 status was available for 417(57%) OPC patients. Regional failures (RF) and the corresponding cervical nodal levels were co-registered to 3D radiation treatment plan dose distributions. Nodal recurrences were marked as “in-field GTV” (high dose region, 70 Gy), “in-field CTV” (elective nodal coverage) or “out-of-field” (not covered electively). Median follow-up for the entire cohort was 57.7 months in surviving patients. Results: Crude rates of RF by sub-site were: OPC 6.8%; OCC 12.3%; LRX 10.3%; HPX 14.9%. Crude rates of RF for HPV+ and HPV- OPC patients, respectively, were: HPV+ 6.6% and HPV- 14.8%. A total of 86 patients failed in the regional nodes (8.1%), with the majority of failures occurring in cervical levels II, III and IV (82%). Forty-seven patients failed “in-field GTV” (4.4%), 27 failed “in-field CTV” (2.5%), 8 failed “in-field GTV” and “in-field CTV” (0.7%) and 4 failed “in field CTV and out-offield” (0.3%). “Out-of-field” failures included three patients with OCC who failed at cervical level VIa and one patient with LRX who failed with intraparotid disease. No patients developed isolated “out-of-field” failures. No patients with OPC failed “out of field” in cervical levels Ia, Ib or V when not covered electively. Conclusion: The majority of post-IMRT regional failures in HNSCC occur in the high dose treatment regions. Out-of-field failures are rare and cervical levels Ia, Ib and V can safely be omitted from elective nodal coverage in OPC. Elective coverage of level VIa/low level IA should be considered in high risk cases of OCC. Author Disclosure: J.E. Leeman: None. J. Li: None. P. Venigalla: None. Z.S. Zumsteg: None. P.B. Romesser: None. N. Katabi: None. S. McBride: None. C. Tsai: None. D.S. Higginson: None. E.J. Sherman: None. B.R. Roman: None. N. Riaz: None. N. Lee: Advisory Board; Merck, Pfizer, Vertex.
2830 Multimodal Assessment of Hearing Function After Chemoradiation for Nasopharyngeal Carcinoma: A Prospective Study S.A. Patel,1 A.A. Aizer,2 E. Weyman,3 H.M. Lu,3 B.Y. Yeap,3 P.M. Busse,3 and A.W. Chan3; 1Harvard Radiation Oncology Program, Boston, MA, 2 Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA, 3Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA Purpose/Objective(s): Hearing loss (HL) after treatment for nasopharyngeal cancer (NPC) is common. Prospective data assessing predictors of ototoxicity are lacking. The purposes of this study were to assess patientreported and objective hearing function and to determine dosimetric predictors of hearing loss after chemoradiation for NPC. Materials/Methods: An IRB-approved, prospective phase II clinical trial was conducted at our institution. Adult patients with biopsy-proven stage
2831 Number of Lymph Nodes Examined Is Associated With Overall Survival in Clinically Node-Negative Oral Cavity Cancer Patients Receiving Definitive SurgerydA Population-Based Analysis Using the National Cancer Data Base C.J. Tsai, S. McBride, N. Riaz, J.E. Leeman, B.R. Roman, S.S. Baxi, E.J. Sherman, R.J. Wong, and N. Lee; Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): For patients with oral cavity cancers, lymph node dissection is both diagnostic and therapeutic. However, it is unclear if extensive nodal dissection is associated with better survival, especially in patients without any detectable nodal disease before surgery. We thus evaluated the survival impact of the number of lymph nodes examined in clinically node-negative oral cavity cancer patients undergoing definitive surgery. Materials/Methods: Using the National Cancer Data Base, we identified 10,422 clinically node-negative patients with non-metastatic oral cavity cancers (oral tongue, floor of mouth, gum, hard palate/alveolar ridge, buccal mucosa, and retromolar trigone) treated with upfront definitive surgery between 2004 and 2012. The length of follow-up was measured from the date of surgery to either the time of death or last contact. Overall survival was estimated using the Kaplan and Meier method and log-rank test. The Cox proportional hazard model was used to compute univariate and multivariate hazard ratios (HRs) comparing number of nodes examined and overall survival. Results: The median number of lymph nodes examined in this cohort was 23 (range: 1-90). Compared to those with < 23 nodes examined, patients with 23 lymph nodes dissected were more likely to 1) be younger than
International Journal of Radiation Oncology Biology Physics
2829
IIB-IVB nasopharyngeal carcinoma were treated with RT and concurrent and adjuvant chemotherapy. Pure tone audiometry for air (AC) and bone conduction (BC) was performed before RT and 12 to 24 months following completion of CRT. The threshold for both AC and BC was measured at 0.25 to 4 kHz, as these frequencies reflect average range of conversational speech. For each frequency, increase in BC threshold indicated sensorineural HL (SNHL), and increase in air-bone gap indicated conductive HL (CHL). DVH was obtained for the right and left middle ear (malleus, incus, stapes, tympanic membrane), Eustachian tube (ET), vestibulocochlear nerve (CNVIII), and cochlea. The relationship between radiation dose to these structures and the onset of SNHL or CHL was evaluated using linear regression analysis. Patient-reported hearing function was assessed prior to and 12-24 months after RT using various quality-of-life domains within the EORTC QLQ H&N35 questionnaire. Results: Between 2006 and 2011, 24 patients were enrolled on the trial; 21 patients with complete follow up data were eligible for this analysis. Median age at diagnosis was 49 years (range 25 - 68). The stage distribution was as follows: 1 stage IIB, 17 stage III, 4 stage IVA, and 2 stage IVB. Patients received 70 Gy of RT, and all but one received 3 cycles of concurrent bolus cisplatin. Each patient received 2-3 cycles of adjuvant cisplatin (n Z 6) or carboplatin (n Z 15) with concurrent 5-FU. Fiftyseven percent of patients reported subjective hearing decline at 12 -24 months following completion of therapy (7 unilateral, 5 bilateral). For each hearing-related question on the EORTC QLQ questionnaire, an average 17% of patients showed a decline in self-reported outcomes. On pure-tone audiometry, V60 of CNVIII was associated with low-frequency SNHL. For every 1% increase in V60 of CNVIII, there was an average 0.27 and 0.37 dB increase in threshold for BC at 0.5 (P Z 0.02), and 1.0 (P Z 0.008) kHz, respectively. Dmax of ET was associated with CHL at 1.0 kHz. For every 1 Gy increase in max dose to ET, there was an average 6.14 dB increase in air-bone gap at 1.0 kHz (P Z 0.001). Conclusion: We have shown that low frequency sensorineural hearing loss is associated with V60 of CNVIII and conductive hearing loss with Dmax of ET. Delineation and avoidance of these structures are prudent. Author Disclosure: S.A. Patel: None. A.A. Aizer: None. E. Weyman: None. H. Lu: None. B.Y. Yeap: None. P.M. Busse: None. A.W. Chan: None.
Patterns of Regional Nodal Failure Following Intensity Modulated Radiation Therapy for Head and Neck Squamous Cell Carcinoma J.E. Leeman,1 J.G. Li,2 P. Venigalla,1 Z.S. Zumsteg,3 P.B. Romesser,1 N. Katabi,1 S. McBride,1 C.J. Tsai,1 D.S. Higginson,1 E.J. Sherman,1 B.R. Roman,1 N. Riaz,4 and N. Lee1; 1Memorial Sloan Kettering Cancer Center, New York, NY, 2Jiangxi Cancer Hospital, Nanchang, China, 3 Cedars-Sinai Medical Center, Los Angeles, CA, 4Memorial SloanKettering Cancer Center, New York, NY Purpose/Objective(s): Intensity modulated radiation therapy (IMRT) plays an integral role in treatment of squamous cell carcinoma of the head and neck (HNSCC) by allowing precise targeting of tumor and at-risk nodal regions. However, practices of elective nodal coverage vary significantly. Herein, we present patterns of regional nodal failure in a large cohort of HNSCC patients treated with IMRT with extended clinical follow-up. Materials/Methods: We reviewed outcomes from 1062 consecutive HNSCC patients treated with IMRT including 734 with oropharyngeal carcinoma (OPC), 155 with oral cavity carcinoma (OCC), 126 with laryngeal carcinoma (LRX) and 47 with hypopharyngeal carcinoma (HPX) between 2001 and 2013. HPV/p16 status was available for 417(57%) OPC patients. Regional failures (RF) and the corresponding cervical nodal levels were co-registered to 3D radiation treatment plan dose distributions. Nodal recurrences were marked as “in-field GTV” (high dose region, 70 Gy), “in-field CTV” (elective nodal coverage) or “out-of-field” (not covered electively). Median follow-up for the entire cohort was 57.7 months in surviving patients. Results: Crude rates of RF by sub-site were: OPC 6.8%; OCC 12.3%; LRX 10.3%; HPX 14.9%. Crude rates of RF for HPV+ and HPV- OPC patients, respectively, were: HPV+ 6.6% and HPV- 14.8%. A total of 86 patients failed in the regional nodes (8.1%), with the majority of failures occurring in cervical levels II, III and IV (82%). Forty-seven patients failed “in-field GTV” (4.4%), 27 failed “in-field CTV” (2.5%), 8 failed “in-field GTV” and “in-field CTV” (0.7%) and 4 failed “in field CTV and out-offield” (0.3%). “Out-of-field” failures included three patients with OCC who failed at cervical level VIa and one patient with LRX who failed with intraparotid disease. No patients developed isolated “out-of-field” failures. No patients with OPC failed “out of field” in cervical levels Ia, Ib or V when not covered electively. Conclusion: The majority of post-IMRT regional failures in HNSCC occur in the high dose treatment regions. Out-of-field failures are rare and cervical levels Ia, Ib and V can safely be omitted from elective nodal coverage in OPC. Elective coverage of level VIa/low level IA should be considered in high risk cases of OCC. Author Disclosure: J.E. Leeman: None. J. Li: None. P. Venigalla: None. Z.S. Zumsteg: None. P.B. Romesser: None. N. Katabi: None. S. McBride: None. C. Tsai: None. D.S. Higginson: None. E.J. Sherman: None. B.R. Roman: None. N. Riaz: None. N. Lee: Advisory Board; Merck, Pfizer, Vertex.
2830 Multimodal Assessment of Hearing Function After Chemoradiation for Nasopharyngeal Carcinoma: A Prospective Study S.A. Patel,1 A.A. Aizer,2 E. Weyman,3 H.M. Lu,3 B.Y. Yeap,3 P.M. Busse,3 and A.W. Chan3; 1Harvard Radiation Oncology Program, Boston, MA, 2 Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA, 3Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA Purpose/Objective(s): Hearing loss (HL) after treatment for nasopharyngeal cancer (NPC) is common. Prospective data assessing predictors of ototoxicity are lacking. The purposes of this study were to assess patientreported and objective hearing function and to determine dosimetric predictors of hearing loss after chemoradiation for NPC. Materials/Methods: An IRB-approved, prospective phase II clinical trial was conducted at our institution. Adult patients with biopsy-proven stage
2831 Number of Lymph Nodes Examined Is Associated With Overall Survival in Clinically Node-Negative Oral Cavity Cancer Patients Receiving Definitive SurgerydA Population-Based Analysis Using the National Cancer Data Base C.J. Tsai, S. McBride, N. Riaz, J.E. Leeman, B.R. Roman, S.S. Baxi, E.J. Sherman, R.J. Wong, and N. Lee; Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): For patients with oral cavity cancers, lymph node dissection is both diagnostic and therapeutic. However, it is unclear if extensive nodal dissection is associated with better survival, especially in patients without any detectable nodal disease before surgery. We thus evaluated the survival impact of the number of lymph nodes examined in clinically node-negative oral cavity cancer patients undergoing definitive surgery. Materials/Methods: Using the National Cancer Data Base, we identified 10,422 clinically node-negative patients with non-metastatic oral cavity cancers (oral tongue, floor of mouth, gum, hard palate/alveolar ridge, buccal mucosa, and retromolar trigone) treated with upfront definitive surgery between 2004 and 2012. The length of follow-up was measured from the date of surgery to either the time of death or last contact. Overall survival was estimated using the Kaplan and Meier method and log-rank test. The Cox proportional hazard model was used to compute univariate and multivariate hazard ratios (HRs) comparing number of nodes examined and overall survival. Results: The median number of lymph nodes examined in this cohort was 23 (range: 1-90). Compared to those with < 23 nodes examined, patients with 23 lymph nodes dissected were more likely to 1) be younger than