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Video Laryngostroboscopy Demonstrates Post–Radiation Therapy Improvement in Dysphonia in Early-Stage Glottic Larynx Cancer
Volume 90 Number 1S Supplement 2014
212 Survival Outcomes of Patients With T4a Larynx Cancer Following Initial Management With Surgery Versus Larynx Preservation Therapy S. Grover, S. Swisher-McClure, and A. Lin; University of Pennsylvania, Philadelphia, PA Purpose/Objective(s): Consensus practice guidelines recommend total laryngectomy (TL) as initial management for medically operable patients with T4a larynx cancer. In addition, patients with T4a larynx cancer are frequently excluded from clinical trials of larynx preservation (LP) because of anticipated poor larynx preservation rates and concerns for inferior survival outcomes. Using a large national cancer registry, we examined recent practice patterns among patients with T4a larynx cancer, and compared survival outcomes between patients receiving TL vs LP. Materials/Methods: Our study included 1,307 patients diagnosed with non-metastatic invasive T4a squamous cell carcinoma of the larynx from 2003-2006 in the National Cancer Database. Treatment groups were defined as initial surgery (TL + adjuvant therapy) vs LP with chemoradiation (CRT). Patients receiving surgery only, radiation alone, or those not receiving any treatment within 100 days of diagnosis were excluded. Univariate and multivariate (MVA) logistic regression models were used to assess predictors (year of diagnosis, age, gender, race, insurance status, type of treatment facility, distance from center, center case volume, N stage, and comorbidity index) of receiving surgical treatment. Survival outcomes were compared using Kaplan-Meier and Cox proportional hazards regression methods. Results: Overall, 65% (n Z 856) of patients received LP and 35% (n Z 451) underwent TL + adjuvant RT or CRT. On MVA, patients with advanced nodal disease were less likely to receive TL compared to patients with N0 disease (N2 vs N0, 25.4% vs 41.2%, OR Z 0.46, 95% CI Z 0.150.82; N3 vs N0, 22.2% vs 41.2%, OR Z 0.34, 95% CI Z 0.15-0.82). Patients treated in facilities with high case-volume were more likely to receive TL compared to those treated at low case-volume facilities (47.1% vs 28.6%, OR Z 2.03, 95% CI Z 1.51-2.73). Patients diagnosed in 2006 were less likely to receive TL compared to patients diagnosed in 2003 (28.1% vs 40%, OR Z 0.60, 95% CI Z 0.43-0.86). Median survival among patients receiving TL vs LP was 60 vs 31 months (p < 0.001). After controlling for potential confounders, patients receiving LP had inferior overall survival compared to those receiving TL (HR Z 1.51, 95% CI Z 1.28-1.75). Conclusions: Approximately two out of three patients with T4a larynx cancer receive LP rather than TL, despite practice guidelines suggesting TL as the preferred initial approach. Use of TL appears to be declining over time. Patients treated in high case-volume centers are more likely to receive primary surgical management. Further research should investigate treatment decision counseling by physicians to their patients, patient decision making, and potential strategies to reduce observed differences in patient survival outcomes. Author Disclosure: S. Grover: None. S. Swisher-McClure: None. A. Lin: None.
213 Video Laryngostroboscopy Demonstrates PosteRadiation Therapy Improvement in Dysphonia in Early-Stage Glottic Larynx Cancer A.E. Marciscano, H.M. Starmer, S.R. Best, L.M. Akst, H. Quon, and A.P. Kiess; Johns Hopkins Hospital, Baltimore, MD Purpose/Objective(s): Video laryngostroboscopy (VLS), an endoscopic tool utilizing rapid pulsed light to view vocal cord (VC) vibration, is the clinical gold standard for evaluation of dysphonia. Though dysphonia is common among patients with early stage glottic cancer, VLS has not been used to assess posteradiation therapy (RT) voice changes. We hypothesized that VLS would show improvement in dysphonia after definitive RT for early glottic cancer. Materials/Methods: Eleven patients underwent RT for stage TisT2N0M0 glottic larynx cancer and were evaluated with serial VLS
Oral Scientific Sessions
S99
examinations pre-RT and post-RT. Two expert laryngologists graded each exam retrospectively in a blinded fashion with scores of 0-4 for 6 parameters: VC vibration, VC mobility, VC closure, supraglottic compression, erythema/edema, and secretions. GRBAS voice perceptive scale was used in tandem with VLS score. Assessments were grouped by time interval from RT: pre-RT, 0-4 mo and 4-24 mo post-RT. Descriptive statistics were reported as mean score +/- standard error of the mean. Results: In total, 40 VLS examinations were scored and 40 GRBAS assessments were reviewed. Pre-RT, ipsilateral (diseased) VC vibration was moderately impaired (mean 2.9 +/- 0.3) and ipsilateral VC mobility was mildly impaired (0.8 +/- 0.2). Post-RT, there was improvement in ipsilateral VC vibration (2.0 +/- 0.3 at 0-4 mo and 2.3 +/- 0.2 at 4-24 mo) and ipsilateral VC mobility (0.4 +/- 0.1 at 0-4 mo and 0.6 +/- 0.2 at 12-24 mo). Pre-RT, contralateral VC vibration was mildly impaired (mean 1.2 +/- 0.3) and contralateral VC mobility was normal (0.1 +/- 0.1). Interestingly, there was an increase in post-RT impairment of contralateral VC vibration (1.4 +/- 0.3 at 0-4 mo and 1.7 +/- 0.2 at 4-24 mo), possibly due to fibrosis. There was mild pre-RT edema/erythema (1.1 +/- 0.2) and normal secretions. As expected, there was increased post-RT edema/erythema (1.8 +/0.2 at 0-4 mo and at 4-24 mo) and thickened secretions (0.7 +/- 0.1 at 0-4 mo and at 4-24 mo). There were no consistent trends in VC closure or supraglottic compression. All GRBAS parameters confirmed post-RT improvement in dysphonia. The overall voice grade (G) was moderately impaired pre-RT (1.9 +/- 0.2) with gradual improvement post-RT (1.4 +/0.2 at 0-4 mo and 1.2 +/-0.2 at 4-24 mo). Conclusions: In this blinded study, VLS proved to be a robust and consistent tool for assessing pre-RT and post-RT dysphonia. We observed a trend toward post-RT improvement in vibration and mobility of the ipsilateral (diseased) vocal cord, as well as mild impairment of contralateral VC vibration, and an overall improvement in perceptive voice quality. Author Disclosure: A.E. Marciscano: None. H.M. Starmer: None. S.R. Best: None. L.M. Akst: None. H. Quon: None. A.P. Kiess: None.
214 Dose Intensified Hypofractionated IMRT With Synchronous Cetuximab for Intermediate-Stage Head and Neck Squamous Cell Carcinoma (HNSCC): Results From the Phase 1/2 INTENSE Trial D. Thomson, K. Ho, L. Ashcroft, K. Denton, K. Mais, K. Garcez, B. Yap, L. Lee, A. Sykes, C. Rowbottom, and N. Slevin; The Christie NHS Foundation Trust, Manchester, United Kingdom Purpose/Objective(s): The addition of chemotherapy to radiation therapy improves tumor control and survival outcomes in locally advanced HNSCC. However, this is at the expense of increased acute and late toxicity. Synchronous cetuximab compared with radiation therapy alone improves tumor control and survival without increased late toxicity. Another strategy to improve loco-regional control is altered fractionation. The effect is more pronounced on the primary tumor and where there is low nodal burden i.e., intermediate stage disease. For this group, we prospectively investigated whether dose intensified hypofractionated IMRT with synchronous cetuximab was safe, effective and could relatively spare late toxicity. Materials/Methods: Between 2008 and 2009, 27 patients of median age 62 years (range, 40-74 years) with stage III (75%) or high risk stage II (25%) oropharyngeal (63%), laryngeal (33%) or hypopharyngeal (4%) HNSCC were recruited to a phase 1/2 trial. They received 3 dose volumes IMRT, with CTV1 receiving 62.5 Gy in 25 daily fractions over 5 weeks (biologically equivalent dose to the tumor, 70.9 Gy10 and late reacting tissues, 114.6 Gy3) and synchronous cetuximab (400 mg/m2 one week prior to radiation therapy and then 250 mg/m2 weekly). Acute toxicity, physician and patient reported late toxicity and quality of life data were collected. Results: The radiation therapy course was completed in 26/27 patients; for 1 patient the final fraction was omitted due to skin toxicity. The median radiation therapy overall treatment time was 34 days. All 6 cycles of cetuximab were received by 23 (85%) patients; 3 (11%) and 1
212 Survival Outcomes of Patients With T4a Larynx Cancer Following Initial Management With Surgery Versus Larynx Preservation Therapy S. Grover, S. Swisher-McClure, and A. Lin; University of Pennsylvania, Philadelphia, PA Purpose/Objective(s): Consensus practice guidelines recommend total laryngectomy (TL) as initial management for medically operable patients with T4a larynx cancer. In addition, patients with T4a larynx cancer are frequently excluded from clinical trials of larynx preservation (LP) because of anticipated poor larynx preservation rates and concerns for inferior survival outcomes. Using a large national cancer registry, we examined recent practice patterns among patients with T4a larynx cancer, and compared survival outcomes between patients receiving TL vs LP. Materials/Methods: Our study included 1,307 patients diagnosed with non-metastatic invasive T4a squamous cell carcinoma of the larynx from 2003-2006 in the National Cancer Database. Treatment groups were defined as initial surgery (TL + adjuvant therapy) vs LP with chemoradiation (CRT). Patients receiving surgery only, radiation alone, or those not receiving any treatment within 100 days of diagnosis were excluded. Univariate and multivariate (MVA) logistic regression models were used to assess predictors (year of diagnosis, age, gender, race, insurance status, type of treatment facility, distance from center, center case volume, N stage, and comorbidity index) of receiving surgical treatment. Survival outcomes were compared using Kaplan-Meier and Cox proportional hazards regression methods. Results: Overall, 65% (n Z 856) of patients received LP and 35% (n Z 451) underwent TL + adjuvant RT or CRT. On MVA, patients with advanced nodal disease were less likely to receive TL compared to patients with N0 disease (N2 vs N0, 25.4% vs 41.2%, OR Z 0.46, 95% CI Z 0.150.82; N3 vs N0, 22.2% vs 41.2%, OR Z 0.34, 95% CI Z 0.15-0.82). Patients treated in facilities with high case-volume were more likely to receive TL compared to those treated at low case-volume facilities (47.1% vs 28.6%, OR Z 2.03, 95% CI Z 1.51-2.73). Patients diagnosed in 2006 were less likely to receive TL compared to patients diagnosed in 2003 (28.1% vs 40%, OR Z 0.60, 95% CI Z 0.43-0.86). Median survival among patients receiving TL vs LP was 60 vs 31 months (p < 0.001). After controlling for potential confounders, patients receiving LP had inferior overall survival compared to those receiving TL (HR Z 1.51, 95% CI Z 1.28-1.75). Conclusions: Approximately two out of three patients with T4a larynx cancer receive LP rather than TL, despite practice guidelines suggesting TL as the preferred initial approach. Use of TL appears to be declining over time. Patients treated in high case-volume centers are more likely to receive primary surgical management. Further research should investigate treatment decision counseling by physicians to their patients, patient decision making, and potential strategies to reduce observed differences in patient survival outcomes. Author Disclosure: S. Grover: None. S. Swisher-McClure: None. A. Lin: None.
213 Video Laryngostroboscopy Demonstrates PosteRadiation Therapy Improvement in Dysphonia in Early-Stage Glottic Larynx Cancer A.E. Marciscano, H.M. Starmer, S.R. Best, L.M. Akst, H. Quon, and A.P. Kiess; Johns Hopkins Hospital, Baltimore, MD Purpose/Objective(s): Video laryngostroboscopy (VLS), an endoscopic tool utilizing rapid pulsed light to view vocal cord (VC) vibration, is the clinical gold standard for evaluation of dysphonia. Though dysphonia is common among patients with early stage glottic cancer, VLS has not been used to assess posteradiation therapy (RT) voice changes. We hypothesized that VLS would show improvement in dysphonia after definitive RT for early glottic cancer. Materials/Methods: Eleven patients underwent RT for stage TisT2N0M0 glottic larynx cancer and were evaluated with serial VLS
Oral Scientific Sessions
S99
examinations pre-RT and post-RT. Two expert laryngologists graded each exam retrospectively in a blinded fashion with scores of 0-4 for 6 parameters: VC vibration, VC mobility, VC closure, supraglottic compression, erythema/edema, and secretions. GRBAS voice perceptive scale was used in tandem with VLS score. Assessments were grouped by time interval from RT: pre-RT, 0-4 mo and 4-24 mo post-RT. Descriptive statistics were reported as mean score +/- standard error of the mean. Results: In total, 40 VLS examinations were scored and 40 GRBAS assessments were reviewed. Pre-RT, ipsilateral (diseased) VC vibration was moderately impaired (mean 2.9 +/- 0.3) and ipsilateral VC mobility was mildly impaired (0.8 +/- 0.2). Post-RT, there was improvement in ipsilateral VC vibration (2.0 +/- 0.3 at 0-4 mo and 2.3 +/- 0.2 at 4-24 mo) and ipsilateral VC mobility (0.4 +/- 0.1 at 0-4 mo and 0.6 +/- 0.2 at 12-24 mo). Pre-RT, contralateral VC vibration was mildly impaired (mean 1.2 +/- 0.3) and contralateral VC mobility was normal (0.1 +/- 0.1). Interestingly, there was an increase in post-RT impairment of contralateral VC vibration (1.4 +/- 0.3 at 0-4 mo and 1.7 +/- 0.2 at 4-24 mo), possibly due to fibrosis. There was mild pre-RT edema/erythema (1.1 +/- 0.2) and normal secretions. As expected, there was increased post-RT edema/erythema (1.8 +/0.2 at 0-4 mo and at 4-24 mo) and thickened secretions (0.7 +/- 0.1 at 0-4 mo and at 4-24 mo). There were no consistent trends in VC closure or supraglottic compression. All GRBAS parameters confirmed post-RT improvement in dysphonia. The overall voice grade (G) was moderately impaired pre-RT (1.9 +/- 0.2) with gradual improvement post-RT (1.4 +/0.2 at 0-4 mo and 1.2 +/-0.2 at 4-24 mo). Conclusions: In this blinded study, VLS proved to be a robust and consistent tool for assessing pre-RT and post-RT dysphonia. We observed a trend toward post-RT improvement in vibration and mobility of the ipsilateral (diseased) vocal cord, as well as mild impairment of contralateral VC vibration, and an overall improvement in perceptive voice quality. Author Disclosure: A.E. Marciscano: None. H.M. Starmer: None. S.R. Best: None. L.M. Akst: None. H. Quon: None. A.P. Kiess: None.
214 Dose Intensified Hypofractionated IMRT With Synchronous Cetuximab for Intermediate-Stage Head and Neck Squamous Cell Carcinoma (HNSCC): Results From the Phase 1/2 INTENSE Trial D. Thomson, K. Ho, L. Ashcroft, K. Denton, K. Mais, K. Garcez, B. Yap, L. Lee, A. Sykes, C. Rowbottom, and N. Slevin; The Christie NHS Foundation Trust, Manchester, United Kingdom Purpose/Objective(s): The addition of chemotherapy to radiation therapy improves tumor control and survival outcomes in locally advanced HNSCC. However, this is at the expense of increased acute and late toxicity. Synchronous cetuximab compared with radiation therapy alone improves tumor control and survival without increased late toxicity. Another strategy to improve loco-regional control is altered fractionation. The effect is more pronounced on the primary tumor and where there is low nodal burden i.e., intermediate stage disease. For this group, we prospectively investigated whether dose intensified hypofractionated IMRT with synchronous cetuximab was safe, effective and could relatively spare late toxicity. Materials/Methods: Between 2008 and 2009, 27 patients of median age 62 years (range, 40-74 years) with stage III (75%) or high risk stage II (25%) oropharyngeal (63%), laryngeal (33%) or hypopharyngeal (4%) HNSCC were recruited to a phase 1/2 trial. They received 3 dose volumes IMRT, with CTV1 receiving 62.5 Gy in 25 daily fractions over 5 weeks (biologically equivalent dose to the tumor, 70.9 Gy10 and late reacting tissues, 114.6 Gy3) and synchronous cetuximab (400 mg/m2 one week prior to radiation therapy and then 250 mg/m2 weekly). Acute toxicity, physician and patient reported late toxicity and quality of life data were collected. Results: The radiation therapy course was completed in 26/27 patients; for 1 patient the final fraction was omitted due to skin toxicity. The median radiation therapy overall treatment time was 34 days. All 6 cycles of cetuximab were received by 23 (85%) patients; 3 (11%) and 1