Long Term Regional Control and Survival in Patients with “Low Risk” Early Stage Oral Tongue Cancer Managed by Partial Glossectomy and Neck Dissection without Postoperative Radiation: The Importance of Depth of Invasion

Proceedings of the 53rd Annual ASTRO Meeting Risk grouping predicted for OS and recurrence. Patients with low-risk disease had a median survival of 162 months compared to 119 months for intermediate-risk, and 39 months for high-risk (p = 0.004). For LRR, there was a trend to improved outcome with low-risk disease; the 7-year actuarial rates of LRR for low-risk was 5%, intermediate-risk 6%, and high-risk 30% (p = 0.08). For DM, there was a statistically significant difference between risk groups (low-risk 5%, intermediate-risk 7%, and high-risk 37%; p = 0.005). Conclusions: Increased follow-up in this study of postoperative radiation therapy demonstrates that pathologic risk grouping remains strong for predicting outcome. Treatment intensification with increased doses and fractionation schedules is not sufficient to make up for aggressive pathology. Both LRR and DM are continued problems in high-risk patients, and this has been addressed in studies of concurrent chemoradiation. Author Disclosure: B.M. Beadle: None. A.S. Garden: None. W.H. Morrison: None. D.I. Rosenthal: None. G.B. Gunn: None. S.J. Frank: None. A.C. Hessel: None. K.K. Ang: None.

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Postoperative IMRT following Surgery for Oral Cavity Squamous Cell Carcinoma: Patterns of Failure

A. K. Chan, S. Huang, L. W. Le, D. P. Goldstein, K. Chan, L. A. Dawson, J. Kim, B. O’Sullivan, B. Cummings, A. J. Hope Princess Margaret Hospital, Toronto, ON, Canada Purpose/Objective(s): To review outcomes of oral cavity squamous cell carcinoma (OCSCC) treated with surgery and post-operative intensity modulated radiation therapy (IMRT). Materials/Methods: All patients with nonmetastatic/non-recurrent OCSCC treated with surgery and postoperative IMRT +/- concurrent chemotherapy between 2005 and 2010 were evaluated. Patient survival and tumor outcomes were prospectively recorded. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), regional control (RC) and distant control (DC). Univariate analysis used chi-square test or t test to compare groups. Results: A total of 180 consecutive patients, with median follow-up of 34 months (range, 6-70 months), were identified. Median age 61 years (range, 21-84) M:F (115:65). AJCC Stages: I (8; 4%), II (26; 14%), III (33; 18%), IVA/B (113; 63%). Disease subsites: oral tongue (83; 46%); floor of mouth (42; 23%); alveolus and hard palate (22; 12%); buccal (17; 10%); retromolar trigone (9; 5%); and lip (7; 4%). Pathological nodal involvement (pN+) (121; 67%), extracapsular extension (ECE) (61; 34%), and perineural invasion (109; 61%), R1 (18%). Median time from surgery to start of RT was 59 days (range, 28-161 days). Median radiation dose was 60 Gy (2 Gy/fraction). Concurrent chemotherapy was delivered in 47 (26%) patients. The 2 year rates of OS, LC, RC, locoregional control (LRC), and DC were 65%, 87%, 83%, 78%, and 83%, respectively. The 2-year estimated rates of LRC by subsites were: oral tongue (72%); floor of mouth (84%); alveolus and hard palate (72%); buccal (94%); retromolar trigone (62%); and lip (100%). Of the 180 patients, 38 (21%) had locoregional failure (LRF); 22 (12%) local, 31 (17%) regional, and 15 (8%) both local and regional. Failures were isolated local in 5 (3%); isolated regional in 8 (4%) and simultaneous local and regional without distant failure in 9 (5%). Prognostic factors for LRF included Stage IV (79% vs. 58%, p = 0.02); pN+ (79% vs. 64%, p = 0.08); ECE (42% vs. 32%, p = 0.23). Positive margin was not a prognostic factor for LRF. Median time to LRF was 8 months (range, 2-39 months). The majority of LRF were in-field (30; 79%). Marginal or out-of-field failures occurred in patients treated with ipsilateral RT (5), primary site only RT (1) and bilateral RT (2) with both patients failing at high level II/skull base. Infield failures with or without distant failure occurred in 10 and 19 patients, respectively. Distant failure occurred in 28 (16%) with isolated distant failure in 12 (7%). Conclusions: With post-operative IMRT, the majority of failures occurred in-field and distantly, but 21% of LRF were marginal or out-of-field, suggesting some patients may benefit from improvements in target delineation. Author DisclosureA.K. Chan: None. S. Huang: None. L.W. Le: None. D.P. Goldstein: None. K. Chan: None. L.A. Dawson: B. Research Grant; Bayer Clinical Research Funding. E. Ownership Interest; Raysearch ownership. J. Kim: None. B. O’Sullivan: None. B. Cummings: None. A.J. Hope: None.

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Long Term Regional Control and Survival in Patients with ‘‘Low Risk’’ Early Stage Oral Tongue Cancer Managed by Partial Glossectomy and Neck Dissection without Postoperative Radiation: The Importance of Depth of Invasion

I. Ganly1, D. Goldstein2, S. Patel1, N. Lee1, P. Gullane2, J. Shah1 Memorial Sloan Kettering Cancer Center, New York, NY, 2University of Toronto, Toronto, ON, Canada

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Purpose/Objective(s): In patients with early-staged oral tongue squamous cell cancer (OTSCC) managed by partial glossectomy (PG) and elective neck dissection (END) (pT1T2N0), the decision for adjuvant postoperative radiation (PORT) is determined by close/positive margins, lymphovascular invasion, and perineural invasion. Patients without these adverse features are considered low risk and are observed. However, there are no long-term outcomes data on these patients. The objectives of our study were to determine the incidence of locoregional failure and disease-specific survival in patients with pT1T2N0 OTSCC and identify factors predictive of failure. Materials/Methods: A combined database of patients with OTSCC treated at Memorial Sloan Kettering Cancer Center and University of Toronto between 1985 and 2005 was established. One hundred sixty-three patients with pT1T2N0 OTSCC managed by PG and END without PORT were identified. Patient, tumor and treatment related characteristics were recorded. Local recurrencefree survival (LRFS), regional recurrence-free survival (RRFS), and disease-specific survival (DSS) were calculated by the Kaplan-Meier method. Predictors of outcome were analyzed by univariate and multivariate analysis. Results: The median age was 55 years (range, 25-82) and 55% were men. Fifty-three percent tumors were pT2 and 59% had a depth of invasion (DOI) .4 mm. With a median follow-up of 66 months (range, 1-171), 16 (10%) patients developed local and 29 (18%) developed regional recurrence. Regional recurrence was ipsilateral (dissected neck) in 61% and contralateral (undissected neck) in 39% of patients. The level of neck recurrence was level I (41%), II (21%), III (21%), IV (10%), and V (3%). The rate of regional recurrence stratified by DOI was 5.7% for tumors \4 mm and 24% for tumors .4 mm. The 5 year LRFS, RRFS,

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and DSS for all patients was 89%, 80% ,and 86%, respectively. There were no factors predictive of local recurrence. However, multivariate analysis showed that DOI was the only independent predictor of neck failure and DSS (RRFS: 94% vs. 72%, p = 0.02; DSS: 97% vs. 81%, p = 0.05 for tumors \4 mm and .4 mm, respectively). Patients who recurred in the neck had a significantly poorer DSS compared to those who did not (33% vs. 97%, p \ 0.0001). Conclusions: Patients with low risk pT1T2N0 OTSCC managed by PG and END without PORT have a greater than expected rate of neck failure with contralateral recurrence accounting for 40% of cases. Failure occurs predominantly in patients with primary tumors with DOI .4 mm. Only one third of patients with neck recurrence are successfully salvaged. DOI .4 mm may be an indication for PORT. A randomized clinical trial for PORT in patients with pT1T2N0 OTSCC with DOI .4 mm may answer this question. Author Disclosure: I. Ganly: None. D. Goldstein: None. S. Patel: None. N. Lee: None. P. Gullane: None. J. Shah: None.

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P16 is Not a Positive Prognostic Indicator for Hypopharyngeal Squamous Cell Carcinoma Treated with Definitive Chemoradiotherapy

D. D. Wilson, A. Shoushtari, D. Saylor, A. Cupino, E. B. Stelow, D. C. Shonka, M. J. Jameson, P. W. Read University of Virginia Medical Center, Charlottesville, VA Purpose/Objective(s): Multiple studies have reported that human papillomavirus (HPV) associated p16 expression in oropharyngeal squamous cell carcinomas (SCC) is a positive prognostic indicator for improved overall survival and locoregional control. There is little data on the prognostic significance of p16 in patients with hypopharyngeal SCC, but one small retrospective study in 1994 showed that HPV was associated with poorer prognosis in laryngeal and hypopharyngeal SCC. The purpose of this study was to determine the prognostic significance of p16 expression for patients with hypopharyngeal SCC treated with definitive chemoradiotherapy with intensity modulated radiation therapy (IMRT). Materials/Methods: Eighteen patients with hypopharyngeal SCC were treated with definitive IMRT from 2002 to 2010 at the University of Virginia and were retrospectively analyzed. All patients received 66-72 gray (Gy), with the exception of 1 patient who failed to respond to 52.4 Gy and then underwent surgical salvage. Seventeen patients received chemotherapy and one patient received radiation alone. Tumor biopsies from each patient were analyzed with immunohistochemistry for p16 expression, and locoregional control and survival were analyzed. P16 expression was considered ‘‘positive’’ if strong nuclear and cytoplasmic staining was present in more than 60% of tumor cells. Results: P16 was positive in 39% of patients and negative in 61% of patients. P16+ and p16- patients had no statistically significant differences in tobacco or alcohol use, age, hypopharyngeal subsite, tumor stage or grade. There were significantly more women in the p16+ group, 43% vs. 0% (p = 0.043). Median follow-up was 26.2 months (range, 4.2-83.8 months). Mean overall survival was 40.9 months for p16+ patients and 67.1 months for p16- patients (p = 0.064). Mean locoregional recurrence-free survival was 25.8 months for p16+ patients and 74.0 months for p16- patients (p = 0.067). Mean disease-free survival was 23.2 months for p16+ patients and 67.0 months for p16- patients (p = 0.038). Conclusions: In contrast to oropharyngeal SCC, patients with hypopharyngeal SCC with p16 expression trended toward poorer overall survival, poorer locoregional control, and significantly shorter disease-free survival in our cohort of patients. Investigators have reported that hypopharyngeal p16+ SCCs are generally HPV negative, suggesting a different mechanism for p16 over-expression. We are performing further analysis to elucidate the molecular mechanisms associated with upregulation of p16 in hypopharyngeal SCC. Although p16 has previously been shown to be a positive prognostic marker for oropharynx SCC, caution must be taken when extrapolating this to other head and neck subsites. Author Disclosure: D.D. Wilson: None. A. Shoushtari: None. D. Saylor: None. A. Cupino: None. E.B. Stelow: None. D.C. Shonka: None. M.J. Jameson: None. P.W. Read: None.

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Outcomes for T2N0M0 Glottic Squamous Cell Carcinoma Treated with IMRT Compared with Conventional Parallel Opposed Fields

A. C. Tiong, S. Huang, B. O’Sullivan, W. Xu, J. Kim, L. A. Dawson, J. Cho, R. Gilbert, S. Breen, J. N. Waldron Princess Margaret Hospital, Toronto, ON, Canada Purpose/Objective(s): The technical feasibility of using IMRT for treating early glottic squamous cell carcinoma, particularly in relation to normal tissue sparing, has been demonstrated. There is, however, a lack of data regarding the clinical outcomes produced by IMRT compared with standard non-conformal radiotherapy techniques (RT). Materials/Methods: The locoregional control rates of patients with T2N0M0 squamous cell carcinoma of the glottis treated radically with radiotherapy in Princess Margaret Hospital between 2003 and 2008 were determined. Patients were treated with either RT (parallel opposed/angled down pairs using physical wedges or multi-leaf collimated virtual wedges), or with IMRT (using a 5 field IMRT plan with 15 to 20 segments). All patients underwent CT simulation and contouring of the GTV. Patients in the RT group were treated with opposed lateral fields defined to treat the GTV including the whole larynx (majority 6 x 6 cm fields) to 60 Gy in 25 fractions. Two CTVs were defined for patients managed with IMRT plans. A 60 Gy dose (CTV60) was defined as a 0.5 to 1.0 cm expansion on the GTV, and a surrounding 50 Gy dose (CTV50) was variably defined to include a further expansion of 0.5 to 2.0 cm on the CTV60. For 17/50 cases the CTV50 was expanded to include the whole larynx. PTVs were defined as 0.5 cm expansions on the CTVs. On-treatment position verification consisted of either electronic portal imaging or cone beam CT imaging with matching of bony anatomy. Results: During the study period, there were 48 patients treated with RT and 50 patients treated with IMRT. These sequential cohorts were balanced with respect to gender, smoking status, cord mobility, anterior commissure and supra and subglottic involvement. The median follow-up time was 2.8 years (range, 0.3-6.9). The 3-year actuarial local recurrence rate was 32% for IMRT (crude rate 14/50) and 20% for RT (crude rate 11/48) (p = 0.54). Overall survival was 74% with nc-RT compared with