Induction Chemotherapy Predicts Cumulative Radiation Dose and Fails to Improve Survival in Advanced Head and Neck Cancer, a National Cancer Data Base Analysis

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International Journal of Radiation Oncology  Biology  Physics

Author Disclosure: C. Fakhry: None. Q. Zang: None. M. Gillison: None. P. Nguyen-Tan: None. D.I. Rosenthal: None. R.S. Weber: None. L. Lambert: None. A. Trotti: None. W.L. Barrett: None. W. Thorstad: None. S.S. Yom: None. S. Wong: None. J.A. Ridge: None. S.S. Rao: None. W.K. Huh: None. E. Vigneault: None. D. Raben: None. J. Harris: None. Q. Le: None.

Author Disclosure: M.C. Ward: None. J. Scharpf: None. D.J. Adelstein: None. B.B. Burkey: None. E. Lamarre: None. N. Houston: None. S. Koyfman: None.

107 Validation and Comparison of Prognostic Scoring Systems in a Cohort of Human PapillomaviruseAssociated Oropharynx Cancers Treated Nonoperatively M.C. Ward,1 J. Scharpf,2 D.J. Adelstein,2 B.B. Burkey,2 E. Lamarre,2 N. Houston,2 and S. Koyfman1; 1Cleveland Clinic Foundation, Cleveland, OH, 2Cleveland Clinic, Cleveland, OH Purpose/Objective(s): The recent human papillomavirus (HPV) epidemic in oropharynx cancer (OPC) presents a demographic separate from the historical tobacco-associated OPC. This population is comparatively younger and healthier than previous patients with tobacco-associated cancers. Comorbidity assessment is a critical component of the pretreatment evaluation, but the optimal system for documentation and research is unclear in this cohort. The purpose of this study was to validate and compare 2 common comorbidity scales: the historic Charlson comorbidity index and the more recent Adult Comorbidity Evaluation-27 (ACE-27). Materials/Methods: From a retrospective institutional review boardeapproved tumor registry, patients with HPV-associated OPC treated nonoperatively from 2001 to 2013 were identified. Both the Charlson score and the ACE-27 category were recorded. The Kaplan-Meier method was used to assess overall survival (OS) by comorbidity system with differences assessed using the log-rank test. Two separate multivariate Cox proportional hazards models were generated, each with the individual comorbidity system as well as the predictors of OS statistically significant on univariate analysis. Results: Two hundred eighty-eight patients were identified, of which 274 were treated with combined chemoradiation therapy and 14 with radiation therapy alone. The cervical nodes were involved in 277 patients, and 285 were stage III-IVB. The median oncologic follow-up was 53.5 months. There were 55 deaths in the group for an estimated 5-year overall survival (OS) of 83%. Patients with no comorbidities measured by the ACE-27 score uniformly had a Charlson score of zero. However, a distribution of Charlson scores noted amongst patients with mild, moderate, or severe ACE-27 categories had a range of Charlson scores: 0-5, 0-4, and 0-8, respectively, each with a median Charlson score of 1. On univariate analysis age, Charlson score, ACE-27 category, pack-years of smoking, and T stage were significantly associated with OS. On multivariate analysis (MVA), pack-years of smoking, T stage, and each comorbidity score remained independently associated with OS. Conclusion: Both the ACE-27 and the Charlson comorbidity index are validated prognostic scales for the measurement of comorbidity in HPVassociated head and neck cancer. Both have advantages: although ACE-27 is more sensitive, the Charlson score may retain a degree of granularity given the range of possible results. Comorbidity should be included in predictive models for OS in an attempt to account for competing risks in this relatively healthy subset of head and neck patients.

Abstract 107; Table 1 MVA with Charlson Variable Age Charlson ACE-27

Pack-years T stage

1 vs 0 2 vs 0 3 vs 0 3-4 vs 1-2

MVA with ACE-27

HR

p

HR

p

0.995 1.629 — — — 1.013 2.3

.763 <.0001 — — — .0053 .0026

1.013 — 1.446 2.434 1.882 4.773 2.154

.475 — .359 .022 .192 .024 .007

108 The Outcomes of Induction Chemotherapy for Head and Neck Cancer Patients S.Y. Wu,1 F.P. Lee,2 K.C. Lin,3 M.T. Lai,2 C.C. Wu,2 T.M. Chen,2 Y.F. Ding,2 and S.P. Yuan2; 1Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, 2Department of otorhinolaryngology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, 3Department of Oral and Maxillofacial Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan Purpose/Objective(s): Until now, the role of induction chemotherapy has remained a subject of controversy. Our study was to directly compare survival in patients receiving induction chemotherapy docetaxel or platinum given before concomitant chemoradiation therapy with upfront chemoradiation therapy alone. Materials/Methods: The National Health Insurance claims database and cancer registry databases in Taiwan were linked for the analysis. Head and neck cancer patients from January 1, 2002 to December 31, 2011 were included in the study. The inclusion criteria were having a head and neck cancer (identified according to the International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 140.0-148.9), being aged >20 years, being classified as American Joint Committee on Cancer (AJCC) clinical cancer stage III-IV (locally advanced head and neck cancers without metastasis), and having undergone induction chemotherapy or concurrent platinum-based chemoradiation therapy (CCRT). Exclusion criteria were having been diagnosed with cancer before the head and neck cancer was confirmed, having distant metastasis, AJCC clinical cancer stage I-II, platinum and docetaxel combined use before RT, docetaxel use during or after RT, induction chemotherapy beyond 8 weeks before RT, only 1 course of induction chemotherapy before RT, cetuximab use, adjuvant chemotherapy within 90 days after completion of RT, less than 7000 cGy dose of RT, curative head and neck cancers surgery before RT, nasopharyngeal cancer, carcinoma in situ, sarcoma, head and neck cancer recurrence, or an unknown gender, and being younger than 20 years of age. The total number of enrolled head and neck cancer patients was 30,990 persons. Results: In total, 10,721 stage III-IV head and neck cancer patients without distant metastasis were included in the study, and the median follow-up duration was 4.18 (interquartile range, 3.25) years. There were 7968 patients in the CCRT group (arm 1); 503 patients in the induction chemotherapy with docetaxel group of arm 2, and 2232 patients in the induction chemotherapy with platinum group of arm 3. We used the CCRT arm as the control arm to investigate the risk of death after induction chemotherapy. After adjustments for age, gender, clinical stage, and comorbidities, the adjusted hazard ratios of overall deaths were 1.37 (95% confidence interval [CI], 1.22e1.53) in arm 2 and 1.44 (95% CI, 1.36e1.52) in arm 3. In disease-specific survival rate analysis, the adjusted HRs of head and neck cancers deaths were 1.29 (95% CI, 1.14-1.46) in arm 2 and 1.47 (95% CI, 1.38-1.56) in arm 3. Conclusion: Our cohort study showed induction chemotherapy with docetaxel or platinum not only did not improve survival but also resulted in more all death and head and neck cancer death risk compared with CCRT. Author Disclosure: S. Wu: None. F. Lee: None. K. Lin: None. M. Lai: None. C. Wu: None. T. Chen: None. Y. Ding: None. S. Yuan: None.

109 Induction Chemotherapy Predicts Cumulative Radiation Dose and Fails to Improve Survival in Advanced Head and Neck Cancer, a National Cancer Data Base Analysis W. Stokes,1 A. Amini,1 J. McDermott,2 A. Jimeno,2 D. Raben,1 D.W. Bowles,2 and S. Karam1; 1Department of Radiation Oncology, University of Colorado Denver, Aurora, CO, 2Department of Medical Oncology, University of Colorado Denver, Aurora, CO

Volume 94  Number 4  2016 Purpose/Objective(s): The role of induction chemotherapy (IC) in advanced head and neck squamous cell carcinoma (HNSCC) remains controversial. In recent randomized trials, the addition of IC to concurrent chemoradiation (CRT) failed to improve overall survival (OS). This failure may stem from the studies’ lack of power due to slow accrual and/or from their inclusion of patients with less advanced nodal disease, prompting the present analysis of the National Cancer Data Base (NCDB). Materials/Methods: The NCDB was queried for subjects diagnosed from 2003 to 2011 with T (any) N2b-3 M0 cancers of the oropharynx, hypopharynx, and larynx, who underwent external beam radiation without surgery. We defined 2 analytic cohorts based on the sequencing of chemotherapy (CT) and radiation therapy (RT): an IC cohort with start of CT preceding RT by 43 to 98 days (thus allowing 2-3 cycles of IC as used in recent trials) and a CRT alone cohort with CT starting within 7 days of RT start. Logistic regression was used to identify factors associated with nonguideline-concordant RT dose (ie, <66 Gy), and Cox regression was used to assess the association of CT sequence on OS. Results: A total of 6086 CRT and 1917 IC subjects were evaluable. As compared to the CRT group, the IC cohort tended to be younger and to have more advanced T and N status and more hypopharynx cancer, were more likely to receive <66 Gy of RT (20.9% vs 14.9%; P<.01), and displayed worse OS (median 52.1 vs 64.9 months, P<.01). After adjusting for age, year, sex, race, location, income, comorbidities, primary site, and T and N status with multivariate analysis, the IC cohort had increased odds of receiving <66 Gy (odds ratio 1.42; 95% confidence interval [CI] 1.241.63; P<.01), but their OS did not significantly differ from that of the CRT cohort (hazard ratio [HR] for mortality 1.07; 95% CI 0.99-1.16; PZ.08). On subgroup analysis, IC status was not associated with improved OS among the 2809 subjects with T4 or N3 disease (HR 1.02; 95% CI 0.921.13; PZ.72), the 1107 patients with N3 disease (HR 1.02; 95% CI 0.861.22; PZ.82), or the 351 subjects with T4N3 disease (HR 0.97; 95% CI 0.73-1.28; PZ.81). Among the 5194 patients without T4 or N3 disease, IC status predicted a slight increase in mortality (HR 1.12; 95% CI 1.00-1.25; PZ.046). Conclusion: In this large group of HNSCC patients with advanced nodal disease from the NCDB, IC subjects were more likely to receive less-thandefinitive doses of RT, and OS was not significantly different from that of CRT subjects, even on subgroup analyses of increasingly advanced disease. Failure of prior studies to demonstrate an OS benefit with IC may have less to do with statistical power or patient selection and more to do with difficulty completing guideline-concordant care following IC. Author Disclosure: W. Stokes: Employee; University of Colorado Denver GME. A. Amini: None. J. McDermott: None. A. Jimeno: None. D. Raben: None. D.W. Bowles: None. S. Karam: None.

110 Patterns of Failure After Definitive Radiation for Oropharyngeal CancerdShould P16 Status and Tumor Growth Rate Alter the Clinical Target Volume? C.T. Murphy,1 M. Dziemainowicz,2 T. Shaikh,1 M. Fareed,1 J.A. Ridge,1 R. Mehra,1 and T.J. Galloway1; 1Fox Chase Cancer Center, Philadelphia, PA, 2Temple University School of Medicine, Philadelphia, PA Purpose/Objective(s): To determine patterns of failure after definitive radiation therapy (RT) for oropharyngeal cancer (OPC) and employ clinical target volume (CTV) expansions based upon p16 status and primary tumor growth rate (TGR). Materials/Methods: One hundred three OPC patients with known p16 status, smoking pack-years, and TGR (defined as percent volume growth/ day) managed with chemoradiation therapy (CRT) were analyzed. Diagnostic computed tomographic scan images of patients with locoregional failure (LRF) were imported into a commercially available contouring system and fused with the radiation treatment planning scan dose distribution using deformable registration. The distance of the LRF from the edge of radiation prescription volume (RxV) was recorded. Cox proportional hazards model was used to estimate the risk of disease recurrence.

Posters

875

Abstract 110; Table 1 RTOG 0129 risk group Low (nZ52) Intermediate (nZ33) High (nZ18)

TGR < 0.74% (nZ51)

TGR > 0.74% (nZ52)

LR failure Distant failure LR failure Distant failure 0/30 0/18 0/3

1/30 1/18 1/3

1/22 4/15 10/15

2/22 3/15 3/15

Results: Seventy-nine patients were p16(+) (77%), and 98 were stage III or IV (95%). Median TGR was 0.74%/day (range 0.01-5.5). Median followup was 30 months (range 0.5-80). Ninety-two percent were treated with CRT. On multivariate analysis, p16(-) status (hazard ratio [HR] 3.4, 95% confidence interval [CI] 1.4-8.3) and increasing TGR (HR 4.8, 95% CI 1.614.5) were the strongest predictors of recurrence. Patterns of failure according to Radiation Therapy Oncology Group (RTOG) 0129 risk group, stratified by median TGR are shown in Table 1. Fourteen of 15 patients with LRF had evaluable postrecurrence scans and plans. The median time to LRF was 4 months (range 0.75-14 months). A majority of failures (11/15, 73%) were marginal to high-dose radiation prescription volume (RxV; ie, the tumor recurred both in and out of the treated volume). Four recurrences developed completely within the highdose RxV. The median distance of the furthest extent of the recurrence from the field edge was 7 mm; the distance from the RxV edge necessary to encompass the LRF with adequate margin ranged from 0 to 20 mm. Eighty percent of failures would have been covered by an expansion of an additional 12 mm outside of the RxV; 3 patients experienced LRF more than 15 mm outside of the high-dose RxV. Conclusion: Locoregional failures in low-risk OPC tumors are rare, such that reductions in CTV margins may be justified in the interest of treatment deintensification. The dominant pattern of failure in intermediate- and high-risk tumors appears to be marginal to the high-dose prescription volume, predominantly among tumors with increased TGR. CTV expansions based upon RTOG 0129 risk group and TGR warrant investigation. Author Disclosure: C.T. Murphy: None. M. Dziemainowicz: None. T. Shaikh: None. M. Fareed: None. J.A. Ridge: None. R. Mehra: None. T.J. Galloway: None.

111 Dosimetric Verification of Dental Stent Efficacy in Head and Neck Radiation Therapy Using Modern Radiation Therapy Techniques: Quality of Life (QOL) and Treatment Compliance Implications E. Allan,1 L. Lu,2 H. Hooman,3 A. Chakravarti,2 M. Van Putten,4 and D. Blakaj1; 1The James Cancer Hospital and Solove Research Institute, Wexner Medical Center at The Ohio State University, Department of Radiation Oncology, Columbus, OH, 2The Ohio State University Wexner Medical Center, Columbus, OH, 3Ohio University - Heritage College of Osteopathic Medicine, Dublin, OH, 4The James Cancer Hospital and Solove Research Institute, Wexner Medical Center at The Ohio State University, Department of Maxillofacial Prosthodontics, Columbus, OH Purpose/Objective(s): Oral mucositis is a commonly observed toxicity during head and neck radiation therapy. Metallic dental restorations produce short-range secondary electrons that deposit dose into nearby tissue causing large, painful ulcers in the adjacent mucosal surfaces. This contributes to patient weight loss during treatment and often leads to breaks in therapy to replan or to allow for recovery. Various protective dental stents have been proposed and tested in very simple phantoms and 2-dimensional (2D) beam arrangements. Our objective was to generate the first quantitative assessment of electron scatter and stent efficacy using an anatomically realistic phantom and a modern beam configuration and delivery method in order to better address our patients’ QOL during treatment. Materials/Methods: We created a tissue-equivalent phantom to simulate a complete upper and lower jaw with 2 sets of removable gold caps on opposing molars. We created a set of 4-mm upper and lower ethylene copolymer dosimetric stents to provide space between the mucosae and teeth as well as between the upper and lower jaw. The phantom was placed