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Risk Factors for Locoregional Recurrence After Transoral Robotic Surgery for HPV+ Oropharyngeal Squamous Cell Carcinoma
S122
International Journal of Radiation Oncology Biology Physics
DNA compared to mRNA suggests that RT induces viral activation and may explain the improved outcome seen in HPV-associated oropharyngeal cancer compared to uninfected patients. Furthermore, at the completion of RT HPV DNA and mRNA are undetectable in the saliva of most patients and 4 to 6 weeks later. Author Disclosure: T.R. Hollen: None. S.B. Zhang: None. W.M. Mendenhall: None. R.J. Amdur: None. A. Zhang: None. P. Okunieff: M. Stock; Paul Okunieff, MD, is a share stockholder in Enterade, LLC, Eva Pharmaceuticals, DiaCarta, LLC, and GainPep.
Author Disclosure: J. Vargo: None. R.L. Ferris: None. J. Ohr: None. D.A. Clump: None. K. Davis: None. J. Johnson: None. M. Gibson: None. B.F. Branstetter: None. D.E. Heron: None.
265 Re-Irradiation With Stereotactic Body Radiation Therapy Plus Cetuximab in Patients With Recurrent Previously-Irradiated Squamous Cell Carcinoma of the Head and Neck: A Prospective Phase II Trial J. Vargo,1 R.L. Ferris,2 J. Ohr,3 D.A. Clump,1 K. Davis,2 J. Johnson,2 M. Gibson,3 B.F. Branstetter,4 and D.E. Heron1; 1University of Pittsburgh Cancer Institute, Dept. Radiation Oncology, Pittsburgh, PA, 2University of Pittsburgh Cancer Institute, Dept. Otolaryngology, Head and Neck Surgery, Pittsburgh, PA, 3University of Pittsburgh Cancer Institute, Dept. Medicine, Div. Medical Oncology, Pittsburgh, PA, 4University of Pittsburgh Cancer Institute, Dept. of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA Purpose/Objective(s): Salvage options for unresectable locally-recurrent, previously-irradiated squamous cell carcinoma of the head and neck (rSCCHN) are limited. While the addition of re-irradiation may improve outcomes over chemotherapy alone, significant acute and late toxicities limits salvage re-irradiation strategies leading to suboptimal outcomes. We therefore designed a phase II protocol to evaluate the efficacy of stereotactic body radiation therapy (SBRT) plus cetuximab for rSCCHN. Materials/Methods: From July 2007 to March 2013, patients > 18 years of age with inoperable locoregionally confined rSCCHN within a previously-irradiated field receiving 60 Gy, ECOG performance status 0-1, and normal hepatic and renal function were enrolled. Patients received concurrent cetuximab (400 mg/m2 on day -7 then 250 mg/m2 on days 0 and +8) plus SBRT (8.0-8.8 Gy per fraction delivered on alternating days over 1-2 weeks for 5 fractions, total 40-44 Gy by treatment volume 25 cc). Primary endpoints were 1-year locoregional progression-free survival (PFS) and NCI CTCAE v3.0 graded toxicity. Results: Fifty patients were enrolled, 48 of which were eligible. Thirty patients (63%) were male, median age was 63, 32 (67%) had prior surgery, 31 (65%) received prior chemotherapy, 11 (23%) received a prior EGFR inhibitor at a median of 12 months prior (range: 6 - 33). Sixty-five percent (n Z 31) were prior smokers > 10 pack years; HPV status was available for 13 patients, 54% of which were HPV positive. The median re-irradiation interval was 18 months (range: 3-423). The median SBRT elapsed days was 9 (range: 8-20). The compliance rate for completion of the prescribed SBRT course was 100%, with only 4% requiring treatment interruptions. Median follow-up for surviving patients was 18 months (range: 10-70). The 1-year local PFS was 60% (95% CI Z 44-75%) and 1year locoregional PFS was 37% (95% CI Z 23-53%). The 1-year distant PFS was 71% (95% CI Z 54-85%), and the 1-year PFS was 33% (95% CI Z 20-49%). The median overall survival was 10 months (95% CI Z 716), with a 1-year overall survival of 40% (95% CI Z 26-54%). At last follow-up, 69% died of disease, 4% died with disease, 15% died without progression, 10% were alive without progression, and 2% alive with progression. Acute grade 3 toxicity was observed in 6% (2 grade 3 mucositis/ dysphagia, 1 grade 3 skin). Late grade 3 toxicity was observed in 6% (1 grade 3 dysphagia, and 2 aerodigestive fistulas). There were no grade 4+ toxicities. Conclusions: SBRT with concurrent cetuximab appears to be a safe succinct salvage treatment for rSCCHN. The 1-year PFS in this cohort appears to be similar to standard of care re-treatment regimen using IMRT with fewer treatment related toxicities. We are further extending this experience with a randomized phase II protocol combining SBRT (40-50 Gy), concurrent cetuximab and 3-month adjuvant cetuximab docetaxel.
266 Dose-Escalated Stereotactic Radiosurgery (SRS) Boost for Unfavorable Locally Advanced Oropharyngeal Cancer: Phase I/II Trial M. Ghaly,1,2 A. Halthore,1 J. Antone,1 H. Zhang,1 J. Cohen,1 H. Sachs,2 K. Beadle,2 M. Aziz,2 B. Kerry-Ann,1 D. Schwartz,1 D. Paul,1 D. Frank,2 B. Saltman,2 and S. Dubner2; 1Hofstra North Shore-LIJ School of Medicine, New Hyde Park, NY, 2Center for Head and Neck Oncology, New Hyde Park, NY Purpose/Objective(s): Management of unfavorable locally advanced oropharyngeal cancer is a common therapeutic dilemma. Large prospective trials have reported poor outcomes after RT or CT-RT, even after an intensive therapeutic approach. We report results of an IRB-approved prospective trial for dose escalation in intermediate and high-risk oropharyngeal cancer. Materials/Methods: Patients with stage III and IV HPV unassociated oropharyngeal cancer or smokers with high nodal stage (i.e., N2b to N3) and unfavorable biomarkers were enrolled in the study. RT dose to gross tumor volumes were escalated using stereotactic radiosurgery (SRS) boost 1 week after CT-RT consisting of concurrent 80 mg/m2 Cisplatin / 3 weeks and 60 Gy of IMRT at 2 Gy/fraction with a strategy of protecting swallowing organs at risk (SWOAR-IMRT). Acute radiation toxicities (n Z 90 days from start of RT) were scored using (CTCAE) Version 4.0 guidelines and late complications by RTOG/EORTC Scheme. Swallowing functional outcomes were monitored using the Performance Status Scale for H&N Cancer Patients (PSS-HN). Overall feeding tube dependence was calculated from the end of RT. Local-regional control and disease free survival was recorded. Results: Eleven patients completed (SRS) boost initial dose level 8 Gy in 1 fraction with median follow-up of 26 months (range 8-30 months). Sixteen patients received their (SRS) boost with dose escalation to 10 Gy fraction and median follow-up of 12 months (range, 6-22 months). Acute G 3 pharyngitis was observed in 53% within the last 2 weeks of CT-RT and no G 4 toxicities were reported. 45% of patients who completed treatment without a feeding tube had rapid recovery to baseline functional outcomes in PSS-HN. Patients who required a feeding tube during treatment experienced a delayed and incomplete recovery of their baseline swallowing function. The 6-month and 1-year rates of feeding tube dependence were 24% and 15%, respectively. Local-regional control and disease-free survival were 81%, 100%, and 81%, 93%, respectively, for both cohorts. Late G3 dysphagia secondary to extensive tumor necrosis was observed in 4 patients and resulted in pharyngeal hemorrhage in two. All four required surgical intervention. Conclusions: Radiation dose escalation with radiosurgery boost offers a viable treatment option for unfavorable oropharyngeal cancer patients who are deemed to be unlikely to be cured with conventional irradiation strategies. This offers patients a therapeutic option with moderate toxicities and functional preservation. Author Disclosure: M. Ghaly: None. A. Halthore: None. J. Antone: None. H. Zhang: None. J. Cohen: None. H. Sachs: None. K. Beadle: None. M. Aziz: None. B. Kerry-Ann: None. D. Schwartz: None. D. Paul: None. D. Frank: None. B. Saltman: None. S. Dubner: None.
267 Risk Factors for Locoregional Recurrence After Transoral Robotic Surgery for HPV+ Oropharyngeal Squamous Cell Carcinoma R. Funk,1 D.G. Stoddard,1 E.F. Vencio,2 J.J. Garcia,1 E.J. Moore,1 R.L. Foote,1 K.A. Price,1 and D.J. Ma1; 1Mayo Clinic, Rochester, MN, 2 Federal University Goia´s, Goia´s, Brazil Purpose/Objective(s): Traditional risk factors predicting locoregional recurrence (LRR) following surgery for head and neck squamous cell
Volume 90 Number 1S Supplement 2014 carcinomas were identified in the pre-HPV era. Patients with HPV positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) present at younger age and have an approximately 50% reduction in death when compared to their HPV- counterparts. Furthermore, transoral robotic surgery (TORS) allows for more detailed intraoperative assessment of microscopic margins. It is unknown if traditional risk factors fully apply to the HPV+ population who undergo TORS. We examined whether traditional indications for adjuvant radiation therapy (RT) (perineural invasion [PNI], angiolymphatic invasion [ALI], T3-4, or N2a-b) or adjuvant chemoradiation therapy (CRT) (extracapsular extension [ECE], or positive margins) also predict for LRR in patients with HPV+ OPSCC. Materials/Methods: After IRB approval, the medical record of 296 consecutive patients treated with TORS for OPSCC were reviewed to identify patients with HPV+ tumors who had indications for adjuvant therapy but did not receive adjuvant therapy. Results: Twenty-one patients with HPV+ base of tongue (n Z 7) or tonsil (n Z 14) OPSCC with a median age of 61 years (range, 39-81 years) who did not receive adjuvant therapy despite the presence of intermediate or high risk features were identified. All patients were p16+, 16 were HPV+ by DNA in situ hybridization. Indications for adjuvant therapy were ALI (n Z 1), PNI (n Z 3), T3 (n Z 5), T4a (n Z 1), N2a (n Z 8), N2b (n Z 5), or ECE (n Z 7). All patients had close margins due to the nature of TORS. Eight patients had multiple indications for adjuvant therapy. No positive margins were noted on final path. Median follow-up after surgery was 22.4 months (range, 7.5-58.7 months). Four of 21 (19%) patients developed LRR at 3.2, 3.4, 4.8, and 5.7 months, respectively. One of 14 (7%) patients with intermediate risk factors only had a LRR, while 43% (3/7) of patients with ECE had a LRR (p Z 0.049). LRR occurred locally (n Z 2, base of tongue), in ipsilateral regional lymph nodes (n Z 1), or in contralateral regional lymph nodes (n Z 1). These patients had 0, 5, 0 and > 10 packyears smoking history, respectively. Two patients were treated with reexcision and adjuvant RT or CRT respectively and are without evidence of disease 19 months later. The third patient received definitive CRT at an outside institution and was lost to follow-up. The final patient refused further definitive CRT after 5200 cGy of a planned 7000 cGy). Further follow-up is pending. Conclusions: In the HPV+ population, ECE remains a risk factor for LRR without adjuvant therapy. However, the role of intermediate risk factors after TORS requires further evaluation with a larger number of patients. Author Disclosure: R. Funk: None. D.G. Stoddard: None. E.F. Vencio: None. J.J. Garcia: None. E.J. Moore: None. R.L. Foote: None. K.A. Price: None. D.J. Ma: None.
268 Functional Outcomes with Surgical and Non-surgical Management of Locally Advanced Oropharyngeal Cancer C.E. Wooten,1 W.A. Wilson,2 S.M. Arnold,3 T. Gal,4 R. Aouad,4 J. Valentino,4 and M.R. Kudrimoti5; 1Albert B. Chandler Hospital, Lexington, KY, 2University of Kentucky Medical Center, Lexington, KY, 3 Markey Cancer Center, Lexington, KY, 4Department of Otolaryngology, University of Kentucky, Lexington, KY, 5University of Kentucky, Albert B. Chandler Hospital, Lexington, KY Purpose/Objective(s): Transoral robotic surgery (TORS) is increasingly utilized in the management of oropharyngeal cancers. However, patients with high risk features such as positive or close margin and/or extracapsular extension require adjuvant chemoradiation/bioradiation (CRT/ BRT) following primary resection (trimodality therapy). We hypothesize a poorer functional outcome with trimodality therapy compared to definitive CRT/BRT. Materials/Methods: An IRB approved retrospective review was performed evaluating all consecutive patients treated in our department for primary oropharyngeal cancers from January 2010 through December 2013. Patients treated by definitive CRT/BRT received IMRT to 70 Gy at 2 Gy/ fraction. CRT patients were treated with q3 weekly cisplatinum and BRT patients were treated with q weekly cetuximab. Adjuvant therapy consisted of IMRT 54-66 Gy and in high risk cases q3 weekly concurrent
Oral Scientific Sessions S123 cisplatinum at 100 mg/m2. Functional outcomes were analyzed for patients with 12 month follow-up by comparison of patients receiving TORS trimodality versus definitive CRT/BRT with Fisher’s exact test. Results: One hundred three patients were identified among whom 40 underwent primary resection (33/40 TORS). Distribution of patients is listed in Table 1. Majority of patients were stage IVA (86%). The 4 year actuarial OS for the TORS group was 79% vs 74% (NS) and 4 year actuarial local control was 94% in TORS vs 86% (NS). Fourteen patients with TORS trimodality and 52 with definitive CRT/BRT had follow-up 12 months. TORS trimodality patients had higher rates chronic aspirations (5/14 vs 6/52, p Z 0.046), velo-pharyngeal dysfunction (4/14 versus 3/52, p Z 0.032) and fistula formation (1/14 vs 0/52). PEG dependency at 12 months with TORS trimodality therapy was 5/14 versus 8/52 for definitive CRT/BRT (p Z 0.13). 11 patients were treated with both TORS and adjuvant radiation alone with 12 month follow-up. TORS and adjuvant radiation alone had low rates of chronic aspirations (1/11), velo-pharyngeal dysfunction (1/11) and fistula formation (0/11). Conclusions: Data suggests that patients requiring trimodality therapy have worse functional outcomes at 12 months versus those receiving definitive CRT/BRT. TORS is best reserved for select patients with lower stage primary and nodal volume disease to reduce risk of post-operative high risk features and thus limit toxicity from trimodality therapy. Oral Scientific Abstract 268; Table
Adjuvant XRT Adjuvant CRT Definitive CRT/BRT T1/T2 T3/T4 N0 N1/N2a N2b N2c
Patient Treatment Demographics
TORS (33)
Non-TORS Resection (7)
16 (48%) 17 (52%)
1 (14%) 6 (86%)
-
30 3 3 13 17
-
(91%) (9%) (9%) (39%) (52%)
7 (100%) 1 2 1 3
(14%) (29%) (14%) (43%)
NonSurgical (63) 63 19 44 3 4 24 32
(100%) (30%) (70%) (5%) (6%) (38%) (51%)
Total (103) 17 23 63 56 47 7 19 42 35
Author Disclosure: C.E. Wooten: None. W.A. Wilson: None. S.M. Arnold: None. T. Gal: None. R. Aouad: None. J. Valentino: None. M.R. Kudrimoti: None.
269 Salvage Spine Stereotactic Body Radiation Therapy (SBRT) for Spinal Metastases That Failed Initial SBRT: A First Report I. Thibault,1 M. Campbell,1,2 C. Tseng,1,2 A. Al-Omair,1,2 F. Lochray,1 D. Letourneau,2 E. Yu,2 Y.K. Lee,1 M.G. Fehlings,3 and A. Sahgal1,2; 1 Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, 2Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada, 3Toronto Western Hospital, University of Toronto, Toronto, ON, Canada Purpose/Objective(s): We report our preliminary experience in patients with spinal metastases initially treated with SBRT, who subsequently progressed with imaging-confirmed local tumor progression, and were treated with a 2nd salvage SBRT course to the same level. Materials/Methods: Fifty-eight metastatic spinal segments in 40 patients were identified from a prospective database of more than 900 spine SBRT cases, as having been retreated with a 2nd SBRT course (salvage) to the same level. Salvage SBRT was delivered between March 2009 and July 2013. Patients were followed with diagnostic MRI of the full spine every 2-3 months. Local failure was defined as any progression on MRI at the treated segment, and overall survival (OS) evaluated according to each patient treated. Results: Prior to the first SBRT course, 24/58 (41%) had been initially treated with conventional external beam radiation therapy and 27/58 had been previously operated upon. Specific to the first SBRT course, the median total dose/number of fractions (fx) was 24 Gy/2 fx (range, 20-35 Gy/1-5 fx). The median time from the 1st SBRT course to local tumor
International Journal of Radiation Oncology Biology Physics
DNA compared to mRNA suggests that RT induces viral activation and may explain the improved outcome seen in HPV-associated oropharyngeal cancer compared to uninfected patients. Furthermore, at the completion of RT HPV DNA and mRNA are undetectable in the saliva of most patients and 4 to 6 weeks later. Author Disclosure: T.R. Hollen: None. S.B. Zhang: None. W.M. Mendenhall: None. R.J. Amdur: None. A. Zhang: None. P. Okunieff: M. Stock; Paul Okunieff, MD, is a share stockholder in Enterade, LLC, Eva Pharmaceuticals, DiaCarta, LLC, and GainPep.
Author Disclosure: J. Vargo: None. R.L. Ferris: None. J. Ohr: None. D.A. Clump: None. K. Davis: None. J. Johnson: None. M. Gibson: None. B.F. Branstetter: None. D.E. Heron: None.
265 Re-Irradiation With Stereotactic Body Radiation Therapy Plus Cetuximab in Patients With Recurrent Previously-Irradiated Squamous Cell Carcinoma of the Head and Neck: A Prospective Phase II Trial J. Vargo,1 R.L. Ferris,2 J. Ohr,3 D.A. Clump,1 K. Davis,2 J. Johnson,2 M. Gibson,3 B.F. Branstetter,4 and D.E. Heron1; 1University of Pittsburgh Cancer Institute, Dept. Radiation Oncology, Pittsburgh, PA, 2University of Pittsburgh Cancer Institute, Dept. Otolaryngology, Head and Neck Surgery, Pittsburgh, PA, 3University of Pittsburgh Cancer Institute, Dept. Medicine, Div. Medical Oncology, Pittsburgh, PA, 4University of Pittsburgh Cancer Institute, Dept. of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA Purpose/Objective(s): Salvage options for unresectable locally-recurrent, previously-irradiated squamous cell carcinoma of the head and neck (rSCCHN) are limited. While the addition of re-irradiation may improve outcomes over chemotherapy alone, significant acute and late toxicities limits salvage re-irradiation strategies leading to suboptimal outcomes. We therefore designed a phase II protocol to evaluate the efficacy of stereotactic body radiation therapy (SBRT) plus cetuximab for rSCCHN. Materials/Methods: From July 2007 to March 2013, patients > 18 years of age with inoperable locoregionally confined rSCCHN within a previously-irradiated field receiving 60 Gy, ECOG performance status 0-1, and normal hepatic and renal function were enrolled. Patients received concurrent cetuximab (400 mg/m2 on day -7 then 250 mg/m2 on days 0 and +8) plus SBRT (8.0-8.8 Gy per fraction delivered on alternating days over 1-2 weeks for 5 fractions, total 40-44 Gy by treatment volume 25 cc). Primary endpoints were 1-year locoregional progression-free survival (PFS) and NCI CTCAE v3.0 graded toxicity. Results: Fifty patients were enrolled, 48 of which were eligible. Thirty patients (63%) were male, median age was 63, 32 (67%) had prior surgery, 31 (65%) received prior chemotherapy, 11 (23%) received a prior EGFR inhibitor at a median of 12 months prior (range: 6 - 33). Sixty-five percent (n Z 31) were prior smokers > 10 pack years; HPV status was available for 13 patients, 54% of which were HPV positive. The median re-irradiation interval was 18 months (range: 3-423). The median SBRT elapsed days was 9 (range: 8-20). The compliance rate for completion of the prescribed SBRT course was 100%, with only 4% requiring treatment interruptions. Median follow-up for surviving patients was 18 months (range: 10-70). The 1-year local PFS was 60% (95% CI Z 44-75%) and 1year locoregional PFS was 37% (95% CI Z 23-53%). The 1-year distant PFS was 71% (95% CI Z 54-85%), and the 1-year PFS was 33% (95% CI Z 20-49%). The median overall survival was 10 months (95% CI Z 716), with a 1-year overall survival of 40% (95% CI Z 26-54%). At last follow-up, 69% died of disease, 4% died with disease, 15% died without progression, 10% were alive without progression, and 2% alive with progression. Acute grade 3 toxicity was observed in 6% (2 grade 3 mucositis/ dysphagia, 1 grade 3 skin). Late grade 3 toxicity was observed in 6% (1 grade 3 dysphagia, and 2 aerodigestive fistulas). There were no grade 4+ toxicities. Conclusions: SBRT with concurrent cetuximab appears to be a safe succinct salvage treatment for rSCCHN. The 1-year PFS in this cohort appears to be similar to standard of care re-treatment regimen using IMRT with fewer treatment related toxicities. We are further extending this experience with a randomized phase II protocol combining SBRT (40-50 Gy), concurrent cetuximab and 3-month adjuvant cetuximab docetaxel.
266 Dose-Escalated Stereotactic Radiosurgery (SRS) Boost for Unfavorable Locally Advanced Oropharyngeal Cancer: Phase I/II Trial M. Ghaly,1,2 A. Halthore,1 J. Antone,1 H. Zhang,1 J. Cohen,1 H. Sachs,2 K. Beadle,2 M. Aziz,2 B. Kerry-Ann,1 D. Schwartz,1 D. Paul,1 D. Frank,2 B. Saltman,2 and S. Dubner2; 1Hofstra North Shore-LIJ School of Medicine, New Hyde Park, NY, 2Center for Head and Neck Oncology, New Hyde Park, NY Purpose/Objective(s): Management of unfavorable locally advanced oropharyngeal cancer is a common therapeutic dilemma. Large prospective trials have reported poor outcomes after RT or CT-RT, even after an intensive therapeutic approach. We report results of an IRB-approved prospective trial for dose escalation in intermediate and high-risk oropharyngeal cancer. Materials/Methods: Patients with stage III and IV HPV unassociated oropharyngeal cancer or smokers with high nodal stage (i.e., N2b to N3) and unfavorable biomarkers were enrolled in the study. RT dose to gross tumor volumes were escalated using stereotactic radiosurgery (SRS) boost 1 week after CT-RT consisting of concurrent 80 mg/m2 Cisplatin / 3 weeks and 60 Gy of IMRT at 2 Gy/fraction with a strategy of protecting swallowing organs at risk (SWOAR-IMRT). Acute radiation toxicities (n Z 90 days from start of RT) were scored using (CTCAE) Version 4.0 guidelines and late complications by RTOG/EORTC Scheme. Swallowing functional outcomes were monitored using the Performance Status Scale for H&N Cancer Patients (PSS-HN). Overall feeding tube dependence was calculated from the end of RT. Local-regional control and disease free survival was recorded. Results: Eleven patients completed (SRS) boost initial dose level 8 Gy in 1 fraction with median follow-up of 26 months (range 8-30 months). Sixteen patients received their (SRS) boost with dose escalation to 10 Gy fraction and median follow-up of 12 months (range, 6-22 months). Acute G 3 pharyngitis was observed in 53% within the last 2 weeks of CT-RT and no G 4 toxicities were reported. 45% of patients who completed treatment without a feeding tube had rapid recovery to baseline functional outcomes in PSS-HN. Patients who required a feeding tube during treatment experienced a delayed and incomplete recovery of their baseline swallowing function. The 6-month and 1-year rates of feeding tube dependence were 24% and 15%, respectively. Local-regional control and disease-free survival were 81%, 100%, and 81%, 93%, respectively, for both cohorts. Late G3 dysphagia secondary to extensive tumor necrosis was observed in 4 patients and resulted in pharyngeal hemorrhage in two. All four required surgical intervention. Conclusions: Radiation dose escalation with radiosurgery boost offers a viable treatment option for unfavorable oropharyngeal cancer patients who are deemed to be unlikely to be cured with conventional irradiation strategies. This offers patients a therapeutic option with moderate toxicities and functional preservation. Author Disclosure: M. Ghaly: None. A. Halthore: None. J. Antone: None. H. Zhang: None. J. Cohen: None. H. Sachs: None. K. Beadle: None. M. Aziz: None. B. Kerry-Ann: None. D. Schwartz: None. D. Paul: None. D. Frank: None. B. Saltman: None. S. Dubner: None.
267 Risk Factors for Locoregional Recurrence After Transoral Robotic Surgery for HPV+ Oropharyngeal Squamous Cell Carcinoma R. Funk,1 D.G. Stoddard,1 E.F. Vencio,2 J.J. Garcia,1 E.J. Moore,1 R.L. Foote,1 K.A. Price,1 and D.J. Ma1; 1Mayo Clinic, Rochester, MN, 2 Federal University Goia´s, Goia´s, Brazil Purpose/Objective(s): Traditional risk factors predicting locoregional recurrence (LRR) following surgery for head and neck squamous cell
Volume 90 Number 1S Supplement 2014 carcinomas were identified in the pre-HPV era. Patients with HPV positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) present at younger age and have an approximately 50% reduction in death when compared to their HPV- counterparts. Furthermore, transoral robotic surgery (TORS) allows for more detailed intraoperative assessment of microscopic margins. It is unknown if traditional risk factors fully apply to the HPV+ population who undergo TORS. We examined whether traditional indications for adjuvant radiation therapy (RT) (perineural invasion [PNI], angiolymphatic invasion [ALI], T3-4, or N2a-b) or adjuvant chemoradiation therapy (CRT) (extracapsular extension [ECE], or positive margins) also predict for LRR in patients with HPV+ OPSCC. Materials/Methods: After IRB approval, the medical record of 296 consecutive patients treated with TORS for OPSCC were reviewed to identify patients with HPV+ tumors who had indications for adjuvant therapy but did not receive adjuvant therapy. Results: Twenty-one patients with HPV+ base of tongue (n Z 7) or tonsil (n Z 14) OPSCC with a median age of 61 years (range, 39-81 years) who did not receive adjuvant therapy despite the presence of intermediate or high risk features were identified. All patients were p16+, 16 were HPV+ by DNA in situ hybridization. Indications for adjuvant therapy were ALI (n Z 1), PNI (n Z 3), T3 (n Z 5), T4a (n Z 1), N2a (n Z 8), N2b (n Z 5), or ECE (n Z 7). All patients had close margins due to the nature of TORS. Eight patients had multiple indications for adjuvant therapy. No positive margins were noted on final path. Median follow-up after surgery was 22.4 months (range, 7.5-58.7 months). Four of 21 (19%) patients developed LRR at 3.2, 3.4, 4.8, and 5.7 months, respectively. One of 14 (7%) patients with intermediate risk factors only had a LRR, while 43% (3/7) of patients with ECE had a LRR (p Z 0.049). LRR occurred locally (n Z 2, base of tongue), in ipsilateral regional lymph nodes (n Z 1), or in contralateral regional lymph nodes (n Z 1). These patients had 0, 5, 0 and > 10 packyears smoking history, respectively. Two patients were treated with reexcision and adjuvant RT or CRT respectively and are without evidence of disease 19 months later. The third patient received definitive CRT at an outside institution and was lost to follow-up. The final patient refused further definitive CRT after 5200 cGy of a planned 7000 cGy). Further follow-up is pending. Conclusions: In the HPV+ population, ECE remains a risk factor for LRR without adjuvant therapy. However, the role of intermediate risk factors after TORS requires further evaluation with a larger number of patients. Author Disclosure: R. Funk: None. D.G. Stoddard: None. E.F. Vencio: None. J.J. Garcia: None. E.J. Moore: None. R.L. Foote: None. K.A. Price: None. D.J. Ma: None.
268 Functional Outcomes with Surgical and Non-surgical Management of Locally Advanced Oropharyngeal Cancer C.E. Wooten,1 W.A. Wilson,2 S.M. Arnold,3 T. Gal,4 R. Aouad,4 J. Valentino,4 and M.R. Kudrimoti5; 1Albert B. Chandler Hospital, Lexington, KY, 2University of Kentucky Medical Center, Lexington, KY, 3 Markey Cancer Center, Lexington, KY, 4Department of Otolaryngology, University of Kentucky, Lexington, KY, 5University of Kentucky, Albert B. Chandler Hospital, Lexington, KY Purpose/Objective(s): Transoral robotic surgery (TORS) is increasingly utilized in the management of oropharyngeal cancers. However, patients with high risk features such as positive or close margin and/or extracapsular extension require adjuvant chemoradiation/bioradiation (CRT/ BRT) following primary resection (trimodality therapy). We hypothesize a poorer functional outcome with trimodality therapy compared to definitive CRT/BRT. Materials/Methods: An IRB approved retrospective review was performed evaluating all consecutive patients treated in our department for primary oropharyngeal cancers from January 2010 through December 2013. Patients treated by definitive CRT/BRT received IMRT to 70 Gy at 2 Gy/ fraction. CRT patients were treated with q3 weekly cisplatinum and BRT patients were treated with q weekly cetuximab. Adjuvant therapy consisted of IMRT 54-66 Gy and in high risk cases q3 weekly concurrent
Oral Scientific Sessions S123 cisplatinum at 100 mg/m2. Functional outcomes were analyzed for patients with 12 month follow-up by comparison of patients receiving TORS trimodality versus definitive CRT/BRT with Fisher’s exact test. Results: One hundred three patients were identified among whom 40 underwent primary resection (33/40 TORS). Distribution of patients is listed in Table 1. Majority of patients were stage IVA (86%). The 4 year actuarial OS for the TORS group was 79% vs 74% (NS) and 4 year actuarial local control was 94% in TORS vs 86% (NS). Fourteen patients with TORS trimodality and 52 with definitive CRT/BRT had follow-up 12 months. TORS trimodality patients had higher rates chronic aspirations (5/14 vs 6/52, p Z 0.046), velo-pharyngeal dysfunction (4/14 versus 3/52, p Z 0.032) and fistula formation (1/14 vs 0/52). PEG dependency at 12 months with TORS trimodality therapy was 5/14 versus 8/52 for definitive CRT/BRT (p Z 0.13). 11 patients were treated with both TORS and adjuvant radiation alone with 12 month follow-up. TORS and adjuvant radiation alone had low rates of chronic aspirations (1/11), velo-pharyngeal dysfunction (1/11) and fistula formation (0/11). Conclusions: Data suggests that patients requiring trimodality therapy have worse functional outcomes at 12 months versus those receiving definitive CRT/BRT. TORS is best reserved for select patients with lower stage primary and nodal volume disease to reduce risk of post-operative high risk features and thus limit toxicity from trimodality therapy. Oral Scientific Abstract 268; Table
Adjuvant XRT Adjuvant CRT Definitive CRT/BRT T1/T2 T3/T4 N0 N1/N2a N2b N2c
Patient Treatment Demographics
TORS (33)
Non-TORS Resection (7)
16 (48%) 17 (52%)
1 (14%) 6 (86%)
-
30 3 3 13 17
-
(91%) (9%) (9%) (39%) (52%)
7 (100%) 1 2 1 3
(14%) (29%) (14%) (43%)
NonSurgical (63) 63 19 44 3 4 24 32
(100%) (30%) (70%) (5%) (6%) (38%) (51%)
Total (103) 17 23 63 56 47 7 19 42 35
Author Disclosure: C.E. Wooten: None. W.A. Wilson: None. S.M. Arnold: None. T. Gal: None. R. Aouad: None. J. Valentino: None. M.R. Kudrimoti: None.
269 Salvage Spine Stereotactic Body Radiation Therapy (SBRT) for Spinal Metastases That Failed Initial SBRT: A First Report I. Thibault,1 M. Campbell,1,2 C. Tseng,1,2 A. Al-Omair,1,2 F. Lochray,1 D. Letourneau,2 E. Yu,2 Y.K. Lee,1 M.G. Fehlings,3 and A. Sahgal1,2; 1 Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, 2Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada, 3Toronto Western Hospital, University of Toronto, Toronto, ON, Canada Purpose/Objective(s): We report our preliminary experience in patients with spinal metastases initially treated with SBRT, who subsequently progressed with imaging-confirmed local tumor progression, and were treated with a 2nd salvage SBRT course to the same level. Materials/Methods: Fifty-eight metastatic spinal segments in 40 patients were identified from a prospective database of more than 900 spine SBRT cases, as having been retreated with a 2nd SBRT course (salvage) to the same level. Salvage SBRT was delivered between March 2009 and July 2013. Patients were followed with diagnostic MRI of the full spine every 2-3 months. Local failure was defined as any progression on MRI at the treated segment, and overall survival (OS) evaluated according to each patient treated. Results: Prior to the first SBRT course, 24/58 (41%) had been initially treated with conventional external beam radiation therapy and 27/58 had been previously operated upon. Specific to the first SBRT course, the median total dose/number of fractions (fx) was 24 Gy/2 fx (range, 20-35 Gy/1-5 fx). The median time from the 1st SBRT course to local tumor