Early Patient Outcomes With Adaptive Radiation Therapy in Head-and-Neck Cancers

Volume 84  Number 3S  Supplement 2012 Poster Viewing Abstract 2814; Table

Poster Viewing Abstracts S523

Clinical Outcomes According to p16 Status and Pharyngeal Subsite

Hypopharyngeal SCC n Z 27

3 yr LRC 3 yr DFS 3 yr OS

Oropharyngeal SCC n Z 127

Nasopharyngeal SCC n Z 9

p16 + (n Z 9)

p16 - (n Z 18)

p value

p16 + (n Z 84)

p16 - (n Z 43)

p value

p16 + (n Z 5)

p16 - (n Z 4)

p value

74% 43% 64%

88% 65% 65%

0.523 0.600 0.877

96% 90% 93%

72% 53% 54%

0.001 <0.001 <0.001

67% 67% 67%

80% 80% 80%

0.608 0.608 0.608

P16 was positive in 33% (9/27) of tumors in the HP, 66% (84/127) in the OP, and 56% (5/9) in the NP. After using ISH for HPV, the prevalence of HPV was found to be 5% in the HP and 33% in the NP. Thus, when used as a test for HPV, p16 had a positive predictive value of 17% in the HP and 60% in the NP. As seen in the Table, p16 status was a significant predictor of clinical outcomes for patients with OP SCC, but not for patients with HP SCC or NP SCC. Conclusions: In our cohort of patients with pharyngeal SCC, p16 expression had significant prognostic value only in patients with OP SCC. Thus, p16 testing alone may be a sufficient surrogate for HPV in the OP. However, due to the lower prevalence of HPV in the HP and NP, the positive predictive value of p16 as a test for HPV is too low to support the use of p16 alone in these subsites. Therefore, we recommend the use of p16 IHC as a screening test for HPV in NP SCC and HP SCC followed by confirmatory HPV ISH for p16 positive tumors. Author Disclosure: D. Wilson: None. E. Crandley: None. E. Stelow: None. N. Majithia: None. A.S. Rahimi: None. M. Jameson: None. P.W. Read: None.

2815 Does Response to Induction Chemotherapy (IC) Predict Outcome After Concurrent Chemoradiation therapy (CCRT) in Locally Advanced Head-and-Neck Cancer (LAHNC)? R. Cotter, V. Gupta, S. Blacksburg, T. Carpenter, K. Misiukiewicz, E. Genden, P. Som, and M. Posner; Mount Sinai School of Medicine, New York, NY Purpose/Objective(s): Recent studies have shown promising results with taxane, platinum, fluorouracil (TPF)-based IC followed by CCRT for LAHNC. Our institution utilizes this approach regularly. In this study we quantify the reduction in gross tumor volume (GTV) from IC and analyze its potential impact on outcome. Materials/Methods: We conducted a retrospective review of 38 patients with LAHNC who were treated with IC followed by definitive CCRT (70 Gy in 35 fractions via IMRT with concurrent platinum-based chemo). CT scans were obtained before and after IC (prior to starting CCRT). These scans were transferred to a treatment planning system and the pre-IC and post-IC GTV were measured. The GTV was also separated into primary GTV (pGTV) and nodal GTV (nGTV) for analysis. Changes in volumes after IC were calculated and were correlated with outcome. Results: Of the 38 patients, primary disease sites were: base of tongue (12), tonsil (11), nasopharynx (7), hypopharynx (3), larynx (3), and unknown (2). 35 patients had squamous cell carcinoma, 2 had undifferentiated carcinoma and 1 had high-grade neuroendocrine carcinoma. Initial disease stage was: III (nZ9), IVa (nZ25), IVb (nZ2), and IVc (nZ2). 21 patients had a smoking history of >10 pack-years. Of 16 tumors tested thus far, 9 were p16+. IC regimens included: taxane, platinum, and fluorouracil (TPF) (nZ28); platinum/taxane (nZ9); or platinum/etoposide (nZ1). The mean reduction in overall GTV after completing IC was 52% (range, 14-85%). The mean reduction in pGTV and nGTV after IC was 49% and 52%, respectively. At a mean follow-up of 10 months (range, 122 months), there has been 1 locoregional recurrence (LRR) and 2 distant failures (DF). The patient with LRR had a 73% reduction in overall GTV, 85% reduction in pGTV, and 53% reduction in nGTV after IC. One of the patients with DF had a high-grade neuroendocrine tumor. He had an overall GTV reduction of 75% after IC (100% pGTV reduction, 72% nGTV reduction). The other patient with DF had 58% GTV reduction after

IC (63% pGTV reduction, 47% nGTV reduction). Both patients who presented with distant metastases (IVc disease) have no evidence of disease at 20 and 22 months after therapy. There was no significant difference in GTV reduction with regards to IC regimen, smoking/drinking history or p16 status. There were no significant associations between change in GTV after IC and LRR or DF. Conclusions: There was no correlation with degree of volumetric response to IC and overall outcome after CCRT for LAHNC. IC resulted in a reduction in gross tumor volume of approximately 50%. Longer followup is needed to determine if response to IC, IC regimen, smoking history and p16 status correlate with LRR, DF, and overall survival. Author Disclosure: R. Cotter: None. V. Gupta: None. S. Blacksburg: None. T. Carpenter: None. K. Misiukiewicz: None. E. Genden: None. P. Som: None. M. Posner: None.

2816 Early Patient Outcomes With Adaptive Radiation Therapy in Headand-Neck Cancers S.R. Amarnath, J.J. Liao, G.E. Laramore, and U. Parvathaneni; University of Washington Affiliated Hospitals, Seattle, WA

Purpose/Objective(s): Adaptive radiation therapy (ART) involves replanning in response to deformations in tumor volume and has the potential to reduce morbidity. However, due diligence is necessary to avoid underestimation of tumor volume and marginal miss, since replanning images often lack clarity due to mid-treatment effects. There are sparse published data regarding the safety of ART with respect to local control and survival for patients with head and neck cancers (HNC). We retrospectively reviewed the outcomes of patients treated at our institution between 2007 and 2012. Materials/Methods: Fifteen consecutive patients with unresected HNC treated definitively with IMRT planning and requiring ART were identified in our database. All patients had AJCC stage IVA/IVB disease. Tstage distribution: 3 T2, 2 T3, and 10 T4. N-stage distribution: 3 N0, 1 N1, 4 N2b, 3 N2c, and 4 N3. 14 patients (93%) received concurrent systemic therapy. Primary tumor location included: 10 oropharynx, 1 oral cavity, 1 sinonasal, 1 hypopharynx, 1 nasopharynx, and 1 orbit. Patients underwent resimulation and replanning midway through radiation treatment if they had significant reduction in gross tumor volume on clinical evaluation (physical exam, nasoendoscopy) and it was felt that additional normal structures could be safely spared with adaptive planning. Contouring was performed manually after fusing the initial and replanning images. Results: Median time from initiation of RT to re-simulation was 23 days. Mean difference in patient weight between the two planning scans was 3.8%. Mean difference in parotid volumes was 16.8%. Mean difference in high dose PTV volumes (PTV70) was 41%. The normal structures that could be additionally spared were determined on a case-by-case basis; examples included optic nerve, parotids, lips, and superior pharyngeal constrictors. There was no unexpected additional toxicity in replanned patients. With median follow-up of 12 months (range: 1-54 months), locoregional control was 93.3% and overall survival 93.3%. Only one patient has experienced a local failure. This was a central failure within the high dose volume at 6 months post-therapy that was not affected by adaptive planning and occurred with synchronous lung metastases. One

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patient died 6 months following treatment from a non-cancer related cause. Conclusion: In our institutional experience, ART can be used safely in locally advanced HNC patients with excellent early locoregional control and survival outcomes. Individualized replanning based on tumor extent, anatomic location and treatment response may reduce doses to normal structures and limit acute and late toxicity. Longer follow up is necessary to ensure that locoregional control is maintained and to evaluate impact on quality of life outcomes. Author Disclosure: S.R. Amarnath: None. J.J. Liao: None. G.E. Laramore: None. U. Parvathaneni: None.

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2817 Brachial Plexus Dose Tolerance in Head-and-Neck Cancer Patients Treated With Sequential Intensity Modulated Radiation Therapy T.O. Thomas,1 T. Refaat,1,2 M. Choi,1 I. Bacchus,1 V. Sathiaseelan,1 and B. Mittal1; 1Northwestern University Med School Affiliated Hospitals, Chicago, IL, 2Alexandria University, Faculty of Medicine, Alexandra, Egypt Purpose/Objective(s): Radiation therapy may induce brachial plexopathy depending on dose per fraction, total dose and volume of brachial plexus (BP) exposed to radiation and concurrent chemotherapy (CT). Current RTOG guidelines suggest dose constraints ranging from 60-66Gy. Based on tumor location some patients may be treated to higher doses of radiation to the BP. We aimed to study the maximum tolerated dose and treatment related adverse events of sequential intensity modulated radiation therapy (sIMRT) with or without concurrent CT on the BP in head and neck (H&N) cancer patients. Materials/Methods: From September 2003 to December 2008 a total of 51 patients with H&N cancer were treated with sIMRT using three planning target volumes (PTV) encompassing corresponding clinical target volumes; PTV1 encompassing gross tumor volume (GTV), high and low risk areas of disease, PTV2 encompassing GTV and high risk areas of disease and PTV3 encompassing GTV. All patients had a minimum of two years follow-up with a mean of 54.3 months (range of 24 to 96.2 months). Total dose prescribed ranged from 54-75Gy in 1.5 to 2.0Gy fractions. BP was delineated on treatment planning CT scans based on the Radiation Therapy Oncology Group (RTOG)-endorsed BP contouring atlas. A reviewer to establish reproducibility verified each BP volume independently. Dose volume histograms were generated on all patients. Signs and symptoms for brachial plexopathy were reviewed in all patients. Results: Of the 51 patients 86% were male and 14% were females with 90% of patients having Stage III/IV disease treated with concomitant chemoradiation (86%). The mean age at treatment was 55.4 years old (range 35-80). Mean volumes for right, left and combined BP were 12.3cc3, 12.2 cc3 and 24.4 cc3 respectively. Mean doses delivered were 48Gy, 49.8Gy and 49.0Gy to right, left, and combined BP respectively. Maximum point dose to right BP was 79.4Gy (median 69.61 Gy) and to the left BP was 81.1Gy (median 70.9 Gy). The mean volume receiving more than 60Gy (V60) was 3.6cc3 (median 3.14 cc3) for the right BP and 3.9cc3 (median 3.4 cc3) for the left BP. The mean volume receiving more than 70Gy (V70) was 0.9cc3 (median 0.04 cc3) for the right BP and 1.7cc3 (median 0.1 cc3) for the left BP. The mean dose delivered to 10% of right BP volume (D10) was 64.1Gy (median 67.2 Gy), and to 20% (D20) was 61.2Gy (median 61.5Gy) and similarly the mean left BP D10 was 65.5Gy (median 65.4Gy) and D20 was 62.0Gy (median 61.2Gy). None of the patients had acute or late brachial plexopathy or any other significant neurological complications. Conclusions: In our study using sIMRT in H&N cancer patients treated with or without CT with a minimum two years follow up it is safe to deliver 67.2 Gy to 10% of the BP volume and up to a maximum point dose of 71 Gy however longer follow up is necessary. Author Disclosure: T.O. Thomas: None. T. Refaat: None. M. Choi: None. I. Bacchus: None. V. Sathiaseelan: None. B. Mittal: None.

Accuracy of F-18 Fluorodeoxyglucose PET/CT 3 Months After Completion of Radiation Therapy for Head-and-Neck Squamous Cancer C.M. Anderson, S. Steen, A. Hoover, L. Karnell, G. Funk, Y. Menda, M. Graham, and J. Buatti; University of Iowa, Iowa City, IA Purpose/Objective(s): The role of PET/CT in response assessment after radiation therapy (RT) remains undefined. Our previously published data on the accuracy of FDG-PET within 12 months of RT included both FDGPET and PET/CT data and was based on an SUV cut-off of 3.0. The purpose of this review is to evaluate accuracy in the PET/CT era using clinical context to determine accuracy. Materials/Methods: This is an IRB-approved retrospective review of 194 patients with head and neck squamous carcinoma treated with RT (median 70 Gy; range: 50-80 Gy) at the University of Iowa after a PET/CT was installed. Patients received treatment between July 2004 and May 2008 and all patients underwent PET/CT after completion of radiation for response assessment at a median of 14 weeks, range: 3-27 weeks. Scans were considered positive or negative in the head and neck by review of the report in the medical record. Reports in which the wording was equivocal were re-reviewed by the principal investigator, CA, and assigned positive or negative based on the ordering clinician’s response to the information. Scans were determined to be true or false based on subsequent pathology reports, imaging, and/or clinical exam findings. Results: Median follow-up for all patients was 2.65 years; median for living patients was 3.12 years. Of the 194 patients who had PET scan at 3 months, 80% were accurately interpreted, with 25 being true positives and 130 being true negatives. 49 (25%) of the 194 scans were positive in the head and neck, of which 24 were false positive (49%). 145 (76%) of the 194 scans were negative, of which 15 were false negative (10%). Additional calculations reflecting the accuracy of interpreting the 3-month PET scan results indicated that sensitivity was 63%, specificity was 84%, the positive predictive value was 51%, and the negative predictive value was 90%. Of the 145 patients with negative scans, 103 (71%) are alive at last follow-up. Of the 49 patients with positive scans, 25 (51%) are alive at last follow-up. Conclusions: Accuracy of PET/CT assessed within clinical context revealed similar specificity, positive predictive value and negative predictive value to our previously published data based on a cut-off of SUV 3.0. A negative post-RT PET/CT is an excellent predictor of outcome. False positive rates remain problematic. Author Disclosure: C.M. Anderson: None. S. Steen: None. A. Hoover: None. L. Karnell: None. G. Funk: None. Y. Menda: E. Research Grant; Seimens Medical Solutions. M. Graham: None. J. Buatti: E. Research Grant; Seimens Medical Solutions, NCI. G. Consultant; UpToDate Editorial Board.

2819 Assessing Utility of Daily Cone Beam CT in Head-and-Neck Cancers: The Effect of Disease Site S. Alcorn, R. Kumar, E. Tryggestad, T. Roland, S. Han-Oh, T. McNutt, R. Hales, and H. Quon; The Johns Hopkins Hospital, Baltimore, MD Purpose/Objective(s): In head and neck (H&N) radiation therapy, the relationship between disease site with respect to the atlanto-axial joint and utility of daily cone beam CT (CBCT) is unknown. We investigate the difference in setup measured between laser alignment (LA) and CBCT in definitive H&N radiation therapy by disease site. Materials/Methods: Using novel software developed to interface with MOSAIQ Oncology Information System, CBCT-derived couch shifts from patients treated from 4/2008 to 3/2012 were analyzed. Patients undergoing palliative treatment were excluded. Remaining patients were divided by disease sites of varying distance from the atlanto-axial joint, as follows: G1-nasal cavity and nasopharynx, G2-oral cavity and salivary glands, and G3-orophaynx, hypopharynx, and larynx. Using pre-treatment CBCTderived couch shifts as the gold standard, the difference in setup in the x