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PO-0674: Current smoking is the only significant predictor of locoregional control in HPV-positive oropharyngeal cancer
S10 genotyping (MPG). Results were correlated with clinical outcome. Statistical analyzes were performed using SPSS.
ESTRO 33, 2014 individual treatment adjustment and follow the behaviour of the CTV during radiotherapy.
Results: In 78 (66 %) of 118 pts HPV serum antibodies could be detected. 61 % pts showed serum antibodies against E2, 20% against E6, 26 % against E7, only 4 % against E1. 19 pts (16 %) showed two or more types of HPV serum antibodies. Statistical analyses were performed for 98 pts (40 laryngeal carcinomas, 14 hypopharynx carcinomas and 44 oropharynx carcinomas). 20 pts were lost of follow up. The presents of HPV Serum antibodies (AB) alone did not correlate with clinical outcome, but pts with a combination of AB-E6 and one more type of AB showed a better 3 ys overall survival (OS) of 82 % vs 69 % , p = 0.1 log rank) E2 or E6 and one more AB predicted better local progression free survival (LPFS, 100 % vs 78 % p= 0.088, log rank.) There was also a trend for better OS (77 % vs 61 %, ns) if HPV serum antibodies were detected one year or later in patient’s blood. Conclusions: HPV serum antibodies have the potential to function as biomarker for HPV-positive HNSCC. But only a combination of more than one antibody seems to predict clinical outcome. Also type of antibody and the length of time of expression might be of importance. PO-0673 Safety of ART with margin reduction evaluated with fiducial markers in head and neck cancer O. Hamming-Vrieze1, S.R. Van Kranen1, S. Van Beek1, W.D. Heemsbergen1, M.W.M. Van den Brekel2, C.R.N. Rasch3, J.J. Sonke1 1 The Netherlands Cancer Institute, Radiation Oncology, Amsterdam, The Netherlands 2 The Netherlands Cancer Institute, Head and Neck Surgery, Amsterdam, The Netherlands 3 Academic Medical Centre, Radiation Oncology, Amsterdam, The Netherlands Purpose/Objective: Adaptive radiotherapy (ART) following tumor regression in head and neck cancer patients raises the question if margins can be reduced to improve sparing of organs at risk. Radiological examinations cannot solve this problem because of their inability to display microscopic disease. In this study, implanted gold markers were used to visualize and quantify the behavior of the CTV. The purpose was to estimate the frequency of CTV increase during the second part of radiation treatment simulating ART after 3 weeks. Materials and Methods: Thirty-four patients with oropharyngeal tumors (17 tonsillar (TON), 7 posterior pharyngeal wall (PPW), 10 base of tongue (BOT)), with a stage III/IV who were treated with curative (chemo)radiotherapy up to 70 Gy in 35 fractions, were included. Helical gold markers (Visicoil, 0.35x2 mm, 3-10/patient, average 6) were implanted at investigation under anesthesia in the CTV near the edge of the GTV. Markers were semi-automatically identified on planning CT (pCT) and daily CBCTs. Local bony anatomy registration was performed to minimize setup errors. Daily marker displacements perpendicular to the GTV surface in week 4 to 7 were analyzed in reference to the average position in week 3 (the anatomy for a mid-treatment adaptive re-planning). Outward displacement was evaluated for each marker and per patient. Subgroup analysis with a Chi-square test was done based on the location of the tumor, the tumor volume (>/< 30 cc) and marker displacement in the first part of treatment (displacement < -0.2 \ > 0.2 cm at week 3). Results: Marker implantation was feasible without complications. Implanted markers were located on pCT (n=34) and daily CBCTs (n=1139), resulting in 6108 daily marker displacements. The average displacement in week 3 was -0.1 cm (0.2 cm SD; range -0.85-0.44 cm). From week 4 onwards, the average displacement relative to week 3 exceeded 0.2 cm for at least 1 week in 17 markers (9% of markers). This occurred in 11 patients (32%). However, the maximum values and SD relative to week 3 were lower than those relative to the pCT suggesting a benefit for ART (table 1). Subgroup analyses showed an increased risk of outward displacement in BOT tumors (45%) and PPW tumors (36%) compared to TON tumors (11%, p<0.03). Outward displacement was not correlated to tumor volume or marker displacement in the first part of treatment, only 4/17 markers had a displacement of more than 0.2 cm in the first part of treatment. Conclusions: Over 90% of fiducial markers followed on CBCT as a surrogate for CTV motion, remained stable from week 4 onwards. However, in reference to week 3, there is a risk of local underdosage in 32% of patients. Especially in patients with base of tongue and posterior pharyngeal wall tumors, overall margin reduction should take these deformations into account. Moreover, without ART the risk of underdosage increases. Implanted markers can be helpful to guide
PO-0674 Current smoking is the only significant predictor of locoregional control in HPV-positive oropharyngeal cancer C. Liskamp1, G.O.R.J. Janssens1, W.J.G. Melchers2, J.H.A.M. Kaanders1, C.G. Verhoef1 1 Radboud University Nijmegen Medical Center, Academic Department of Radiation Oncology, Nijmegen, The Netherlands 2 Radboud University Nijmegen Medical Center, Academic Department of Medical Microbiology, Nijmegen, The Netherlands Purpose/Objective: HPV-positive (HPV+) oropharyngeal carcinoma represents a tumor category with a relatively good prognosis and a distinct tumor biology as compared to HPV-negative (HPV-) oropharyngeal carcinomas. Our purpose was to identify prognostic predictors in HPV-positive patients. Materials and Methods: Medical records of 162 patients treated between 09-2005 and 09-2011 with IMRT for oropharyngeal cancer were reviewed. HPV status was determined using PCR analysis in 142 patients. Potential prognostic factors for 3-year locoregional control (LRC) and overall survival (OS) were evaluated in 82 HPV-positive patients and in 60 HPVnegative patients. These factors included age, gender, ECOG performance score, Age Adjusted Charlson Comorbidity index, current smoking, packyears of smoking, alcohol abuse, pretreatment hemoglobin level, UICC tumor stage, tumor volume and chemotherapy. Univariate analysis was performed followed by a Cox Regression analysis. Results: For the whole group the 3 year LRC and OS were both 70% (HPV+ vs. HPV-: LRC 79% vs 62% (p= 0.03) and OS 78% vs. 62% (p= 0.04)). In HPV+ tumors ECOG performance status (p= 0.02) and smoking (p= 0.02) were significant prognostic factors for locoregional control (LRC), smoking remained significant (p= 0.03) and ECOG showed a trend on multivariate analysis. For overall survival (OS), Age-Adjusted Charlson Comorbidity Index (p=0.04) and smoking (p =0.05) were significant, both remained significant on multivariate analysis (p= 0.03 and p= 0.03, respectively). In HPV- tumors, age (p <0.01), ECOG performance score (p=0.02), and tumor volume (p=0.02) were significant prognostic factors for LRC. Only age remained significant in multivariate analysis(p=0.02), while tumor volume showed a trend (p=0.054). Tumor volume (p =0.04) and age (p <0.01) were significant predictors for OS on univariate analysis. In multivariate analysis age (p <0.01) remained significant and tumor volume (p=0.08) showed a trend. Conclusions: Our findings confirm the high radiosensitivity of HPVpositive tumors, and a very strong influence of actual smoking behaviour on outcome. Smoking is the only prognostic factor for LRC on multivariate analysis; for OS it remained significant together with comorbidity. We found an absolute benefit in LRC of 18% and in OS of 19 % for patients who did not smoke during treatment. Smoking cessation strategies are of utmost importance to achieve optimal treatment outcomes in these patients. PO-0675 The toxicity of induction chemotherapy on salivary gland function prior to curative IMRT for head and neck cancer T. Richards1, G.H. Carpenter2, K.J. Harrington1, G.B. Proctor2, C.M. Nutting1 1 The Royal Marsden Hospital NHS Foundation Trust & Institute of Cancer Research, Head & Neck Unit, London, United Kingdom 2 King's College London, Salivary Research Unit, London, United Kingdom Purpose/Objective: Concomitant chemoradiotherapy (ChRT) for head and neck cancer (HNC) improves overall survival (OS) vs. RT alone. The
ESTRO 33, 2014 individual treatment adjustment and follow the behaviour of the CTV during radiotherapy.
Results: In 78 (66 %) of 118 pts HPV serum antibodies could be detected. 61 % pts showed serum antibodies against E2, 20% against E6, 26 % against E7, only 4 % against E1. 19 pts (16 %) showed two or more types of HPV serum antibodies. Statistical analyses were performed for 98 pts (40 laryngeal carcinomas, 14 hypopharynx carcinomas and 44 oropharynx carcinomas). 20 pts were lost of follow up. The presents of HPV Serum antibodies (AB) alone did not correlate with clinical outcome, but pts with a combination of AB-E6 and one more type of AB showed a better 3 ys overall survival (OS) of 82 % vs 69 % , p = 0.1 log rank) E2 or E6 and one more AB predicted better local progression free survival (LPFS, 100 % vs 78 % p= 0.088, log rank.) There was also a trend for better OS (77 % vs 61 %, ns) if HPV serum antibodies were detected one year or later in patient’s blood. Conclusions: HPV serum antibodies have the potential to function as biomarker for HPV-positive HNSCC. But only a combination of more than one antibody seems to predict clinical outcome. Also type of antibody and the length of time of expression might be of importance. PO-0673 Safety of ART with margin reduction evaluated with fiducial markers in head and neck cancer O. Hamming-Vrieze1, S.R. Van Kranen1, S. Van Beek1, W.D. Heemsbergen1, M.W.M. Van den Brekel2, C.R.N. Rasch3, J.J. Sonke1 1 The Netherlands Cancer Institute, Radiation Oncology, Amsterdam, The Netherlands 2 The Netherlands Cancer Institute, Head and Neck Surgery, Amsterdam, The Netherlands 3 Academic Medical Centre, Radiation Oncology, Amsterdam, The Netherlands Purpose/Objective: Adaptive radiotherapy (ART) following tumor regression in head and neck cancer patients raises the question if margins can be reduced to improve sparing of organs at risk. Radiological examinations cannot solve this problem because of their inability to display microscopic disease. In this study, implanted gold markers were used to visualize and quantify the behavior of the CTV. The purpose was to estimate the frequency of CTV increase during the second part of radiation treatment simulating ART after 3 weeks. Materials and Methods: Thirty-four patients with oropharyngeal tumors (17 tonsillar (TON), 7 posterior pharyngeal wall (PPW), 10 base of tongue (BOT)), with a stage III/IV who were treated with curative (chemo)radiotherapy up to 70 Gy in 35 fractions, were included. Helical gold markers (Visicoil, 0.35x2 mm, 3-10/patient, average 6) were implanted at investigation under anesthesia in the CTV near the edge of the GTV. Markers were semi-automatically identified on planning CT (pCT) and daily CBCTs. Local bony anatomy registration was performed to minimize setup errors. Daily marker displacements perpendicular to the GTV surface in week 4 to 7 were analyzed in reference to the average position in week 3 (the anatomy for a mid-treatment adaptive re-planning). Outward displacement was evaluated for each marker and per patient. Subgroup analysis with a Chi-square test was done based on the location of the tumor, the tumor volume (>/< 30 cc) and marker displacement in the first part of treatment (displacement < -0.2 \ > 0.2 cm at week 3). Results: Marker implantation was feasible without complications. Implanted markers were located on pCT (n=34) and daily CBCTs (n=1139), resulting in 6108 daily marker displacements. The average displacement in week 3 was -0.1 cm (0.2 cm SD; range -0.85-0.44 cm). From week 4 onwards, the average displacement relative to week 3 exceeded 0.2 cm for at least 1 week in 17 markers (9% of markers). This occurred in 11 patients (32%). However, the maximum values and SD relative to week 3 were lower than those relative to the pCT suggesting a benefit for ART (table 1). Subgroup analyses showed an increased risk of outward displacement in BOT tumors (45%) and PPW tumors (36%) compared to TON tumors (11%, p<0.03). Outward displacement was not correlated to tumor volume or marker displacement in the first part of treatment, only 4/17 markers had a displacement of more than 0.2 cm in the first part of treatment. Conclusions: Over 90% of fiducial markers followed on CBCT as a surrogate for CTV motion, remained stable from week 4 onwards. However, in reference to week 3, there is a risk of local underdosage in 32% of patients. Especially in patients with base of tongue and posterior pharyngeal wall tumors, overall margin reduction should take these deformations into account. Moreover, without ART the risk of underdosage increases. Implanted markers can be helpful to guide
PO-0674 Current smoking is the only significant predictor of locoregional control in HPV-positive oropharyngeal cancer C. Liskamp1, G.O.R.J. Janssens1, W.J.G. Melchers2, J.H.A.M. Kaanders1, C.G. Verhoef1 1 Radboud University Nijmegen Medical Center, Academic Department of Radiation Oncology, Nijmegen, The Netherlands 2 Radboud University Nijmegen Medical Center, Academic Department of Medical Microbiology, Nijmegen, The Netherlands Purpose/Objective: HPV-positive (HPV+) oropharyngeal carcinoma represents a tumor category with a relatively good prognosis and a distinct tumor biology as compared to HPV-negative (HPV-) oropharyngeal carcinomas. Our purpose was to identify prognostic predictors in HPV-positive patients. Materials and Methods: Medical records of 162 patients treated between 09-2005 and 09-2011 with IMRT for oropharyngeal cancer were reviewed. HPV status was determined using PCR analysis in 142 patients. Potential prognostic factors for 3-year locoregional control (LRC) and overall survival (OS) were evaluated in 82 HPV-positive patients and in 60 HPVnegative patients. These factors included age, gender, ECOG performance score, Age Adjusted Charlson Comorbidity index, current smoking, packyears of smoking, alcohol abuse, pretreatment hemoglobin level, UICC tumor stage, tumor volume and chemotherapy. Univariate analysis was performed followed by a Cox Regression analysis. Results: For the whole group the 3 year LRC and OS were both 70% (HPV+ vs. HPV-: LRC 79% vs 62% (p= 0.03) and OS 78% vs. 62% (p= 0.04)). In HPV+ tumors ECOG performance status (p= 0.02) and smoking (p= 0.02) were significant prognostic factors for locoregional control (LRC), smoking remained significant (p= 0.03) and ECOG showed a trend on multivariate analysis. For overall survival (OS), Age-Adjusted Charlson Comorbidity Index (p=0.04) and smoking (p =0.05) were significant, both remained significant on multivariate analysis (p= 0.03 and p= 0.03, respectively). In HPV- tumors, age (p <0.01), ECOG performance score (p=0.02), and tumor volume (p=0.02) were significant prognostic factors for LRC. Only age remained significant in multivariate analysis(p=0.02), while tumor volume showed a trend (p=0.054). Tumor volume (p =0.04) and age (p <0.01) were significant predictors for OS on univariate analysis. In multivariate analysis age (p <0.01) remained significant and tumor volume (p=0.08) showed a trend. Conclusions: Our findings confirm the high radiosensitivity of HPVpositive tumors, and a very strong influence of actual smoking behaviour on outcome. Smoking is the only prognostic factor for LRC on multivariate analysis; for OS it remained significant together with comorbidity. We found an absolute benefit in LRC of 18% and in OS of 19 % for patients who did not smoke during treatment. Smoking cessation strategies are of utmost importance to achieve optimal treatment outcomes in these patients. PO-0675 The toxicity of induction chemotherapy on salivary gland function prior to curative IMRT for head and neck cancer T. Richards1, G.H. Carpenter2, K.J. Harrington1, G.B. Proctor2, C.M. Nutting1 1 The Royal Marsden Hospital NHS Foundation Trust & Institute of Cancer Research, Head & Neck Unit, London, United Kingdom 2 King's College London, Salivary Research Unit, London, United Kingdom Purpose/Objective: Concomitant chemoradiotherapy (ChRT) for head and neck cancer (HNC) improves overall survival (OS) vs. RT alone. The