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OC-017: Refining UICC TNM stage and prognostic groups for non-metastatic HPV-related oropharyngeal carcinomas
5TH ICHNO
5th ICHNO Purpose/Objective: The final report of RTOG 9003 showed no difference in any grade > 3, 4, or 5 toxicities, feeding tube use after 180 days and at 1 year when comparing any experimental altered fractionatoin arm to the standard fractionation (SFX) arm. The purpose of this study is to report the Patient Reported Outcomes (PRO) of patients treated on RTOG 9003. Materials and Methods: RTOG 9003, a phase III trial, compared altered fractionation (hyperfractionation {HFX}, accelerated fractionation continuous {AFX-C}, or accelerated fractionation split {AFX-S}) to SFX. Quality of life (QOL) was added 6 months after trial activation. FACT questionnaires were completed at baseline (pre-treatment), at 3, 6, 9, and 12 months from start of treatment, and then every 6 months through year 5. At follow-up only patients with baseline FACT and applicable follow-up FACT were included in the analysis. Scores for each follow-up time point (raw values and change from baseline) were compared between each experimental arm and the SFX arm using t-test. Longitudinal trends were evaluated using the general linear model. An unplanned analysis comparing FACT by p16-status (limited to patients with oropharynx cancer) was performed. Results: RTOG 9003 opened to patient accrual on September 30, 1991 and closed on August 1, 1997 after enrolling 1113 patients. Thirty-seven patients did not meet inclusion/exclusion criteria or withdrew consent, 80 were enrolled prior to FACT being added to the study, and 286 did not complete baseline FACT, yielding 710 analyzable patients. Demographic differences were seen between those patients with and without baseline FACT scores (age, race, KPS, p16 status. N and AJCC stage) but both groups had similar local-regional failure and overall survival. No significant difference in FACT scores were seen between treatment groups at baseline but HFX and AFX-C had significantly lower FACT scores compared to SFX (means 97.5 vs. 104, p=0.01, and 96.7 vs. 104, p=0.006, respectively) at 3 months while only AFX-C change from baseline was significantly lower than SFX (means -10.4 vs. -5.4, p=0.05). A difference in FACT scores was noted at 48 months for all experimental arms compared to the SFX arm but changes from baseline were not significantly different. When compared by P16 status, FACT scores change from baseline were significantly lower for p16 positive patients compared with p16 negative patients, (mean-6.8, p=0.04), at 3 months with no difference noted in later measurement points. Conclusions: PRO are becoming an important endpoint in clinical trials. This is the first report of PRO in patients treated on RTOG 9003 showing a similarity to the toxicity results reported earlier. The unplanned analysis comparing p16 positive and negative status of patients with oropharyngeal cancer is interesting and hypothesis generating; however, it needs to be confirmed.
Proffered papers: Session 1: OC-017 Refining UICC TNM stage and prognostic groups for nonmetastatic HPV-related oropharyngeal carcinomas B. O'Sullivan1, S. Huang1, J. Waldron1, A. Bayley1, J. Kim1, A. Hope1, J. Ringash1, J. Cho1, M. Giuliani1, W. Xu2 1 Princess Margaret Cancer Centre / University of Toronto, Radiation Oncology, Toronto, Canada 2 Princess Margaret Cancer Centre / University of Toronto, Biostatistics, Toronto, Canada Purpose/Objective: The current TNM staging for oropharyngeal cancer (OPC) was designed for HPV-unrelated [HPV(-)] disease. Emerging evidence suggests it is unsuited for HPV-related [HPV(+)] OPC. This study is intended to
page 13
S8 refine stage grouping for non-metastatic HPV(+) OPC patient and to develop prognostic risk groups as ordained by the UICC. This would permit non-anatomic factors reflecting the biology of the tumour, or characteristics of the host/patient, to be incorporated into the prognostic risk groups while also maintaining relevant anatomically derived stage groups within the existing UICC TNM framework. Materials and Methods: All non-metastatic p16-confirmed OPC treated with radiotherapy +/- chemo from 2000-2010 were included. Overall survival (OS) was compared among TNM stages for HPV(+) and HPV(-) cases separately. Two different modeling methods were explored to derive a better stage schema for HPV(+): recursive partitioning analysis (RPA) derived new RPA-stages objectively; Cox regression was used to calculate adjusted hazard ratio (AHR) to derive AHRstages. The performance of the survival prediction of both the RPA-stage and AHR-stage were assessed separately and ranked against the current UICC 7th edition TNM stages. Prognostic groups were derived by a further RPA, combining RPA-stage and other prognostic factors identified by multivariate analysis. Results: The cohort comprised 573 HPV(+) and 237 HPV(-) with median follow-up 5.1 years. Lower 5-year OS with higher UICC TNM stage (I / II / III / IV) was evident for HPV (70% / 58% / 49% / 29%, p=0.003) but not for HPV(+) cases (88% / 77% / 71% / 74%, p=0.712). RPA divided HPV(+) into RPA-I (T1-3N0-N2b), RPA-II (T1-3N2c), and RPA-III (T4 or N3) (5-year OS: 81%, 76%, and 54%, p<0.001). AHR also yielded a valid AHR-stage classification. RPA-stage demonstrated the best survival prediction against AHR-stage and UICC-stage. A further RPA that included RPA-stage, age, and smoking packyears (PY) derived four valid prognostic groups for survival: group-I (T1-3N0-N2c _<=20 PY), group-IIA (T1-3N0-N2c_>20 PY), group-IIB (T4 or N3_age <=70), and group-III (T4 or N3_age >70) (5-year OS: 89%, 64%, 57%, and 40%, p<0.001). Conclusions: This large cohort study confirms that the current UICC/AJCC TNM stage is unsuited for HPV(+) OPC although acceptable for HPV(-) patients. A refined RPA-based TNM stage grouping significantly improves survival prediction compared to the UICC 7th edition TNM, and prognostication is further improved by an RPA-based prognostic grouping within the UICC TNM framework for non-metastatic HPV(+) OPC. The results of current study should be validated in an independent dataset comprised full spectrum of disease stage. They also demonstrate that the UICC template can be used to incorporate non-anatomic factors into the classification while also permitting anatomic factors to be refined. This is relevant for all cancers within the TNM classification. OC-018 GORTEC randomized trial evaluating OTD70DERM on dermatitis in head and neck cancer undergoing RT cetuximab Y. Tao1, A. Auperin2, C. Sire3, M. Martin4, M.G. Saliou5, E. Bardet6, X. Sun7, C. Morand8, I. D'Onofrio9, J. Bourhis10 1 Institut Gustave Roussy, Radiation Oncology, Villejuif, France 2 Institut Gustave Roussy, Biostatistics, Villejuif, France 3 Centre Hospitalier de Bretagne Sud, Radiation Oncology, Lorient, France 4 Centre Hospitalier Intercommunal de Créteil, Radiation Oncology, Creteil, France 5 Centre Etienne Dolet, Radiation Oncology, Saint Nazaire, France 6 Centre René Gauducheau, Radiation Oncology, SaintHerblain, France 7 Centre Hospitalier Montbéliard, Radiation Oncology, Montbéliard, France 8 Centre Hospitalier Départemental Les Oudairies, Radiation Oncology, La Roche-sur-Yon, France 9 Centre Médical de Forcilles, Radiation Oncology, Ferolles-
5th ICHNO Purpose/Objective: The final report of RTOG 9003 showed no difference in any grade > 3, 4, or 5 toxicities, feeding tube use after 180 days and at 1 year when comparing any experimental altered fractionatoin arm to the standard fractionation (SFX) arm. The purpose of this study is to report the Patient Reported Outcomes (PRO) of patients treated on RTOG 9003. Materials and Methods: RTOG 9003, a phase III trial, compared altered fractionation (hyperfractionation {HFX}, accelerated fractionation continuous {AFX-C}, or accelerated fractionation split {AFX-S}) to SFX. Quality of life (QOL) was added 6 months after trial activation. FACT questionnaires were completed at baseline (pre-treatment), at 3, 6, 9, and 12 months from start of treatment, and then every 6 months through year 5. At follow-up only patients with baseline FACT and applicable follow-up FACT were included in the analysis. Scores for each follow-up time point (raw values and change from baseline) were compared between each experimental arm and the SFX arm using t-test. Longitudinal trends were evaluated using the general linear model. An unplanned analysis comparing FACT by p16-status (limited to patients with oropharynx cancer) was performed. Results: RTOG 9003 opened to patient accrual on September 30, 1991 and closed on August 1, 1997 after enrolling 1113 patients. Thirty-seven patients did not meet inclusion/exclusion criteria or withdrew consent, 80 were enrolled prior to FACT being added to the study, and 286 did not complete baseline FACT, yielding 710 analyzable patients. Demographic differences were seen between those patients with and without baseline FACT scores (age, race, KPS, p16 status. N and AJCC stage) but both groups had similar local-regional failure and overall survival. No significant difference in FACT scores were seen between treatment groups at baseline but HFX and AFX-C had significantly lower FACT scores compared to SFX (means 97.5 vs. 104, p=0.01, and 96.7 vs. 104, p=0.006, respectively) at 3 months while only AFX-C change from baseline was significantly lower than SFX (means -10.4 vs. -5.4, p=0.05). A difference in FACT scores was noted at 48 months for all experimental arms compared to the SFX arm but changes from baseline were not significantly different. When compared by P16 status, FACT scores change from baseline were significantly lower for p16 positive patients compared with p16 negative patients, (mean-6.8, p=0.04), at 3 months with no difference noted in later measurement points. Conclusions: PRO are becoming an important endpoint in clinical trials. This is the first report of PRO in patients treated on RTOG 9003 showing a similarity to the toxicity results reported earlier. The unplanned analysis comparing p16 positive and negative status of patients with oropharyngeal cancer is interesting and hypothesis generating; however, it needs to be confirmed.
Proffered papers: Session 1: OC-017 Refining UICC TNM stage and prognostic groups for nonmetastatic HPV-related oropharyngeal carcinomas B. O'Sullivan1, S. Huang1, J. Waldron1, A. Bayley1, J. Kim1, A. Hope1, J. Ringash1, J. Cho1, M. Giuliani1, W. Xu2 1 Princess Margaret Cancer Centre / University of Toronto, Radiation Oncology, Toronto, Canada 2 Princess Margaret Cancer Centre / University of Toronto, Biostatistics, Toronto, Canada Purpose/Objective: The current TNM staging for oropharyngeal cancer (OPC) was designed for HPV-unrelated [HPV(-)] disease. Emerging evidence suggests it is unsuited for HPV-related [HPV(+)] OPC. This study is intended to
page 13
S8 refine stage grouping for non-metastatic HPV(+) OPC patient and to develop prognostic risk groups as ordained by the UICC. This would permit non-anatomic factors reflecting the biology of the tumour, or characteristics of the host/patient, to be incorporated into the prognostic risk groups while also maintaining relevant anatomically derived stage groups within the existing UICC TNM framework. Materials and Methods: All non-metastatic p16-confirmed OPC treated with radiotherapy +/- chemo from 2000-2010 were included. Overall survival (OS) was compared among TNM stages for HPV(+) and HPV(-) cases separately. Two different modeling methods were explored to derive a better stage schema for HPV(+): recursive partitioning analysis (RPA) derived new RPA-stages objectively; Cox regression was used to calculate adjusted hazard ratio (AHR) to derive AHRstages. The performance of the survival prediction of both the RPA-stage and AHR-stage were assessed separately and ranked against the current UICC 7th edition TNM stages. Prognostic groups were derived by a further RPA, combining RPA-stage and other prognostic factors identified by multivariate analysis. Results: The cohort comprised 573 HPV(+) and 237 HPV(-) with median follow-up 5.1 years. Lower 5-year OS with higher UICC TNM stage (I / II / III / IV) was evident for HPV (70% / 58% / 49% / 29%, p=0.003) but not for HPV(+) cases (88% / 77% / 71% / 74%, p=0.712). RPA divided HPV(+) into RPA-I (T1-3N0-N2b), RPA-II (T1-3N2c), and RPA-III (T4 or N3) (5-year OS: 81%, 76%, and 54%, p<0.001). AHR also yielded a valid AHR-stage classification. RPA-stage demonstrated the best survival prediction against AHR-stage and UICC-stage. A further RPA that included RPA-stage, age, and smoking packyears (PY) derived four valid prognostic groups for survival: group-I (T1-3N0-N2c _<=20 PY), group-IIA (T1-3N0-N2c_>20 PY), group-IIB (T4 or N3_age <=70), and group-III (T4 or N3_age >70) (5-year OS: 89%, 64%, 57%, and 40%, p<0.001). Conclusions: This large cohort study confirms that the current UICC/AJCC TNM stage is unsuited for HPV(+) OPC although acceptable for HPV(-) patients. A refined RPA-based TNM stage grouping significantly improves survival prediction compared to the UICC 7th edition TNM, and prognostication is further improved by an RPA-based prognostic grouping within the UICC TNM framework for non-metastatic HPV(+) OPC. The results of current study should be validated in an independent dataset comprised full spectrum of disease stage. They also demonstrate that the UICC template can be used to incorporate non-anatomic factors into the classification while also permitting anatomic factors to be refined. This is relevant for all cancers within the TNM classification. OC-018 GORTEC randomized trial evaluating OTD70DERM on dermatitis in head and neck cancer undergoing RT cetuximab Y. Tao1, A. Auperin2, C. Sire3, M. Martin4, M.G. Saliou5, E. Bardet6, X. Sun7, C. Morand8, I. D'Onofrio9, J. Bourhis10 1 Institut Gustave Roussy, Radiation Oncology, Villejuif, France 2 Institut Gustave Roussy, Biostatistics, Villejuif, France 3 Centre Hospitalier de Bretagne Sud, Radiation Oncology, Lorient, France 4 Centre Hospitalier Intercommunal de Créteil, Radiation Oncology, Creteil, France 5 Centre Etienne Dolet, Radiation Oncology, Saint Nazaire, France 6 Centre René Gauducheau, Radiation Oncology, SaintHerblain, France 7 Centre Hospitalier Montbéliard, Radiation Oncology, Montbéliard, France 8 Centre Hospitalier Départemental Les Oudairies, Radiation Oncology, La Roche-sur-Yon, France 9 Centre Médical de Forcilles, Radiation Oncology, Ferolles-