- Email: [email protected]
hypopharyngeal carcinoma
5TH ICHNO
S41 parotid (SW-MCO: 5.2 Gy 95%CI 4.9 – 5.6 Gy; TFD-MCO: 4.8 Gy 95%CI 4.5 – 5.1 Gy), ipsilateral parotid (SW-MCO: 6.5 Gy 95%CI 6.2 – 6.7 Gy; TFD-MCO: 7.4 Gy 95%CI 7.2 – 7.7 Gy) and the oral cavity (SW-MCO: 2.2 Gy 95%CI 1.8 – 2.5 Gy; TFDMCO: 2.0 Gy 95%CI 1.6 – 2.4 Gy). The SW-MCO plans showed no differences in NTCP estimates for dysphagia and slightly higher NTCP estimates for tube feeding dependence (0.7% 95%CI 0.6% – 0.8%). The TFD-MCO plans resulted in slightly lower NTCP estimates for dysphagia (1.3% 95%CI 1.2% – 1.3%). In 3% of patients the TFD estimates reduced with >5%. Results per patient are shown in figure 1. Comparisons for the OARs are listed in table 1.
Conclusions: Automated treatment planning using NTCPbased MCO significantly reduced the dose to several OARs by more optimally distributing dose among multiple OARs. However, pushing dose in one region consequently led to increased dose in other regions. To further improve HNC radiotherapy, techniques such as adaptive radiotherapy and proton therapy are required. PO-091 TPExtreme randomized trial: Docetaxel-Platinum(P)Cetuximab(C) versus 5FU-P-C in recurrent/metastatic HNSCC J. Guigay1, U. Keilholz2, R. Mesia3, N. Vintonenko4, J. Bourhis5, A. Auperin6 1 Centre Antoine Lacassagne - Head&Neck Unicancer Group, Cancer Research Center - Medical Oncology, Nice, France 2 Charite Comprehensive Cancer Center - AIO Group, Medical Oncology, Berlin, Germany 3 Institut Català d'Oncologica - TTCC Group, L'Hospitalet Llobregat - Medical Oncology, Barcelona, Spain 4 GORTEC CORAD, Clinical Research, Tours, France 5 GORTEC, Radio-Oncology, Lausanne, Switzerland 6 Gustave Roussy, Biostatistics and Epidemiology, Villejuif, France Purpose/Objective: The EXTREME regimen (6 cycles of 5FU– cisplatin-cetuximab followed by cetuximab maintenance) is currently the standard of care in first line recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The GORTEC phase II trial evaluating the TPEx regimen (4 cycles of docetaxel–cisplatin-cetuximab followed by cetuximab maintenance) demonstrated good results (median overall survival (OS) 14 months, overall response rate 54%) with acceptable safety profile, excellent dose intensity, high rate of patients who started maintenance and easy implementation. The aim of the current trial is to compare TPEx and EXTREME regimens. Materials and Methods: International, randomized, openlabel trial. Main inclusion criteria are: histologically confirmed HNSCC with metastasis or recurrence not suitable
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5th ICHNO for locoregional treatment, age 18-70 years, PS 60 ml/min, prior total dose of cisplatin < 300 mg/m². The control arm EXTREME consists of 6 cycles, every 21 days, of cisplatin 100 mg/m² day1, 5FU 4000 mg/m² continuous infusion day1-4, and weekly cetuximab 250 mg/m² (after a loading dose of 400 mg/m²) followed by weekly cetuximab 250 mg/m² maintenance. The experimental arm TPEx consists of 4 cycles, every 21 days, of docetaxel 75 mg/m² day1, cisplatin 75 mg/m² day1, and weekly cetuximab 250 mg/m² (after a loading dose of 400 mg/m²), followed by maintenance cetuximab 500 mg/m² every 2 weeks. If cisplatin is not tolerated or when the total cumulative dose reaches 600 mg/m², it must be replaced by carboplatin AUC5. Prophylactic administration of G-CSF must be done systematically after each chemotherapy cycle in the TPEx arm. Cetuximab maintenance is given only in patients with at least disease stabilization and is continued until PD or unacceptable toxicity. The primary endpoint is OS. Assuming a 2-sided type I error of 0.05, observing 295 deaths will provide a 80% power to detect a hazard ratio of 0.72. 295 deaths are expected out of a total of 416 patients. Secondary endpoints are objective response rate, best response rate, PFS, time-to-progression, toxicity and quality of life. Tumor response assessments are planned every 6 weeks until week18, then every 8 weeks until progression and will be reviewed by a blinded central image review committee. HPV central analysis and cost-effectiveness study are ancillary studies. 75 sites in France (GORTEC), Germany (AIO-Studien-gGmbH) and Spain (TTCC) will participate in the trial. Patients are randomized between the 2 arms (1:1) by minimization on PS, type of evolution, previous cetuximab treatment and country.
Results: The first patient has been enrolled in October 2014. Results are expected by the end of 2017. Conclusions: This randomized trial will establish if TPEx regimen is a relevant substitute for EXTREME as 1st line treatment in fit patients with R/M HNSCC. Under the aegis of HN Intergroup GORTEC-GETTEC-GERCOR and in collaboration with H&N UNICANCER group. Grant from Merck Serono. PO-092 Phase II study of TPF and cetuximab+RT in locally advanced laryngeal/hypopharyngeal carcinoma F. Arias1, I. Hernández1, G. Asín1, J. Contreras2, E. Villar2, A.M. Pérez3, V. Casado3, T. Bonfill4, R. Vera1 1 Complejo Hospitalario de Navarra, Oncología, Pamplona, Spain 2 Hospital Regional Universitario Carlos Haya, Oncología, Málaga, Spain 3 Hospital Universitario Fundación Jiménez Díaz, Oncología, Madrid, Spain 4 Hospital Universitario Parc Taulí, Oncología, Barcelona, Spain
5TH ICHNO
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5th ICHNO Purpose/Objective: Neoadjuvantdocetaxel, cisplatin, and 5fluorouracil (TPF) may improve survival in same locally advanced head and neck cancer (LAHNC). Cetuximab improves the tumor response and survival in LAHNC and this effect seems to improve when boost concomitant scheme is used. In 2008 we begun a Phase II Trial with TPF followed by RT (boost concomitant) plus cetuximab in LA laryngeal/hypopharyngeal carcinoma. The primary endpoint was 2-year progression free survival (PFS) for those patients with complete response (CR) or partial response (PR) after receiving TPF. Secondary endpoints included: overall survival (OS), specific total laryngectomy-free survival, and quality of life (QoL). Adverse events were assessed for safety. Materials and Methods: Phase II, open, multicenter study in patients with locally advanced laryngeal/hypopharyngeal carcinoma. All patients received 3 cycles of induction chemotherapy with TPF, followed by cetuximab + radiation therapy (RT) or surgery. Radiotherapy consisted of 72 Gy/6 weeks in boost concomitant regimen. IMRT was not allowed in this study. Survival data was analysed using Kaplan-Meier. Patients that discontinued the study for any reason were censored. Results: The study was prematurely closed because of low recruitment. A total of 25 patients started the treatment: 21 of them (78%) had CR/PR after TPF. Two-years PFS 47.9% (95% CI: 15.7, 74.6). For patients with CR/PR after TPF, median survival time was 21.1 months. For all patients, twoyear PFS was 37.8% (95% CI: 12.4, 63.6), and median survival time was 21.1 months. Secondary end points were: overall survival, 42.1% (95% CI: 13.4, 68.8); specific survival free of laryngectomy, 54.2 (95% CI: 16.7, 81.1); the evaluation of quality of life increased with time. There were seven deaths during the study: three were related to disease progression, one sudden death, one due to hepatic insufficiency, one pancreatic adenocarcinoma, and one fulminant acute hepatitis. The most frequent serious adverse events (SAEs) were febrile neutropenia (20%, n=5) and mucositis (16%, n=4). Other SAEs observed were: headache, epithelitis, hepatic insufficiency, febrile neutropenia, pancytopenia with septic shock, ORL bleeding and tracheotomy. Conclusions: This study was prematurely terminated because of the difficulties in the recruitment of patients. Descriptive results are presented about efficacy and safety of the treatment with TPF and cetuximab+RT 'boost concomitant' in locally advanced laryngeal/hypopharyngeal carcinoma. Our preliminary data, do not support this approach due to higher toxicity and similar results than other standard treatments. PO-093 Influence on toxicity mucositis depending on contouring the oral cavity: our experience J. Marin1, M.A. Garcia1, I. Prieto1, A.M. Perez1 1 Fundación Jimenez Diaz, Radiation Oncology Department, Madrid, Spain Purpose/Objective: Acute mucositis in the oral cavity (OC) is an important adverse reaction in the locally advanced head and neck cancer patients treated with radiotherapy. The impact of the treatment in the quality of life in these patients can be negative, reducing the adherence and efficacy of the therapy. Minor risk of severe mucositis can be achieved by lowering the D mean and D max constrains to the OC as an organ at risk (OAR) without compromise the prescribed dose to the PTV. There is no consensus of which is the best way of contouring the OC as OAR. The aim of this study is to assess whether that the way we contour the OC reduces the mucositis without compromising the treatment plan.
S42 Materials and Methods:
Nineteen patients with locally advance head and neck cancer treated with radical IMRT were analysed for this study. Treatment was calculated according to international recommendations utilising Intensity Modulated Radiotherapy (IMRT) technique with 7 fields and dynamic multileaf collimator, delivering dose between 66 and 70 Gy to the PTV. The Monaco treatment planning system with Monte Carlo algorithm was used. The same physician made the contouring of the PTV volume and the OC. The oral cavity included: hard palate mucosa, floor of the mouth, orbicular muscle and lips, upper and lower teeth and gingiva, oral vestibule and the ventral 2/3 portion of the tongue. Patients were followed weekly by the physician recording and classifying the grade of mucositis in two groups (Group A: asymptomatic or mild ulcers and Group B: severe ulcers or mayor bleeding pseudo membrane). Oral cavity D mean, D max, V50Gy, V45Gy, V40Gy, V35Gy, V30Gy, V25Gy and V20Gy were recorded and compared. We used a standard statistical analysis to describe the D mean, D max and volumes with the grade of mucositis appearance. We have compared our results with similar published series. Results:
The median age of this group was 57 y (range: 45-84y), 12 patients were female and 7 were male with an optimal performance status (Karnofsky Index 90% mean). In the group A, 15 patients (78.9%) were assessed with mucositis toxicity grade ≤2 and in-group B, only 4 patients (21%) reached a mucositis toxicity grade ≥3 with no severe complications. In the 19 cases the OC volumes mean was 96.4cc accomplishing lower doses in the oral cavity has an organ at risk. We also evaluated the V20, V25, V30, V45 and V50 of the OC. PTV dose compliance was not compromised with the tighter values of D mean 18.8Gy and D max 38.3Gy. Conclusions: This descriptive study reveals that this oral cavity contouring shows lower D mean and D max in the OC as OAR comparing with the literature available, making possible to achieve tighter constraints dose and decreasing the oral toxicity. Further research comparing different ways of contour the OC is needed to obtain consensus and a lower mucositis profile.
S41 parotid (SW-MCO: 5.2 Gy 95%CI 4.9 – 5.6 Gy; TFD-MCO: 4.8 Gy 95%CI 4.5 – 5.1 Gy), ipsilateral parotid (SW-MCO: 6.5 Gy 95%CI 6.2 – 6.7 Gy; TFD-MCO: 7.4 Gy 95%CI 7.2 – 7.7 Gy) and the oral cavity (SW-MCO: 2.2 Gy 95%CI 1.8 – 2.5 Gy; TFDMCO: 2.0 Gy 95%CI 1.6 – 2.4 Gy). The SW-MCO plans showed no differences in NTCP estimates for dysphagia and slightly higher NTCP estimates for tube feeding dependence (0.7% 95%CI 0.6% – 0.8%). The TFD-MCO plans resulted in slightly lower NTCP estimates for dysphagia (1.3% 95%CI 1.2% – 1.3%). In 3% of patients the TFD estimates reduced with >5%. Results per patient are shown in figure 1. Comparisons for the OARs are listed in table 1.
Conclusions: Automated treatment planning using NTCPbased MCO significantly reduced the dose to several OARs by more optimally distributing dose among multiple OARs. However, pushing dose in one region consequently led to increased dose in other regions. To further improve HNC radiotherapy, techniques such as adaptive radiotherapy and proton therapy are required. PO-091 TPExtreme randomized trial: Docetaxel-Platinum(P)Cetuximab(C) versus 5FU-P-C in recurrent/metastatic HNSCC J. Guigay1, U. Keilholz2, R. Mesia3, N. Vintonenko4, J. Bourhis5, A. Auperin6 1 Centre Antoine Lacassagne - Head&Neck Unicancer Group, Cancer Research Center - Medical Oncology, Nice, France 2 Charite Comprehensive Cancer Center - AIO Group, Medical Oncology, Berlin, Germany 3 Institut Català d'Oncologica - TTCC Group, L'Hospitalet Llobregat - Medical Oncology, Barcelona, Spain 4 GORTEC CORAD, Clinical Research, Tours, France 5 GORTEC, Radio-Oncology, Lausanne, Switzerland 6 Gustave Roussy, Biostatistics and Epidemiology, Villejuif, France Purpose/Objective: The EXTREME regimen (6 cycles of 5FU– cisplatin-cetuximab followed by cetuximab maintenance) is currently the standard of care in first line recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The GORTEC phase II trial evaluating the TPEx regimen (4 cycles of docetaxel–cisplatin-cetuximab followed by cetuximab maintenance) demonstrated good results (median overall survival (OS) 14 months, overall response rate 54%) with acceptable safety profile, excellent dose intensity, high rate of patients who started maintenance and easy implementation. The aim of the current trial is to compare TPEx and EXTREME regimens. Materials and Methods: International, randomized, openlabel trial. Main inclusion criteria are: histologically confirmed HNSCC with metastasis or recurrence not suitable
page 46
5th ICHNO for locoregional treatment, age 18-70 years, PS 60 ml/min, prior total dose of cisplatin < 300 mg/m². The control arm EXTREME consists of 6 cycles, every 21 days, of cisplatin 100 mg/m² day1, 5FU 4000 mg/m² continuous infusion day1-4, and weekly cetuximab 250 mg/m² (after a loading dose of 400 mg/m²) followed by weekly cetuximab 250 mg/m² maintenance. The experimental arm TPEx consists of 4 cycles, every 21 days, of docetaxel 75 mg/m² day1, cisplatin 75 mg/m² day1, and weekly cetuximab 250 mg/m² (after a loading dose of 400 mg/m²), followed by maintenance cetuximab 500 mg/m² every 2 weeks. If cisplatin is not tolerated or when the total cumulative dose reaches 600 mg/m², it must be replaced by carboplatin AUC5. Prophylactic administration of G-CSF must be done systematically after each chemotherapy cycle in the TPEx arm. Cetuximab maintenance is given only in patients with at least disease stabilization and is continued until PD or unacceptable toxicity. The primary endpoint is OS. Assuming a 2-sided type I error of 0.05, observing 295 deaths will provide a 80% power to detect a hazard ratio of 0.72. 295 deaths are expected out of a total of 416 patients. Secondary endpoints are objective response rate, best response rate, PFS, time-to-progression, toxicity and quality of life. Tumor response assessments are planned every 6 weeks until week18, then every 8 weeks until progression and will be reviewed by a blinded central image review committee. HPV central analysis and cost-effectiveness study are ancillary studies. 75 sites in France (GORTEC), Germany (AIO-Studien-gGmbH) and Spain (TTCC) will participate in the trial. Patients are randomized between the 2 arms (1:1) by minimization on PS, type of evolution, previous cetuximab treatment and country.
Results: The first patient has been enrolled in October 2014. Results are expected by the end of 2017. Conclusions: This randomized trial will establish if TPEx regimen is a relevant substitute for EXTREME as 1st line treatment in fit patients with R/M HNSCC. Under the aegis of HN Intergroup GORTEC-GETTEC-GERCOR and in collaboration with H&N UNICANCER group. Grant from Merck Serono. PO-092 Phase II study of TPF and cetuximab+RT in locally advanced laryngeal/hypopharyngeal carcinoma F. Arias1, I. Hernández1, G. Asín1, J. Contreras2, E. Villar2, A.M. Pérez3, V. Casado3, T. Bonfill4, R. Vera1 1 Complejo Hospitalario de Navarra, Oncología, Pamplona, Spain 2 Hospital Regional Universitario Carlos Haya, Oncología, Málaga, Spain 3 Hospital Universitario Fundación Jiménez Díaz, Oncología, Madrid, Spain 4 Hospital Universitario Parc Taulí, Oncología, Barcelona, Spain
5TH ICHNO
page 47
5th ICHNO Purpose/Objective: Neoadjuvantdocetaxel, cisplatin, and 5fluorouracil (TPF) may improve survival in same locally advanced head and neck cancer (LAHNC). Cetuximab improves the tumor response and survival in LAHNC and this effect seems to improve when boost concomitant scheme is used. In 2008 we begun a Phase II Trial with TPF followed by RT (boost concomitant) plus cetuximab in LA laryngeal/hypopharyngeal carcinoma. The primary endpoint was 2-year progression free survival (PFS) for those patients with complete response (CR) or partial response (PR) after receiving TPF. Secondary endpoints included: overall survival (OS), specific total laryngectomy-free survival, and quality of life (QoL). Adverse events were assessed for safety. Materials and Methods: Phase II, open, multicenter study in patients with locally advanced laryngeal/hypopharyngeal carcinoma. All patients received 3 cycles of induction chemotherapy with TPF, followed by cetuximab + radiation therapy (RT) or surgery. Radiotherapy consisted of 72 Gy/6 weeks in boost concomitant regimen. IMRT was not allowed in this study. Survival data was analysed using Kaplan-Meier. Patients that discontinued the study for any reason were censored. Results: The study was prematurely closed because of low recruitment. A total of 25 patients started the treatment: 21 of them (78%) had CR/PR after TPF. Two-years PFS 47.9% (95% CI: 15.7, 74.6). For patients with CR/PR after TPF, median survival time was 21.1 months. For all patients, twoyear PFS was 37.8% (95% CI: 12.4, 63.6), and median survival time was 21.1 months. Secondary end points were: overall survival, 42.1% (95% CI: 13.4, 68.8); specific survival free of laryngectomy, 54.2 (95% CI: 16.7, 81.1); the evaluation of quality of life increased with time. There were seven deaths during the study: three were related to disease progression, one sudden death, one due to hepatic insufficiency, one pancreatic adenocarcinoma, and one fulminant acute hepatitis. The most frequent serious adverse events (SAEs) were febrile neutropenia (20%, n=5) and mucositis (16%, n=4). Other SAEs observed were: headache, epithelitis, hepatic insufficiency, febrile neutropenia, pancytopenia with septic shock, ORL bleeding and tracheotomy. Conclusions: This study was prematurely terminated because of the difficulties in the recruitment of patients. Descriptive results are presented about efficacy and safety of the treatment with TPF and cetuximab+RT 'boost concomitant' in locally advanced laryngeal/hypopharyngeal carcinoma. Our preliminary data, do not support this approach due to higher toxicity and similar results than other standard treatments. PO-093 Influence on toxicity mucositis depending on contouring the oral cavity: our experience J. Marin1, M.A. Garcia1, I. Prieto1, A.M. Perez1 1 Fundación Jimenez Diaz, Radiation Oncology Department, Madrid, Spain Purpose/Objective: Acute mucositis in the oral cavity (OC) is an important adverse reaction in the locally advanced head and neck cancer patients treated with radiotherapy. The impact of the treatment in the quality of life in these patients can be negative, reducing the adherence and efficacy of the therapy. Minor risk of severe mucositis can be achieved by lowering the D mean and D max constrains to the OC as an organ at risk (OAR) without compromise the prescribed dose to the PTV. There is no consensus of which is the best way of contouring the OC as OAR. The aim of this study is to assess whether that the way we contour the OC reduces the mucositis without compromising the treatment plan.
S42 Materials and Methods:
Nineteen patients with locally advance head and neck cancer treated with radical IMRT were analysed for this study. Treatment was calculated according to international recommendations utilising Intensity Modulated Radiotherapy (IMRT) technique with 7 fields and dynamic multileaf collimator, delivering dose between 66 and 70 Gy to the PTV. The Monaco treatment planning system with Monte Carlo algorithm was used. The same physician made the contouring of the PTV volume and the OC. The oral cavity included: hard palate mucosa, floor of the mouth, orbicular muscle and lips, upper and lower teeth and gingiva, oral vestibule and the ventral 2/3 portion of the tongue. Patients were followed weekly by the physician recording and classifying the grade of mucositis in two groups (Group A: asymptomatic or mild ulcers and Group B: severe ulcers or mayor bleeding pseudo membrane). Oral cavity D mean, D max, V50Gy, V45Gy, V40Gy, V35Gy, V30Gy, V25Gy and V20Gy were recorded and compared. We used a standard statistical analysis to describe the D mean, D max and volumes with the grade of mucositis appearance. We have compared our results with similar published series. Results:
The median age of this group was 57 y (range: 45-84y), 12 patients were female and 7 were male with an optimal performance status (Karnofsky Index 90% mean). In the group A, 15 patients (78.9%) were assessed with mucositis toxicity grade ≤2 and in-group B, only 4 patients (21%) reached a mucositis toxicity grade ≥3 with no severe complications. In the 19 cases the OC volumes mean was 96.4cc accomplishing lower doses in the oral cavity has an organ at risk. We also evaluated the V20, V25, V30, V45 and V50 of the OC. PTV dose compliance was not compromised with the tighter values of D mean 18.8Gy and D max 38.3Gy. Conclusions: This descriptive study reveals that this oral cavity contouring shows lower D mean and D max in the OC as OAR comparing with the literature available, making possible to achieve tighter constraints dose and decreasing the oral toxicity. Further research comparing different ways of contour the OC is needed to obtain consensus and a lower mucositis profile.