- Email: [email protected]
RT) with or without induction TPF in Locally Advanced head and neck
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Charité Comprehensive Cancer Center, Berlin, Germany Hopsital Universitario Vall d'Hebron, Medical Oncology, Barcelona, Spain 19 Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, USA 20 Boehringer Ingelheim Danmark A/S, Denmark 21 University of California San Diego Moores Cancer Center, La Jolla, USA 18
Purpose/Objective: Patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progress after first-line platinum-based therapy have a dismal prognosis and limited efficacious treatment options. Afatinib, an irreversible ErbB family blocker, showed anti-tumour activity in a phase II trial in this setting (Seiwert et al. Ann Oncol 2014). LUX-Head & Neck 1, a global, openlabel, randomised phase III trial, evaluated second-line afatinib vs methotrexate (MTX) in patients with R/M HNSCC who progressed on/after platinum-based therapy (NCT01345682). Materials and Methods: Patients were randomised 2:1 to 40 mg/day oral afatinib (n=322) or 40 mg/m2/week intravenous MTX (n=161), stratified by Eastern Cooperative Oncology Group performance status (0/1) and prior use of anti-EGFR antibody therapy (Yes/No) in the R/M setting. The primary endpoint was progression-free survival (PFS) by independent central review; overall survival (OS) was the key secondary endpoint. Other endpoints included objective response rate (ORR), patient-reported outcomes (PROs), tumour shrinkage, and adverse events (AEs). Disease control rate (DCR) was also assessed. Results: Patient baseline characteristics were well balanced between treatment groups (Table). Afatinib significantly improved the primary endpoint of PFS vs MTX by independent central review (median 2.6 vs 1.7 months; HR=0.80 [95% CI 0.65–0.98; p=0.03]; Figure); similar results were observed by investigator assessment. A trend towards improved PFS with afatinib was observed in a subgroup of patients aged ≥65 years (HR=0.68 [95% CI 0.45–1.03]). OS was not significantly improved with afatinib vs MTX (median 6.8 vs 6.0 months; HR=0.96 [0.77–1.19]). DCR was higher with afatinib vs MTX (49.1% vs 38.5%; p=0.04); ORR was 10.2% vs 5.6%, respectively (p=0.10). Tumour shrinkage was observed in 34.8% of afatinib-treated patients vs 22.4% of MTX-treated patients. Afatinib significantly delayed deterioration of global health status, pain and swallowing (all p≤0.03); significantly less pain over time was observed in afatinib-treated patients (p=0.03). Median duration of treatment was 83 days (range, 2–546) with afatinib and 43 days (range, 1–442) with MTX. The most frequent grade 3/4 treatment-related AEs were rash/acne (9.7%) and diarrhoea (9.4%) with afatinib, and stomatitis (8.1%) and neutropenia (6.9%) with MTX. Fewer treatment-related AEs led to dose reductions (32.2% vs 41.9%), drug discontinuations (7.2% vs 16.3%) or fatal outcome (2 [0.6%] vs 5 [3.1%]) in afatinib-treated patients. Conclusions: In this phase III trial in patients with R/M HNSCC after failure of platinum-based therapy, second-line afatinib significantly improved the primary endpoint of PFS vs MTX, with a manageable safety profile. A significant delay in deterioration of PROs and less pain over time was also observed with afatinib compared to MTX.
OC-006 Concomitant treatment (CRT or cetuximab/RT) with or without induction TPF in Locally Advanced head and neck Cancer M.G. Ghi1, A. Paccagnella1, D. Ferrari2, P. Foa2, M. Cossu Rocca3, E. Verri3, F. Morelli4, G. Azzarello5, C. D'Ambrosio6, C. Casanova7, M. Guaraldi8, E. Massa9, C. Rossetto10, A. Bonetti11, S. Siena12, A. Frattegiani13, H. Koussis14, G. Pieri15, A. Gava16, I. Floriani17, For the GSTTC Italian Study Group 1Ospedale SS Giovanni e Paolo, Medical Oncology, Venezia, Italy 2
San Paolo Hospital, Medical Oncology Unit, Milano, Italy Medical Oncology Unit of Urogenital and Head and Neck Tumors, European Institute of Oncology, Milano, Italy 3
4 IRCCS Casa Sollievo della Sofferenza, Medical Oncology, San Giovanni Rotondo, Italy 5
Azienda ULSS 13, Internal Medical Sciences, Mirano, Italy University Hospital, Oncology, Modena, Italy 7 Azienda USL, Medical Oncology, Ravenna, Italy 8 Policlinico Sant'Orsola-Malpighi, Medical Oncology, Bologna, Italy 6
9 Azienda Ospedaliero Universitaria, Internal Medical Science, Cagliari, Italy 10
University Hospital, Oncology, Udine, Italy 11 Mater Salutis Hospital-AULSS 21 della Regione Veneto, Legnago, Italy 12
Niguarda Ca' Granda Hospital, Milano, Italy Azienda Ospedaliera, Raditation Therapy, Perugia, Italy Istituto Oncologico Veneto - IRCCS, Padova, Italy 15 Ospedali Riuniti di Trieste, Oncology, Trieste, Italy 16 Ospedale Cà Foncello, Radiation Therapy Department, Treviso, Italy 13 14
17 Laboratorio Trials Clinici, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy
Background: Platinum-based CRT is the standard treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma (LASCCHN). Cetuximab/RT (CET/RT) is superior to RT alone
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5th ICHNO and it is an alternative treatment to CRT as no phase III studies comparing these 2 strategies are available so far. Induction TPF resulted to be superior to cisplatin/5fluorouracil but its efficacy when added to concomitant treatment is to be demonstrated. This openlabel multicenter 2x2 factorial study (NCT01086826) was designed to assess two primary endpoints: the overall survival (OS) of induction vs. no induction and the Grade 3-4 in-field mucosal toxicity of CRT vs. CET/RT. Methods: 421 patients with LASCCHN of the oral cavity, oropharynx, hypopharynx, stage III-IV, ECOG PS 0-1 were randomized to one of four treatment options: Arm A1: CRT (2 cycles of cisplatin/5fluorouracil concomitant to standard RT fractionation); Arm A2: CET/RT; Arm B1: 3 cycles of TPF followed by the same CRT; Arm B2: 3 cycles of TPF followed by CET/RT. The superiority hypothesis of OS comparison of TPF induction vs. no induction (Arms B1+B2 vs. A1+A2), requires 204 deaths to detect a relative reduction of 33% with 2-sided 5% significance level for the log-rank test and a power of 80%. Results: 414 out of 421 patients were finally analyzed: 206 in induction and 208 in concomitant arm. At a median followup of 45 months 240 events for PFS and 204 deaths were observed. Median PFS was 30.5 mos in induction vs 19 mos in concomitant arm with a 3-year PFS of 47.2% vs 38.8% (HR: 0.74; 95%CI 0.58-0.96; p=0.024), respectively. Median OS was 54.7 mos in induction vs 31.7 mos in concomitant arm with a 3-year OS of 57.5% vs 46.4% (HR: 0.74; 95%CI 0.56-0.97; p=0.031) respectively. Compliance to concomitant treatments was not affected by induction TPF. Conclusions: Induction TPF followed by CRT or CET/RT significantly improved PFS and OS (independently from the type of concomitant strategy) in LASCCHN patients without compromising compliance to the concomitant treatments. OC-007 Is accelerated radiotherapy alone equivalent to chemoradiation in patients with moderate advanced HNSCC? K. Skladowski1, A. Wygoda1, M. Snetura2, T. Rutkowski1, L. Michalecki1, A. Heyda1, A. Hajduk1, M. Kentnowski1, B. Lukaszczyk-Widel1, B. Maciejewski3 1 Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology I Dept, Radiation Oncology and Chemotherapy, Gliwice, Poland 2 Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology I Dept, Cancer Pathology, Gliwice, Poland 3 Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology I Dept, Radiation Oncology, Gliwice, Poland Purpose/Objective: The current indication for radiation therapy alone with altered fractionation regimens in patients with head and neck squamous cell cancer is not known. On the one hand - an indirect comparison with concurrent chemo-radiation (CCR), based on existed meta-analyses, suggests that CCR has yielded a larger survival benefit than that achieved with AF, on the other - this benefit is seen predominantly in locally more advanced HNSCC (T3-4, N2-3), thus AF is believed as a reasonable treatment for patients with less advanced disease, or patients who are not suitable for chemotherapy. To study that problem we have conducted the randomized trial directly comparing CCR with accelerated radiotherapy alone (ARA). Materials and Methods: Over 5 years (2008-13) consecutive 101 pts with oropharynx (46), hypopharynx (19) and larynx (36) cancer in moderate clinical stage, i.e. T2N1-2 (29), T3N0-2 (56) and T4AN0-2 (16), with N+ limited to less or equal 3 cm in diameter, have been randomizing and treating by ARA (53) or CCR (48). ARA was delivered by 7 fractions of 1.8 Gy per week to 72 Gy in 40 fractions over 40 days; in CCR 70 Gy in 35
S4 fractions over 49 days was combined with 3 courses of cisplatin (100 mg/m2/d on day 1, 22 and 43). All OPC pts had examined HPV status. Radiation was delivered to all pts as an IMRT/IGRT. Results: Median follow-up is 40 months. In CCR the number of administered cisplatin courses was as follows: 1 in 5 pts. (10%), 2 in 30 pts. (62%) and 3 in 13 pts. (28%). HPV status was evaluated as positive (+ve) in 11 (29%) and negative (-ve) in 35 (71%) OPC pts. The actuarial rates of 3-year OS and DFS are respectively, 58% and 56% for ARA compare to 79% and 73% for CCR (p=0.02 and p=0.05, respectively). Both OS and DFS were worse in ARA arm as a consequence of higher rates in: primary and neck failures, distant metastases and comorbidity deaths (25%, 9%, 9% and 9%, respectively), compare to CCR arm (14%, 6%, 4% and 4%, respectively). In CCR arm DFS rate was 77% for pts who received 2 or 3 courses of cisplatin and 50% for those who received 1 course only. Sub-site analysis revealed that benefit of CCR was disappeared only in pts with T2 and HPV+ve tumors - all HPV+ve OPC pts remain alive with no cancer failure, whereas OS for HPV-ve pts was 55% in ARA and 78% in CCR. There are no significant differences between the trial arms in acute and late toxicity, as well as, in quality of live, except of better social functioning in CCR pts. Conclusions: 3-year results of the trial have proven that CCR takes an advantage over ARA in pts with MAHNSCC - CCR with conventional 7 weeks fractionation and, at least, 2 courses of cisplatin is more effective than ARA with 6 weeks. The only treatment target for ARA could be now the population of HNSCC pts with: stage T2, moderate stage HPV+ve OPC and contraindication to cisplatin. OC-008 POPART vs CPORT in squamous cell head and neck cancer: Results of a multicenter randomised study of the Dutch head and neck Study Group H. Langendijk1, J.H. Kaanders2, P. Doornaert3, F.R. Burlage1, P.L.A. Van den Ende4, S.B. Oei5, R.B. Keus6, S. Nuyts7, C.R. Leemans8, H. Van Tinteren9, C.H. Terhaard10 1 University Medical Center Groningen University of Groningen, Radiation Oncology, Groningen, The Netherlands 2 Radboud University Nijmegen Medical Centre, Radiation Oncology, Nijmegen, The Netherlands 3 VU University Medical Center, Radiation Oncology, Amsterdam, The Netherlands 4 (MAASTRO) GROW University Hospital, Radiation Oncology, Maastricht, The Netherlands 5 Dr. Bernard Verbeeten Instituut, Radiation Oncology, Tilburg, The Netherlands 6 Arnhem Radiotherapeutic Institute, Radiation Oncology, Arnhem, The Netherlands 7 University Hospitals Leuven, Radiation Oncology, Leuven, Belgium 8 VU University Medical Center, Department of Otolaryngology/Head and Neck Surgery, Amsterdam, The Netherlands 9 The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Medical Statistics, Amsterdam, The Netherlands 10 University Medical Center Utrecht, Radiotherapy, Utrecht, The Netherlands
Background: In head and neck squamous cell carcinoma (HNSCC), the overall treatment time of radiation (OTT) is significantly associated with locoregional control (LRC), which is consistent with rapid repopulation of cancer clonogens during radiotherapy. However, the importance of the OTT in the postoperative setting is less clear. Therefore, the main objective of this phase III study was to determine the value of reduction of the OTT of postoperative radiotherapy in high risk patients primarily treated with surgery.
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Charité Comprehensive Cancer Center, Berlin, Germany Hopsital Universitario Vall d'Hebron, Medical Oncology, Barcelona, Spain 19 Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, USA 20 Boehringer Ingelheim Danmark A/S, Denmark 21 University of California San Diego Moores Cancer Center, La Jolla, USA 18
Purpose/Objective: Patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progress after first-line platinum-based therapy have a dismal prognosis and limited efficacious treatment options. Afatinib, an irreversible ErbB family blocker, showed anti-tumour activity in a phase II trial in this setting (Seiwert et al. Ann Oncol 2014). LUX-Head & Neck 1, a global, openlabel, randomised phase III trial, evaluated second-line afatinib vs methotrexate (MTX) in patients with R/M HNSCC who progressed on/after platinum-based therapy (NCT01345682). Materials and Methods: Patients were randomised 2:1 to 40 mg/day oral afatinib (n=322) or 40 mg/m2/week intravenous MTX (n=161), stratified by Eastern Cooperative Oncology Group performance status (0/1) and prior use of anti-EGFR antibody therapy (Yes/No) in the R/M setting. The primary endpoint was progression-free survival (PFS) by independent central review; overall survival (OS) was the key secondary endpoint. Other endpoints included objective response rate (ORR), patient-reported outcomes (PROs), tumour shrinkage, and adverse events (AEs). Disease control rate (DCR) was also assessed. Results: Patient baseline characteristics were well balanced between treatment groups (Table). Afatinib significantly improved the primary endpoint of PFS vs MTX by independent central review (median 2.6 vs 1.7 months; HR=0.80 [95% CI 0.65–0.98; p=0.03]; Figure); similar results were observed by investigator assessment. A trend towards improved PFS with afatinib was observed in a subgroup of patients aged ≥65 years (HR=0.68 [95% CI 0.45–1.03]). OS was not significantly improved with afatinib vs MTX (median 6.8 vs 6.0 months; HR=0.96 [0.77–1.19]). DCR was higher with afatinib vs MTX (49.1% vs 38.5%; p=0.04); ORR was 10.2% vs 5.6%, respectively (p=0.10). Tumour shrinkage was observed in 34.8% of afatinib-treated patients vs 22.4% of MTX-treated patients. Afatinib significantly delayed deterioration of global health status, pain and swallowing (all p≤0.03); significantly less pain over time was observed in afatinib-treated patients (p=0.03). Median duration of treatment was 83 days (range, 2–546) with afatinib and 43 days (range, 1–442) with MTX. The most frequent grade 3/4 treatment-related AEs were rash/acne (9.7%) and diarrhoea (9.4%) with afatinib, and stomatitis (8.1%) and neutropenia (6.9%) with MTX. Fewer treatment-related AEs led to dose reductions (32.2% vs 41.9%), drug discontinuations (7.2% vs 16.3%) or fatal outcome (2 [0.6%] vs 5 [3.1%]) in afatinib-treated patients. Conclusions: In this phase III trial in patients with R/M HNSCC after failure of platinum-based therapy, second-line afatinib significantly improved the primary endpoint of PFS vs MTX, with a manageable safety profile. A significant delay in deterioration of PROs and less pain over time was also observed with afatinib compared to MTX.
OC-006 Concomitant treatment (CRT or cetuximab/RT) with or without induction TPF in Locally Advanced head and neck Cancer M.G. Ghi1, A. Paccagnella1, D. Ferrari2, P. Foa2, M. Cossu Rocca3, E. Verri3, F. Morelli4, G. Azzarello5, C. D'Ambrosio6, C. Casanova7, M. Guaraldi8, E. Massa9, C. Rossetto10, A. Bonetti11, S. Siena12, A. Frattegiani13, H. Koussis14, G. Pieri15, A. Gava16, I. Floriani17, For the GSTTC Italian Study Group 1Ospedale SS Giovanni e Paolo, Medical Oncology, Venezia, Italy 2
San Paolo Hospital, Medical Oncology Unit, Milano, Italy Medical Oncology Unit of Urogenital and Head and Neck Tumors, European Institute of Oncology, Milano, Italy 3
4 IRCCS Casa Sollievo della Sofferenza, Medical Oncology, San Giovanni Rotondo, Italy 5
Azienda ULSS 13, Internal Medical Sciences, Mirano, Italy University Hospital, Oncology, Modena, Italy 7 Azienda USL, Medical Oncology, Ravenna, Italy 8 Policlinico Sant'Orsola-Malpighi, Medical Oncology, Bologna, Italy 6
9 Azienda Ospedaliero Universitaria, Internal Medical Science, Cagliari, Italy 10
University Hospital, Oncology, Udine, Italy 11 Mater Salutis Hospital-AULSS 21 della Regione Veneto, Legnago, Italy 12
Niguarda Ca' Granda Hospital, Milano, Italy Azienda Ospedaliera, Raditation Therapy, Perugia, Italy Istituto Oncologico Veneto - IRCCS, Padova, Italy 15 Ospedali Riuniti di Trieste, Oncology, Trieste, Italy 16 Ospedale Cà Foncello, Radiation Therapy Department, Treviso, Italy 13 14
17 Laboratorio Trials Clinici, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy
Background: Platinum-based CRT is the standard treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma (LASCCHN). Cetuximab/RT (CET/RT) is superior to RT alone
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5th ICHNO and it is an alternative treatment to CRT as no phase III studies comparing these 2 strategies are available so far. Induction TPF resulted to be superior to cisplatin/5fluorouracil but its efficacy when added to concomitant treatment is to be demonstrated. This openlabel multicenter 2x2 factorial study (NCT01086826) was designed to assess two primary endpoints: the overall survival (OS) of induction vs. no induction and the Grade 3-4 in-field mucosal toxicity of CRT vs. CET/RT. Methods: 421 patients with LASCCHN of the oral cavity, oropharynx, hypopharynx, stage III-IV, ECOG PS 0-1 were randomized to one of four treatment options: Arm A1: CRT (2 cycles of cisplatin/5fluorouracil concomitant to standard RT fractionation); Arm A2: CET/RT; Arm B1: 3 cycles of TPF followed by the same CRT; Arm B2: 3 cycles of TPF followed by CET/RT. The superiority hypothesis of OS comparison of TPF induction vs. no induction (Arms B1+B2 vs. A1+A2), requires 204 deaths to detect a relative reduction of 33% with 2-sided 5% significance level for the log-rank test and a power of 80%. Results: 414 out of 421 patients were finally analyzed: 206 in induction and 208 in concomitant arm. At a median followup of 45 months 240 events for PFS and 204 deaths were observed. Median PFS was 30.5 mos in induction vs 19 mos in concomitant arm with a 3-year PFS of 47.2% vs 38.8% (HR: 0.74; 95%CI 0.58-0.96; p=0.024), respectively. Median OS was 54.7 mos in induction vs 31.7 mos in concomitant arm with a 3-year OS of 57.5% vs 46.4% (HR: 0.74; 95%CI 0.56-0.97; p=0.031) respectively. Compliance to concomitant treatments was not affected by induction TPF. Conclusions: Induction TPF followed by CRT or CET/RT significantly improved PFS and OS (independently from the type of concomitant strategy) in LASCCHN patients without compromising compliance to the concomitant treatments. OC-007 Is accelerated radiotherapy alone equivalent to chemoradiation in patients with moderate advanced HNSCC? K. Skladowski1, A. Wygoda1, M. Snetura2, T. Rutkowski1, L. Michalecki1, A. Heyda1, A. Hajduk1, M. Kentnowski1, B. Lukaszczyk-Widel1, B. Maciejewski3 1 Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology I Dept, Radiation Oncology and Chemotherapy, Gliwice, Poland 2 Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology I Dept, Cancer Pathology, Gliwice, Poland 3 Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology I Dept, Radiation Oncology, Gliwice, Poland Purpose/Objective: The current indication for radiation therapy alone with altered fractionation regimens in patients with head and neck squamous cell cancer is not known. On the one hand - an indirect comparison with concurrent chemo-radiation (CCR), based on existed meta-analyses, suggests that CCR has yielded a larger survival benefit than that achieved with AF, on the other - this benefit is seen predominantly in locally more advanced HNSCC (T3-4, N2-3), thus AF is believed as a reasonable treatment for patients with less advanced disease, or patients who are not suitable for chemotherapy. To study that problem we have conducted the randomized trial directly comparing CCR with accelerated radiotherapy alone (ARA). Materials and Methods: Over 5 years (2008-13) consecutive 101 pts with oropharynx (46), hypopharynx (19) and larynx (36) cancer in moderate clinical stage, i.e. T2N1-2 (29), T3N0-2 (56) and T4AN0-2 (16), with N+ limited to less or equal 3 cm in diameter, have been randomizing and treating by ARA (53) or CCR (48). ARA was delivered by 7 fractions of 1.8 Gy per week to 72 Gy in 40 fractions over 40 days; in CCR 70 Gy in 35
S4 fractions over 49 days was combined with 3 courses of cisplatin (100 mg/m2/d on day 1, 22 and 43). All OPC pts had examined HPV status. Radiation was delivered to all pts as an IMRT/IGRT. Results: Median follow-up is 40 months. In CCR the number of administered cisplatin courses was as follows: 1 in 5 pts. (10%), 2 in 30 pts. (62%) and 3 in 13 pts. (28%). HPV status was evaluated as positive (+ve) in 11 (29%) and negative (-ve) in 35 (71%) OPC pts. The actuarial rates of 3-year OS and DFS are respectively, 58% and 56% for ARA compare to 79% and 73% for CCR (p=0.02 and p=0.05, respectively). Both OS and DFS were worse in ARA arm as a consequence of higher rates in: primary and neck failures, distant metastases and comorbidity deaths (25%, 9%, 9% and 9%, respectively), compare to CCR arm (14%, 6%, 4% and 4%, respectively). In CCR arm DFS rate was 77% for pts who received 2 or 3 courses of cisplatin and 50% for those who received 1 course only. Sub-site analysis revealed that benefit of CCR was disappeared only in pts with T2 and HPV+ve tumors - all HPV+ve OPC pts remain alive with no cancer failure, whereas OS for HPV-ve pts was 55% in ARA and 78% in CCR. There are no significant differences between the trial arms in acute and late toxicity, as well as, in quality of live, except of better social functioning in CCR pts. Conclusions: 3-year results of the trial have proven that CCR takes an advantage over ARA in pts with MAHNSCC - CCR with conventional 7 weeks fractionation and, at least, 2 courses of cisplatin is more effective than ARA with 6 weeks. The only treatment target for ARA could be now the population of HNSCC pts with: stage T2, moderate stage HPV+ve OPC and contraindication to cisplatin. OC-008 POPART vs CPORT in squamous cell head and neck cancer: Results of a multicenter randomised study of the Dutch head and neck Study Group H. Langendijk1, J.H. Kaanders2, P. Doornaert3, F.R. Burlage1, P.L.A. Van den Ende4, S.B. Oei5, R.B. Keus6, S. Nuyts7, C.R. Leemans8, H. Van Tinteren9, C.H. Terhaard10 1 University Medical Center Groningen University of Groningen, Radiation Oncology, Groningen, The Netherlands 2 Radboud University Nijmegen Medical Centre, Radiation Oncology, Nijmegen, The Netherlands 3 VU University Medical Center, Radiation Oncology, Amsterdam, The Netherlands 4 (MAASTRO) GROW University Hospital, Radiation Oncology, Maastricht, The Netherlands 5 Dr. Bernard Verbeeten Instituut, Radiation Oncology, Tilburg, The Netherlands 6 Arnhem Radiotherapeutic Institute, Radiation Oncology, Arnhem, The Netherlands 7 University Hospitals Leuven, Radiation Oncology, Leuven, Belgium 8 VU University Medical Center, Department of Otolaryngology/Head and Neck Surgery, Amsterdam, The Netherlands 9 The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Medical Statistics, Amsterdam, The Netherlands 10 University Medical Center Utrecht, Radiotherapy, Utrecht, The Netherlands
Background: In head and neck squamous cell carcinoma (HNSCC), the overall treatment time of radiation (OTT) is significantly associated with locoregional control (LRC), which is consistent with rapid repopulation of cancer clonogens during radiotherapy. However, the importance of the OTT in the postoperative setting is less clear. Therefore, the main objective of this phase III study was to determine the value of reduction of the OTT of postoperative radiotherapy in high risk patients primarily treated with surgery.