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SP-012: Update of neck dissection trial
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6th ICHNO
received neck dissection and those who did not receive neck dissection. We will also analyse the determinants of overall quality of life and of swallowing including factors such as neck dissection and HPV status. In addition we will also report on the functional and survival outcomes of different types of neck dissection in the context of definitive chemoradiotherapy. SP-012 Update of neck dissection trial A.D'Cruz1 1 Tata Memorial Hospital, Mumbai, India Abstract text BACKGROUND: Appropriate management of the neck in clinically node negative early oral cancer has been a matter of debate for decades. A prospective phase III randomized controlled trial (RCT) was designed to address the issues of: 1. The superiority of elective neck dissection (END) over the wait and watch (WW) policy followed by therapeutic neck dissection (TND) when needed 2. The addition of ultrasonography to routine physical examination on follow up would help in earlier detection of neck metastasis influencing salvage and survival. METHODS: Patients with lateralized T1 or T2 squamous carcinoma of oral cavity, amenable to peroral excision were included in the trial. At initial surgery all patients underwent a wide local excision of the primary with appropriate margins. They were randomized to either END or WW policy for the neck management. Patients were randomized a second time to follow up with physical examination plus neck ultrasound (PE+USG) versus physical examination (PE) alone. Stratification was based on size, site, gender and preoperative neck ultrasound. The primary end point was overall survival (OS) and secondary end point was disease-free survival (DFS). The trial was planned to demonstrate a 10% superiority ( = 0.05 and = 0.2) in OS for END vs. TND, assuming 60% 5year OS in TND arm, with a planned sample size of 710. RESULTS: This study was terminated after 596 patients were randomized between January 2004 and June 2014. An interim intent-to-treat analysis of initial 500 patients (255 in TND, 245 END) was performed as mandated by Data and Safety Monitoring Committee based on the number of observed deaths in each arm. Both arms were balanced for site and stage. There were 427 tongue, 68 buccal mucosa and 5 floor of mouth tumours; 221 were TI and 279 T2. At a median follow-up of 39 months 146 recurred in TND and 81 in END arms. The 3-year OS was significantly higher in END compared to TND arm (80.0% vs. 67.5%, HR = 0.64; 95% CI, 0.45 to 0.92; P=0.01) as was 3-year DFS (69.5% vs. 45.9%, HR = 0.45; 95% CI, 0.34 to 0.59; P<0.001). After adjusting for stratification factors in Cox regression, END continued to be significantly superior to TND for both OS and DFS. In the follow up randomization 252 patients were allocated to PE+USG and 244 to PE. In addition to the stratification factors both arms were balanced for the surgical procedure (END vs. TND) as well. There were 118 recurrences with 67 deaths in PE+USG and 109 recurrences with 62 deaths in PE, respectively. There was no OS difference between PE+USG and PE in unadjusted analysis (3-year OS 73.3% and 73.8%, respectively, HR = 1.02, 95%CI 0.73-1.45, p = 0.89) and after adjustment (HR = 0.81, 95%CI 0.51-1.29, p = 0.37) for stratification factors, prognostic factors, surgical treatment (END vs. TND) and an interaction term between two study questions, in a Cox model. END vs. TND continued to be highly significant for OS in this model (HR = 0.54, 95%CI 0.32 - 0.92, p = 0.02). Within TND (wait and watch) arm there was no significant difference between PE+USG and PE (3-year OS 67.3% and 67.6% respectively, HR = 0.96, 95%CI 0.62–1.5, p = 0.86). CONCLUSIONS: There were 8 excess deaths for every 15
excess recurrences in the TND arm. Elective neck dissection in patients with early oral SCC results in 36% reduction in mortality and should be considered the standard of care. Neck ultrasound confers no survival advantage over physical examination in postoperative follow-up of clinically node negative early stage oral cancer patients. N Engl J Med 2015;373:521-9 SP-013 Update on the ARCON study J. Kaanders1, W. Bots1, C. Terhaard2, M. Vergeer3, P. Doornaert2, H. Bijl4, P. Van den Ende5, M. De Jong6, G. P. Span1 Janssens2, 1 Radboud umc, Radiation Oncology, Nijmegen, The Netherlands 2 UMC Utrecht, Radiation Oncology, Utrecht, The Netherlands 3 VUMC Amsterdam, Radiation Oncology, Amsterdam, The Netherlands 4 UMC Groningen, Radiation Oncology, Groningen, The Netherlands 5 Maastro Clinic, Radiation Oncology, Maastricht, The Netherlands 6 Leiden UMC, Radiation Oncology, Leiden, The Netherlands Abstract text Purpose: "ARCON" combines accelerated radiotherapy to counteract tumor repopulation with carbogen breathing and nicotinamide to reduce chronic and acute hypoxia. We report the long-term results from a randomized phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with clinical stage T2-4 squamous cell laryngeal cancer were randomized to AR (N=174) and ARCON (N=171). AR was given to a total dose of 68 Gy in 2 Gy fractions within 36-38 days on the primary tumor and the pathological lymph nodes. In the experimental arm, a dose reduction to 64 Gy on the laryngeal cartilage was required and radiotherapy was combined with carbogen breathing during irradiation and administration of nicotinamide (60 mg/kg) 1-1.5 h before the first fraction of every day. Results: After a median follow-up of 72 months, local control rate at 5 years was 78% with no difference between the study arms. The 5-year regional control was significantly better with ARCON (93% for ARCON versus 86% for AR, p=0.04). Analysis of late radiation morbidity did not reveal significant differences between the AR and ARCON treatment arms with respect to skin and subcutaneous tissues (severe telangiectasia, 8% v 8%; P = .56; severe subcutaneous fibrosis, 7% v 9%; P = .26; severe subcutaneous edema, 8% v 4%; P = .09) and mucous membranes (mucosal ulceration, 8% v 6%; P = .36; nasogastric tube feeding, 6% v 6%; P = .61, respectively). Twelve patients in the AR group and six patients in the ARCON group required a tracheostomy for severe edema with dyspnea and/or stridor. All patients who developed a cartilage necrosis could be managed conservatively. Four of the patients received a tracheostomy (n = 1 for AR, n = 3 for ARCON), and there was no need for laryngectomy. One year after diagnosis, 3% of patients in both groups needed nasogastric tube feeding (P = .88). At 2 years from baseline, the percentage of patients reporting moderate to severe complaints of dry mouth, sticky saliva, or changes in taste/smell was 30%, 22% and 18%, respectively, while the majority of patients had no or few complaints of swallowing (79%) or speech (64%). Conclusion: Long-term morbidity was mild and quality of life was high with no difference between the study arms.
This is an Open Access article under the CC BY-NC-ND license.
6th ICHNO
received neck dissection and those who did not receive neck dissection. We will also analyse the determinants of overall quality of life and of swallowing including factors such as neck dissection and HPV status. In addition we will also report on the functional and survival outcomes of different types of neck dissection in the context of definitive chemoradiotherapy. SP-012 Update of neck dissection trial A.D'Cruz1 1 Tata Memorial Hospital, Mumbai, India Abstract text BACKGROUND: Appropriate management of the neck in clinically node negative early oral cancer has been a matter of debate for decades. A prospective phase III randomized controlled trial (RCT) was designed to address the issues of: 1. The superiority of elective neck dissection (END) over the wait and watch (WW) policy followed by therapeutic neck dissection (TND) when needed 2. The addition of ultrasonography to routine physical examination on follow up would help in earlier detection of neck metastasis influencing salvage and survival. METHODS: Patients with lateralized T1 or T2 squamous carcinoma of oral cavity, amenable to peroral excision were included in the trial. At initial surgery all patients underwent a wide local excision of the primary with appropriate margins. They were randomized to either END or WW policy for the neck management. Patients were randomized a second time to follow up with physical examination plus neck ultrasound (PE+USG) versus physical examination (PE) alone. Stratification was based on size, site, gender and preoperative neck ultrasound. The primary end point was overall survival (OS) and secondary end point was disease-free survival (DFS). The trial was planned to demonstrate a 10% superiority ( = 0.05 and = 0.2) in OS for END vs. TND, assuming 60% 5year OS in TND arm, with a planned sample size of 710. RESULTS: This study was terminated after 596 patients were randomized between January 2004 and June 2014. An interim intent-to-treat analysis of initial 500 patients (255 in TND, 245 END) was performed as mandated by Data and Safety Monitoring Committee based on the number of observed deaths in each arm. Both arms were balanced for site and stage. There were 427 tongue, 68 buccal mucosa and 5 floor of mouth tumours; 221 were TI and 279 T2. At a median follow-up of 39 months 146 recurred in TND and 81 in END arms. The 3-year OS was significantly higher in END compared to TND arm (80.0% vs. 67.5%, HR = 0.64; 95% CI, 0.45 to 0.92; P=0.01) as was 3-year DFS (69.5% vs. 45.9%, HR = 0.45; 95% CI, 0.34 to 0.59; P<0.001). After adjusting for stratification factors in Cox regression, END continued to be significantly superior to TND for both OS and DFS. In the follow up randomization 252 patients were allocated to PE+USG and 244 to PE. In addition to the stratification factors both arms were balanced for the surgical procedure (END vs. TND) as well. There were 118 recurrences with 67 deaths in PE+USG and 109 recurrences with 62 deaths in PE, respectively. There was no OS difference between PE+USG and PE in unadjusted analysis (3-year OS 73.3% and 73.8%, respectively, HR = 1.02, 95%CI 0.73-1.45, p = 0.89) and after adjustment (HR = 0.81, 95%CI 0.51-1.29, p = 0.37) for stratification factors, prognostic factors, surgical treatment (END vs. TND) and an interaction term between two study questions, in a Cox model. END vs. TND continued to be highly significant for OS in this model (HR = 0.54, 95%CI 0.32 - 0.92, p = 0.02). Within TND (wait and watch) arm there was no significant difference between PE+USG and PE (3-year OS 67.3% and 67.6% respectively, HR = 0.96, 95%CI 0.62–1.5, p = 0.86). CONCLUSIONS: There were 8 excess deaths for every 15
excess recurrences in the TND arm. Elective neck dissection in patients with early oral SCC results in 36% reduction in mortality and should be considered the standard of care. Neck ultrasound confers no survival advantage over physical examination in postoperative follow-up of clinically node negative early stage oral cancer patients. N Engl J Med 2015;373:521-9 SP-013 Update on the ARCON study J. Kaanders1, W. Bots1, C. Terhaard2, M. Vergeer3, P. Doornaert2, H. Bijl4, P. Van den Ende5, M. De Jong6, G. P. Span1 Janssens2, 1 Radboud umc, Radiation Oncology, Nijmegen, The Netherlands 2 UMC Utrecht, Radiation Oncology, Utrecht, The Netherlands 3 VUMC Amsterdam, Radiation Oncology, Amsterdam, The Netherlands 4 UMC Groningen, Radiation Oncology, Groningen, The Netherlands 5 Maastro Clinic, Radiation Oncology, Maastricht, The Netherlands 6 Leiden UMC, Radiation Oncology, Leiden, The Netherlands Abstract text Purpose: "ARCON" combines accelerated radiotherapy to counteract tumor repopulation with carbogen breathing and nicotinamide to reduce chronic and acute hypoxia. We report the long-term results from a randomized phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with clinical stage T2-4 squamous cell laryngeal cancer were randomized to AR (N=174) and ARCON (N=171). AR was given to a total dose of 68 Gy in 2 Gy fractions within 36-38 days on the primary tumor and the pathological lymph nodes. In the experimental arm, a dose reduction to 64 Gy on the laryngeal cartilage was required and radiotherapy was combined with carbogen breathing during irradiation and administration of nicotinamide (60 mg/kg) 1-1.5 h before the first fraction of every day. Results: After a median follow-up of 72 months, local control rate at 5 years was 78% with no difference between the study arms. The 5-year regional control was significantly better with ARCON (93% for ARCON versus 86% for AR, p=0.04). Analysis of late radiation morbidity did not reveal significant differences between the AR and ARCON treatment arms with respect to skin and subcutaneous tissues (severe telangiectasia, 8% v 8%; P = .56; severe subcutaneous fibrosis, 7% v 9%; P = .26; severe subcutaneous edema, 8% v 4%; P = .09) and mucous membranes (mucosal ulceration, 8% v 6%; P = .36; nasogastric tube feeding, 6% v 6%; P = .61, respectively). Twelve patients in the AR group and six patients in the ARCON group required a tracheostomy for severe edema with dyspnea and/or stridor. All patients who developed a cartilage necrosis could be managed conservatively. Four of the patients received a tracheostomy (n = 1 for AR, n = 3 for ARCON), and there was no need for laryngectomy. One year after diagnosis, 3% of patients in both groups needed nasogastric tube feeding (P = .88). At 2 years from baseline, the percentage of patients reporting moderate to severe complaints of dry mouth, sticky saliva, or changes in taste/smell was 30%, 22% and 18%, respectively, while the majority of patients had no or few complaints of swallowing (79%) or speech (64%). Conclusion: Long-term morbidity was mild and quality of life was high with no difference between the study arms.
This is an Open Access article under the CC BY-NC-ND license.