- Email: [email protected]
SP-023: Lessons learned from running surgical clinical trials
5TH ICHNO
S11 Krasnodar Region, Chief of Medicine, Moscow, Russian Federation 4 Rostov Cancer Research Center, Chief of Medicine, Moscow, Russian Federation 5 Rostov Cancer Research Center, Head and Neck Oncology, Moscow, Russian Federation 6 Institute of Advanced Studies FMBA Russia, Head and Neck Oncology, Moscow, Russian Federation Purpose/Objective: Incidence of chronicle diseases of head and neck, leading to disability, is growing rapidly. The most formidable is increasing rate of head and neck cancer. Early cancer diagnosis gives patient a real chance to recover from this dangerous pathology. Materials and Methods: In September 2014 in terms of Second European Week of Early Head and Neck Cancer Diagnosis the 'open doors' campaign was held. Campaign duration was 4 days total. This year the number of diagnostic spots increased to 26. Ordinary patients were examined by team of specialists including otolaryngologist, maxillo-facial surgeon/stomatologist, oncologist, ultrasound specialist and dermatologist in a 'green line' regimen. Each specialist was filling in corresponding fields in the unitary examination card of the patient. 5800 patients were examined. The scanning expedition to big regional factory was conducted which allowed to examine 1080 patients at one spot. Results: 34,3% of all patients had different pathology, including multiply. Most frequent pathology were: chronic rhinitis, pharyngitis, laryngitis – 10,4%, hyperplastic processes in nasal cavity and paranasal sinuses - 9,6%, traumatic lesions of oral mucosa – 8,7 %, nodular disease of thyroid gland 4,1%, Obligate form of pre-cancer of the oral and nasal cavities mucosa were found in 2.7% cases, malignant tumors were diagnosed 2.5% of cases. The highest turnout was registered in territories with good awareness of the population and regular screening actions. Residents of big cities showed the smallest rate of participation in the event. Even opening new diagnostic spots (10) did not increased participation rate in big cities. The most effective screening method was scanning expedition. All patients with pathology diagnosed during screening have been redirected to specialized hospitals for further examination and treatment. Conclusions: The screening campaign showed its medical and social helpfulness. A significant cohort of patients studied, giving grounds for a statistically correct interpretation of the quantity and quality of pathology of the head and neck in the population. Team approach in examination demonstrated high efficiency in diagnosing and proved it’s the costeffectiveness due to the significant number of diagnosed pathology and subsequent further examination and treatment of patients through insurance companies and high-tech treatment programs.
Symposium: Innovative design of clinical trials in the era of personalised medicine SP-023 Lessons learned from running surgical clinical trials H. Mehanna1 1 University of Birmingham, Institute of Head and Neck Studies and Education, Birmingham, United Kingdom Surgical clinical trials are uncommon, and often considered to be the most challenging clinical tials to run. In this talk we will discuss some of the challenges faced in running surgical clinical trials. We will give some real-life examples of these challenges, and some solutions that we have found successful. We will also then enumerate the top ten lessons learnt from running multicentre surgical trials
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5th ICHNO SP-024 Biomarker driven clinical trials J.P. Machiels1 1 UCL Cliniques Univ. St.Luc, Oncology, Brussels, Belgium Despite progress in the therapeutic management of patients with squamous cell carcinoma of the head and neck (SCCHN), the mortality rate of patients presenting with advanced disease remains high. One approach to improve treatment efficacy is to add novel molecular targeted agents to the classical treatment regimens. Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) have shown clinical benefits in palliative and curative settings. However, only a minority of patients presenting with recurrent or metastatic (R/M) SCCHN have meaningful tumor regression with these agents and virtually all who do develop acquired tumor resistance after a few months of treatment. For these reasons, other inhibitors of EGFR or molecules that interfere with known molecular pathways activated in squamous cell carcinoma of the head and neck are of considerable interest, either as single agents or in combination with other treatment modalities.Recently, deep sequencing technology has allowed a better characterization of the implicated genes. Somatic mutations in TP53 (47–72%), NOTCH1 (14–19%), CDKN2A (9–22%), PIK3CA (6–21%), FBXW7 (5%), HRAS (4–8%), FAT1 (23%) and CASP8 (8%) have been reported. Beside these mutations, some genes or their related proteins have been found to be altered by other mechanims (amplification, deletion, epigenetic). Altogether, activating mutations in classical oncogenes seem relatively rare in SCCHN and most of the genetic alterations occur in tumor suppressor genes. These findings are important for the further development of novel therapies for SCCHN although developping new compounds to restore the activity of altered tumor suppressor genes is extremely challenging. In this review, we will discuss the different molecular therapeutic approaches explored in SCCHN. We will also outline new trial designs that could be used to accelerate the investigation of emerging therapeutic agents in this disease. SP-025 Model based approach for testing new radiation technologies, including particle therapies H. Langendijk 1 University Medical Center Groningen, Radiation Oncology, Groningen, The Netherlands Introduction: Randomized controlled trials (RCT’s) are considered the holy grail of evidence-based medicine. However, most technology innovations and medical devices in health care have not been introduced based on the results of RCT’s. In general, setting up traditional RCT’s testing new technologies is considered complicated and sometimes even impossible, e.g. because of user-dependency, speedy technological developments, high and nonreimbursable costs, limited availability or because the clinical benefit is so large that testing in an RCT is regarded unethical. So far, new radiation technologies have been introduced witout any testing in RCT’s and is mainly based on the assumption that lower dose to healthy tissues will result in less side effects. However, in order to justify high investments, such as in the case of proton therapy, the demand for alternative evidencebased methodologies is rising. The model-based approach such a alternative evidence-based method for selection of patients that will benefit most from new radiation technologies that are primarily aimign at reduction of radiation-induced side effects (RISE) and to validate these technologies. The model-based approach: The model-based approach consists of 4 steps. The first step is the development of validated Normal Tissue Complication Probability (NTCP) models, which are multivariable prediction models describing
S11 Krasnodar Region, Chief of Medicine, Moscow, Russian Federation 4 Rostov Cancer Research Center, Chief of Medicine, Moscow, Russian Federation 5 Rostov Cancer Research Center, Head and Neck Oncology, Moscow, Russian Federation 6 Institute of Advanced Studies FMBA Russia, Head and Neck Oncology, Moscow, Russian Federation Purpose/Objective: Incidence of chronicle diseases of head and neck, leading to disability, is growing rapidly. The most formidable is increasing rate of head and neck cancer. Early cancer diagnosis gives patient a real chance to recover from this dangerous pathology. Materials and Methods: In September 2014 in terms of Second European Week of Early Head and Neck Cancer Diagnosis the 'open doors' campaign was held. Campaign duration was 4 days total. This year the number of diagnostic spots increased to 26. Ordinary patients were examined by team of specialists including otolaryngologist, maxillo-facial surgeon/stomatologist, oncologist, ultrasound specialist and dermatologist in a 'green line' regimen. Each specialist was filling in corresponding fields in the unitary examination card of the patient. 5800 patients were examined. The scanning expedition to big regional factory was conducted which allowed to examine 1080 patients at one spot. Results: 34,3% of all patients had different pathology, including multiply. Most frequent pathology were: chronic rhinitis, pharyngitis, laryngitis – 10,4%, hyperplastic processes in nasal cavity and paranasal sinuses - 9,6%, traumatic lesions of oral mucosa – 8,7 %, nodular disease of thyroid gland 4,1%, Obligate form of pre-cancer of the oral and nasal cavities mucosa were found in 2.7% cases, malignant tumors were diagnosed 2.5% of cases. The highest turnout was registered in territories with good awareness of the population and regular screening actions. Residents of big cities showed the smallest rate of participation in the event. Even opening new diagnostic spots (10) did not increased participation rate in big cities. The most effective screening method was scanning expedition. All patients with pathology diagnosed during screening have been redirected to specialized hospitals for further examination and treatment. Conclusions: The screening campaign showed its medical and social helpfulness. A significant cohort of patients studied, giving grounds for a statistically correct interpretation of the quantity and quality of pathology of the head and neck in the population. Team approach in examination demonstrated high efficiency in diagnosing and proved it’s the costeffectiveness due to the significant number of diagnosed pathology and subsequent further examination and treatment of patients through insurance companies and high-tech treatment programs.
Symposium: Innovative design of clinical trials in the era of personalised medicine SP-023 Lessons learned from running surgical clinical trials H. Mehanna1 1 University of Birmingham, Institute of Head and Neck Studies and Education, Birmingham, United Kingdom Surgical clinical trials are uncommon, and often considered to be the most challenging clinical tials to run. In this talk we will discuss some of the challenges faced in running surgical clinical trials. We will give some real-life examples of these challenges, and some solutions that we have found successful. We will also then enumerate the top ten lessons learnt from running multicentre surgical trials
page 16
5th ICHNO SP-024 Biomarker driven clinical trials J.P. Machiels1 1 UCL Cliniques Univ. St.Luc, Oncology, Brussels, Belgium Despite progress in the therapeutic management of patients with squamous cell carcinoma of the head and neck (SCCHN), the mortality rate of patients presenting with advanced disease remains high. One approach to improve treatment efficacy is to add novel molecular targeted agents to the classical treatment regimens. Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) have shown clinical benefits in palliative and curative settings. However, only a minority of patients presenting with recurrent or metastatic (R/M) SCCHN have meaningful tumor regression with these agents and virtually all who do develop acquired tumor resistance after a few months of treatment. For these reasons, other inhibitors of EGFR or molecules that interfere with known molecular pathways activated in squamous cell carcinoma of the head and neck are of considerable interest, either as single agents or in combination with other treatment modalities.Recently, deep sequencing technology has allowed a better characterization of the implicated genes. Somatic mutations in TP53 (47–72%), NOTCH1 (14–19%), CDKN2A (9–22%), PIK3CA (6–21%), FBXW7 (5%), HRAS (4–8%), FAT1 (23%) and CASP8 (8%) have been reported. Beside these mutations, some genes or their related proteins have been found to be altered by other mechanims (amplification, deletion, epigenetic). Altogether, activating mutations in classical oncogenes seem relatively rare in SCCHN and most of the genetic alterations occur in tumor suppressor genes. These findings are important for the further development of novel therapies for SCCHN although developping new compounds to restore the activity of altered tumor suppressor genes is extremely challenging. In this review, we will discuss the different molecular therapeutic approaches explored in SCCHN. We will also outline new trial designs that could be used to accelerate the investigation of emerging therapeutic agents in this disease. SP-025 Model based approach for testing new radiation technologies, including particle therapies H. Langendijk 1 University Medical Center Groningen, Radiation Oncology, Groningen, The Netherlands Introduction: Randomized controlled trials (RCT’s) are considered the holy grail of evidence-based medicine. However, most technology innovations and medical devices in health care have not been introduced based on the results of RCT’s. In general, setting up traditional RCT’s testing new technologies is considered complicated and sometimes even impossible, e.g. because of user-dependency, speedy technological developments, high and nonreimbursable costs, limited availability or because the clinical benefit is so large that testing in an RCT is regarded unethical. So far, new radiation technologies have been introduced witout any testing in RCT’s and is mainly based on the assumption that lower dose to healthy tissues will result in less side effects. However, in order to justify high investments, such as in the case of proton therapy, the demand for alternative evidencebased methodologies is rising. The model-based approach such a alternative evidence-based method for selection of patients that will benefit most from new radiation technologies that are primarily aimign at reduction of radiation-induced side effects (RISE) and to validate these technologies. The model-based approach: The model-based approach consists of 4 steps. The first step is the development of validated Normal Tissue Complication Probability (NTCP) models, which are multivariable prediction models describing