- Email: [email protected]
93 speaker ADAPTIVE RADIOTHERAPY BY MOLECULAR IMAGING CHANGES
S 34
S YMPOSIUM
Symposium Head & Neck cancer - Vision for the future: What ‘we’ will ask for in the new grant applications? Biological and image guided adaptive radiotherapy 89 speaker UNDERSTANDING AND TAKING ADVANTAGE OF THE TUMOR BIOLOGY R. Brakenhoff Abstract not received.
90 speaker LOCALIZE THE ENEMY: IMAGING IN H&N CANCER V. Grégoire Abstract not received.
91 speaker ADAPTIVE RADIATION TREATMENT OF HEAD AND NECK CANCER IN THE FUTURE – ADVANCED TREATMENT PLANNING AND DELIVERY C. Grau1 1 A ARHUS U NIVERSITY H OSPITAL, Aarhus C, Denmark
M ONDAY, M AY 9, 2011
specifically target and inhibit proteins that are of importance for the tumor growth and survival. Non-invasive assessment of the response of the tumor to preoperative CRT is essential for further selection of patients who could be spared invasive surgery. The usefulness of molecular markers present in the tumor tissue and blood of the patients and of non invasive imaging techniques such as (Diffusion-Weighted (DW-)MRI and 18-F Fluoro-deoxyglucose positron emission tomography (18FDG-PET) needs careful study. Strong evidence has emerged indicating that changes in 18FDG uptake, measured by the standardized uptake value (SUV) appear to be a valid predictive factor for outcome (Capirci C et al. Biomed Pharmacother 2004; Capirci C et al. Eur J Nucl Med Mol Imaging 2007; Janssen MH et al. Int J Radiat Oncol Biol Phys 2010; Capirci C et al. Int J Radiat Oncol Biol Phys 2009). These results were recently confirmed by results on 20 patients at our centre (Lambrecht M et al. Acta Oncol 2010). While conventional MRI lacks functional information, DW-MRI has overcome these shortcomings and provides functional information of the tumor microenvironment (Koh DM, et al. Am J Roentgenol 2007). DW-MRI has proven its value in head and neck squamous cell carcinoma (Vandecaveye V et al. Int J Radiat Oncol Biol Phys 2007). Preliminary results in our centre showed that DWI is more accurate for early response prediction than volumetric measurements and can be used to estimate 2-year locoregional control and disease free survival in head and neck cancer (Vandecaveye V et al. Eur Radiol 2010). This implies that DW-MRI might be able to predict tumor response early. Patients with a good response to treatment generally show a lower ADC prior to treatment and with a higher ΔADC during and after chemoradiation. The hypothesis is that a low initial ADC value represents a more restrictive environment with less interstitial edema, necrosis and a higher cellularity. This necrosis is generally associated with an acidic environment and a low oxygen concentration which influences the response to radiotherapy and chemotherapy.
Abstract not received.
ESTRO-ESSO Joint Symposium: Vision for the future: What ‘we’ will ask for in the new grant applications? - Translational research / High technology 92 speaker ADAPTIVE RADIOTHERAPY IN RECTAL CANCER: FUTURE OR FUTILE? C. Marijnen1 1
L EIDEN U NIVERSITY M EDICAL C ENTER, Leiden, Netherlands
Abstract not received. 94 speaker 93 speaker ADAPTIVE RADIOTHERAPY BY MOLECULAR IMAGING CHANGES K. Haustermans1 1 L EUVENS K ANKER I NSTITUUT (LKI), U NIVERSITY H OSPITAL G ASTHUIS BERG, Radiation Oncology, Leuven, Belgium
Rectal cancer is a frequent and curable malignancy in the Western world. The introduction of the total mesorectal excision (TME) with its wider lateral margins reduced the number of locoregional recurrences drastically [MacFarlane, 1993; Kapiteijn 2001]. Preoperative radiotherapy has proven its worth in reducing local control rates and overall survival in all stages of rectal cancer [Kapiteijn 2001], which was further increased by the addition of fluorouracil based chemotherapy schedules [Sauer 2004]. Besides the increased local control rate, chemoradiation (CRT) has the additional advantage of inducing a significant tumor downsizing and even downstaging [Bosset, 2005; Valentini, 2001]. In 10-30% of the patients no residual tumor tissue after CRT can be observed. These patients have a favorable long term outcome. Currently, the standard therapy for each patient is preoperative treatment followed by extensive surgery regardless of the tumor response. However, the last decade the question arose whether extensive surgery can be avoided and replaced by minimal invasive surgery or no surgery at all for patients with a pathologic complete response (pCR) without compromising tumor control [Habr-Gama, 2004]. To date however, the only way to ascertain pCR is pathologic examination of the resection specimen. In contrast with the patient group with a good prognosis, for which (invasive) surgery could be omitted, patients with ’ugly’ tumors could benefit from a more intensified treatment by addition of molecular targeted drugs. Therefore, standard (chemo)radiotherapy can be combined with molecular targeted agents that
ADAPTIVE RADIOTHERAPY BY PREDICTIVE BIOLOGICAL MARKERS C. Rödel1 1 K LINIKUM DER J OHANN W OLFGANG G OETHE U NIVERSITÄT, Department of Radiotherapy Oncology, Frankfurt, Germany
The rapidly increasing knowledge of the molecular basis and pathways that influence and modify radiation response has led to the identification of biological markers that may help to predict responsiveness to radiotherapy or combined modality treatments. Such biomarkers and molecular signatures may be investigated using high-throughput technologies (genomics, transcriptomics, proteomics) with the aim to fully implement patient-specific "biological stratification" of radiation treatments. Within the next decade, it should be possible to combine such information with advanced delivery technologies to design biologically adapted radiation therapy, e.g. radiation dose escalation to more radioresistant regions within the tumor. Changes in tumor and normal tissue biology during early treatment may also be predictive of tumor response and adaptive strategies during treatment may help to optimize outcomes. Moreover, these molecular structures can be specifically targeted by modern anticancer drug development with the aim of overcoming radioresistance of tumor cells or protecting normal tissues. Promising modifiers of radiation response are now entering early clinical trials. Stratification based on classical parameters plus predictive biological markers is required to fully exploit the potential of innovative molecular drugs for improving radiotherapy.
S YMPOSIUM
Symposium Head & Neck cancer - Vision for the future: What ‘we’ will ask for in the new grant applications? Biological and image guided adaptive radiotherapy 89 speaker UNDERSTANDING AND TAKING ADVANTAGE OF THE TUMOR BIOLOGY R. Brakenhoff Abstract not received.
90 speaker LOCALIZE THE ENEMY: IMAGING IN H&N CANCER V. Grégoire Abstract not received.
91 speaker ADAPTIVE RADIATION TREATMENT OF HEAD AND NECK CANCER IN THE FUTURE – ADVANCED TREATMENT PLANNING AND DELIVERY C. Grau1 1 A ARHUS U NIVERSITY H OSPITAL, Aarhus C, Denmark
M ONDAY, M AY 9, 2011
specifically target and inhibit proteins that are of importance for the tumor growth and survival. Non-invasive assessment of the response of the tumor to preoperative CRT is essential for further selection of patients who could be spared invasive surgery. The usefulness of molecular markers present in the tumor tissue and blood of the patients and of non invasive imaging techniques such as (Diffusion-Weighted (DW-)MRI and 18-F Fluoro-deoxyglucose positron emission tomography (18FDG-PET) needs careful study. Strong evidence has emerged indicating that changes in 18FDG uptake, measured by the standardized uptake value (SUV) appear to be a valid predictive factor for outcome (Capirci C et al. Biomed Pharmacother 2004; Capirci C et al. Eur J Nucl Med Mol Imaging 2007; Janssen MH et al. Int J Radiat Oncol Biol Phys 2010; Capirci C et al. Int J Radiat Oncol Biol Phys 2009). These results were recently confirmed by results on 20 patients at our centre (Lambrecht M et al. Acta Oncol 2010). While conventional MRI lacks functional information, DW-MRI has overcome these shortcomings and provides functional information of the tumor microenvironment (Koh DM, et al. Am J Roentgenol 2007). DW-MRI has proven its value in head and neck squamous cell carcinoma (Vandecaveye V et al. Int J Radiat Oncol Biol Phys 2007). Preliminary results in our centre showed that DWI is more accurate for early response prediction than volumetric measurements and can be used to estimate 2-year locoregional control and disease free survival in head and neck cancer (Vandecaveye V et al. Eur Radiol 2010). This implies that DW-MRI might be able to predict tumor response early. Patients with a good response to treatment generally show a lower ADC prior to treatment and with a higher ΔADC during and after chemoradiation. The hypothesis is that a low initial ADC value represents a more restrictive environment with less interstitial edema, necrosis and a higher cellularity. This necrosis is generally associated with an acidic environment and a low oxygen concentration which influences the response to radiotherapy and chemotherapy.
Abstract not received.
ESTRO-ESSO Joint Symposium: Vision for the future: What ‘we’ will ask for in the new grant applications? - Translational research / High technology 92 speaker ADAPTIVE RADIOTHERAPY IN RECTAL CANCER: FUTURE OR FUTILE? C. Marijnen1 1
L EIDEN U NIVERSITY M EDICAL C ENTER, Leiden, Netherlands
Abstract not received. 94 speaker 93 speaker ADAPTIVE RADIOTHERAPY BY MOLECULAR IMAGING CHANGES K. Haustermans1 1 L EUVENS K ANKER I NSTITUUT (LKI), U NIVERSITY H OSPITAL G ASTHUIS BERG, Radiation Oncology, Leuven, Belgium
Rectal cancer is a frequent and curable malignancy in the Western world. The introduction of the total mesorectal excision (TME) with its wider lateral margins reduced the number of locoregional recurrences drastically [MacFarlane, 1993; Kapiteijn 2001]. Preoperative radiotherapy has proven its worth in reducing local control rates and overall survival in all stages of rectal cancer [Kapiteijn 2001], which was further increased by the addition of fluorouracil based chemotherapy schedules [Sauer 2004]. Besides the increased local control rate, chemoradiation (CRT) has the additional advantage of inducing a significant tumor downsizing and even downstaging [Bosset, 2005; Valentini, 2001]. In 10-30% of the patients no residual tumor tissue after CRT can be observed. These patients have a favorable long term outcome. Currently, the standard therapy for each patient is preoperative treatment followed by extensive surgery regardless of the tumor response. However, the last decade the question arose whether extensive surgery can be avoided and replaced by minimal invasive surgery or no surgery at all for patients with a pathologic complete response (pCR) without compromising tumor control [Habr-Gama, 2004]. To date however, the only way to ascertain pCR is pathologic examination of the resection specimen. In contrast with the patient group with a good prognosis, for which (invasive) surgery could be omitted, patients with ’ugly’ tumors could benefit from a more intensified treatment by addition of molecular targeted drugs. Therefore, standard (chemo)radiotherapy can be combined with molecular targeted agents that
ADAPTIVE RADIOTHERAPY BY PREDICTIVE BIOLOGICAL MARKERS C. Rödel1 1 K LINIKUM DER J OHANN W OLFGANG G OETHE U NIVERSITÄT, Department of Radiotherapy Oncology, Frankfurt, Germany
The rapidly increasing knowledge of the molecular basis and pathways that influence and modify radiation response has led to the identification of biological markers that may help to predict responsiveness to radiotherapy or combined modality treatments. Such biomarkers and molecular signatures may be investigated using high-throughput technologies (genomics, transcriptomics, proteomics) with the aim to fully implement patient-specific "biological stratification" of radiation treatments. Within the next decade, it should be possible to combine such information with advanced delivery technologies to design biologically adapted radiation therapy, e.g. radiation dose escalation to more radioresistant regions within the tumor. Changes in tumor and normal tissue biology during early treatment may also be predictive of tumor response and adaptive strategies during treatment may help to optimize outcomes. Moreover, these molecular structures can be specifically targeted by modern anticancer drug development with the aim of overcoming radioresistance of tumor cells or protecting normal tissues. Promising modifiers of radiation response are now entering early clinical trials. Stratification based on classical parameters plus predictive biological markers is required to fully exploit the potential of innovative molecular drugs for improving radiotherapy.