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SP-0058: Current status and future perspective of response adaptation
S28 ESTRO 36 _______________________________________________________________________________________________
Symposium: Response adapted treatment SP-0057 Mechanisms and biomarkers of tumour response heterogeneity S. Chopra1 1 Advanced Centre for Treatment- Research and Education in Cancer- Mumbai, Radiation Oncology, Mumbai, India Heterogeneity of response to therapeutic radiation is a well-known phenomenon and is attributed to differential evolution of tumour subpopulations that may harbor resistant clones. Aberrant vasculature during early tumour growth results in heterogenous microenvironment. Tumour hypoxia and resultant acidic microenvironment therefore becomes an early event triggering various downstream pathways that support development and sustainence of aggressive tumour phenotype. Hypoxic environment is known to allow clonal evolution of stem cell phenotype through expression of stem cell genes like SOX-2/OCT-4/NANOG and increase in reactive oxygen species which may in turn lead to increased DNA damage repair and reduced cell kill after radiation, epithelial to mesenchymal transformation and distant metastasis. Recent research suggests that cancer stem cells may not be in a fixed but in a dynamic state of cellular plasticity that is dependent on the microenvironment stimulus. Specific niching patterns for cells with stem cell phenotype have been identified for certain tumour types. As microenvironment may play a crucial role in nurturing and sustaining aggressive cellular phenotypes, there may be considerable merit in imaging and targeting microenviornmental niches with radiation.The role of the above possible mechanisms in radiation resistance and biomarkers that may be linked to aggressive cellular phenotype and tumour milieu will be discussed with specific examples from solid tumours that are treated with radiation. SP-0058 Current status and future perspective of response adaptation D. Zips1 1 University Hospital Tübingen Eberhard Karls University Tübingen, Tübingen, Germany In my presentation I will introduce the rationale of the biological concept of delta imaging for individualized patient management. I will discuss supporting findings and preclinical proof-of-concept using PET/ fMRI and I will review current clinical evidence with examples in HN, rectal, prostate cancer. SP-0059 Response optimised treatment planning and guidance B. Vanderstraeten1 1 University Hospital Ghent, Radiotherapy - RTP, Gent, Belgium Biological imaging modalities like PET or fMRI aim to unravel tumor heterogeneity, e.g. by identifying the most radiation resistant parts of a tumor. As the total dose that can be delivered is limited by normal tissue toxicity, biological image-guided radiotherapy opts for dose modification based on pre-treatment imaging or pertreatment response assessment. The dichotomous nature of target contouring, where voxels are either “in” or “out” and hence intended to receive a homogeneous or no dose, is not in agreement with reality. Dose painting by numbers has been suggested to translate treatment response to dose modification by means of a voxel-based dose prescription. Despite the present uncertainties about the applicability of dose painting and the need for accurate biological models, physicists and technologists should be prepared
for the challenges that per-treatment dose modification poses to treatment planning and delivery systems. This lecture will focus on the realization of individual dose modification in treatment planning, including different treatment modalities and techniques, treatment planning system requirements, the feasibility of dose painting in adaptive treatment schedules and automated planning. Practical examples for head and neck and prostate cancer will be shown. The higher the intentional inhomogeneity of the dose distribution, the higher the risk of getting things wrong during treatment delivery because of set-up errors or changes in patient anatomy. Apart from treatment adaptation, it is important to minimize the uncertainties in delivery and account for residual uncertainties in planning. Using statistical models to predict tumor presence on a voxel level, the robustness against geometric errors can be improved. Because of the existing technical challenges, extensive collaboration between radiologists, radiation biologists, radiation oncologists and physicists is needed. Proffered Papers: Dosimetry and detector development for particle therapy OC-0060 Reference dosimetry of proton pencil beams based on dose-area product C. Gomà1, S. Safai2, S. Vörös3 1 University Hospitals Leuven, Department of Radiation Oncology, Leuven, Belgium 2 Paul Scherrer Institute, Center for Proton Therapy, Villigen PSI, Switzerland 3 Federal Institute of Metrology METAS, Ionising Radiation, Bern-Wabern, Switzerland Purpose or Objective To study the feasibility of a novel approach to the reference dosimetry of proton pencil beams based on dose-area product (DAPw)—the integral of the absorbed dose to water (Dw) over the plane perpendicular to the beam direction. The DAPw of a proton pencil beam is a quantity needed for beam modeling in most TPS. Currently, it is calculated indirectly through the determination of Dw in a broad composite field together with the reciprocity theorem. This work investigates the direct determination of DAPw with reference dosimetry. Material and Methods The reciprocity theorem establishes an analytical relationship between (i) the DAPw of a single proton pencil beam and (ii) the Dw at the center of a broad composite field generated by the superposition of proton pencil beams regularly-spaced at a distance of δx and δy (DAPw = Dw δx δy). The feasibility of reference dosimetry based on DAPw (DAPw = MQ · NDAP,w · kQ) was therefore assessed by comparison with the standard and well-established reference dosimetry in a composite 10x10 cm2 field based on Dw (Dw = MQ · ND,w · kQ). First, we calibrated a PTW Bragg Peak chamber (BPC) and a PTW Markus chamber in a PSDL 60 Co beam, in terms of DAPw and Dw respectively. Second, we calculated the beam quality correction factor (kQ) of the two ionization chambers using Monte Carlo simulation. Finally, we compared (i) the direct determination of DAPw of a single pencil beam using the BPC, and (ii) the indirect determination of DAPw (DAPw = Dw δx δy) using the Markus chamber to determine Dw at the center of a broad composite field. The two approaches were compared for proton energies ranging from 70 to 230 MeV. Results The BPC was successfully calibrated in terms of DAPw in a 60 Co beam. The uncertainty of the calibration coefficient was estimated to be 0.2% larger than in the standard case, due to the uncertainty in the BPC sensitive area. Figure 1 shows that direct and indirect determination of DAPw were
Symposium: Response adapted treatment SP-0057 Mechanisms and biomarkers of tumour response heterogeneity S. Chopra1 1 Advanced Centre for Treatment- Research and Education in Cancer- Mumbai, Radiation Oncology, Mumbai, India Heterogeneity of response to therapeutic radiation is a well-known phenomenon and is attributed to differential evolution of tumour subpopulations that may harbor resistant clones. Aberrant vasculature during early tumour growth results in heterogenous microenvironment. Tumour hypoxia and resultant acidic microenvironment therefore becomes an early event triggering various downstream pathways that support development and sustainence of aggressive tumour phenotype. Hypoxic environment is known to allow clonal evolution of stem cell phenotype through expression of stem cell genes like SOX-2/OCT-4/NANOG and increase in reactive oxygen species which may in turn lead to increased DNA damage repair and reduced cell kill after radiation, epithelial to mesenchymal transformation and distant metastasis. Recent research suggests that cancer stem cells may not be in a fixed but in a dynamic state of cellular plasticity that is dependent on the microenvironment stimulus. Specific niching patterns for cells with stem cell phenotype have been identified for certain tumour types. As microenvironment may play a crucial role in nurturing and sustaining aggressive cellular phenotypes, there may be considerable merit in imaging and targeting microenviornmental niches with radiation.The role of the above possible mechanisms in radiation resistance and biomarkers that may be linked to aggressive cellular phenotype and tumour milieu will be discussed with specific examples from solid tumours that are treated with radiation. SP-0058 Current status and future perspective of response adaptation D. Zips1 1 University Hospital Tübingen Eberhard Karls University Tübingen, Tübingen, Germany In my presentation I will introduce the rationale of the biological concept of delta imaging for individualized patient management. I will discuss supporting findings and preclinical proof-of-concept using PET/ fMRI and I will review current clinical evidence with examples in HN, rectal, prostate cancer. SP-0059 Response optimised treatment planning and guidance B. Vanderstraeten1 1 University Hospital Ghent, Radiotherapy - RTP, Gent, Belgium Biological imaging modalities like PET or fMRI aim to unravel tumor heterogeneity, e.g. by identifying the most radiation resistant parts of a tumor. As the total dose that can be delivered is limited by normal tissue toxicity, biological image-guided radiotherapy opts for dose modification based on pre-treatment imaging or pertreatment response assessment. The dichotomous nature of target contouring, where voxels are either “in” or “out” and hence intended to receive a homogeneous or no dose, is not in agreement with reality. Dose painting by numbers has been suggested to translate treatment response to dose modification by means of a voxel-based dose prescription. Despite the present uncertainties about the applicability of dose painting and the need for accurate biological models, physicists and technologists should be prepared
for the challenges that per-treatment dose modification poses to treatment planning and delivery systems. This lecture will focus on the realization of individual dose modification in treatment planning, including different treatment modalities and techniques, treatment planning system requirements, the feasibility of dose painting in adaptive treatment schedules and automated planning. Practical examples for head and neck and prostate cancer will be shown. The higher the intentional inhomogeneity of the dose distribution, the higher the risk of getting things wrong during treatment delivery because of set-up errors or changes in patient anatomy. Apart from treatment adaptation, it is important to minimize the uncertainties in delivery and account for residual uncertainties in planning. Using statistical models to predict tumor presence on a voxel level, the robustness against geometric errors can be improved. Because of the existing technical challenges, extensive collaboration between radiologists, radiation biologists, radiation oncologists and physicists is needed. Proffered Papers: Dosimetry and detector development for particle therapy OC-0060 Reference dosimetry of proton pencil beams based on dose-area product C. Gomà1, S. Safai2, S. Vörös3 1 University Hospitals Leuven, Department of Radiation Oncology, Leuven, Belgium 2 Paul Scherrer Institute, Center for Proton Therapy, Villigen PSI, Switzerland 3 Federal Institute of Metrology METAS, Ionising Radiation, Bern-Wabern, Switzerland Purpose or Objective To study the feasibility of a novel approach to the reference dosimetry of proton pencil beams based on dose-area product (DAPw)—the integral of the absorbed dose to water (Dw) over the plane perpendicular to the beam direction. The DAPw of a proton pencil beam is a quantity needed for beam modeling in most TPS. Currently, it is calculated indirectly through the determination of Dw in a broad composite field together with the reciprocity theorem. This work investigates the direct determination of DAPw with reference dosimetry. Material and Methods The reciprocity theorem establishes an analytical relationship between (i) the DAPw of a single proton pencil beam and (ii) the Dw at the center of a broad composite field generated by the superposition of proton pencil beams regularly-spaced at a distance of δx and δy (DAPw = Dw δx δy). The feasibility of reference dosimetry based on DAPw (DAPw = MQ · NDAP,w · kQ) was therefore assessed by comparison with the standard and well-established reference dosimetry in a composite 10x10 cm2 field based on Dw (Dw = MQ · ND,w · kQ). First, we calibrated a PTW Bragg Peak chamber (BPC) and a PTW Markus chamber in a PSDL 60 Co beam, in terms of DAPw and Dw respectively. Second, we calculated the beam quality correction factor (kQ) of the two ionization chambers using Monte Carlo simulation. Finally, we compared (i) the direct determination of DAPw of a single pencil beam using the BPC, and (ii) the indirect determination of DAPw (DAPw = Dw δx δy) using the Markus chamber to determine Dw at the center of a broad composite field. The two approaches were compared for proton energies ranging from 70 to 230 MeV. Results The BPC was successfully calibrated in terms of DAPw in a 60 Co beam. The uncertainty of the calibration coefficient was estimated to be 0.2% larger than in the standard case, due to the uncertainty in the BPC sensitive area. Figure 1 shows that direct and indirect determination of DAPw were