Medikal Fizik Çalışmaları

Transcription

1 Medikal Fizik Çalışmaları 9 Kasım Vildan ALPAN Amerikan Hastanesi MDACC Kanser Merkezi, İstanbul

2 Learning Objectives To get an overview of the main current research directions in radiation therapy physics Five abstracts selected based on (a) their high scores from reviewers (b) their relevance to this audience (c) variety in treatment sites To understand the clinical impact of physics research in radiation oncology

3 Major Themes Treatment Planning and Delivery (in SRS/SBRT) Incident Learning for Stereotactic Radiation Therapy from RO-ILS: Radiation Oncology Incident Learning System (liver SBRT) Imaging for Response Assessment / Outcome analysis and modeling Radiogenomic Analysis of a Peritumoral CT Image Feature and its Prognostic Value in Early Stage NSCLC Regional dose differences associated with radiation-induced acute severe dysphagia (for H&N tumors)

4 Incident Learning for Stereotactic Radiation Therapy from RO-ILS: Radiation Oncology Incident Learning System D. J. Hoopes 1, E. C. Ford 2, G. A. Ezzell 3, A. P. Dicker 4, B. S. Chera 5, and L. Potters 6 1 University of California, San Diego, La Jolla, CA, 2 University of Washington Medical Center, Seattle, WA, 3 Mayo Clinic Arizona, Phoenix, AZ, 4 Sidney Kimmel Medical College at Thomas Jefferson University, Sidney Kimmel Cancer Center, Philadelphia, PA, 5 Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, NC, 6 Department of Radiation Medicine, Northwell Health, Lake Success, NY

5 Study Design / Purpose/Objective(s) The mission of RO-ILS is to facilitate safer and higher quality care in radiation oncology by providing a mechanism for shared learning. It is a voluntary incident learning system sponsored by ASTRO and AAPM. More than 300 facilities participate and more than 3000 cases have been submitted. Incident Learning REPORT ANALYZE MAKE IMPROVMENTS This study: Examine the patterns of errors reported for Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiation Therapy (SBRT) using RO-ILS Lung Example: Conventional (2Gy x 30) vs SBRT (18Gy x 3), i.e. potentially half the targeting margin for error in a tenth of the total delivery sessions SRS/SBRT incidents were compared to non-stereotactic incidents.

6 Results Feb 2014 to Dec 2016: 2681 total incidents submitted 217 (8%) incidents were SRS/SBRT (no distinction) 40% SRS/SBRT RO-ILS Incidents Severity Scores, n=217 38% 35% 30% 25% 20% 15% 10% 5% 18% 24% 16% 4% Common event types: incorrect shift/alignment collisions/clearance incorrect site incorrect contours 0% Severity Scores 1 (Low) (High)

7 Results Near-miss Therapeutic Radiation Incident Unsafe Condition Other Process Operational Improvement SRS/SBRT, n=217 40% 25% 24% 7% 4% Non-SRS/SRT, n= % 34% 28% P-value Radiation incident: Error that reached the patient, and may or may not have caused harm. Differences between stereotactic and non-stereotactic events were statistically significant. Not shown: One third of the stereotactic events involved multiple patients (potential systematic errors). Stereotactic incidents are more likely to be near misses and less likely to reach the patient than conventional incidents

8 Results Dose Deviation (n=217) No deviation 92% Organ at Risk (OAR) 1% <5% of target dose 6% 5-25% of target dose 1% % target dose None >100% of target dose <1% In 92% of reported incidents, the error cause no dose deviation!

9 Authors Conclusions Significant dose deviations are uncommon in RO-ILS despite the complexity and risk of SRS/SBRT SRS/SBRT incidents are less likely to reach the patient than conventional incidents (heightened quality assurance requirements?)

10 Comments PRO: Illustrates the value of the RO-ILS system (Manuscript Common error pathways seen in the RO- ILS data that demonstrate opportunities for improving treatment safety in press in PRO; Demonstrates common error pathways in radiation oncology (most importantly errors defining targets, errors in manual processes, error in chart checks): This analysis of RO-ILS event data underscores the truism that verifying inputs to a process is more effective than testing outputs, especially when the output testing (e.g. plan checking by physics) is unlikely to discover the faulty input (e.g. target definition). CON: Voluntary reporting may cause bias Unclear how this knowledge can be used to improve treatments other than increase awareness

11 Radiogenomic Analysis of a Peritumoral CT Image Feature and Its Prognostic Value in Early Stage NSCLC J. Lee 1, Y. Cui 2, M. F. Gensheimer 3, B. W. Loo Jr 3, M. Diehn 3, and R. Li 4 1 Stanford University, Palo Alto, CA, 2 Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan, 3 Stanford Cancer Institute, Stanford, CA, 4 Stanford University, Stanford, CA

12 Study Design / Purpose/Objective(s) Early-Stage NSCLC Increased prevalence with screening. Excellent local control after surgery or SABR. Distant metastasis remains a major problem (20-30%). Biomarkers are need to inform adjuvant therapy. Typical Prognostic Imaging Biomarkers Tumor size: TNM staging Most radiomic studies focus on gross tumor only Tumor texture and morphology: less established Few look beyond the tumor and invaded surrounding tissue Study aims: Identify patients with high risk of relapse. Determine the prognostic value of pleural contact. Identify the molecular basis of pleural contact.

13 Study Design / Methods Pleural invasion has been shown to correlate with poor prognosis in resected NSCLC Simple attachment to pleura does not necessarily imply invasion. Quantitative PCI: quantify relation of tumor and surrounding pleura based on CT Retrospectively analyzed 7 NSCLC cohorts (n=1069). PCI = pleural contact length Dmax PCI: 0.5 2cm PCI: 1 Stage I only.

14 Study Design / Methods Cohorts 1-2: Discovery cohort (n=117; pre-treatment CT and outcomes available) and external validation cohort (n=88). Cohort 3: Publicly available (n=89) patients with both imaging and gene expression data to identify the molecular basis of PCI and build a gene expression-based surrogate (radiogenomic classifier). Cohorts 4-7: Further tested prognostic relevance using four datasets (n=775) with publically available gene expression data and linked survival information.

15 Overall survival Overall survival Results Cohorts 1-2: PCI was prognostic, while pleural attachment was not. A cutoff of 0.8, PCI stratified patients (when using both internal and external cohorts) PCI was associated with survival beyond age, gender, tumor size, histology. Correlation did hold for small and large tumor volumes Stanford cohort European cohort

16 Results Cohort 3: 89 patients with gene expression (1919 genes correlated with PCI) and CT image data Extracellular matrix (ECM) remodeling was enriched among genes correlated with PCI (false discovery rate (FDR)=0.005) Remodeling of the ECM plays an important role in cancer invasion/metastasis. Cohorts 4-7: 775 patients with gene expression and survival in GEO (gene expression omnibus). The genomic surrogate of PCI: stratified patients for overall survival in all 4 cohorts remained a strong, independent prognostic factor GSE30219

17 Results PCI significantly stratified patients for overall survival in both discovery (log-rank test P = ) and validation (log-rank test P = ) imaging cohorts. PCI stratified patients for distant metastasis in the discovery cohort (log-rank test P = ). PCI was significantly associated with genes related to extracellular matrix organization/disassembly and collagen catabolic process (Spearmen test P < 0.05). This suggests association between PCI and metastasis-prone tumor microenvironment. The radiogenomic classifier stratified patients for overall survival in each of four gene expression cohorts (log-rank test P range: < to 0.019) and remained an independent predictor when adjusting for age, gender, and tumor stage (Wald test P = ).

18 Authors Conclusions Pleural contact index (PCI) can serve as a noninvasive prognostic marker and might be used to guide risk-adapted therapy in early stage NSCLC. Tumors with higher PCI may be driven by ECM remodeling. Prospective studies are needed to confirm these findings. Radiogenomic strategy can be used to identify biological meaningful and clinical relevant imaging biomarkers in other cancer types.

19 Comments PRO: Biomarkers are needed that can reliably predict disease recurrence and more aggressive disease to guide the management of lung cancer considering the toxicities associated with chemotherapy. Association between imaging (PCI) and molecular (ECM) phenotypes. CON: Study shows correlative relations but not causative relations Retrospective study Many published prognostic markers simply correlate with tumor volume (study found moderate correlation between PCI and tumor volume in one cohort) Study has recently been published: Eur Radiol Aug 7

20 Regional dose differences associated with radiation-induced acute severe dysphagia S. Monti 1, G. Palma 2, V. D'Avino 2, M. Gerardi 3, D. Ciardo 3, D. Alterio 3, B. A. Jereczek-Fossa 3,4, M. Quarantelli 2, R. Pacelli 5, and L. Cella 2 1 IRCCS SDN, Napoli, Italy, 2 National Research Council, Institute of Biostructures and Bioimaging, Napoli, Italy, 3 Istituto Europeo di Oncologia, Milano, Italy, 4 Department of Oncology and Hematooncology, University of Milan, Milano, Italy, 5 Federico II University School of Medicine, Department of Advanced Biomedical Sciences, Napoli, Italy

21 Study Design / Purpose/Objective(s) To apply a voxel-based analysis (VBA) to explore correlation between radiation induced acute dysphagia (RIAD) and local dose release in patients treated for head and neck (H&N) tumors. Different dose distributions can have the same DVH! Alpha Bravo VBA permits to overcome the limitations of DVH-based or single organ analysis Definition and contouring of swallowing-related normal tissues can be time consuming and prone to operator variations

22 Study Design / Methods 42 Head & Neck (H&N) patients treated with definitive RT and no previous surgery: 23 3D CRT 19 IMRT Median total prescribed dose of 70 Gy (35 fractions of 2 Gy) 41 patients received concurrent (35/42) or induction (6/42) chemotherapy 9 patients developed a severe (CTCAE v4.0 grade 3) RIAD. None of the clinical variables showed a significant correlation with RIAD.

23 Study Design / Methods Planning CTs are registered to the common coordinate system (CCS) by an elastic image registration (EIR) tool. The obtained deformation fields are used to warp the dose maps into the CCS. A statistical mapping scheme (TFCE) is applied to extract the clusters of voxels (S 0.05 ) significantly associated with higher doses released in patients developing the radiation induced toxicity.

24 Results Dose distributions given to patients who (a) developed RIAD (b) did not developed RIAD The TFCE analysis showed that a significantly higher dose was delivered to RIAD patients in two voxel clusters (c) dose difference map (d) statistical significant dose difference located in the cricopharyngeus muscle and the cervical esophagus. (a) (c) (b) (d)

25 Results Dose differences between groups Overall S 0.05 volume = 5.1 cm 3 ; Mean dose in S 0.05 separates RIAD (median = 48 Gy) non-riad (median = 33 Gy) ROC-AUC = S 0.05

26 Authors Conclusions The work goes beyond the organ-based philosophy in the analysis of radiation induced toxicity in H&N H&N sites are challenging for registration process due to: High mobility of the structures Considerable inter-patient anatomical variability A correlation was found between RIAD and local dose differences in regions that are likely associated with the swallowing function

27 Comments PRO: Voxel based analysis does not require prior knowledge of anatomical regions Correlation between the dose delivered in a specific region of the swallowinginvolved organs and the RIAD onset can be exploited to construct an avoidance criterion in the planning optimization strategy. Data may allow further insight into spatial distribution of radiation sensitivity. CON: Patient variability (results apply to average patient) Small cohort Study has been published: Scientific Reports 7: 7220 (2017)

28 TEŞEKKÜRLER La Jolla/ San Diego