J.M. Wilson

The Application of Functional Imaging Techniques to Personalise Chemoradiotherapy in Upper Gastrointestinal Malignancies

Functional imaging gives information about physiological heterogeneity in tumours. The utility of functional imaging tests in providing predictive and prognostic information after chemoradiotherapy for both oesophageal cancer and pancreatic cancer will be reviewed. The benefit of incorporating functional imaging into radiotherapy planning is also evaluated. In cancers of the upper gastrointestinal tract, the vast majority of functional imaging studies have used 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Few studies in locally advanced pancreatic cancer have investigated the utility of functional imaging in risk-stratifying patients or aiding target volume definition. Certain themes from the oesophageal data emerge, including the need for a multiparametric assessment of functional images and the added value of response assessment rather than relying on single time point measures. The sensitivity and specificity of FDG-PET to predict treatment response and survival are not currently high enough to inform treatment decisions. This suggests that a multimodal, multiparametric approach may be required. FDG-PET improves target volume definition in oesophageal cancer by improving the accuracy of tumour length definition and by improving the nodal staging of patients. The ideal functional imaging test would accurately identify patients who are unlikely to achieve a pathological complete response after chemoradiotherapy and would aid the delineation of a biological target volume that could be used for treatment intensification. The current limitations of published studies prevent integrating imaging-derived parameters into decision making on an individual patient basis. These limitations should inform future trial design in oesophageal and pancreatic cancers.

Correlating Tumour Histology and ex vivo MRI Using Dense Modality-Independent Patch-Based Descriptors

Histological images provide reliable information on tissue characteristics which can be used to validate and improve our understanding for developing radiological imaging analysis methods. However, due to the large amount of deformation in histology stemming from resected tissues, estimating spatial correspondence with other imaging modalities is a challenging image registration problem. In this work we develop a three-stage framework for nonlinear registration between ex vivo MRI and histology of rectal cancer. For this multi-modality image registration task, two similarity metrics from patch-based feature transformations were used: the dense Scale Invariant Feature Transform (dense SIFT) and the Modality Independent Neighbourhood Descriptor (MIND). The potential of our method is demonstrated on a dataset of eight rectal histology images from two patients using annotated landmarks. The mean registration error was 1.80 mm after the rigid registration steps which improved to 1.08 mm after nonlinear motion correction using dense SIFT and to 1.52 mm using MIND.

Challenges in using 18 F-fluorodeoxyglucose-PET-CT to define a biological radiotherapy boost volume in locally advanced pancreatic cancer

BackgroundThe best method of identifying regions within pancreatic tumours that might benefit from an increased radiotherapy dose is not known. We investigated the utility of pre-treatment FDG-PET in predicting the spatial distribution of residual metabolic activity following chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC).Methods17 patients had FDG-PET/CT scans at baseline and six weeks post-CRT. Tumour segmentation was performed at 40% and 50% of SUVmax at baseline and 60%, 70%, 80% and 90% post-CRT. FDG-PET scans were non-rigidly registered to the radiotherapy planning CT using the CT component of the FDG-PET/CT. Percentage overlap of the post-CRT volumes with the pre-CRT volumes with one another and the gross tumour volume (GTV) was calculated.ResultsSUVmax decreased during CRT (median pre- 8.0 and post- 3.6, p < 0.0001). For spatial correlation analysis, 9 pairs of scans were included (Four were excluded following complete metabolic response, one patient had a non-FDG avid tumour, one had no post-CRT imaging, one had diffuse FDG uptake that could not be separated from normal tissues and one had an elevated blood glucose). The Pre40% and 50% of SUVmax volumes covered a mean of 50.8% and 30.3% of the GTV respectively. The mean% overlap of the 90%, 80%, 70%, 60% of SUVmax post-CRT with the Pre40% and Pre50% volumes were 83.3%, 84.0%, 83.7%, 77.9% and 77.8%, 69.9%, 74.5%, 64.8% respectively.ConclusionsRegions of residual metabolic activity following CRT can be predicted from the baseline FDG-PET and could aid definition of a biological target volume for non-uniform dose prescriptions.

Correlation of 18F-Fluorodeoxyglucose Positron Emission Tomography Parameters with Patterns of Disease Progression in Locally Advanced Pancreatic Cancer after Definitive Chemoradiotherapy

Aims A proportion of patients with pancreatic cancer never develop metastatic disease. We evaluated a role for 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in identifying a subset of patients with locally advanced pancreatic cancer (LAPC) who never develop metastatic disease and only experience local disease and may therefore benefit from local treatment intensification. Material and methods Patients with histologically confirmed LAPC entered a single-centre phase II study of definitive upfront chemoradiotherapy (CRT). All patients underwent FDG-PET/CT before and 6 weeks after CRT. Tumour volume, standardised uptake values (SUVmax, SUVpeak, SUVmean, SUVmedian) and total lesion glycolysis (TLG) were measured on each scan and the response in each parameter was evaluated. The presence or absence of metastatic disease was noted on contrast-enhanced CT carried out every 3 months for 1 year and then at clinician discretion. Results Twenty-three patients with LAPC were recruited; 17/23 completed treatment and had interpretable sequential imaging. Twenty-four per cent of patients only ever experienced local disease. Median pre-CRT FDG-PET parameters were significantly lower in patients with local disease only during follow-up compared with those who developed metastatic disease: SUVmax 3.8 versus 8.6 (P = 0.006), SUVpeak 2.5 versus 7.5 (P = 0.002), SUVmean 1.8 versus 3.3 (P = 0.001), SUVmedian 1.7 versus 3.0 (P = 0.002), TLG 26.9 versus 115.9 (P = 0.006). Tumour volume, post-CRT FDG-PET values and their relative change were not statistically different between local disease and metastatic disease groups. Receiver operating characteristic curves for pre-CRT FDG-PET parameters to predict those who never develop metastatic disease all had areas under the curve (AUCs) ≥ 0.932. Pre-CRT FDG-PET SUVmax < 6.2 predicted patients with local disease only during follow-up with 100.0% sensitivity and 92.3% specificity, 80.0% positive predictive value and 100% negative predictive value. Conclusions Our findings suggest that patients with less FDG-avid tumours are less likely to metastasise and may therefore benefit from upfront local treatment intensification.

WE-AB-202-10: Modelling Individual Tumor-Specific Control Probability for Hypoxia in Rectal Cancer

PURPOSE To investigate hypoxia-guided dose-boosting for increased tumour control and improved normal tissue sparing using FMISO-PET images METHODS: Individual tumor-specific control probability (iTSCP) was calculated using a modified linear-quadratic model with rectal-specific radiosensitivity parameters for three limiting-case assumptions of the hypoxia / FMISO uptake relationship. 18 FMISO-PET images from 2 patients (T3N0M0) from the RHYTHM trial (Investigating Hypoxia in Rectal Tumours NCT02157246) were chosen to delineate a hypoxic region (GTV_MISO defined as tumor-to-muscle ratio > 1.3) within the anatomical GTV. Three VMAT treatment plans were created in Eclipse (Varian): STANDARD (45Gy / 25 fractions to PTV4500); BOOST_GTV (simultaneous integrated boost of 60Gy / 25fr to GTV +0.5cm) and BOOST_MISO (60Gy / 25fr to GTV_MISO+0.5cm). GTV mean dose (in EQD2), iTSCP and normal tissue dose-volume metrics (small bowel, bladder, anus, and femoral heads) were recorded. RESULTS Patient A showed small hypoxic volume (15.8% of GTV) and Patient B moderate hypoxic volume (40.2% of GTV). Dose escalation to 60Gy was achievable, and doses to femoral heads and small bowel in BOOST plans were comparable to STANDARD plans. For patient A, a reduced maximum bladder dose was observed in BOOST_MISO compared to BOOST_GTV (D0.1cc 49.2Gy vs 54.0Gy). For patient B, a smaller high dose volume was observed for the anus region in BOOST_MISO compared to BOOST_GTV (V55Gy 19.9% vs 100%), which could potentially reduce symptoms of fecal incontinence. For BOOST_MISO, the largest iTSCPs (A: 95.5% / B: 90.0%) assumed local correlation between FMISO uptake and hypoxia, and approached iTSCP values seen for BOOST_GTV (A: 96.1% / B: 90.5%). CONCLUSION Hypoxia-guided dose-boosting is predicted to improve local control in rectal tumors when FMISO is spatially correlated to hypoxia, and to reduce dose to organs-at-risk compared to boosting the whole GTV. This could lead to organ-preserving treatment strategies for locally-advanced rectal cancer, thereby improving quality of life. Oxford Cancer Imaging Centre (OCIC); Cancer Research UK (CRUK); Medical Research Council (MRC).