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Chapter 2 discusses how imaging is fundamentally important to the management of the cancer patient, how anatomical imaging is the mainstay for patient evaluation, and how functional and hybrid (combined functional–anatomical) imaging have acquired an increasing role. Additionally, it offers guidance on obtaining the most accurate and reliable information possible with the most appropriate imaging modality and why the relative performance of the imaging test has to be defined. Staging and prognosis is discussed, as well as therapeutic uses and image-guided radiotherapy. The chapter concludes by looking at how imaging is used in response assessment and future directions in imaging.

A feasibility study was performed to determine if CT-based radiomics could play an augmentative role in predicting neoadjuvant rectal score (NAR), locoregional failure free survival (LRFFS), distant metastasis free survival (DMFS), disease free survival (DFS) and overall survival (OS) in locally advanced rectal cancer (LARC). The NAR score, which takes into account the pathological tumour and nodal stage as well as clinical tumour stage, is a validated surrogate endpoint used for early determination of treatment response whereby a low NAR score ( 16) has been correlated with poorer outcomes. CT images of 191 patients with LARC were used in this study. Primary tumour (GTV) and mesorectum (CTV) were contoured separately and radiomics features were extracted from both segments. Two NAR models (NAR > 16 and NAR 16 and NAR 16 and NAR

Background A positive circumferential resection margin (CRM) has been associated with higher rates of locoregional recurrence and worse survival in oesophageal cancer. The aim of this study was to establish if clinicopathological and radiological variables might predict CRM positivity in patients who received neoadjuvant chemotherapy before surgery for oesophageal adenocarcinoma. Methods Multivariable analysis of clinicopathological and CT imaging characteristics considered potentially predictive of CRM was performed at initial staging and following neoadjuvant chemotherapy. Prediction models were constructed. The area under the curve (AUC) with 95% confidence intervals (c.i.) from 1000 bootstrapping was assessed. Results A total of 223 patients were included in the study. Poor differentiation (odds ratio (OR) 2·84, 95 per cent c.i. 1·39 to 6·01) and advanced clinical tumour status (T3–4) (OR 2·93, 1·03 to 9·48) were independently associated with an increased CRM risk at diagnosis. CT‐assessed lack of response (stable or progressive disease) following chemotherapy independently corresponded with an increased risk of CRM positivity (OR 3·38, 1·43 to 8·50). Additional CT evidence of local invasion and higher CT tumour volume (14 cm3) improved the performance of a prediction model, including all the above parameters, with an AUC (c‐index) of 0·76 (0·67 to 0·83). Variables associated with significantly higher rates of locoregional recurrence were pN status (P = 0·020), lymphovascular invasion (P = 0·007) and poor response to chemotherapy (Mandard score 4–5) (P = 0·006). CRM positivity was associated with a higher locoregional recurrence rate, but this was not statistically significant (P = 0·092). Conclusion The presence of advanced cT status, poor tumour differentiation, and CT‐assessed lack of response to chemotherapy, higher tumour volume and local invasion can be used to identify patients at risk of a positive CRM following neoadjuvant chemotherapy., A positive circumferential resection margin (CRM) has been shown to be an adverse prognostic indicator after oesophagectomy for adenocarcinoma. Clinical tumour status, tumour volume, poor differentiation, lack of response following chemotherapy and radiological assessment of invasion can be used to predict CRM positivity in oesophageal adenocarcinoma. CRM assessment is still important

Objective: Chemoradiation (CRT) may induce a change in systemic inflammatory state which could affect clinical outcomes in oesophageal cancer. We aimed to evaluate the changes and prognostic significance of systemic inflammatory markers following definitive CRT in oesophageal squamous cell carcinoma. Methods: A total of 53 patients treated with concurrent CRT were included in this retrospective analysis. We compared neutrophils, lymphocytes, platelets, neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) before and after CRT using Wilcoxon signed-rank test. Overall survival (OS) and progression-free survival (PFS) were calculated. Univariable and multivariable survival analysis were performed using Cox regression analysis. Clinical univariable survival prognostic factors with p < 0.1 were included in a multivariable cox regression analysis for backward stepwise model selection. Results: Both NLR (median ∆+2.8 [IQR −0.11, 8.62], p < 001) and PLR (median ∆+227 [81.3–523.5], p < 0.001) increased significantly after CRT. Higher levels of pre-CRT, post-CRT and change (∆) in NLR and PLR were associated with inferior OS and PFS. Post-CRT NLR (HR 1.04, 95% CI 1.02–1.07, p < 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.005), cT-stage (HR 3.83, 95% CI 1.39–10.60, p = 0.01) and RT dose (HR 0.41, 95% CI 0.21–0.81, p = 0.01) were independent prognostic factors for OS in multivariable analysis. Change in NLR (HR 1.04, 95% CI 1.01–1.06, p = 0.001), post-CRT platelets (HR 1.03, 95% CI 1.01–1.05, p = 0.002), cT-stage (HR 3.98, 95% CI 1.55–10.25, p = 0.004) and RT dose (HR 0.41, 95% CI 0.21–0.80, p = 0.009) were independent prognostic factors for PFS. Conclusion: Both NLR and PLR increased following definitive CRT. Post-CRT NLR and ∆NLR were associated with adverse survival in oesophageal SCC. Advances in knowledge: We showed that CRT increased PLR and NLR, possibly reflecting a systemic inflammatory state which were associated with poor clinical outcomes in oesophageal SCC.

The aim of this retrospective national cohort study is to assess the association between various radiation heart dosimetric parameters (RHDPs), acute myocardial infarct (AMI) and overall survival (OS) outcomes in non-small cell lung cancer (NSCLC) patients treated with post-operative thoracic radiotherapy (PORT) using contemporary radiation techniques. We identified patients with stage I to III NSCLC treated with PORT at the 2 national cancer institutions from 2007 to 2014. We linked their electronic medical records to the national AMI and death registries. Univariable Cox regression was performed to assess the association between various RHDPs, AMI, and OS. We included 43 eligible patients with median follow-up of 36.6 months. Median age was 64 years. Majority of the patients had pathological stage III disease (72%). Median prescription dose was 60Gy. Median mean heart dose (MHD) was 9.4Gy. There were no AMI events. The 5-year OS was 34%. Univariable Cox regression showed that age was significantly associated with OS (hazard ratio, 1.06; 95% confidence interval, 1.01 to 1.10; P = .008). Radiation heart doses, including MHD, volume of heart receiving at least 5, 25, 30, 40, 50Gy and dose to 30% of heart volume, were not significantly associated with OS. There is insufficient evidence to conclude that RHDPs are associated with OS for patients with NSCLC treated with PORT in this study. Studies with larger sample size and longer term follow-up are needed to assess AMI outcome.

18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) is established for characterising indeterminate pulmonary nodules and staging lung cancer where there is curative intent. Whilst a sensitive technique, specificity for characterising lung cancer is limited. There is recognition that evaluation of other aspects of abnormal cancer biology in addition to glucose metabolism may be more helpful in characterising tumours and predicting response to novel targeted cancer therapeutics. Therefore, efforts have been made to develop and evaluate new radiopharmaceuticals in order to improve the sensitivity and specificity of PET imaging in lung cancer with regards to characterisation, treatment stratification and therapeutic monitoring. 18F-fluorothymidine (18F-FLT) is a marker of cellular proliferation. It shows a lower accumulation in tumours than 18F-FDG as it only accumulates in the cells that are in the S phase of growth and demonstrates a low sensitivity for nodal staging. Its main role is in evaluating treatment response. Methionine is an essential amino acid. 11C-methionine is more specific and sensitive than 18F-FDG in differentiating benign and malignant thoracic nodules. 18Ffluoromisonidazole (18F-FMISO) is used for imaging tumour hypoxia. Tumour response to treatment is significantly related to the level of tumour oxygenation. Angiogenesis is the process by which new blood vessels are formed in tumours and is involved in tumour growth and metastatic tumour spread and is a therapeutic target. Most clinical studies have focused on targeted integrin PET imaging of which αvβ3 integrin is the most extensively investigated. It is upregulated on activated endothelial cells in association with tumour angiogenesis. Neuroendocrine tumour tracers, particularly 68Ga-DOTA-peptides, have an established role in imaging of carcinoid tumours. Whilst most of these tracers have predominantly been used in the research environment, they offer exciting opportunities for improving staging, characterisation, stratification and response assessment in an era of increased personalised therapy in lung cancer.

Background We compared the prognostic impact of various systemic inflammatory markers in oesophageal cancer. Methods We retrospectively evaluated 77 patients treated with CRT for oesophageal cancer in a tertiary institution between 2006-2015. Baseline and post-CRT inflammatory parameters including haemoglobin, neutrophil, lymphocyte, platelet and albumin levels were recorded. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were derived. Primary end-point was overall survival (OS). Pre- and post-CRT values were compared using Wilcoxon Sign-Rank test. The prognostic ability of these parameters were evaluated using Cox regression analysis. Medians (IQRs) were presented. Bonferroni correction was applied; p Results Haemoglobin (-2 (-2.8,-0.8), p Conclusions NLR and PLR may be more sensitive markers of systemic inflammatory milieu compared to individual serum indices which were all suppressed after CRT in oesophageal cancer. Systemic inflammatory status after CRT indicated by raised NLR/PLR is a negative prognostic factor and could be an adjunctive clinical risk stratification tool for adjuvant therapy in the future.

Purpose We aimed to assess computed tomography (CT) intratumoral heterogeneity changes, and compared the prognostic ability of the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, an alternate response method (Crabb), and CT heterogeneity in non-small cell lung cancer treated with chemotherapy with and without bevacizumab. Materials and methods Forty patients treated with chemotherapy (group C) or chemotherapy and bevacizumab (group BC) underwent contrast-enhanced CT at baseline and after 1, 3, and 6 cycles of chemotherapy. Radiologic response was assessed using RECIST 1.1 and an alternate method. CT heterogeneity analysis generating global and locoregional parameters depicting tumor image spatial intensity characteristics was performed. Heterogeneity parameters between the 2 groups were compared using the Mann-Whitney U test. Associations between heterogeneity parameters and radiologic response with overall survival were assessed using Cox regression. Results Global and locoregional heterogeneity parameters changed with treatment, with increased tumor heterogeneity in group BC. Entropy [group C: median -0.2% (interquartile range -2.2, 1.7) vs. group BC: 0.7% (-0.7, 3.5), P=0.10] and busyness [-27.7% (-62.2, -5.0) vs. -11.5% (-29.1, 92.4), P=0.10] showed a greater reduction in group C, whereas uniformity [1.9% (-8.0, 9.8) vs. -5.0% (-13.9, 5.6), P=0.10] showed a relative increase after 1 cycle but did not reach statistical significance. Two (9%) and 1 (6%) additional responders were identified using the alternate method compared with RECIST in group C and group BC, respectively. Heterogeneity parameters were not significant prognostic factors. Conclusions The alternate response method described by Crabb identified more responders compared with RECIST. However, both criteria and baseline imaging heterogeneity parameters were not prognostic of survival.

In recent years, there has been increasing interest in the influence of body composition on oncological patient outcomes. Visceral obesity, sarcopenia and sarcopenic obesity have been identified as adverse factors in cancer patients. Imaging quantification of body composition such as lean muscle mass and fat distribution is a potentially valuable tool. This review describes the following imaging techniques that may be used to assess body composition: dual-energy X-ray absorptiometry (DXA), computed tomography (CT) and magnetic resonance imaging (MRI). CT and MRI are acquired as part of oncological patient care, thus providing an opportunity to integrate body composition assessment into the standard clinical pathway and allowing supportive care to be commenced as appropriate to improve outcome. • Sarcopenia, sarcopenic obesity and visceral obesity are adverse prognostic factors in cancer patients. • CT and MRI are the current gold standard in body composition evaluation. • Body composition may affect chemotherapy tolerance and toxicities.

Stereotactic body radiotherapy (SBRT) is increasingly used in the management of unresectable liver metastases and hepatocellular carcinoma (HCC) as it allows delivery of high-dose conformal radiotherapy with limited toxicities. However, it may be difficult to differentiate viable tumour from radiotherapy-related changes after SBRT. The imaging changes observed after SBRT may also differ from those observed following conventionally fractionated radiotherapy. Hence, we aim to review the imaging changes that occur within the tumour and adjacent normal liver after SBRT which may help to identify local relapse in clinical practice.

Introduction: Most international clinical practice guidelines for prostate cancer (PCa) are driven by data derived in a Western setting. However, tumour biology and clinical disease progression are likely to differ in the Asian population. We compare the performance of the revised American Joint Committee on Cancer (AJCC) prognostic groups with the commonly used D’Amico Risk Classification and conventional predictors for PCa, in a large cohort of Asian patients. Materials and Methods: We retrospectively reviewed data for 404 consecutive Singaporean patients receiving definitive radiotherapy at our centre between December 1996 and October 2006. The primary outcome was biochemical relapse-free survival (BRFS), defined using the Phoenix definition. The secondary outcome was overall survival (OS). Prognostic risk groups were defined using AJCC 7th edition (AJCC7) and 6th edition (AJCC6). Univariate analysis (UVA) and multivariate analysis (MVA) were performed for the following putative risk factors: age, Gleason score, prognostic grouping, tumour classification, radiation delivery technique, radiotherapy dose, hormonal therapy and initial PSA value. Results: For the cohort, median age was 69 years. Median follow-up was 66.3 months. Five-year BRFS rate was 84.3% with 71 biochemical relapses and 5-year OS rate was 89.1% with 54 deaths. The concordance-indices for BRFS prediction were 0.588, 0.550 and 0.567 for AJCC7, AJCC6 and D’Amico respectively. Initial PSA, T-stage and AJCC7 were prognostic for BRFS on UVA. Comparison of AJCC7 vs. D’Amico showed no statistical additional value of either classification system although D’Amico was superior when compared to AJCC6 in predicting BRFS. T-stage ≥3 and D’Amico were significant prognostic factors for BRFS on MVA. Conclusion: In our local, predominantly Chinese population, neither AJCC6 nor AJCC7 demonstrated a high predictive accuracy for BRFS although AJCC7 has a slightly better predictive ability than AJCC6. Key words: D'amico, Intensity modulated radiotherapy, Prognosis, Risk stratification

Radiomics is an evolving field in which the extraction of large amounts of features from diagnostic medical images may be used to predict underlying molecular and genetic characteristics, thereby improving treatment response prediction and prognostication and potentially allowing personalisation of cancer treatment. There is increasing interest in extracting additional data from PET images, particularly novel features that describe the heterogeneity of voxel intensities, but a number of potential limitations need to be recognised and overcome. Nevertheless, some early data suggest that extraction of additional quantitative data may offer further predictive and prognostic information in individual patients.

To assess the changes in computed tomography (CT) tumor heterogeneity following neoadjuvant chemotherapy in esophageal cancer. Thirty-one consecutive patients who received neoadjuvant chemotherapy for esophageal cancer were identified. Analysis of primary tumor heterogeneity (texture) was performed on staging and post-chemotherapy CT scans. Image texture parameters (mean grey-level intensity, entropy, uniformity, kurtosis, skewness, standard deviation of histogram) were derived for different levels of image filtration (0-2.5). Proportional changes in each parameter following treatment were obtained. Comparison between pathological tumor response and texture parameters was analyzed using Mann-Whitney U-test. The relationship between CT texture and overall survival) was estimated using the Kaplan-Meier method. Tumor texture became more homogeneous after treatment with a significant decrease in entropy and increase in uniformity (filter 1.0 and 2.5). Pretreatment (filter 1.5, P = 0.006) and posttreatment standard deviation of histogram (filter 1.0, P = 0.009) showed a borderline association with pathological tumor response. A proportional change in skewness

To determine the association between tumor heterogeneity, morphologic tumor response, and overall survival in primary esophageal cancer treated with chemotherapy and radiation therapy (CRT).After an institutional review board waiver was obtained, contrast material-enhanced computed tomographic (CT) studies in 36 patients with stage T2 or greater esophageal tumors who underwent contrast-enhanced CT before and after CRT between 2005 and 2008 were analyzed in terms of whole-tumor texture, with quantification of entropy, uniformity, mean gray-level intensity, kurtosis, standard deviation of the histogram, and skewness for fine to coarse textures (filters 1.0-2.5, respectively). The association between texture parameters and survival time was assessed by using Kaplan-Meier analysis and a Cox proportional hazards model. Survival models involving texture parameters and combinations of texture and morphologic response assessment were compared with morphologic assessment alone by means of receiver operating characteristic (ROC) analysis.Posttreatment medium entropy of less than 7.356 (median overall survival, 33.2 vs 11.7 months; P = .0002), coarse entropy of less than 7.116 (median overall survival, 33.2 vs 11.7 months; P = .0002), and medium uniformity of 0.007 or greater (median overall survival, 33.2 vs 11.7 months; P = .0002) were associated with improved survival time. These remained significant prognostic factors after adjustment for stage and age: entropy (filter 2.0: hazard ratio [HR] = 5.038, P = .0004; filter 2.5: HR = 5.038, P = .0004) and uniformity (HR = 0.199, P = .0004). Survival models that included a combination of pretreatment entropy and uniformity with maximal wall thickness assessment, respectively, performed better than morphologic assessment alone (area under the ROC curve, 0.767 vs 0.487 [P = .00005] and 0.802 vs 0.487 [P = .0003]).Posttreatment texture parameters are associated with survival time, and the combination of pretreatment texture parameters and maximal wall thickness performed better in survival models than morphologic tumor response alone.

Background The optimal sequence for primary-directed palliative radiotherapy in esophageal cancer is unknown. As the survival outcomes of these patients are poor, it is important to balance survival benefits from systemic chemotherapy against the benefits of primary-directed radiotherapy. Methods We have retrospectively reviewed esophageal cancer patients who received palliative radiotherapy to the primary lesion and grouped them according to the sequence of treatment: chemotherapy followed by radiotherapy (C-RT), radiotherapy followed by chemotherapy (RT-C), or radiotherapy alone (RTa). We are interested in overall survival and the time spent on radiotherapy as a percentage of the time between start of radiotherapy to death (T-SPORT). Results 92 patients receiving primary-directed radiotherapy were included in the study. Median overall survival in the C-RT and RT-C groups were 1.14 (0.82-1.72) and 0.95 (0.56-1.36) months respectively, which were significantly longer than the RTa group of 0.50 (0.38-0.74). On multivariate analysis, the groups receiving chemotherapy have similar hazard ratios when compared to RT alone (C-RT: HR 0.50 (0.30-0.84), p = 0.008; RT-C: 0.51 (0.28 - 0.93), p = 0.03). Median T-SPORT was 10.04% in C-RT group, similar to RTa group of 12.39%, whilst the RT-C group had the lowest value of 4.47%. Conclusion We demonstrate that systemic chemotherapy has survival benefit regardless of sequence in the palliative management of esophageal cancer. Patients having primary-directed palliative radiotherapy before chemotherapy do not have worse overall survival. By having radiotherapy early, these patients spend a lower portion of remaining lifespan receiving radiotherapy, with subsequent more time to experience the benefits of treatment.

We investigated the implications of HER2 amplification in Asian women with small, node-negative breast cancer in low- and middle-income countries (LMCs). We reviewed the charts patients treated between 1989 and 2009 with breast conservation therapy for node-negative breast cancers measuring ≤2 cm. Disease-free survival (DFS), ipsilateral breast tumor recurrence (IBTR), distant disease-free survival (DDFS), and overall survival (OS) rates were estimated using the Kaplan–Meier method and were compared by the log-rank test. Potential covariates—age, tumor grade, hormone receptor status—were analyzed by multivariate analysis. A total of 519 patients were studied including 204 (39%) and 315 (61%) patients diagnosed with pT1ab and pT1c tumors, respectively. Median follow-up was 57 months. HER2 amplification was found in 17.1% of all patients and in 16.7% patients with pT1ab tumors. Among patients with T1ab tumors, 73.0 and 9.3% underwent adjuvant hormonal and chemotherapy, respectively; 3 of 34 T1ab patients with HER2-amplified tumors received trastuzumab. HER2 amplification was associated with poorer 5-year DFS (83.7% vs. 95.5%, P

Purpose To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation (CCRT), against CCRT alone. Patients and Methods Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m 2 , carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m 2 given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m 2 ), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5% significance level and 80% power. Results Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P =.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P =.362), and distant metastases–free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P =.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms. Conclusion Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.

Lung cancer is the leading cause of cancer death in the United States. It is estimated that more than 228,000 new cases will be diagnosed in 2013, accounting for approximately 159,000 or 27% of all cancer deaths. Survival in these patients remains poor despite advances in surgery, definitive radiotherapy, and chemotherapy for primary and metastatic non-small cell lung cancer. Five-year relative survival rates remain at 27% for regional disease and 54% for node-negative disease. With the increasing personalization of therapy, there remains a need for better prognostic and predictive markers to direct patient management in lung cancer. Hypoxia and angiogenesis play an important role in the development and progression of lung cancer. Targeted and non-targeted imaging techniques in the preclinical and clinical setting, combined with advanced postprocessing techniques to assess tumor heterogeneity, may enable clinicians to better characterize lung tumors, and to predict and assess response to treatment. In this review, we summarize our current understanding of angiogenesis in lung cancer and discuss the available imaging techniques to assess this in the preclinical and clinical setting.

Sarcopenia and changes in body composition following neoadjuvant chemotherapy (NAC) may affect clinical outcome. We assessed the associations between CT body composition changes following NAC and outcomes in oesophageal cancer.A total of 35 patients who received NAC followed by oesophagectomy, and underwent CT assessment pre- and post-NAC were included. Fat mass (FM), fat-free mass (FFM), subcutaneous fat to muscle ratio (FMR) and visceral to subcutaneous adipose tissue ratio (VA/SA) were derived from CT. Changes in FM, FFM, FMR, VA/SA and sarcopenia were correlated to chemotherapy dose reductions, postoperative complications, length of hospital stay (LOS), circumferential resection margin (CRM), pathological chemotherapy response, disease-free survival (DFS) and overall survival (OS).Nine (26 %) patients were sarcopenic before NAC and this increased to 15 (43 %) after NAC. Average weight loss was 3.7 % ± 6.4 (SD) in comparison to FM index (-1.2 ± 4.2), FFM index (-4.6 ± 6.8), FMR (-1.2 ± 24.3) and VA/SA (-62.3 ± 12.7). Changes in FM index (p = 0.022), FMR (p = 0.028), VA/SA (p = 0.024) and weight (p = 0.007) were significant univariable factors for CRM status. There was no significant association between changes in body composition and survival.Loss of FM, differential loss of VA/SA and skeletal muscle were associated with risk of CRM positivity.• Changes in CT body composition occur after neoadjuvant chemotherapy in oesophageal cancer. • Sarcopenia was more prevalent after neoadjuvant chemotherapy. • Fat mass, fat-free mass and weight decreased after neoadjuvant chemotherapy. • Changes in body composition were associated with CRM positivity. • Changes in body composition did not affect perioperative complications and survival.

A method is presented to build a surrogate-driven motion model of a lung tumour from a cone-beam CT scan, which does not require markers. By monitoring an external surrogate in real time, it is envisaged that the motion model be used to drive gated or tracked treatments. The motion model would be built immediately before each fraction of treatment and can account for inter-fraction variation. The method could also provide a better assessment of tumour shape and motion prior to delivery of each fraction of stereotactic ablative radiotherapy. The two-step method involves enhancing the tumour region in the projections, and then fitting the surrogate-driven motion model. On simulated data, the mean absolute error was reduced to 1 mm. For patient data, errors were determined by comparing estimated and clinically identified tumour positions in the projections, scaled to mm at the isocentre. Averaged over all used scans, the mean absolute error was under 2.5 mm in superior-inferior and transverse directions.

There is evidence in some solid tumors that textural features of tumoral uptake in (18)F-FDG PET images are associated with response to chemoradiotherapy and survival. We have investigated whether a similar relationship exists in non-small cell lung cancer (NSCLC). Methods Fifty-three patients (mean age, 65.8 y; 31 men, 22 women) with NSCLC treated with chemoradiotherapy underwent pretreatment (18)F-FDG PET/CT scans. Response was assessed by CT Response Evaluation Criteria in Solid Tumors (RECIST) at 12 wk. Overall survival (OS), progression-free survival (PFS), and local PFS (LPFS) were recorded. Primary tumor texture was measured by the parameters coarseness, contrast, busyness, and complexity. The following parameters were also derived from the PET data: primary tumor standardized uptake values (SUVs) (mean SUV, maximum SUV, and peak SUV), metabolic tumor volume, and total lesion glycolysis. Results Compared with nonresponders, RECIST responders showed lower coarseness (mean, 0.012 vs. 0.027; P = 0.004) and higher contrast (mean, 0.11 vs. 0.044; P = 0.002) and busyness (mean, 0.76 vs. 0.37; P = 0.027). Neither complexity nor any of the SUV parameters predicted RECIST response. By Kaplan-Meier analysis, OS, PFS, and LPFS were lower in patients with high primary tumor coarseness (median, 21.1 mo vs. not reached, P = 0.003; 12.6 vs. 25.8 mo, P = 0.002; and 12.9 vs. 20.5 mo, P = 0.016, respectively). Tumor coarseness was an independent predictor of OS on multivariable analysis. Contrast and busyness did not show significant associations with OS (P = 0.075 and 0.059, respectively), but PFS and LPFS were longer in patients with high levels of each (for contrast: median of 20.5 vs. 12.6 mo, P = 0.015, and median not reached vs. 24 mo, P = 0.02; and for busyness: median of 20.5 vs. 12.6 mo, P = 0.01, and median not reached vs. 24 mo, P = 0.006). Neither complexity nor any of the SUV parameters showed significant associations with the survival parameters. Conclusion In NSCLC, baseline (18)F-FDG PET scan uptake showing abnormal texture as measured by coarseness, contrast, and busyness is associated with nonresponse to chemoradiotherapy by RECIST and with poorer prognosis. Measurement of tumor metabolic heterogeneity with these parameters may provide indices that can be used to stratify patients in clinical trials for lung cancer chemoradiotherapy.

Locally advanced nasopharyngeal carcinoma (NPC) is still associated with significant locoregional failure and poor overall survival (OS) after chemoradiation. The maximal therapeutic effect of conventional chemotherapy combined with radiation may have been reached and there is a clinical need to identify additional adverse prognostic factors that could be targeted therapeutically. Hypoxia, a known prognostic factor in head and neck cancers is an attractive target in NPC with various treatment strategies available such as hypoxic cell sensitisers/cytotoxins and increasing intratumoral oxygen delivery, to overcome the poorer outcomes associated with this phenotype. Thus, we aim to review the clinical significance of hypoxia as well as the current and future of molecular hypoxia imaging in NPC.

42 Background: Trastuzumab (T) is the standard of care in advanced HER2+ gastroesophageal (GE) adenocarcinoma with response in 47% of patients. We evaluated its pathological effects in a HER2+ OE19 xenograft model aiming to improve future treatment intensification/response assessment. Methods: SCID mice (n = 23) bearing subcutaneous OE19 tumors were treated with intraperitoneal saline (control), Cisplatin 4mg/kg once a week (C), Trastuzumab 20mg/kg twice a week (T) or Cisplatin and Trastuzumab (CT) for 2 weeks. Volumetric tumor response was measured by MRI. Excised tumors were stained for IHC markers of hypoxia (Pimonidazole), proliferation (Ki-67) and angiogenesis (CD34). Hypoxic (HF) and proliferative fractions (PF) were defined as the ratios of tumor area positively stained for Pimonidazole/Ki-67 to area of whole tumor section. Microvessel density (MVD) was defined as the average number of blood vessels/endothelial cells identified within 0.01cm2field at x100 magnification. Pathological assessment was performed for whole tumor, centre and rim. Mean±SD are presented. Kruskal-Wallis test was used to compare HF, PR, MVD and volumetric change between groups; significance at < 0.05. Results: Tumor growth was reduced in CT (+83% from baseline MRI) compared to control (+600%), C (+275%) and T (+129%) groups (p= 0.015). Monotherapy treated tumors had lower HF (C 0.08±0.03, T 0.09±0.07) compared to CT (0.16±0.06) and control (0.15±0.04) (p= 0.039). T and CT treated animals had higher MVD (T 23.5±12.7, CT 37.3±10.3) compared to control (18.1±10.4) and C (18.1±7.5) (p= 0.014). Whole tumor PF was lower in the monotherapy groups but this was not significant (p =0.123). PF and MVD were higher in tumor centre compared to rim in T and CT groups compared to control but there was no spatial difference in hypoxia distribution. Conclusions: Tumor control was improved with combination treatment but no synergistic pathological effect was seen; CT treated tumors were more hypoxic/angiogenic compared to monotherapy with greater cellular density/angiogenesis within tumor centre. This could be due to predominant early cytostatic effect and ongoing angiogenic normalisation with CT therapy at 2 weeks.

e15108 Background: Standard CT imaging is limited for determining neoadjuvant treatment response in esophageal cancer but there is increasing interest in assessing multiparametric MRI (mpMRI) in th...

e19124 Background: Imaging heterogeneity may reflect biological heterogeneity. Changes in tumoral heterogeneity in NSCLC treated with chemotherapy ± bevacizumab in a prospective study, and their as...

We propose a method to build a fully deformable motion model directly from cone-beam CT (CBCT) projections. This allows inter-fraction variations in the respiratory motion to be accounted for. It is envisaged that the model be used to track the tumour, and monitor organs at risk (OAR), during gated or tracked radiotherapy (RT) treatment of lung cancer. The method is tested on CBCT projections from a simulated phantom in two cases. The simulations are generated from a patient respiratory trace and associated CBCT scanner geometry. Without and with motion correction, l2 norm maximum errors were reduced from 24.5 to 0.698 mm in case 1, and 20.0 to 0.101 mm in case 2, respectively.

To investigate if cone beam CT (CBCT) can be used to estimate the delivered dose in head and neck intensity-modulated radiotherapy (IMRT).15 patients (10 without replan and 5 with replan) were identified retrospectively. Weekly CBCT was co-registered with original planning CT. Original high-dose clinical target volume (CTV1), low-dose CTV (CTV2), brainstem, spinal cord, parotids and external body contours were copied to each CBCT and modified to account for anatomical changes. Corresponding planning target volumes (PTVs) and planning organ-at-risk volumes were created. The original plan was applied and calculated using modified per-treatment volumes on the original CT. Percentage volumetric, cumulative (planned dose delivered prior to CBCT + adaptive dose delivered after CBCT) and actual delivered (summation of weekly adaptive doses) dosimetric differences between each per-treatment and original plan were calculated.There was greater volumetric change in the parotids with an average weekly difference of between -4.1% and -27.0% compared with the CTVs/PTVs (-1.8% to -5.0%). The average weekly cumulative dosimetric differences were as follows: CTV/PTV (range, -3.0% to 2.2%), ipsilateral parotid volume receiving ≥26 Gy (V26) (range, 0.5-3.2%) and contralateral V26 (range, 1.9-6.3%). In patients who required replan, the average volumetric reductions were greater: CTV1 (-2.5%), CTV2 (-6.9%), PTV1 (-4.7%), PTV2 (-11.5%), ipsilateral (-10.4%) and contralateral parotids (-12.1%), but did not result in significant dosimetric changes.The dosimetric changes during head and neck simultaneous integrated boost IMRT do not necessitate adaptive radiotherapy in most patients.Our study shows that CBCT could be used for dose estimation during head and neck IMRT.

Introduction Accurate delivery of radiotherapy in head and neck (HNN) cancers is often complicated by anatomical changes which could be detected by serial cone-beam CTs (CBCT). We hypothesized that CBCT could be used to estimate the actual dose delivered instead of regular planning scans as part of our adaptive planning strategy. Material and methods Ten consecutive HNN patients who were treated with definitive simultaneous integrated boost Intensity-Modulated Radiotherapy (SIB-IMRT) up to a dose of 65–70 Gy in 30–35 fractions between February and August 2012 were identified retrospectively. Weekly CBCT corresponding to median doses of 2.17 Gy, 13.00 Gy, 23.84 Gy, 34.67 Gy, 45.51 Gy and 56.34 Gy were rigidly co-registered with pre-treatment CT. Pre-treatment high-dose CTV (CTV1), low-dose CTV (CTV2) and OARs were copied to each weekly CBCT and modified according to the anatomical changes by a single oncologist (C.Y). CTVs were expanded by 4 mm to form PTVs. The original plan was applied and calculated using the modified weekly volumes on the pre-treatment CT using the Monaco® treatment planning system. Mean percentage volumetric and dosimetric differences between each weekly modified plan and pre-treatment plan were calculated. Results PTV1 and PTV2 were smaller towards the end of radiotherapy (mean volumetric differences: −4.9% and −2.8% respectively). However, the weekly dosimetric changes (D98, D95, D50, D2) of PTV1 and PTV2 were negligible and clinically insignificant (PTV1: −1.04% to +2.25% and PTV2: −3.83% to +0.83%). The mean differences in brainstem and spinal cord Dmax varied between −4.71% to −0.52% and −5.11% to −1.52% respectively. Parotid volumes decreased during radiotherapy: ipsilateral reduction 3.66–15.40% and contralateral reduction 4.76–16.38%. Parotid V26 was higher than planned throughout treatment (ipsilateral 0.05–2.57%; contralateral 1.44–9.61%). Conclusions The dosimetric changes that occur during HNN SIB-IMRT do not necessitate ART in our cohort of patients. Serial CBCTs could be used to evaluate progressive dosimetric changes during HNN IMRT for adaptive radiotherapy.

respiratory gating, but controversy exists regarding the technique. One is regarding the reproducibility of breathing and another is regarding the correlation between the surrogate and tumor motion. Some studies suggested audio instructions could partly solve these problems. The purpose of this study was to evaluate respiratory-gated SBRT using audio coaching. Materials/Methods: CT images for treatment planning were obtained using 4D-CT under audio instruction. Images were reconstructed into 10 phases of the respiratory cycle (0-90%). When the target motion was greater than 1 cm in the craniocaudal (CC) direction, the respiratorygating method was applied. Clinical target volumes around end-expiration were merged individually to form the internal target volume (ITV). The planning target volume (PTV) margin was 5 mm. Patient set-up was verified using cone-beam CT. Tumor motion was checked by fluoroscopy of an on-board imager system before every treatment. When a phase shift between the tumor motion and the duty cycle occurred, the thresholds for gating were modified. Electronic portal images were used to verify the tumor position during SBRT. Between March 2010 and August 2011, 15 patients with 17 lesions of primary or metastatic lung cancer underwent respiratory-gated SBRT using audio coaching. In 10 of them, we compared the variability of the cycle, amplitude and lowest point of respiratory waves between audio coaching and free-breathing conditions. Results: The individually selected percentage of the duty cycle was 30% to 60%. The thresholds for gating were adjusted in 5 patients before treatment. Compared to the entire tumor motion, the amplitude of tumor motion during irradiation was decreased by 0.8-4.1 cm in the CC direction using respiratory gating. The mean ITV and PTV were decreased by 37.6% (range, 16-60%) and 33.8% (range, 1556%), respectively (p

112 Background: The epidemiology of prostate cancer (PCa) varies widely internationally. Although prostate cancer is usually regarded as uncommon in Asia, dramatic rises in recent years have resulted in it being ranking third by incidence in Singapore. Conventional prognostic parameters derived from Western populations have been integrated into systems such as the new AJCC seventh edition staging system, the validity of which is unclear in Asia. We thus sought to validate its performance, alongside other prognostic factors in a large Asian series of radiotherapy patients. Methods: A retrospective review of 404 consecutive Singaporean patients receiving radical radiotherapy between 1997 and 2005 at the National Cancer Centre was performed. The primary outcome was biochemical relapse free survival (BRFS), defined by the Phoenix criteria. Prognostic risk groups were defined using AJCC seventh edition. Univariate analysis (UVA) and multivariate analysis (MVA) was performed for other putative risk factors: age, race, Gleason score, prognostic risk grouping, tumour classification, radiation delivery technique, radiotherapy dose, hormonal therapy (HT) and initial PSA. Results: Median age was 69; median BRFS was 55 months with 71 biochemical relapses. 4 risk factors showed univariate association with BRFS: AJCC risk groups (p=0.038), T-stage (p=0.018), RT dose (p=0.025) and initial PSA value (p=0.013) with AJCC risk groups and initial PSA value remaining significant after MVA ( Table ). Harrell's c-index for AJCC risk grouping was 0.56, with no significant difference seen in outcomes between AJCC risk group II and III. Conclusions: Our results validate the new AJCC seventh edition prostate cancer prognostic risk grouping in an Asian radiotherapy population for the first time; the actual association however is relatively weak possibly due to differences in biology, screening or epidemiology. [Table: see text] No significant financial relationships to disclose.