Manu Shastry

Tumor heterogeneity and permeability as measured on the CT component of PET/CT predict survival in patients with non-small cell lung cancer.

Purpose: We prospectively examined the role of tumor textural heterogeneity on positron emission tomography/computed tomography (PET/CT) in predicting survival compared with other clinical and imaging parameters in patients with non–small cell lung cancer (NSCLC). Experimental Design: The feasibility study consisted of 56 assessed consecutive patients with NSCLC (32 males, 24 females; mean age 67 ± 9.7 years) who underwent combined fluorodeoxyglucose (FDG) PET/CT. The validation study population consisted of 66 prospectively recruited consecutive consenting patients with NSCLC (37 males, 29 females; mean age, 67.5 ± 7.8 years) who successfully underwent combined FDG PET/CT-dynamic contrast-enhanced (DCE) CT. Images were used to derive tumoral PET/CT textural heterogeneity, DCE CT permeability, and FDG uptake (SUVmax). The mean follow-up periods were 22.6 ± 13.3 months and 28.5± 13.2 months for the feasibility and validation studies, respectively. Optimum threshold was determined for clinical stage and each of the above biomarkers (where available) from the feasibility study population. Kaplan–Meier analysis was used to assess the ability of the biomarkers to predict survival in the validation study. Cox regression determined survival factor independence. Results: Univariate analysis revealed that tumor CT-derived heterogeneity (P < 0.001), PET-derived heterogeneity (P = 0.003), CT-derived permeability (P = 0.002), and stage (P < 0·001) were all significant survival predictors. The thresholds used in this study were derived from a previously conducted feasibility study. Tumor SUVmax did not predict survival. Using multivariable analysis, tumor CT textural heterogeneity (P = 0.021), stage (P = 0.001), and permeability (P < 0.001) were independent survival predictors. These predictors were independent of patient treatment. Conclusions: Tumor stage and CT-derived textural heterogeneity were the best predictors of survival in NSCLC. The use of CT-derived textural heterogeneity should assist the management of many patients with NSCLC. Clin Cancer Res; 19(13); 3591–9. ©2013 AACR.

Commercial software upgrades may significantly alter Perfusion CT parameter values in colorectal cancer

ObjectiveTo determine how commercial software platform upgrades impact on derived parameters for colorectal cancer.Materials and methodsFollowing ethical approval, 30 patients with suspected colorectal cancer underwent Perfusion CT using integrated 64 detector PET/CT before surgery. Analysis was performed using software based on modified distributed parameter analysis (Perfusion software version 4; Perfusion 4.0), then repeated using the previous version (Perfusion software version 3; Perfusion 3.0). Tumour blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface area product (PS) were determined for identical regions-of-interest. Slice-by-slice and ‘whole tumour’ variance was assessed by Bland-Altman analysis.ResultsMean BF, BV and PS was 20.4%, 59.5%, and 106% higher, and MTT 14.3% shorter for Perfusion 4.0 than Perfusion 3.0. The mean difference (95% limits of agreement) were +13.5 (−44.9 to 72.0), +2.61 (−0.06 to 5.28), −1.23 (−6.83 to 4.36), and +14.2 (−4.43 to 32.8) for BF, BV, MTT and PS respectively. Within subject coefficient of variation was 36.6%, 38.0%, 27.4% and 60.6% for BF, BV, MTT and PS respectively indicating moderate to poor agreement.ConclusionSoftware version upgrades of the same software platform may result in significantly different parameter values, requiring adjustments for cross-version comparison.

The Flow–Metabolic Phenotype of Primary Colorectal Cancer: Assessment by Integrated 18F-FDG PET/Perfusion CT with Histopathologic Correlation

The aim of this study was to assess the in vivo flow–metabolic phenotype in primary colorectal cancer with integrated 18F-FDG PET/perfusion CT and its relationship to gold standard histopathologic assessment of angiogenesis and hypoxia. Methods: 45 patients (26 male and 19 female; mean age, 67.6 y) with primary colorectal cancer underwent integrated 18F-FDG PET/perfusion CT, deriving tumor glucose metabolism (maximum standardized uptake value) and regional blood flow. From this cohort, 35 underwent surgery subsequently, without intervening neoadjuvant treatment, allowing histopathologic correlation with tumor stage, CD105 microvessel density, vascular endothelial growth factor (VEGF), glucose transporter protein 1 (Glut-1), and hypoxia-inducible factor 1 expression. Results: The flow–metabolic ratio was significantly lower for tumors with higher VEGF (3.65 vs. 5.98; P = 0.01) or hypoxia-inducible factor 1 expression (3.63 vs. 5.48; P = 0.04) versus tumors with lower expression. There were significant negative correlations between the tumor flow–metabolic ratio and VEGF expression (r = −0.55, P = 0.0008), indicating that tumors with low blood flow but higher metabolism were associated with higher VEGF expression. Flow and metabolism were coupled in higher-stage (stage III/IV) tumors but not lower-stage tumors (stage I/II) (r = 0.47, P = 0.03, vs. r = 0.09, P = 0.65, respectively. Conclusion: Tumors with a low-flow–high-metabolism phenotype demonstrated higher VEGF expression and may reflect a more angiogenic phenotype.

Defining the Role of PET–CT in Staging Early Breast Cancer

INTRODUCTION Currently, there is a lack of data on the role of combined positron emission tomography-computed tomography (PET-CT) in the staging of early invasive primary breast cancer. We therefore evaluated the role of (18)F-fluorodeoxyglucose ((18)F-FDG)-PET-CT in this patient population. METHODS We prospectively recruited 70 consecutive patients (69 women, one man; mean age, 61.9 ± 8.1 years) with early primary breast cancer for staging with (18)F-FDG-PET-CT. All PET-CT images were interpreted by two readers (independently of each other). A third reader adjudicated any discrepancies. All readers had ≥5 years of specific experience. Ethics board approval and informed consent were obtained. RESULTS The mean clinical follow-up was 22.7 ± 12.6 months. The primary tumor was identified with PET-CT in 64 of 70 patients. Of the unidentified lesions, surgical pathology revealed two intraductal carcinomas, one invasive tubular carcinoma, and three invasive lobular carcinomas. Undiagnosed multifocal breast disease was shown in seven of 70 patients. PET-CT identified avid axillary lymph nodes in 19 of 70 patients, compared with 24 of 70 confirmed during surgery. There were four patients who were axillary node positive on PET but had no axillary disease at surgery. Five patients were reported with avid metastases. Two of those patients were treated for metastatic disease (nodal, lung, and liver in one and bone metastases in the other) following further imaging and clinical assessment. In the other three patients, lesions (lung, n = 1; pleural, n = 1; paratrachael node, n = 1) were subsequently diagnosed as benign lesions. CONCLUSION Integrated (18)F-FDG-PET-CT may have a role in staging patients presenting with early breast cancer.

Integrated (18)F-FDG PET/CT and perfusion CT of primary colorectal cancer: effect of inter- and intraobserver agreement on metabolic-vascular parameters.

OBJECTIVE The purpose of this article is to assess the effect of observers on combined metabolic-vascular parameters in colorectal cancer. SUBJECTS AND METHODS Twenty-five prospective patients (12 men and 13 women; mean age, 66.9 years) with proven primary colorectal adenocarcinoma underwent integrated (18)F-FDG PET/perfusion CT to assess tumor metabolism (mean and maximum standardized uptake value [SUV(mean) and SUV(max), respectively]) and vascularization (blood flow [BF], blood volume [BV], permeability surface-area product, and standardized perfusion value). Intra- and interobserver agreement for PET, perfusion CT, and combined metabolic-flow parameters were determined by Bland-Altman statistics and intraclass correlation coefficients (ICCs). RESULTS The mean tumor size was 3.8 ± 1.6 cm; there were five stage IA/B, six stage IIA/B, eight stage IIIA/B, and six stage IV tumors. Intra- and interobserver agreement for individual parameters was fair to good, with mean differences between observers of -0.74 for SUV(max), -0.16 for SUV(mean), 9.72 for BF, 0.15 for BV, -0.76 for permeability surface-area product, and 0.09 for standardized perfusion value. ICCs were 0.44-0.99 and 0.38-0.89 for intra- and interobserver agreement, respectively. Interobserver agreement was variable for combined metabolic-flow parameters but better for metabolic-flow difference than for metabolic-flow ratio: ICCs were 0.69-0.88 for the metabolic-flow difference and 0.44-0.94 for the metabolic-flow ratio. CONCLUSION Combined parameters to assess the metabolic-flow relationship are influenced by observer variation. Intra- and interobserver agreement are better for the metabolic-flow differences than for the ratios, suggesting that metabolic-flow differences may be a more robust parameter for clinical practice.

Integrated 18F-fluorodeoxyglucose-positron emission tomography/dynamic contrast-enhanced computed tomography to phenotype non-small cell lung carcinoma.

We applied modern molecular and functional imaging to the pretreatment assessment of lung cancer using combined dynamic contrast-enhanced computed tomography (DCE-CT) and 18F-fluorodeoxyglucose–positron emission tomography (18F-FDG-PET) to phenotype tumors. Seventy-four lung cancer patients were prospectively recruited for 18F-FDG-PET/DCE-CT using PET/64-detector CT. After technical failures, there were 64 patients (35 males, 29 females; mean age [± SD] 67.5 ± 7.9 years). DCE-CT yielded tumor peak enhancement (PE) and standardized perfusion value (SPV). The uptake of 18F-FDG quantified on PET as the standardized uptake value (SUVmax) assessed tumor metabolism. The median values for SUVmax and SPV were used to define four vascular-metabolic phenotypes. There were associations (Spearman rank correlation [rs]) between tumor size and vascular-metabolic parameters: SUVmax versus size (rs = .40, p = .001) and SUV/PE versus size (r = .43, p < .001). Patients with earlier-stage (1-HA, n = 30) disease had mean (± SD) SUV/PE 0.36 ± 0.28 versus 0.56 ± 0.32 in later-stage (stage IIB-IV, n = 34) disease (p = .007). The low metabolism with high vascularity phenotype was significantly more common among adenocarcinomas (p = .018), whereas the high metabolism with high vascularity phenotype was more common among squamous cell carcinomas (p = .024). Other non-small cell lung carcinoma tumor types demonstrated a high prevalence of the high metabolism with low vascularity phenotype (p = .028). We show that tumor subtypes have different vascular-metabolic associations, which can be helpful clinically in managing lung cancer patients to hone targeted therapy.

A retrospective study of disease recurrence post thoracotomy for non-small cell lung cancer

Background Surgery is the treatment of choice for early stage non-small cell lung cancer (NSCLC). However, curative intent is commonly not achieved due to inaccurate clinical staging and disease recurrence. Aim We aimed to determine the incidence of futile thoracotomies (FT) in patients with NSCLC following surgery with curative intent. In addition, we wished to identify prognostic factors that predicted FT. Methods In this analytical retrospective cohort study, thoracotomy cases between October 2003 and September 2008 at a single institution were identified. Confirmed cases of primary NSCLC only were included. A thoracotomy was deemed futile if any one of the following criteria were met: pathologically confirmed N2, N3, or M1 disease, an exploratory thoracotomy, or a thoracotomy in a patient who developed recurrent disease or died within 1 year of surgery. When a PET scan was performed, the SUVmax of the primary tumour was reported by a radiologist blinded to the clinical information. Case notes and hospital systems were interrogated for evidence of recurrence and survival. Statistical analysis was performed with STATA version 10 for Windows. Results We identified 171 consecutive patients with NSCLC who underwent lung resection with curative intent. 105 (61%) were male and mean age at the time of surgery was 66 years. 134 (78%) had lobectomy, 8 bi-lobectomy, 19 pneumonectomy and 10 sub-lobar resection (segmentectomy or wedge resection). Overall 46 (27%) underwent FT. Nine patients (5.2%) had clinically unsuspected N2 disease at pathological staging. An SUVmax of the primary tumour greater than 8 was associated with an increased risk of FT (RR 2.35 (p=0.03)) (Abstract P222 Table 1). The presence of lymphovascular invasion was also associated with a increased risk of FT (RR 1.71 (p=0.04)). Those with a primary tumour greater than or equal to 3 cm in size had a RR of 1.91 (p=0.02) of FT. Conclusions Between 2003 and 2008, 27% of patients at our cardiothoracic centre for lung cancer underwent a futile thoracotomy. High SUVmax, the presence of lymphovascular invasion and tumour size ≥3 cm are predictors of FT. Future, prospective studies employing adjuvant chemotherapy in these patient groups are warranted.