Metabolic tumour and nodal response to neoadjuvant chemotherapy on FDG PET-CT as a predictor of pathological response and survival in patients with oesophageal adenocarcinoma.

OBJECTIVES: 2-deoxy-2[18F]Fluoro-D-glucose (FDG) PET-CT has an emerging role in assessing response to neoadjuvant therapy in oesophageal cancer. This study evaluated FDG PET-CT in predicting pathological tumour response (pTR), pathological nodal response (pNR) and survival. METHODS: Cohort study of 75 patients with oesophageal or oesophago-gastric junction (GOJ) adenocarcinoma treated with neoadjuvant chemotherapy then surgery at Guy's and St Thomas' NHS Foundation Trust, London (2017-2020). Standardised uptake value (SUV) metrics on pre- and post-treatment FDG PET-CT in the primary tumour (mTR) and loco-regional lymph nodes (mNR) were derived. Optimum SUVmax thresholds for predicting pathological response were identified using receiver operating characteristic analysis. Predictive accuracy was compared to PERCIST (30% SUVmax reduction) and MUNICON (35%) criteria. Survival was assessed using Cox regression. RESULTS: Optimum tumour SUVmax decrease for predicting pTR was 51.2%. A 50% cut-off predicted pTR with 73.5% sensitivity, 69.2% specificity and greater accuracy than PERCIST or MUNICON (area under the curve [AUC] 0.714, PERCIST 0.631, MUNICON 0.659). Using a 30% SUVmax threshold, mNR predicted pNR with high sensitivity but low specificity (AUC 0.749, sensitivity 92.6%, specificity 57.1%, p = 0.010). pTR, mTR, pNR and mNR were independent predictive factors for survival (pTR hazard ratio [HR] 0.10 95% confidence interval [CI] 0.03-0.34; mTR HR 0.17 95% CI 0.06-0.48; pNR HR 0.17 95% CI 0.06-0.54; mNR HR 0.13 95% CI 0.02-0.66). CONCLUSIONS: Metabolic tumour and nodal response predicted pTR and pNR, respectively, in patients with oesophageal or GOJ adenocarcinoma. However, currently utilised response criteria may not be optimal. pTR, mTR, pNR and mNR were independent predictors of survival. KEY POINTS: • FDG PET-CT has an emerging role in evaluating response to neoadjuvant therapy in patients with oesophageal cancer. • Prospective cohort study demonstrated that metabolic response in the primary tumour and lymph nodes was predictive of pathological response in a cohort of patients with adenocarcinoma of the oesophagus or oesophago-gastric junction treated with neoadjuvant chemotherapy followed by surgical resection. • Patients who demonstrated a response to neoadjuvant chemotherapy in the primary tumour or lymph nodes on FDG PET-CT demonstrated better survival and reduced rates of tumour recurrence.

Staging FDG PET-CT changes management in patients with gastric adenocarcinoma who are eligible for radical treatment.

AIM: 18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) is valuable in the management of patients with oesophageal cancer, but a role in gastric cancer staging is debated. Our aim was to review the role of FDG PET-CT in a large gastric cancer cohort in a tertiary UK centre. METHODS: We retrospectively reviewed data from 330 patients presenting with gastric adenocarcinoma between March 2014 and December 2016 of whom 105 underwent pre-treatment staging FDG PET-CT scans. FDG PET-CT scans were graded qualitatively and quantitatively (SUVmax) and compared with staging diagnostic CT and operative pathology results (n = 30) in those undergoing resection. RESULTS: Of the 105 patients (74 M, median age 73 years) 86% of primary tumours were metabolically active (uptake greater than normal stomach) on FDG PET-CT [41/44 (93%) of the intestinal histological subtype (SUVmax 14.1 ± 1.3) compared to 36/46 (78%) of non-intestinal types (SUVmax 9.0 ± 0.9), p = 0.005]. FDG PET-CT upstaged nodal or metastastic staging of 20 patients (19%; 13 intestinal, 6 non-intestinal, 1 not reported), with 17 showing distant metastases not evident on other imaging. On histological analysis, available in 30 patients, FDG PET-CT showed low sensitivity (40%) but higher specificity (73%) for nodal involvement. CONCLUSION: FDG PET-CT provides new information in a clinically useful proportion of patients, which leads to changes in treatment strategy, most frequently by detecting previously unidentified metastases, particularly in those with intestinal-type tumours.

Non-Small Cell Lung Cancer Treated with Erlotinib: Heterogeneity of (18)F-FDG Uptake at PET-Association with Treatment Response and Prognosis.

PURPOSE: To determine if first-order and high-order textural features on fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET) images of non-small cell lung cancer (NSCLC) (a) at baseline, (b) at 6 weeks, or (c) the percentage change between baseline and 6 weeks can predict response or survival in patients treated with erlotinib. MATERIALS AND METHODS: Institutional review board approval was obtained for post hoc analysis of data from a prospective single-center study for which informed consent was obtained. The study included 47 patients with NSCLC who underwent (18)F-FDG PET/computed tomography (CT) at baseline (n = 47) and 6 weeks (n = 40) after commencing treatment with erlotinib. First-order and high-order primary tumor texture features reflecting image heterogeneity, standardized uptake values, metabolic tumor volume, and total lesion glycolysis were measured for all (18)F-FDG PET studies. Response to erlotinib was assessed by using the Response Evaluation Criteria in Solid Tumors (RECIST) on CT images obtained at 12 weeks (n = 32). Associations between PET parameters, overall survival (OS), and RECIST-based treatment response were tested by Cox and logistic regression analyses, respectively. RESULTS: Median OS was 14.1 months. According to CT RECIST at 12 weeks, there were 21 nonresponders and 11 responders. Response to erlotinib was associated with reduced heterogeneity (first-order standard deviation, P = .01; entropy, P = .001; uniformity, P = .001). At multivariable analysis, high-order contrast at 6 weeks (P = .002) and percentage change in first-order entropy (P = .03) were independently associated with survival. Percentage change in first-order entropy was also independently associated with treatment response (P = .01). CONCLUSION: Response to erlotinib is associated with reduced heterogeneity at (18)F-FDG PET. Changes in first-order entropy are independently associated with OS and treatment response.

The association of 18F-FDG PET/CT parameters with survival in malignant pleural mesothelioma.

PURPOSE: Malignant pleural mesothelioma (MPM) is a disease with poor prognosis despite multimodal therapy but there is variation in survival between patients. Prognostic information is therefore potentially valuable in managing patients, particularly in the context of clinical trials where patients could be stratified according to risk. Therefore we have evaluated the prognostic ability of parameters derived from baseline 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT). METHODS: In order to determine the relationships between metabolic activity and prognosis we reviewed all (18)F-FDG PET/CT scans used for pretreatment staging of MPM patients in our institution between January 2005 and December 2011 (n = 60) and measured standardised uptake values (SUV) including mean, maximum and peak values, metabolic tumour volume (MTV) and total lesion glycolysis (TLG). Overall survival (OS) or time to last censor was recorded, as well as histological subtypes. RESULTS: Median follow-up was 12.7 months (1.9-60.9) and median OS was 14.1 months (1.9-54.9). By univariable analysis histological subtype (p = 0.013), TLG (p = 0.024) and MTV (p = 0.038) were significantly associated with OS and SUVmax was borderline (p = 0.051). On multivariable analysis histological subtype and TLG were associated with OS but at borderline statistical significance (p = 0.060 and 0.058, respectively). No statistically significant differences in any PET parameters were found between the epithelioid and non-epithelioid histological subtypes. CONCLUSION: (18)F-FDG PET/CT parameters that take into account functional volume (MTV, TLG) show significant associations with survival in patients with MPM before adjusting for histological subtype and are worthy of further evaluation to determine their ability to stratify patients in clinical trials.

Quantifying tumour heterogeneity in 18F-FDG PET/CT imaging by texture analysis.

(18)F-Fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) is now routinely used in oncological imaging for diagnosis and staging and increasingly to determine early response to treatment, often employing semiquantitative measures of lesion activity such as the standardized uptake value (SUV). However, the ability to predict the behaviour of a tumour in terms of future therapy response or prognosis using SUVs from a baseline scan prior to treatment is limited. It is recognized that medical images contain more useful information than may be perceived with the naked eye, leading to the field of "radiomics" whereby additional features can be extracted by computational postprocessing techniques. In recent years, evidence has slowly accumulated showing that parameters obtained by texture analysis of radiological images, reflecting the underlying spatial variation and heterogeneity of voxel intensities within a tumour, may yield additional predictive and prognostic information. It is hoped that measurement of these textural features may allow better tissue characterization as well as better stratification of treatment in clinical trials, or individualization of future cancer treatment in the clinic, than is possible with current imaging biomarkers. In this review we focus on the literature describing the emerging methods of texture analysis in (18)FDG PET/CT, as well as other imaging modalities, and how the measurement of spatial variation of voxel grey-scale intensity within an image may provide additional predictive and prognostic information, and postulate the underlying biological mechanisms.

Do emergency physicians and radiologists reliably interpret pelvic radiographs obtained as part of a trauma series?

INTRODUCTION: Interpretation of pelvic radiography is an important component of the primary survey and is commonly performed by emergency physicians. Radiologists bring unique skills to trauma care, including choice of imaging modality and image interpretation. It is not clear if this limited resource is most efficiently used in the resuscitation room. No studies have compared radiologists and trauma clinicians in their ability to interpret pelvic radiographs following trauma. OBJECTIVE: To determine the sensitivity and specificity of trauma experienced and trauma inexperienced emergency physicians in detecting pelvic fractures compared with radiologists, the latter subgroup combined report being used as the gold standard. SETTING AND METHODS: Prospective cohort study conducted in two large teaching hospitals in central London. All participants reviewed 144 consecutive pelvic radiographs performed each as part of a 'trauma series' and known to have undergone concomitant pelvic CT imaging. RESULTS: No statistically significant difference was found between radiologists and emergency physicians from a trauma centre in pelvic radiograph interpretation. Radiologist reporting was associated with an improved specificity compared with emergency physicians working in a non-trauma hospital (p=0.049). The study population missed 30% of fractures on plain radiography against the gold standard of CT. DISCUSSION: The ability to interpret trauma series pelvic radiographs is comparable between emergency physicians and radiologists. If this were also true of trauma chest radiographs, then the most valuable use of the radiologist may not be the resuscitation room but in rapid reporting of more complex imaging techniques. However, plain radiography is insensitive for pelvic fracture detection compared with CT, even in expert hands.

Optimisation of CT protocols in PET-CT across different scanner models using different automatic exposure control methods and iterative reconstruction algorithms.

BACKGROUND: A significant proportion of the radiation dose from a PET-CT examination is dependent on the CT protocol, which should be optimised for clinical purposes. Matching protocols on different scanners within an imaging centre is important for the consistency of image quality and dose. This paper describes our experience translating low-dose CT protocols between scanner models utilising different automatic exposure control (AEC) methods and reconstruction algorithms. METHODS: The scanners investigated were a newly installed Siemens Biograph mCT PET with 64-slice SOMATOM Definition AS CT using sinogram affirmed iterative reconstruction (SAFIRE) and two GE Discovery 710 PET scanners with 128-slice Optima 660 CT using adaptive statistical reconstruction (ASiR). Following exploratory phantom work, 33 adult patients of various sizes were scanned using the Siemens scanner and matched to patients scanned using our established GE protocol to give 33 patient pairs. A comparison of volumetric CT dose index (CTDIvol) and image noise within these patient pairs informed optimisation, specifically for obese patients. Another matched patient study containing 27 patient pairs was used to confirm protocol matching. Size-specific dose estimates (SSDEs) were calculated for patients in the second cohort. With the acquisition protocol for the Siemens scanner determined, clinicians visually graded the images to identify optimal reconstruction parameters. RESULTS: In the first matched patient study, the mean percentage difference in CTDIvol for Siemens compared to GE was - 10.7% (range - 41.7 to 50.1%), and the mean percentage difference in noise measured in the patients' liver was 7.6% (range - 31.0 to 76.8%). In the second matched patient study, the mean percentage difference in CTDIvol for Siemens compared to GE was - 20.5% (range - 43.1 to 1.9%), and the mean percentage difference in noise was 19.8% (range - 27.0 to 146.8%). For these patients, the mean SSDEs for patients scanned on the Siemens and GE scanners were 3.27 (range 2.83 to 4.22) mGy and 4.09 (range 2.81 to 4.82) mGy, respectively. The analysis of the visual grading study indicated no preference for any of the SAFIRE strengths. CONCLUSIONS: Given the different implementations of acquisition parameters and reconstruction algorithms between vendors, careful consideration is required to ensure optimisation and standardisation of protocols.

18F-FDG PET rarely provides additional information to 11C-methionine PET imaging in hyperparathyroidism.

AIM: The aim of this study was to assess the utility of combined C-methionine and F-FDG PET/CT imaging in hyperparathyroidism. PATIENTS AND METHODS: We reviewed all scans performed for hyperparathyroidism with both C-methionine and F-FDG PET/CT or PET in our institution since 1993. Forty-three patients (47 pairs of scans) were included (13 men and 30 women) with a mean age of 63 years. C-methionine and F-FDG PET/CT scans were classified as positive or negative for localization of abnormal parathyroid tissue, and the site of uptake was noted in the positive scans. Other concurrent imaging (Tc-MIBI scintigraphy, ultrasonography, CT, or MRI) findings were also noted when performed. Clinical follow-up information was available in 27 patients (30 episodes). RESULTS: Of the 47 PET scan episodes, 23 (49%) were positive. Twenty-two C-methionine scans showed abnormal focal localization of which 10 also showed concordant abnormal F-FDG uptake. One patient was positive with F-FDG and negative with C-methionine.Of the 16 patients who underwent subsequent surgery, 6 had concordant C-methionine, F-FDG, and surgical findings; 6 had concordant C-methionine and surgical findings; 1 had concordant F-FDG and surgical findings; and 3 had both PET scans negative but had adenomas excised during surgery.Of the 3 with both PET scans negative and discordant surgical findings, 1 had mediastinal parathyroid lipoadenoma excised and 2 had normally sited parathyroid adenoma excised. CONCLUSIONS: F-FDG PET/CT rarely provides additional information and could be saved for patients in whom C-methionine PET/CT is negative.

Potential role of multislice SPECT/CT in impingement syndrome and soft-tissue pathology of the ankle and foot.

INTRODUCTION: Impingement syndrome and soft-tissue pathology have been recognized as significant causes of chronic ankle pain. Conventional bone scintigraphy was traditionally used for osseous pathology, but with the advent of single photon emission computed tomography/computed tomography (SPECT/CT) the role of bone scintigraphy in these patients is being reconsidered. AIM: The aim of this study was to assess the potential role of multislice SPECT/CT in diagnosing impingement syndrome and soft-tissue pathology of the ankle and foot. MATERIALS AND METHODS: A total of 209 patients (age range: 19-80 years) underwent a two-phase Tc-99m methylene diphosphonate bone scan followed by SPECT/CT between 2006 and 2009 for various ankle and foot pathologies. These scans were reviewed for impingement syndrome and soft-tissue pathology. The diagnosis made on SPECT/CT was compared with the clinical diagnosis, and two-phase bone scan findings and additional findings obtained from SPECT/CT were noted. RESULTS: Out of the 209 patients, 43 (21%) were diagnosed with impingement syndrome or soft-tissue pathology. Clinical diagnosis versus bone SPECT/CT: in 24/43 (56%) patients, SPECT/CT provided information not suspected on clinical diagnosis. In 19/43 (44%) patients, SPECT/CT confirmed the clinical diagnosis. Two-phase bone scan versus SPECT/CT: in 31/43 (72%) patients, SPECT/CT provided additional information, which was not diagnosed on the conventional two-phase bone scan. The findings of the two-phase bone scan and SPECT/CT were concordant in 12/43 (28%) patients. CONCLUSION: Tc-99m methylene diphosphonate bone SPECT/CT is useful in localizing and characterizing impingement syndrome and soft-tissue pathology in patients with ankle/foot pain. SPECT/CT may complement MRI and ultrasonography in the investigation of impingement syndrome and soft-tissue pathology.

Patterns of disease progression on 18F-fluorodeoxyglucose positron emission tomography-computed tomography in patients with malignant pleural mesothelioma undergoing multimodality therapy with pleurectomy/decortication.

INTRODUCTION: The aim of this study was to evaluate the patterns of disease progression in patients treated with pleurectomy/decortication (P/D), hyperthermic pleural lavage with povidone-iodine, prophylactic radiotherapy and adjuvant chemotherapy, using F-fluorodeoxyglucose (18F-FDG) PET/computed tomography (PET/CT). MATERIALS AND METHODS: This was a retrospective study of 65 patients treated with a multimodality therapy including P/D between October 2004 and March 2012. Thirty-two patients underwent 18F-FDG PET/CT within 6 weeks of completion of adjuvant chemotherapy and 6-monthly thereafter at our institution. The first site of relapse on 18F-FDG PET/CT was recorded, and all scans were reviewed by an independent observer. RESULTS: Thirty-two patients (27 male, median age 61 years, range 45-73) underwent their 18F-FDG PET/CT scans at our institution. Eighteen of the 32 patients were alive at last follow-up (median follow-up 42 months, range 16-76). Nine patients were alive with disease recurrence. Fourteen patients died of disease progression (median survival 24.7 months, range 15-38). The median maximum standardized uptake value (SUVmax) in relapsing mesothelioma was 10.9 (range 4.9-27.3). There was a statistically significant correlation between the SUVmax and tumour lesion glycolysis of recurrent mesothelioma and overall survival (P=0.05). The site of disease recurrence was the pleura in the majority of the alive patients and was extrapleural in the dead patients. There was a statistically significant correlation between disease-free survival and complete macroscopic resection (P=0.02). CONCLUSION: After P/D with hyperthermic pleural lavage with povidone-iodine, prophylactic radiotherapy and adjuvant chemotherapy, the most frequent site of recurrence is the pleural cavity. Peritoneal seeding is rare. The tumour SUVmax and tumour lesion glycolysis correlate significantly with overall survival.

Are pretreatment 18F-FDG PET tumor textural features in non-small cell lung cancer associated with response and survival after chemoradiotherapy?

UNLABELLED: 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.