Radiogenomic analysis of primary breast cancer reveals [18F]-fluorodeoxglucose dynamic flux-constants are positively associated with immune pathways and outperform static uptake measures in associating with glucose metabolism.

BACKGROUND: PET imaging of 18F-fluorodeoxygucose (FDG) is used widely for tumour staging and assessment of treatment response, but the biology associated with FDG uptake is still not fully elucidated. We therefore carried out gene set enrichment analyses (GSEA) of RNA sequencing data to find KEGG pathways associated with FDG uptake in primary breast cancers. METHODS: Pre-treatment data were analysed from a window-of-opportunity study in which 30 patients underwent static and dynamic FDG-PET and tumour biopsy. Kinetic models were fitted to dynamic images, and GSEA was performed for enrichment scores reflecting Pearson and Spearman coefficients of correlations between gene expression and imaging. RESULTS: A total of 38 pathways were associated with kinetic model flux-constants or static measures of FDG uptake, all positively. The associated pathways included glycolysis/gluconeogenesis ('GLYC-GLUC') which mediates FDG uptake and was associated with model flux-constants but not with static uptake measures, and 28 pathways related to immune-response or inflammation. More pathways, 32, were associated with the flux-constant K of the simple Patlak model than with any other imaging index. Numbers of pathways categorised as being associated with individual micro-parameters of the kinetic models were substantially fewer than numbers associated with flux-constants, and lay around levels expected by chance. CONCLUSIONS: In pre-treatment images GLYC-GLUC was associated with FDG kinetic flux-constants including Patlak K, but not with static uptake measures. Immune-related pathways were associated with flux-constants and static uptake. Patlak K was associated with more pathways than were the flux-constants of more complex kinetic models. On the basis of these results Patlak analysis of dynamic FDG-PET scans is advantageous, compared to other kinetic analyses or static imaging, in studies seeking to infer tumour-to-tumour differences in biology from differences in imaging. Trial registration NCT01266486, December 24th 2010.

COVID-19 pneumonia imaging follow-up: when and how? A proposition from ESTI and ESR.

This document from the European Society of Thoracic Imaging (ESTI) and the European Society of Radiology (ESR) discusses the role of imaging in the long-term follow-up of COVID-19 patients, to define which patients may benefit from imaging, and what imaging modalities and protocols should be used. Insights into imaging features encountered on computed tomography (CT) scans and potential pitfalls are discussed and possible areas for future review and research are also included. KEY POINTS: • Post-COVID-19 pneumonia changes are mainly consistent with prior organizing pneumonia and are likely to disappear within 12 months of recovery from the acute infection in the majority of patients. • At present, with the longest series of follow-up examinations reported not exceeding 12 months, the development of persistent or progressive fibrosis in at least some individuals cannot yet be excluded. • Residual ground glass opacification may be associated with persisting bronchial dilatation and distortion, and might be termed "fibrotic-like changes" probably consistent with prior organizing pneumonia.

Characterising 18F-fluciclovine uptake in breast cancer through the use of dynamic PET/CT imaging.

BACKGROUND: 18F-fluciclovine is a synthetic amino acid positron emission tomography (PET) radiotracer that is approved for use in prostate cancer. In this clinical study, we characterised the kinetic model best describing the uptake of 18F-fluciclovine in breast cancer and assessed differences in tracer kinetics and static parameters for different breast cancer receptor subtypes and tumour grades. METHODS: Thirty-nine patients with pathologically proven breast cancer underwent 20-min dynamic PET/computed tomography imaging following the administration of 18F-fluciclovine. Uptake into primary breast tumours was evaluated using one- and two-tissue reversible compartmental kinetic models and static parameters. RESULTS: A reversible one-tissue compartment model was shown to best describe tracer uptake in breast cancer. No significant differences were seen in kinetic or static parameters for different tumour receptor subtypes or grades. Kinetic and static parameters showed a good correlation. CONCLUSIONS: 18F-fluciclovine has potential in the imaging of primary breast cancer, but kinetic analysis may not have additional value over static measures of tracer uptake. CLINICAL TRIAL REGISTRATION: NCT03036943.

Parenchymal involvement on CT pulmonary angiography in SARS-CoV-2 Alpha variant infection and correlation of COVID-19 CT severity score with clinical disease severity and short-term prognosis in a UK cohort.

AIM: To determine if there is a difference in radiological, biochemical, or clinical severity between patients infected with Alpha-variant SARS-CoV-2 compared with those infected with pre-existing strains, and to determine if the computed tomography (CT) severity score (CTSS) for COVID-19 pneumonitis correlates with clinical severity and can prognosticate outcomes. MATERIALS AND METHODS: Blinded CTSS scoring was applied to 137 hospital patients who had undergone both CT pulmonary angiography (CTPA) and whole-genome sequencing of SARS-CoV-2 within 14 days of CTPA between 1/12/20-5/1/21. RESULTS: There was no evidence of a difference in imaging severity on CTPA, viral load, clinical parameters of severity, or outcomes between Alpha and preceding variants. CTSS on CTPA strongly correlates with clinical and biochemical severity at the time of CTPA, and with patient outcomes. Classifying CTSS into a binary value of "high" and "low", with a cut-off score of 14, patients with a high score have a significantly increased risk of deterioration, as defined by subsequent admission to critical care or death (multivariate hazard ratio [HR] 2.76, p<0.001), and hospital length of stay (17.4 versus 7.9 days, p<0.0001). CONCLUSION: There was no evidence of a difference in radiological severity of Alpha variant infection compared with pre-existing strains. High CTSS applied to CTPA is associated with increased risk of COVID-19 severity and poorer clinical outcomes and may be of use particularly in settings where CT is not performed for diagnosis of COVID-19 but rather is used following clinical deterioration.

CT appearances of pleural infection: analysis of the Second Multi-centre Intra-pleural Sepsis Trial (MIST 2) cohort.

AIM: To determine the prevalence of pleural abnormalities and describe the computed tomography (CT) features observed in a well-characterised population of patients with pleural infection. MATERIALS AND METHODS: A retrospective study of a subgroup of patients from the Second Multi-centre Intra-pleural Sepsis Trial (MIST 2) trial was carried out. Patients were diagnosed with pleural infection on robust clinical criteria. CT examinations were assessed by three observers independently for the presence of predefined features. Planned subgroup comparisons of patients with and without evidence of parenchymal infection were performed. RESULTS: Eighty-one patients were included. Parietal pleural thickening and enhancement were seen in 98.7% of patients. Visceral pleural changes were observed in most, including several previously undescribed features. Consolidation was observed in 61.7% of patients and there was a significant association of parenchymal consolidation with CT evidence of small airways infection (p<0.001) and visceral pleural thickening and enhancement (p<0.05). Features of parenchymal infection were absent in one third of patients. CONCLUSION: This study provides a comprehensive account of the parietal pleural, visceral pleural, and parenchymal changes of pleural infection on CT. Parenchymal infection is absent in a significant proportion of patients with pleural infection, suggesting that a pneumonic process may not be necessary for the development of pleural infection.

Baseline PET/CT imaging parameters for prediction of treatment outcome in Hodgkin and diffuse large B cell lymphoma: a systematic review.

PURPOSE: To systematically review the literature evaluating clinical utility of imaging metrics derived from baseline fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for prediction of progression-free (PFS) and overall survival (OS) in patients with classical Hodgkin lymphoma (HL) and diffuse large B cell lymphoma (DLBCL). METHODS: A search of MEDLINE/PubMed, Web of Science, Cochrane, Scopus and clinicaltrials.gov databases was undertaken for articles evaluating PET/CT imaging metrics as outcome predictors in HL and DLBCL. PRISMA guidelines were followed. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. RESULTS: Forty-one articles were included (31 DLBCL, 10 HL). Significant predictive ability was reported in 5/20 DLBCL studies assessing SUVmax (PFS: HR 0.13-7.35, OS: HR 0.83-11.23), 17/19 assessing metabolic tumour volume (MTV) (PFS: HR 2.09-11.20, OS: HR 2.40-10.32) and 10/13 assessing total lesion glycolysis (TLG) (PFS: HR 1.078-11.21, OS: HR 2.40-4.82). Significant predictive ability was reported in 1/4 HL studies assessing SUVmax (HR not reported), 6/8 assessing MTV (PFS: HR 1.2-10.71, OS: HR 1.00-13.20) and 2/3 assessing TLG (HR not reported). There are 7/41 studies assessing the use of radiomics (4 DLBCL, 2 HL); 5/41 studies had internal validation and 2/41 included external validation. All studies had overall moderate or high risk of bias. CONCLUSION: Most studies are retrospective, underpowered, heterogenous in their methodology and lack external validation of described models. Further work in protocol harmonisation, automated segmentation techniques and optimum performance cut-off is required to develop robust methodologies amenable for clinical utility.

Multi-observer concordance and accuracy of the British Thoracic Society scale and other visual assessment qualitative criteria for solid pulmonary nodule assessment using FDG PET-CT.

AIM: To compare the interobserver reliability and diagnostic accuracy of the British Thoracic Society (BTS) scale and other visual assessment criteria in the context of 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)-computed tomography (CT) evaluation of solid pulmonary nodules (SPNs). MATERIALS AND METHODS: Fifty patients who underwent FDG PET-CT for assessment of a SPN were identified. Seven reporters with varied experience at four centres graded FDG uptake visually using the British Thoracic Society (BTS) four-point scale. Five reporters also scored SPNs according to three- and five-point visual assessment scales and using semi-quantitative assessment (maximum standardised uptake value [SUVmax]). Interobserver reliability was assessed with the intra-class correlation coefficient (ICC) and weighted Cohen's kappa (κ). Diagnostic performance was evaluated by receiver operator characteristic (ROC) analysis. RESULTS: Good interobserver reliability was demonstrated with the BTS scale (ICC=0.78, 95% confidence interval [CI]: 0.69-0.85) and five-point scale (ICC=0.78, 95 CI 0.68-0.86), whilst the three-point scale demonstrated moderate reliability (ICC=0.70, 95% CI: 0.59-0.80). Almost perfect agreement was achieved between two consultants (κ=0.85), and substantial agreement between two other consultants (κ=0.78) using the BTS scale. ROC curves for the BTS and five-point scales demonstrated equivalent accuracy (BTS area under the ROC curve [AUC]=0.768; five-point AUC=0.768). SUVmax was no more accurate compared to the BTS scale (SUVmax AUC=0.794; BTS AUC=0.768, p=0.43). CONCLUSIONS: The BTS scale can be applied reliably by reporters with varied levels of PET-CT reporting experience, across different centres and has a diagnostic performance that is not surpassed by alternative scales.

Chest CT screening for COVID-19 in elective and emergency surgical patients: experience from a UK tertiary centre.

AIM: To determine the incidence of possible COVID-19-related lung changes on preoperative screening computed tomography (CT) for COVID-19 and how their findings influenced decision-making. To also to determine whether the patients were managed as COVID-19 patients after their imaging findings, and the proportion who had SARS-CoV2 reverse transcriptionpolymerase chain reaction (RT-PCR) testing. MATERIALS AND METHODS: A retrospective study was undertaken of consecutive patients having imaging prior to urgent elective surgery (n=156) or acute abdominal imaging (n=283). Lung findings were categorised according to the British Society of Thoracic Imaging (BSTI) guidelines. RT-PCR testing, management, and outcomes were determined from the electronic patient records. RESULTS: 3% (13/439) of CT examinations demonstrated findings of classic/probable COVID-19 pneumonia, whilst 4% (19/439) had findings indeterminate for COVID-19. Of the total cohort, 1.6% (7/439) subsequently had confirmed RT-PCR-positive COVID-19. Importantly, all the patients with a normal chest or alternative diagnoses on CT who had PCR testing within the next 7 days, had a negative RT-PCR (92/407). There was a change in surgical outcome in 6% (10/156) of the elective surgical cohort with no change to surgical management was demonstrated in the acute abdominal emergency cohort requiring surgery (2/283). CONCLUSION: There was a 7% (32/439) incidence of potential COVID-19-related lung changes in patients having preoperative CT. Although this altered surgical management in the elective surgical cohort, no change to surgical management was demonstrated in the acute abdominal emergency cohort requiring surgery.

Artificial intelligence and radiomics in pulmonary nodule management: current status and future applications.

Artificial intelligence (AI) has been present in some guise within the field of radiology for over 50 years. The first studies investigating computer-aided diagnosis in thoracic radiology date back to the 1960s, and in the subsequent years, the main application of these techniques has been the detection and classification of pulmonary nodules. In addition, there have been other less intensely researched applications, such as the diagnosis of interstitial lung disease, chronic obstructive pulmonary disease, and the detection of pulmonary emboli. Despite extensive literature on the use of convolutional neural networks in thoracic imaging over the last few decades, we are yet to see these systems in use in clinical practice. The article reviews current state-of-the-art applications of AI and in detection, classification, and follow-up of pulmonary nodules and how deep-learning techniques might influence these going forward. Finally, we postulate the impact of these advancements on the role of radiologists and the importance of radiologists in the development and evaluation of these techniques.

18Fluorocholine PET/CT scanning with arterial phase-enhanced CT is useful for persistent/recurrent primary hyperparathyroidism: first UK case series results.

INTRODUCTION: Redo parathyroidectomy for persistent/recurrent primary hyperparathyroidism is associated with a higher risk of complications and should be planned only with convincing localisation. We assessed whether 18fluorocholine positron emission tomography/computed tomography could identify parathyroid adenoma(s) in patients with persistent/recurrent primary hyperparathyroidism and negative conventional scans. MATERIALS AND METHODS: A departmental database was used to identify patients with failed localisation attempts (sestamibi single photon emission computed tomography/computed tomography and/or computed tomography/magnetic resonance imaging and/or selective parathyroid hormone sampling) after previous unsuccessful surgery for primary hyperparathyroidism. 18Fluorocholine positron emission tomography was performed in all patients and redo surgery offered to those with positive findings. RESULTS: 18Fluorocholine positron emission tomography incorporating arterial and portal phase enhanced computed tomography was performed in 12 patients with persistent/recurrent primary hyperparathyroidism (four men and eight women). Seven patients (58%) were cured after excision of adenomas located in ectopic positions (n = 3) or in anatomical position (n = 4). Five patients (42%) had persistent hypercalcaemia and repeat 18fluorocholine scan confirmed that the area highlighted on preoperative scans was excised. The arterial phase enhancement of the computed tomography was significantly different between cured and not-cured patients (P = 0.007). All seven cured patients had either a strong or weak enhancing pattern on computed tomography. Standardised uptake value at 60 minutes in patients with successful surgery (range 2.7-15.7, median 4.05) was higher than in patients with failed surgery (range 1.8-5.8, median 3.2) but was not statistically significant (P = 0.300). DISCUSSION: 18fluorocholine scanning can identify elusive parathyroid adenomas, including those that are ectopic, and is useful in the management of patients with persistent/recurrent primary hyperparathyroidism when first-line scans are negative. The grading of the arterial phase of computed tomography can help to differentiate between true adenomas and false positive targets (lymph nodes).

Local control, safety, and survival following image-guided percutaneous microwave thermal ablation in primary lung malignancy.

AIM: To determine local control, safety, and survival following percutaneous computed tomography (CT)-guided high-power microwave ablation (MWA) in the treatment of primary lung malignancy at a single institution. MATERIAL AND METHODS: From July 2010 to June 2016, 52 patients (mean age 76.3 years, range 55-91 years) with 61 unresectable primary lung cancers of mean diameter 23.8 mm (range 26-55 mm) underwent MWA in 55 ablation sessions. Tumours were diagnosed at biopsy, or positron-emission tomography (PET) avidity (mean SUV max = 10.51) and interval growth. Statistical analysis was performed by Kaplan-Meier modelling and Cox and logistic regression. RESULTS: Local tumour progression (LTP) was diagnosed in six lesions (10%). Median time to local recurrence was 3 months (range 2-14 months). There was a near 12-fold increased odds of local recurrence if the lesion size was >3 cm (95% confidence interval [CI]: 1.84-75.14; p=0.009). The median inpatient stay was 1 day, with no intra-procedural deaths and a 0% 30-day post-ablation mortality rate. Pneumothorax requiring drain was the most serious complication, occurring in 22% (n=12) of patients. Presence of severe emphysema and predicted forced expiratory volume in 1 second (FEV1) of <50% were found to predict future requirement of a drain (odds ratio [OR] 8.17, 95% CI: 1.62-41.37, p=0.01 and OR: 5.14, 95% CI: 1.28-20.68, p=0.02 respectively), when adjusted for age and gender. Tumour size >3 cm had a hazard ratio of 4.37 compared with tumour size ≤3 cm (95% CI: 1.45-13.17, p=0.009) of risk of cancer death at any time, by Cox regression. CONCLUSION: MWA for primary lung malignancy is a safe and effective treatment for primary lung tumours with outcomes that may be comparable to stereotactic body radiation therapy.

Reliability and validity of the World Health Organization reading standards for paediatric chest radiographs used in the field in an impact study of Pneumococcal Conjugate Vaccine in Kilifi, Kenya.

BACKGROUND: Radiologically-confirmed pneumonia (RCP) is a specific end-point used in trials of Pneumococcal Conjugate Vaccine (PCV) to estimate vaccine efficacy. However, chest radiograph (CXR) interpretation varies within and between readers. We measured the repeatability and reliability of paediatric CXR interpretation using percent agreement and Cohen's Kappa and the validity of field readings against expert review in a study of the impact of PCV on pneumonia. METHODS: CXRs were obtained from 2716 children admitted between 2006 and 2014 to Kilifi County Hospital, Kilifi, Kenya, with clinically-defined severe or very-severe pneumonia. Five clinicians and radiologists attended a three-day training course on CXR interpretation using a WHO standard. All CXRs were read once by two local primary readers. Discordant readings and 13% of concordant readings were arbitrated by a panel of three expert radiologists. To assess repeatability, a 5% median random sample was presented twice. Sensitivity and specificity of the primary readers' interpretations was estimated against the 'gold-standard' of the arbitrators' results. RESULTS: Of 2716 CXRs, 2 were uninterpretable and 159 were evaluated twice. The percent agreement and Kappa for RCP were 89% and 0.68 and ranged between 84-97% and 0.19-0.68, respectively, for all pathological findings. Intra-observer repeatability was similar to inter-observer reliability. Sensitivities of the primary readers to detect RCP were 69% and 73%; specificities were 96% and 95%. CONCLUSION: Intra- and inter-observer agreements on interpretations of radiologically-confirmed pneumonia are fair to good. Reasonable sensitivity and high specificity make radiologically-confirmed pneumonia, determined in the field, a suitable measure of relative vaccine effectiveness.

Pulmonary nodules: Assessing the imaging biomarkers of malignancy in a "coffee-break".

INTRODUCTION: Although nodule volumetry is a recognized biomarker of malignancy in pulmonary nodules (PNs), caution is needed in its interpretation because of variables such as respiratory volume variation and inter-scan variability of up to 25%. CT Texture Analysis (CTTA) is a potential independent biomarker of malignancy but inter-scan variability and respiratory volume variation has not been assessed. METHODS: In this prospective cohort study, 40 patients (20 with an indeterminate PN and 20 with pulmonary metastases) underwent two LDCTs within a 60-min period (the "Coffee-break") with the aim of assessing the repeatability of CTTA and semi-automated volume measurements. Texture features were extracted from each automatic contoured region surrounding the PN. Patients were also randomized to two inspiratory control groups: normal breath hold, and controlled lung volume to study the influence of inspiratory control on these measurements. RESULTS: The mean difference in volume between the two scans was 6.3%,SD:29.9%. The textural features displayed 95% CI below ±17.8%, and were less variable than nodule volume (95%CI ±â€¯28.9%). All features had high repeatability, calculated by the concordance correlation coefficient, (0.84 ≤ CCC ≤ 0.99). All measurements were more repeatable for the controlled lung volume group than the normal breath-hold group. CONCLUSION: CTTA repeatability was comparable to automatic volumetric measurements, and appears to be improved using controlled volume breath holding.

Survey of UK imaging practice for the investigation of pulmonary embolism in pregnancy.

AIM: To determine the utilisation of computed tomography pulmonary angiography (CTPA) and lung scintigraphy in the UK, and to assess their diagnostic qualities in the investigation of suspected pulmonary embolism (PE) in pregnancy. MATERIALS AND METHODS: Data were collected via electronic questionnaire in the UK from 24 sites. Data on the choice of imaging technique, radiation dose, technical adequacy, weeks' gestation, presenting symptoms, and further management of patients with indeterminate imaging were collected. RESULTS: The sample represented a population of 15.5 million and showed wide variation in the probability of investigation of suspected PE with rates per live birth of 0.06-2.2%. Nine hundred and ninety-one patients were imaged and there were 48 positive scans, an incidence of 0.038%. Of the 269 CTPAs performed, 5.9% were positive, 8.9% were technically inadequate. Of the 769 scintigraphy scans performed, 3.8% were positive and 9.1% were indeterminate; 63% of positive scans were in the third trimester. Most inadequate/indeterminate scans were in the third trimester. The calculated typical radiation dose to the breast and fetus from CTPA ranged from 14 to 2 mGy and 0.02 to 0.002mGy, respectively, and approximately 0.28 and 0.2 mGy, respectively, from scintigraphy. CONCLUSION: The incidence of PE in this population was extremely low and the number of indeterminate or inadequate scans was comparable. This suggests choice of imaging should be made based upon availability and radiation exposure.

An aerosol challenge model of tuberculosis in Mauritian cynomolgus macaques.

BACKGROUND: New interventions for tuberculosis are urgently needed. Non-human primate (NHP) models provide the most relevant pre-clinical models of human disease and play a critical role in vaccine development. Models utilising Asian cynomolgus macaque populations are well established but the restricted genetic diversity of the Mauritian cynomolgus macaques may be of added value. METHODS: Mauritian cynomolgus macaques were exposed to a range of doses of M. tuberculosis delivered by aerosol, and the outcome was assessed using clinical, imaging and pathology-based measures. RESULTS: All macaques developed characteristic clinical signs and disease features of tuberculosis (TB). Disease burden and the ability to control disease were dependent on exposure dose. Mauritian cynomolgus macaques showed less variation in pulmonary disease burden and total gross pathology scores within exposure dose groups than either Indian rhesus macaques or Chinese cynomolgus macaques. CONCLUSIONS: The genetic homogeneity of Mauritian cynomolgus macaques makes them a potentially useful model of human tuberculosis.

State-of-the-art: Radiological investigation of pleural disease.

Pleural disease is common. Radiological investigation of pleural effusion, thickening, masses, and pneumothorax is key in diagnosing and determining management. Conventional chest radiograph (CXR) remains as the initial investigation of choice for patients with suspected pleural disease. When abnormalities are detected, thoracic ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) can each play important roles in further investigation, but appropriate modality selection is critical. US adds significant value in the identification of pleural fluid and pleural nodularity, guiding pleural procedures and, increasingly, as "point of care" assessment for pneumothorax, but is highly operator dependent. CT scan is the modality of choice for further assessment of pleural disease: Characterising pleural thickening, some pleural effusions and demonstration of homogeneity of pleural masses and areas of fatty attenuation or calcification. MRI has specific utility for soft tissue abnormalities and may have a role for younger patients requiring follow-up serial imaging. MRI and PET/CT may provide additional information in malignant pleural disease regarding prognosis and response to therapy. This article summarises existing techniques, highlighting the benefits and applications of these different imaging modalities and provides an up to date review of the evidence.

Metabolic nodal response as a prognostic marker after neoadjuvant therapy for oesophageal cancer.

BACKGROUND: The ability to predict recurrence and survival after neoadjuvant chemotherapy (NAC) and surgery for oesophageal cancer remains elusive. This study evaluated the role of [18 F]fluorodeoxyglucose (FDG) PET-CT in assessing tumour and nodal response as a prognostic marker. METHODS: This was a single-centre UK cohort study. From 2006 to 2014, patients with oesophageal cancer staged with PET-CT before NAC, and restaged by CT or PET-CT before resection, were included. Pathological tumour response was evaluated using Mandard regression grades. Metabolic tumour and nodal responses (mTR and mNR respectively) were quantified using absolute and threshold reductions. RESULTS: Among 294 included patients, mTR and mNR independently predicted prognosis before surgery. After surgery, mNR (but not mTR), pathological tumour response, resection margin status and pathological node category predicted prognosis. Patients with FDG-avid nodal disease after NAC were at high risk of recurrence/death at 1 and 2 years (43 and 71 per cent respectively; P = 0·030 and P = 0·025 versus patients without avid nodes), and had a worse prognosis than patients with non-avid nodal metastases: hazard ratio 4·19 (95 per cent c.i. 1·87 to 9·40) and 2·11 (1·12 to 3·97) respectively versus patients without nodal metastases. Considering mTR and mNR response separately improved prognostication. CONCLUSION: mNR is a novel prognostic factor, independent of conventional N status. Primary and nodal tumours may respond discordantly and patients with FDG-avid nodes after NAC have a poor prognosis.