Objective: We sought to assess the incidence, pattern and predictors of occult mediastinal lymph node involvement (N2) in non-small cell lung cancer patients with negative mediastinal uptake of 2-deoxy-2-[18 F]-fluoro-D-glucose ( 18 FDG) on integrated positron emission tomographycomputerised tomography (PET-CT). Methods: All patients who underwent surgical resection in our unit over a 30-month period were reviewed (n = 215). All patients had preoperative PET-CT prior to lung resection as an adjunct to a dedicated chest CT. Diabetic patients, patients who received neoadjuvant chemotherapy and those with positive mediastinal nodes on PET-CT (N2/N3) were excluded from this study. The population of interest was 153 non-small cell cancer patients (NSCLC), all of which had no FDG uptake in the mediastinum. No preoperative mediastinoscopy was carried out in this group and all underwent curative intent surgical resection. The pathological results were retrospectively reviewed and correlated with CT and integrated PET-CT findings. Results: The incidence of occult N2 disease in NSCLC patients with negative mediastinal uptake of 18 FDG on PET-CTwas 16% (25 of 153). The highest incidence of occult N2 involvement was in American thoracic society (ATS) 7 (16 of 25 patients, 64%) followed by ATS 4 (seven patients of 25, 28%). In univariate analysis, the following were significant predictors of occult N2 disease: centrally located tumours (P = 0.049), right upper lobe tumours (P = 0.04), enlarged lymph nodes (>1 cm) on CT (P = 0.048) and PET positive uptake in N1 nodes (P = 0.006). In multivariate analysis, the following were independent predictors of occult N2 disease: centrally located tumours, right upper lobe tumours and PET positive uptake in N1 nodes (P < 0.05). Conclusions: In NSCLC patients who are clinically staged as N2/ N3 negative in the mediastinum by integrated PET-CT, 16% will have occult N2 disease following resection. Patients with the following: centrally located tumours, right upper lobe tumours and positive N1 nodes on PET should have preoperative cervical mediastinoscopy to rule out N2 nodal involvement, especially in ATS stations 7 and 4 as the incidence of occult nodal metastasis in these nodes is high. This study has potential implications in decision-making and planning best treatment approach. #

SUV(max) correlates with tumour characteristics, surgical stage and prognosis following resection. SUV(max) may be a useful preoperative tool, in addition to other known prognostic markers, in allocating patients with potentially poor prognosis preoperatively to neoadjuvant chemotherapy prior to resection in order to improve their overall survival. Prospective and randomised trials are warranted.

To determine whether [18 F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) could predict the pathological response in oesophageal cancer after only the first week of neoadjuvant chemoradiation. Thirty-two patients with localised oesophageal cancer had a pretreatment PET scan and a repeat after the first week of chemoradiation. The change in mean maximum standardised uptake value (SUV) and volume of metabolically active tissue (MTV) was compared with the tumour regression grade (TRG) in the final histology. Those who achieved a TRG of 1 and 2 were deemed responders and 3 -5 nonresponders. In the responders (28%), the SUV fell from 12.6 (76.3) to 8.1 (72.9) after 1 week of chemoradiation (P ¼ 0.070). In nonresponders (72%), the results were 9.7 (75.4) and 7.1 (73.8), respectively (P ¼ 0.003). The MTV in responders fell from 36.6 (722.7) to 22.3 (710.4) cm 3 (P ¼ 0.180), while in nonresponders, this fell from 35.9 (736.7) to 31.9 (752.7) cm 3 (P ¼ 0.405). There were no significant differences between responders and nonresponders. The hypothesis that early repeat FDG-PET scanning may predict histomorphologic response was not proven. This may reflect an inflammatory effect of radiation that obscures tumour-specific metabolic changes at this time. This assessment may have limited application in predicting response to multimodal regimens for oesophageal cancer.

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This study evaluated the role of 18 F-FDG PET as an early predictor of histopathologic response to neoadjuvant chemoradiotherapy and overall survival in patients with adenocarcinoma of the esophagus undergoing multimodal therapy. Methods: Thirty-seven patients with locally advanced adenocarcinoma of the esophagus underwent pretreatment and an intratreatment 18 F-FDG PET scan in the second week of a 6-wk regimen of neoadjuvant chemoradiotherapy. Histopathologic response and overall survival were correlated with percentage change in 18 F-FDG uptake (%Dmax-imum standardized uptake value [%DSUVmax]). Results: In 16 patients (43%), treatment induced a histopathologic response (,10% viable tumor cells), which was associated with a significant (P , 0.05) survival benefit. The optimal reduction in 18 F-FDG uptake, which separated histopathologic responders and nonresponders, was a 226.4% DSUVmax (receiver-operating-characteristic curve analysis). At this separation, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy (area under the receiver operating characteristic curve) were 62.5%, 71.4%, 62.5%, 71.4%, and 67.4%, respectively, for intratreatment 18 F-FDG PET scans. Kaplan-Meier survival analysis of 18 F-FDG PET responders (.26.4% reduction in SUVmax), compared with 18 F-FDG PET nonresponders (,26.4% reduction in SUVmax), revealed no survival benefit for responders (P 5 0.6812). Conclusion: The %DSUVmax during the second week of induction chemoradiation did not correlate either with histopathologic response or with survival. Our results show that, in contrast to published reports on neoadjuvant chemotherapy, combined chemoradiotherapy in patients with adenocarcinoma of the esophagus lowers the predictive accuracy of early repeated 18 F-FDG PET in identifying histopathologic responders and those with chances for increased survival below clinically applicable levels.