Intrinsic or acquired resistance to chemotherapeutic agents is a common phenomenon and a major challenge in the treatment of cancer patients. Chemoresistance is defined by a complex network of factors including multi-drug resistance proteins, reduced cellular uptake of the drug, enhanced DNA repair, intracellular drug inactivation, and evasion of apoptosis. Pre-clinical models have demonstrated that many chemotherapy drugs, such as platinum-based agents, antracyclines, and taxanes, promote the activation of the NF-κB pathway. NF-κB is a key transcription factor, playing a role in the development and progression of cancer and chemoresistance through the activation of a multitude of mediators including anti-apoptotic genes. Consequently, NF-κB has emerged as a promising anti-cancer target. Here, we describe the role of NF-κB in cancer and in the development of resistance, particularly cisplatin. Additionally, the potential benefits and disadvantages of targeting NF-κB signaling by pharmacological intervention will be addressed.

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 tomography-computerised tomography (PET-CT). 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. The incidence of occult N2 disease in NSCLC patients with negative mediastinal uptake of (18)FDG on PET-CT was 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 (>1cm) 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). 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.

We sought to assess the clinical implication and prognostic significance of maximum standardised uptake value (SUV(max)) of primary non-small cell lung cancer (NSCLC) staged by integrated PET-CT. A retrospective review was carried out on 176 consecutive patients with histologically proven NSCLC who underwent staging with integrated PET-CT prior to curative intent surgical resection. SUV(max) of primary NSCLC were measured and correlated with tumour characteristics, lymph node involvement, surgical stage, type of surgical resection and survival following resection. SUV(max) was significantly higher in centrally located tumours, tumours > or =4.0 cm, squamous cell subtype, poorly differentiated tumours, advanced T stage, advanced nodal stage, pleural invasion, and patients requiring complex surgical resection. SUV(max) value of 15 was the best discriminative cut-off value for survival generated by log-rank test. When patients were stratified based on this value, those with SUV(max) >15 were more likely to have centrally located tumours, squamous cell subtype, advanced T stage, advanced nodal stage, advanced American Joint Committee on Cancer (AJCC) stage, larger tumour size and required more advanced surgical resections than a simple lobectomy. Overall survival was significantly longer for patients with SUV(max) < or =15 than those with SUV(max) >15. Furthermore, nodal stage specific survival following resection (i.e. non-N2 and N2) were significantly better in patients with SUV(max) < or =15 than SUV(max) >15. 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.