Role of computed tomography in lung cancer staging

PURPOSE OF REVIEW: Computed tomography has always been an important imaging technique in lung cancer staging but, due to its well-known limitations, additional imaging and/or invasive tests are usually performed. Purpose of this review is to determine whether new developments in CT and in the other staging techniques have changed the role of CT. RECENT FINDINGS: Despite important technical improvements and the availability of new CT applications, the recent literature confirms the limitations of CT in staging patients with NSCLC. Most attention was given however to other invasive and noninvasive staging techniques and their accuracy in comparison with CT. It was shown that FDG-PET is very useful in the preoperative patient with NSCLC and that it is, especially in N-staging, more accurate than CT. Also combining CT or FDG-PET with EUS-FNA biopsy seems to be a good approach in some indications. Finally, the first reports on the use of integrated PET-CT scanners in lung cancer staging were published and very promising results were shown. SUMMARY: Computed tomography stays nevertheless the routine imaging procedure for staging patients with NSCLC although performing a PET scan in addition to this CT examination seems to be a good approach that can reduce but certainly not always avoid invasive staging procedures. Mediastinoscopy is still generally considered the standard of care when tissue needs to be obtained from suspicious nodes on FDG-PET and/or CT, although minimally invasive biopsy techniques could replace to a large extent this more invasive technique in the near future.     

Pretreatment with VEGF(R)-inhibitors reduces interstitial fluid pressure,increases intraperitoneal chemotherapy drug penetration,and impedes tumor growth in a mouse colorectal carcinomatosis model

Cytoreductive surgery combined with intraperitoneal chemotherapy (IPC) is currently the standard treatment for selected patients with peritoneal carcinomatosis of colorectal cancer. However, especially after incomplete cytoreduction, disease progression is common and this is likely due to limited tissue penetration and efficacy of intraperitoneal cytotoxic drugs. Tumor microenvironment-targeting drugs, such as VEGF(R) and PDGFR inhibitors, can lower the heightened interstitial fluid pressure in tumors, a barrier to drug delivery. Here, we investigated whether tumor microenvironment-targeting drugs enhance the effectiveness of intraperitoneal chemotherapy. A mouse xenograft model with two large peritoneal implants of colorectal cancer cells was developed to study drug distribution and tumor physiology during intraperitoneal Oxaliplatin perfusion. Mice were treated for six days with either Placebo, Imatinib (anti-PDGFR, daily), Bevacizumab (anti-VEGF, twice) or Pazopanib (anti-PDGFR, -VEGFR; daily) followed by intraperitoneal oxaliplatin chemotherapy. Bevacizumab and Pazopanib significantly lowered interstitial fluid pressure, increased Oxaliplatin penetration (assessed by laser ablation inductively coupled plasma mass spectrometry) and delayed tumor growth of peritoneal implants (assessed by MRI). Our findings suggest that VEGF(R)-inhibition may improve the efficacy of IPC, particularly for patients for whom a complete cytoreduction might not be feasible.     

Combined targeting of EGFR/HER promotes anti-tumor efficacy in subsets of KRAS mutant lung cancer resistant to single EGFR blockade

KRAS is a frequently mutated oncogene in lung cancer and among the most refractory to EGFR targeted therapy. Recently, preclinical evidence in pancreatic cancer has demonstrated that mutant KRAS can be regulated by EGFR. However, the distinct correlation between the EGFR/HER family members and mutant KRAS has not been investigated. Here, we show that non-small cell lung cancer cell lines harboring differing isoforms of mutant KRAS, can be broadly divided into EGFR/HER dependent and EGFR/HER independent groups. Combined therapeutic targeting of EGFR, HER2 and HER3 in isoforms regulated by extracellular growth signals promotes in vitro and in vivo efficacy. We also provide evidence that depletion of EGFR via RNA interference specifically abolishes the EGFR/KRAS interaction in the dependent subset. Taken together, these findings suggest that upstream inhibition of the EGFR/HER receptors may be effective in treating a subset of KRAS mutant lung cancers.