Clinical and genetic landscape of treatment naive cervical cancer: Alterations in PIK3CA and in epigenetic modulators associated with sub-optimal outcome.

BACKGROUND: There is a lack of information as to which molecular processes, present at diagnosis, favor tumour escape from standard-of-care treatments in cervical cancer (CC). RAIDs consortium (www.raids-fp7.eu), conducted a prospectively monitored trial, [BioRAIDs (NCT02428842)] with the objectives to generate high quality samples and molecular assessments to stratify patient populations and to identify molecular patterns associated with poor outcome. METHODS: Between 2013 and 2017, RAIDs collected a prospective CC sample and clinical dataset involving 419 participant patients from 18 centers in seven EU countries. Next Generation Sequencing has so far been carried out on a total of 182 samples from 377 evaluable (48%) patients, allowing to define dominant genetic alterations. Reverse phase protein expression arrays (RPPA) was applied to group patients into clusters. Activation of key genetic pathways and protein expression signatures were tested for associations with outcome. FINDINGS: At a median follow up (FU) of 22 months, progression-free survival rates of this FIGO stage IB1-IV population, treated predominantly (87%) by chemoradiation, were65•4% [CI95%: 60•2-71.1]. Dominant oncogenic alterations were seen in PIK3CA (40%), while dominant suppressor gene alterations were seen in KMT2D (15%) and KMT2C (16%). Cumulative frequency of loss-of-function (LOF) mutations in any epigenetic modulator gene alteration was 47% and it was associated with PIK3CA gene alterations in 32%. Patients with tumours harboring alterations in both pathways had a significantly poorer PFS. A new finding was the detection of a high frequency of gains of TLR4 gene amplifications (10%), as well as amplifications, mutations, and non-frame-shift deletions of Androgen receptor (AR) gene in 7% of patients. Finally, RPPA protein expression analysis defined three expression clusters. INTERPRETATION: Our data suggests that patient population may be stratified into four different treatment strategies based on molecular markers at the outset. FUND: European Union's Seventh Program grant agreement No 304810.

PET/CT fusion in radiotherapy planning for lung cancer--Case reports.

INTRODUCTION: Application of imaging methods, namely computed tomography (CT), magnetic resonance imaging (MRI) and in recent years positron emission tomography/computed tomography (PET/CT), and the progress of computer technology have allowed the construction of effective computed systems for treatment planning (TPS) and introducing the concept of virtual simulation in 3D conformal radiotherapy planning. CASE REPORT: We hereby presented two patients with the diagnosis of non-small cell lung cancer who did PET/CT examination. Both patients had surgery earlier and local recidives are diagnosed with PET/CT. PET/CT of the first patient described the focus of intense ¹8F-fluorodeoxyglucose (¹8FDG) accumulation 2.99 x 2.9 x 2.1 cm in diameter in the projection of soft-tissue volume in the left corner, at operating clips height, corresponding to metabolically active recurrence of the tumor. Mediastinum and right lung parenchyma were without focal accumulation of ¹8FDG. Control PET/CT after 3 months was without detectable focus of intense pathological ¹8FDG accumulation--good therapeutic response, (metabolic disease remission). On the other hand, in the second case PET/CT showed a focus of intense ¹8FDG accumulation screening in the scar tissue of the apical part of the right lung, 20 x 16 mm, corresponding to metabolically active tumor recurrence. In the lung parenchyma on the left and in the mediastinum no visible focus of intense ¹8FDG accumulation was descrbed. Radiography included using 3D conformal radiotherapy with fusion PET/CT scan and CT simulations. CONCLUSION: PET/CT provides important information for planning conformal radiotherapy, especially in dose escalation, sparing of organ at risk and better locoregional control of the disease.