Potential utility of early metabolic response by 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography in a selected group of breast cancer patients receiving preoperative chemotherapy.

INTRODUCTION: To assess (18)F-2-fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography's ((18)F-FDG-PET/CT) potential clinical utility to allow early treatment changes during preoperative chemotherapy (PCT) in patients with early/locally advanced breast cancer (BC). PATIENTS AND METHODS: Sixty newly diagnosed early/locally advanced BC patients received 6-8 cycles of PCT. Optimal pathologic response (pR) was the absence of cancer cells in breast and axillary lymph nodes. All other conditions were defined as pathologic non-response (pNR). (18)F-FDG-PET/CT maximum standardised uptake value (SUV(max)) was measured at baseline and after 2 cycles of PCT. Metabolic response was defined as SUV(max) percentage changes (Δ-SUV) >50% and was compared with pR rates. RESULTS: Thirteen (22%) patients achieved pR; according to immunohistochemistry, 16% of ER-positive/HER2-negative patients, 29% and 27% of HER2-positive and triple negative patients respectively achieved pR. (18)F-FDG-PET/CT showed the highest specificity (38%) and negative predictive value (100%) in ER-positive/HER2-negative patients. In this subgroup, at a median follow-up of 36.6 months, median disease-free survival was still not reached in metabolic responders while it was 37 months in metabolic non-responders (p=0.049). DISCUSSION: Early metabolic non-response was always associated to pNR and poor prognosis in ER-positive/HER2-negative patients. In this subgroup, (18)F-FDG-PET/CT might be useful to select patients who will probably benefit from early therapeutic strategy modifications.

[18F]FDG-PET/CT monitoring early identifies advanced ovarian cancer patients who will benefit from prolonged neo-adjuvant chemotherapy.

AIM: The most accepted standard duration of neoadjuvant chemotherapy (na-CHT) before debulking surgery for advanced ovarian cancer (AOC) is 3 courses. However a percentage of patients could benefit from additional courses. [(18)F]FDG-PET/CT monitoring during na-CHT could predict early pathological response and allow the delivery of an optimal na-CHT duration. METHODS: Consecutive patients with AOC unsuitable for optimal up front surgery and fit for na-CHT were monitored by FDG-PET/CT at baseline and after 3 and 6 courses of carboplatin-paclitaxel CHT. At the end of na-CHT patients were re-evaluated to undergo definitive optimal surgery (i.e. without post-surgical residual disease). Percentage changes in maximal standardized uptake value (∆-SUVmax) were compared with the pathological response. Only patients with pathological complete response (pCR) or minimal residual disease (pMRD) were considered as pathological responders (pR), while all the other cases were considered non-responders (NR). RESULTS: Baseline FDG-PET/CT was abnormal in all 42 enrolled patients (median SUVmax 11, range 3-20). After 3 and 6 courses median SUVmax decreased to 3 (<2-21) and <2, i.e. value equal to normal surrounding tissues uptake (<2-17), respectively. After 3 courses, 17 (40%) patients presented ∆-SUVmax=100%, (i.e. SUVmax <2): 15 of them (88%) subsequently resulted pR and achieved no postsurgical residual disease at the end of na-CHT, while 2 (12%) were NR with postsurgical residual tumor ≤ 1cm. Out of 25 patients with ∆-SUVmax <100% after 3 courses, 6 (24%) were pR and 19 (76%) NR at the end of na-CHT. CONCLUSION: Patients with AOC who present normalization of SUVmax after 3 courses of na-CT have a high likelihood of benefiting from 3 additional courses in order to obtain pCR or pMDR and receiving optimal surgery.

Contrast-enhanced US and MRI for assessing the response of breast cancer to neoadjuvant chemotherapy().

PURPOSE: To evaluate the response of breast cancers to neoadjuvant chemotherapy (NAC) with second-generation contrast-enhanced ultrasound (CEUS) and magnetic resonance (MR). MATERIALS AND METHODS: We studied 16 women aged 33-74 years (mean, 53 years; median, 38 years) with locally advanced breast carcinoma or large operable breast cancer (>2 cm; T2-T4, N0-N3, M0) that had been detected by mammography, conventional ultrasonography, and biopsy. CEUS (with SonoVue, 5 ml) and MR (with Gd-DTPA; 0.2 mM/kg) were performed under blinded conditions before, during, and after 6-8 cycles of NAC. Lesions were measured and time/signal intensity (T/SI) curves were calculated during both the examinations. The data obtained were analyzed in light of the results of surgical pathology. RESULTS: Six patients had complete responses manifested by the disappearance of enhancement at both CEUS and MR. Six others had partial responses (reduction of lesion enhancement >50%). In 5/6, T/SI curves obtained with CEUS and MR were both indicative of malignancy (flat curves at CEUS, type I curves at MR); the sixth had a discontinuous curve at CEUS and a type II curve at MR. Four patients had lesional enhancement reductions of <50%. In 3, concordant pictures emerged from the analysis of T/SI curves (discontinuous curves in CEUS, type II and III curves in MR); the fourth had a flat CEUS curve and a type I MR curve. Responses to NAC classified on the basis of MR and CEUS findings showed good correlation with the pathological response. CONCLUSIONS: T/SI curves recorded during CEUS correlate with those obtained during MR and may be a valid index of response to the therapy.

Antisense oligodeoxynucleotide attenuates in vivo expression of c-fos in the paraventricular hypothalamic nucleus of the rat brain.

The proto-oncogene, c-fos, is expressed in neurons in response to stimulation by growth factors, neurotransmitters, and immunocytokines. In order to determine whether interleukin-1 beta (IL-1 beta)-induced Fos protein expression in the paraventricular hypothalamic nucleus (PVN) can be reduced or eliminated by a c-fos antisense oligodeoxynucleotide, rats were injected with c-fos antisense and Fos expression was examined immunocytochemically. Our results indicate that c-fos antisense oligodeoxynucleotide treatment decreases the density of Fos immuno-labeled nuclei in the PVN following IL-1 beta administration. These data suggest that, with the use of antisense technology, it may be possible to determine the role of proto-oncogene proteins in specific brain areas.