Prophylactic irradiation of para-aortic lymph nodes for patients with locally advanced cervical cancers with and without high CA9 expression (KROG 07-01): A randomized, open-label, multicenter, phase 2 trial.

BACKGROUND AND PURPOSE: The efficacy of prophylactic extended-field irradiation (EFI) plus concomitant cisplatin in patients with locally advanced uterine cervical cancer (LAUCC) is unknown, nor is it known whether tumor carbonic anhydrase IX (CA9) expression level, a hypoxia marker, influences survival outcome. MATERIAL AND METHODS: We recruited patients with UCC, FIGO stage IB1 with pelvic lymph node (LN) metastases to IVA with negative para-aortic LN on PET/CT. CA9 expression was examined and patients were randomized to either EFI or pelvic only radiotherapy (PRT) in each CA9 group. The primary outcomes were para-aortic recurrence-free survival (PARFS) and disease-free survival (DFS). RESULTS: Between 2006 and 2011, 79 patients with CA9-positive and 37 with CA9-negative tumors were enrolled, respectively. The median follow-up period was 69.2months (range 6.8-102.1). For CA9-positive patients, 5-year PARFS was 100% and 81.7% for those receiving EFI and PRT (p=0.007), respectively. DFS was 78.6% for EFI and 71.3% for PRT patients (p=0.353). For CA9-negative patients, 5y PARFS was 100% and 94.1% for EFI and PRT (p=0.317), respectively. DFS was 100% for EFI and 70.7% for PRT (p=0.018). CONCLUSION: EFI significantly reduced recurrences in PAN in patients with CA9-positive tumors, but survival outcome was not improved, due to high local recurrence and high distant metastases rates. This study indicates the necessity for new therapeutic strategies for LAUCC patients whose tumors show high CA9 expression.

The size of the metastatic lymph node is an independent prognostic factor for the patients with cervical cancer treated by definitive radiotherapy.

BACKGROUND AND PURPOSE: Lymph node (LN) metastasis is a well-known prognostic factor of the cervical cancer. In the current study, the size of metastatic LN was evaluated for its significance in the patients treated with definitive radiotherapy. MATERIALS AND METHODS: LN metastasis was evaluated for the 268 consecutive patients. The short-axis diameters of the largest LN were measured on magnetic resonance images for the 155 patients with LN metastasis. All the patients were classified into three groups: the negative lymphadenopathy (group N), the small (<15mm) lymphadenopathy (group SP), and the large (≥15mm) lymphadenopathy (group LP). RESULTS: Patients in the group LP showed significantly lower survival rates than the groups N and SP (5-year overall survival rates of 89%, 82%, and 58%, for groups N, SP, and LP, respectively, P<0.001; 5-year disease-free survival rates of 80%, 67%, and 50%, respectively, P<0.001). Regarding the pattern of failure, patients in the group LP showed inferior regional control rates and higher distant metastasis. CONCLUSION: The current study shows that the patients with large metastatic LNs are at increased risk of dying from early distant metastasis with substantial number of combined regional failures. Adoption of more effective systemic treatment as well as high radiotherapy dose for LNs may improve cure rates for these patients.

Development of a quadruple imaging modality by using nanoparticles.

The combination of nanotechnology with molecular imaging has great potential for the development of diagnostics and therapeutics, and multimodal imaging enables versatile applications from cell tracking in animals to clinical applications. Herein, we report a multimodal nanoparticle imaging system that is capable of concurrent fluorescence, bioluminescence, bioluminescence resonance energy transfer (BRET), positron emission tomography (PET) and magnetic resonance (MR) imaging in vivo. A cobalt-ferrite nanoparticle surrounded by rhodamine (MF) was conjugated with luciferase (MFB) and p-SCN-bn-NOTA (2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclonane-1,4,7-triacetic acid) followed by (68)GaCl(3) (magnetic-fluorescent-bioluminescent-radioisotopic particle, MFBR). Confocal microscopy revealed good transfection efficiency of MFB into cells and BRET was also observed in MFB. A good correlation among rhodamine, luciferase, and (68)GaCl(3) was found in MFBR, and the activities of each imaging modality increased dose-dependently with the amount of MFBR in the C6 cells. In vivo optical images were acquired from the thighs of mice after intramuscular and subcutaneous injections of MFBR-laden cells. MicroPET and MR images showed intense radioactivity and ferromagnetic intensities with MFBR-laden cells. The multimodal imaging strategy could be used as potential imaging tools to track cells.

Role of positron emission tomography in pretreatment lymph node staging of uterine cervical cancer: a prospective surgicopathologic correlation study.

We evaluated the accuracy of FDG-PET in diagnosing metastatic para-aortic and pelvic lymph nodes in patients with cervical cancer by comparing this noninvasive imaging technique with surgicopathologic results. We performed FDG-PET in 54 patients with cervical cancer at FIGO stages IB-IVA who were about to undergo lymphadenectomy. For region-specific comparisons, we divided the nodes into eight regions (four on each side: para-aortic, common iliac, external iliac, and internal iliac/obturator). Histological examination revealed metastases in 15 (28%) of the patients, with region-specific analysis identifying 37 (8.6%) metastases in 432 regions. The region-specific findings of FDG-PET exhibited a sensitivity of 38% and a positive predictive value (PPV) of 56%. The sensitivity increased to 52% and 65% when we restricted the pathologic criterion for metastases to tumour-invasion diameters of >5 and >10 mm, respectively. These results indicate that FDG-PET exhibited low sensitivity and PPV (especially for microscopic metastases) and hence cannot replace surgical staging, although it might still be useful for detecting metastases in patients with clinical conditions that make surgical staging inappropriate.