Therapeutic Effects of CT-guided Radiofrequency Ablation with Concurrent Platinum-Doublet Chemotherapy in a Rabbit VX2 Lung Tumor Model

Abstract

Purpose To evaluate survival time with concurrent, combined use of radiofrequency ablation (RFA) and one of the commonly used platinum-doublet chemotherapies (cisplatin [CDDP]/paclitaxel [PTX], CDDP/vinorelbine [VNR], CDDP/adriamycin [ADR], or CDDP/pemetrexed [MTA] combinations) by using a rabbit VX2 lung tumor model. Materials and Methods The experiment was approved by the institutional animal care committee. VX2 cells were implanted into the lungs of 60 rabbits randomized into groups treated with supportive care (control group), RFA alone, chemotherapy alone (CDDP/PTX, CDDP/VNR, CDDP/ADR, or CDDP/MTA), or a combination of RFA and chemotherapy (RFA/CDDP/PTX, RFA/CDDP/VNR, RFA/CDDP/ADR, or RFA/CDDP/MTA). RFA was performed and followed by intravenous chemotherapy. Survival time was evaluated by using the Kaplan-Meier method. Results The median survival time of the control, RFA-alone, CDDP/PTX, CDDP/VNR, CDDP/ADR, CDDP/MTA, RFA/CDDP/PTX, RFA/CDDP/VNR, RFA/CDDP/ADR, and RFA/CDDP/MTA groups was 26.5, 40, 39, 26.5, 28, 26, 120, 16.5, 42, and 26.5 days, respectively. Survival of the RFA/CDDP/PTX group was significantly longer than that of the control (P = .0006), CDDP/PTX (P = .0117), and RFA-alone (P = .0495) groups. Survival was also significantly prolonged with combined RFA/CDDP/ADR treatment versus supportive care (P = .026), but not with RFA alone (P = .765) or CDDP/ADR (P = .167). Survival times in the RFA/CDDP/VNR and RFA/CDDP/MTA groups were significantly shorter than that in the RFA-alone group (P = .0282 and P = .0197, respectively). Conclusion The combination of RFA and systemic chemotherapy with CDDP/PTX may benefit survival. However, RFA with systemic CDDP may have a survival disadvantage when combined with VNR or MTA. RSNA, 2016.

Combination therapy involving radiofrequency ablation and targeted chemotherapy with bevacizumab plus paclitaxel and cisplatin in a rabbit VX2 lung tumor model

“…However, in that study, as well, long-term follow-up was not performed. The findings of this study were consistent with earlier study findings that the administration of CDDP/PTX after lung RFA was most effective against rabbit VX2 tumors [ 15 ], but the survival of adding BCM to combination RFA and CDDP/PTX was significantly shorter than that in the without BCM group [i.e., RFA/CDDP/PTX/BCM vs RFA/CDDP/PTX (37 vs 120 days)]. Thus, adding BCM to combination therapy involving lung RFA and systemic chemotherapy with CDDP/PTX may produce a negative effect.…”

“…VX2 carcinoma cells (Japan SLC Inc., Hamamatsu, Japan) were used to establish a model of lung tumors. Isolation and implantation of the VX2 tumor (the only tumor established in rabbits) were performed as previously described [ 15 , 16 ]. In brief, a suspension of single VX2 tumor cells (2.5 × 10 6 cell/mL) was prepared, of which 0.2 mL were injected with a 20-gauge needle into the left lower lobes of the lungs of each of 69 rabbits using single helical computed tomography (CT) guidance with the following parameters: voltage 120 kV; current 60 mA; collimation 3 mm; slice thickness 3 mm; pitch 1 and field of view (FOV) 20 cm, ReconMatrix size 320 × 320 (ProSpeed; GE Healthcare, Milwaukee, WI, USA.).…”

“…Although simultaneous lung RFA and chemotherapy with BCM may be considered feasible in human patients, the VX2 tumor may exhibit different treatment responses and is considered more malignant than human lung tumors. Secondly, the schedule of chemotherapy: we followed earlier studies of chemotherapy performed immediately after RFA for VX2 lung model [ 15 ], but it may be clinically relevant to give anticancer drugs prior to RFA. Thirdly, tumor response was not evaluated longitudinally by CT, because general anesthesia is necessary in animals during CT scanning, and it may affect survival.…”

“…For these reasons, survival was the primary endpoint. Lastly, the present study did not include a histopathological examination, since histopathological changes of lung VX2 tumors after RFA have been previously studied [ 14 , 15 ]. But, further study will be necessary to confirm the histological changes when adding to BCM with combination RFA and chemotherapy.…”

“…There appear to be no studies using RFA + systemic chemotherapy added to BCM to treat lung tumors. In an earlier study, a rabbit VX2 lung tumor model was subjected to RFA, followed by chemotherapy using cisplatin (CDDP)/paclitaxel (PTX), and survival was extended [ 15 ]. A combination of RFA with chemotherapy may increase intratumoral drug accumulation by increasing blood flow and membrane permeability and provide survival benefit.…”