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CT guided cryoablation for locally recurrent or metastatic bone and soft tissue tumor: initial experience
© The Author(s). 2016
Received: 17 December 2015
Accepted: 10 October 2016
Published: 13 October 2016
Historically, local control of recurrent sarcomas has been limited to radiotherapy when surgical re-resection is not feasible. For metastatic carcinomas to the bone or soft tissue, radiotherapy and some interventional radiology treatment along with other systemic therapies have been widely advocated due to the possibility of disseminated disease. These techniques are effective in alleviating pain and achieving local control for some tumor types, but it has not been effective for prolonged local control of most tumors. Recently, cryoablation has been reported to have satisfactory results in lung and liver carcinoma treatment. In this study, we analyzed the clinical outcome of CT-guided cryoablation for malignant bone and soft tissue tumors to elucidate potential problems associated with this procedure.
Since 2011, 11 CT-guided cryoablations in 9 patients were performed for locally recurrent or metastatic bone and soft tissue tumors (7 males and 2 females) at our institute. The patients’ average age was 74.8 years (range 61–86) and the median follow up period was 24.1 months (range 5–48). Histological diagnosis included renal cell carcinoma (n = 4), dedifferentiated liposarcoma (n = 2), myxofibrosarcoma (n = 2), chordoma (n = 1), hepatocellular carcinoma (n = 1), and thyroid carcinoma (n = 1). Cryoablation methods, clinical outcomes, complications, and oncological outcomes were analyzed.
There were 5 recurrent tumors and 6 metastatic tumors, and all cases had contraindication to either surgery, chemotherapy or radiotherapy. Two and 3 cycles of cryoablation were performed for bone and soft tissue tumors, respectively. The average length of the procedure was 101.1 min (range 63–187), and the average number of probes was 2.4 (range 2–3). Complications included 1 case of urinary retention in a patient with sacral chordoma who underwent prior carbon ion radiotherapy, 1 transient femoral nerve palsy, and 1 minor wound complication. At the final follow up, 4 patients showed no evidence of disease, 2 were alive with disease, and 3 died of disease.
Reports regarding CT-guided cryoablation for musculoskeletal tumors are rare and the clinical outcomes have not been extensively studied. In our case series, CT-guided cryoablation had analgesic efficacy and there were no cases of local recurrence post procedure during the follow-up period. Although collection of further data regarding use of this technique is necessary, our data suggest that cryoablation is a promising option in medically inoperable musculoskeletal tumors.
Recurrent and metastatic bone and soft tissue tumors pose significant problems because of their refractory nature. Re-resection of local sarcoma recurrence has the potential to cure the patient, but it is often difficult to treat because it is almost impossible to discern the extent of tumor infiltration after multiple operations . Metastasis of carcinoma to the bone and soft tissue is also challenging due to the morbidity of patients. Various radiotherapy techniques have been reported to be effective in alleviating pain and achieving local control. Approximately 60 % of patients reportedly experience pain relief after radiotherapy . Recently, carbon ion radiotherapy has been reported to be effective for local control of certain unresectable sarcomas, but its long-term outcomes require further analysis . When radiation therapy is contraindicated for specific reasons, locally recurrent or metastatic bone and soft tissue tumor are often treated by palliative care.
Cryoablation is a therapeutic procedure wherein hollow cryoprobes are inserted into the tumor, causing a decrease in the local temperature below 40° C. Freezing for longer than 1 min causes cell death and subsequent thawing further ensures disruption of the cellular integrity [4, 5]. Its effectiveness for alleviating pain has been reported in musculoskeletal metastases from carcinomas, but its utility in the curative intent for metastases and local recurrence is scarce. Furthermore, only 2 case series have reported the effectiveness of cryoablation for primary musculoskeletal tumors [6, 7].
The purpose of this study was to assess the feasibility, safety and efficacy of cryosurgical ablation for locally recurrent sarcoma and metastatic carcinomas.
Local control is typically achieved in approximately 60–90 % of sarcomas after wide resection, depending on the tumor location [10, 11]. Various methods, from local adjuvant therapies to novel molecular therapeutics, have the potential to further improve the outcome; however, the prognosis has not improved in the past decades possibly due to the difficulty when facing local recurrence and distant metastasis . Although re-resection with or without radiotherapy is the gold standard for local recurrence of sarcomas, further surgery is often not feasible because of the uncertain spread of the lesion under imaging, the lack of an adequate barrier in additional wide resection and patient morbidity after multiple operations and systemic therapies [13, 14] . Furthermore, bone metastasis of sarcomas is a debilitating event that impairs the quality of life. Local recurrences have been reported to worsen the outcome due to consequent metastasis . Metastasis of carcinomas is also difficult to treat, owing to patient morbidity after extensive treatment of the primary lesion. Carcinomas usually present with systematic metastasis which limits the treatment to radiotherapy or various interventional radiology treatment. The outcome of bone metastasis has seen great improvement through the advent of bone modifying agents such as bisphosphonates and anti - RANKL antibody, denosumab. However, there are also side effects, such as osteonecrosis of the jaw and atypical fractures. Metastasis to soft tissue is problematic when it causes a mass effect or compression of vital organs. Some cancers have improved after excision of the tumor bulk, such as in oligometastatic cases, but surgery is often challenging when it occurs in deep-seated locations. Reducing the sarcoma burden has been implicated as an adjunct to aggressive salvage chemotherapy [16, 17]. With the advent of newer drugs targeting molecular susceptibility, novel minimally invasive techniques, such as cryoablation, could be integrated for future treatment.
There has been wide variety of image guided thermal ablations, including radiofrequency, microwave, laser, high intensity ultrasound, irreversible electroporation, and cryotherapy. Percutaneous thermal ablation offers minimal invasive procedures, but each technique has their own clinical applications. Radiofrequency was the first reported percutaneous thermal ablation technique, and its efficacy has been widely reported for various tumor types. It is especially effective for small lesions, such as osteoid osteoma, for which the heat is sufficient to eradicate lesions that are usually less than 2 cm in diameter . However, a limitation is that the area of ablation is not readily visualized under imaging modalities . Other techniques that utilize laser and ultrasound technology have also shown efficacy, albeit in small case series for musculoskeletal tumors. Laser ablation is primarily employed in small lesions, such as osteoid osteoma, and high - intensity focused ultrasound is limited to surface lesions because an appropriate acoustic window under MRI is necessary for this technology .
Cryotherapy was first reported in the mid - 19th century , and its percutaneous application was subsequently modified for musculoskeletal tumors . Cryotherapy has a strong advantage in that it can treat irregularly shaped lesions by using multiple synergistic probes as well as monitor the area of ablation, as an ice ball, to ensure accuracy. Furthermore, unlike with radiotherapy, it can be applied repeatedly. Additionally, the post procedural pain is minimal, and recovery is swift with the possible additive effect of a systemic antitumor immune response by cryoablation .
The effectiveness of cryoablation for palliating pain from cancer metastasis has been reported by several groups [20, 24]. Furthermore, cryoablation has been able to achieve local control of asymptomatic cancer metastasis with limited systematic spread. In a single center retrospective study, local control was achieved for over 85 % of metastases at a median time of 21 months . Additionally, cryoablation for oligometastatic renal cell carcinoma has been implicated to result in higher overall survival compared to systematic treatments alone . Recently, there have been sporadic reports of the use of cryoablation for soft tissue sarcomas [22, 27]. In a recent feasibility study with soft tissue sarcoma relapse, location in the wall of the trunk, shoulders and pelvic girdle; tumors with local aggressiveness; deep tumors or tumors less or equal to 5 cm, and liposarcoma and myxofibrosarcoma were deemed suitable for cryoablation . Although the study populations are generally small, improved local control, analgesic efficacy, reduced complication and reduction of convalescence after the procedure has been reported .
Clinically, the disadvantages of cryoablation include its medical cost (it is not covered by the National Health Insurance in Japan), the necessity of an argon gas supply, equipment maintenance, and a large storage area . Technically, there are several limitations to this procedure: the lesion should have an adequate distance from the skin, neurovascular structure and other viscera, and should not be localized in a weight - bearing bone. The average time of the procedure has been longer than for other percutaneous thermal ablation techniques performed at our institute (data not shown).
There are a few limitations in the present study. Most critically, the sample size is relatively small, as is the case for past reports using a small case series. The wide differences in follow - up duration stems from the lack of insurance coverage for this procedure in Japan which costs approximately 9000 U.S. dollars. This has been the major obstacle in recruiting large number of patients. In addition, the results may have been biased because only relatively small sized lesions were included in the study. Nevertheless, ablation for asymptomatic metastases or local recurrence for local control has not been thoroughly reported, and our data should provide a basis for further clinical studies to clarify the efficacy of this technique in treating such patients.
The outcomes from this study suggest that cryoablation is clinically safe and feasible, because no local recurrence was observed in any of the cases. Further prospective randomized studies are warranted to elucidate the optimum protocol for this technique and effectiveness for a variety of histologically different tumors.
This work did not receive funding.
Availability of data and materials
All relevant materials are provided in the manuscript.
MS performed the data analysis and manuscript writing. KK, RN, KN, and KH performed the collection and assembly of data. SO, MI, and HY contributed to writing of the manuscript. SN, MN, MM and KC provided administrative support. HM was responsible for providing the study materials for evaluating the patients and provided final approval of the manuscript. All authors read and approved the final manuscript.
The authors declare that they have no competing interest.
Consent to publish
Ethics approval and consent to participate
This study was approved by the ethics committee of Keio University School of Medicine. Written informed consent was obtained from each participant enrolled in the study.
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