Journal of Radiation and Cancer Research

ORIGINAL ARTICLE
Year
: 2020  |  Volume : 11  |  Issue : 3  |  Page : 94--99

Prospective evaluation of fiducial migration and complications after placement for hepatocellular carcinoma treated with stereotactic body radiotherapy using cyberkinife and influence on treatment delivery: A tertiary cancer centre experience


Kaushik Kataki1, Debnarayan Dutta1, Ram Madhavan1, Manoj Kalita2,  
1 Department of Radiation Oncology and Radiation Physics, Amrita Institute of Medical Sciences, Kochi, Kerala, India
2 Department of Biostatistics and Epidemiology, Dr B Borooah Cancer Institute, Guwahati, Assam, India

Correspondence Address:
Dr. Kaushik Kataki
Department of Radiation Oncology and Radiation Physics, Amrita Institute of Medical Sciences, Kochi, Kerala
India

Abstract

Background: Hepatocellular carcinoma (HCC) is the most common primary tumor of the hepatobiliary system. The Cyberknife represents a new, frameless stereotactic radiosurgery system with image-guided radiation delivery using fiducials as markers to overcome the movement of intra-abdominal organs due to respiration. However fiducial placement and treatment have its issues such as migration and other complications. Objectives: We evaluated the accuracy and feasibility of fiducial placement under image guidance and complications during and after placement such as migration including pain score. Materials and methods: A prospective observational study was carried out on 36 subjects with clinically and radiologically diagnosed hepatocellular carcinoma receiving Cyberknife based stereotactic based radiotherapy (SBRT). Fiducial markers for SBRT were introduced under percutaneous Ultrasound (US) or CT guidance. After placement, fiducial migration rate, pain score, fiducial placement related complications were noted during and after therapy. IBM SPSS statistical software version 21 was used for statistical analysis. Results: 8.4% had gross fiducial displacement on the day of the procedure. 90.9% had minimal migration during treatment.There was no gross migration seen during treatment or post-treatment. Post fiducial placement, 2.8 % had a major complication in the form of liver decompensation resulting in death while minor complications were observed in 13.9%. The average pain score was minimal (0.86) post fiducial placement. There was no pain in any of the patients during or after the treatment. Conclusion: Image-guided implantation of fiducial markers in the liver for stereotactic body radiation therapy had a high technical success rate and is a safe procedure with rare complications.There is minimal fiducial migration seen during the treatment. But being a descriptive study with a small sample size limits the generalizability of our study findings..



How to cite this article:
Kataki K, Dutta D, Madhavan R, Kalita M. Prospective evaluation of fiducial migration and complications after placement for hepatocellular carcinoma treated with stereotactic body radiotherapy using cyberkinife and influence on treatment delivery: A tertiary cancer centre experience.J Radiat Cancer Res 2020;11:94-99


How to cite this URL:
Kataki K, Dutta D, Madhavan R, Kalita M. Prospective evaluation of fiducial migration and complications after placement for hepatocellular carcinoma treated with stereotactic body radiotherapy using cyberkinife and influence on treatment delivery: A tertiary cancer centre experience. J Radiat Cancer Res [serial online] 2020 [cited 2020 Dec 3 ];11:94-99
Available from: https://www.journalrcr.org/text.asp?2020/11/3/94/296557


Full Text



 Introduction



The hepatobiliary system refers to the liver, bile ducts, and gallbladder. Tumors of the liver and biliary tree, mainly hepatocellular carcinoma (HCC) and cholangiocarcinoma, are the second leading cause of cancer-related death worldwide and the sixth leading cause of cancer-related death among men in developed countries.[1] The most common adult malignant liver tumors are HCC, metastases to the liver, fibrolamellar HCC, epithelioid hemangioendothelioma, and angiosarcoma. The yearly worldwide burden of hepatobiliary malignancy is estimated to be 782,500 new liver cancer cases and 745,500 liver cancer-related deaths, according to the Global Cancer Statistics of 2012.[2] The range of treatments for HCC may range from surgical resection, chemotherapy, and radiotherapy alone or in combination. Stereotactic-based radiotherapy (SBRT) is a highly sophisticated, noninvasive, image-guided, radiation therapy that allows the delivery of a precise dose of radiation using multiple, photon beams that intersect at a stereotactically determined target and therefore emits higher doses of radiation delivery to the tumor when sparing surrounding normal tissue.[3] SBRT is an effective therapy for patients with HCC with an overall best response rate (complete response + partial response) of 73%.[3] The CyberKnife represents a new, frameless stereotactic radiosurgery system which efficiently incorporates advance robotics with computerized image reconstruction to allow highly conformal image-guided radiation delivery.[4] There are some technical difficulties when SBRT is applied to the liver. The movement of intra-abdominal organs due to respiration has to be taken into consideration when using SBRT for effective dose delivery to the target. The liver is one of the organs moving continuously caused by respiration. Fiducial markers can be used for tumor tracking in CyberKnife-based SBRT and are generally introduced under percutaneous ultrasound (US) or computed tomography (CT) guidance.[5] While previous studies[6],[7] have reported the efficacy and safety of US- or CT-guided, fiducial marker implants in the liver, the number of these studies is limited due to the small number of patients. Moreover, they did not specifically mention the efficacy of guided, fiducial marker insertion in poorly conspicuous lesions. However, fiducial placement has its own issues and need to be addressed. It leads to a delay in treatment. The procedure is associated with additional costs, and the fiducials can create significant imaging artifacts on CT.[8] The fiducial placement procedure is also associated with potential risks and complications such as pain, vasovagal attack, pneumothorax, hemothorax, perforation of nontarget organs, bile peritonitis, infection, hemobilia, neuralgia, and tumor seeding.[9] The literature on fiducial-related complications and migration-related parameters from India is very scarce, and also the compliance, acceptability, and pain-related issues might not be similar in the Indian population as seen in Western population and studies. Therefore, we carried out our study to evaluate the accuracy and feasibility of fiducial placement under image guidance and to evaluate the fiducial migration rate, pain score, and fiducial placement-related complications.

 Methods



Selection and description of participants

We carried out a prospective observational study on 36 patients after getting approval from the institutional ethics committee. Since no prospective study could be located in the existing literature to assess the accuracy of fiducial placement and the fiducial migration rate in HCC in the Indian population, we did a pilot study and included 30 consecutive patients who were clinically, radiologically, or pathologically diagnosed with HCC and eligible for fiducial placement and CyberKnife-based radiation treatment in Amrita Institute of Medical Sciences, Kochi, between May 2017 to August 2018. We excluded patients who were unfit for fiducial placement and with poor performance status.

Technical information

Objectives

Primary

To evaluate the accuracy and feasibility of fiducial placement under image guidance and to evaluate the fiducial migration rate in patients with clinically and radiologically diagnosed HCC receiving CyberKnife-based SBRT.

Secondary

To assess the pain score and fiducial placement-related complications in the patient.

All baseline blood investigations were performed including a complete hemogram, preoperative serology, prothrombin time with the international normalized ratio, liver function tests, and renal function tests. Fiducial placement was done under computed tomographic (Siemens Somatom Emotion 16-slice CT) or ultrasonographic (Philips IU 22 USG) guidance under sterile conditions by an interventional radiologist in the presence of radiation oncologist to guide the placement of the fiducials. Three gold fiducials were inserted percutaneously under image guidance using a cylindrical 20-cm long 18-gauge puncture needle, with a preloaded fiducial marker. Each fiducial was a cylinder made from 99% pure gold with whorl on the surface. It weighed 17 g and has a size of 1.2 mm × 5.0 mm (Reference: GF1521, Gold Fiducial Marker, Manufacturer: IZI Medical Products, Owings Mills, MD 21117, U.S.A). The accuracy of fiducial placement was scored by the interventional radiologist and the radiation oncologist independently based on a self-devised fiducial placement accuracy scoring system looking into parameters such as interfiducial distance, interfiducial angle, distance from the center of the tumor, and any gross displacement or complications.

Points were given for each of the parameters accordingly and then summed up to get a total score and grade. Postprocedure pain scoring at 30 min postprocedure was done using Wong–Baker visual analog pain scale[10] and any complications during or after the procedure were recorded and graded using SIR[11] complication grading system. Any intervention for complications and the postprocedure recovery time was also documented and graded as per a self-devised grading system. A thin-slice (1.25 mm) CT scan along with anteroposterior and lateral X-Ray of the liver at the end of expiration using a stereotactic body frame (Vacloc) for immobilization in the supine position was performed in the in-house dedicated CT simulation machine (GE optima series 580 WRT 360-slice, 120 kV, 450 mA). The images were taken from manubrium sterni to L5 vertebrae to assess for any gross migration or complications. It was termed as the day 0 scan. Planning CT was taken on day 3 postfiducial placement along with additional thin-slice (1.25 mm) CT and AP and lateral X-ray of the liver at the end of expiration using a Vacloc for immobilization to assess the migration of fiducial from baseline. Pretreatment pain score, complications, and intervention for complication on day 3 postfiducial placement were also documented. The thin-slice CT scans and the X-ray images of day 0 and day 3 were fused on Medvision image viewing software. The XYZ coordinates of the fiducial markers were analyzed, and the maximum and minimum migration from baseline were documented. The planning CT images were then transferred to the CyberKnife workstation (Accuray Multiplan Version 5.3.0), where contouring of target volumes and organs at risk were done according to the RTOG guidelines followed by planning. Treatment was started on day 4 postfiducial placement, and it was delivered through Accuray CyberKnife (Model: M6 F1+) over 5 days (day 4 to day 8). At the end of 5 days of treatment (day 8 postfiducial placement), posttreatment pain score, complications, and intervention for complication were documented.

Statistical analysis

Descriptive statistics was carried out by mean and standard deviation for quantitative variables, and Chi-square test was done for qualitative variables. P < 0.05 was considered statistically significant at 95% confidence interval. IBM SPSS statistical software version 21 was used for statistical analysis.

 Results



A total of 36 participants were included in the final analysis. As shown in [Table 1], among the study population, 13 (36.1%) participants were aged up to 60 years and 23 (63.9%) were more than 60 years. Of the total study population, 33 (91.7%) participants were male and 3 (8.3%) were female. Among the study population, 19 (52.8%) participants had ECOG performance score 0, 14 (38.9%) participants had ECOG performance score 1, and 2 (8.3%) participants had ECOG performance score 2. Among the study population, 32 (88.9%) participants had Child–Pugh score A, 3 (8.3%) participants had Child–Pugh score B, and 1 (2.8%) participant had Child–Pugh score C. Among the study population, 23 (63.9%) participants had associated portal vein thrombosis (PVT). The mean total dose delivered was 37.51 ± 8.034 Gy [Table 1].{Table 1}

Among the total study population, CT was used as the imaging modality for fiducial placement in 25 (69.4%) participants, USG was used in 7 (19.4%) participants, and both CT and USG guidance were used in 4 (11.1%) participants. For all 36 (100%) participants, three fiducials were placed. The mean duration of the procedure was 23.83 ± 13.34 min, ranged between 9 and 56 min. The mean of maximum interfiducial distance was 4.77 ± 1.12 cm, and the mean minimum interfiducial distance was 2.54 ± 0.81 cm. The mean for maximum interfiducial angle was 82.7 ± 26.58°, and the mean of minimum interfiducial angle was 28.47 ± 11.86°. The mean maximum distance from the tumor center was 5.09 ± 1.24 cm, and the mean minimum distance from the tumor center was 2.09 ± 0.65 cm. Among the study population, 3 (8.4%) participants had gross fiducial displacement on the day of the procedure [Table 2].{Table 2}

As shown in [Table 3], the mean postfiducial placement pain score (day 0) was 0.86 ± 1.46. Among the study population, 30 (83.3%) participants had no complication on the day of fiducial placement postprocedure, 5 (13.9%) participants had a minor complication, and 1 (2.8%) participant had a major complication [Table 3].{Table 3}

The mean of average maximum interfractional migration was 0.29 ± 0.03 mm. The mean of average minimum interfractional migration was 0.1 ± 0.02 mm. The mean of total migration at the end of treatment on day 8 postfiducial placement was 2.37 ± 0.27 mm. Among the study population, 1 (3.0%) participant had moderate migration (3–6), 30 (90.9%) participants had minimal migration (2–3), and 2 (6.1%) participants had no migration (<2) from baseline when measured on day 8 postfiducial placement at the end of treatment. There were no gross migrations during treatment or posttreatment. The only gross displacement seen was just after fiducial placement procedure on day 0 [Table 4].{Table 4}

 Discussion



HCC is the most common primary tumor of the liver, generally developed within a context of chronic liver disease, most often cirrhosis.[12] SBRT is a technique that allows the delivery of a precise dose of radiation to a tumor when sparing adjacent normal tissues. However, the movement of intra-abdominal organs due to respiration has hampered the use of SBRT. The CyberKnife is a unique noninvasive radiosurgical system, capable of treating any part of the body from any of approximately 1600 different targeting angles, creating a highly conformal three-dimensional radiosurgical treatment volume, guided by orthogonal X ray-based targeting feedback, and delivering radiation by a highly collimated, robotically controlled linear accelerator. There is no well-known prospective study looking into the actual rate of fiducial migration, the accuracy of fiducial placement and its utility in treatment planning, pain score, and procedure-related parameters in the Indian population. Hence, we undertook this study. Our study objectives were similar to that of Park et al., Ohta et al., and Choi et al. Park et al. evaluated the efficacy and safety of US-guided marker implantation for SBRT. Ohta et al. evaluated the technical and clinical success rates of the procedure of fiducial markers placement for SBRT and the frequencies of complications.[5],[13],[14] Choi et al. determined the safety and technical feasibility of endoscopic ultrasonography-guided fiducial placement for SBRT.[14] In our study, the proportion of people with successful fiducial placement in the liver was 91.6%. 8.4% (n = 3/36) had gross fiducial displacement on the day of the procedure. Two fiducials (2.7%) migrated into the lung, whereas one fiducial (5.5%) migrated into the abdomen. There was no gross migration seen during treatment or posttreatment.

The only gross displacement outside the liver was seen just after the fiducial placement procedure on day 0. Technical success was achieved in 291 (97.3%) fiducial marker implantations by Park et al., which was slightly higher than seen in our study.[5] Park et al. in their study observed that eight markers (2.7%) developed migration.[5] Of those eight migrated markers, seven were not seen on the planning CT. Postfiducial placement, no complications were observed in 83.3% of the patients in our study. In the study by Park et al.,[5] no one had major complications, whereas 12% had minor complications. In our study, 2.8% had a major complication in the form of liver decompensation resulting in the death of the subject within 24 h of the procedure. Further, two more patients had decompensation before the start of treatment and hence could not continue. 13.9% of patients had minor complications in the form of pain, mild pneumothorax, or fatigue postprocedure, which required symptomatic treatment only. The amount of pain reported after postfiducial placement was very minimal in our study, with the average pain score being 0.86. Pain scoring was not evaluated by Park et al. and Choi et al. for comparison with their studies.[5],[14] Choi et al. in their study observed that one patient (3.1%) developed mild pancreatitis posttreatment,[14] but in our study, no one had any pain or complication during or posttreatment. Park et al. in their study also observed no complications during this interval.[5] No major complications such as coil migration or bleeding were observed by Ohta et al.[13] In our study, 90.9% had minimal migration from baseline in the range of 2–3 mm when evaluated at the end of treatment with the mean for total migration being 2.33 ± 0.27 mm.

With regard to sociodemographic factors affecting our study results, the majority of our participants (63.9%) were aged more than 60 years, and 91.7% were male. Similarly, Park et al. also observed the majority were male (73%).[5] In their study, 82% had a Child–Pugh score of category “A,” and similarly, in our study, 88.9% of participants had a Child–Pugh score classification of “A.” In our study, liver segments VIII (44.4%), VI (38.9%), IV (27.8%), V (27.8%), and VII (27.8%) were commonly involved. In our study, 63.9% had associated PVT, but only 5% had PVT in the study by Park et al. Park et al. also observed a higher tumor incidence in segment IV.[5] SBRT typically consists of one to five treatment sessions delivered over the course of one to two weeks. Among our study population, the mean dose per fraction was 8.342 ± 2.06 Gy, whereas the mean total dose given was 37.51 ± 8.034 Gy. Park et al. in their study did not mention the dose of radiation used.[5] Similar to our study, Choi et al. in their study delivered fractional doses of 6–8 Gy, delivered to target volume for consecutive 4 days.[14]

In CyberKnife-based SBRT using the X-ray-based real-time image guidance system, a fiducial marker is usually placed in or near the tumor for tumor tracking during treatment. Depending on the location of the tumor, a radiation oncologist may work with a pulmonologist, gastroenterologist, or interventional radiologist to have one to four fiducial markers placed near the tumor. Placement of the fiducial marker is almost always an outpatient procedure. Optimal positioning of fiducials in relation to a lesion might vary according to the equipment used for SBRT. When performing fiducial implantations for SBRT using CyberKnife, it is advised to maintain a minimum spacing of 15 mm and a minimum 15° angle between the fiducials.[7] At least a 1-cm distance between the fiducial marker and the tumor was recommended to avoid tumor margin blurring. Fiducial markers can develop artifacts and obscure margins of the tumor, especially in small lesions. This is important as an indistinct tumor margin offers only limited evaluation of a tumor on planning and follow-up CT studies. Kothary et al. reported that if the tumor diameter is <2 cm, a marker inserted into the tumor may obscure the tumor margin.[5],[7] In our study, 69.4% had CT as the imaging modality for fiducial placement, whereas 19.4% had USG. Park et al. in their study performed all procedures under USG guidance.[5] The mean duration of fiducial placement was 23.8 min in our study. Other authors (Park et al.) did not assess or mention the duration of fiducial placement as a significant factor in their studies.[5] In our study, the mean maximum distance from the tumor center was 5.09 cm, whereas the minimum was 2.09 cm. The mean distance between the tumor margin and the markers was 3.1 cm in their study.[5] Oldrini et al. in their study also observed that the mean distance between the markers and the lesion was 3.2 cm.[15] Park et al. in their study found that 72% had fiducial markers located in an ideal location.[5] In our study, the maximum mean interfiducial distance was 4.77 cm, whereas the minimum means interfiducial distance was 2.54 cm, but Oldrini et al. in their study observed that the mean distance between the markers was only 1.7 cm.[15] This variation could have been caused due to the tumor size and other morphological differences. The mean interfiducial angle in our study was 82.7° with a range of 12°–117.5°. Other authors did not focus on these angles, and hence data from the literature regarding these angles were limited.

Strength and limitations

Our study was the first of its kind in our region to prospectively evaluate the fiducial placement-related parameters, complications, and fiducial migration. The key limitation of the current study was the descriptive nature of the study and a very small sample size without a proper sampling frame. Due to the descriptive nature of the study, no analysis could be done on the factors associated with postfiducial complications among the study population. The role of potential confounding factors also could not be evaluated due to limited sample size and the descriptive nature of the study. Considering the single center nature of the study, the generalizability of study findings is limited. Use of activated breath coordinator system during simulation and treatment would have resulted in stricter immobilization and hence a more accurate assessment of fiducial migration compared to other studies.

 Conclusions



Our study results showed that imaging-guided implantation of fiducial markers in the liver for stereotactic body radiation therapy had a high technical success rate and is a safe procedure with rare complications. There is a minimal migration of fiducials seen postfiducial placement and during the treatment and it does not lead to any break in treatment or complications. Hence, there is also a potential for shortening the waiting time before starting treatment postfiducial placement.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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