Eficacia, seguridad y eficiencia de la radioterapia corporal estereotáctica aplicada con marcadores de referencia en oncología

Introduction Stereotactic body radiotherapy (SBRT) is a technology that involves delivering high doses of radiation, in few sessios and with high precision, to a specific tumor localization minimizing radiation exposure to adjacent healthy tissues. Reference or fiducial markers are small radiopaque objects placed inside or around the tumor to mark the target area of radiation to ensure precise localization of the tumor, prevent external anatomy movements, and provide more targeted radiation delivery during oncology treatments. Their placement is not compulsory, but they could help to improve the precision of the SBRT procedure and reduce the toxicity compared to conventional radiotherapy techniques. Objective The objective is to evaluate the efficacy, safety and efficiency of SBRT techonology along with reference markers in the treatment of cancer patients, preferably with liver neoplasia. Method An exploratory literature search was conducted to identify SRs and HTA reports. It was found that the evidence related to the proposed preferred clinical indication was scarce. Therefore, a SR of the literature was carried out including observational studies and RCTs, and the range of oncological conditions was expanded. The following reference databases were consulted up to September 2024 (with open-source and controlled language): Medline (Ovid), Embase, Cochrane Library, WOS (SCI), INAHTA, and CINAHL. The CDA-AMC website and the AHRQ, ICTPR, NICE, RedETS, Clinical Trials, and TripDataBase databases were also explored as complementary resources. Likewise, secondary manual searches were conducted to identify additional studies. Study selection, data extraction, and quality analysis were performed independently by peer review. The results were synthesized qualitatively. Study quality was assessed using AMSTAR-2 tool for systematic reviews and NOS tool for cohort studies. Results Of a total of 1,732 references retrieved, ten studies were included, nine were retrospective observational studies (liver, lung, pancreatic, and prostate cancer), and one SR with MA (prostate cancer). Three ongoing RCTs were also located (liver and prostate cancer). The evidence identified is limited, in terms of patient clinical and demographic conditions, the image technologies applied with the index test (SBRT), the absence of comparators, and the presence or absence of fiducial markers. Three studies have good quality, six low quality, and one critically low quality. Two prostate cancer studies were identified: a SR with MA and a retrospective cohort. In the SR the authors evaluated the rates of GU and GI toxicity in patients treated with SBRT technology with adaptative RM or CT guidance and reference markers. The analysis showed that the risk of short-term GU and GI adverse events decreased with RM guidance, 16 % and 4 %, compared with CT and fiducial markers, 28 % and 9 %, respectively. Among CT studies, when comparing the use or not of markers, the decrease in GU and GI toxicity was not statistically significant. The cohort study evaluated the distribution of radiation dose in the tumor area using RM or IGRT with fiducial markers, and the associated adverse events. RM showed higher precision in the restriction zone, rate of 98 %, similar to IGRT guidance with reference markers (98 %). However, IGRT without markers showed lower compliance rate (62 %) indicating higher probability of radiation in healthy tissues. No serious adverse events were reported. Two retrospective cohorts of NSCLC patients were identified. The outcomes evaluated were local control and survival rates, and adverse events in patients treated with SBRT with or without fiducial markers. The first cohort used two guidance techniques: 1) Synchrony® SBRT guidance with the insertion of two types of fiducial markers (gold coiled and spherical), and 2) Xsight® Spine guidance without fiducial markers. The probability of local control, disease-free survival, and overall survival were similar at 2 and 5 years, with no stastistically significant differences between the groups with or without fiducial markers. No serious adverse events were reported, except for the insertion of spherical gold markers due to intrathoracic implantation. In the second cohort, the rates of local control, disease-free survival, and overall survival at 2 years did not show statistically differences with a reference marker-guided system (Synchrony® Respiratory Motion Tracking System) compared to two non-marker methods (Xsight® Spine Tracking System o Xsight® Lung Tracking System). No serious adverse events were reported. A retrospective cohort of pancreatic cancer patients was identified. Local recurrence, overall survival, metastasis-free survival, recurrence-free survival, progression-free survival, and adverse events were evaluated for SBRT with or without fiducial marker implantation. None of the variables showed statistically significant differences when comparing the two groups. No serious adverse events were reported. Regarding liver cancer, five studies were identified which evaluated local control, disease progression and survival rates, and adverse events at 1 and/or 2 years after SBRT treatment with or without fiducial marker implantation. One study analized the prognostic factores associated to local control and overall survival. Only one study included a comparator group with and without markers. In the remaining four studies all patients had implanted markers. The comparison revealed that the overall survival rate of patients with reference markers was more favorable than without markers (72.6 % vs. 42.1 %, respectively, p = 0.013). In the remaining studies, the presence of markers offered acceptable control, overall survival, and disease-free survival rates, but without the possibility of comparison. No serious adverse events associated with the intervention or marker implantation were detected. Additionally, three ongoing RCTs were identified. Two studies evaluated GU and GI toxicity, local control and survival rates, and quality of life in patients with prostate cancer undergoing different radiotherapy techniques compared with SBRT, with or without fiducial markers implantation. The third study was focused on evaluating the efficacy and safety of fiducial marker implantation along with SBRT for the treatment of liver cancer. Conclusions The SR identified studies with limited evidence on the efficacy and safety of SBRT technology along with fiducial markers. No studies on efficiency were identified. Nine studies about prostate, pancreatic, lung and liver cancer are retrospective observational studies (4 without a comparator group) that evaluate local tumor control, survival, disease progression, recurrence, toxicity, and/or delimitation of the applied radiation doses. One study is a SR with MA which evaluates the differences in the use of fiducial markers with SBRT on GU and GI toxicity in patients with prostate cancer. The studies show variability in terms of the patients' clinical indications, presence of markers and comparators, and guidance techniques along with SBRT. The quality assessment resulted in low and critically low quality in seven of the analyzed studies. The application of SBRT technology along with fiducial markers would be an effective first-line alternative for the treatment of cancer patients, or for those in whom surgery is not possible or whose are clinically compromised. The use of fiducial markers would allow more precise and controlled radiation dose. Their use is associated with non-severe adverse events. However, due to the limited evidence identified in the SR, an evaluation of the efficacy and safety of SBRT technology with reference markers has not been possible in order to obtain consistent conclusions. Prospective studies with larger numbers of patients and different clinical conditions are needed to compare SBRT technology with and without the implantation of fiducial markers, to determine the efficacy and influence of the markers in the presence of adverse events derived from their implantation and/or type. Likewise, it would be recommended for these studies to include organizational, economic, and patient perspective aspects, evidence not detected in this report.