Prospective analysis of hydrogel spacer for patients with prostate cancer undergoing radiotherapy.

OBJECTIVE: To report on the dosimetric benefits and late toxicity outcomes after injection of hydrogel spacer (HS) between the prostate and rectum for patients treated with prostate radiotherapy (RT). PATIENTS AND METHODS: In all, 76 patients with a clinical stage of T1-T3a prostate cancer underwent general anaesthesia for fiducial marker insertion plus injection of the HS into the perirectal space before intensity-modulated RT (IMRT) or volumetric-modulated arc RT (VMAT). HS safety, dosimetric benefits, and the immediate- to long-term effects of gastrointestinal (GI) toxicity were assessed. RESULTS: There were no postoperative complications reported. The mean (range) prostate size was 66.0 (25.0-187.0) mm. Rectal dose volume parameters were observed and the volume of rectum receiving 70 Gy (rV70 ), 75 Gy (rV75 ) and 78 Gy (rV78 ) was 7.8%, 3.6% and 0.4%, respectively. In all, 21% of patients (16/76) developed acute Grade 1 GI toxicities, but all were resolved completely by 3 months after treatment; whilst, 3% of patients (2/76) developed late Grade 1 GI toxicities. No patients had acute or late Grade ≥2 GI toxicities. CONCLUSION: Injection of HS resulted in a reduction of irradiated rectal dose volumes along with minimal GI toxicities, irrespective of prostate size.

Transperineal gold marker implantation for image-guided external beam radiotherapy of prostate cancer : A single institution, prospective study.

PURPOSE: To present the feasibility and complications of transperineal fiducial marker implantation in prostate cancer patients undergoing image-guided radiotherapy (IGRT) METHODS AND MATERIALS: Between November 2011 and April 2016, three radiopaque, gold-plated markers were transperineally implanted into the prostate of 300 patients under transrectal ultrasound guidance and with local anaesthesia. A week after the procedure patients filled in a questionnaire regarding pain, dysuria, urinary frequency, nocturia, rectal bleeding, hematuria, hematospermia or fever symptoms caused by the implantation. Pain was scored on a 1-10 scale, where score 1 meant very weak and score 10 meant unbearable pain. The implanted gold markers were used for daily verification and online correction of patients' setup during IGRT. RESULTS: Based on the questionnaires no patient experienced fever, infection, dysuria or rectal bleeding after implantation. Among the 300 patients, 12 (4%) had hematospermia, 43 (14%) hematuria, which lasted for an average of 3.4 and 1.8 days, respectively. The average pain score was 4.6 (range 0-9). Of 300 patients 87 (29%) felt any pain after the intervention, which took an average of 1.5 days. None of the patients needed analgesics after implantation. Overall, 105 patients (35%) reported less, 80 patients (27%) more, and 94 patients (31%) equal amount of pain during marker implantation compared to biopsy. The 21 patients who had a biopsy performed under general anesthesia did not answer this question. CONCLUSION: Transperineal gold marker implantation under local anesthesia was well tolerated. Complications were limited; rate and frequency of perioperative pain was comparable to the pain caused by biopsy. The method can be performed safely in clinical practice.

A review of the use of fiducial markers for image-guided bladder radiotherapy.

BACKGROUND: Enhancing target visualization and reducing set-up errors in image-guided radiotherapy (IGRT) are issues faced when trying to implement more conformal and partial bladder techniques. This review examines the evidence available pertaining to the clinical use of Lipiodol and gold fiducials for IGRT for bladder cancer. MATERIAL AND METHODS: Nine published articles relating to the feasibility of using Lipiodol injections or gold fiducial markers in IGRT for bladder patients were recruited from a database search strategy. Set-up errors were evaluated in addition to the stability and visibility of each on verification imaging. Adverse reactions from the insertion of each method were also assessed. RESULTS: Both Lipiodol and gold fiducials have the potential to remain stable and visible in the bladder, however, fading, washout and seed loss was also reported. Set-up errors can be reduced by using Lipiodol or fiducial registration when compared to other registration techniques. Adverse reactions reported were minimal for each. CONCLUSION: Current evidence suggests that Lipiodol injections and gold fiducial markers present as promising and highly accurate methods of overcoming interfraction bladder motion in IGRT.

Fiducial markers and spacers in prostate radiotherapy: current applications.

OBJECTIVES: To review the use of fiducial markers and spacers in prostate radiotherapy (RT). MATERIALS AND METHODS: We reviewed the literature on the use of fiducial markers to improve accuracy in delivery of RT for prostate cancer. We discuss the rationale for fiducials, the types available, the procedures and complications. We also reviewed the current literature on the novel use of spacers to reduce rectal toxicity during prostate irradiation. RESULTS: Prostate motion is a significant problem both during and between RT treatments. Intraprostatic fiducials allow accurate prostate localisation ensuring RT treatment accuracy. Insertion of gold fiducials are a cost-effective marker that can be easily and quickly implanted and at least three fiducials are recommended. Severe complications from fiducial implantation are uncommon and marker migration is very rarely clinically significant. Spacers are a novel method to distance the rectum from the prostate during RT, reducing acute rectal toxicity, and have no detrimental impact on health-related quality of life. CONCLUSIONS: Intraprostatic fiducials are now standard of care when delivering prostate RT and early data shows benefit of spacers in reducing RT rectal toxicity.

Comparative analysis of traditional and coiled fiducials implanted during EUS for pancreatic cancer patients receiving stereotactic body radiation therapy.

BACKGROUND: EUS-guided fiducial placement facilitates image-guided radiation therapy (IGRT). OBJECTIVE: To compare 2 types of commercially available fiducials for technical success, complications, visibility, and migration. DESIGN: Retrospective, single-center, comparative study. SETTING: Tertiary-care medical center. INTERVENTIONS: Traditional fiducials (TFs) (5-mm length, 0.8-mm diameter) and Visicoil fiducials (VFs) (10-mm length, 0.35-mm diameter) were compared. Fiducials were placed using linear 19-gauge (for TFs) or 22-gauge (for VFs) needles. A subjective visualization scoring system (0-2; 0 = not visible, 1 = barely visible, 2 = clearly visible) was used to assess visibility on CT. Fiducial migration was calculated as a change in interfiducial distance. MAIN OUTCOME MEASUREMENTS: Technical success, complications, visibility, and migration of 2 types of fiducials. RESULTS: Thirty-nine patients with locally advanced pancreatic cancer underwent EUS-guided placement of 103 fiducials (77 TFs, 26 VFs). The mean number of fiducials placed per patient was 2.66 (standard deviation 0.67) for the 19-gauge needle and 2.60 (standard deviation 0.70) for the 22-gauge needle (P = .83). No intra- or postprocedural complications were encountered. The median visibility score for TFs was significantly better than that for VFs, both when scores of 0 were and were not included (2.00, interquartile range [IQR] 2.00-2.00 vs 1.75, IQR 1.50-2.00, P = .009 and 2.00, IQR 2.00-2.00 vs 2.00, IQR 1.50-2.00, P < .0001, respectively). The mean migration was not significantly different between the 2 types of fiducials (0.8 mm [IQR 0.4-1.6 mm] for TFs vs 1.3 mm [IQR 0.6-1.5 mm] for VFs; P = .72). LIMITATIONS: Retrospective, nonrandomized design. CONCLUSIONS: Visibility was significantly better for TFs compared with VFs. The degree of fiducial migration was not significantly different for TFs and VFs. There was no significant difference in the mean number of fiducials placed, indicating a similar degree of technical difficulty for TF and VF deployment.

Safety profile and technical success of imaging-guided percutaneous fiducial seed placement with and without core biopsy in the abdomen and pelvis.

OBJECTIVE: The purpose of this study is to determine whether complications associated with combining biopsy and percutaneous fiducial seed placement in the abdomen and pelvis exceeds that of either procedure alone or prohibits completion of the combined procedure. MATERIALS AND METHODS: A retrospective review was performed of 188 consecutive patients who underwent CT- or ultrasound-guided placement of fiducial seeds in the abdomen or pelvis, either alone (group 1, n = 117) or with concomitant biopsy (group 2, n = 71), from October 2005 through April 2010. Complications classified according to the Society of Interventional Radiology guidelines were compared between both groups using the Z test for proportions, as were the number of seeds per patient and seed migration and technical success rates. RESULTS: One hundred eighty-eight patients underwent percutaneous placement of 533 fiducial seeds in the abdomen and pelvis. Eight patients (4.3%) had complications. Five were minor (four small hematomas and one pneumothorax) and three were major (two cases of bleeding and one of sepsis). There was no significant difference between groups with respect to minor complication rates, number of seeds placed per patient (p = 0.85), or technical success (p = 0.33). Significantly more major complications (p = 0.04) occurred in group 2, but the rate was similar to that for percutaneous biopsy alone as reported in the literature. Group 2 also had more seed migration (p = 0.02). CONCLUSION: Biopsy and fiducial seed placement in the abdomen and pelvis can be performed in the same session rather than separately, with a high rate of technical success and without an increased risk of complications when compared with either procedure alone.

CT-guided microcoil localization of pulmonary nodules: the effect of the position of microcoil proximal end on the incidence of microcoil dislocation.

OBJECTIVES: To evaluate the effect of the position of microcoil proximal end on the incidence of microcoil dislocation during CT-guided microcoil localization of pulmonary nodules (PNs). METHODS: This retrospective study included all patients with PNs who received CT-guided microcoil localization before video-assisted thoracoscopic urgery (VATS) resection from June 2016 to December 2019 in our institution. The microcoil distal end was less than 1 cm away from the nodule, and the microcoil proximal end was in the pleural cavity (the pleural cavity group) or chest wall (the chest wall group). The length of microcoil outside the pleura was measured and divided into less than 0.5 cm (group A), 0.5 to 2 cm (group B) and more than 2 cm (group C). Microcoil dislocation was defined as complete retraction into the lung (type I) or complete withdrawal from the lung (type II). The rate of microcoil dislocation between different groups was compared. RESULTS: A total of 519 consecutive patients with 571 PNs were included in this study. According to the position of microcoils proximal end on post-marking CT, there were 95 microcoils in the pleural cavity group and 476 in the chest wall group. The number of microcoils in group A, B, and C were 67, 448 and 56, respectively. VATS showed dislocation of 42 microcoils, of which 30 were type II and 12 were type I. There was no statistical difference in the rate of microcoil dislocation between the pleural cavity group and the chest wall group (6.3% vs 7.6%, x2 = 0.18, p = 0.433). The difference in the rate of microcoil dislocation among group A, B, and C was statistically significant (11.9%, 5.8%, and 14.3% for group A, B, and C, respectively, x2 = 7.60, p = 0.008). In group A, 75% (6/8) of dislocations were type I, while all eight dislocations were type II in group C. CONCLUSIONS: During CT-guided microcoil localization of PNs, placing the microcoil proximal end in the pleura cavity or chest wall had no significant effect on the incidence of microcoil dislocation. The length of microcoil outside the pleura should be 0.5 to 2 cm to reduce the rate of microcoil dislocation. ADVANCES IN KNOWLEDGE:: CT-guided microcoil localization can effectively guide VATS to resect invisible and impalpable PNs. Microcoil dislocation is the main cause of localization failure. The length of microcoil outside the pleura is significantly correlated with the rate and type of microcoil dislocation. Placing the microcoil proximal end in the pleura cavity or chest wall has no significant effect on the rate of microcoil dislocation.

Ultrasound-guided transrectal implantation of fiducial markers for image-guided radiotherapy of prostate cancer without local anesthesia: Patient-reported gastrointestinal-genitourinary system complications and pain.

PURPOSE: The present study evaluates procedure-associated pain and side effects in the gastrointestinal-genitourinary system in patients with early-stage prostate cancer who were treated with image-guided radiotherapy (IGRT), accompanied by an ultrasound-guided transrectal implantation of fiducial markers, without local anesthesia. MATERIALS AND METHODS: A total of 46 patients who referred to our clinics between 2012 and 2017 with a diagnosis of early-stage prostate cancer were included in the study. Before undergoing radiotherapy, all patients were implanted with three intraprostatic fiducial markers through the ultrasound-guided transrectal approach without local anesthesia. The patients underwent radiotherapy after the clinical target volumes were established, in accordance with the respective risk groups, and localization of the markers was confirmed before each therapy session. The levels of procedure-associated pain and side effects were graded immediately after the procedure through the use of a patient-based scoring system. RESULTS: The faces pain scale - revised version was used for the measurement of the severity of procedure-associated pain. Of the total study sample, the facial expressions of 38 patients (35%) corresponded to level 0 in the study, seven (15%) to level 2, and a single patient (2%) to level 4. None of the facial expressions of the patients corresponded to levels 6, 8, or 10. The evaluation of procedure-related genitourinary and gastrointestinal system side effects indicated that nine patients (20%) experienced side effects, while no side effects were reported in 37 patients (80%). The reported side effects included rectal bleeding in two patients (4%), dysuria in three patients (6%), hematuria in five patients (11%), and frequent urination in five patients (11%). None of the patients experienced fever or hematospermia. All side effects were reported by the respondents as "a little," while only one patient answered positively to the question on the frequency of urination. Among the patients who answered "yes" and "a little" to the questions evaluating genitourinary and gastrointestinal system side effects, the severity of these events was reported as Grade 1, corresponding to mild adverse, in only 9 (20%) patients. None of the patients experienced a Grade 2 or higher severe adverse event. In the comparison of the severity of pain of the patients during the fiducial marker procedure without local anesthesia with the severity of pain during the biopsy, 24 patients (80%) reported "lower" levels of pain, while five patients (20%) reported "equal" levels of pain. None of the patients stated that they had experienced "more" pain. CONCLUSION: IGRT accompanied by an ultrasound-guided implantation of fiducial markers without local anesthesia can be considered a safe method, given the associated acceptable levels of pain, low side effect profiles, and high prostate-specific antigen control rates.

Patient and clinician satisfaction and clinical outcomes of Magseed compared with wire-guided localisation for impalpable breast lesions.

BACKGROUND: Guide-wire localisation remains the most commonly used technique for localisation of impalpable breast lesions in the UK. One alternative is magnetic seed localisation. We aimed to investigate patient and clinician satisfaction in two consecutive cohorts, describe re-excision and positive margin rates, and explore reasons for positive margins and the implications for localisation techniques. METHODS: A single-institution prospective service evaluation of two cohorts of consecutive cases of wire and then Magseed localisation was carried out. Data were collected on patient and clinician satisfaction, clinico-pathological findings, and causes of involved margins. T tests were used to compare continuous variables and Chi-squared test for satisfaction outcomes. RESULTS: 168 consecutive cases used wire-guided localisation (WGL) and 128 subsequent cases used Magseeds. Patients reported less anxiety between localisation and surgery in the Magseed group, and clinicians reported greater ease of use of Magseeds. There were no differences in lesion size, surgical complexity, or re-excision rate between the groups. In a subset of patients receiving standard wide local excision (i.e., excluding mammoplasties), the impact on margin involvement was investigated. There was no significant difference in radiological under-sizing or accuracy of localisation. However, specimen weight and eccentricity of the lesion were statistically significantly lower in the Magseed group. Despite this, re-excision rates were not significantly different (p = 0.4). CONCLUSIONS: This is the first large study of satisfaction with localisation and showed clinician preference for Magseed and a reduction in patient anxiety. It also demonstrated similar positive margin rates despite smaller specimen weights in the Magseed group. Magnetic seed localisation offers an acceptable clinical alternative to guide wire localisation. The impact on local service provision should also be considered.

Implantation of electromagnetic transponders following radical prostatectomy for delivery of IMRT.

INTRODUCTION: Radiation therapy (RT) after radical prostatectomy (RP) has been associated with a survival benefit in both the adjuvant and salvage setting. Nevertheless, optimal targeting of the prostate bed following surgery remains challenging. The Calypso 4D Localization System (Calypso Medical Technologies, Seattle, WA, USA) is a target positioning device that continuously monitors the location of three implantable electromagnetic transponders. We describe our technique of ultrasound-guided placement of these transponders into the prostate bed for adjuvant and salvage RT. METHODS: Seventeen patients presenting to Fox Chase Cancer Center for postoperative RT underwent transrectal ultrasound-guided placement of Calypso beacons. The three transponders were placed approximately 1 cm apart in a triangular fashion around the vesico-urethral anastomosis and in the retrovesicular tissue. RESULTS: All patients were successfully implanted without periprocedural complications. Appropriate beacon position was confirmed by CT scan performed at the time of RT simulation. Intensity-modulated radiation therapy was delivered at a dose of 68 Gy (range 64-68). Treatment was well-tolerated with no Grade 3 or 4 toxicities. Grade > 2 enteritis was not observed, and there were no cases of rectal bleeding. Genitourinary toxicity was noted in 10 patients and consisted of Grade 1 and 2 frequency and dysuria. No patient developed gross hematuria or urinary retention. All patients (9/9) with at least 6 months of follow up after treatment had an undetectable PSA. CONCLUSIONS: The placement of Calypso transponders for adjuvant/salvage RT is a safe and efficacious method for treatment targeting with an acceptable acute toxicity profile.

Anchored Transponder Guided Lung Radiation Therapy.

PURPOSE: The Calypso Beacon transponder has been modified by the addition of a nitinol anchor feature to allow for positional stability when implanted bronchoscopically into the lung. The purpose of this study was to confirm the feasibility and safety of anchored transponder placement and feasibility of lung target localization and tracking. METHODS AND MATERIALS: This study enrolled patients with histologically confirmed cancer in the lung (primary or metastatic) who were scheduled to receive external beam radiation therapy. Three anchored transponders were implanted via flexible bronchoscopy into small (approximately 2- to 2.5-mm diameter) airways. Patient alignment at each radiation fraction was performed with the Calypso system, and anchored transponder position was tracked during radiation delivery. The primary endpoint was defined as the ability to localize at least 85% of the patients during the first week of treatment. Four follow-up visits were specified including a posttreatment assessment and every 3 months up to 1 year. RESULTS: A total of 69 patients underwent anchored transponder placement, and all 207 implanted anchored transponders were visible on the treatment-planning simulation computed tomography scan. Sixty-seven patients underwent radiation therapy, and localization was successful in 66 cases (98.5%). With 1 failure in 67 cases, the P value for rejecting the null hypothesis was <.001 and the primary objective of the study met. Five adverse events in 5 patients were potentially attributed to the study device or implantation procedure, consisting of pneumonia (2 cases), pleural abscess (1 case), and pneumothorax (2 cases). Two serious events (cardiac arrest and acute hypotension) were attributed to anesthesia during the implantation procedure. CONCLUSIONS: This study strongly supports that anchored transponders are safe, positionally stable, and useful for lung tumor localization and monitoring.

Prospective observational study on the safety of an original fiducial marker insertion for radiotherapy in gynecological cancer by a simple method.

Our observational study aimed to verify the safety of our original titanium fiducial markers in gynecological cancer by using a simple insertion method. We prospectively evaluated the safety in patients with gynecological cancer who had undergone our insertion procedure of the titanium markers. The decision to implant a titanium marker was at the discretion of each radiation oncologist. The fiducial markers were manufactured by severing ligating clips for surgery into 3-6 mm pieces and were sterilized thereafter. We inserted an 18-gauge injection needle containing the marker before the marker was extruded by a 22-gauge Cattelan needle or shape memory alloy wire into the tumor or tissues close to the tumor. Severe complications within 3 months after implantation were scored according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.0. Between August 2016 and December 2018, we enrolled 46 patients. Of 46, 44 underwent implantation. The median age was 58.5 years. The most common primary site was the cervix. Two patients experienced detachment of the markers after implantation. No Grade 3 or higher level of complications was observed. Our simple insertion technique for original titanium fiducial markers was well-tolerated.

Evaluation of a strategy using pretherapeutic fiducial marker placement to avoid missing liver metastases.

Background: Hepatic surgery is appropriate for selected patients with colorectal liver metastases (CRLM). Advances in chemotherapy have led to modification of management, particularly when metastases disappear. Treatment should address all initial CRLM sites based on pretherapeutic cross-sectional imaging. This study aimed to evaluate pretherapeutic fiducial marker placement to optimize CRLM treatment. Methods: This pilot investigation included patients with CRLM who were considered for potentially curative treatment between 2009 and 2016. According to a multidisciplinary team decision, lesions smaller than 25 mm in diameter that were more than 10 mm deep in the hepatic parenchyma and located outside the field of a planned resection were marked. Complication rates and clinicopathological data were analysed. Results: Some 76 metastases were marked in 43 patients among 217 patients with CRLM treated with curative intent. Of these, 23 marked CRLM (30 per cent), with a mean(s.d.) size of 11·0(3·4) mm, disappeared with preoperative chemotherapy. There were four complications associated with marking: two intrahepatic haematomas, one fiducial migration and one misplacement. After a median follow-up of 47·7 (range 18·1-144·9) months, no needle-track seeding was noted. Of four disappearing CRLM that were marked and resected, two presented with persistent active disease. Other missing lesions were treated with thermoablation. Conclusion: Pretherapeutic fiducial marker placement appears useful for the curative management of CRLM.

Impact of proximal radiopaque coronary bypass graft markers on postbypass surgery coronary angiography.

BACKGROUND: Implantation of radiopaque bypass graft markers during coronary artery bypass surgery (CABG) has the potential of facilitating subsequent coronary angiography. This study sought to investigate the impact of proximal coronary bypass graft markers on angiographic outcomes during subsequent coronary angiography in a large cohort. METHODS AND RESULTS: Between 2005 and 2016, we enrolled 1378 patients (331 with and 1047 without bypass graft markers) with a history of CABG who underwent their first subsequent coronary angiography at our institution. Primary endpoints were radiation time and absolute amount of contrast media used. In unadjusted analyses, radiation time, duration of angiography, dose area product, and the amount of contrast agent were significantly lower in patients with proximal bypass graft markers (P < .001). After full adjustment, proximal coronary bypass graft markers remained a significant predictor for less radiation time and a lower consumption of contrast agent but not for dose area product, which was mainly associated with body mass index and sex. Bypass graft markers were not associated with a lower graft patency. CONCLUSIONS: Radiopaque coronary bypass graft markers can improve the detection of bypass grafts during subsequent coronary angiography and are associated with a lower radiation time and less consumption of contrast agent. Thus, this easy and cost-efficient technique might significantly reduce the risk of coronary angiography after CABG.

Rectal Culture and Sensitivity Analysis for Reducing Sepsis Risk After Fiducial Marker Placement.

PURPOSE: Placement of fiducial markers for prostate radiotherapy (RT) is associated with a 2% to 3% risk of bacterial urinary tract infection (UTI) that may progress to sepsis necessitating hospitalization. These bacterial UTIs are primarily due to flouroquinolone (FQ) resistant Escherichia coli (E. coli). The incidence of this complication has increased in recent years. The purpose of this study is to determine whether rectal culture and sensitivity (C&S) to identify FQ resistant E. coli obtained before placement of fiducial markers for prostate RT reduces the likelihood of this complication. METHODS: In total, 412 patients treated with RT at the University of Florida Proton Therapy Institute between 2015 and 2017 were included in the study. Rectal C&S were obtained at the time of initial consultation which preceded placement of fiducial markers for planning and realignment for prostate RT. Patients in whom resistant E. coli were identified had their prophylactic antibiotic regimen modified accordingly. Whether bacterial UTI requiring hospitalization following fiducial placement occurred was prospectively recorded in the medical record on the first day of RT. RESULTS: One of 412 patients (0.2%) developed bacterial sepsis requiring hospitalization after fiducial placement. CONCLUSION: Rectal C&S to identify FQ resistant E. coli before placement of fiducial markers for prostate RT likely reduces the risk of bacterial UTI necessitating hospitalization.