Long-term clinical outcomes of lipiodol marking using standard gastroscopy for image-guided radiotherapy of upper gastrointestinal cancers.

BACKGROUND: Image-guided radiotherapy (IGRT) has significantly improved the precision in which radiotherapy is delivered in cancer treatment. Typically, IGRT uses bony landmarks and key anatomical structures to locate the tumor. Recent studies have demonstrated the feasibility of peri-tumor fiducials in enabling even more accurate delineation of target and normal tissue. The use of gold coils as fiducials in gastrointestinal tumors has been extensively studied. However, placement requires expertise and specialized endoscopic ultrasound equipment. This article reports the long-term outcomes of using a standard gastroscopy to inject liquid fiducials for the treatment of oesophageal and gastric tumors with IGRT. AIM: To assess the long-term outcomes of liquid fiducial-guided IGRT in a cohort of oesophageal and gastric cancer patients. METHODS: A retrospective cohort study of consecutive adults with Oesophagogastric cancers referred for liquid fiducial placement before definitive/neo-adjuvant or palliative IGRT between 2013 and 2021 at a tertiary hospital in Melbourne, Australia was conducted. Up to four liquid fiducials were inserted per patient, each injection consisting of 0.2-0.5mL of a 1:1 mixture of iodized oil (Lipiodol; Aspen Pharmacare) and n-butyl 2-cyanoacrylate (Histoacryl®; B. Braun). A 23-gauge injector (Cook Medical) was used for the injection. All procedures were performed by or under the supervision of a gastroenterologist. Liquid fiducial-based IGRT (LF-IGRT) consisted of computer-assisted direct matching of the fiducial region on cone-beam computerised tomography at the time of radiotherapy. Patients received standard-IGRT (S-IGRT) if fiducial visibility was insufficient, consisting of bone match as a surrogate for tumor position. Radiotherapy was delivered to 54Gy in 30 fractions for curative patients and up to 45Gy in 15 fractions for palliative treatments. RESULTS: 52 patients were referred for liquid fiducial placement within the study period. A total of 51 patients underwent liquid fiducial implantation. Of these a total of 31 patients received radiotherapy. Among these, the median age was 77.4 years with a range between 57.5 and 88.8, and 64.5% were male. Twenty-seven out of the 31 patients were able to have LF-IGRT while four had S-IGRT. There were no complications after endoscopic implantation of liquid fiducials in our cohort. The cohort overall survival (OS) post-radiotherapy was 19 mo (range 0 to 87 mo). Whilst the progression-free survival (PFS) post-radiotherapy was 13 mo (range 0 to 74 mo). For those treated with curative intent, the median OS was 22.0 mo (range 0 to 87 mo) with a PFS median of 14.0 mo (range 0 to 74 mo). Grade 3 complication rate post-radiotherapy was 29%. CONCLUSION: LF-IGRT is feasible in 87.1% of patients undergoing liquid fiducial placement through standard gastroscopy injection technique. Our cohort has an overall survival of 19 mo and PFS of 13 mo. Further studies are warranted to determine the long-term outcomes of liquid-fiducial based IGRT.

Preloaded 22-gauge fine-needle system facilitates placement of a higher number of fiducials for image-guided radiation therapy compared with traditional backloaded 19-gauge approach.

BACKGROUND AND AIMS: Image-guided radiation therapy (IGRT) often relies on EUS-guided fiducial markers. Previously used manually backloaded fiducial needles have multiple potential limitations including safety and efficiency concerns. Our aim was to evaluate the efficacy, feasibility, and safety of EUS-guided placement of gold fiducials using a novel preloaded 22-gauge needle compared with a traditional, backloaded 19-gauge needle. METHODS: This was a single-center comparative cohort study. Patients with pancreatic and hepatobiliary malignancy who underwent EUS-guided fiducial placement (EUS-FP) between October 2014 and February 2018 were included. The main outcome was the technical success of fiducial placement. Secondary outcomes were mean procedure time, fiducial visibility during IGRT, technical success of IGRT delivery, and adverse events. RESULTS: One hundred fourteen patients underwent EUS-FP during the study period. Of these, 111 patients had successful placement of a minimum of 2 fiducials. Fifty-six patients underwent placement using a backloaded 19-gauge needle and 58 patients underwent placement using a 22-gauge preloaded needle. The mean number of fiducials placed successfully at the target site was significantly higher in the 22-gauge group compared with the 19-gauge group (3.53 ± .96 vs 3.11 ± .61, respectively; P = .006). In the 22-gauge group, the clinical goal of placing 4 fiducials was achieved in 78%, compared with 23% in the 19-gauge group (P < .001). In univariate analyses, gender, age, procedure time, tumor size, and location did not influence the number of successfully placed fiducials. Technical success of IGRT with fiducial tracking was high in both the 19-gauge (51/56, 91%) and the 22-gauge group (47/58, 81%; P = .12). CONCLUSIONS: EUS-FP using a preloaded 22-gauge needle is feasible, effective, and safe and allows for a higher number of fiducials placed when compared with the traditional backloaded 19-gauge needle.

Sialendoscopy and CT navigation assistance in the surgery of sialolithiasis.

BACKGROUND: A sialendoscopy-assisted combined approach is well established in the surgery of sialolithiasis. In cases of proximal salivary stones, transcutaneous sialendoscopy-assisted extractions with parotid and submandibular gland preservation is the primary intention of treatment. We recently added computer tomography (CT) navigation to improve the results of this challenging surgery equally in both localizations. PATIENTS AND METHODS: Al l the patients who submitted to sialendoscopy and sialendoscopy-assisted procedures at the tertiary institution between January 2012 and October 2020 were included in the present study. From November 2019, CT navigation was added in cases with sialolithiasis and a presumably poor sialendoscopic visibility. We evaluated the parameters of the disease, diagnostic procedures, sialendoscopic findings and outcomes, with or without optical surgical navigation. RESULTS: We performed 178 successful salivary stone removals in 372 patients, of which 118 were combined sialendos-copy-assisted approaches, including 16 transcutaneous proximal, 10 submandibular and 6 parotid stone operations. Surgical navigation was used in six patients, four times for submandibular and twice for parotid sialolithiasis. These were all non-palpable, sialendoscopically invisible or partially visible stones, and we managed to preserve five of the six salivary glands. CONCLUSIONS: The addition of CT navigation to sialendoscopy-assisted procedures for non-palpable, sialendoscopically invisible and fixed stones is a significant advantage in managing sialolithiasis. By consistently performing sialendoscopy and related preservation procedures, we significantly reduced the need for sialoadenectomies in patients with obstructive salivary gland disease.

Impact of breath-hold level on positional error aligned by stent/Lipiodol in Hepatobiliary radiotherapy with breath-hold respiratory control.

BACKGROUND: Respiratory motion management with breath hold for patients with hepatobiliary cancers remain a challenge in the precise positioning for radiotherapy. We compared different image-guided alignment markers for estimating positional errors, and investigated the factors associated with positional errors under breath-hold control. METHODS: Spirometric motion management system (SDX) for breath holds was used in 44 patients with hepatobiliary tumor. Among them, 28 patients had a stent or embolized materials (lipiodol) as alignment markers. Cone-beam computed tomography (CBCT) and kV-orthogonal images were compared for accuracy between different alignment references. Breath-hold level (BHL) was practiced, and BHL variation (ΔBHL) was defined as the standard deviation in differences between actual BHLs and baseline BHL. Mean BHL, ΔBHL, and body-related factors were analyzed for the association with positional errors. RESULTS: Using the reference CBCT, the correlations of positional errors were significantly higher in those with stent/lipiodol than when the vertebral bone was used for alignment in three dimensions. Patients with mean BHL > 1.4 L were significantly taller (167.6 cm vs. 161.6 cm, p = 0.03) and heavier (67.1 kg vs. 57.4 kg, p = 0.02), and had different positional error in the craniocaudal direction (- 0.26 cm [caudally] vs. + 0.09 cm [cranially], p = 0.01) than those with mean BHL < 1.4 L. Positional errors were similar for patients with ΔBHL< 0.03 L and > 0.03 L. CONCLUSION: Under rigorous breath-hold respiratory control, BHL correlated with body weight and height. With more accurate alignment reference by stent/lipiodol, actual BHL but not breath-hold variation was associated with craniocaudal positional errors.

Correlative X-ray and neutron tomography of root systems using cadmium fiducial markers.

The interactions between plant roots and soil are an area of active research, particularly in terms of water and nutrient uptake. Because noninvasive, in vivo studies are required, tomographic imaging appears an obvious method to use, but no one imaging modality is well suited to capture the complete system. X-ray imaging gives clear insight to soil structure and composition; however, water is comparatively transparent to X-rays and biological matter also displays poor contrast with respect to the pores between soil particles. Neutron imaging presents a complementary view where water and biological matter are better distinguished but the soil minerals are not imaged as clearly as they would be with X-rays. This work aims to develop robust methods for complementary X-ray/neutron tomographic imaging of plant root samples which should lead to new insight into water and nutrient transport in soil. The key challenges of this project are to develop experiments that will meet the requirements of both imaging modalities as well as the biological requirements of the plant samples and to develop ways to register a pair of reconstructed volume images of a sample that will typically have been produced with entirely separate facilities. The use of cadmium fiducial markers for registration has been investigated. Simulations were conducted to investigate the expected registration accuracy as the quantity and distribution of the markers varied. The findings of these simulations were then tested experimentally as plant samples were grown and imaged using neutrons with the IMAT instrument at ISIS Neutron and Muon Source at the STFC Rutherford Appleton Laboratory in Harwell, and with X-rays at µ-VIS X-ray Imaging Centre at the University of Southampton. LAY DESCRIPTION: The interactions between plant roots and soil are an area of active research, particularly in terms of water and nutrient uptake. The samples used in this research are typically imaged so that they can be studied without digging up the roots and destroying the sample in the process. X-ray and neutron imaging techniques have both been used as each can show different materials within the sample. Because neither can show all the components of the system by itself, this work explores methods for combining scans of the same sample to give a more complete image of the system. In particular this work focusses on the use of fiducial markers as a strategy for preparing the samples in such a way that the resulting images can be aligned. The effectiveness of this method was tested in simulation and then in practice. The samples used within this work were imaged using neutrons on the IMAT instrument at ISIS Neutron and Muon Source at the STFC Rutherford Appleton Laboratory in Harwell, and with X-rays at µ-VIS X-ray Imaging Centre at the University of Southampton.

An integrated physico-chemical approach for explaining the differential impact of FLASH versus conventional dose rate irradiation on cancer and normal tissue responses.

For decades the field of radiation oncology has sought to improve the therapeutic ratio through innovations in physics, chemistry, and biology. To date, technological advancements in image guided beam delivery techniques have provided clinicians with their best options for improving this critical tool in cancer care. Medical physics has focused on the preferential targeting of tumors while minimizing the collateral dose to the surrounding normal tissues, yielding only incremental progress. However, recent developments involving ultra-high dose rate irradiation termed FLASH radiotherapy (FLASH-RT), that were initiated nearly 50 years ago, have stimulated a renaissance in the field of radiotherapy, long awaiting a breakthrough modality able to enhance therapeutic responses and limit normal tissue injury. Compared to conventional dose rates used clinically (0.1-0.2 Gy/s), FLASH can implement dose rates of electrons or X-rays in excess of 100 Gy/s. The implications of this ultra-fast delivery of dose are significant and need to be re-evaluated to appreciate the fundamental aspects underlying this seemingly unique radiobiology. The capability of FLASH to significantly spare normal tissue complications in multiple animal models, when compared to conventional rates of dose-delivery, while maintaining persistent growth inhibition of select tumor models has generated considerable excitement, as well as skepticism. Based on fundamental principles of radiation physics, radio-chemistry, and tumor vs. normal cell redox metabolism, this article presents a series of testable, biologically relevant hypotheses, which may help rationalize the differential effects of FLASH irradiation observed between normal tissue and tumors.

Fiducial markers: can the urologist do better?

INTRODUCTION: Radiotherapy to the bladder has a risk of toxicity to pelvic structures, which can be reduced by using fiducial markers for targeting. Injectable contrast offers an alternative marker to gold seeds, which may fall out or exacerbate scarring. Combining contrast agents with tissue glue can minimize dispersion through tissue, enhancing its utility. We evaluated combinations of contrast agents and tissue glue using porcine bladder, for feasibility and utility as fiducial markers to aid image-guided radiotherapy. METHODS: Different contrast agents (Lipiodol ultra or Urografin) were combined with different tissue glues (Histoacryl, Tisseal or Glubran2). The mixtures were endoscopically injected into porcine bladder submucosa to identify the area of interest with multiple fiducial markers. The porcine bladders were imaged within a phantom porcine pelvis using standard radiation therapy imaging modalities. The feasibility as an injectable fiducial marker and visibility of each fiducial marker on imaging were scored as binary outcomes by two proceduralists and two radiation therapists, respectively. RESULTS: Lipiodol-glue combinations were successfully administered as multiple fiducials that were evident on CT and CBCT. Lipiodol with Histoacryl or Glubran2 was visible on kV imaging. The Lipiodol Glubran2 combination was deemed subjectively easiest to use at delivery, and a better fiducial on KV imaging. CONCLUSION: This study demonstrates the feasibility of mixing contrast medium Lipiodol with Histoacryl or Glubran2 tissue glue, which, injected endoscopically, provides discrete and visible fiducial markers to aid image-guided radiotherapy. Although promising, further study is required to assess the durability of these markers through a course of radiotherapy.

Calcium Phosphate Cement Paste Injection as a Fiducial Marker of Cervical Cancer.

BACKGROUND/AIM: Calcium phosphate cement (CPC) is used to fill bone voids in dental, orthopedic, and craniofacial applications. This study evaluated CPC marker as an injectable non-metallic fiducial marker. MATERIALS AND METHODS: Six patients received 3-5 injections of CPC paste placed at a depth of 10 mm into tumors of the cervix before treatment planning CT (TPCT). Patients were treated with external-beam radiotherapy (EBRT) and high-dose rate brachytherapy (BT). We investigated marker visibility on cone-beam CT (CBCT), T2-weighted MRI, and interfraction of the marker motion for cervical cancer patients. RESULTS: Of a total of 22 visible CPC markers at TPCT, 17 CPC markers were visible on the first CBCT. Excluding one patient, all markers were visible on CBCT during EBRT. Of 16 visible CPC markers on CBCT, 13 CPC markers were visible on the magnetic resonance imaging (MRI) obtained before BT. For CPC marker centroid movement, the mean-of-means/systematic variation/random variation were 0.2/0.4/1.4, -1.6/5.1/4.1, and -3.4/2.1/2.8 mm for the left-right, dorsal-ventral, and cranial-caudal directions, respectively. CONCLUSION: This is the first report of a CPC marker injected into tumors of the cervix. It can be visualized on CBCT and MRI with reductions in marker loss and artifacts.

A pilot study of highly hypofractionated intensity-modulated radiation therapy over 3 weeks for localized prostate cancer.

The purpose of this pilot study was to evaluate the feasibility of highly hypofractionated intensity-modulated radiation therapy (IMRT) in 15 fractions over 3 weeks for treating localized prostate cancer based on prostate position-based image-guided radiation therapy. Twenty-five patients with National Comprehensive Cancer Network (NCCN) very low- to unfavorable intermediate-risk prostate cancer were enrolled in this study from April 2014 to September 2015 to receive highly hypofractionated IMRT (without intraprostatic fiducial markers) delivering 54 Gy in 15 fractions over 3 weeks. Patients with intermediate-risk disease underwent neoadjuvant androgen suppression for 4-8 months. Twenty-four patients were treated with highly hypofractionated IMRT, and one was treated with conventionally fractionated IMRT because the dose constraint of the small bowel seemed difficult to achieve during the simulation. Seventeen percent had very low- or low-risk, 42% had favorable intermediate-risk, and 42% had unfavorable intermediate-risk disease according to NCCN guidelines. The median follow-up period was 31 months (range, 24-42 months). No Grade ≥3 acute toxicity was observed, and the incidence rates of Grade 2 acute genitourinary and gastrointestinal toxicities were 21% and 4%, respectively. No Grade ≥2 late toxicity was observed. Biochemical relapse was observed in one patient at 15 months, and the biochemical relapse-free survival rate was 95.8% at 2 years. A prostate-specific antigen bounce of ≥0.4 ng/ml was observed in 11 patients (46%). The highly hypofractionated IMRT regimen is feasible in patients with localized prostate cancer and is more convenient than conventionally fractionated schedules for patients and health-care providers.

Partial Bladder Boost Using Lipiodol Marking During Image-guided Radiotherapy for Bladder Cancer.

BACKGROUND/AIM: Secure dose escalation is required to compensate avoidance of concurrent chemotherapy in radiotherapy for increasing elderly bladder cancer. We aimed to evaluate the efficacy of lipiodol submucosally injected as a fiducial marker during image-guided radiotherapy (Lip-IGRT) for muscle invasive bladder cancer (BC). PATIENTS AND METHODS: Twenty-three patients with T2a-4aN0-1M0 BC underwent whole-bladder irradiation of 46 Gy and Lip-IGRT of 20 Gy, conventionally. The bladder volume exposed to 19 Gy (bV19:%) on Lip-IGRT was referred as an index predicting cystitis. RESULTS: Lipiodol consistently highlighted the boundaries of 20 tumors (88%) on planning and portal verification images. Three of 4 patients under oral anticoagulant agents usage were complicated with grade ≥2 hematuria for 3 days (a patient with a bV19 of >50%) or more than a year (2 patients with bV19 of <50%) after the injection. The 3-year overall survival and disease-free survival rates were 70.4% and 71.1%, respectively. CONCLUSION: Lipiodol marking is an effective way of demarcating BC. However, it is necessary to address the comorbidities of elderly patients.

Closed-form fiducial confidence intervals for some functions of independent binomial parameters with comparisons.

Approximate closed-form confidence intervals (CIs) for estimating the difference, relative risk, odds ratio, and linear combination of proportions are proposed. These CIs are developed using the fiducial approach and the modified normal-based approximation to the percentiles of a linear combination of independent random variables. These confidence intervals are easy to calculate as the computation requires only the percentiles of beta distributions. The proposed confidence intervals are compared with the popular score confidence intervals with respect to coverage probabilities and expected widths. Comparison studies indicate that the proposed confidence intervals are comparable with the corresponding score confidence intervals, and better in some cases, for all the problems considered. The methods are illustrated using several examples.

Breast cancer recurrence following radioguided seed localization and standard wire localization of nonpalpable invasive and in situ breast cancers: 5-Year follow-up from a randomized controlled trial.

BACKGROUND: This study compared 5-year breast cancer (BC) recurrence rates in patients randomized to radioguided seed localization (RSL) or wire localization (WL) for non-palpable BC undergoing breast conserving surgery. METHODS: Chart review of follow-up visits and surveillance imaging was conducted. Data collected included patient and tumour factors, adjuvant therapies and BC recurrence (local recurrence (LR), regional recurrence (RR), and distant metastasis (DM)). Univariate analysis was used. RESULTS: Follow-up data were available for 298 patients (98%) and median follow-up time was 65 months. There were 11 (4%) cases of BC recurrence and median time to recurrence was 26 months. LR occurred in 8 patients (6 WL and 2 RSL; p = 0.28). Positive margins at first surgery (p = 0.024) and final surgery (p = 0.004) predicted for BC recurrence. CONCLUSIONS: There was no detectable difference in BC recurrence between WL and RSL groups and positive margins at initial or final surgery both predicted for BC recurrence.

Does T'ai Chi Gait Reduce External Knee Adduction Moment?

INTRODUCTION: T'ai chi chuan is a beneficial exercise of improving health and function. Biomechanical insights of t'ai chi chuan are less understood. OBJECTIVES: To study t'ai chi gait (TCG), a common form of t'ai chi chuan in order to quantify external knee adduction moment (EKAM) as a key indicator of mechanical loading of the medial compartment of the knee compared with normal walking (NW). DESIGN: A quantitative biomechanics approach to determine peak EKAM for NW and TCG. RESULTS: There were a tri-modal pattern of EKAM during TCG and a bimodal pattern of EKAM during normal walking. In addition, subsequent analysis showed a 25%-47% reduction in peak EKAM during double support phases of TCG compared with NW; the peak EKAM of TCG during single-limb support phase showed significantly higher magnitude than the other two double-support phases. CONCLUSION: These results indicate that t'ai chi chuan might be a beneficial intervention for reducing the medial mechanical load at the knee joint, particularly during the first double-support phases of TCG, but the special consideration of higher peak EKAM of single-limb support phase is needed during regular t'ai chi chuan practice.

Effect of Acupuncture on Reducing Duration of Postoperative Ileus After Gastrectomy in Patients with Gastric Cancer: A Pilot Study Using Sitz Marker.

OBJECTIVES: Postoperative ileus (POI) is a common problem after abdominal surgery. Acupuncture is being accepted as an option for reducing POI and managing various functional gastrointestinal disorders. Therefore, this pilot study was conducted to evaluate the effect of acupuncture on reducing duration of POI and other surgical outcomes in patients who underwent gastric surgery. DESIGN: A prospective, randomized, controlled pilot study was conducted on patients who underwent gastric cancer surgery from January 2013 to December 2013. Ten patients were randomly assigned into the acupuncture (A) or nonacupuncture (NA) groups at a 1:1 ratio. INTERVENTIONS: The acupuncture treatment was performed by Korean traditional medicine doctors (KMDs). The style of acupuncture was Korean. In the A group, acupuncture treatment was given once daily for 5 consecutive days starting on postoperative day 1. Each patient received acupuncture at 16 acupoints based on expert consensus provided by qualified and experienced KMDs. No acupuncture treatment was performed in the NA group. OUTCOME MEASURES: The primary outcome measure was the number of remnant Sitz markers in the small intestine on abdominal radiography. Secondary outcome measures were time to first flatus, start of sips water, start of soft diet, hospital stay, and laboratory findings. RESULTS: The A group had significantly fewer remnant Sitz markers in the small intestine on postoperative days 3 and 5 compared with those in the NA group (p = 0.025 and 0.005). A significant difference was observed in the numbers of remnant Sitz marker in the small intestine with respect to time difference by group (p = 0.019). The A group showed relatively better surgical outcomes, but without statistical significance. CONCLUSIONS: Although further studies are warranted, acupuncture may reduce duration of POI after gastric surgery and could be a potential factor in enhanced recovery after surgery protocols.

Is determination of the hip rotation center during computer-assisted surgery influenced by the pinless femoral sensor attachment method? An in vitro preliminary study comparing osseous pin fixation.

INTRODUCTION: Computer-assisted surgery improves the positioning of hip prostheses but requires use of transosseous pins requiring a complementary approach exposing the patient to rare but at times serious complications. The use of sensor arrays attached to the skin could advantageously replace pins provided that comparable results are obtained, but their validity has not yet been assessed. We conducted a prospective in vitro study to: measure the possible error of a cutaneous versus transosseous fixation to determine the hip rotation center (HRC) position and determine the inter- and intraobserver reproducibility of the cutaneous versus the transosseous fixation. HYPOTHESIS: Use of cutaneous sensor arrays while recording the HRC is sufficiently reliable for its calculation algorithm to provide measurement accuracy within 5mm. MATERIALS AND METHODS: A rigid array attached with either a silicone strap or an adhesive were compared to a transosseous array. Four series of 96 HRC measurements were collected by four operators on two cadavers, half with an array attached with a strap and half with an adhesive. The results were compared to those obtained by a sensor attached with transosseous pins. RESULTS: On condition that the hip-knee is mobilized in extension, a sensor array attached with an adhesive gives results with comparable accuracy (standard deviation [SD]: 2.89mm [1.9-4.8]) to the results obtained with a transosseous fixation (SD: 1.2mm [0.9-1.6]), with no significant inter- or intraobserver variation (0.97

Predictive Parameters of Symptomatic Hematochezia Following 5-Fraction Gantry-Based SABR in Prostate Cancer.

PURPOSE: This study identified predictors of high-grade late hematochezia (HH) following 5-fraction gantry-based stereotactic ablative radiation therapy (SABR). METHODS AND MATERIALS: Hematochezia data for 258 patients who received 35 to 40 Gy SABR in 5-fractions as part of sequential phase 2 prospective trials was retrieved. Grade 2 or higher late rectal bleeding was labeled HH. Hematochezia needing steroid suppositories, 4% formalin, or 1 to 2 sessions of argon plasma coagulation (APC) was labeled grade 2. More than 2 sessions of APC, blood transfusion, or a course of hyperbaric oxygen was grade 3 and development of visceral fistula, grade 4. Various dosimetric and clinical factors were analyzed using univariate and multivariate analyses. Receiver operating characteristic (ROC) curve analysis and recursive partitioning analysis were used to determine clinically valid cut-off points and identify risk groups, respectively. RESULTS: HH was observed in 19.4%, grade ≥3 toxicity in 3.1%. Median follow-up was 29.7 months (interquartile range [IQR]: 20.6-61.7) Median time to develop HH was 11.7 months (IQR: 9.0-15.2) from the start of radiation. At 2 years, cumulative HH was 4.9%, 27.2%, and 42.1% in patients who received 35 Gy to prostate (4-mm planning target volume [PTV] margin), 40 Gy to prostate (5-mm PTV margin), and 40 Gy to prostate/seminal vesicles (5-mm PTV margin), respectively (P<.0001). In the ROC analysis, volume of rectum receiving radiation dose of 38 Gy (V38) was a strong predictor of HH with an area under the curve of 0.65. In multivariate analysis, rectal V38 (≥2.0 cm(3); odds ratio [OR]: 4.7); use of anticoagulants in the follow-up period (OR: 6.5) and presence of hemorrhoids (OR: 2.7) were the strongest predictors. Recursive partitioning analysis showed rectal V38 < 2.0 cm(3), and use of anticoagulants or rectal V38 ≥ 2.0 cm(3) plus 1 other risk factor resulted in an HH risk of >30%. CONCLUSIONS: Rectal V38 and 2 clinical factors were strong predictors of HH following 5-fraction SABR. Planning constraints should keep rectal V38 below 2.0 cm(3).

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.

Lipiodol versus diaphragm in 4D-CBCT-guided stereotactic radiotherapy of hepatocellular carcinomas.

PURPOSE: The purpose of this work was to investigate the potential of lipiodol as a direct tumor surrogate alternative to the diaphragm surrogate on four-dimensional cone-beam computed tomography (4D-CBCT) image guidance for stereotactic radiotherapy of hepatocellular carcinomas. METHODS: A total of 29 hepatocellular carcinomas (HCC) patients treated by stereotactic radiotherapy following transarterial chemoembolization (TACE) with homogeneous or partial defective lipiodol retention were included. In all, 4-7 pretreatment 4D-CBCT scans were selected for each patient. For each scan, either lipiodol or the diaphragm was used for 4D registration. Resulting lipiodol/diaphragm motion ranges and position errors relative to the reconstructed midventilation images were analyzed to obtain the motion variations, and group mean (ΔM), systematic (Σ), and random (σ) errors of the treatment setup. RESULTS: Of the lipiodolized tumors, 55 % qualified for direct localization on the 4D-CBCT. Significant correlations of lipiodol and diaphragm positions were found in the left-right (LR), craniocaudal (CC), and anteroposterior (AP) directions. ΔM and σ obtained with lipiodol and diaphragm were similar, agreed to within 0.5 mm in the LR and AP, and 0.3 mm in the CC directions, and Σ differed by 1.4 (LR), 1.1 (CC), and 0.6 (AP) mm. Variations of diaphragm motion range > 5 mm were not observed with lipiodol and in one patient with diaphragm. The margin required for the tumor prediction error using the diaphragm surrogate was 6.7 (LR), 11.7 (CC), and 4.1 (AP) mm. CONCLUSION: Image-guidance combining lipiodol with 4D-CBCT enabled accurate localization of HCC and thus margin reduction. A major limitation was the degraded lipiodol contrast on 4D-CBCT.