Failure modes and effects analysis of pediatric I-131 MIBG therapy: Program design and potential pitfalls.

BACKGROUND: There is growing interest among pediatric institutions for implementing iodine-131 (I-131) meta-iodobenzylguanidine (MIBG) therapy for treating children with high-risk neuroblastoma. Due to regulations on the medical use of radioactive material (RAM), and the complexity and safety risks associated with the procedure, a multidisciplinary team involving radiation therapy/safety experts is required. Here, we describe methods for implementing pediatric I-131 MIBG therapy and evaluate our program's robustness via failure modes and effects analysis (FMEA). METHODS: We formed a multidisciplinary team, involving pediatric oncology, radiation oncology, and radiation safety staff. To evaluate the robustness of the therapy workflow and quantitatively assess potential safety risks, an FMEA was performed. Failure modes were scored (1-10) for their risk of occurrence (O), severity (S), and being undetected (D). Risk priority number (RPN) was calculated from a product of these scores and used to identify high-risk failure modes. RESULTS: A total of 176 failure modes were identified and scored. The majority (94%) of failure modes scored low (RPN <100). The highest risk failure modes were related to training and to drug-infusion procedures, with the highest S scores being (a) caregivers did not understand radiation safety training (O = 5.5, S = 7, D = 5.5, RPN = 212); (b) infusion training of staff was inadequate (O = 5, S = 8, D = 5, RPN = 200); and (c) air in intravenous lines/not monitoring for air in lines (O = 4.5, S = 8, D = 5, RPN = 180). CONCLUSION: Through use of FMEA methodology, we successfully identified multiple potential points of failure that have allowed us to proactively mitigate risks when implementing a pediatric MIBG program.

Accelerated Partial Breast Irradiation: A Safe, Effective, and Convenient Early Breast Cancer Treatment Option.

Accelerated partial breast irradiation (APBI) is an excellent treatment option for many women with early stage breast cancer. Patient selection criteria include age over 40, status post lumpectomy, breast cancer (invasive or in situ disease) measuring <3 cm, negative margins (at least 2 mm), negative lymph nodes, and no lymphovascular space invasion. APBI is effective, well tolerated, and convenient. Women with early stage breast cancer and theii caregivers should be aware of this potential treatment option.

Handling Patient Emergencies During Radiopharmaceutical Therapy.

PURPOSE: Radiopharmaceutical therapy (RPT) is a rapidly growing treatment modality. Though uncommon, patients may experience complications during their RPT treatment, which may trigger a rapid response from the hospital team. However, members of this team are typically not familiar with precautions for radiation safety. During these events, it is important to prioritize the patient's health over all else. There are some practices that can help minimize the risk of radiation contamination spread and exposure to staff while tending to the patient. METHODS AND MATERIALS: We formed a team to develop a standard protocol for handling patient emergencies during RPT treatment. This team consisted of an authorized user, radiation safety officer, medical physicist, nurse, RPT administration staff, and a quality/safety coordinator. The focus for developing this standardized protocol for RPT patient emergencies was 3-fold: (1) stabilize the patient; (2) reduce radiation exposure to staff; and (3) limit the spread of radiation contamination. RESULTS: We modified our hospital's existing rapid response protocol to account for the additional staff and tasks needed to accomplish all 3 of these goals. Each team member was assigned specific responsibilities, which include serving as a gatekeeper to restrict traffic, managing the crash cart, performing chest compressions, timing chest compressions, documenting the situation, and monitoring/managing radiation safety in the area. We developed a small, easy-to-read card for rapid response staff to read while they are en route to the area so they can be aware of and prepare for the unique circumstances that RPT treatments present. CONCLUSIONS: Though rapid response events with RPT patients are uncommon, it is important to have a standardized protocol for how to handle these situations beforehand rather than improvise in the moment. We have provided an example of how our team adapted our hospital's current rapid response protocol to accommodate RPT patients.

Clinical Outcomes of Patients With Unresectable Primary Liver Cancer Treated With Yttrium-90 Radioembolization With an Escalated Dose.

Purpose: Yttrium-90 (90Y) radioembolization with an escalated dose has been shown to improve clinical outcomes compared with standard dose radioembolization, but there are few data on the local control of primary liver tumors. We reported the clinical outcomes of patients with unresectable primary liver tumors treated with 90Y radioembolization with an escalated dose. Methods and Materials: Clinical data of patients with unresectable hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and biphenotypic tumors (cHCC-CC) treated with radioembolization with an escalated dose (≥150 Gy) between 2013 and 2020 with >3 months follow-up were retrospectively reviewed. The primary endpoint was freedom from local progression. Clinical response was defined by Modified Response Evaluation Criteria in Solid Tumours and toxic effects were assessed using Common Terminology Criteria for Adverse Events version 5.0. Results: Fifty-three patients with HCC and 15 patients with CC/cHCC-CC were analyzed. The median dose delivered was 205 Gy (interquartile range, 183-253 Gy) and 198 Gy (interquartile range, 154-234 Gy) for patients with HCC and CC/cHCC-CC, respectively. The 1-year freedom from local progression rate was 54% (95% confidence interval [CI], 38%-78%) for patients with HCC and 66% (95% CI, 42%-100%) for patients with CC/cHCC-CC. For patients with HCC, United Network for Organ Sharing nodal stage 1 (P = .01), nonsolitary tumors (P = .02), pretreatment α-fetoprotein of >7.7 ng/mL (P = .006), and ≤268 Gy dose delivered (P = .003) were predictors for local progression on multivariate Cox analysis. No patients with HCC who received a dose >268 Gy had a local tumor progression. The 1-year overall survival for patients with HCC was 74% (95% CI, 61%-89%). After radioembolization, 5 (7%) patients had grade 3 ascites, and 4 (6%) patients had grade 3/4 hyperbilirubinemia. Conclusions: Treatment of unresectable primary liver tumors with 90Y radioembolization with an escalated dose was safe and well tolerated. Delivery of >268 Gy may improve local tumor control of HCC. Determination of the maximum tolerated dose needs to be performed in the context of future prospective dose-escalation trials to further evaluate the safety and efficacy of such an approach.

Initial experience and lessons learned with implementing Lutetium-177-dotatate radiopharmaceutical therapy in a radiation oncology-based program.

PURPOSE: To assist radiation oncology centers in implementing Lutetium-177-dotatate (177Lu) radiopharmaceutical therapy for midgut neuroendocrine tumors. Here we describe our workflow and how it was revised based on our initial experience on an expanded access protocol (EAP). METHODS: A treatment team/area was identified. An IV-pump-based infusion technique was implemented. Exposure-based techniques were implemented to determine completion of administration, administered activity, and patient releasability. Acute toxicities were assessed at each fraction. A workflow failure modes and effects analysis (FMEA) was performed. RESULTS: A total of 22 patients were treated: 11 patients during EAP (36 administrations) and 11 patients after EAP (44 administrations). Mean 177Lu infusion time was 37 min (range 26-65 min). Mean administered activity was 97% (range 90-99%). Mean patient exposures at 1 m were 1.9 mR/h (range 1.0-4.1 mR/h) post-177Lu and 0.9 mR/h (range 0.4-1.8 mR/h) at discharge, rendering patients releasable with instructions. Treatment area was decontaminated and released same day. All patients in the EAP experienced nausea, and nearly half experienced emesis despite premedication with antiemetics. Peripheral IV-line complications occurred in six treatments (16.7%), halting administration in 2 cases (5.6%). We transitioned to peripherally inserted central catheter (PICC)-lines and revised amino acid formulary after the EAP. The second cohort of 11 patients after EAP were analyzed for PICC-line complications and acute toxicity. Nausea and emesis rates decreased (nausea G1+ 61%-27%; emesis G1+ 23%-7%), and no PICC complications were observed. FMEA revealed that a failure in amino acid preparation was the highest risk. CONCLUSION: 177Lu-dotatate can be administered safely in an outpatient radiation oncology department.

Efficiency of using the day-of-implant CT for planning of SAVI APBI.

PURPOSE: The purpose of the study was to develop an optimized, efficient workflow for using the day-of-implant (DOI) CT for treatment planning of accelerated partial breast irradiation brachytherapy using the strut-adjusted volume implant (SAVI) device. METHODS AND MATERIALS: For 62 consecutive SAVI patients, a DOI CT was acquired and used for treatment planning. A "verification" CT was acquired 24-72 h after implant and immediately before the first fraction, then registered to the DOI CT. If the DOI CT-based plan was no longer optimal, a replan was performed. An array of metrics describing the geometry of the device and its relative position in the patient from the DOI CTs for these patients was collected. These metrics from the DOI CT were evaluated to determine what features could predict for the need to replan before the first treatment fraction. Logistical regression analysis including χ2 tests was used to determine if different factors correlated with replanning. RESULTS: Twenty-two of 62 patients (35%) required replanning. Only the presence of splayed struts, where splay was toward the skin, and the use of a nine strut ("8-1") SAVI were significantly correlated (p < 0.05) with replanning. Within these individual populations, no additional factors showed a significant statistical correlation for requiring replanning. CONCLUSIONS: For strut-based accelerated partial breast irradiation brachytherapy, it was feasible to treat with a plan based on the DOI CT for a majority (65%) of patients. Some factors correlate to needing replanning; recognizing these could be used to optimize treatment workflow for certain patients, increasing clinical efficiency while enhancing the quality of patient care.

Outpatient-based high-dose-rate interstitial brachytherapy for gynecologic malignancies.

PURPOSE: To evaluate outpatient-based high-dose-rate (HDR) interstitial brachytherapy (ISBT) in the treatment of gynecologic malignancies. METHODS AND MATERIALS: Between December 2006 and July 2012, 50 patients were treated with twice-daily outpatient-based HDR iridium-192 ISBT at our institution. Thirty-two patients had vaginal cancers, 13 vulvar, 3 urethral, and 2 cervical cancers. The most common histologies were squamous cell carcinoma (58%) and endometrioid adenocarcinoma (26%). Twenty-six patients were treated with definitive radiation therapy with or without platinum-based chemotherapy, 16 were treated for recurrent disease, 5 were treated in the postoperative setting, and 3 were treated palliatively. Forty patients received external beam radiation therapy before ISBT. RESULTS: Median followup was 13.7 months. Median interstitial dose was 18 Gy in 2.25 Gy twice-daily fractions prescribed to the implant volume. Median external beam dose was 50.4 Gy in 1.8 Gy daily fractions prescribed to the primary disease site. Eight patients (16%) were seen in the emergency room or were admitted to the hospital during treatment. Six patients (17%) experienced significant complications after treatment (3 ulcerations at the primary site, 1 vaginal necrosis, 1 vaginal abscess, and 1 patient with urinary obstruction). Larger volume encompassing 100% of the prescribed dose was correlated with significant complications on multivariate analysis (p = 0.039). Actuarial local control at 1 year was 72%, with univariate analysis demonstrating worse local control for nonendometrioid adenocarcinoma compared with squamous cell carcinoma (20% vs. 84%, p = 0.044). CONCLUSIONS: Outpatient-based HDR ISBT is feasible and safe, with toxicity and local control rates consistent with historical outcomes.

Performance evaluation of an 85-cm-bore X-ray computed tomography scanner designed for radiation oncology and comparison with current diagnostic CT scanners.

INTRODUCTION: The demand for computed tomography (CT) virtual simulation is constantly increasing with the wider adoption of three-dimensional conformal and intensity-modulated radiation therapy. Virtual simulation CT studies are typically acquired on conventional diagnostic scanners equipped with an external patient positioning laser system and specialized planning and visualization software. Virtual simulation technology has matured to a point where conventional simulators may be replaced with CT scanners. However, diagnostic CT scanner gantry bores (typically 65-70 cm) can present an obstacle to the CT simulation process by limiting patient positions, compared to those that can be attained in a conventional simulator. For example, breast cancer patients cannot always be scanned in the treatment position without compromising reproducibility and appropriateness of setup. Extremely large patients or patients requiring special immobilization or large setup devices are often unable to enter the limited-bore gantry. A dedicated 85-cm-bore radiation oncology CT scanner has the potential to eliminate these problems. The scanner should provide diagnostic-quality images at diagnostic-comparable dose levels. The purpose of this study was to independently evaluate the performance of a novel 85-cm-bore CT X-ray scanner designed specifically for radiation oncology and compare it against diagnostic-type, 70-cm-bore scanners that may be used in the same setting. MATERIALS AND METHODS: We performed image quality and dosimetric measurements on an 85-cm-bore CT scanner (AcQSim CT, Marconi Medical Systems, Inc., Cleveland, OH) and a 70-cm-bore, diagnostic-type scanner (UltraZ CT, Marconi Medical Systems, Inc.). Image quality measurements were performed using a manufacturer-supplied phantom (Performance Phantom, Marconi Medical Systems, Inc.), following the manufacturer's suggested testing procedures, and an independent image quality phantom (CATPHAN 500, The Phantom Laboratory, New York, NY). The standard image quality parameters evaluated for the purpose of comparison were as follows: slice thickness accuracy, high-contrast resolution (limiting spatial resolution), low-contrast resolution, uniformity and noise, and CT number accuracy and linearity. Standard head and body protocols were employed throughout most of our measurements and were kept equal between the two scanners. The computed tomography dose index was measured for standard head and body imaging protocols using accepted methods and procedures. For comparison purposes, data for a diagnostic-type, 70-cm-bore scanner (GE HighSpeed CT/i) were extracted from the literature. The results obtained for the 85-cm-bore scanner are compared with the following: (1) manufacturer-provided autoperformance phantom test results (validating its use for routine quality assurance), (2) a similar set of measurements performed on a conventional 70-cm-bore, diagnostic-type CT scanner (UltraZ CT, Marconi Medical Systems, Inc.), and (3) current available data on other diagnostic-type CT scanners (GE HighSpeed CT/i). RESULTS: Head and body doses seem on average to be slightly (1-2 cGy) higher for the 85-cm-bore unit than for conventional 70-cm units. Measured slice thickness was within acceptable criteria, +/-0.5 mm. There does not seem to be any significant difference in high-contrast resolution. Both units render a limiting value of approximately 7-8 lp/cm for slice thickness 8-10 mm. Both units exhibit comparable CT number uniformity, accuracy, and linearity. Noise levels seem to be slightly increased (by approximately 0.05-0.2%) for the large-bore geometry. Low-contrast resolution for both units was comparable (4.5-5.5 mm @ 0.35%). All image quality parameters are well within diagnostic acceptable levels. CONCLUSION: The overall imaging performance and mechanical integrity of the 85-cm-bore scanner are comparable to those of conventional diagnostic scanners that may be employed in a radiation oncology setting.

Cervical gross tumor volume dose predicts local control using magnetic resonance imaging/diffusion-weighted imaging-guided high-dose-rate and positron emission tomography/computed tomography-guided intensity modulated radiation therapy.

PURPOSE: Magnetic resonance imaging/diffusion weighted-imaging (MRI/DWI)-guided high-dose-rate (HDR) brachytherapy and (18)F-fluorodeoxyglucose (FDG) - positron emission tomography/computed tomography (PET/CT)-guided intensity modulated radiation therapy (IMRT) for the definitive treatment of cervical cancer is a novel treatment technique. The purpose of this study was to report our analysis of dose-volume parameters predicting gross tumor volume (GTV) control. METHODS AND MATERIALS: We analyzed the records of 134 patients with International Federation of Gynecology and Obstetrics stages IB1-IVB cervical cancer treated with combined MRI-guided HDR and IMRT from July 2009 to July 2011. IMRT was targeted to the metabolic tumor volume and lymph nodes by use of FDG-PET/CT simulation. The GTV for each HDR fraction was delineated by use of T2-weighted or apparent diffusion coefficient maps from diffusion-weighted sequences. The D100, D90, and Dmean delivered to the GTV from HDR and IMRT were summed to EQD2. RESULTS: One hundred twenty-five patients received all irradiation treatment as planned, and 9 did not complete treatment. All 134 patients are included in this analysis. Treatment failure in the cervix occurred in 24 patients (18.0%). Patients with cervix failures had a lower D100, D90, and Dmean than those who did not experience failure in the cervix. The respective doses to the GTV were 41, 58, and 136 Gy for failures compared with 67, 99, and 236 Gy for those who did not experience failure (P<.001). Probit analysis estimated the minimum D100, D90, and Dmean doses required for ≥90% local control to be 69, 98, and 260 Gy (P<.001). CONCLUSIONS: Total dose delivered to the GTV from combined MRI-guided HDR and PET/CT-guided IMRT is highly correlated with local tumor control. The findings can be directly applied in the clinic for dose adaptation to maximize local control.