Transarterial Chemoembolization with LC Bead LUMI followed by Stereotactic Body Radiation Therapy in Treatment of Hepatocellular Carcinoma.

PURPOSE: Transarterial chemoembolization (TACE) in combination with stereotactic body radiation therapy (SBRT) is a promising therapy for patients with hepatocellular carcinoma (HCC). A radiopaque drug-eluting embolic bead used during TACE, called LC Bead LUMI (Boston Scientific), was developed to allow improved visualization during TACE. The purpose of this case series is to assess the visibility of LUMI after TACE and discuss its potential use as an alignment tool for SBRT. METHODS: Fourteen patients with HCC (median age 69) received TACE using LUMI immediately followed by SBRT to 50 Gy in 5 fractions (13 patients) or 40 Gy in 5 fractions (1). Computed tomography (CT) simulation and cone beam CT (CBCT) images taken before each fraction were compared with immediate post-TACE imaging. Success of the LUMI bead opacification was graded from excellent to poor visualization. Patients were followed to assess target lesion response, disease control, survival, and the long-term visibility of LUMI beads. RESULTS: CBCT immediately after TACE with LUMI displayed excellent tumor visibility for 6 of 13 patients (46.2%), moderate tumor visibility for 4 patients (30.8%), and poor tumor visibility for 3 patients (23.1%). When comparing CBCTs used for SBRT image verification to post-TACE CBCT, 53.8% remained unchanged and 46.2% deteriorated from excellent to moderate or moderate to poor, but none deteriorated from excellent to poor visualization. Median follow-up was 13 months (range 2-35). On average, LUMI beads were visible on noncontrast CT up to 20 months after SBRT. CONCLUSIONS: LC Bead LUMI has the ability to provide liver tumor demarcation on noncontrast and cone beam CT weeks to months following TACE. It can serve as an alignment tool and could improve the therapeutic ratio in liver SBRT by allowing for tumor margin reduction with a potential decrease in the risk of toxicity when treating HCC in facilities without magnetic resonance imaging-linear accelerator.

First report on the feasibility of a permanently implantable uni-directional planar low dose rate brachytherapy sheet for patients with resectable or borderline resectable pancreatic cancer.

BACKGROUND: Margin negative resection in pancreatic cancer remains the only curative option but is challenging, especially with the retroperitoneal margin. Intraoperative radiation therapy (IORT) can improve rates of local control but requires specially designed facilities and equipment. This retrospective review describes initial results of a novel implantable mesh of uni-directional low dose rate (LDR) Pd-103 sources (sheet) used to deliver a focal margin-directed high-dose boost in patients with concern for close or positive margins. METHODS: Eleven consecutive patients from a single institution with resectable or borderline resectable pancreatic cancer with concern for positive margins were selected for sheet placement and retrospectively reviewed. Procedural outcomes, including the time to implant the device and complications, and clinical outcomes, including survival and patterns of failure, are reported. A dosimetric comparison of the LDR sheet with hypothetical stereotactic body radiotherapy (SBRT) boost is reported. RESULTS: One patient had a resectable disease, and 10 patients had a borderline resectable disease and underwent neoadjuvant treatment. Sheet placement added 15 min to procedural time with no procedural or sheet-related complications. At a median follow up of 13 months, 64% (n = 7) of patients are alive and 55% (n = 6) are disease-free. Compared to a hypothetical SBRT boost, the LDR sheet delivered a negligible dose to kidneys, liver, and spinal cord with a 50% reduction in max dose to the small bowel. CONCLUSION: This is the first report of the use of an implantable uni-directional LDR brachytherapy sheet in patients with resected pancreatic cancer with concern for margin clearance, with no associated toxicity and favorable clinical outcomes.

Image Registration and Verification Workshop: A Pilot Study.

Image guided radiation therapy is essential to ensure complex treatment plans are delivered safely. Residents in radiation oncology have little to no structured training on how to order or evaluate patient setup imaging. We created a joint image verification workshop for medical and physics residents to learn about setup imaging options available, understand information needed to review patient setup, practice image review, and promote interprofessional collaboration during training. The workshop consisted of a didactic session and a hands-on portion for practice with setup images from example patients. Residents completed pre- and postsurveys where each rated their ability on a 10-point scale to (1) assess the appropriateness of an imaging modality for a given treatment and (2) independently check verification images. The workshop was given twice. Nine residents participated in 2018 and 7 again in 2019, along with 2 new residents. Participant scores were paired for analysis. First-time participants had a significant improvement in both areas (1-tailed t test, α = 0.05): meanA:6.27 vs 7.27, P = .029, meanB:5.36 vs 7.18, P = .003. Between workshops (2-tailed t test, α = 0.05), repeat participants had a small increase in self-confidence for assessing the appropriateness of imaging (7.14 vs 7.64, P = .038), whereas comfort with independently checking films decreased (7.29 vs 6.00, P = .022). Postworkshop results (1-tailed t test, α = 0.05) were statistically equivalent for both workshops. A formal interprofessional image verification workshop provides valuable resident education, but repeat exposures are necessary to maintain skills.

Volume, Dose, and Fractionation Considerations for IMRT-based Reirradiation in Head and Neck Cancer: A Multi-institution Analysis.

PURPOSE: Limited data exist to guide the treatment technique for reirradiation of recurrent or second primary squamous carcinoma of the head and neck. We performed a multi-institution retrospective cohort study to investigate the effect of the elective treatment volume, dose, and fractionation on outcomes and toxicity. METHODS AND MATERIALS: Patients with recurrent or second primary squamous carcinoma originating in a previously irradiated field (≥40 Gy) who had undergone reirradiation with intensity modulated radiation therapy (IMRT); (≥40 Gy re-IMRT) were included. The effect of elective nodal treatment, dose, and fractionation on overall survival (OS), locoregional control, and acute and late toxicity were assessed. The Kaplan-Meier and Gray's competing risks methods were used for actuarial endpoints. RESULTS: From 8 institutions, 505 patients were included in the present updated analysis. The elective neck was not treated in 56.4% of patients. The median dose of re-IMRT was 60 Gy (range 39.6-79.2). Hyperfractionation was used in 20.2%. Systemic therapy was integrated for 77.4% of patients. Elective nodal radiation therapy did not appear to decrease the risk of locoregional failure (LRF) or improve the OS rate. Doses of ≥66 Gy were associated with improvements in both LRF and OS in the definitive re-IMRT setting. However, dose did not obviously affect LRF or OS in the postoperative re-IMRT setting. Hyperfractionation was not associated with improved LRF or OS. The rate of acute grade ≥3 toxicity was 22.1% overall. On multivariable logistic regression, elective neck irradiation was associated with increased acute toxicity in the postoperative setting. The rate of overall late grade ≥3 toxicity was 16.7%, with patients treated postoperatively with hyperfractionation experiencing the highest rates. CONCLUSIONS: Doses of ≥66 Gy might be associated with improved outcomes in high-performance patients undergoing definitive re-IMRT. Postoperatively, doses of 50 to 66 Gy appear adequate after removal of gross disease. Hyperfractionation and elective neck irradiation were not associated with an obvious benefit and might increase toxicity.

Refining Patient Selection for Reirradiation of Head and Neck Squamous Carcinoma in the IMRT Era: A Multi-institution Cohort Study by the MIRI Collaborative.

PURPOSE: The therapeutic ratio of reirradiation for recurrent or second primary (RSP) squamous carcinoma of the head and neck may be improved in the intensity modulated radiation therapy (IMRT) era. However, patient selection for reirradiation remains challenging. We performed a multi-institution cohort study to investigate modern outcomes after IMRT-based reirradiation and to identify prognostic subgroups. PATIENTS AND METHODS: Patients with RSP squamous carcinoma originating in a previously irradiated field (≥40 Gy) who underwent reirradiation with IMRT (≥40 Gy re-IMRT) were included. Locoregional failure and late toxicity were calculated using the Gray competing risk method. Cox proportional hazards regression was used to identify factors associated with overall survival (OS). Factors associated with OS were entered into a recursive partitioning analysis (RPA) for OS. RESULTS: From 7 institutions, 412 patients were included. The median dose of re-IMRT was 60 Gy, and the median time between RT courses was 2.4 years. Chemotherapy was used in 76% of patients. The rates of grade ≥3, grade ≥4, and grade 5 acute toxicities were 19%, 4.4%, and 1.2%, respectively. The 2-year cumulative incidence of grade ≥3 late toxicity adjusted for the competing risks of recurrence or death was 14.2%. RPA identified 3 prognostic subgroups with distinct and homogenous OS (P<.001): class I included patients >2 years from their initial course of RT with resected tumors (2-year OS, 61.9%); class II included patients >2 years with unresected tumors or those ≤2 years and without feeding tube or tracheostomy dependence (2-year OS, 40.0%), and the remaining patients formed class III (2-year OS, 16.8%). Fifty-nine percent of class III patients underwent postoperative re-irradiation. CONCLUSIONS: This study informs outcomes and expectations with IMRT-based reirradiation. The RPA classification identifies 3 distinct subgroups, which can guide patient selection for therapy and clinical trial design. RPA class III patients are not ideal candidates for protracted chemoradiation regardless of resection status.

A Multi-institutional Comparison of SBRT and IMRT for Definitive Reirradiation of Recurrent or Second Primary Head and Neck Cancer.

PURPOSE: Two modern methods of reirradiation, intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT), are established for patients with recurrent or second primary squamous cell carcinoma of the head and neck (rSCCHN). We performed a retrospective multi-institutional analysis to compare methods. METHODS AND MATERIALS: Data from patients with unresectable rSCCHN previously irradiated to ≥40 Gy who underwent reirradiation with IMRT or SBRT were collected from 8 institutions. First, the prognostic value of our IMRT-based recursive partitioning analysis (RPA) separating those patients with unresectable tumors with an intertreatment interval >2 years or those with ≤2 years and without feeding tube or tracheostomy dependence (class II) from other patients with unresected tumors (class III) was investigated among SBRT patients. Overall survival (OS) and locoregional failure were then compared between IMRT and SBRT by use of 2 methods to control for baseline differences: Cox regression weighted by the inverse probability of treatment and subset analysis by RPA classification. RESULTS: The study included 414 patients with unresectable rSCCHN: 217 with IMRT and 197 with SBRT. The unadjusted 2-year OS rate was 35.4% for IMRT and 16.3% for SBRT (P<.01). Among SBRT patients, RPA classification retained an independent association with OS. On Cox regression weighted by the inverse probability of treatment, no significant differences in OS or locoregional failure between IMRT and SBRT were demonstrated. Analysis by RPA class showed similar OS between IMRT and SBRT for class III patients. In all class II patients, IMRT was associated with improved OS (P<.001). Further subset analysis demonstrated comparable OS when ≥35 Gy was delivered with SBRT to small tumor volumes. Acute grade ≥4 toxicity was greater in the IMRT group than in the SBRT group (5.1% vs 0.5%, P<.01), with no significant difference in late toxicity. CONCLUSIONS: Reirradiation both with SBRT and with IMRT appear relatively safe with favorable toxicity compared with historical studies. Outcomes vary by RPA class, which informs clinical trial design. Survival is poor in class III patients, and alternative strategies are needed.