Prior External Beam Radiation Research Articles

Intraoperative radiation therapy for pediatric sarcomas and other solid tumors.

To evaluate local failure (LF) and toxicity after intraoperative radiation therapy (IORT) in pediatric solid tumors (ST). A single-institution retrospective study of 96 pediatric patients (108 applications) with ST treated from 1995 to 2022 with IORT. LF was calculated via cumulative incidence function and overall survival (OS) by Kaplan-Meier method, both from the day of surgery. Median age at time of IORT was 8years (range: 0.8-20.9years). Median follow-up for all patients and surviving patients was 16months and 3years, respectively. The most common histologies included rhabdomyosarcoma (n=42), Ewing sarcoma (n=10), and Wilms tumor (n=9). Most (95%) received chemotherapy, 37% had prior external beam radiation therapy to the site of IORT, and 46% had a prior surgery for tumor resection. About half (54%) were treated with upfront IORT to the primary tumor due to difficult circumstances such as very young age or challenging anatomy. The median IORT dose was 12Gy (range: 4-18Gy), and median area treated was 24cm2 (range: 2-198cm2). The cumulative incidence of LF was 17% at 2years and 23% at 5years. Toxicity from IORT was reasonable, with postoperative complications likely related to IORT seen in 15 (16%) patients. Our study represents the largest and most recent analysis of efficacy and safety of IORT in pediatric patients with ST. Less than one quarter of all patients failed locally with acceptable toxicities. Overall, IORT is an effective and safe technique to achieve local control in patients with challenging circumstances.

Intraoperative Radiation Therapy for Relapsed or Refractory High-Risk Neuroblastoma: A 27-Year Experience

To evaluate outcomes after intraoperative radiation therapy (IORT) in high-risk neuroblastoma (NB), including local control, overall survival, and toxicity. This was a single institution retrospective study of 92 pediatric patients with NB treated with IORT from 1995 to 2022. Each IORT application was considered a separate event for a total of 110 sites treated. Local failure was calculated using the cumulative incidence function and survival by Kaplan-Meier method from the day of surgery. All patients had high-risk relapsed or treatment refractory disease. Median age was 6 years (range, 2-34 years). Median follow-up for all patients and surviving patients was 16 months and 4 years, respectively. All patients previously received chemotherapy, 93% had prior external beam radiation therapy to the site of IORT (median dose, 21.6 Gy; range, 10-36 Gy), and 94% had a prior surgery for tumor resection. The median IORT dose was 12 Gy (range, 8-18 Gy) and median area treated was 18 cm2 (range, 2.5-60 cm2). The cumulative incidence of local failure was 23% at 2 years and 29% at 5 years. The overall survival (OS) was 44% at 2 years and 29% at 5 years. Local failure after IORT was associated with worse OS (hazard ratio, 1.74; 95% CI, 1.07-2.84; P = .0267). Toxicity from IORT was rare, with postoperative complications likely related to IORT seen in 7 (8%) patients. Our study represents the largest, most recent analysis of the efficacy and safety of IORT in patients with relapsed or refractory NB. Less than one-third of patients failed locally at 5 years, and achieving local control affected overall survival. Minimal toxicities directly related to IORT were observed. Overall, IORT is an effective and safe technique to achieve local control in high-risk relapsed or refractory neuroblastoma.

Safety outcomes in patients with metastatic castration-resistant prostate cancer treated with radium-223 following external beam radiation therapy: REASSURE US subset.

106 Background: In the Phase 3 ALSYMPCA trial, radium-223 (Ra-223) demonstrated an overall survival (OS) benefit and a favorable safety profile in patients with metastatic castration-resistant prostate cancer (mCRPC). REASSURE (NCT02141438) is a global, prospective, single-arm, observational study of Ra-223 use in patients with mCRPC with bone metastases within routine clinical settings. Utilizing data from the second planned interim analysis, we evaluated safety outcomes in patients with mCRPC treated with Ra-223 following external beam radiation therapy (EBRT) in the US. Methods: In this descriptive analysis (data cutoff 3-20-2019), we included patients who received EBRT to bone prior to Ra-223 (≤2 years prior to Ra-223 first dose); results are presented relative to the overall US subset of patients enrolled into REASSURE. The focus of this abstract is on incidence of hematological toxicities, bone fractures, and second primary malignancies (SPM). Results: Of N=498 patients in the US subset, 118 patients received prior EBRT to bone. Median duration of observation was 11.7 months among patients who received EBRT and 11.9 months for the overall US subset. Any-grade drug-related hematological treatment-emergent adverse events (TEAEs) occurred in 8% (10/118) and 9% (47/498) of patients who received EBRT and the overall subset, respectively (Table). Grade ≥3 drug-related hematological TEAEs occurred in 5% (6/118) and 6% (32/498) of patients who received EBRT and the overall subset, respectively. Bone fractures occurred in 7% (8/118) and 4% (19/498) of patients who received EBRT and the overall subset, respectively. Six SPMs occurred in 5/118 patients who received EBRT (4%), and 11 SPMs occurred in 10/498 patients in the overall subset (2%). Results of bone fracture events by bone health agent use will be included in the full presentation. Conclusions: In this descriptive analysis of real-world data, patients who received EBRT prior to Ra-223 did not demonstrate an increased incidence of hematological toxicities relative to the overall US subset. Although percent of SPMs and bone fractures seems higher among patients treated with EBRT relative to the overall US subset, the real-world incidence of these events remains low. [Table: see text]

Previous external beam radiation therapy for pelvic malignancy increases complications of total hip arthroplasty.

External beam radiation therapy (EBRT) has known effects on bone health. No large database studies have looked at the effects of pelvic EBRT on total hip arthroplasty (THA) outcomes. The purpose of this study was to evaluate 90-day and long-term (>2 years) complication rates following THA in patients with a history of pelvic malignancy and EBRT. Patients were retrospectively identified using a national insurance claims database. Subjects who underwent THA for osteoarthritis or avascular necrosis were included if they had at least 2-year follow-up and were stratified into 3 cohorts: (1) prior pelvic malignancy diagnosis (prostate, cervical, uterine, ovarian, or rectal) and EBRT (Group A); (2) prior malignancy diagnosis but no EBRT (Group B); and (3) neither prior malignancy diagnosis nor EBRT (Group C). Univariate and multivariate analyses were conducted to evaluate for an association between prior EBRT and the incidence of 90-day and 2-year complication rates using chi-square, student t-tests, and logistic regression analyses where appropriate. 671,554 patients met the inclusion criteria. Group A had higher odds of all-cause revision, septic revision, and loosening with revision after 2 years when compared to Group C and Group B (p < 0.001). Group A subjects had higher rates of 90-day deep vein thrombosis, sepsis, and stroke (p < 0.001) than groups B and C. Prior EBRT for pelvic malignancy was associated with significantly increased rates of all-cause revision, septic revision, and loosening as well as 90-day medical complications.

Efficacy and safety of near-infrared fluorescence identification of the thoracic duct during left lateral neck dissection

BackgroundThoracic duct leaks occur in up to 5% of left lateral neck dissections. No one imaging modality is routinely used to identify the thoracic duct intraoperatively. The goal of our study was to evaluate the efficacy and safety of indocyanine green lymphangiography for intraoperative identification of the thoracic duct compared to traditional methods using ambient and evaluate the optimal timing of indocyanine green administration. MethodsWe enrolled all patients who underwent left lateral neck dissection at our institution from 2018 to 2022 in this prospective clinical trial. After indocyanine green injection into the dorsum of the foot, we performed intraoperative imaging was performed with a near-infrared fluorescence camera. We reported the data using descriptive statistics. ResultsOf the 42 patients we enrolled, 14 had prior neck surgery, and 3 had prior external beam radiation. We visualized the thoracic duct with ambient light in 48% of patients and with near-infrared fluorescence visualization in 64%. In 17% of patients, we could identify the thoracic duct only using near-infrared fluorescence visualization, which occurred within 3 minutes of injection, and were required to re-dose 5 patients. We visualized the thoracic duct with near-infrared fluorescence in all patients with prior neck radiation and 77% of patients with prior neck surgery. One adverse reaction occurred (hypotension), and 5 intraoperative thoracic duct injuries occurred that were ligated. There with no chylous fistulas postoperatively. ConclusionThis trial demonstrates that near-infrared fluorescence identification of the thoracic duct is feasible and safe with indocyanine green lymphangiography, even in patients with prior neck surgery or radiation.

Initial Clinical Outcomes of a Phase II Trial of Focal Salvage LDR Brachytherapy for Local Recurrence of Prostate Cancer after External Beam Radiation Therapy.

To evaluate the clinical outcomes of focal salvage low dose rate brachytherapy (FSB) for biopsy proven local recurrence of prostate cancer after definitive external beam radiation therapy (EBRT). Patients with a Phoenix definition PSA recurrence (nadir + 2.0ng/dL) after definitive EBRT for localized prostate cancer and a negative metastatic work up were enrolled in a Phase II clinical trial. Patients first underwent MR-guided transperineal mapping biopsy of the prostate using a template grid. Patients with a pathologically confirmed recurrence underwent FSB using iodine-125 seeds to a prescription dose of 145 Gy. The brachytherapy planning target volume (PTV) was defined by the positions of the pathologically negative core biopsies adjacent to the positive core biopsies as recorded on the template grid during the biopsy procedure. An intraoperative treatment plan was then developed to cover the PTV with the 145 Gy isodose line. Follow up included assessment of genitourinary (GU) and gastrointestinal (GI) toxicities using Common Terminology Criteria for Adverse Events version 4.03 (CTCAEv4.03), patient reported outcomes using the International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index-26 (EPIC-26) forms, and serial PSA blood draws. Ten patients underwent FSB. The median prior EBRT dose was 7805 cGy (interquartile range IQR 7560-7920) and the median time from completion of EBRT to FSB was 81 months (IQR 68-134). The median PSA prior to FSB was 3.2 ng/dL (IQR 2.3 - 4.5). The median follow up after FSB was 32 months (IQR 18-57). Eight patients were free of Phoenix definition PSA failure at last follow up. Of the two patients who experienced a PSA failure, one developed distant metastases 5 months after FSB and the other a biopsy proven seminal vesicle recurrence 3 years after FSB. The median change in post FSB IPSS score compared to the pre-FSB IPSS score was an increase of 1.5 (IQR -1.5 to 8) at 3 month follow up and an increase of 3.5 (IQR 0.5 to 5.5) at last follow up (≥1 year). The median change in post FSB EPIC-26 urinary domain score compared to the pre-FSB score was -1 (IQR -26 to +14.5) at 3 month follow up and +2 (IQR -12.5 to +14.5) at last follow up (≥1 year). The median change in post FSB EPIC-26 bowel domain score compared to the pre-FSB score was -2 (IQR -9.5 to 0.0) at 3 month follow up and 0 (IQR -6.0 to +3.0) at last follow up (≥1 year). No patients experienced post FSB Grade 3 or higher GU or GI toxicities. High dose FSB for a local recurrence of prostate cancer after EBRT can be delivered with good biochemical control and a favorable toxicity profile. Further clinical trial enrollment and longer follow up will be needed to better assess long term outcomes.

Prospective Evaluation of MRI-Based Endoluminal Brachytherapy with Novel Applicator for Anorectal Cancer

To present results of patients treated on a prospective dose escalation trial of MRI-based endoluminal high dose rate (HDR) brachytherapy (BT) and concurrent chemotherapy utilizing a novel double-balloon applicator for recurrent or inoperable rectal and anal cancer. A total of 15 patients were enrolled on a prospective, institutional review board-approved dose escalation protocol evaluating endoluminal HDR-BT with concurrent chemotherapy. Inclusion criteria were histologically confirmed locally residual or recurrent cancer of the rectum or anus and prior pelvic external beam radiation therapy (EBRT). BT was delivered with a novel anorectal applicator consisting of an inner balloon, which supported 8 channels for the radioactive source, and a compliant outer balloon for optimal deformation against exophytic lesions. Applicator insertion and treatment delivery were performed under general anesthesia in 3 weekly sessions. MRI-based treatment planning was performed while under anesthesia during the first session only. Capecitabine (825 mg/m2 BID) was administered Monday-Friday on the weeks of BT. Efficacy and toxicity were evaluated by clinical assessment and MRI examinations at pre-defined intervals (3, 6, and 12 months for the first year) after the procedure. From 1/2015 to 4/2018 15 patients at a median age of 65 years (43-86) with recurrent or residual cancer (9 rectal, 6 anal) were enrolled and treated at the initial dose level of 15 Gy in 3 fractions (n = 6), the intermediate dose level of 18 Gy in 3 fractions (n = 3), and the highest dose level of 21 Gy in 3 fractions (n = 6). Treatment was delivered as planned for 14 patients; 1 patient was treated with a single-channel Bougie applicator for the third fraction due to the development of severe circumferential narrowing that prevented insertion of the endorectal applicator. On first MRI imaging post-BT, 7 patients had a complete response, 5 patients had a partial response, 1 patient had progressive disease, and 2 patients had indeterminate imaging. At a median follow up of 26 months (7-88), 10 patients (6 rectal and 4 anal) have developed a local recurrence (2 also with distant disease) which were treated with surgery (4), systemic therapy (1), or no known therapy (3). Acute (<6 months post-RT) grade 2 and 3 toxicities were observed in 1 (rectal bleeding) and 2 (anorectal pain) patients, respectively, and the only late grade 3 toxicity observed was rectal bleeding in 1 patient. Endoluminal HDR BT with MRI-based treatment planning and a novel double-balloon applicator was feasible up to a dose level of 21Gy in 3 fractions in patients with non-operable rectal or anal cancers and history of prior EBRT. The clinical efficacy and toxicity associated with this treatment should be more clearly defined with analyses of larger cohorts of patients.

Intraoperative Radiation Therapy for Pediatric Patients: A 25 Year Experience

To assess outcomes after intra-operative radiation therapy (IORT) in pediatric patients, including local control, overall survival, and toxicity. Single institution retrospective study of 184 pediatric patients treated with IORT from 1995-2022. Each IORT application was considered a separate event for a total of 213 sites treated. Local failure was calculated using the cumulative incidence function and survival by Kaplan-Meier method from the day of surgery. Median follow up for all patients was 14 months while median follow up for surviving patients was 3 years. Median patient age was 6 years (range 9 months to 21 years) and half were male. Patients were generally high risk with 76% having relapsed or refractory disease. Tumor types included neuroblastoma (n = 88), soft tissue sarcoma (n = 69), Wilms tumor (n = 11), and other solid tumors (n = 24). The majority (97%) of patients had prior chemotherapy, 69% had at least one prior attempt at resection, and 65% had prior external beam radiation to the site of IORT. Location of IORT included the retroperitoneum (n = 99), anterior abdominal wall (n = 14), pelvic region (n = 49), chest and thorax (n = 36), head (n = 5), neck (n = 7), and axilla/shoulder (n = 3), with a median dose of 12 Gy (range 4 to 18 Gy). Overall survival was 47% and 32% at 2 and 5 years respectively. Rates of local failure were 20% and 26% at 2 and 5 years. Local failure had a significant impact on overall survival (p = 0.009). Analyzing specific tumor types at 2 years, the rate of local failure and overall survival were 22% and 57% for soft tissue sarcomas, 23% and 39% for neuroblastoma, and 10% and 60% for Wilms tumor. Direct toxicity from IORT was rare, however there were several cases of surgical complications where a potential contribution from IORT could not be ruled out. The most common complications included abscesses in the surgical field, fistula or stricture development, and hydronephrosis. There were no post-operative mortalities related to IORT. Our study represents the largest scale analysis of efficacy and safety of IORT in patients with pediatric solid tumors. Less than one third of patients failed locally at 5 years. Achieving local control impacted overall survival, emphasizing the importance of local control in these patients. Minimal radiation related toxicities were observed. Overall, IORT is an effective technique to achieve local control in children with high-risk solid tumors.

Stereotactic Body Radiation Therapy for Large Volume Solid Tumor Spinal Metastases Involving Three or More Contiguous Vertebral Levels

Data for treating 3 or more contiguous vertebral bodies with SBRT is limited. The purpose of this study was to explore oncologic outcomes and toxicity of spine SBRT delivered to large volume solid tumor metastases involving 3 or more contiguous vertebral levels. Patients treated with spine SBRT for vertebral metastases involving 3 or more contiguous levels between 2009 and 2021 were retrospectively reviewed. Data on demographics, dosimetry, toxicity, and outcomes were collected. Radiographic local failure was defined as progressive disease on CT and/or MRI in the treatment volume compared to the pre-SBRT baseline. Local control (LC) and overall survival (OS) were calculated from end of SBRT using the Kaplan-Meier and log-rank test. A total of 141 patients were included with a median follow-up of 9.7 months. The majority of patients had either 3 (74%) or 4 (16%) involved contiguous vertebral levels. Twenty-two percent, 57%, 14%, and 7% of treated lesion began in the cervical, thoracic, lumbar, and sacral vertebral levels, respectively. The most common primary sites were NSCLC (15.6%), kidney (14.9%), and breast (13.5%). Thirty-two percent of patients had prior external beam radiation to the same vertebral level, 63% had prior surgery, and 43% had prior vertebral fracture. Paraspinal extension was identified in 26% at time of SBRT. Median pre-SBRT Bilsky grade was 2 (range 0-3). The median total prescription dose was 27 Gy (range: 12-43 Gy) with the most common dose (Gy)/fractionation schedules of 27/5 (32%), 30/5 (25%), and 25/5 (18%). The median Dmax was 4727 cGy (range 2070-7857) with a median prescription isodose of 58% (range 48-97). The median OS was 12.4 months (95% CI 9.6-15.3). 1- and 2- year OS were 51% and 35%, respectively. Local progression occurred across all histologies, most commonly in colon and NSCLC (16.7%). 1- and 2-year LC were 70% and 57%, respectively. In the radiation-naïve cohort, 1- and 2-year LC were 75% and 63%, respectively and 52% and 34% in the prior radiation group with no statistically significant difference in time to local progression (p = 0.075). There was no statistically significant difference in LC when comparing 3 versus 4 or more contiguous lesions (p = 0.66). Forty percent of patients that progressed underwent salvage treatment (58% surgery, 33% SBRT, 8% systemic therapy). Post-SBRT vertebral compression fracture rate was 11.6%. We present the largest series to date of patients treated with SBRT for large volume spinal metastases involving 3 or more contiguous levels. These data suggest reasonable local control and low toxicity with SBRT; therefore, SBRT should be considered a practical modality to offer this cohort.

Surgically targeted radiation therapy (STaRT) for recurrent brain metastases: Initial clinical experience

PURPOSEThis study evaluates the outcomes of recurrent brain metastasis treated with resection and brachytherapy using a novel Cesium-131 carrier, termed surgically targeted radiation therapy (STaRT), and compares them to the first course of external beam radiotherapy (EBRT). METHODSConsecutive patients who underwent STaRT between August 2020 and June 2022 were included. All patients underwent maximal safe resection with pathologic confirmation of viable disease prior to STaRT to 60 Gy to a 5-mm depth from the surface of the resection cavity. Complications were assessed using CTCAE version 5.0. RESULTSTen patients with 12 recurrent brain metastases after EBRT (median 15.5 months, range: 4.9–44.7) met the inclusion criteria. The median BED10Gy90% and 95% were 132.2 Gy (113.9–265.1 Gy) and 116.0 Gy (96.8–250.6 Gy), respectively. The median maximum point dose BED10Gy for the target was 1076.0 Gy (range: 120.7–1478.3 Gy). The 6-month and 1-year local control rates were 66.7% and 33.3% for the prior EBRT course; these rates were 100% and 100% for STaRT, respectively (p < 0.001). At a median follow-up of 14.5 months, there was one instance of grade two radiation necrosis. Surgery-attributed complications were observed in two patients including pseudomeningocele and minor headache. CONCLUSIONSSTaRT with Cs-131 presents an alternative approach for operable recurrent brain metastases and was associated with superior local control than the first course of EBRT in this series. Our initial clinical experience shows that STaRT is associated with a high local control rate, modest surgical complication rate, and low radiation necrosis risk in the reirradiation setting.

Prime-boost immunotherapeutic trial in men with biochemical recurrence after definitive local therapy for prostate cancer.

TPS5119 Background: VTP-850 is a heterologous prime-boost immunotherapeutic consisting of 2 nonreplicating viral-vectored components: ChAdOx1-PCAQ, based on an adenoviral vector, and MVA-PCAQ, based on a modified vaccinia virus Ankara (MVA) vector. Both components encode the same 4 prostate cancer antigens: prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), six transmembrane epithelial antigen of prostate 1 (STEAP1), and 5T4, an oncofetal antigen. Preclinical studies in inbred, outbred, and HLA-A2 transgenic mice show that VTP-850 is highly immunogenic. Immune responses were measured in splenocytes using IFN-γ ELISpot assay, multiparameter flow cytometry, and targeted in vivo killing assays. The results indicate that VTP-850 can elicit T cell responses to each of the 4 encoded antigens, with the responses to PSA of greatest magnitude in all mouse strains studied. Intravenous administration of the boost resulted in a 6-fold increase in the magnitude of antigen-specific T cells induced and increased in vivo killing relative to the intramuscular boosting route1. Methods: This is a first-in-human multicenter Phase 1/2 trial to evaluate safety, PSA response rate and duration, and immunogenicity of VTP-850 in men with biochemical recurrence of prostate cancer after definitive local therapy. Phase 1 (15-18 participants) will follow a 3+3 design to determine the recommended phase 2 regimen; dose level of both ChAdOx1-PCAQ and MVA-PCAQ, and route of administration of MVA-PCAQ (IM or IV). Phase 2 will consist of 2 stages. In Stage 1, 19 additional participants will be enrolled at the chosen Phase 2 regimen. If 4 or more of the 25 participants (including the 6 Phase 1 participants who received the same regimen) have a PSA response (defined as ≥50% reduction in serum PSA compared to baseline at any time, measured twice consecutively, at least 2 weeks apart), Stage 2 will enroll 100 additional participants. Participants will be followed for 6 months or until start of new therapy (e.g. ADT) or until development of metastatic disease. Participants who have a PSA response during the 6 months follow up will be followed for up to an additional 18 months. Patients who have undergone primary therapy for prostate cancer and have biochemical recurrence are eligible. Patients must have nonmetastatic (M0) disease; serum PSA of &gt; 0.3 ng/mL for participants with prior radical prostatectomy or serum PSA of 2 ng/mL above nadir for participants with prior external beam radiation or brachytherapy; PSA doubling time ≤12 months; and testosterone &gt; 75 ng/dL. They cannot have received ADT within 6 months prior to Day 1 and cannot have received prior chemotherapy, immunotherapy or experimental agent for prostate cancer. The trial is open in the USA, with sites in Spain and Italy planned to open later in 2023. 1. Vardeu A et al 2022. Clinical trial information: NCT05617040 .

68Ga-FAPI-46 PET for cancer imaging: A prospective single-arm clinical trial.

3064 Background: Fibroblast activation protein (FAP) is expressed at high levels on tumor associated fibroblasts. FAP-directed radioligand positron-emission-tomography (FAP-PET) is a novel diagnostic tool for cancer. However, we currently do not understand the diagnostic performance of FAP-PET as compared to standard FDG-PET. Here we aim to compare tumor detection by FDG- vs. FAP-PET with independent validation of discrepant findings. Methods: Patients with (a) proven or suspected malignancy, (b) longest tumor diameter &gt;1 cm, (c) intended surgery or biopsy, and (d) no prior external beam radiation or systemic tumor therapy within 3 months underwent FDG- and FAP-PET for tumor localization on subsequent days. Clinical reads were analyzed prospectively on a per-patient and per-region basis (local, locoregional nodal, distant organ or soft tissue, bone). Discrepant findings were validated as true vs. false positive by histopathology or image follow-up. Tracer uptake in tumor tissue was assessed by SUVmax. Results: In total n=100 patients (median 62 years, male/female n=68/32) underwent FDG- and FAP-PET. Five most frequent tumor entities and respective median FDG vs FAP uptake were RCC (n=19; SUVmax 8.4 vs. 7.1), sarcoma (n=18; 10.3 vs. 10.9), NSCLC (n=10; 12.4 vs. 13.7), lymphoma (n=9; 18.3 vs. 10.9), and PDAC (n=8; 4.1 vs. 7.3). On a per-patient basis, FDG- vs FAP-PET localized malignancy in n=93/94 patients. FDG- vs FAP-PET was concordant for the assessment of 362/400 (91%) regions. n=16/400 (4%) regions were negative on FDG- and positive on FAP-PET (88% true, 12% false positive). n=22/400 (6%) regions were negative on FAP- and positive on FDG-PET (57% true, 43% false positive). Two false positive FDG-PET findings were due to tracer uptake in reactive lymph nodes. There were no PET-related adverse events. Conclusions: In patients with various tumor entities, standard FDG- and novel FAP-PET localized tumor equally well. Additionally, FAP-PET was associated with a lower rate of false positive findings, especially in lymph node assessments. Clinical trial information: NCT05160051 . [Table: see text]

Percutaneous Cryoablation of Plasmacytomas: Oncologic Effectiveness and Adverse Events

PurposeTo evaluate the oncologic outcomes and adverse events associated with cryoablation of plasmacytomas. Materials and MethodsRetrospective review of an institutional percutaneous ablation database showed that 43 patients underwent 46 percutaneous cryoablation procedures for treatment of 44 plasmacytomas between May 2004 and March 2021. The treatment of 25 (25 of 44, 56.8%) tumors was augmented with bone consolidation/cementoplasty. The median patient age was 64 years (interquartile range [IQR], 54–69), and 30 of 43 (69.8%) patients were men. The median maximum plasmacytoma diameter was 5.0 cm (IQR, 3.1–7.0). Thirty of 44 (68.2%) tumors were periacetabular, vertebral, or located in the iliac wing. Twenty-nine of 44 (65.9%) cryoablated plasmacytomas were recurrent tumors after prior external beam radiation therapy (EBRT). Survival analyses were performed using the Kaplan-Meier method. Adverse events were graded using Society of Interventional Radiology criteria. ResultsThe 5-year estimated local tumor recurrence–free survival was 85.3% (95% CI, 74.1%–98.1%), the 5-year estimated new plasmacytoma–free survival was 49.9% (95% CI, 33.9%–73.4%), and the 5-year estimated overall survival was 70.4% (95% CI, 56.9%–87.1%). Nine of 46 (19.6%) major adverse events occurred in 8 patients, including 3 of 46 (6.5%) new or progressive pathologic fractures at the ablation site requiring surgical intervention, 3 of 46 (6.5%) nerve injuries, 1 of 46 (2.2%) avascular necrosis and femoral head collapse, 1 of 46 (2.2%) septic arthritis, and 1 of 46 (2.2%) acute renal failure caused by rhabdomyolysis. ConclusionsPercutaneous cryoablation is a viable treatment option for patients with plasmacytomas, including those with recurrent plasmacytomas after EBRT. Postcryoablation adverse events are relatively common.

Shoulder arthroplasty after prior external beam radiation therapy: a matched cohort analysis.

External beam radiation therapy (XRT) is a commonly used therapeutic modality for the treatment of various chest wall and axillary malignancies. Despite the known risk of local soft tissue dysfunction, and possibly compromised bone ingrowth for cementless implants, there remains limited data on the impact of prior XRT in a shoulder arthroplasty (SA) cohort. This study evaluated the outcomes of primary SA in patients with prior XRT compared to a matched cohort (MC). Over a 27-year time period (1993-2020), 80 primary SAs (7 hemiarthroplasties [HAs], 29 anatomic total shoulder arthroplasties [aTSAs], and 44 reverse shoulder arthroplasties [rTSAs]) with previous XRT to the upper chest or axillary region and a minimum of 2-year follow-up were included. This cohort was matched (1:2) according to age, sex, body mass index (BMI), implant, and year of surgery with patients who had undergone HA or TSA for osteoarthritis or RSA for cuff tear arthropathy. Clinical outcomes including pain, active shoulder range of motion (ROM), strength, complications, and reoperations inclusive of revision surgery were assessed. The XRT cohort consisted of 71 (88.8%) women with a mean age of 70.9 (range, 43-87) years, BMI of 30.9±7.6, and follow-up period of 6.6 years (range, 2.0-28.2). In these patients, SA led to substantial improvements in pain, ROM, and strength across the entire cohort. When compared to the MC, the XRT group demonstrated a lower final postoperative forward elevation (FE) (111° vs. 126°; P=.013) and less improvements in pain (5.3 vs. 6.2; P=.002), FE (34° vs. 54°; P=.002), and external rotation (13° vs. 24°; P<.001). There were 14 (17.5%) complications and 7 reoperations in the XRT group, with rotator cuff failure after HA or TSA (n=4 of 36; 11.1%) as the most common complication and no instances of loose humeral components. The XRT group had a higher rate of complications (17.5% vs. 8.1%; P=.03) but not reoperations (8.8% vs. 3.1%; P=.059). When evaluated by implant, rTSA demonstrated the lowest rate of reoperations followed by aTSA and HA (2.3% vs. 10.3% vs. 42.9%; P=.002). Primary SA is an effective treatment modality for the improvement of pain, motion, and strength in patients with a history of prior XRT. However, when compared to patients without prior XRT, less clinical improvement and a higher rate of postoperative complications were observed.

Secondary ovarian cancer after external beam radiotherapy for nonovarian pelvic malignancy.

To examine characteristics and survival of patients who developed secondary ovarian cancer after external beam radiotherapy (EBRT) for a prior nonovarian pelvic malignancy. This is a population-based retrospective cohort study, querying the Surveillance, Epidemiology, and End Result program from 1975 to 2016. 167,269 women who received EBRT for 7 malignancies (anus, rectum, bladder, cervix, uterus, vulva, or vagina) were examined to identify subsequent secondary ovarian cancer diagnosis after EBRT. Then, within the ovarian cancer cohort (n=147,618), characteristics and survival of patients with secondary ovarian cancer after EBRT were compared to those with ovarian cancer who did not receive prior EBRT. Following EBRT for a pelvic malignancy, 215 (1.3 per 1000) patients developed secondary ovarian cancer. Among those, the most frequent prior malignancy was cervical cancer (45.6%), followed by rectal cancer (20.9%). The median time from prior EBRT to secondary ovarian cancer was 8.8 years (interquartile range, 2.8-14.5). In multivariable analysis, patients with secondary ovarian cancer after EBRT were more likely to be older, and have a recent year of diagnosis, but less likely to have early-disease compared to ovarian cancer patients without prior EBRT (all, P<0.05). In weighted model, patients with secondary ovarian cancer after EBRT had decreased overall survival compared to those with ovarian cancer without prior EBRT (5-year rates, 19.6% versus 39.9%, hazard ratio 1.62, 95% confidence interval 1.43-1.85). Similar association was observed in ages <70, ≥70, White, non-White, early-disease, and advanced-disease in sensitivity analyses. Radiotherapy-related secondary ovarian cancer may be associated with decreased overall survival.

The Impact of Tumor Size and Histology on Local Control when Utilizing High-Dose-Rate Interstitial Brachytherapy for Gynecologic Malignancies

<h3>Purpose/Objective(s)</h3> To report long-term results of an outpatient template-based high dose rate interstitial brachytherapy (HDR ISBT) program for the treatment of gynecologic malignancies. <h3>Materials/Methods</h3> Patients treated at an academic hospital with outpatient template-based HDR ISBT without spinal or general anesthesia between 2006-2020 were retrospectively reviewed for this study. Patients who had previously received HDR ISBT were excluded. Baseline patient, tumor, and treatment characteristics, including tumor size, tumor histology, total EQD2 including prior external beam radiation therapy (EBRT), and/or prior chemotherapy were collected. EQD2 was calculated using an alpha/beta ratio of ten. Local control (LC) was estimated utilizing the Kaplan-Meier method. Factors associated with LC were evaluated using Cox regression analyses. <h3>Results</h3> 150 patients received HDR ISBT for a gynecologic tumor (Table 1) and median follow up time was 2.98 years (0.89-4.82). 54 local failures occurred in this patient population. Of these, 28% (15/54) were due to progression, 34% (18/54) were due to persistent disease, and 38% (20/54) were due to local recurrence. LC for all patients was 71% (64%-79%), 58% (50%-68%), and 57% (48%-67%) at one, three, and five years. LC was inferior in patients with tumors ≥3 cm (p=0.039) and non-endometrial adenocarcinoma histology (p=0.017). On multivariate analysis, non-endometrial adenocarcinoma (HR=2.423, 95% CI=1.011-5.808, p=0.047) and tumor size ≥3 cm (HR=2.903, 95% CI 1.053-3.441, p=0.033) were associated with lower LC. <h3>Conclusion</h3> The majority of patients who received outpatient-based twice daily HDR ISBT had long term LC in this series. Larger tumor size and non-endometrial adenocarcinoma histology were detrimental to LC.

The impact of tumor size and histology on local control when utilizing high-dose-rate interstitial brachytherapy for gynecologic malignancies

ObjectiveTo report long-term results of an outpatient template-based high-dose-rate interstitial brachytherapy (HDR ISBT) program for the treatment of gynecologic malignancies. MethodsPatients treated between 2006 and 2020 at an academic hospital with outpatient template based HDR ISBT without spinal or general anesthesia were reviewed. Patients who had previously received HDR ISBT were excluded. Baseline patient, tumor, and treatment characteristics, such as tumor size, histology, and/or total EQD2 including prior external beam radiation therapy (EBRT) were recorded. Local control and overall survival were estimated using the Kaplan-Meier method, and factors associated with local control and overall survival were evaluated using Cox regression analyses. Results150 patients received HDR ISBT for a gynecologic tumor and the median follow-up time was 2.98 years (0.89–4.82). Of those, 74/150 (49%) were treated definitively, 69/150 (46%) were treated for tumor recurrence/persistence, and 7/150 (5%) were treated for durable palliation. Median tumor size was 3.00 cm (1.50–4.00). 124/150 (83%) patients received EBRT prior to HDR ISBT. Median HDR ISBT dose was 18 Gy delivered in eight fractions. Local control was 71% (64%–79%), 58% (50%–68%), and 57% (48%–67%) at one, three, and five years, respectively. On multivariate analysis, non-endometrial adenocarcinoma histology (HR = 2.423, 95% CI = 1.011–5.808, p = 0.047) and tumor size ≥ 3 cm (HR = 2.903, 95% CI 1.053–3.441, p = 0.033) were associated with lower local control. ConclusionsThe majority of patients who received outpatient-based twice daily HDR ISBT had long-term local control. Larger tumor size and non-endometrial adenocarcinoma histology were detrimental to local control.

Increased risk of secondary bladder cancer after radiation therapy for endometrial cancer

To investigate the effect of radiation therapy (RT) after endometrial cancer (EC) diagnosis on the risk of occurring secondary bladder cancer (SBC) as well as on the survival outcome of those patients who suffered with SBC. Data was extracted from the Surveillance, Epidemiology, and End Results database between 1973 and 2015. Chi-squared test was utilized to compare clinicopathological characteristics among different groups. The Fine and Gray’s competing risk model was utilized to assess cumulative incidence and risk of occurring SBC in EC survivors. The Kaplan–Meier method and the Cox regression model were used for survival analysis. As a result, a total of 108,060 EC patients were included, among which 37,118 (34.3%) patients received RT while others did not. The incidence of SBC was 1.31%, 1.76% and 0.96% among patients who received prior brachytherapy, external-beam radiotherapy (EBRT) and others, respectively. Both of the EBRT (standardized incidence ratio (SIR) = 2.24, 95% CI [1.94–2.58]) and brachytherapy (SIR = 1.76, 95% CI [1.44–2.13]) group had a higher incidence of SBC than the general population in USA. The competing risk analysis demonstrated that receiving EBRT (HR = 1.97, 95% CI [1.64–2.36]) or brachytherapy (HR = 1.46, 95% CI [1.14–1.87]) were all independent risk factors for developing SBC. A survival detriment was only observed in SBC patients who received prior EBRT after EC diagnosis, but not for brachytherapy, when compared with those who did not undergo RT. Additionally, there were no significant survival differences between primary bladder cancer and SBC with or without prior RT history. Patients who underwent RT after EC had an increased risk of developing bladder cancer as secondary primary cancer. The prognosis of these SBC patients varied depending on types of RT that received after EC diagnosis.

A comparative study of dosimetric parameters of 3D-printed non-coplanar template-assisted CT-guided iodine-125 seed implantation brachytherapy in patients with inguinal lymph node metastatic carcinomas.

To compare the pre-plan and post-plan dosimetric parameter differences of 3D-printed non-coplanar templates (3D-PNCT)-assisted computed tomography (CT)-guided iodine-125 (125I) radioactive seed implantation brachytherapy (RISI) in patients with inguinal lymph node metastasis (ILNM). This was a retrospective study of 15 patients with ILNM carcinomas treated with 3D-PNCT-assisted CT-guided RISI between May, 2015 and April, 2018. All patients underwent prior external beam radiotherapy (EBRT) or surgery. Dosimetric parameters included D90, D100 (dose delivered to 90% and 100% of the volume, respectively), V100, V150, V200 (percentage of target volume receiving 100%, 150%, and 200% of the prescribed dose, respectively). Quality parameters included conformal index (CI), external index (EI), and homogeneity index (HI). Paired t-test and Bland-Altman analysis were applied to compared pre-plan and post-plan parameters. The median gross tumor volume (GTV) in the pre-plan was 8.7 ml (range, 0.8-185.1 ml). There were statistically significant differences in V100, V150, CI, and EI (p < 0.05). Bland-Altman analysis indicated that accidental error of RISI was small. In 1 of the 15 cases, D90 and D100 exceeded the prescribed therapeutic accuracy. In 1 of the 15 cases, V150, EI, and GTV were outside the specified accuracy range (95% confidence interval). 3D-PNCT-assisted CT-guided RISI is a safe, accurate, and feasible choice in ILNM treatment. The procedure of RISI has significantly improved. The pre-plan can be accurately executed by 3D-PNCT-assisted CT-guided RISI.

Salvage Low-Dose-Rate Prostate Brachytherapy: Clinical Outcomes of a Phase 2 Trial for Local Recurrence after External Beam Radiation Therapy (NRG Oncology/RTOG 0526)

We report efficacy of a prospective phase 2 trial (NCT00450411) of salvage low-dose-rate (LDR) prostate brachytherapy (BT) for local failure (LF) after prior external beam radiation therapy (EBRT) with minimum 5-years' follow-up. Eligible patients had low/intermediate risk prostate cancer (PCa) before EBRT and biopsy-proven LF >30 months after EBRT, with prostate-specific antigen <10 ng/mL and no regional/distant disease. The primary endpoint, late gastrointestinal and genitourinary adverse events (Common Terminology Criteria for Adverse Events v3.0) grade ≥3 were 14%. With minimum 5-year follow-up after salvage BT, secondary clinical outcomes including disease-free survival (DFS; includes death from any cause), disease-specific survival, and overall survival (OS) were estimated using the Kaplan-Meier method and modelled using Cox proportional hazards regression. Local tumor progression (ie, LF), distant failure (DF), and biochemical failure (BF) were estimated using cumulative incidence. Time to LF, DF, and BF were modeled by cause-specific Cox proportional hazards regression. From May 2007 to January 2014, 20 centers registered 100 patients (92 analyzable). Median follow-up is 6.7 years (range, 0.3-11.2); median age 70 years (range, 55-82); median prior EBRT dose 74 Gy [interquartile range (IQR):70 - 76] at a median of 85 months prior (IQR 60-119 months). Androgen deprivation was combined with salvage BT in 16%. Ten-year OS is 70% [95% confidence interval (CI) 58% - 83%]. Nineteen patients died (5 PCa, 10 other, 4 unknown). Ten-year failure rates are local 5% (95% CI, 1-11), distant 19% (95% CI, 10-29), and biochemical 46% (95% CI, 34-57). DFS is 61% at 5 years and 33% at 10 years. No baseline characteristic was significantly associated with any clinical outcome. This is the first prospective multicenter trial reporting outcomes of salvage LDR BT for LF after EBRT. Five-year freedom from BF is 68%, comparable to other salvage modalities. Although further LF is rare (5%), BF climbs to 46% by 10 years.