Outcomes of Late-Line Systemic Treatment in GIST: Does Sequence Matter?

Ripretinib and avapritinib have demonstrated activity in the late-line treatment of gastrointestinal stomal tumors (GISTs). We investigated whether patients previously treated with ripretinib benefit from avapritinib, and vice versa. Patients diagnosed with metastatic/unresectable GIST and treated with both drugs at two institutions in 2000-2021 were included. Patients were grouped by drug sequence: ripretinib-avapritinib (RA) or avapritinib-ripretinib (AR). Radiographic response was evaluated using RECIST 1.1. Kaplan-Meier and log-rank tests were used to compare time-to-progression (TTP) and overall survival (OS). Thirty-four patients (17 per group) were identified, with a median age of 48 years. The most common primary site was the small bowel (17/34, 50%), followed by the stomach (10/34, 29.4%). Baseline characteristics and tumor mutations were not significantly different between groups. Response rates (RRs) for ripretinib were 18% for RA and 12% for AR; RRs for avapritinib were 12% for AR and 18% for RA. Median TTPs for ripretinib were 3.65 months (95%CI 2-5.95) for RA and 4.73 months (1.87-15.84) for AR. Median TTPs for avapritinib were 5.39 months (2.86-18.99) for AR and 4.11 months (1.91-11.4) for RA. Median OS rates following RA or AR initiation were 29.63 (95%CI 13.8-50.53) and 33.7 (20.03-50.57) months, respectively. Both ripretinib and avapritinib were efficacious in the late-line treatment of GIST, with no evidence that efficacy depended on sequencing.

Adaptive Darwinian off-target resistance mechanisms to selective RET inhibition in RET driven cancer.

Patients treated with RET protein tyrosine kinase inhibitors (TKIs) selpercatinib or pralsetinib develop RET TKI resistance by secondary RET mutations or alterative oncogenes, of which alterative oncogenes pose a greater challenge for disease management because of multiple potential mechanisms and the unclear tolerability of drug combinations. A patient with metastatic medullary thyroid carcinoma (MTC) harboring a RET activation loop D898_E901del mutation was treated with selpercatinib. Molecular alterations were monitored with tissue biopsies and cfDNA during the treatment. The selpercatinib-responsive MTC progressed with an acquired ETV6::NTRK3 fusion, which was controlled by selpercatinib plus the NTRK inhibitor larotrectinib. Subsequently, tumor progressed with an acquired EML4::ALK fusion. Combination of selpercatinib with the dual NTRK/ALK inhibitor entrectinib reduced the tumor burden, which was followed by appearance of NTRK3 solvent-front G623R mutation. Preclinical experiments validated selpercatinib plus larotrectinib or entrectinib inhibited RET/NTRK3 dependent cells, whereas selpercatinib plus entrectinib was necessary to inhibit cells with RET/NTRK3/ALK triple alterations or a mixture of cell population carrying these genetic alterations. Thus, RET-altered MTC adapted to selpercatinib and larotrectinib with acquisition of ETV6::NTRK3 and EML4::ALK oncogenes can be managed by combination of selpercatinib and entrectinib providing proof-of-concept of urgency of incorporating molecular profiling in real-time and personalized N-of-1 care transcending one-size-fits-all approach.

Definitive single fraction spine stereotactic radiosurgery for metastatic sarcoma: Simultaneous integrated boost is associated with high tumor control and low vertebral fracture risk.

INTRODUCTION: Sarcoma spinal metastases (SSM) are particularly difficult to manage given their poor response rates to chemotherapy and inherent radioresistance. We evaluated outcomes in a cohort of patients with SSM uniformly treated using single-fraction simultaneous-integrated-boost (SIB) spine stereotactic radiosurgery (SSRS). MATERIALS AND METHODS: A retrospective review was conducted at a single tertiary institution treated with SSRS for SSM between April 2007-April 2023. 16-24 Gy was delivered to the GTV and 16 Gy uniformly to the CTV. Kaplan-Meier analysis was conducted to assess time to progression of disease (PD) with proportionate hazards modelling used to determine hazard ratios (HR) and respective 95 % confidence intervals (CI). RESULTS: 70 patients with 100 lesions underwent SSRS for SSM. Median follow-up was 19.3 months (IQR 7.7-27.8). Median age was 55 years (IQR42-63). Median GTV and CTVs were 14.5 cm3 (IQR 5-32) and 52.7 cm3 (IQR 29.5-87.5) respectively. Median GTV prescription dose and biologically equivalent dose (BED) [α/ß = 10] was 24 Gy and 81.6 Gy respectively. 85 lesions received 24 Gy to the GTV. 27 % of patients had Bilsky 1b or greater disease. 16 of 100 lesions recurred representing a crude local failure rate of 16 % with a median time to failure of 10.4 months (IQR 5.7-18) in cases which failed locally. 1-year actuarial local control (LC) was 89 %. Median overall survival (OS) was 15.3 months (IQR 7.7-25) from SSRS. Every 1 Gy increase in GTV absolute minimum dose (DMin) across the range (5.8-25 Gy) was associated with a reduced risk of local failure (HR = 0.871 [95 % CI 0.782-0.97], p = 0.009). 9 % of patients developed vertebral compression fractures at a median of 13 months post SSRS (IQR 7-25). CONCLUSION: This study represents one of the most homogenously treated and the largest cohorts of patients with SSM treated with single-fraction SSRS. Despite inherent radioresistance, SSRS confers durable and high rates of local control in SSM without unexpected long-term toxicity rates.

Whole-body MRI in oncology: A comprehensive review.

Whole-Body Magnetic Resonance Imaging (WB-MRI) has cemented its position as a pivotal tool in oncological diagnostics. It offers unparalleled soft tissue contrast resolution and the advantage of sidestepping ionizing radiation. This review explores the diverse applications of WB-MRI in oncology. We discuss its transformative role in detecting and diagnosing a spectrum of cancers, emphasizing conditions like multiple myeloma and cancers with a proclivity for bone metastases. WB-MRI's capability to encompass the entire body in a singular scan has ushered in novel paradigms in cancer screening, especially for individuals harboring hereditary cancer syndromes or at heightened risk for metastatic disease. Additionally, its contribution to the clinical landscape, aiding in the holistic management of multifocal and systemic malignancies, is explored. The article accentuates the technical strides achieved in WB-MRI, its myriad clinical utilities, and the challenges in integration into standard oncological care. In essence, this review underscores the transformative potential of WB-MRI, emphasizing its promise as a cornerstone modality in shaping the future trajectory of cancer diagnostics and treatment.

Cancer Radiomic and Perfusion Imaging Automated Framework: Validation on Musculoskeletal Tumors.

PURPOSE: Limitations from commercial software applications prevent the implementation of a robust and cost-efficient high-throughput cancer imaging radiomic feature extraction and perfusion analysis workflow. This study aimed to develop and validate a cancer research computational solution using open-source software for vendor- and sequence-neutral high-throughput image processing and feature extraction. METHODS: The Cancer Radiomic and Perfusion Imaging (CARPI) automated framework is a Python-based software application that is vendor- and sequence-neutral. CARPI uses contour files generated using an application of the user's choice and performs automated radiomic feature extraction and perfusion analysis. This workflow solution was validated using two clinical data sets, one consisted of 40 pelvic chondrosarcomas and 42 sacral chordomas with a total of 82 patients, and a second data set consisted of 26 patients with undifferentiated pleomorphic sarcoma (UPS) imaged at multiple points during presurgical treatment. RESULTS: Three hundred sixteen volumetric contour files were processed using CARPI. The application automatically extracted 107 radiomic features from multiple magnetic resonance imaging sequences and seven semiquantitative perfusion parameters from time-intensity curves. Statistically significant differences (P < .00047) were found in 18 of 107 radiomic features in chordoma versus chondrosarcoma, including six first-order and 12 high-order features. In UPS postradiation, the apparent diffusion coefficient mean increased 41% in good responders (P = .0017), while firstorder_10Percentile (P = .0312) was statistically significant between good and partial/nonresponders. CONCLUSION: The CARPI processing of two clinical validation data sets confirmed the software application's ability to differentiate between different types of tumors and help predict patient response to treatment on the basis of radiomic features. Benchmark comparison with five similar open-source solutions demonstrated the advantages of CARPI in the automated perfusion feature extraction, relational database generation, and graphic report export features, although lacking a user-friendly graphical user interface and predictive model building.

Management and Outcomes of Patients with Refractory Solitary Plasmacytoma after Treatment with Definitive Radiation Therapy.

PURPOSE: Radiation therapy (RT) is the standard treatment for solitary plasmacytoma (SP); however, the optimal management of RT-refractory SPs is unknown. We examined outcomes after early systemic therapy, surgical resection, or observation for patients with RT-refractory disease and assessed the potential impact of treatment selection on disease outcomes. METHODS AND MATERIALS: We retrospectively reviewed patients with SP treated with definitive radiation and evaluated at a single institution with persistent disease on imaging or biopsy. Descriptive statistics were used to characterize patient and disease characteristics and treatment outcomes. RESULTS: Of 102 total SP patients, 17 (17%) were RT-refractory. The median RT dose was 45 Gy, and median follow-up was 71 months from end of RT. Fifteen patients had additional treatment for refractory disease at a median time of 9.5 months after RT, with the following subsequent interventions: surgical resection (n = 4), additional RT (n = 2), systemic therapy without evidence of multiple myeloma (MM; n = 4), systemic therapy for progression to MM (n = 5), and observation (n = 2). Of 4 patients treated with surgical resection, 3 progressed to MM 22 to 43 months after diagnosis. Of 2 patients treated with additional RT, neither responded, and both had pathologic confirmation of residual disease after the second course. Four patients treated with systemic therapy without MM all had complete responses on positron emission tomography and no subsequent MM progression. Eight patients were initially observed after RT for ≥12 months (n = 8) or ≥24 months (n = 6). Of the 2 patients in continued observation, both had stable/unchanged avidity after radiation treatment for 12 and 22 months and ultimately had a slow decrease of disease avidity over multiple years. CONCLUSIONS: Patients with RT-refractory SPs can achieve good local control with alternative therapies, such as surgery or systemic therapy, if needed. Additional RT does not seem to be effective. Given the known high rates of progression from SP to MM, close observation of asymptomatic persistent disease until disease progression is likely sufficient in most cases.

Quantification of MRI Artifacts in Carbon Fiber Reinforced Polyetheretherketone Thoracolumbar Pedicle Screw Constructs prior to Spinal Stereotactic Radiosurgery.

PURPOSE: Carbon fiber reinforced polyetheretherketone (CFRP) is a nonmetallic material that is a subject of growing interest in the field of spinal instrumentation manufacturing. The radiolucency and low magnetic susceptibility of CFRP has potential to create less interference with diagnostic imaging compared with titanium implants. However, an objective comparison of the image artifact produced by titanium and CFRP implants has not been described. Spinal oncology, particularly after resection of spinal tumors and at the time of spinal stereotactic radiosurgery planning, relies heavily on imaging interpretation for evaluating resection, adjuvant treatment planning, and surveillance. We present a study comparing measurements of postoperative magnetic resonance imaging artifacts between titanium and CFRP pedicle screw constructs in the setting of separation surgery for metastatic disease. METHODS AND MATERIALS: The diameter of the signal drop around the screws (pedicle screw artifact) and the diameter of the spinal canal free from artifacts (canal visualization) were measured in consecutive patients who had spinal instrumentation followed by spinal stereotactic radiosurgery in the June 2019 to May 2022 timeframe. The spinal cord presented a shift at the screw level in sagittal images which was also measured (Sagittal Distortion, SagD). RESULTS: Fifty patients, corresponding to 356 screws and 183 vertebral levels, were evaluated overall. CFRP produced less artifacts in all the 3 parameters compared with titanium: mean pedicle screw artifact (CFRP = 5.8 mm, Ti = 13.2 mm), canal visualization (CFRP = 19.2 mm, Ti = 15.5 mm), and SagD (CFRP = .5 mm, Ti = 1.9 mm), all P < .001. In practice, these findings translate into better-quality magnetic resonance imaging. CONCLUSIONS: The initial perceived advantages are easier evaluation of postoperative imaging, facilitating radiation treatment planning, recurrence detection, and avoidance in repeating a suboptimal computed tomography myelogram. Further clinical studies analyzing long-term outcomes of patients treated with CFRP implants are necessary.

Adolescent and young adult Hodgkin lymphoma patients at risk for subcutaneous fat gain during early cancer treatment: a brief report.

Computed tomography scans were assessed for subcutaneous fat area and density at thoracic vertebra 4 in 65 adolescent and young adult (AYA) patients with Hodgkin lymphoma. Subcutaneous fat was quantified over 3 timepoints; (1) baseline, (2) end of initial anthracycline treatment (EOT) and (3) 1 year. Fat area increased at EOT (62.3 ± 5.4 cm/m2 vs 53.5 ± 5.0 cm/m2, p < 0.01) and 1 year (65.8 ± 5.6 cm/m2 vs 53.5 ± 5.0 cm/m2, p < 0.01) compared to baseline. Fat density significantly decreased at EOT (-91.2 ± 1.4 HU vs -86.5 ± 1.4 HU, p < 0.01) and at 1 year (-90.3 ± 1.6 HU vs -86.5 ± 1.4 HU, p = 0.01) compared to baseline. Female, radiation receiving, and anthracycline dosage >250mg/m2subgroups experienced significant fat gain (p < 0.05 for all). Female AYA Hodgkin lymphoma patients receiving radiation, and/or high-dose anthracyclines may be at higher risk of subcutaneous fat gain during therapy.

Role of Apparent Diffusion Coefficient Map-Based First- and High-Order Radiomic Features for the Discrimination of Sacral Chordomas and Chondrosarcomas With Overlapping Conventional Imaging Features.

PURPOSE: Chondrosarcomas arise from the lateral pelvis; however, midline chondrosarcomas (10%) display similar imaging features to chordoma, causing a diagnostic challenge. This study aims to determine the diagnostic accuracy of apparent diffusion coefficient (ADC)-based radiomic features and two novel diffusion indices for differentiating sacral chordomas and chondrosarcomas. METHODS: A retrospective, multireader review was performed of 82 pelvic MRIs (42 chordomas and 40 chondrosarcomas) between December 2014 and September 2021, split into training (n = 69) and validation (n = 13) data sets. Lesions were segmented on a single slice from ADC maps. Eight first-order features (minimum, mean, median, and maximum ADC, standard deviation, skewness, kurtosis, and entropy) and two novel indices: restriction index (RI, proportion of lesions with restricted diffusion) and facilitation index (FI, proportion of lesions with facilitated diffusion) were estimated. One hundred seven radiomic features comparing patients with chondrosarcoma versus chordoma were sorted based on mean group differences. RESULTS: There was good to excellent interobserver reliability for eight of the 10 ADC metrics on the training data set. Significant differences were observed (P < .005) for RI, FI, median, mean, and skewness using the training data set. Optimal cutpoints for diagnosis of chordoma were RI > 0.015; FI < 0.25; mean ADC < 1.7 × 10-3 mm2/s; and skewness >0.177. The optimal decision tree relied on FI. In a secondary analysis, significant differences (P < .00047) in chondrosarcoma versus chordoma were found in 18 of 107 radiomic features, including six first-order and 12 high-order features. CONCLUSION: The novel ADC index, FI, in addition to ADC mean, skewness, and 12 high-order radiomic features, could help differentiate sacral chordomas from chondrosarcomas.

Early skeletal muscle loss in adolescent and young adult cancer patients treated with anthracycline chemotherapy.

BACKGROUND: Early skeletal muscle loss has been observed in adolescent and young adult (AYA) sarcoma patients undergoing treatment. Identification of individuals within the AYA populace that are at greatest risk of anthracycline-induced skeletal muscle loss is unknown. Moreover, investigations which seek out underlying causes of skeletal muscle degradation during chemotherapy are critical for understanding, preventing, and reducing chronic health conditions associated with poor skeletal muscle status. METHODS: Computed tomography (CT) scans were used to investigate changes in skeletal muscle of 153 AYA sarcoma and Hodgkin lymphoma patients at thoracic vertebra 4 after anthracycline treatment. Images were examined at three time points during the first year of treatment. In parallel, we used translational juvenile mouse models to assess the impact of doxorubicin (DOX) in the soleus and gastrocnemius on muscle wasting. RESULTS: Significant reductions in total skeletal muscle index and density were seen after chemotherapy in AYA cancer patients (p < 0.01 & p = 0.04, respectively). The severity of skeletal muscle loss varied by subgroup (i.e., cancer type, sex, and treatment). Murine models demonstrated a reduction in skeletal muscle fiber cross-sectional area, increased apoptosis and collagen volume for both the soleus and gastrocnemius after DOX treatment (all p < 0.05). After DOX, hindlimb skeletal muscle blood flow was significantly reduced (p < 0.01). CONCLUSION: Significant skeletal muscle loss is experienced early during treatment in AYA cancer patients. Reductions in skeletal muscle blood flow may be a key contributing factor to anthracycline doxorubicin induced skeletal muscle loss.

Management of chordoma and chondrosarcoma with definitive dose-escalated single-fraction spine stereotactic radiosurgery.

PURPOSE: The management of chordoma or chondrosarcoma involving the spine is often challenging due to adjacent critical structures and tumor radioresistance. Spine stereotactic radiosurgery (SSRS) has radiobiologic advantages compared with conventional radiotherapy, though there is limited evidence on SSRS in this population. We sought to characterize the long-term local control (LC) of patients treated with SSRS. METHODS: We retrospectively reviewed patients with chordoma or chondrosarcoma treated with dose-escalated SSRS, defined as 24 Gy in 1 fraction to the gross tumor volume. Overall survival (OS) was calculated by Kaplan-Meier functions. Competing risk analysis using the cause-specific hazard function estimated LC time. RESULTS: Fifteen patients, including 12 with chordoma and 3 with chondrosarcoma, with 22 lesions were included. SSRS intent was definitive, single-modality in 95% of cases (N = 21) and post-operative in 1 case (5%). After a median censored follow-up time of 5 years (IQR 4 to 8 years), median LC time was not reached (IQR 8 years to not reached), with LC rates of 100%, 100%, and 90% at 1 year, 2 years, and 5 years. The median OS was 8 years (IQR 3 years to not reached). Late grade 3 toxicity occurred after 23% of treatments (N = 5, fracture), all of which were managed successfully with stabilization. CONCLUSION: Definitive dose-escalated SSRS to 24 Gy in 1 fraction appears to be a safe and effective treatment for achieving durable local control in chordoma or chondrosarcoma involving the spine, and may hold particular importance as a low-morbidity alternative to surgery in selected cases.

Poor Sit-to-Stand Performance in Adolescent and Young Adult Patients with Sarcoma.

Background: Adolescents and young adult (AYA) patients with sarcoma are at heightened risk of reduced physical capacity and disease-related weakness. Sit-to-stand (STS) performance correlates with lower extremity functionality and activities of daily living; however, little is known regarding the relationship between muscular status and STS performance in patients with sarcoma. This study assessed STS performance in patients with sarcoma and the association between STS performance and the skeletal muscle index (SMI) and skeletal muscle density (SMD). Methods: This study included 30 patients with sarcoma (15-39 years old) treated with high-dose doxorubicin. Patients performed the five-times-STS test before starting treatment and 1 year after the baseline test. STS performance was correlated with SMI and SMD. SMI and SMD were quantified using computed tomography scans taken at the level of the 4th thoracic vertebra (T4). Results: Mean performance on the STS test at baseline and 1 year was 2.2-fold and 1.8-fold slower than the age-matched general population, respectively. A lower SMI was associated with worse performance on the STS test (p = 0.01). Similarly, lower SMD at baseline was also associated with poorer STS performance (p < 0.01). Conclusion: Patients with sarcoma have very poor STS performance at baseline and 1 year, which was accompanied by low SMI and SMD at T4.The inability for AYAs to return to healthy age normative STS standards by 1 year may indicate a need for early interventions to enhance skeletal muscle recovery and promote physical activity during and after treatment.

Histological transformation to gliosarcoma with combined BRAF/MEK inhibition in BRAF V600E mutated glioblastoma.

The identification of BRAF V600 mutation in multiple cancers beyond melanoma and the development of combined BRAF and MEK targeting agents have altered the landscape of tissue-agnostic precision oncology therapies with an impact on survival outcomes. Despite initial efficacy, resistance emerges, and it is pertinent to identify putative resistance mechanisms. We report a case of recurrent glioblastoma (GBM) harboring BRAF V600E alteration who initially responded to combined BRAF + MEK inhibition and subsequently developed treatment resistance by histological transformation to gliosarcoma and acquisition of oncogenic KRAS G12D and an NF1 L1083R mutation. This documented case represents an initial evidence of a developing phenomenon in cancer research as it provides the first evidence of an emergent KRAS G12D/NF1 L1083R aberration with histological transformation occurring concurrently with primary BRAF V600E-altered glioblastoma as a previously unrecognized acquired mechanism of resistance in the setting of combined BRAF and MEK inhibition. This novel finding not only sheds new light on the RAS/MAPK pathway but also highlights the potential for morphological transformation to gliosarcoma, underscoring the critical need for further investigation in this area.

Risk factors for sacral fracture following en bloc chordoma resection.

OBJECTIVE: The purpose of this study was to analyze risk factors for sacral fracture following noninstrumented partial sacral amputation for en bloc chordoma resection. METHODS: A multicenter retrospective chart review identified patients who underwent noninstrumented partial sacral amputation for en bloc chordoma resection with pre- and postoperative imaging. Hounsfield units (HU) were measured in the S1 level. Sacral amputation level nomenclature was based on the highest sacral level with bone removed (e.g., S1 foramen amputation at the S1-2 vestigial disc is an S2 sacral amputation). Variables collected included basic demographics, patient comorbidities, surgical approach, preoperative radiographic details, neoadjuvant and adjuvant radiation therapy, and postoperative sacral fracture data. RESULTS: A total of 101 patients (60 men, 41 women) were included; they had an average age of 69 years, BMI of 29 kg/m2, and follow-up of 60 months. The sacral amputation level was S1 (2%), S2 (37%), S3 (44%), S4 (9%), and S5 (9%). Patients had a posterior-only approach (77%) or a combined anterior-posterior approach (23%), with 10 patients (10%) having partial sacroiliac (SI) joint resection. Twenty-seven patients (27%) suffered a postoperative sacral fracture, all occurring between 1 and 7 months after the index surgery. Multivariable logistic regression analysis demonstrated S1 or S2 sacral amputation level (p = 0.001), combined anterior-posterior approach (p = 0.0064), and low superior S1 HU (p = 0.027) to be independent predictors of sacral fracture. The fracture rate for patients with superior S1 HU < 225, 225-300, and > 300 was 38%, 15%, and 9%, respectively. An optimal superior S1 HU cutoff of 300 was found to maximize sensitivity (89%) and specificity (42%) in predicting postamputation sacral fracture. In addition, the fracture rate for patients who underwent partial SI joint resection was 100%. CONCLUSIONS: Patients with S1 or S2 partial sacral amputations, a combined anterior-posterior surgical approach, low superior S1 HU, and partial SI joint resection are at higher risk for postoperative sacral fracture following en bloc chordoma resection and should be considered for spinopelvic instrumentation at the index procedure.

Intraosseous hibernoma: clinicopathologic and imaging analysis of 18 cases.

AIMS: Intraosseous hibernomas are rarely reported tumours with brown adipocytic differentiation of unknown aetiology, with only 38 cases documented in the literature. We sought to further characterise the clinicopathologic, imaging and molecular features of these tumours. METHODS AND RESULT: Eighteen cases were identified occurring in eight females and 10 males (median age = 65 years, range = 7-75). Imaging indication was cancer surveillance/staging in 11 patients and clinical concern for a metastasis was raised in 13 patients. The innominate bone (7), sacrum (5), mobile spine (4), humerus (1) and femur (1) were involved. Median tumour size was 1.5 cm (range = 0.8-3.8). Tumours were sclerotic (11), mixed sclerotic and lytic (4) or occult (1). Microscopically, tumours were composed of large polygonal cells with distinct cell membranes, finely vacuolated cytoplasm, central or paracentral small bland nuclei with prominent scalloping. Growth around trabecular bone was observed. Tumour cells were immunoreactive for S100 protein (15/15) and adipophilin (5/5), while negative for keratin AE1/AE3(/PCK26) (0/14) and brachyury (0/2). Chromosomal microarray analysis, performed on four cases, did not show clinically significant copy number variation across the genome or on 11q, the site of AIP and MEN1. CONCLUSION: Analysis of 18 cases of intraosseous hibernoma, to our knowledge, the largest series to date, revealed that these tumours are most often detected in the spine and pelvis of older adults. Tumours were generally small, sclerotic and frequently found incidentally and can raise concern for metastasis. Whether or not these tumours are related to soft tissue hibernomas is uncertain.

Safety and efficacy of salvage conventional re-irradiation following stereotactic radiosurgery for spine metastases.

PURPOSE: There has been limited work assessing the use of re-irradiation (re-RT) for local failure following stereotactic spinal radiosurgery (SSRS). We reviewed our institutional experience of conventionally-fractionated external beam radiation (cEBRT) for salvage therapy following SSRS local failure. MATERIALS AND METHODS: We performed a retrospective review of 54 patients that underwent salvage conventional re-RT at previously SSRS-treated sites. Local control following re-RT was defined as the absence of progression at the treated site as determined by magnetic resonance imaging. RESULTS: Competing risk analysis for local failure was performed using a Fine-Gray model. The median follow-up time was 25 months and median overall survival (OS) was 16 months (95% confidence interval [CI], 10.8-24.9 months) following cEBRT re-RT. Multivariable Cox proportional-hazards analysis revealed Karnofsky performance score prior to re-RT (hazard ratio [HR] = 0.95; 95% CI, 0.93-0.98; p = 0.003) and time to local failure (HR = 0.97; 95% CI, 0.94-1.00; p = 0.04) were associated with longer OS, while male sex (HR = 3.92; 95% CI, 1.64-9.33; p = 0.002) was associated with shorter OS. Local control at 12 months was 81% (95% CI, 69.3-94.0). Competing risk multivariable regression revealed radioresistant tumors (subhazard ratio [subHR] = 0.36; 95% CI, 0.15-0.90; p = 0.028) and epidural disease (subHR = 0.31; 95% CI, 0.12-0.78; p =0.013) were associated with increased risk of local failure. At 12 months, 91% of patients maintained ambulatory function. CONCLUSION: Our data suggest that cEBRT following SSRS local failure can be used safely and effectively. Further investigation is needed into optimal patient selection for cEBRT in the retreatment setting.

Safety and Efficacy of Dose-Escalated Radiation Therapy With a Simultaneous Integrated Boost for the Treatment of Spinal Metastases.

PURPOSE: Intensity modulated radiation therapy (RT) for spine metastases using a simultaneous integrated boost (SSIB) was shown as an alternative to the treatment of select osseous metastases that are not amenable to spine stereotactic radiosurgery. We sought to update our clinical experience using SSIB in patients for whom dose escalation was warranted but spine stereotactic radiosurgery was not feasible. METHODS AND MATERIALS: A total of 58 patients with 63 spinal metastatic sites treated with SSIB between 2012 and 2021 were retrospectively reviewed. The gross tumor volume and clinical target volume were prescribed 40 and 30 Gy in 10 fractions, respectively. RESULTS: The median follow-up time was 31 months. Of 79% of patients who reported pain before RT with SSIB, 82% reported an improvement following treatment. Patient-reported pain scores on a 10-point scale revealed a significant decrease in pain at 1, 3, 6, and 12 months after SSIB (P < .0001). Additionally, there were limited toxicities; only 1 patient suffered grade 3 toxicity (pain) following RT. There were no reports of radiation-induced myelopathy at last follow-up, and 8 patients (13%) experienced a vertebral column fracture post-treatment. Local control was 88% (95% confidence interval [CI], 80%-98%) and 74% (95% CI, 59%-91%) at 1 and 2 years, respectively. Overall survival was 64% (95% CI, 53%-78%) and 45% (95% CI, 34%-61%) at 1 and 2 years, respectively. The median overall survival was 18 months (95% CI, 13-27 months). Multivariable analysis using patient, tumor, and dosimetric characteristics revealed that a higher Karnofsky performance status before RT (hazard ratio, 0.44, 0.22-0.89; P = .02) was associated with longer survival. CONCLUSIONS: These data demonstrate excellent pain relief and local control with limited acute toxicities following treatment with RT using SSIB to 40 Gy. Collectively, our data suggest that dose escalation to spine metastases using SSIB can be safe and efficacious for patients, especially those with radioresistant disease. Further investigation is warranted to validate these findings.

Advances in the management of spinal metastases: what the radiologist needs to know.

Spine is the most frequently involved site of osseous metastases. With improved disease-specific survival in patients with Stage IV cancer, durability of local disease control has become an important goal for treatment of spinal metastases. Herein, we review the multidisciplinary management of spine metastases, including conventional external beam radiation therapy, spine stereotactic radiosurgery, and minimally invasive and open surgical treatment options. We also present a simplified framework for management of spinal metastases used at The University of Texas MD Anderson Cancer Center, focusing on the important decision points where the radiologist can contribute.

Diffusion-weighted imaging (DWI) in diagnosis, staging, and treatment response assessment of multiple myeloma: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the role of diffusion-weighted imaging (DWI) in the initial diagnosis, staging, and assessment of treatment response in patients with multiple myeloma (MM). MATERIALS AND METHODS: A systematic literature review was conducted in PubMed, the Cochrane Library, EMBASE, Scopus, and Web of Science databases. The primary endpoints were defined as the diagnostic performance of DWI for disease detection, staging of MM, and assessing response to treatment in these patients. RESULTS: Of 5881 initially reviewed publications, 33 were included in the final qualitative and quantitative meta-analysis. The diagnostic performance of DWI in the detection of patients with MM revealed pooled sensitivity and specificity of 86% (95% CI: 84-89) and 63% (95% CI: 56-70), respectively, with a diagnostic odds ratio (OR) of 14.98 (95% CI: 4.24-52.91). The pooled risk difference of 0.19 (95% CI: - 0.04-0.42) was reported in favor of upstaging with DWI compared to conventional MRI (P value = 0.1). Treatment response evaluation and ADCmean value changes across different studies showed sensitivity and specificity of approximately 78% (95% CI: 72-83) and 73% (95% CI: 61-83), respectively, with a diagnostic OR of 7.21 in distinguishing responders from non-responders. CONCLUSIONS: DWI is not only a promising tool for the diagnosis of MM, but it is also useful in the initial staging and re-staging of the disease and treatment response assessment. This can aid clinicians with earlier initiation or change in treatment strategy, which could have prognostic significance for patients.

Retrospective evaluation of the role of gemcitabine-docetaxel in well-differentiated and dedifferentiated liposarcoma.

OBJECTIVE: Well-differentiated (WDLPS) and dedifferentiated liposarcoma (DDLPS) account for the majority of liposarcomas. Although gemcitabine-docetaxel is used as second-line treatment in soft tissue sarcomas, its efficacy in WDLPS/DDLPS is not established. This study retrospectively analyzed the efficacy of gemcitabine regimens in WDLPS/DDLPS. METHODS: All patients with WDLPS or DDLPS who received gemcitabine-based chemotherapy at our institution between September 2002 and January 2021 were included. Response was evaluated by an independent radiologist using RECIST 1.1. The Kaplan-Meier method was used to estimate distributions of survival outcomes and log-rank tests were used to compare survival outcomes between subgroups. RESULTS: Sixty-five WDLPS/DDLPS patients were included. Seven patients (10.8%) received a gemcitabine-based regimen more than once, totaling 72 treatments. The median age at the start of treatment was 66 years (range 32-80 years). Sixty-five (90.3%) regimens were gemcitabine-docetaxel, and 7 (9.7%) were gemcitabine alone. Majorities of treatments were for disease that was recurrent/metastatic (86.1%), was abdominal/retroperitoneal (83.3%), and had DDLPS components (88.9%), while 25.0% of treatments were for multifocal disease. The overall response rate was 9.7% (7/72). All responses were in patients with documented DDLPS. The median time to progression was 9.2 months (95% CI 5.3-12.3 months). The median overall survival from the start of therapy was 18.8 months (95% CI 13.1-32.4 months). CONCLUSION: Gemcitabine-docetaxel is an efficacious second-line treatment for DDLPS. Though cross study comparisons are not advisable, response to gemcitabine-docetaxel compares favorably to current standard options trabectedin and eribulin. This combination is a valid comparator arm for future second-line trials in DDLPS.