Dosimetric Features of Ultra-Hypofractionated Intensity Modulated Proton Therapy for Prostate Cancer.

Purpose: To report clinical and dosimetric characteristics of 5-fraction stereotactic ablative radiotherapy (SABR) using intensity modulated proton therapy (IMPT) for localized prostate cancer. Materials and Methods: All patients receiving IMPT SABR from 2017 to 2021 for localized prostate cancer at our institution were included. Five fractions were delivered every other day to the prostate +/- seminal vesicles [clinical target volume (CTV)] with 3 mm/3% robustness. A 4-field arrangement with 2 anterior oblique and 2 opposed lateral beams was used in most patients (97%), and most (99%) had a retroprostatic hydrogel spacer. Results: A total of 534 patients with low (14%), favorable intermediate (45%), unfavorable intermediate (36%), high (4.0%), or very high-risk (0.6%) disease are evaluated. Prescription dose was 36.25 Gy (31%), 38 Gy (38%), or 40 Gy (31%) was prescribed. Median volume percentage of CTV receiving at least 100% of prescription dose [V100% (%)] was 100% [interquartile range: 99.99-100]. Rectum V50% (%), V80% (%), and V90% (%) were significantly lower in patients who had spacer, with a mean difference of -9.70%, -6.59%, and -4.42%, respectively, compared to those who did not have spacer. Femoral head dose was lower with a 4-field arrangement. Mean differences in left and right femoral head V40% (%) were -6.99% and -10.74%, respectively. Conclusion: We provide a large, novel report of patients treated with IMPT SABR for localized prostate cancer. Four-field IMPT with hydrogel spacer provides significant sparing of rectum and femoral heads without compromising target coverage.

Evaluation of Alisertib Alone or Combined With Fulvestrant in Patients With Endocrine-Resistant Advanced Breast Cancer: The Phase 2 TBCRC041 Randomized Clinical Trial.

Importance: Aurora A kinase (AURKA) activation, related in part to AURKA amplification and variants, is associated with downregulation of estrogen receptor (ER) α expression, endocrine resistance, and implicated in cyclin-dependent kinase 4/6 inhibitor (CDK 4/6i) resistance. Alisertib, a selective AURKA inhibitor, upregulates ERα and restores endocrine sensitivity in preclinical metastatic breast cancer (MBC) models. The safety and preliminary efficacy of alisertib was demonstrated in early-phase trials; however, its activity in CDK 4/6i-resistant MBC is unknown. Objective: To assess the effect of adding fulvestrant to alisertib on objective tumor response rates (ORRs) in endocrine-resistant MBC. Design, Setting, and Participants: This phase 2 randomized clinical trial was conducted through the Translational Breast Cancer Research Consortium, which enrolled participants from July 2017 to November 2019. Postmenopausal women with endocrine-resistant, ERBB2 (formerly HER2)-negative MBC who were previously treated with fulvestrant were eligible. Stratification factors included prior treatment with CDK 4/6i, baseline metastatic tumor ERα level measurement (<10%, ≥10%), and primary or secondary endocrine resistance. Among 114 preregistered patients, 96 (84.2%) registered and 91 (79.8%) were evaluable for the primary end point. Data analysis began after January 10, 2022. Interventions: Alisertib, 50 mg, oral, daily on days 1 to 3, 8 to 10, and 15 to 17 of a 28-day cycle (arm 1) or alisertib same dose/schedule with standard-dose fulvestrant (arm 2). Main Outcomes and Measures: Improvement in ORR in arm 2 of at least 20% greater than arm 1 when the expected ORR for arm 1 was 20%. Results: All 91 evaluable patients (mean [SD] age, 58.5 [11.3] years; 1 American Indian/Alaskan Native [1.1%], 2 Asian [2.2%], 6 Black/African American [6.6%], 5 Hispanic [5.5%], and 79 [86.8%] White individuals; arm 1, 46 [50.5%]; arm 2, 45 [49.5%]) had received prior treatment with CDK 4/6i. The ORR was 19.6%; (90% CI, 10.6%-31.7%) for arm 1 and 20.0% (90% CI, 10.9%-32.3%) for arm 2. In arm 1, the 24-week clinical benefit rate and median progression-free survival time were 41.3% (90% CI, 29.0%-54.5%) and 5.6 months (95% CI, 3.9-10.0), respectively, and in arm 2 they were 28.9% (90% CI, 18.0%-42.0%) and 5.4 months (95% CI, 3.9-7.8), respectively. The most common grade 3 or higher adverse events attributed to alisertib were neutropenia (41.8%) and anemia (13.2%). Reasons for discontinuing treatment were disease progression (arm 1, 38 [82.6%]; arm 2, 31 [68.9%]) and toxic effects or refusal (arm 1, 5 [10.9%]; arm 2, 12 [26.7%]). Conclusions and Relevance: This randomized clinical trial found that adding fulvestrant to treatment with alisertib did not increase ORR or PFS; however, promising clinical activity was observed with alisertib monotherapy among patients with endocrine-resistant and CDK 4/6i-resistant MBC. The overall safety profile was tolerable. Trial Registration: ClinicalTrials.gov Identifier: NCT02860000.

Radiolocalization of atypical lesions for intraoperative identification: technical factors, localization quality, success rates, patient safety, and spectrum of applications.

BACKGROUND: To retrospectively analyze perilesional technetium Tc-99m MAA injection for intraoperative localization of atypical soft-tissue and bone lesions within a single tertiary referral center in order to determine technique, safety, and clinical utility of these procedures. METHODS: An IRB compliant, retrospective electronic chart review (2010-2017) exploring surgical excision of atypical (non-pulmonary, non-breast, non-sentinel node) lesions guided by Tc-99m MAA perilesional injection. Patient demographics, lesion location, lesion size, radiotracer injection technique, radiotracer injection complications, scintigraphy technique, scintigraphic quality, intraoperative time, lesion identification in surgery, and pathological diagnoses were recorded. RESULTS: Twenty-two atypical radiolocalization exams were identified. Lesion sites included rib (7), lymph node (4), abdominal wall (3), mesenteric (3), gallbladder fossa (1), retroperitoneum (1), parietal pleura (1), anterior mediastinum (1), and iliac bone (1). Average lesion size was 14 mm (range 5-23 mm). Eighteen (82%) radiotracer injections used computed tomography guidance and 4 (18%) used ultrasound guidance. The mean activity of Tc-99m MAA administered was 11.8 MBq (0.32 mCi). A 22-gauge needle was most often used for perilesional injection. No injection complications were reported. The lesions were identified with a hand-held gamma probe during surgery in 100% of cases. Of the samples sent to pathology, 100% were identified and given a diagnosis. CONCLUSION: Radiolocalization of atypical lesions may be a valuable technique, guiding minimally invasive surgical removal of lesions that would otherwise be difficult to identify intraoperatively such as non-palpable rib, central mesenteric nodal, and abdominal wall lesions.

Reducing seed migration to near zero with stranded-seed implants: Comparison of seed migration rates to the chest in 1000 permanent prostate brachytherapy patients undergoing implants with loose or stranded seeds.

PURPOSE: Pulmonary seed emboli to the chest may occur after permanent prostate brachytherapy (PPB). The purpose of this study is to analyze factors associated with seed migration to the chest in a large series of PPB patients from a single institution undergoing implant with either loose seeds (LS), mixed loose and stranded seeds (MS), or exclusively stranded seeds in an absorbable vicryl suture (VS). METHODS AND MATERIALS: Between May 1998 and July 2015, a total of 1000 consecutive PPB patients with postoperative diagnostic chest x-rays at 4 months after implant were analyzed for seed migration. Patients were grouped based on seed implant technique: LS = 391 (39.1%), MS = 43 (4.3%), or VS = 566 (56.6%). Univariate and multivariate analysis were performed using Cox proportional hazards regression models to determine predictors of seed migration. RESULTS: Overall, 18.8% of patients experienced seed migration to the chest. The incidence of seed migration per patient was 45.5%, 11.6%, and 0.9% (p < 0.0001), for patients receiving LS, MS, or VS PPB, respectively. The right and left lower lobes were the most frequent sites of pulmonary seed migration. On multivariable analysis, planimetry volume (p = 0.0002; HR = 0.7 per 10 cc [0.6-0.8]), number of seeds implanted (p < 0.0001, HR = 2.4 per 25 seeds [1.7-3.4]), LS implant (p < 0.0001, HR = 15.9 [5.9-42.1]), and MS implant (p = 0.001, HR = 7.9 [2.3-28.1]) were associated with seed migration to the chest. CONCLUSIONS: In this large series, significantly higher rates of seed migration to the chest are observed in implants using any LS with observed hazard ratios of 15.9 and 7.9 for LS and MS respectively, as compared with implants using solely stranded seeds.

A Prospective Correlation of Tissue Histopathology With Nucleic Acid Yield in Metastatic Castration-Resistant Prostate Cancer Biopsy Specimens.

OBJECTIVE: To determine histopathologic, exome, and transcriptome nucleic acid material yield from prospectively collected metastatic tissue biopsy specimens in patients with metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Patients with mCRPC initiating abiraterone acetate therapy underwent 2 serial metastatic site core needle biopsies after study activation on May 17, 2013. Multiple cores were obtained, and from each core, 1- to 2-mm segments were separated and formalin fixed for histopathologic examination. Tumor purity was determined for DNA and RNA from the rest of the biopsy specimen. RNA quality was assessed by calculation of an RNA integrity number and a DV200 score. RESULTS: A total of 89 patients underwent 172 uniformly processed core needle biopsies (89 on visit 1 and 83 on visit 2) between May 30, 2013, and September 10, 2015. Metastatic sites biopsied included bone (131), lymph nodes (31), liver (5), lung (3), and pelvic soft tissues (2). Of the 172 biopsy specimens, 85 (49%) had at least one of the multiple cores positive for tumor on histopathologic examination (53 of 88 [60%] from visit 1 and 32 of 83 [39%] from visit 2; P=.006). Metastatic carcinoma was observed in 50 of 130 bone lesion specimens (38%), compared to 35 of 41 nonbone specimens (85%) (P<.001). More than 10% tumoral DNA purity was observed in 89% and 80% of visit 1 and visit 2 biopsy specimens, respectively. Similarly, more than 10% tumor RNA purity was observed in 79% of visit 1 vs 59% for visit 2 (P=.008). In all, 134 of 172 procedures (78%) yielded tumor material either by histopathologic or nucleic acid purity analysis. CONCLUSION: This study found that biopsy specimens from mCRPC sites yield adequate histopathologic, exome, and transcriptome material in most, but not all, cases. This finding has relevance for future genome sequencing studies on the introduction of targeted therapeutic agents. TRIAL REGISTRATION: clinicaltrials.gov Identifier: 01953640.

Percutaneous ureteral biopsy: safety and diagnostic yield.

PURPOSE: To evaluate safety and diagnostic yield of percutaneous CT-guided biopsy of extrarenal upper urinary tract lesions. MATERIALS AND METHODS: Retrospective review of our institutional database of image-guided biopsies yielded 44 CT-guided percutaneous biopsies in 44 unique patients that targeted ureteral (30, 68%) or other non-renal upper urinary tract lesions (14, 32%) between January 1, 2000 and May 1, 2017. Indications, pre-biopsy imaging, biopsy technique, peri-procedural antithrombotic use, complications including bleeding defined by Society of Interventional Radiology criteria, pathology results, and subsequent imaging were reviewed up to 3 months after the procedure to evaluate safety and diagnostic yield. RESULTS: Mean patient age was 66 (range 27-88) and 23/44 patients were male. The majority (34/44) of lesions were sampled with an 18-gauge biopsy device via a 17-gauge introducer needle, and the remaining 10/44 lesions were sampled with a 19/20 gauge system. The mean number of core samples obtained was 4 (range 2-10). No major complications occurred. Specifically, no patient developed a urine leak or urinary obstruction. Minor complications occurred in 3/44 (7%) biopsies, all retroperitoneal hemorrhages that did not require transfusion or other intervention. Biopsy was adequate for pathologic examination in 41 of 44 (93%) cases. Among patients undergoing surgical resection, biopsy diagnosis was concordant with surgical pathology in 9/10 (90%) cases and discordant in 1/10 (10%). CONCLUSION: CT-guided percutaneous biopsy of upper urinary tract lesions can be performed safely, with high diagnostic yield, and with a high rate of concordance on subsequent surgical pathology.

Imaging findings of mammary and systemic silicone deposition secondary to breast implants.

In patients with silicone breast implants, implant rupture can occur, which can be intra- or extracapsular. Following implant rupture, silicone can travel through the lymphatic system into regional and distant lymph nodes. The purpose of this pictorial essay is to present findings of silicone implant rupture with intramammary and systemic silicone deposition as seen on dual energy CT, ultrasound, mammogram, PET/CT and MRI. We include imaging findings of silicone deposition in the breast in cases of intra- and extracapsular rupture. We also present silicone deposition in mediastinal, axillary, and internal mammary lymph nodes, as well as in the liver and spleen. To our knowledge, deposition of silicone in the liver and spleen has not been previously demonstrated on cross-sectional imaging. While all imaging modalities were able to detect silicone in the spleen, ultrasound appeared to be more sensitive than dual energy CT or MRI for detection of silicone deposition in the liver.

Peri-procedural use of anticoagulants in radiology: an evidence-based review.

Peri-procedural anticoagulant management hinges on the balance of hemorrhagic and thrombotic complications. The radiologist is tasked with accurately assessing the hemorrhagic risk for patients undergoing procedures, taking into account procedural bleeding rates, underlying coagulopathy based on lab tests, and use of anticoagulants. The purpose of this article is to provide a contemporary review of commonly used anticoagulants and, incorporating published evidence, review their management related to image-guided procedures.

Mutational Landscapes of Sequential Prostate Metastases and Matched Patient Derived Xenografts during Enzalutamide Therapy.

Developing patient derived models from individual tumors that capture the biological heterogeneity and mutation landscape in advanced prostate cancer is challenging, but essential for understanding tumor progression and delivery of personalized therapy in metastatic castrate resistant prostate cancer stage. To demonstrate the feasibility of developing patient derived xenograft models in this stage, we present a case study wherein xenografts were derived from cancer metastases in a patient progressing on androgen deprivation therapy and prior to initiating pre-chemotherapy enzalutamide treatment. Tissue biopsies from a metastatic rib lesion were obtained for sequencing before and after initiating enzalutamide treatment over a twelve-week period and also implanted subcutaneously as well as under the renal capsule in immuno-deficient mice. The genome and transcriptome landscapes of xenografts and the original patient tumor tissues were compared by performing whole exome and transcriptome sequencing of the metastatic tumor tissues and the xenografts at both time points. After comparing the somatic mutations, copy number variations, gene fusions and gene expression we found that the patient's genomic and transcriptomic alterations were preserved in the patient derived xenografts with high fidelity. These xenograft models provide an opportunity for predicting efficacy of existing and potentially novel drugs that is based on individual metastatic tumor expression signature and molecular pharmacology for delivery of precision medicine.

The Timing and Presentation of Major Hemorrhage After 18,947 Image-Guided Percutaneous Biopsies.

OBJECTIVE: The objective of our study was to characterize the temporal and clinical manifestation of major bleeding events after biopsy to guide clinicians in the institution of appropriate surveillance. MATERIALS AND METHODS: We performed a retrospective review of percutaneous image-guided biopsies performed between September 1, 2005, and May 31, 2012, including 18,947 biopsy events. According to routine protocol, follow-up telephone calls were made to patients 24 hours after biopsy, and chart review was performed 3 months after biopsy. Bleeding complications were defined using the Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) established by the National Cancer Institute. In patients with a grade 3 or greater bleeding complication, a retrospective chart review was performed to characterize the details of the complication including the timing of the complication and the primary clinical presentation of the event. RESULTS: Grade 3 hemorrhage was associated with 64 of 18,947 (0.3%) procedures, and there were three deaths associated with the biopsy event (0.02% or ≈ 2/10,000). Hemorrhage was most commonly associated with biopsy of a native kidney (17/1407, 1.2%). Twenty patients (31%) presented with a bleeding complication within 1 hour of biopsy. Twenty-seven patients (42%) presented within 2 hours of biopsy. Fifty-two patients (81%) presented within 24 hours, and the remaining 12 patients (19%) presented more than 24 hours after biopsy. Pain was the most common presentation of patients with bleeding complications, occurring in 39 (61%) patients. CONCLUSION: The incidence of major bleeding after percutaneous biopsies is very low, but delayed complications occur more frequently than anticipated. Pain is the most common clinical presentation of major bleeding complications.

Critical care ultrasonography differentiates ARDS, pulmonary edema, and other causes in the early course of acute hypoxemic respiratory failure.

BACKGROUND: Pathogenic causes of acute hypoxemic respiratory failure (AHRF) can be difficult to identify at early clinical presentation. We evaluated the diagnostic utility of combined cardiac and thoracic critical care ultrasonography (CCUS). METHODS: Adult patients in the ICU were prospectively enrolled from January through September 2010 with a Pao2/Fio2 ratio < 300 on arterial blood gas (ABG) analysis within 6 h of a new hypoxemic event or the ICU admission. Focused cardiac and thoracic CCUS was conducted within 6 h of ABG testing. Causes of AHRF were categorized into cardiogenic pulmonary edema (CPE), ARDS, and miscellaneous causes after reviewing the hospitalization course in electronic medical records. RESULTS: One hundred thirty-four patients were enrolled (median Pao2/Fio2 ratio, 191; interquartile range, 122-253). Fifty-nine patients (44%) received a diagnosis of CPE; 42 (31%), ARDS; and 33 (25%), miscellaneous cause. Analysis of CCUS findings showed that a low B-line ratio (proportion of chest zones with positive B-lines relative to all zones examined) was predictive of miscellaneous cause vs CPE or ARDS (receiver operating characteristic area under the curve [AUC], 0.82; 95% CI, 0.75-0.88). For further differentiation of CPE from ARDS, left-sided pleural effusion (> 20 mm), moderately or severely decreased left ventricular function, and a large inferior vena cava minimal diameter (> 23 mm) were predictive of CPE (AUC, 0.79; 95% CI, 0.70-0.87). CONCLUSIONS: Combined cardiac and thoracic CCUS assists in early bedside differential diagnosis of ARDS, CPE, and other causes of AHRF.

Subtraction color map of contrast-enhanced and unenhanced CT for the prediction of pancreatic necrosis in early stage of acute pancreatitis.

OBJECTIVE: The objective of our study was to evaluate the accuracy of subtraction color-map images created from contrast-enhanced CT (CECT) and unenhanced CT for the diagnosis of pancreatic necrosis in the early stage of acute pancreatitis. MATERIALS AND METHODS: Forty-eight patients underwent unenhanced CT and CECT within 72 hours from the onset of acute pancreatitis. Subtraction color-map images were created from unenhanced CT and CECT using a 3D nonrigid registration method. Three radiologists reviewed two image sets: CECT alone and subtraction color-map images in conjunction with CECT. Readers evaluated each image set for the presence of pancreatic necrosis. The reference standard for pancreatic necrosis was CT or MRI 1 week or more after the onset of acute pancreatitis. The performance of each image set for the prediction of pancreatic necrosis was calculated and compared using the McNemar test. RESULTS: Eleven of the 48 patients developed pancreatic necrosis. There were no technical failures creating the subtraction images. The sensitivity, specificity, and accuracy for predicting pancreatic necrosis with CECT were 64%, 97%, and 90%, respectively, for reader 1; 73%, 87%, and 83% for reader 2; and 73%, 87%, and 83% for reader 3. The sensitivity, specificity, and accuracy for predicting pancreatic necrosis with the subtraction color maps were 100%, 100%, and 100%, respectively, for reader 1; 100%, 95%, and 96% for reader 2; and 82%, 92%, and 90% for reader 3. Accuracy significantly improved with the addition of subtraction color maps compared with CECT alone for reader 1 (p = 0.03) and reader 2 (p = 0.02) but not for reader 3 (p = 0.37). CONCLUSION: A subtraction color map is accurate in the diagnosis of pancreatic necrosis in the early stage of acute pancreatitis.

Percutaneous cryoablation of musculoskeletal oligometastatic disease for complete remission.

PURPOSE: To assess the safety and effectiveness of percutaneous cryoablation to treat limited metastases to the musculoskeletal system, with the goal of complete disease remission. MATERIALS AND METHODS: In a single-institution retrospective study of data from December 2003 to October 2011, 43 consecutive patients underwent initial cryoablation of limited (five or fewer) musculoskeletal metastases with the goal of complete disease remission (ie, no clinical or radiographic evidence of disease). Three patients were lost to follow-up. As a result, the present report describes 40 patients who underwent 40 cryoablation procedures to treat 52 tumors. RESULTS: Local control was achieved in 45 of 52 tumors (87%; 95% confidence interval [CI], 75%-93%) at a median follow-up of 21 months (range, 4-62 mo). Thirteen of 19 treated bone metastases (68%) and 32 of 33 soft-tissue metastases (97%) showed local control (P = .007). One- and 2-year overall survival rates were 91% (95% CI, 75%-97%) and 84% (95% CI, 65%-93%), respectively. Median overall survival was 47 months (95% CI, 26-62 mo). One- and 2-year disease-free survival rates were 22% (95% CI, 11%-37%) and 7% (95% CI,<1% to 26%), respectively. Median disease-free survival was 7 months (95% CI, 5-10 mo). Two of 40 procedures (5%) were associated with major complications. CONCLUSIONS: Percutaneous cryoablation is a safe and effective treatment to achieve local tumor control and short-term complete disease remission in patients with limited metastatic disease to the musculoskeletal system.