Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial.

BACKGROUND: Few standard treatment options are available for patients with metastatic sarcomas. We did this trial to evaluate the efficacy, safety, and changes in the tumour microenvironment for durvalumab, an anti-PD-L1 drug, and tremelimumab, an anti-CTLA-4 drug, across multiple sarcoma subtypes. METHODS: In this single-centre phase 2 trial, done at The University of Texas MD Anderson Cancer Center (Houston, TX USA), patients aged 18 years or older with advanced or metastatic sarcoma with an Eastern Cooperative Oncology Group performance status of 0 or 1 who had received at least one previous line of systemic therapy were enrolled in disease subtype-specific groups (liposarcoma, leiomyosarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma, synovial sarcoma, osteosarcoma, alveolar soft-part sarcoma, chordoma, and other sarcomas). Patients received 1500 mg intravenous durvalumab and 75 mg intravenous tremelimumab for four cycles, followed by durvalumab alone every 4 weeks for up to 12 months. The primary endpoint was progression-free survival at 12 weeks in the intention-to-treat population (all patients who received at least one dose of treatment). Safety was also analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02815995, and is completed. FINDINGS: Between Aug 17, 2016, and April 9, 2018, 62 patients were enrolled, of whom 57 (92%) received treatment and were included in the intention-to-treat population. With a median follow-up of 37·2 months (IQR 1·8-10·1), progression-free survival at 12 weeks was 49% (95% CI 36-61). 21 grade 3-4 treatment-related adverse events were reported, the most common of which were increased lipase (four [7%] of 57 patients), colitis (three [5%] patients), and pneumonitis (three [5%] patients). Nine (16%) patients had a treatment related serious adverse event. One patient had grade 5 pneumonitis and colitis. INTERPRETATION: The combination of durvalumab and tremelimumab is an active treatment regimen for advanced or metastatic sarcoma and merits evaluation in specific subsets in future trials. FUNDING: AstraZeneca.

Adequacy of small biopsy and cytology specimens for comprehensive genomic profiling of patients with non-small-cell lung cancer to determine eligibility for immune checkpoint inhibitor and targeted therapy.

AIMS: In advanced-stage non-small-cell lung cancer (NSCLC), incomplete genotyping for guideline-recommended genomic biomarkers poses a significant challenge to making informed and timely clinical decisions. We report our institution's experience in assessing the adequacy of small specimens for comprehensive genomic profiling for guideline-recommended lung cancer biomarker testing. METHODS: We performed a retrospective evaluation of all image-guided procedures for NSCLC performed in our institution between October 2016 and July 2018, including core needle biopsy (CNB) and fine-needle aspiration (FNA) in patients who had undergone genomic profiling for lung cancer. Lung cancer biomarker adequacy, defined as successful testing of guideline-recommended biomarkers including, epidermal growth factor receptor (EGFR); serine/threonine protein kinase B-Raf (BRAF); anaplastic lymphoma kinase (ALK); proto-oncogene tyrosine protein kinase ROS (ROS1); Rearranged during Transfection (RET); Tyrosine protein kinase Met (MET); and programmed cell death ligand 1 (PD-L1), was evaluated. RESULTS: A total of 865 cases were evaluated in this study, 785 of which included testing of all lung cancer biomarkers. Lung tissue was adequate for biomarker testing in 84% of cases; this rate increased to 87% when biomarker testing was combined with concurrently acquired FNA or CNB specimens. Biomarker testing success correlated strongly with DNA concentration (p<0.0001) and the use of 22G needles in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) procedures (p=0.0035). Biomarker testing of CNB specimens showed a significantly higher success rate than did biomarker testing of cytology FNA specimens (p=0.0005). The adequacy of EBUS-TBNA samples was not significantly different from that of the transthoracic needle aspiration samples (p=0.40). Variables such as age, gender, lesion size, site, diagnosis and number of needle passes showed no significant correlation with success rates in lung cancer biomarker testing. CONCLUSION: The growing numbers of therapeutic biomarkers in NSCLC requires judicious triage of limited-volume tissue from small specimens. Our study showed that thoracic small tissue specimens can be used successfully to provide prognostic and predictive information for the current guideline-recommended biomarkers for NSCLC in most cases.

Outcomes of Percutaneous Thermal Ablation for Biopsy-Proven T1a Renal Cell Carcinoma in Patients With Other Primary Malignancies.

OBJECTIVE. The purpose of this article is to investigate the oncologic effectiveness and survival outcomes of percutaneous image-guided thermal ablation for clinical T1a renal cell carcinoma (RCC) in patients with other primary nonrenal malignancies. MATERIALS AND METHODS. We reviewed records of patients with histologically proven T1a RCC (< 4.0 cm) treated with thermal ablation over a period of 10 years between January 2005 and December 2014. We recorded past or current history of primary malignancy other than RCC, status of the primary malignancy, tumor histology (in remission or under therapy), and whether patient was currently alive or not, and if not, the date and reason of death. Three cohorts were studied: patients with RCC only (group A), patients with RCC and other primary malignancy in remission (group B), and patients with RCC and other primary malignancy under treatment (group C). The Kaplan-Meier product-limit estimator was used to estimate the survival rates. RESULTS. One hundred nine patients met the inclusion criteria (109 lesions, 110 ablation procedures). There were 46, 45, and 18 patients in the A, B, and C groups, respectively. The 5-year survival was 87%, 63%, and 40% for groups A, B, and C, respectively. The local recurrence-free survival for the whole sample was 95% at 3, 5, and 10 years. The disease-free survival was 96%, 93%, and 91% at 3, 5, and 10 years. Although a significant difference is noted between the three cohorts in overall survival (p = .02); for RCC, there were no significance differences in the local recurrence-free, disease-free, metastasis-free, and cancer-specific survivals. In addition, there was no difference in outcomes for patients in group B (in remission) when compared with those in group C (under treatment). CONCLUSION. Thermal ablation is an effective and safe modality of treatment of T1a RCC in patients with other primary malignancies that are in remission or under treatment.

Implementation of a Novel Web-Based Lesion Selection Tool to Improve Acquisition of Tumor Biopsy Specimens.

Introduction: For maximum utility of molecular characterization by next-generation sequencing (NGS) and better understanding of tumor microenvironment with immune correlates analysis, biopsy specimens must yield adequate tumor tissue, and sequential biopsy specimens should sample a consistent site. We developed a web-based lesion selection tool (LST) that enables management and tracking of the biopsy specimen collections. Methods: Of 145 patients, the LST was used for 88 patients; the other 57 served as controls. We evaluated consistency of the lesion biopsied in longitudinal collections, number of cores obtained, and cores with adequate tumor cellularity for NGS. The Fisher exact test and Wilcoxon rank sum test were used to identify differences between the groups. Results: The analysis included 30 of 88 (34%) patients in the LST group and 52 of 57 (91%) in the control group. The LST workflow ensured 100% consistency in the lesions biopsied compared with 75% in the control group in longitudinal collections and increased the proportion of patients in whom at least five cores were collected per biopsy. Conclusions: The novel LST platform facilitates coordination, performance, and management of longitudinal biopsy specimens. Use of the LST enables sampling of the designated lesion consistently, which is likely to accurately inform us the effect of the treatment on tumor microenvironment and evolution of resistant pathways. Such studies are important translational component of any clinical trials and research as they guide the development of next line of therapy, which has significant effect on clinical utility. However, validation of this approach in a larger study is warranted.

Durability of partial splenic artery embolization on platelet counts for cancer patients with hypersplenism-related thrombocytopenia.

PURPOSE: Partial splenic artery embolization (PSAE) has shown promise in increasing platelet counts in cancer patients with hypersplenism-related thrombocytopenia. The purpose of this study was to identify response predictors and to longitudinally evaluate PSAE efficacy and durability in a large cohort of cancer patients with hypersplenism-related thrombocytopenia. METHODS: A single-institution, IRB-approved, HIPAA-compliant retrospective review of all PSAEs for thrombocytopenia between 2012 and 2015 was performed. Patients were classified as complete responders (CR, no platelet value < 100 × 109/L following PSAE), partial responders (PR, initial increase in platelets but subsequent decrease in platelets < 100 × 109/L), and non-responders (NR, platelets never > 100 × 109/L following PSAE). RESULTS: Of the 98 patients included in the study, 58 had CR (59%), 28 had PR (29%), and 12 patients had NR (12%). The percent splenic tissue embolized was significantly greater in the CR group compared to the PR group (P = 0.001). The percent volume of splenic tissue embolized was linearly correlated with the magnitude of platelet increase without a minimum threshold. At least one line of chemotherapy was successfully restarted in 97% of patients, and 41% of patients did not experience recurrence of thrombocytopenia for the duration of their survival. The major complication rate was 8%, with readmission following initial hospitalization for persistent "post-embolization syndrome" symptoms the most common. CONCLUSIONS: In cancer patients with hypersplenism-related thrombocytopenia, PSAE is a safe intervention that effects a durable elevation in platelet counts across a range of malignancies and following the re-initiation of chemotherapy.

Comparison of Real-Time Fluorescence Confocal Digital Microscopy With Hematoxylin-Eosin-Stained Sections of Core-Needle Biopsy Specimens.

Importance: Strategies to procure high-quality core-needle biopsy (CNB) specimens are critical for making basic tissue diagnoses and for ancillary testing. Objectives: To investigate acquisition of fluorescence confocal microscopy (FCM) images of interventional radiology (IR)-guided CNB in real time in the radiology suite and to compare the accuracy of FCM diagnoses with those of hematoxylin-eosin (H&E)-stained CNB sections. Design, Setting, and Participants: In this diagnostic study, FCM imaging of IR-guided CNBs was performed in the radiology suite at a major cancer center for patients with an imaging abnormality from August 1, 2016, to April 30, 2019. The time taken to acquire FCM images and the quality of FCM images based on percentage of interpretable tissue with optimal resolution was recorded. The FCM images were read by 2 pathologists and categorized as nondiagnostic, benign/atypical, or suspicious/malignant; these diagnoses were compared with those made using H&E-stained tissue sections. Cases with discrepant diagnosis were reassessed by the pathologists together for a consensus diagnosis. Data were analyzed from June 3 to July 19, 2019. Interventions: Each IR-guided CNB was stained with 0.6mM acridine orange, subjected to FCM imaging, and then processed to generate H&E-stained sections. Main Outcomes and Measures: Mean time taken for acquisition of FCM images, quality of FCM images based on interpretable percentage of the image, and accuracy of diagnostic categorization based on FCM images compared with H&E-stained sections. Results: A total of 105 patients (57 male [54.3%]; mean [SD] age, 63 [13] years) underwent IR-guided CNBs in a mean (SD) of 7 (2) minutes each. The FCM images showed at least 20% of the tissue with optimal quality in 101 CNB specimens (96.2%). The FCM images were accurately interpreted by the 2 pathologists in 100 of 105 cases (95.2%) (2 false-positive and 3 false-negative) and 90 of 105 cases (85.7%) (6 false-positive and 9 false-negative). A reassessment of 14 discordant diagnoses resulted in consensus diagnoses that were accurate in 101 of 105 cases (96.2%) (1 false-positive and 3 false-negative). Conclusions and Relevance: The ease of acquisition of FCM images of acceptable quality and the high accuracy of the diagnoses suggest that FCM may be useful for rapid evaluation of IR-guided CNBs. This approach warrants further investigation.

Management and outcomes of ruptured, perforated or fistulized tumors of mesenchymal origin.

BACKGROUND: Patients with ruptured, perforated or fistulized (RPF) sarcomas commonly have issues such as sepsis and malnutrition and are usually unsuitable for oncologic resection in the emergency setting. We present our approach for managing a series of patients and the outcomes which were achieved with multidisciplinary care. METHODS: We reviewed records of patients referred to the section of sarcoma surgical oncology. Clinicopathologic factors, preoperative and operative interventions as well as short-term oncologic outcomes were assessed. RESULTS: Sixteen patients were identified between 1 January 1998 to 31 December 2018. Median age was 42.8 years. Histologies were; Gastrointestinal stromal tumors (7), desmoid (4), spindle cell tumor (2), dedifferentiated liposarcoma (2), and nonseminomatous germ cell tumor (1). Five patients had preoperative sepsis, 8 received antimicrobials, and 50% required hospitalization with a median stay of 21 days. Total parenteral nutrition was administered to 5 (31.3%) patients. Median tumor size and estimated blood loss were 13.1 cm and 350 mL respectively. No perioperative mortality occurred. Two patients have expired at a median follow-up of 16.1 months. CONCLUSION: Preoperative optimization, including the use of percutaneous drains, and antibiotics to control sepsis, where necessary, can lead to eventual oncologic resection with acceptable morbidity and no short-term mortality for patients with RPF sarcomas.

Exposure to anti-PD-1 causes functional differences in tumor-infiltrating lymphocytes in rare solid tumors.

The pervasive use of therapeutic antibodies targeting programmed cell death protein 1 (PD-1) to boost anti-tumor immunity has positioned this approach to become the standard-of-care for some solid tumor malignancies. However, little is known as to how blockade of PD-1 may alter the function or phenotype of tumor-infiltrating lymphocytes (TIL). We used our ongoing Phase II clinical trial of pembrolizumab for patients with rare solid tumors from various types (NCT02721732) with matched core biopsies taken at baseline and after initial dose of anti-PD-1 (15-21 days post-dose) to elucidate this question. One fresh core needle biopsy was used to propagate TIL ex vivo to analyze phenotype and function using flow cytometry in both CD8+ and CD4+ TIL populations. An enriched CTLA-4 expression in the CD4+ TIL population was observed in TIL expanded from the on-treatment samples compared to TIL expanded from the matched baseline (n = 22, p = 0.0007) but was not observed in patients who experienced tumor regression. Impact on functionality was evaluated by measuring secretion of 65 soluble factors by expanded TIL from 26 patients at baseline and on-treatment. The CD8+ TIL population demonstrated a diminished cytokine secretion profile post-pembrolizumab. Overall, our study assesses the ramifications of one dose of anti-PD-1 on TIL in rare solid tumor types.

Confocal Fluorescence Microscopy Platform Suitable for Rapid Evaluation of Small Fragments of Tissue in Surgical Pathology Practice.

CONTEXT.­: Rapid advances in the fields of biophotonics, computer science, and instrumentation have allowed for high-resolution imaging of biologic tissues. OBJECTIVE.­: To evaluate the quality of images from an optimized confocal fluorescence microscopy (CFM) platform for rapid evaluation of small fragments of tissue, compared with hematoxylin-eosin staining. DESIGN.­: Tissue fragments (up to 1.0 × 0.3 cm) were stained with 0.6 mM acridine orange for 60 seconds and imaged using a CFM platform at 488-nm and 785-nm wavelength. The imaged tissues were then fixed in formalin and processed to generate hematoxylin-eosin-stained tissue sections. The quality of CFM images was scored on a scale of 0 to 3 on the basis of the percentage of the CFM images with recognizable tissue architecture (0, 0%; 1, <20%; 2, 20%-50%; 3, >50%). The diagnoses made using CFM images were compared with those made using histopathologic analysis of the hematoxylin-eosin-stained tissue sections. RESULTS.­: We imaged 118 tissue fragments obtained from 40 breast, 23 lung, 39 kidney, and 16 liver surgical excision specimens. We acquired CFM images in 2 to 3 minutes; 95.8% (113 of 118) of images showed a quality score of 3, and 4.2% (5 of 118) had a score of 2. We achieved a sensitivity of 95.5%, specificity of 97.3%, positive predictive value of 95.5%, and negative predictive value of 97.3%. CONCLUSIONS.­: Our results demonstrate the suitability of the CFM platform for rapid and accurate evaluation of small tissue fragments in surgical pathology practice.

Risk factors for recurrent percutaneous nephrostomy catheter-related infections.

PURPOSE: Percutaneous nephrostomy (PCN) catheters are mainly indicated for urinary tract obstructions. Unfortunately, the rate for infection and recurrence remains elevated. Our objective was to identify the risk factors leading to recurrent PCN-related infections (PCNI) in cancer patients. METHODS: We retrospectively reviewed 571 patients who underwent initial PCN catheter placement at our institution. Of these, we identified patients with a definite PCNI and catheter exchange, with a minimum 30-day follow-up. We defined PCNI as presence of a urine culture positive for bacteria (≥ 104 CFU/mL) plus symptoms of urinary tract infection. A PCNI was considered recurrent if the same organism was isolated. Antibiotics were considered concordant if they were active against all identified organisms. RESULTS: A total of 81 patients (14%) developed an initial PCNI. Of 47 patients with 30-day follow-up, 10 patients (21%) were identified as having a recurrent PCNI. In terms of demographic characteristics, clinical manifestations, and microbiological data, there was no statistically significant difference between the recurrent and non-recurrent groups. However, in multivariate logistic regression analysis, two factors were independently associated with a decrease in recurrent PCNI: concordant antibiotic use (OR 0.04; p = 0.008) and PCN catheter exchange within 4 days of infection (OR 0.1; p = 0.048). CONCLUSIONS: To decrease the high rate of recurrent infections, associated costs, and potential delay in further chemotherapy, we recommend that once antimicrobial susceptibility test results are available and the patient is known to be receiving concordant antimicrobials, clinicians proceed with immediate PCN catheter exchange, ideally within the first 4 days of the infection.

MRI-Guided Interventions in Musculoskeletal System.

Image-guided interventions in the musculoskeletal system require accurate detection and characterization of lesions involving bone and soft tissues. Magnetic resonance imaging (MRI) has superior soft tissue contrast resolution particularly in bone and soft tissues where computed tomography and ultrasonography have significant limitations. In addition, the multiplanar imaging capabilities of MRI facilitate targeting lesions and tracking interventional devices. Although conventional diagnostic MRI sequences suffer from motion sensitivity and prolonged imaging time, recently developed fast imaging sequences allow for rapid acquisition of high-quality images, rendering MRI more suitable for image-guided interventions. Although computed tomography and ultrasonography still dominate the spectrum of image-guided interventions in the musculoskeletal system, many MRI-guided procedures have been developed and are well established in routine clinical work. In addition, new techniques and novel MRI-guided applications are being developed to address complex clinical problems in a minimally invasive fashion.

Investigation of tissue cellularity at the tip of the core biopsy needle with optical coherence tomography.

We report the development and the pre-clinical testing of a new technology based on optical coherence tomography (OCT) for investigating tissue composition at the tip of the core biopsy needle. While ultrasound, computed tomography, and magnetic resonance imaging are routinely used to guide needle placement within a tumor, they still do not provide the resolution needed to investigate tissue cellularity (ratio between viable tumor and benign stroma) at the needle tip prior to taking a biopsy core. High resolution OCT imaging, however, can be used to investigate tissue morphology at the micron scale, and thus to determine if the biopsy core would likely have the expected composition. Therefore, we implemented this capability within a custom-made biopsy gun and evaluated its capability for a correct estimation of tumor tissue cellularity. A pilot study on a rabbit model of soft tissue cancer has shown the capability of this technique to provide correct evaluation of tumor tissue cellularity in over 85% of the cases. These initial results indicate the potential benefit of the OCT-based approach for improving the success of the core biopsy procedures.

Ex Vivo Confocal Fluorescence Microscopy for Rapid Evaluation of Tissues in Surgical Pathology Practice.

CONTEXT: - Optical imaging techniques are currently available for imaging tissues without the need for any type of extensive tissue preparation. There are several applications for their potential use in surgical pathology practice. OBJECTIVE: - To evaluate the feasibility of using a confocal fluorescence microscopy (CFM) platform for ex vivo examination of tissues obtained from surgical resections of breast, lung, kidney, and liver. DESIGN: - Tissue fragments (0.5-1.0 cm) were immersed in 0.6 mM acridine orange for 6 seconds and imaged using a CFM platform at a 488-nm wavelength. The imaged tissues were subsequently fixed in formalin and processed routinely to generate hematoxylin-eosin-stained tissue sections. Mosaics of the grayscale CFM images were studied at different magnifications for recognition of the tissue and were compared with conventional histopathologic examination of hematoxylin-eosin tissue sections. RESULTS: - We imaged 55 tissue fragments obtained from 16 breast (29%), 18 lung (33%), 14 kidney (25%), and 7 liver (13%) surgical excision specimens. Acridine orange labeled the nuclei, creating the contrast between nucleus and cytoplasm and thereby recapitulating the tissue architecture. We could obtain CFM images of good quality within 5 to 10 minutes that allowed recognition of the cytomorphologic details for categorization of the imaged tissue and were similar to histologic examination of hematoxylin-eosin tissue sections. CONCLUSIONS: - The ease and speed of acquisition of CFM images together with the resolution and resemblance of the CFM images to hematoxylin-eosin sections suggest that the CFM platform has excellent potential for use in surgical pathology practice.

Portomesenteric Venous Stenting for Palliation of Ascites and Variceal Bleeding Caused by Prehepatic Portal Hypertension.

BACKGROUND: The purpose of this study was to evaluate percutaneous transhepatic portal vein stenting (PVS) for palliation of refractory ascites and/or variceal bleeding caused by extrahepatic portomesenteric venous stenosis in patients with pancreaticobiliary cancer. MATERIALS AND METHODS: A single-institution, retrospective review of patients who underwent PVS between January 2007 and July 2015 was performed. A total of 38 patients were identified, of whom 28 met the inclusion criterion of PVS performed primarily for refractory ascites or variceal bleeding. In addition to technical success and overall survival, clinical success was measured by fraction of remaining life palliated. The palliative effect of PVS was also quantified by measuring changes in liver and ascites volumes after the procedure. RESULTS: Technical success was 93% (26/28). Stent deployment involved more than one portomesenteric vessel in most patients (20/26). The cumulative probability of symptom recurrence at 6, 12, 18, and 24 months was 12%, 16%, 26%, and 40%, respectively. There was a significant difference (p < .001) in the probability of symptom recurrence, recurrence of abdominal ascites, and increase in liver volume between patients whose stents remained patent and those whose stents demonstrated partial or complete occlusion. The mean fraction of remaining life palliated was 87%. All but two patients were found to have improvement in clinical symptoms for the majority of their lives after the procedure. There were no major or minor complications. CONCLUSION: As a low-risk procedure with a high clinical success rate, PVS can play a substantial role in improving quality of life in patients with portomesenteric stenoses. IMPLICATIONS FOR PRACTICE: Portomesenteric venous stenosis is a challenging complication of pancreaticobiliary malignancy. Portomesenteric stenoses can lead to esophageal, gastric, and mesenteric variceal bleeding, as well as abdominal ascites. The purpose of this study was to evaluate the safety and efficacy of portal vein stenting (PVS) in patients with cancer who have symptomatic portal hypertension caused by portomesenteric venous compression. As a low-risk procedure with a high clinical success rate, PVS can play a substantial role in improving quality of life in patients with portomesenteric stenoses.

Characteristics of percutaneous core biopsies adequate for next generation genomic sequencing.

PURPOSE: Determine the characteristics of percutaneous core biopsies that are adequate for a next generation sequencing (NGS) genomic panel. MATERIALS AND METHODS: All patients undergoing percutaneous core biopsies in interventional radiology (IR) with samples evaluated for a 46-gene NGS panel during 1-year were included in this retrospective study. Patient and procedure variables were collected. An imaging-based likelihood of adequacy score incorporating targeting and sampling factors was assigned to each biopsied lesion. Univariate and multivariate logistic regression was performed. RESULTS: 153 patients were included (58.2% female, average age 59.5 years). The most common malignancy was lung cancer (40.5%), most common biopsied site was lung (36%), and average size of biopsied lesions was 3.8 cm (+/- 2.7). Adequacy for NGS was 69.9%. Univariate analysis showed higher likelihood of adequacy score (p = 0.004), primary malignancy type (p = 0.03), and absence of prior systemic therapy (p = 0.018) were associated with adequacy for NGS. Multivariate analysis showed higher adequacy for lesions with likelihood of adequacy scored 3 (high) versus lesions scored 1 (low) (OR, 7.82; p = 0.002). Melanoma lesions had higher adequacy for NGS versus breast cancer lesions (OR 9.5; p = 0.01). Absence of prior systemic therapy (OR, 6.1; p = 0.02) and systemic therapy 3 months before biopsy yielded greater adequacy for NGS. Lesions <3 cm had greater adequacy for NGS than larger lesions (OR 2.72, p = 0.02). CONCLUSION: As targeted therapy becomes standard for more cancers, percutaneous biopsy specimens adequate for NGS genomic testing will be needed. An imaging-based likelihood of adequacy score assigned by IR physicians and other pre-procedure variables can help predict the likelihood of biopsy adequacy for NGS.

Cryoablation of Bone Metastases from Renal Cell Carcinoma for Local Tumor Control.

BACKGROUND: Patients with bone metastases from renal cell carcinoma often are not surgical candidates and have a poor prognosis. There are limited data on the use of cryoablation as a locoregional therapy for bone metastases. Our objective was to assess the local tumor-control rate following cryoablation of bone metastases in the setting of renal cell carcinoma. METHODS: We retrospectively reviewed the medical records of patients with metastatic renal cell carcinoma who underwent cryoablation for bone metastases between 2007 and 2014. We excluded patients if the intent of treatment was for pain palliation only, if cryoablation was performed without an attempt for complete tumor control (cytoreduction), or if the patient had no further follow-up beyond the cryoablation procedure. We recorded patient demographics, procedural variables, and complications. Cross-sectional imaging and clinical follow-up were reviewed to determine disease recurrence. The median overall survival and recurrence-free survival were determined using the Kaplan-Meier method. RESULTS: Forty patients (30 male and 10 female) with 50 bone metastases were included for analysis. The mean patient age was 62 years (range, 47 to 82 years). The median follow-up was 35 months (95% confidence interval [CI], 22.7 to 74.4 months). Twenty-five (62.5%) of the 40 patients had oligometastatic disease, defined as ≤5 metastases at the time of ablation. The mean tumor size was 3.4 ± 1.5 cm. Metastases in the pelvic region represented 68% of the treated tumors (34 of 50). The overall local tumor-control rate per lesion was 82% (41 of 50). Patients with oligometastatic disease experienced better local tumor control (96% [24 of 25]) compared with patients who had >5 metastases (53.3% [8 of 15]) (p = 0.001). The local tumor-control rate was better for lesions for which a larger mean difference between maximum ice-ball diameter and maximum lesion diameter was achieved (2.2 ± 0.9 cm for those without recurrence versus 1.35 ± 1.2 cm for those with recurrence; p = 0.005). There were 3 grade-3 complications and 1 grade-4 complication. CONCLUSIONS: Cryoablation can be effective for achieving local oncologic control in bone metastases from renal cell carcinoma and may represent a valuable alternative to surgical metastasectomy in select patients. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Impact of an inferior vena cava filter retrieval algorithm on filter retrieval rates in a cancer population.

OBJECTIVE: Our primary purpose was to assess the impact of an inferior vena cava filter retrieval algorithm in a cancer population. Because cancer patients are at persistently elevated risk for development of venous thromboembolism (VTE), our secondary purpose was to assess the incidence of recurrent VTE in patients who underwent filter retrieval. METHODS: Patients with malignant disease who had retrievable filters placed at a tertiary care cancer hospital from August 2010 to July 2014 were retrospectively studied. A filter retrieval algorithm was established in August 2012. Patients and referring physicians were contacted in the postintervention period when review of the medical record indicated that filter retrieval was clinically appropriate. Patients were classified into preintervention (August 2010-July 2012) and postintervention (August 2012-July 2014) study cohorts. Retrieval rates and clinical pathologic records were reviewed. RESULTS: Filter retrieval was attempted in 34 (17.4%) of 195 patients in the preintervention cohort and 66 (32.8%) of 201 patients in the postintervention cohort (P < .01). The median time to filter retrieval in the preintervention and postintervention cohorts was 60 days (range, 20-428 days) and 107 days (range, 9-600 days), respectively (P = .16). In the preintervention cohort, 49 of 195 (25.1%) patients were lost to follow-up compared with 24 of 201 (11.9%) patients in the postintervention cohort (P < .01). Survival was calculated from the date of filter placement to death, when available. The overall survival for patients whose filters were retrieved was longer compared with the overall survival for patients whose filters were not retrieved (P < .0001). Of the 80 patients who underwent successful filter retrieval, two patients (2.5%) suffered from recurrent VTE (n = 1 nonfatal pulmonary embolism; n = 1 deep venous thrombosis). Both patients were treated with anticoagulation without filter replacement. CONCLUSIONS: Inferior vena cava filter retrieval rates can be significantly increased in patients with malignant disease with a low rate (2.5%) of recurrent VTE after filter retrieval.

Endovascular Embolization by Transcatheter Delivery of Particles: Past, Present, and Future.

Minimally invasive techniques to occlude flow within blood vessels, initially pioneered in the 1970s with autologous materials and subsequently advanced with increasingly sophisticated engineered biomaterials, are routinely performed for a variety of medical conditions. Contemporary interventional radiologists have at their disposal a wide armamentarium of occlusive agents to treat a range of disease processes through a small incision in the skin. In this review, we provide a historical perspective on endovascular embolization tools, summarize the current state-of-the-art, and highlight burgeoning technologies that promise to advance the field in the near future.

Development of a predictive model for 6 month survival in patients with venous thromboembolism and solid malignancy requiring IVC filter placement.

PURPOSE: Our purpose was to develop a predictive model for short-term survival (i.e. <6 months) following inferior vena cava filter placement in patients with venous thromboembolism (VTE) and solid malignancy. METHODS: Clinical and laboratory parameters were retrospectively reviewed for patients with solid malignancy who received a filter between January 2009 and December 2011 at a tertiary care cancer center. Multivariate Cox proportional hazards modeling was used to assess variables associated with 6 month survival following filter placement in patients with VTE and solid malignancy. Significant variables were used to generate a predictive model. RESULTS: 397 patients with solid malignancy received a filter during the study period. Three variables were associated with 6 month survival: (1) serum albumin [hazard ratio (HR) 0.496, P < 0.0001], (2) recent or planned surgery (<30 days) (HR 0.409, P < 0.0001), (3) TNM staging (stage 1 or 2 vs. stage 4, HR 0.177, P = 0.0001; stage 3 vs. stage 4, HR 0.367, P = 0.0002). These variables were used to develop a predictive model to estimate 6 month survival with an area under the receiver operating characteristic curve of 0.815, sensitivity of 0.782, and specificity of 0.715. CONCLUSIONS: Six month survival in patients with VTE and solid malignancy requiring filter placement can be predicted from three patient variables. Our predictive model could be used to help physicians decide whether a permanent or retrievable filter may be more appropriate as well as to assess the risks and benefits for filter retrieval within the context of survival longevity in patients with cancer.

Concurrent fine needle aspirations and core needle biopsies: a comparative study of substrates for next-generation sequencing in solid organ malignancies.

Minimally invasive procedures, such as fine needle aspiration and core needle biopsy, are commonly used for the diagnosis in solid organ malignancies. In the era of targeted therapy, it is crucial for molecular testing to be performed on these limited volume specimens. Although several recent studies have demonstrated the utility of small biopsy specimens for molecular testing, there remains debate as to whether core needle biopsy specimens are more reliable than fine needle aspiration for molecular studies. In this study, we reviewed concurrently acquired fine needle aspiration and core needle biopsy samples (n=24), and compared overall cellularity, tumor fraction, and the results of next-generation sequencing. All somatic mutations detected in core needle biopsy samples were also detected in fine needle aspiration samples. The estimated tumor fraction was significantly higher in fine needle aspiration smears than core needle biopsy samples (P=0.003), whereas the overall DNA yield from smears was significantly lower than that obtained from the core needle biopsy specimens (P=0.01). The normalized average amplicon coverage for the genes analyzed was significantly higher in cytology smears than paired core needle biopsy samples, with lower numbers of failed amplicons and higher overall mutation allelic frequencies seen in the former. We further evaluated 100 malignant fine needle aspiration and core needle biopsy samples, acquired concurrently, for overall cellularity and tumor fraction. Overall cellularity and tumor fraction of fine needle aspiration samples was significantly higher than concurrently acquired core needle biopsy samples (P<0.001). In conclusion, we show that fine needle aspiration samples frequently provide better cellularity, higher tumor fraction, and superior sequencing metrics than concurrently acquired core needle biopsy samples. Cytologic specimens, therefore, should be better integrated into routine molecular diagnostics workflow to maximize limited tissues for clinically relevant genomic testing.