18 F-sodium fluoride positron emission tomography quantitation of bone metastases in African American and non-African American men with metastatic prostate cancer.

BACKGROUND: Bone is the most common site of metastases in men with prostate cancer. The objective of this study was to explore potential racial differences in the distribution of tumor metastases in the axial and appendicular skeleton. METHODS: We conducted a retrospective review of patients with metastatic prostate cancer to the bone as detected by 18 F-sodium fluoride positron emission tomography/computed tomography (18 F-NaF PET/CT) scans. In addition to describing patients' demographics and clinical characteristics, the metastatic bone lesions, and healthy bone regions were detected and quantified volumetrically using a quantitative imaging platform (TRAQinform IQ, AIQ Solutions). RESULTS: Forty men met the inclusion criteria with 17 (42%) identifying as African Americans and 23 (58%) identifying as non-African Americans. Most of the patients had axial (skull, ribcage, and spine) disease. The location and the number of lesions in the skeleton of metastatic prostate cancer patients with low disease burden were not different by race. CONCLUSIONS: In low-disease burden patients with metastatic prostate cancer, there were no overall differences by race in the location and number of lesions in axial or appendicular skeleton. Therefore, given equal access to molecular imaging, African Americans might derive similar benefits. Whether this holds true for patients with a higher disease burden or for other molecular imaging techniques is a topic for further study.

Cryoablation Without Excision for Low-Risk Early-Stage Breast Cancer: 3-Year Interim Analysis of Ipsilateral Breast Tumor Recurrence in the ICE3 Trial.

BACKGROUND: The ICE3 trial is designed to evaluate the safety and efficacy of breast cryoablation, enabling women older than 60 years with low-risk early-stage breast cancers to benefit from a nonsurgical treatment and to avoid the associated surgical risks. METHODS: The ICE3 trial is a prospective, multi-center, single-arm, non-randomized trial including women age 60 years or older with unifocal, ultrasound-visible invasive ductal carcinoma size 1.5 cm or smaller and classified as low to intermediate grade, hormone receptor (HR)-positive, and human epidermal growth factor receptor 2 (HER2)-negative. Ipsilateral breast tumor recurrence (IBTR) at 5 years was the primary outcome. A 3-year interim analysis of IBTR was performed, and the IBTR probability was estimated using the Kaplan-Meier method. RESULTS: Full eligibility for the study was met by 194 patients, who received successful cryoablation per protocol. The mean age was 75 years (range, 55-94 years). The mean tumor length was 8.1 mm (range, 8-14.9 mm), and the mean tumor width was 7.4 mm (range, 2.8-14 mm). During a mean follow-up period of 34.83 months, the IBTR rate was 2.06% (4/194 patients). Device-related adverse events were reported as mild in 18.4% and moderate in 2.4% of the patients. No severe device-related adverse events were reported. More than 95% of the patients and 98% of the physicians reported satisfaction with the cosmetic results at the clinical follow-up evaluation. CONCLUSIONS: Breast cryoablation presents a promising alternative to surgery while offering the benefits of a minimally invasive procedure with minimal risks. Further study within a clinical trial or registry is needed to confirm cryoablation as a viable alternative to surgical excision for appropriately selected low-risk patients.

Methylene Blue/Collagen Mixture for CT-Guided Presurgical Lung Nodule Marking: High Efficacy and Safety.

PURPOSE: To assess outcomes of computed tomography (CT)-guided methylene blue/collagen marking of preoperative lung nodules before video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracic surgery (RATS). MATERIALS AND METHODS: A retrospective cohort study assessing 25 methylene blue/collagen solution CT-guided lung nodule localization procedures on 26 nodules in 25 patients was performed. The procedures were performed by a fellowship-trained radiologist 1-2 hours before scheduled surgery under local anesthesia. Approximately 4-6 ml of methylene blue/collagen solution was injected in a perinodular location under CT guidance with a 19-gauge trocar needle and along the track to the visceral pleural surface. Post-procedural CT images confirmed appropriate lung nodule location marking. RESULTS: Perinodular CT-guided trocar needle placement was achieved in all marking procedures (n = 26/26). Increased consolidation near the target nodule was also demonstrated in all patients on the post-procedural localized CT scans. One patient with moderate emphysema developed a small to moderate-sized pneumothorax (∼20%-30%), and an 8-Fr thoracentesis catheter was placed under CT guidance before surgery. There was no bleeding or hemoptysis in any patient. Methylene blue/collagen solution was readily visible by the thoracic surgeon in association with all target nodules. One patient required conversion to open procedure due to the proximal portion of the right lower lobe pulmonary artery segmental branch. Of the 26 identified nodules, pathology specimens confirmed the adequacy of nodule resection in all cases. CONCLUSIONS: Preoperative CT-guided methylene blue/collagen solution injection offers a safe and highly effective technique for marking subpleural lung nodules undergoing VATS or RATS.

Percutaneous Cryoablation of Renal Tumors: Is It Time for a New Paradigm Shift?

PURPOSE: To retrospectively assess long-term outcomes of percutaneous renal cryoablation, including factors affecting complications and local recurrence rates. MATERIALS AND METHODS: A total of 357 computed tomographic (CT) fluoroscopy-guided percutaneous cryoablation procedures were performed for 382 masses in 302 outpatients; 347 were biopsy-proven renal-cell carcinoma (RCC) or Bosniak category > III masses (n = 28). Benign pathologic conditions (n = 18) or metastatic non-RCC disease (n = 17) were included to analyze procedural complication rate, but recurrence rates, tumor staging, and nephrometry score were limited to RCCs. The average tumor diameter was 2.9 cm (range, 1-10.3 cm), and median nephrometry score for RCC was 8 (mean, 7.4). Protection of adjacent vital structures was performed in 34% of procedures (n = 121), and ureteral stent placement was performed for 9.2% (n = 33). All major complications were graded per surgical Clavien-Dindo criteria. RESULTS: The average CT-visible cryoablation zone diameter was 5 cm (range, 2.5-10.5 cm). Grade ≥ 3 complications occurred in 2.8% of procedures (n = 10), and appeared related to only high nephrometry scores (P = .0086) and larger tumors (P = .0034). No significant changes in renal function before and after the procedure were noted (P = .18). At a mean follow-up of 31.8 months, the local tumor recurrence rate was 3.2% (11 of 347) for RCC, and no significant difference was noted between tumors larger or smaller than 3 cm (P = .15). The difference reached significance only among the small number of stage ≥ T2 RCC tumors (P = .0039). CONCLUSIONS: Long-term follow-up of percutaneous renal cryoablation demonstrates low recurrence rates with preserved renal function, even for patients with high nephrometry scores and body mass index, assuming thorough cytotoxic technique and protection measures.

Gene expression analysis of bone metastasis and circulating tumor cells from metastatic castrate-resistant prostate cancer patients.

BACKGROUND: Characterization of genes linked to bone metastasis is critical for identification of novel prognostic or predictive biomarkers and potential therapeutic targets in metastatic castrate-resistant prostate cancer (mCRPC). Although bone marrow core biopsies (BMBx) can be obtained for gene profiling, the procedure itself is invasive and uncommon practice in mCRPC patients. Conversely, circulating tumor cells (CTCs), which are likely to stem from bone metastases, can be isolated from blood. The goals of this exploratory study were to establish a sensitive methodology to analyze gene expression in BMBx and CTCs, and to determine whether the presence or absence of detectable gene expression is concordant in matching samples from mCRPC patients. METHODS: The CellSearch(®) platform was used to enrich and enumerate CTCs. Low numbers of PC3 prostate cancer (PCa) cells were spiked into normal blood to assess cell recovery rate. RNA extracted from recovered PC3 cells was amplified using an Eberwine-based procedure to obtain antisense mRNA (aRNA), and assess the linearity of the RNA amplification method. In this pilot study, RNAs extracted from CTCs and PCa cells microdissected from formalin-fixed paraffin-embedded BMBx, were amplified to obtain aRNA and assess the expression of eight genes functionally relevant to PCa bone metastasis using RT-PCR. RESULTS: RNAs were successfully extracted from as few as 1-5 PCa cells in blood samples. The relative expression levels of reference genes were maintained after RNA amplification. The integrity of the amplified RNA was also demonstrated by RT-PCR analysis using primer sets that target the 5'-end, middle, and 3'-end of reference mRNA. We found that in 21 out of 28 comparisons, the presence or absence of detectable gene expression in CTCs and PCa cells microdissected from single bone lesions of the same patients was concordant. CONCLUSIONS: This exploratory analysis suggests that aRNA amplification through in vitro transcription may be useful as a method to detect gene expression in small numbers of CTCs and tumor cells microdissected from bone metastatic lesions. In some cases, gene expression in CTCs and BMBxs was not concordant, raising questions about using CTC gene expression to make clinical decisions.

Soft-tissue cryoablation in diffuse locations: feasibility and intermediate term outcomes.

PURPOSE: To assess whether diverse tumor location(s) show differences in percutaneous cryoablation (PCA) outcomes of cancer control, morbidity, and ablation volume reduction for many soft-tissue tumor types. MATERIALS AND METHODS: A total of 220 computed tomography (CT)- and/or ultrasonography-guided percutaneous cryotherapy procedures were performed for 251 oligometastatic tumors from multiple primary cancers in 126 patients. Tumor location was grouped according to regional sites: retroperitoneal, superficial, intraperitoneal, bone, and head and neck. PCA complications were graded according to Common Terminology Criteria for Adverse Events (version 4.0). Local tumor recurrence and involution were calculated from ablation zone measurements, grouped into 1-, 3-, 6-, 12-, 18-, and 24-month (or later) statistical bins. RESULTS: Tumor and procedure numbers for each site were 75 and 69 retroperitoneal, 76 and 62 superficial, 39 and 32 intraperitoneal, 34 and 34 bone, and 27 and 26 head and neck. Average diameters of tumor and visible ice during ablation were 3.4 and 5.5 cm, respectively. Major complications (ie, grade >3) attributable to PCA occurred after five procedures (2.3%). At 11 months average follow-up (range, 0-82 mo), a 10% total recurrence rate (26 of 251) was noted; three occurred within the ablation zone, for a local progression rate of 1.2%. Average time to recurrence was 4.9 months, and, at 21 months, the initial ablation zone had reduced in volume by 93%. CONCLUSIONS: CT-guided PCA is a broadly safe, effective local cancer control option for oligometastatic disease with soft-tissue tumors in most anatomic sites. Other than bowel and nerve proximity, PCA also shows good healing if proper visualization and precautions are followed.

Percutaneous cryoablation of metastatic lesions from non-small-cell lung carcinoma: initial survival, local control, and cost observations.

PURPOSE: To assess feasibility, complications, local tumor recurrences, overall survival (OS), and estimates of cost effectiveness for multisite cryoablation (MCA) of oligometastatic non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: A total of 49 computed tomography- and/or ultrasound-guided percutaneous MCA procedures were performed on 60 tumors in 31 patients (19 women and 12 men) with oligometastatic NSCLC. Average patient age was 65 years. Tumor location was grouped according to common metastatic sites. Median OS was determined by Kaplan-Meier method and defined life-years gained (LYGs). Estimates of MCA costs per LYG were compared with established values for systemic therapies. RESULTS: Total numbers of tumors and cryoablation procedures for each anatomic site were as follows: lung, 20 and 18; liver, nine and seven; superficial, 12 and 11; adrenal, seven and seven; paraaortic/isolated, two and two; and bone, 10 and seven. A mean of 1.6 procedures per patient were performed, with a median clinical follow-up of 11 months. Major complication and local recurrence rates were 8% (four of 49) and 8% (five of 60), respectively. Median OS for MCA was 1.33 years, with an estimated 1-year survival rate of approximately 53%. MCA appeared cost-effective even when added to the cost of best supportive care or systemic regimens, with an adjunctive cost-effectiveness ratio of $49,008-$87,074. CONCLUSIONS: MCA was associated with very low morbidity and local tumor recurrence rates for all anatomic sites, and possibly increased OS. Even as an adjunct to systemic therapies, MCA appeared cost-effective for palliation of oligometastatic NSCLC.

Percutaneous cryoablation of metastatic renal cell carcinoma for local tumor control: feasibility, outcomes, and estimated cost-effectiveness for palliation.

PURPOSE: To assess complications, local tumor recurrences, overall survival (OS), and estimates of cost-effectiveness for multisite cryoablation (MCA) of oligometastatic renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 60 computed tomography- and/or ultrasound-guided percutaneous MCA procedures were performed on 72 tumors in 27 patients (three women and 24 men). Average patient age was 63 years. Tumor location was grouped according to common metastatic sites. Established surgical selection criteria graded patient status. Median OS was determined by Kaplan-Meier method and defined life-years gained (LYGs). Estimates of MCA costs per LYG were compared with established values for systemic therapies. RESULTS: Total number of tumors and cryoablation procedures for each anatomic site are as follows: nephrectomy bed, 11 and 11; adrenal gland, nine and eight; paraaortic, seven and six; lung, 14 and 13; bone, 13 and 13; superficial, 12 and nine; intraperitoneal, five and three; and liver, one and one. A mean of 2.2 procedures per patient were performed, with a median clinical follow-up of 16 months. Major complication and local recurrence rates were 2% (one of 60) and 3% (two of 72), respectively. No patients were graded as having good surgical risk, but median OS was 2.69 years, with an estimated 5-year survival rate of 27%. Cryoablation remained cost-effective with or without the presence of systemic therapies according to historical cost comparisons, with an adjunctive cost-effectiveness ratio of $28,312-$59,554 per LYG. CONCLUSIONS: MCA was associated with very low morbidity and local tumor recurrence rates for all anatomic sites, with apparent increased OS. Even as an adjunct to systemic therapies, MCA appeared cost-effective for palliation of oligometastatic RCC.

Percutaneous cryoablation of adrenal metastases: technical feasibility and safety.

PURPOSE: To assess the technical feasibility and outcomes of adrenal metastases cryoablation. MATERIALS AND METHODS: This is an IRB approved retrospective review of adrenal metastases cryoablation between April 2003 and October 2018. Forty percutaneous cryoablation procedures were performed on 40 adrenal metastases in 34 patients. Histology, tumor size, ablation zone size, major vessel proximity, local recurrences, complications, and anesthesia-managed hypertension monitoring was collected. Complications were graded according to the Common Terminology of Complications and Adverse Events (CTCAE). RESULTS: Mean tumor and ablation size was 3.2 cm and 5.2 cm, respectively. Local recurrence rate was 10.0% (N = 4/40) for a mean follow-up time of 1.8 years. Recurrences for tumors > 3 cm (21.0%, N = 4/19) was greater than for tumors ≤ 3 cm (0.0%, N = 0/21) (p = 0.027). Proximity of major vasculature (i.e., IVC & aorta) did not statistically effect recurrence rates (p = 0.52), however, those that recurred near vasculature were > 4 cm. Major complication (≥ grade 3) rate was 5.0% (N = 2/40), with one major complication attributable to the procedure. Immediate escalation of blood pressure during the passive stick phase (between freeze cycles) or post procedure thaw phase was greater in patients with residual adrenal tissue (N = 21/38) versus masses replacing the entire adrenal gland (N = 17/38), (p = 0.0020). Lower blood pressure elevation was noted in patients with residual adrenal tissue who were pre-treated with alpha blockade (p = 0.015). CONCLUSIONS: CT-guided percutaneous cryoablation is a safe, effective and low morbidity alternative for patients with adrenal metastases. Transient hypertension is related only to residual viable adrenal tissue but can be safely managed and prophylactically treated.

The ECLIPSE Study: Efficacy of Cryoablation on Metastatic Lung Tumors With a 5-Year Follow-Up.

INTRODUCTION: The ECLIPSE study aimed to evaluate the feasibility and efficacy of cryoablation (CA) for local tumor control in patients with pulmonary metastatic disease in 5 years of follow-up. METHODS: ECLIPSE was a prospective, multicenter, single-arm study that included patients treated with CA if they had one to five metastatic lung tumors, each with a diameter of less than or equal to 3.5 cm. Patients were followed up in the course of 5 years. The primary end point was local tumor control, both per tumor and per patient; secondary end points included cancer-specific survival, overall survival, and quality of life (QoL). QoL was evaluated using the Karnofsky Performance Score, the Eastern Cooperative Oncology Group performance score, and the Short Form-12 health survey. RESULTS: The study included 40 patients across four sites (three in United States and one in Europe). A total of 60 metastatic pulmonary tumors were treated with 48 CA procedures. Overall local tumor control rates were 87.9% (29 of 33) and 79.2% (19 of 24) per tumor, 83.3% (20 of 24) and 75.0% (15 of 20) per patient, at 3 and 5 years, respectively. A total of five treated patients had local progression throughout the duration of the study. Disease-specific survival rate was 74.8% at 3 years and 55.3% at 5 years, whereas overall survival at 3 and 5 years was 63.2% and 46.7%, respectively. Patient QoL scores did not reach statistical significance. CONCLUSIONS: CA is an effective means of long-term local tumor control in patients with metastatic pulmonary tumors.

Adrenal Metastases as Sanctuary Sites in Advanced Renal Cancer.

Involvement of the adrenal gland in kidney cancer represents a unique site of metastasis with a distinct clinical course. The cases are typically resistant to immune therapy and need local therapy management. A case series of patients with adrenal metastases was reviewed to highlight the nuances of clinical course and therapy. We reviewed renal cancer carcinoma (RCC) cases with adrenal metastases at Karmanos Cancer Center, Detroit MI. Medical records were reviewed to collect relevant case information. Next-generation sequencing, tumor mutation burden testing, and programmed death ligand biomarkers were evaluated in five cases. Twelve cases were reviewed; all were males with a median age of 49.5 years. Three patients presented with adrenal metastases only and were treated with local therapy. Three received interleukin-2 (IL-2). One patient relapsed with bilateral adrenal lesions after 11 years of remission, post-IL-2 therapy. Five cases received immune checkpoint inhibitor (ICI) and one received antivascular therapy. ICI therapy was followed by ablation of residual adrenal metastases in three patients. Genomic profiling was available in five cases. All were BAP1 and PD-L1 negative.Pathogenic mutations in PBRM1, SETD2, and VHL were noted. All patients with residual adrenal metastases responded to antivascular therapies or to local ablation. One patient died 17 years after diagnosis and 11 patients are alive at a median follow-up of 9.5 years. Adrenal metastases in RCC have a distinct clinical course. They can represent a sanctuary site of relapse/residual disease following treatment with immune therapy. Management with local therapy can induce durable remissions. Systemic management with antivascular therapies also demonstrated favorable responses. Further investigation should focus on the unique clinical course and optimal management of adrenal metastases in kidney cancer.

CT-guided percutaneous cryotherapy of renal masses.

PURPOSE: To assess the results of initial and current techniques for percutaneous renal cryotherapy, including long-term imaging outcomes. MATERIALS AND METHODS: Computed tomography (CT)-guided percutaneous cryotherapy was performed on 49 masses in 48 outpatients and procedure comfort noted for each. These 49 masses included 36 primary renal cell carcinomas (RCCs), 3 oncocytomas, 1 angiomyolipoma, 6 renal inflammatory lesions, 2 benign parenchymal changes, and 1 colon cancer metastasis. All complications were graded according to standardized criteria. RESULTS: Patients received only local anesthesia and moderate sedation during the procedure and were discharged with minimal discomfort within 4-6 hours. All cryotherapy zones were well defined by CT during ablation as hypodense ice with an average diameter of 5.3 cm, covering an average tumor size of 3.3 cm. Average ablation zone diameters showed significant reduction over time (P < .001), becoming significantly less than the original tumor size by 12 months (P < .05). Major and minor complications were seen in 3 (6%) and 11 (22%) procedures, respectively. At a mean follow-up of 1.6 years (range, 1 week to 3.8 years) for primary RCC patients, four failures (11.1%) by imaging criteria were noted, but one proved to be inflammatory tissue at re-biopsy (estimated neoplastic failure rate = 3/36 = 8.3%). CONCLUSIONS: Percutaneous renal cryotherapy is a well-tolerated outpatient procedure that allows safe, CT monitoring of ice formation beyond visible tumor margins. With appropriate cryoprobe placements, a low failure rate appears less dependent on tumor size or location. Ablation volume involution was >80% after 6 months.

Percutaneous cryoablation of hepatic tumors: long-term experience of a large U.S. series.

PURPOSE: To report our long-term experience with percutaneous cryotherapy for primary and metastatic liver tumors, including historical perspectives on complications over time and local recurrence rates. MATERIALS AND METHODS: Following IRB approval under HIPAA compliance, 342 CT fluoroscopic-guided, percutaneous cryotherapy procedures were performed for 443 masses in 212 outpatients with hepatocellular carcinoma (HCC; N = 36), or metastatic disease (N = 176), grouped as colorectal carcinoma (CRC) and non-CRC metastases. Tumor and ablation sizes were noted in relation to adjacent vasculature. All complications were graded according to standardized criteria. Patients were followed by CT and/or MRI at 1, 3, 6, 12, 18, 24 months and yearly thereafter. Local recurrences were defined as either "procedural" within the ice ablation zone, or "satellite" within 1 cm of the ablation rim to evaluate recurrence patterns. RESULTS: Average tumor diameter of 2.8 cm was treated by average cryoprobe number of 4.5, which produced CT-visible ice ablation zone diameters averaging 5.2 cm. Grade >3 complications were primarily hematologic [N = 20/342; (5.8%)], and appeared related to pre-procedural anemia/thrombocytopenia, carcinoid tumor type, and large ablation volumes. No significant central biliary leak, strictures, or bilomas were noted. At a mean follow-up of 1.8 years, local tumor recurrences were 5.5%, 11.1%, and 9.4% for HCC, CRC, and non-CRC metastases, respectively, consisting mainly of satellite foci. No significant difference was noted for local recurrences near major blood vessels or tumors >3 cm diameter. CONCLUSIONS: Percutaneous hepatic cryotherapy is a well-visualized, safe procedure that produces very low local recurrence rates, even for tumors near vasculature and diameters over 3 cm. Cryoablation deserves to be in the armamentarium of percutaneous hepatic ablation, especially with careful patient selection for tumors <4 cm and patients with platelet counts >100,000. Percutaneous hepatic cryoablation represents a highly flexible technique with particular benefits near central biliary structures and/or adjacent crucial structures.

Evaluating Cryoablation of Metastatic Lung Tumors in Patients--Safety and Efficacy: The ECLIPSE Trial--Interim Analysis at 1 Year.

INTRODUCTION: To assess the feasibility, safety and local tumor control of cryoablation for treatment of pulmonary metastases. MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act (HIPAA) compliant, IRB-approved, multicenter, prospective, single arm study included 40 patients with 60 lung metastases treated during 48 cryoablation sessions, with currently a minimum of 12 months of follow-up. Patients were enrolled according to the following key inclusion criteria: 1 to 5 metastases from extrapulmonary cancers, with a maximal diameter of 3.5 cm. Local tumor control, disease-specific and overall survival rates were estimated using the Kaplan-Meier method. Complications and changes in physical function and quality of life were also evaluated using Karnofsky performance scale, Eastern Cooperative Oncology Group performance status classification, and Short Form-12 health survey. RESULTS: Patients were 62.6 ± 13.3 years old (26-83). The most common primary cancers were colon (40%), kidney (23%), and sarcomas (8%). Mean size of metastases was 1.4 ± 0.7 cm (0.3-3.4), and metastases were bilateral in 20% of patients. Cryoablation was performed under general anesthesia (67%) or conscious sedation (33%). Local tumor control rates were 56 of 58 (96.6%) and 49 of 52 (94.2%) at 6 and 12 months, respectively. Patient's quality of life was unchanged over the follow-up period. One-year overall survival rate was 97.5%. The rate of pneumothorax requiring chest tube insertion was 18.8%. There were three Common Terminology Criteria for Adverse Events grade 3 procedural complications during the immediate follow-up period (pneumothorax requiring pleurodesis, noncardiac chest pain, and thrombosis of an arteriovenous fistula), with no grade 4 or 5 complications. CONCLUSION: Cryoablation is a safe and effective treatment for pulmonary metastases with preserved quality of life following intervention.