Cryoablation of Primary Breast Cancer in Patients Ineligible for Clinical Trials: A Multiinstitutional Study.

Background: Breast cancer cryoablation clinical trials have strict inclusion criteria that exclude patients with potentially treatable disease. Objective: This study's purpose was to evaluate the safety and outcomes of breast cancer cryoablation without surgical excision in patients ineligible for prospective cryoablation clinical trials due to unfavorable patient or tumor characteristics. Methods: This retrospective study included women who underwent cryoablation of biopsy-proven unifocal primary breast cancer with locally curative intent, without surgical excision, despite being ineligible for (and thus excluded from) cryoablation clinical trials, across seven institutions between January 1, 2000 and August 26, 2021. Adverse events (AEs) were recorded. Cryoablation procedures were classified as technically successful if they were not prematurely terminated and achieved intended treatment parameters and the first imaging follow-up showed no evidence of residual disease. Results of follow-up biopsies were recorded. Ipsilateral breast tumor recurrences (IBTR) diagnosed during follow-up were identified and classified as true recurrence or new primary disease. A competing-risk model was used to estimate the cumulative incidence of IBTR accounting for death before IBTR. Results: The final study sample included 112 patients (median age, 71 years). A total of 7/112 (6.3%) patients had a minor AE; no moderate or major AE occurred. A total of 110/112 (98.2%) cryoablation procedures were technically successful. During median follow-up of 2.0 years, 22/110 (20.0%) patients underwent biopsy for suspicious imaging findings in the ipsilateral breast, yielding benign concordant findings in 9/22 (40.9%) and IBTR in 12/22 (54.5%). Overall, 12/110 (10.9%) patients experienced IBTR, including 7 with true recurrence and 5 with new primary disease; 3/12 (25.0%) patients with IBTR had received earlier adjuvant or neoadjuvant therapy. When accounting for death as a competing risk, the cumulative incidence of IBTR was 5.3%, 12.2%, and 18.2% at 1, 2, and 3 years, respectively. Conclusion: In select individuals with unfavorable patient or tumor characteristics, breast cancer cryoablation provides a safe alternative to surgery with good outcomes. These findings may be particularly relevant in patients who are also poor surgical candidates. Clinical Impact: Breast cancer cryoablation can be safely applied in a larger patient population than defined by clinical trial inclusion criteria.

Successful cryoablation of breast cancer.

The current standard of care for screen-detected breast cancers is surgical excision. Cryotherapy is a promising non- surgical alternative treatment for these cancers and is performed under local anesthesia as an outpatient, circumventing the risks that come with an operation. New research also shows promising results for the treatment of breast cancer when cryotherapy is combined with immune modulation as it may help prevent tumor recurrence. We herein report a case of breast cancer treated successfully with cryoablation. A brief literature review of cryoablation as a treatment for breast cancer is added.

Preoperative MRI Evaluation of Axillary Lymph Nodes in Invasive Ductal Carcinoma: Comparison of Luminal A Versus Luminal B Subtypes in a Paradigm Using Ki-67 and Receptor Status.

OBJECTIVE: The purpose of this study is to assess whether luminal A versus luminal B molecular subtypes of breast cancer affect the diagnostic utility of preoperative MRI evaluation of the axilla. MATERIALS AND METHODS: This study identified 125 patients who underwent preoperative breast MRI evaluation of tumors classifiable as luminal A or luminal B molecular subtypes between January 2012 and August 2014. The subtypes were classified on the basis of immunohistochemical staining surrogates combining receptor status and the Ki-67 proliferation index. Statistical analysis was performed using chi-square analysis and one-way ANOVA. When a statistically significant difference was found, follow-up analysis involving pairwise comparison using the Bonferroni correction was performed. Multivariate logistic regression analysis was also used to determine whether the molecular subtype was independently predictive of lymph node involvement. RESULTS: A total of 80 patients had tumors classifiable as the luminal A molecular subtype, whereas 45 patients had tumors classifiable as the luminal B subtype. Pathologically proven axillary lymph node (ALN) disease occurred statistically significantly more frequently in luminal B tumors (18/45 [40.0%]) than in luminal A tumors (11/80 [13.8%]; p < 0.01). In addition, pathologically proven ALN disease was 4.3 times more likely to occur in luminal B tumors after controlling for patient age, tumor size, and tumor grade (p < 0.01). We found no difference in the negative predictive value of the MRI assessment of the axilla when luminal A tumors were compared with luminal B tumors. The positive predictive value of MRI evaluation of ALNs is statistically significantly higher for luminal B tumors than for luminal A tumors (76.2% vs 28.0%, respectively; p = 0.004). CONCLUSION: With the use of molecular subtype classification including the Ki-67 proliferation index, suspicious nodes detected in luminal B tumors by MRI are likely to have positive findings and warrant preoperative tissue sampling. Conversely, in view of the high false-positive rate of suspicious nodes detected in luminal A tumors by MRI, proceeding straight to sentinel lymph node biopsy for all cases, except for those with highly suspicious findings, is suggested. These results should, however, be validated in a larger prospective study.

Diagnostic performance of CT attenuation values of focal 18F-FDG avid breast lesions detected on whole-body PET-CT in postoperative breast cancer patients.

To assess whether CT attenuation values help in differentiating benign from malignant etiology of focal (18) F-FDG avid breast lesions detected on whole-body PET/CT exam in postoperative breast cancer patients. Institutional review board approval and waived informed consent were obtained for this HIPAA-compliant retrospective study. Between January 2009 and July 2011, a total of 85 patients had 97 focal (18) F-FDG avid breast lesions on whole-body PET/CT. Of these, 54 (56%) lesions were biopsy-proven primary invasive breast carcinoma that had not undergone treatment at the time of PET/CT, 35 (36%) were benign lesions, and 8 were locally recurrent breast carcinoma. Mean attenuation values were retrospectively measured in Hounsfield units (HU) for the correlative lesion on the CT portion of the exam. Receiver-operating characteristic curves (ROC) were calculated to determine the optimal cutoff values of HU that would best discriminate between benign and malignant lesions. Interobserver agreement for measured mean attenuation values was assessed by calculating the intraclass correlation coefficient (ICC). Mean HU for the benign lesions group and the local recurrence lesions group was -11.0 ± 30.3 versus 32.9 ± 6.87 (p < 0.0002). ROC curve analysis comparing benign breast lesions to local recurrence lesions found an optimal cutoff value of 17 HU (area under curve = 0.982, p < 0.0001, Sensitivity = 100%, Specificity = 89%). ICC with regard to interobserver agreement in measuring the mean HU of the benign lesions was 0.84 (95% confidence interval 0.64-0.93) and for the malignant lesions was 0.88 (95% confidence interval 0.77-0.94). A CT attenuation threshold value of less than 17 HU suggests benign etiology of focal (18) FDG avid breast lesions in postoperative breast cancer patients. If confirmed by additional studies, these findings may provide additional information to guide the treating physician regarding decisions for supplementary imaging or the need to biopsy.

Conventional and advanced MRI features of pediatric intracranial tumors: posterior fossa and suprasellar tumors.

OBJECTIVE: In this article, we review the most common posterior fossa and suprasellar intracranial neoplasms in the pediatric population. We briefly discuss basic MRI concepts used in the initial evaluation of a pediatric brain tumor and then discuss sophisticated MRI techniques that give insight into the physiology and chemical makeup of these tumors to help the radiologist make a more specific diagnosis. CONCLUSION: Diagnosis and treatment of pediatric CNS tumors necessitate a multi-disciplinary approach and require expertise and diligence of all parties involved. Imaging is an essential component has evolved greatly over the past decade. We are becoming better at making a preoperative diagnosis of that tumor type, detecting recurrence, and guiding surgical management to avoid injury to vital brain structures.

Conventional and advanced MRI features of pediatric intracranial tumors: supratentorial tumors.

OBJECTIVE. Our objective is to review the imaging characteristics and applications of conventional and advanced neuroimaging techniques of supratentorial intracranial masses in the pediatric population. Specifically, we review astrocytomas, oligodendrogliomas, primary neuroectodermal tumors, dysembryoplastic neuroepithelial tumors, gangliogliomas, arachnoid cysts, and choroid plexus and pineal region masses. CONCLUSION. Advanced imaging methods, such as MR spectroscopy, perfusion MRI, functional MRI, diffusion-tensor imaging, and tractography, help develop a more accurate differential diagnosis and aid in planning tumor treatment.

Could ultrasound-guided cryoablation be used to manage "low-risk" DCIS?: a feasibility case report.

Management of ductal carcinoma in-situ (DCIS) is controversial as there is concern that the majority of diagnoses will never become life threatening such that a subset of patients may be overtreated with surgery. Active surveillance is an alternative proposed management strategy; however, we cannot accurately predict which DCIS will never progress to invasive disease potentially undertreating a large proportion of women. We present a case of a 58-year-old female with DCIS successfully treated with only ultrasound-guided cryoablation without resection. A follow-up needle biopsy of the ablation zone was benign and imaging follow-up has demonstrated no evidence of disease at 14-months. Cryoablation of DCIS is feasible with appropriate patient selection and warrants further investigation as an alternative to surgical resection or active surveillance.

Abbreviated Screening Breast MRI in Women at Higher-than-Average Risk for Breast Cancer with Prior Normal Full Protocol MRI.

OBJECTIVE: To compare the performance of abbreviated screening breast MRI (ABMR) versus full protocol MRI (FPMR) in women at higher-than-average risk for breast cancer with a prior normal FPMR. METHODS: ABMR was performed on higher-than-average-risk women who had a prior normal FPMR. ABMR protocol consisted of short inversion time inversion recovery imaging, precontrast, and two early postcontrast sequences acquired in under 10 minutes. Retrospective review of ABMR examinations performed from July 2016 to July 2018 was compared with a control group who underwent routine screening with FPMR who had a prior normal FPMR performed from July 2014 to June 2016. Screening outcome metrics were calculated and compared, adjusting for differences in patient demographics. RESULTS: The study cohort included 481 ABMR examinations, while the control group included 440 FPMR studies. There was no significant difference in the abnormal interpretation rate (AIR) or cancer detection rate (CDR) for the ABMR versus the FPMR group (AIR 6.0% vs 6.8% respectively, odds ratio (OR) 0.91, 95% confidence interval (CI): 0.53-1.5, P = 0.73; CDR 8.3 vs 11 cancers detected per 1000 examinations respectively, OR 0.73, 95% CI: 0.20-2.7, P = 0.64). The PPV2 and PPV3 for the ABMR group was 19% and 21% versus 16% and 16% for the FPMR group, with no statistical difference. Sensitivity was 100% in each group with no interval cancers. There was no difference in specificity between the ABMR and FPMR groups, 93% versus 94%, respectively (P = 0.73). CONCLUSION: ABMR may be used to screen higher-than-average-risk women with a prior normal FPMR as outcome metrics are equivalent to FPMR.

Dual radiotracer analysis of cholinergic neuronal changes in prediabetic mouse pancreas.

BACKGROUND: Pancreatic neuronal changes associated with beta cell loss in type 1 diabetes mellitus are complex, involving, in part, parasympathetic mechanisms to compensate for preclinical hyperglycemia. The parasympathetic neurotransmitter acetylcholine (ACh) mediates insulin release via M3 muscarinic receptors on islet beta cells. The vesicular ACh transporter (VAChT) receptor has been shown to be a useful marker of cholinergic activity in vivo. The positron emission tomography (PET) radiotracer (+)-4-[(18)F]fluorobenzyltrozamicol ([(18)F]FBT) binds to the VAChT receptor on presynaptic cholinergic neurons and can be quantified by PET. The compound 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), available in a tritiated form, binds to M3 muscarinic receptors on beta cells and is a potential target for assessing pancreatic beta cell mass. In this study, we investigate the feasibility of dual radiotracer analysis in identifying neurofunctional changes that may signify type 1 diabetes mellitus in its early preclinical state. METHODS: Ex vivo determinations of pancreatic uptake were performed in prediabetic nonobese diabetic mice and controls after intravenous injection of [(18)F]FBT or 4-[(3)H]DAMP. Beta cell loss in prediabetic mice was confirmed using immunohistochemical methods. RESULTS: [(18)F]FBT uptake was significantly higher in prediabetic pancreata than controls: 3.22 +/- 0.81 and 2.51 +/- 1.04, respectively (P < 0.03). 4-[(3)H]DAMP uptake was significantly lower in prediabetic pancreata than controls: 0.612 +/- 0.161 and 0.968 +/- 0.364, respectively (P = 0.01). CONCLUSIONS: These data suggest that a combination of radiotracer imaging agents that bind to neuronal elements intimately involved in insulin production may be an effective method of evaluating changes associated with early beta cell loss using PET.

Safety and Efficacy of Ultrasound-Guided Cryoablation for Benign Breast Fibroepithelial Lesions.

OBJECTIVE: The purpose of this study is to evaluate the safety and efficacy of cryoablation for benign breast fibroepithelial lesions (FELs) that otherwise warrant surgical excision, including symptomatic fibroadenomas, growing fibroadenomas, and cellular FELs. METHODS: All patients from 2016-2018 who had ultrasound-guided cryoablation of a symptomatic and/or growing fibroadenoma or cellular fibroepithelial lesion were reviewed. The electronic medical record was reviewed for any procedure-related complications and reduction in mass volume by ultrasound and was recorded to assess for efficacy. Patients were surveyed using a seven-point Likert scale to assess satisfaction with the procedure and a ten-point visual analog pain scale to assess level of discomfort. RESULTS: Twenty-four women (average age 37.1 years, range 19-57 years) with 26 FELs were treated with no adverse events and 100% technical success. Thirteen cellular FELs and 13 symptomatic and/or growing fibroadenomas were ablated. Twenty-two patients had an average imaging follow-up of 11.7 months (range 5-23 months), and 18 patients completed the follow-up survey. There was 92% (22/24) clinical success, defined as a greater-than-50% reduction in mass volume. Average reduction in mass volume was 86% overall. Eighty-five percent (17/20) would recommend the procedure to others and reported pain during the procedure to be minimal (average 2.4 out of 10) with overall satisfaction rating of 6.2 out of 7. Twelve symptomatic masses demonstrated a significant reduction in pain after cryoablation (P = 0.01). CONCLUSION: Cryoablation is a safe and efficacious minimally invasive nonsurgical alternative for the treatment of benign breast FELs.

Diffusion tensor imaging in the normal breast: influences of fibroglandular tissue composition and background parenchymal enhancement.

OBJECTIVE: To evaluate effects of fibroglandular tissue (FGT) composition and background parenchymal enhancement (BPE) on diffusion tensor imaging (DTI) parameters in normal breast tissue. METHODS: DTI analysis was performed on 35 breasts with regions of interest drawn to include only normal tissue. Breasts were dichotomized by FGT composition and by BPE; DTI parameters were compared. RESULTS: The λ1 principal diffusion coefficient was lower in breasts with moderate/marked BPE versus those with minimal/mild BPE (P=.039). All other parameters were unaffected. CONCLUSION: λ1 is sensitive to differences in BPE within normal breast tissue that should be taken into account in DTI evaluation.

Phyllodes tumor: review of key imaging characteristics.

Phyllodes tumor of the breast is rare and often resembles the more commonly seen fibroadenoma at imaging and histologically. As core biopsy cannot always distinguish the two, assessing radiologic-pathologic concordance is essential to guide appropriate clinical management. We review the imaging characteristics of phyllodes tumor at mammography, ultrasound, and MRI to help the interpreting radiologist be aware of key imaging features that should alert him to the possibility of a phyllodes tumor even if not verified by initial core biopsy.

Breast fibromatosis response to tamoxifen: dynamic MRI findings and review of the current treatment options.

Breast fibromatosis is a rare entity responsible for 0.2% of all solid breast tumors. It has been associated with scars, pregnancy, implants, and familial adenomatous polyposis. We present an interesting case of breast fibromatosis in a 29 year old woman which encroached upon her saline implant and subsequently filled its cavity once the implant was removed. The patient was put on tamoxifen therapy and at 14 month follow-up there was a significant decrease in the size of the mass. Dynamic MRI images are offered for review and current treatment options are discussed.