Utilization of Circulating Tumor DNA in the Surveillance Setting.

INTRODUCTION: National guidelines give recommendations regarding cancer surveillance follow-up. In many early staged cancers radiographic imaging and labs are not routinely recommended unless patients are symptomatic. This can cause a gap in care because commonly when patients present symptomatically, they have progressed and transitioned to later-stage cancer. This study demonstrates how circulating tumor DNA (ctDNA) can be used alongside current guidelines to help screen patients for recurrence in the surveillance setting. METHODS: A retrospective chart review was performed. Fifty-five charts were reviewed of patients who received ctDNA testing drawn in follow-up after their primary tumor or metastatic disease was rendered surgically or radiographically disease-free. A customized signature profile, using the sixteen most prevalent genomic markers from a patient's primary tumor or biopsy, is developed by whole-exome sequencing. Serial blood draws are then drawn to assess for specific DNA markers using polymerase chain reaction (PCR) assays. RESULTS: Fifty-five charts were reviewed in patients who had stage I-III breast, pancreatic, melanoma, and colorectal cancer. Of the fifty-five, a total of seven had a positive test. Of the seven positive tests, six patients were found to have recurrent/metastatic disease. One positive test was performed four weeks postoperatively but by the second draw ten weeks postoperatively had non-detectable ctDNA. The remaining forty-eight patients had non-detectable ctDNA levels and to date have not had any evidence of recurrence based on standard follow-up guidelines. CONCLUSION: The utilization of ctDNA in the surveillance setting can be used to help detect recurrence in the surveillance setting.

Wide Local Excision for Eccrine Porocarcinoma of the Forearm.

Eccrine porocarcinoma is a rare and aggressive cutaneous malignancy that develops in the seventh and eight decades of life. We present a 76-year-old male with eccrine porocarcinoma developing from a long standing previously benign lesion who underwent successful treatment with wide local excision. It can also develop de novo, presenting most commonly as a mass or nodule. Tissue biopsy with histopathology is required to confirm the diagnosis. Wide local excision is recommended for local disease. Radiation and chemotherapy can be used as adjuncts in advanced and metastatic disease. Given its rarity, there are no guidelines to direct therapy for locally advance or metastatic disease and for follow-up. Further studies are needed to better understand and guide management of this entity.

Pathologic Tumor Size versus Mammography, Sonography, and MRI in Breast Cancer Based on Pathologic Subtypes.

INTRODUCTION: The standard of care for imaging of breast pathology has historically been mammography and sonography. MRI is a modern adjunct in the surgeon's toolkit. We looked to examine the differences in imaging modalities and their ability to predict the size in relation to the pathologic size after excision with focus on pathologic subtypes. METHODS: We analyzed patient records across a 4-year period from 2017 to 2021 who were treated surgically for breast cancer at our facility. We used a retrospective chart review to collect measurements that were recorded of the tumors by the radiologist for available mammography, ultrasound, and MRI which were compared to pathology report measurements of the final specimens. We subdivided the results by pathologic subtypes including invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and ductal carcinoma in situ (DCIS). RESULTS: 658 total patients met criteria for analysis. Mammography overestimated specimens with DCIS by 1.93 mm (P = .15), US underestimated by .56 (.55), and MRI overestimated by 5.77 mm (P < .01). There was no statistically significant difference in any modalities with IDC. With specimens of ILC, all 3 imaging modalities underestimated tumor size, with only US being significant. DISCUSSION: Mammography and MRI consistently overestimated tumor size with the exception of ILC while US underestimated tumor size on all pathologic subtypes. MRI significantly overestimated tumor size in DCIS by 5.77 mm. Mammography was the most accurate imaging modality for all pathologic subtypes and never had a statistically significant difference from actual tumor size.

Mucocele-like Lesions of the Breast.

Mucocele-like lesions of the breast (MLL) are believed to be due to mucinous ducts extruding their contents into the surrounding stroma. MLLs are a rare entity usually identified by calcifications noted on routine screening mammography. Surgical excision has been recommended due to the propensity for these lesions to harbor atypical ductal hyperplasia (ADH) or malignancy. A 44-year-old female patient presented to the breast center after undergoing routine mammography which showed a group of coarse appearing microcalcifications in the outer third of the breast. After further workup, a core needle biopsy was obtained with pathology showing benign breast tissue with acellular stromal mucin pools containing dystrophic calcifications. The patient underwent surgical excision with final pathology revealing ductal carcinoma in-situ and ADH with prominent mucin production throughout the stroma.

Integration of a 31-Gene Expression Profile Into Clinical Decision-Making in the Treatment of Cutaneous Melanoma.

BACKGROUND: The practice of utilizing gene expression profile (GEP) for the evaluation and treatment of cutaneous melanomas has been found to predict the risk of sentinel-node metastasis and recurrence. Information obtained from this assay has been used to determine clinical decision-making, including serving as an indication for sentinel lymph node biopsy and also for the intensity of screening measures. METHODS: Herein we present our early experience in utilizing 31-GEP in intermediate melanomas and its effect on clinical management. A retrospective review was conducted of patients who had undergone treatment for melanoma whose tumors had been subjected to 31-GEP. Additionally, patient characteristics, attributes of the original tumor biopsied, findings on final pathology, and procedures performed were evaluated. RESULTS: 31-GEP stratified patients into 4 groups; groups 1A and 1B are considered low risk of metastasis or recurrence, while 2A and 2B are considered high risk. Over the study period, 31-GEP was conducted on 26 cutaneous melanoma patients. Testing and treatment data are available for 23 of these patients. Eleven patients were found to be low risk (9 as 1A, 2 as 1B), 12 were found to be high risk (4 as 2A, 8 as 2B). Decision-making was altered such that sentinel lymph node biopsy was omitted in 2 cases in which the patients were found to be low risk with age >65 years. DISCUSSION: In 8 cases of node-negative disease in genetically high-risk patients, surveillance measures were augmented with positron emission tomography/computed tomography. Utilization of 31-GEP is ongoing at our institution.

Comparison of Call-Back Rates between Digital Mammography and Digital Breast Tomosynthesis.

The effect of mammographic screening on the natural history and evolution of breast cancer treatment cannot be overstated; however, despite intensive and resource consuming screening, advanced breast cancer is still diagnosed frequently. The development of three-dimensional mammography or digital breast tomosynthesis (DBT) has already demonstrated greater sensitivity in the diagnosis of breast pathology and effectiveness in identifying early breast cancers. In addition to being a more sensitive screening tool, other studies indicate DBT has a lower call-back rate when compared with traditional DM. This study compares call-back rates between these two screening tools. A single institution, retrospective review was conducted of almost 20,000 patient records who underwent digital mammography or DBT in the years 2016 to 2018. These charts were analyzed for documentation of imaging type, Breast Imaging Reporting and Data System 0 status, call-back status, and type of further imaging that was required. Charts for 19,863 patients were reviewed, 17,899 digital mammography examinations were conducted compared with 11,331 DBT examinations resulting in 1,066 and 689 Breast Imaging Reporting and Data System 0 studies, respectively. Of the DM call-backs, 82.08 per cent were recommended for additional radiographic imaging and 17.82 per cent for ultrasound imaging. In the DBT group, only 39.77 per cent of call-backs were recommended for additional radiographic imaging and 60.09 per cent for ultrasound imaging. Our data suggest that DBT results in less call-back for additional mammographic images as compared with digital mammography. DBT may offer benefits over DM, including less imaging before biopsy, less time before biopsy, quicker diagnosis, and improved patient satisfaction.

Evaluating the frequency of upgrade to malignancy following surgical excision of high-risk breast lesions and ductal carcinoma in situ identified by core needle biopsy.

Excision of high-risk breast lesions (HRL) continues to be standard of care. Previous studies have shown that HRLs can be upgraded to carcinoma in situ (CIS) or invasive carcinoma (IC) upon excision. A single institution retrospective review was conducted to determine the rate of upgrade of HRLs and ductal carcinoma in situ (DCIS) identified on image-guided biopsy upon excision. Eight hundred and fifty-seven patients who underwent core needle biopsy (CNB) following the detection of suspicious lesions (BI-RADS IV) on mammograms were identified. HRLs and DCIS warranting subsequent surgical excision were found in 129 of 857 patients (15.1%). Overall, 19.6% (10/51) of DCIS, 52.4% (11/21) of ADH, and 17.6% (3/17) of papillomas were upgraded on surgical excision. A statistically significant difference was found between the concordant and discordant groups regarding the number of cores obtained (P = 0.01) and the needle size used to retrieve specimens on CNB (P = 0.01). This study reveals an upgrade rate of 26.7% of HRLs and DCIS diagnosed by CNB on surgical excision and emphasizes the continued use of large bore needles with an adequate number of core specimens when investigating a suspicious breast lesion.

Nuclear Factor-κB is Activated in Filter-Implanted Vena Cava.

BACKGROUND: Implantation of a retrievable vena cava filter (VCF) is an effective method for preventing pulmonary embolism. Retrieval of filters, however, may be difficult due to intimal hyperplasia and inflammation in the cava wall. The transcription factor nuclear factor-kappaB (NF-κB) plays an important role in regulation of numerous genes participating in the inflammatory and proliferative responses of cells. The present study was to determine whether VCF implantation resulted in activation of NF-κB in the venous neointima. METHODS: Filters were placed in vena cava (VC) in four swine for 30 days and then removed. Intimal specimens adhering to the filter struts were analyzed with reference to normal VC tissues. Immunohistochemical analyses were used to assess the NF-κB subunits p65 and p50 and the phosphorylated inhibitor of κB-α (phosphor-IκB-α) in the tissues. NF-κB DNA-binding activity was measured with enzyme-linked immunosorbent assay. RESULTS: As compared to normal VC tissues, the intimal tissues contained higher percentages of cell nucleus-located p65 and p50, and NF-κB DNA-binding activity. Elevated immunoreactivities of p65, p50 and phosphor-IκB-α were also present in the intima. CONCLUSION: The present study demonstrates for the first time that VCF implantation caused NF-κB activation in neointima. We further demonstrate the activation is at least partly due to phosphorylation of IκB-α. Our data suggest that NF-κB activation would significantly contribute to development of intimal hyperplasia and inflammation in filter-inserted vena cava walls. NF-κB might be a therapeutic target for inhibiting filter-induced neointima and improving filter retrieval.

A 12-Year Single-Institution Experience with Accelerated Partial Breast Irradiation.

Accelerated partial breast irradiation (APBI) using the implanted brachytherapy device MammoSite® was approved for routine use by the Food and Drug Administration in 2002. The American Society of Breast Surgeons MammoSite® Breast Brachytherapy Registry served as a guideline for our institution to begin offering this treatment in 2005. This report reviews our available data to provide an analysis of patient outcomes over 12 years of use at a single institution. A retrospective review was conducted of records of 150 patients who underwent APBI or attempted APBI after breast-sparing surgeries between 2006 and 2017. These charts were analyzed for documentation of patient age, cancer stage, incidence of recurrence, and posttreatment complications. Of the patients evaluated, 99 per cent (149/150) completed treatment. The median time since treatment completion is now 8.9 years. One hundred eleven patients (74% ) are now greater than five years posttreatment. Ipsilateral breast recurrence was found in 2.7 per cent of patients (4/149), and 1.3 per cent of patients (2/149) developed new primary breast tumors. Acute complications, mostly skin erythema (21%), were uncommon and self-limited. Subacute effects were generally fibrosis (13%) and mild local pain (9.4%). APBI for breast cancer after breast-conserving surgery continues to be used at our institution for select patients with good outcomes. Local control and toxicity are similar to that reported in the literature. Five-year local recurrence rates compare favorably with national trials. Occasional complications included fibrosis, persistent pain, and skin irritation.

In support of the Choosing Wisely campaign: Perceived higher risk leads to unnecessary imaging in accelerated partial breast irradiation?

Accelerated partial breast irradiation (APBI) is an increasingly utilized modality for early stage breast cancer as part of breast conservation therapy (BCT). There remains concern regarding local recurrence, requiring more frequent post-radiation surveillance imaging. The purpose of this study is to determine clinical significance of frequent surveillance in this perceived higher risk population. Patients treated at a community academic medical center from 2005 to 2013 with partial breast radiation were retrospectively identified. All patients were treated with lumpectomy followed by balloon based APBI. Diagnostic, clinical, radiographic, and outcomes data were collected. One hundred and sixty-nine patients were identified. Median age at time of diagnosis was 63. Stage was 0, I, and II in 27%, 64%, and 9%, respectively. Most patients had pure invasive ductal cancer. Ninety-two percent and 99% of patients had imaging performed by 6 and 12 months (± 3 months) respectively. Median interval between end of radiation and first image, and subsequent 3 images were 6, 6, 9, and 12 months, respectively. Median follow-up was 49 months for all patients (range 7-106). Six patients experienced local recurrence: 4 invasive, all clinically detected, and none within the first 2 years. One patient had mammographically detected recurrent ductal carcinoma in situ. No mammographic images within the first year lead to diagnosis of recurrent cancer. APBI via balloon base brachytherapy offered women excellent locoregional control rates. Frequent mammographic surveillance did not result in increased detection of early recurrent disease. The result of our study are in line with the Choosing Wisely campaign recommendations to perform no more than annual follow-up for women who have completed radiation as part of BCT, with first imaging done at 6-12 months. We recommend mammographic surveillance be performed no more frequently than annually, with first image after BCT to be done 12 months from completion of radiation.

Mammographic Screening at Age 40 or 45? What Difference Does It Make? The Potential Impact of American Cancer Society Mammography Screening Guidelines.

this is a 10-year retrospective chart review evaluating the potential impact of the most recent American Cancer Society mammography screening guidelines which excludes female patients aged 40 to 44 years from routine annual screening mammography. Instead they recommend screening mammography starting at age 45 with the option to begin screening earlier if the patient desires. The institutional cancer registry was systematically searched to identify all women aged 40 to 44 years treated for breast cancer over a 10-year period. These women were separated into two cohorts: screening mammography detected cancer (SMDC) and nonscreening mammography detected cancer (NSMDC). Statistical analysis of the cohorts was performed for lymph node status (SLN), five-year disease-free survival, and five-year overall survival. Women with SMDC had a significantly lower incidence of SLN positive cancer than the NSMDC group, 9 of 63 (14.3%) versus 36 of 81 (44 %; P < 0.001). The five-year disease-free survival for both groups was 84 per cent for SMDC and 80 per cent for NSMDC; this was not statistically significant. The five-year overall survival was statistically significant at 94 per cent for the SMDC group and 80 per cent for the NSMDC group (P < 0.05). This review demonstrates the significance of mammographic screening for early detection and treatment of breast cancer. Mammographic screening in women aged 40 to 44 detected tumors with fewer nodal metastases, resulting in improved survival and reaffirming the need for annual mammographic screening in this age group.

The Clinical Utility and Cost of Postoperative Mammography Completed within One Year of Breast Conserving Therapy: Is It Worth It?

Breast conserving therapy (BCT), lumpectomy followed by radiotherapy, is an effective treatment for a majority of breast cancers. According to the National Comprehensive Cancer Network, mammographic imaging should be completed at least six months after completion of radiation. This study evaluates the clinical significance and financial cost of postoperative breast imaging within one year of BCT. Patients treated with BCT between 2014 and 2016 at an academic center were identified retrospectively. The medical records were reviewed to identify the timing and type of the first imaging study after BCT. This study evaluated the clinical significance and the cost of postoperative imaging. A total of 128 patients were included into the study. Seventy-six patients received mammograms 3 to 12 months after BCT. Six of the 76 postoperative mammograms required additional imaging/intervention for a total of seven additional imaging studies and three procedures, all of which revealed benign findings. None of these patients had physical examination findings that were of clinical concern. The total cost of postoperative imaging and procedures performed less than a year after BCT was estimated to be $32,506. Postoperative imaging performed on breast cancer patients less than a year after BCT proved to be of no medical benefit and revealed no additional significant pathology. The mammographic surveillance in this study did not lead to the diagnosis of recurrent malignancy or second primary lesions and placed additional financial burden on the patient population. This study demonstrates that breast imaging within a year after BCT had no clinical impact and resulted in increased cost of care.

Presenting Stage in Colon Cancer Is Associated with Insurance Status.

Colorectal cancer continues to be the third most common cause of cancer death in the United States. Access to health care is also a nationwide problem. The purpose of the current study is to see if insurance status is associated with stage of colon cancer at presentation. The tumor registry was queried for all patients with colon cancer from 2009 to 2014. Demographics, including insurance status was statistically analyzed to determine if an association existed between insurance status and stage of colon cancer at the time of presentation. There were 434 patients identified that underwent colonic resection during the study period; 224 were female and 210 were male. Of the 434 patients, 388 were insured and 46 were uninsured. When insurance status was compared with stage at diagnosis there was a statistically significant difference between the two groups. For patients that were uninsured, 13.01 per cent presented with stage I disease, 15.22 per cent with stage II disease, 34.78 per cent with stage III disease, and 36.96 with stage IV disease. For insured patients, 24.03 per cent present with stage I disease, 26.10 with stage II disease, 23.26 per cent with stage III disease, and 29.61 per cent with stage IV disease (P = 0.047). Access to health care continues to be a large problem and results in patients without insurance presenting with a high stage of disease.

Evaluation of Cardiopulmonary Complication Rates after Port Insertion: Is a Postoperative X-Ray Needed?

It is customary for a postoperative chest radiograph to be obtained after fluoroscopic guided port insertion to exclude acute complications. In this review, we provide a cost-benefit analysis by examination of acute postoperative complications detected by postoperative port insertion chest films at our institution. We conducted a retrospective chart review of complications associated with port insertion procedures performed over a 5-year period. Our study included only ultrasound-assisted internal jugular venous or landmark guided subclavian ports placed with the assistance of fluoroscopy. A total of 519 port insertions were reviewed and there was noted to be a postoperative complication rate of 0.58 per cent. The operative note for each complication described a procedural abnormality that suggested a chest film would be of medical benefit. The total price of postoperative chest radiographs was $179,400. Performing chest X-ray films on asymptomatic patients after fluoroscopic guided placement of ports proved to be of no medical advantage to 516 out of 519 patients. Given the extremely low complication rate and financial burden placed on the patient population, we propose discontinuing routine use of postoperative port placement chest radiographs as a way to alleviate unwarranted medical cost.

The Pathologic Finding of Combined Lobular Carcinoma In Situ and Invasive Lobular Cancer May Indicate more than Just a High-Risk Marker Role of Lobular Carcinoma In Situ.

For years, lobular carcinoma In Situ (LCIS) has been considered a high-risk marker for developing breast cancer. It is well known that ductal carcinoma In Situ is a precursor for the development of invasive ductal carcinoma, and ductal carcinoma In Situ is reported to be present in invasive ductal carcinoma in at least 40 per cent of cases. A similar relationship between LCIS and invasive lobular carcinoma (ILC) remains in question. This study evaluates the incidence of synchronous LCIS and ILC at our institution. This is a retrospective review of our tumor registry database of women diagnosed with LCIS or ILC from 2000 to 2014. Pathology reports were evaluated to determine the incidence of pure ILC and mixed ILC/LCIS. Those with both LCIS/ILC (mixed group) and those with pure ILC (pure group) were compared for age, surgical intervention, lymph node involvement, tumor size, nuclear grade, and margins between these two groups. A total of 182 women were identified with LCIS, ILC, or mixed LCIS and ILC. There were 76 subjects with pure ILC and 90 with mixed LCIS and ILC. The median and age range for each group were 63.6 (range: 40-97) for the mixed and 64.1 (range: 40-86) for pure groups. Tumor size was evaluated for each group and the median tumor size was 2.5 cm (range: 0.1-7.0cm) for the mixed group and 3.0 cm (range: 0.5-12.5 cm) for the pure group. Nodal involvement was present in 35.23 per cent of the mixed group and 46.3 per cent in the pure group. Surgical treatment for each group was similar, with mastectomy being the preferred surgical option over breast conservation therapy in the mixed and pure groups, 67.07 and 64.71 per cent, respectively. Presently, LCIS is considered a marker, or risk factor, for development of future breast cancer. This retrospective study does identify a strong relationship, 54 per cent, between LCIS and ILC at diagnosis. This high percentage of concurrent LCIS and ILC in surgical/pathological specimens supports the notion that LCIS may in fact have a precursory role in development of invasive lobular carcinoma of the breast. Additional studies to further investigate this relationship between LCIS and ILC, including genomic analysis, are presently underway.

Long term radiographic findings of breast brachytherapy: Implications of surgical volume.

PURPOSE: Little is known about long-term radiographic findings after treatment with accelerated partial breast irradiation (APBI). METHODS: Univariate and multivariate analysis of factors leading to formation and resolution of seroma were performed in patients treated with lumpectomy and APBI. RESULTS: Post-treatment images of 129 patients were reviewed by one radiologist. Median surgical excision volume was 108.9 cc (range 20.5-681.9). Primary mode of imaging was mammogram. Median time from end of RT to first and last surveillance image was 6 and 54 months, respectively. Median number of images was 7 (range 3-12). Seroma was identified in 98 (76%) patients, with median maximum diameter of 3.9 cm. Forty (41%) patients experienced resolution of seroma, at a median time of 29 months (range 6-74). On univariate analysis, surgical excision volume was associated with seroma formation, and tumor stage and margin re-excision were significant on univariate and multivariate analysis. No factors were associated with seroma resolution. CONCLUSION: Seroma formation after APBI resolves around 2.5 years for many patients, but persists for others possibly due to primary tumor and surgical excision volumes. With revised criteria on the definition of positive margins, smaller volumes may lead to decreased risk of seroma formation for future patients.

Mapping the spatial distribution and activity of (226)Ra at legacy sites through Machine Learning interpretation of gamma-ray spectrometry data.

Radium ((226)Ra) contamination derived from military, industrial, and pharmaceutical products can be found at a number of historical sites across the world posing a risk to human health. The analysis of spectral data derived using gamma-ray spectrometry can offer a powerful tool to rapidly estimate and map the activity, depth, and lateral distribution of (226)Ra contamination covering an extensive area. Subsequently, reliable risk assessments can be developed for individual sites in a fraction of the timeframe compared to traditional labour-intensive sampling techniques: for example soil coring. However, local heterogeneity of the natural background, statistical counting uncertainty, and non-linear source response are confounding problems associated with gamma-ray spectral analysis. This is particularly challenging, when attempting to deal with enhanced concentrations of a naturally occurring radionuclide such as (226)Ra. As a result, conventional surveys tend to attribute the highest activities to the largest total signal received by a detector (Gross counts): an assumption that tends to neglect higher activities at depth. To overcome these limitations, a methodology was developed making use of Monte Carlo simulations, Principal Component Analysis and Machine Learning based algorithms to derive depth and activity estimates for (226)Ra contamination. The approach was applied on spectra taken using two gamma-ray detectors (Lanthanum Bromide and Sodium Iodide), with the aim of identifying an optimised combination of detector and spectral processing routine. It was confirmed that, through a combination of Neural Networks and Lanthanum Bromide, the most accurate depth and activity estimates could be found. The advantage of the method was demonstrated by mapping depth and activity estimates at a case study site in Scotland. There the method identified significantly higher activity (<3 Bq g(-1)) occurring at depth (>0.4m), that conventional gross counting algorithms failed to identify. It was concluded that the method could easily be employed to identify areas of high activity potentially occurring at depth, prior to intrusive investigation using conventional sampling techniques.

Remediating radium contaminated legacy sites: Advances made through machine learning in routine monitoring of "hot" particles.

The extensive use of radium during the 20th century for industrial, military and pharmaceutical purposes has led to a large number of contaminated legacy sites across Europe and North America. Sites that pose a high risk to the general public can present expensive and long-term remediation projects. Often the most pragmatic remediation approach is through routine monitoring operating gamma-ray detectors to identify, in real-time, the signal from the most hazardous heterogeneous contamination (hot particles); thus facilitating their removal and safe disposal. However, current detection systems do not fully utilise all spectral information resulting in low detection rates and ultimately an increased risk to the human health. The aim of this study was to establish an optimised detector-algorithm combination. To achieve this, field data was collected using two handheld detectors (sodium iodide and lanthanum bromide) and a number of Monte Carlo simulated hot particles were randomly injected into the field data. This allowed for the detection rate of conventional deterministic (gross counts) and machine learning (neural networks and support vector machines) algorithms to be assessed. The results demonstrated that a Neural Network operated on a sodium iodide detector provided the best detection capability. Compared to deterministic approaches, this optimised detection system could detect a hot particle on average 10cm deeper into the soil column or with half of the activity at the same depth. It was also found that noise presented by internal contamination restricted lanthanum bromide for this application.