Ductal Carcinoma In Situ with Microinvasion on Core Biopsy: Evaluating Tumor Upstaging Rate, Lymph Node Metastasis Rate, and Associated Predictive Variables.

INTRODUCTION: The role of sentinel lymph node biopsy (SLNB) when ductal carcinoma in situ with microinvasion (DCISM) is identified on core biopsy is unclear. OBJECTIVE: Our aim was to assess the upstage rate to invasive cancer and axillary lymph node metastasis in patients diagnosed with DCISM, and whether predictive variables could be identified that may help inform who would most likely benefit from a surgical axillary evaluation. METHODS: We performed a retrospective review of 70 patients diagnosed with DCISM on core biopsy. Patients with concomitant or prior invasive cancer were excluded. Demographic, clinical, radiographic, histologic, and treatment data were collected. Fisher's exact test and univariable and multivariable logistic regression were performed to identify variables that may be associated with tumor upstaging and nodal metastasis. Time-to-event distributions were summarized using the Kaplan-Meier method. RESULTS: On final surgical pathology, 49 patients (70%) had a final diagnosis of DCISM or T1mi cancer, whereas 21 patients (30%) were upstaged to measurable invasive cancer (> 1 mm). One of 49 patients (2%) with DCISM on final pathology and 4 of 21 patients (19%) with measurable invasive cancer showed sentinel lymph node metastases. CONCLUSION: Although the upstage rate to measurable invasive cancer in our cohort of patients with DCISM on core biopsy was 30%, findings of a positive SLNB remain low at 7%. No predictive variables were identified to inform whether the routine practice of SLNB may be omitted in some patients with DCISM.

Rate of radial scars by core biopsy and upgrading to malignancy or high-risk lesions before and after introduction of digital breast tomosynthesis.

PURPOSE: Radial scars (RS) commonly present mammographically as architectural distortions, but these lesions may be associated with non-invasive and invasive breast cancer. Digital breast tomosynthesis (DBT) has resulted in higher detection rates of architectural distortion particularly in patients with dense breast tissue. We hypothesized that rates of clinically relevant lesions confirmed surgically would be lower in patients who received DBT imaging compared with those who received standard digital breast imaging. METHODS: We performed a retrospective review of 223 patients diagnosed with pure RS by core biopsy and surgical excision before and after DBT was introduced. The rate of upgrading to malignancy or high-risk lesion was evaluated. Demographics, biopsy type, and histologic data were analyzed. Univariable logistic regression analysis was used to identify variables that may be associated with upgrading. RESULTS: The rate of identifying RS increased from 0.04-.13% (P < 0.0001) with DBT imaging. The upgrade rate on surgical specimen to invasive or non-invasive cancer was similar before and after DBT; 6% versus 3%, as were findings of a high-risk lesion; 12% versus 22%. No predictive factors were identified for patients upgraded to malignant neoplasms or high-risk lesions. CONCLUSIONS: The likelihood of identifying RS has increased with DBT imaging, but rates of upgrading to a malignant neoplasm or high-risk lesion were similar to those before DBT. Although the rate of upgrading to malignancy after DBT was low, an excisional biopsy should be considered as 22% of patients were upgraded to high-risk lesions. These patients are candidates for chemoprevention and/or high-risk surveillance.

Changes in margin re-excision rates: Experience incorporating the "no ink on tumor" guideline into practice.

INTRODUCTION: Prior to the "no ink on tumor" SSO/ASTRO consensus guideline, approximately 20% of women with stage I/II breast cancers undergoing breast conservation surgery at our institution underwent margin re-excision. On May 20, 2013, our institution changed the definition of negative margins from 2 mm to "no ink on tumor." METHODS: A retrospective review was conducted of patients who had surgery at our institution with clinical stage I/II breast cancers between June 1, 2011 and May 1, 2015. In the pre-guideline cohort (pre) and post-guideline cohort (post), negative margins were 2 mm and "no ink on tumor," respectively. RESULTS: Implementation of the guideline resulted in a significant decrease in the positive/close margin rate (29.6% pre vs 10.1% post; P < 0.001) and numerical decrease in re-excision rate (20.4% pre vs 16.3% post; P = 0.104). No significant difference was found in local recurrence between the cohorts with limited follow-up (1.2% pre vs 1.5% post; P = 0.787). CONCLUSION: The implementation of the "no ink on tumor" guideline at our institution has resulted in a significant decrease in positive margin rates and a numerical decrease in margin re-excisions. In addition to margin status, surgeons continue to use individual patient and histologic factors to decide for or against margin re-excision.

Reporting of mitotic rate in cutaneous melanoma: A study using the national cancer data base.

BACKGROUND: The seventh edition of the American Joint Commission on Cancer staging manual (AJCC7, published 2009), updated thin cutaneous melanoma staging protocols with the incorporation of mitotic rate (MR). In these patients, higher MR is associated with decreased survival. This study utilizes the National Cancer Data Base (NCDB) to evaluate MR reporting since AJCC7. METHODS: The NCDB was queried for patients with primary cutaneous melanoma from 1998 to 2013. Because MR reporting was infrequent prior to implementing AJCC7, records from 2010 to 2013 were analyzed. Categorical variables were compared with chi-square tests; univariate and multivariate logistic regression models were constructed to determine the effects of covariates on MR reporting. RESULTS: A total of 107,134 patients met inclusion criteria. From 2010 to 2013, MR reporting increased dramatically (64.3-80.9%). On multivariate analysis, factors significantly related to increased MR reporting include later diagnosis year, T-classification (T1a and b vs. T1), facility type (academic vs. other specified types of cancer programs), facility volume, patient income, level of education, and county population (metropolitan vs. urban and rural). CONCLUSIONS: MR reporting increased dramatically after the introduction of AJCC7; however, disparities in reporting remain across facility types. Further investigation of procedures performed in academic settings that may influence reporting of MR is warranted. J. Surg. Oncol. 2017;115:281-286. © 2017 Wiley Periodicals, Inc.

Pediatric and Adolescent Melanoma: A National Cancer Data Base Update.

BACKGROUND: Studies suggest that the biology of pediatric and adolescent melanoma differs from that of adult disease. We report the largest series to date examining the natural history of pediatric and adolescent melanoma. We aim to elucidate the natural history of pediatric and adolescent melanoma and to examine the appropriateness of diagnostic and therapeutic modalities developed for adults and that are currently being used in children. METHODS: A retrospective cohort study was conducted of patients with an index diagnosis of cutaneous non-metastatic melanoma from 1998 to 2011 using the National Cancer Data Base (NCDB; n = 420,416). Three age-based cohorts were analyzed: 1-10 years (pediatric), 11-20 years (adolescent), and ≥21 years (adult). Multivariate analyses were used to identify factors associated with overall survival (OS). RESULTS: Pediatric melanoma patients have longer OS than their adolescent (hazard ratio [HR] 0.50, 95 % CI 0.25-0.98) and adult counterparts (HR 0.11, 95 % CI 0.06-0.21). Adolescents have longer OS than adults. No difference was found in OS in pediatric patients who are node-positive versus node-negative. In pediatric patients, sentinel lymph node biopsy and completion lymph node dissection are not associated with increased OS. In adolescents, nodal positivity is a significant negative prognostic indicator (HR 4.82, 95 % CI 3.38-6.87). CONCLUSIONS: Age-based differences in melanoma outcomes warrant different considerations for diagnostic and therapeutic approaches in each group in order to maximize quality of life while minimizing complications and costs. Prospective, multicenter studies should evaluate the role of diagnostic procedures for pediatric patients.

Chemosaturation with percutaneous hepatic perfusion for unresectable metastatic melanoma or sarcoma to the liver: a single institution experience.

BACKGROUND: Patients with unresectable melanoma or sarcoma hepatic metastasis have a poor prognosis with few therapeutic options. Percutaneous hepatic perfusion (PHP), isolating and perfusing the liver with chemotherapy, provides a promising minimally invasive management option. We reviewed our institutional experience with PHP. METHODS: We retrospectively reviewed patients with unresectable melanoma or sarcoma hepatic metastasis treated with PHP from 2008 to 2013 and evaluated therapeutic response, morbidity, hepatic progression free survival (hPFS), and overall survival (OS). RESULTS: Ten patients were treated with 27 PHPs (median 3). Diagnoses were ocular melanoma (n = 5), cutaneous melanoma (n = 3), unknown primary melanoma (n = 1), and sarcoma (n = 1). Median hPFS was 240 days, 9 of 10 patients (90%) demonstrated stable disease or partial response to treatment. At a median follow up of 11.5 months, 4 of 10 (40%) remain alive. There were no perioperative mortalities. Myelosuppresion was the most common morbidity, managed on an outpatient basis with growth factors. The median hospital stay was 3 days. CONCLUSIONS: Patients with metastatic melanoma and sarcoma to the liver have limited treatment options. Our experience with PHP demonstrates promising results with minimal morbidity and should be considered (pending FDA approval) as a management option for unresectable melanoma or sarcoma hepatic metastasis.

Cutaneous angiosarcoma: a single-institution experience.

BACKGROUND: Cutaneous angiosarcoma (CAS) is a rare, aggressive vascular sarcoma with a poor prognosis, historically associated with 5-year overall survival (OS) rates between 10 and 30 %. METHODS: This is a single-institution retrospective review of patients treated for CAS from 1999-2011. Demographics, primary tumor characteristics, treatment, and outcomes were analyzed. RESULTS: A total of 88 patients were identified (median age 70 years and 57 % female). Median tumor size was 3 cm. Median follow-up was 22 months. The 5-year OS and recurrence-free survival (RFS) were 35.2 and 32.3 %, respectively; median was 22.1 months. Also, 36 patients (41 %) received surgery alone, 7 (8 %) received XRT alone, and 41 (47 %) received surgery and XRT. Of the 67 of 88 patients who were disease-free after treatment, 33 (50 %) recurred (median of 12.3 months). Surgery alone had the highest 5-year OS (46.9 %) and RFS (39.9 %) (p = ns). Four presentation groups were identified: (1) XRT-induced, n = 30 (34 %), 26 of 30 occurred in females with a prior breast cancer, (2) sporadic CAS on head and neck (H/N), n = 38, (3) sporadic CAS on trunk/extremities, n = 13, and (4) Stewart-Treves n = 7. Those with trunk/extremity CAS had the highest 5-year OS (64.8 %), with H/N CAS having the worst 5-year OS (21.5 %). On MV analysis, only tumor size <5 cm correlated with improved OS (p = 0.014). DISCUSSION: In this large series, there appears to be a better overall prognosis than historically reported, especially in Stewart-Treves and CAS on trunk or extremities. While surgery alone was associated with better OS and RFS compared with other treatment modalities, this was not statistically significant. Tumor size was a significant prognostic factor for OS.

Antiviral prevention of sepsis induced cytomegalovirus reactivation in immunocompetent mice.

INTRODUCTION: Immunocompetent patients can reactivate latent cytomegalovirus (CMV) during critical illness and reactivation is associated with significantly worse outcomes. Prior to clinical trials in humans to prove causality, we sought to determine an optimal antiviral treatment strategy. METHODS: Mice latently infected with murine CMV (MCMV) received a septic reactivation trigger and were randomized to receive one of four ganciclovir regimens or saline. Lungs were evaluated for viral transcriptional reactivation and fibrosis after each regimen. Influences of ganciclovir on early sepsis-induced pulmonary inflammation and T-cell activation were studied after sepsis induction. RESULTS: All ganciclovir regimens reduced measurable MCMV transcriptional reactivation, and 10mg/day for 7 or 21 days was most effective. Lower dose (5mg/kg/day) or delayed therapy was associated with significant breakthrough reactivation. Higher doses of ganciclovir given early were associated with the lowest incidence of pulmonary fibrosis, and delay of therapy for 1 week was associated with significantly worse pulmonary fibrosis. Although bacterial sepsis induced activation of MCMV-specific pulmonary T-cells, this activation was not influenced by ganciclovir. CONCLUSION: These results suggest that antiviral treatment trials in humans should use 10mg/kg/day ganciclovir administered as early as possible in at-risk patients to minimize reactivation events and associated pulmonary injury.