Analysis of Time Between Skin Lesion and Lymph Node Biopsies and Lymph Node Metastasis in Patients With Melanoma.

This cohort study assesses whether increasing time to surgery is associated with sentinel lymph node status in patients with cutaneous melanoma stage T1b or higher.

Adjuvant Therapy for Stage III Melanoma Without Immediate Completion Lymph Node Dissection.

INTRODUCTION: For patients with stage III melanoma with occult lymph node metastasis, the use of adjuvant therapy is increasing, and completion lymph node dissection (CLND) is decreasing. We sought to evaluate the use of modern adjuvant therapy and outcomes for patients with stage III melanoma who did not undergo CLND. METHODS: Patients with a positive SLNB from 2015 to 2020 who did not undergo CLND were evaluated retrospectively. Nodal recurrence, recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and melanoma-specific survival were evaluated. RESULTS: Among 90 patients, 56 (62%) received adjuvant therapy and 34 (38%) underwent observation alone. Patients who received adjuvant therapy were younger (mean age: 53 vs. 65, p < 0.001) and had higher overall stage (Stage IIIb/c 75% vs. 54%, p = 0.041). Disease recurred in 12 of 34 patients (35%) in the observation group and 11 of 56 patients (20%) in the adjuvant therapy group. The most common first site of recurrence was distant recurrence alone (5/34 patients) in the observation group and nodal recurrence alone (8/90 patients) in the adjuvant therapy group. Despite more adverse nodal features in the adjuvant therapy group, 24-month nodal recurrence rate and RFS were not significantly different between the adjuvant and observation cohorts (nodal recurrence rate: 26% vs. 20%, p = 0.68; RFS: 75% vs. 61%, p = 0.39). Among patients with stage IIIb/c disease, adjuvant therapy was associated with a significantly improved 24-month DMFS (86% vs. 59%, p = 0.04). CONCLUSIONS: In this early report, modern adjuvant therapy in patients who forego CLND is associated with longer DMFS among patients with stage IIIb/c disease.

Increasing omission of radiation therapy and sentinel node biopsy in elderly patients with early stage, hormone-positive breast cancer.

Prospective evidence demonstrates that there is limited benefit of axillary staging with sentinel lymph node biopsy (SLNB) or radiation therapy (RT) in patients over age 70 with clinical stage I, hormone-positive breast cancer. The clinical impact of this literature is unknown. Our hypothesis is that omission of SLNB and RT has increased over time in these patients, and patient and tumor characteristics can predict when omission strategies are used. A single-center tumor registry was queried for all patients over age 70 with ER+, Her2/neu-negative, clinical T1N0 invasive breast cancer from 2009 to 2017, who underwent breast conservation (n = 141). Date of treatment, age, tumor characteristics, use of SLNB, and use of RT were evaluated. The trend of treatment strategy over time was evaluated. Multivariable analysis was performed on the subgroup of patients after publication of the long-term follow-up CALGB 9343 data1 . Patients undergoing treatment with omission of RT and SLNB increased over the study period (P = .0006). Patients who did not receive RT were older (78.76 years ± 5.48 vs 73.37 ± 3.63, P < .01). There was no difference between tumor grade and size between uses of RT. Of patients who received SLNB (n = 84), only 3 (3.5%) had a positive LN. On multivariable analysis of patients who were treated after publication of the CALGB 9343 data (2014-2017), only age was predictive of being treated with RT (OR, 0.77; 95% CI, 0.67-0.88). Omission of both RT and SLNB are increasing in clinical practice in appropriately selected patients. The likelihood that patients are offered omission of these interventions increases with age. Low nodal positivity rates suggest that this strategy may be underutilized. Tumor grade and size were not predictive of omission of RT in this group of low-risk patients. Long-term data are needed as these approaches are increasingly adopted.

Utility of Quantitative SPECT/CT Lymphoscintigraphy in Guiding Sentinel Lymph Node Biopsy in Head and Neck Melanoma.

PURPOSE: To investigate the use of advanced SPECT/CT quantification in guiding surgical selection of positive sentinel lymph nodes (SLNs) in head and neck melanoma. METHODS: We retrospectively reviewed data from patients with cutaneous head and neck melanoma who underwent lymphoscintigraphy with SPECT/CT prior to SLN biopsy (SLNB). Quantification of radiotracer uptake from SPECT/CT data was performed using in-house segmentation software. SLNs identified using SPECT/CT were compared to SLNs identified surgically using an intraoperative γ-probe. A radioactivity count threshold using SPECT/CT for detecting a positive SLN was calculated. RESULTS: One hundred and five patients were included. Median number of SLNs detected was 3/patient with SPECT/CT and 2/patient with intraoperative γ-probe. The hottest node identified by SPECT/CT and intraoperative γ-probe were identical in 85% of patients. All 20 histologically positive SLNs were identified by SPECT/CT and γ-probe. On follow-up, all nodal recurrences occurred at lymph node levels with the hottest node identified by SPECT/CT and either the hottest or second hottest node identified by γ-probe during SLNB. Using our data, a SPECT/CT radioactivity count threshold of 20% would eliminate the unnecessary removal of 11% of SPECT/CT identified nodes and 12% of intraoperatively detected nodes. CONCLUSION: Utilizing SPECT/CT quantification, we propose that a radioactivity count threshold can be developed to help guide the selective removal of lymph nodes in head and neck SLNB. Furthermore, the nodal level containing the hottest node identified by SPECT/CT quantification must be thoroughly investigated for SLNs and undergo careful follow-up and surveillance for recurrence.

A nomogram to predict node positivity in patients with thin melanomas helps inform shared patient decision making.

OBJECTIVE: To develop a nomogram to estimate the probability of positive sentinel lymph node (+SLN) for patients with thin melanoma and to characterize its potential impact on sentinel lymph node biopsy (SLNB) rates. METHODS: Patients diagnosed with thin (0.5-1.0 mm) melanoma were identified from the National Cancer Database 2012 to 2015. A multivariable logistic regression model was used to examine factors associated with +SLN, and a nomogram to predict +SLN was constructed. Nomogram performance was evaluated and diagnostic test statistics were calculated. RESULTS: Of the 21 971 patients included 10 108 (46.0%) underwent SLNB, with a 4.0% +SLN rate. On multivariable analysis, age, Breslow thickness, lymphovascular invasion, ulceration, and Clark level were significantly associated with SLN status. The area under the receiver operating curve was 0.67 (95% confidence interval, 0.65-0.70). While 15 249 (69.4%) patients had either T1b tumors or T1a tumors with at least one adverse feature, only 2846 (13.0%) had a nomogram predicted probability of a +SLN ≥5%. Using this cut-off, the indication for a SLNB in these patients would be reduced by 81.3% as compared to the American Joint Committee on Cancer 8th edition staging criteria. CONCLUSIONS: The risk predictions obtained from the nomogram allow for more accurate selection of patients who could benefit from SLNB.

Frequency and implications of occipital and posterior auricular sentinel lymph nodes in scalp melanoma.

BACKGROUND: Patients with scalp melanoma have poor oncologic outcomes compared with those with other cutaneous sites. Sentinel lymph node (SLN) biopsy provides prognostic information but is challenging in the head and neck. We explore the anatomic distribution of scalp melanoma and describe the most common sites of SLN drainage and of SLN metastatic disease. METHODS: Retrospective review of scalp melanoma patients who underwent SLN biopsy. Melanoma location was classified as frontal, coronal apex, coronal temporal, or posterior scalp. SLN location was classified by lymph node level and region. RESULTS: We identified 128 patients with scalp melanoma. The most common primary tumor location was the posterior scalp (43%) and the most frequent SLN drainage site was the level 2 lymph node basin (48%). Total 31 patients (24%) had metastatic disease in an SLN. Scalp SLNs, classified as being in the posterior auricular or occipital region, were localized in 26% of patients. For patients in which a scalp SLN was identified, 30% had a positive scalp SLN (n = 10). CONCLUSIONS: Scalp SLNs are frequent drainage sites for scalp melanoma and, when found, have a 30% chance of harboring metastatic disease. Surgeons, radiologists, and pathologists should be vigilant in identifying, removing, and analyzing scalp SLNs.

Postbiopsy Pigmentation is Prognostic in Head and Neck Melanoma.

PURPOSE: To assess postbiopsy pigmentation (PBP) as a prognostic feature in patients with cutaneous head and neck (H&N) melanoma. METHODS: Retrospective review of patients undergoing sentinel lymph node biopsy (SLNB) for H&N melanoma (1998-2018). PBP was defined as visible remaining pigment at the scar or biopsy site that was documented on physical exam by both a medical oncologist and a surgeon at initial consultation. Variables associated with disease-free survival (DFS) and overall survival (OS) were analyzed using multivariable Cox proportional hazards models. RESULTS: Among 300 patients, 34.3% (n = 103) had PBP and 44.7% (n = 134) had microscopic residual disease on final pathology after wide local excision. Prognostic factors associated with DFS included advanced age, tumor depth, ulceration, PBP, and positive SLNB (p < 0.05). Patients with PBP fared worse than their counterparts without PBP in 5-year DFS [44.1% (31.1-56.3%) vs. 73.0% (64.1-80.0%); p < 0.001] and 5-year OS [65.0% (50.0-76.6%) vs. 83.6% (75.7-89.2%); p = 0.005]. After multivariable adjustment, PBP remained associated with shorter DFS [hazard ratio (HR) 1.72, 95% confidence interval (CI) 1.01-2.93; p = 0.047], but was not prognostic of OS. CONCLUSIONS: In patients with H&N melanoma, PBP is associated with significantly shorter DFS. Patients with PBP may warrant greater consideration for SLNB and closer postoperative surveillance.

SPECT/CT Adds Distinct Lymph Node Basins and Influences Radiologic Findings and Surgical Approach for Sentinel Lymph Node Biopsy in Head and Neck Melanoma.

BACKGROUND: Planar lymphoscintigraphy (PL) has a lower detection rate of sentinel lymph nodes (SLNs) in head and neck melanoma compared with other sites. We assessed situations when single-photon emission computed tomography/computed tomography (SPECT/CT) identified nodes not seen by PL. We also evaluated the impact of SPECT/CT on surgical approach and oncologic outcomes. METHODS: Patients who underwent SLN biopsy (SLNB) for head and neck melanoma with PL and SPECT/CT between November 2011 and December 2016 were included. Surgeons and radiologists completed a real-time survey inquiring about the utility of SPECT/CT. Patients were divided into two groups: patients with nodal basins identified by both PL and SPECT/CT ('PL + SPECT/CT'), and patients in whom SPECT/CT identified additional nodal basins not seen on PL ('SPECT/CT only'). Patient demographics and long-term outcomes including follow-up duration, recurrence, and survival are described. RESULTS: In the PL + SPECT/CT group, 73 (61.9%) patients were included and 45 (38.1%) patients were included in the SPECT/CT-only group. SPECT/CT added 51 basins to those seen on PL, primarily in the supraclavicular region (43.1%). Eighteen patients had positive node(s) in the PL + SPECT/CT group compared with two patients in the SPECT/CT-only group. Surgeons reported that 81% of the time, SPECT/CT influenced the location of incision for SLNB. CONCLUSIONS: SPECT/CT influences the location of incision and contributes most to identification of nodes in the supraclavicular region. It also detects additional SLN basins when compared with PL. Further studies are necessary to determine when these additional basins require sampling.

Patterns of Fractionation and Boost Usage in Adjuvant External Beam Radiotherapy for Ductal Carcinoma in Situ in the United States.

BACKGROUND: While the roles of hypofractionated (HFxn) radiotherapy and lumpectomy boost in the adjuvant management of invasive breast cancer are supported by the results of clinical trials, randomized data supporting their use for ductal carcinoma in situ (DCIS) are forthcoming. We sought to evaluate current national trends and identify factors associated with HFxn and boost usage using the National Cancer Database. PATIENTS AND METHODS: We queried the National Cancer Database for women diagnosed with DCIS from 2004 to 2014 undergoing external beam radiotherapy after breast conservation surgery. Patients were categorized as receiving either conventional fractionation (CFxn) or HFxn and as either receiving or not receiving a boost. Multiple logistic regression was performed to identify demographic, clinical, and treatment factor associations. RESULTS: A total of 101,615 women were identified, with 87,641 (86.2%) receiving CFxn, 13,974 (13.8%) receiving HFxn, and most patients in each group (84.9% and 57.7%, respectively) receiving a boost. Implementation of HFxn increased from 4.3% in 2004 to 33.0% in 2014, and the use of a boost declined from 83.3% to 74.6%. HFxn receipt was independently associated with later year of diagnosis, older age, higher income, greater distance from treatment facility, greater facility volume, academic facility type, Western residence, smaller lesions, and nonreceipt of a boost. Factors associated with boost receipt included earlier year of diagnosis, younger age, higher income, community facility type, adverse pathologic features, and nonreceipt of HFxn. CONCLUSION: Although CFxn with a boost remains the most common external beam radiotherapy strategy for DCIS, implementation of HFxn without a boost appears to be increasing. Practice patterns at present seem to be driven by guidelines for invasive breast cancer and nonclinical factors.

Re-excision rates after breast conserving surgery following the 2014 SSO-ASTRO guidelines.

BACKGROUND: In 2014, SSO-ASTRO published guidelines which recommended "no ink on tumor" as adequate margins for patients undergoing breast conservation for invasive breast cancer. In 2016, new SSO-ASTRO-ASCO guidelines recommended 2 mm margins for DCIS. We evaluated whether these guidelines affected re-excision rates at our institution. METHODS: Patients treated with breast conservation surgery from January 1, 2010-March 1, 2016 were identified. Re-excision rates, tumor characteristics, and presence of residual disease were recorded. The 2016 guidelines were retrospectively applied to the same cohort and expected re-excision rates calculated. RESULTS: Re-excision rates did not significantly decline before and after 2014 guideline adoption (11.9% before, 10.9% after; p = 0.65) or when the 2016 guidelines were retrospectively applied (8.4%; p = 0.10). CONCLUSIONS: The 2014 and 2016 guidelines had minimal impact on our re-excision rates, as most re-excisions were done for DCIS and 2016 guidelines supported our prior institutional practices of 2 mm margins for these patients.

Implications of Sentinel Lymph Node Drainage to Multiple Basins in Head and Neck Melanoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) for head and neck melanoma is challenging due to unpredictable drainage. We sought to determine the frequency of drainage to multiple lymphatic basins and asked if this was associated with prognosis in a large, single-center cohort. METHODS: We queried patients diagnosed with head and neck melanomas who had a SLNB performed from January 1998 to April 2016. Demographic and clinical characteristics were compared using Student's t test, Pearson chi-square analysis, log-rank test, Wilcoxon-Mann-Whitney test, and Kaplan-Meier curves. RESULTS: We identified 269 patients with head and neck melanoma that had SLNBs performed in the following locations: 223 neck, 92 parotid/preauricular, 29 occipital/posterior auricular, 1 axilla. There were 68 (25%) patients who had drainage to multiple basins. These patients were similar to those with single basin drainage in age, gender distribution, Breslow depth, and percent with a positive SLNB (all p > 0.05). Fewer patients with drainage to multiple basins had a completion lymph node dissection (CLND, p = 0.03). A trend toward increased 3-year locoregional recurrence was seen for patients with drainage to multiple basins in univariate analysis (27% vs. 18%, p = 0.10) but was lost in multivariate analysis (p = 0.49), possibly because of higher recurrence rates in patients with positive nodes but no CLND (p = 0.02). No difference was detected for distant recurrence or overall survival based on SLN drainage. CONCLUSIONS: Head and neck melanoma SLNB drainage to multiple basins is common. Drainage to multiple basins does not seem to be associated with increased sentinel lymph node positivity, locoregional recurrence, distant recurrence, or survival.

Breast Cancer Following Radiation for Hodgkin Lymphoma: Clinical Scenarios and Risk-Reducing Strategies.

Since most patients with Hodgkin lymphoma survive their disease, long-term issues such as development of second primary malignancies arise, especially in patients treated with multimodal therapy including radiation therapy plus chemotherapy. The risk of breast cancer is significantly elevated in women exposed to high-dose ionizing radiation to the chest before age 40. The case of a 48-year-old patient with a lump in her right breast is presented as a clinical scenario in this article. We review available strategies for screening and risk reduction through chemoprevention or risk-reducing surgery, as well as challenges for management of breast cancer in patients with prior exposure to radiation for Hodgkin lymphoma. The Children's Oncology Group clinical practice guidelines for long-term follow-up care of pediatric cancer survivors provide recommendations that have been endorsed by American and European oncologists.

SPECT/CT Improves Detection of Metastatic Sentinel Lymph Nodes in Patients with Head and Neck Melanoma.

BACKGROUND: A positive sentinel lymph node (SLN) is the most important prognostic factor for predicting survival in cutaneous melanoma. This study aimed to evaluate how the addition of single-photon emission computed tomography (SPECT) and computed tomography (CT) to planar lymphoscintigraphy (PL) alters SLN identification, yield, and localization of metastatic nodes in head and neck melanoma. METHODS: This retrospective review examined patients undergoing SLN biopsy for cutaneous melanoma of the head and neck between July 2003 and December 2015. Patient demographics and pathologic outcomes were compared for patients undergoing SPECT-CT versus PL. A multivariable logistic regression analysis was used to identify factors associated with the identification of a positive SLN. RESULTS: Among 176 patients undergoing SLN biopsy, 91 underwent PL and 85 underwent SPECT-CT and PL. The patients in the SPECT-CT group were older than the PL patients (p = 0.050) but the groups did not differ in gender (p = 0.447), Breslow thickness (p = 0.744), or total number of SLNs identified (p = 0.633). As shown by the multivariate regression analysis, only Breslow thickness [odds ratio (OR) 1.47; 95 % confidence interval (CI) 1.17-1.84] and SPECT-CT (OR 3.58; 95 % CI 1.24-10.4) were associated with a positive SLN. CONCLUSION: The use of SPECT-CT for patients with head and neck cutaneous melanoma significantly increases the likelihood of retrieving a positive SLN. Long-term follow-up evaluation is needed for further definition of the impact that SPECT-CT has on recurrence and survival.

Association of sentinel lymph node diameter with melanoma metastasis.

BACKGROUND: Lymph nodes are an important part of the immune system and the size of the lymph node reflects local immunologic activity. The purpose of this study was to examine the association between sentinel lymph node (SLN) size and the presence of nodal metastasis in patients with melanoma. METHODS: Retrospective review of a prospectively maintained database of patients undergoing SLN biopsy for cutaneous melanoma between February 1995 and January 2013. The maximum pathologic diameter and the volume of the largest node was used. A nodal diameter of 1.5 cm, included in 2 interquartile ranges of both positive and negative SLNs, was used as the cutoff for multivariate regression. RESULTS: Of 1,017 SLN biopsies, 826 (81%) had complete size measurements and were included in the analysis. Patients with a positive SLN were younger (median 50 vs 53 years, P = .032), had deeper primary lesions (2 vs 1.4 mm, P < .001), and had larger SLN volume (.8 vs .6 cc, P = .009) or maximum diameter (1.9 vs. 1.6 cm, P = .03). Sex, pathologic ulceration, mitosis, and the type or location of the primary was not statistically different. On multivariate analysis; age, depth of primary, and both SLN volume and maximum diameter remained significant. An SLN greater than 1.5 cm in maximum diameter has a 60% increased odds ratio of being positive after adjusting for age, sex, and depth of primary lesion (P = .046). CONCLUSIONS: Larger SLN maximum diameter is associated with nodal positivity independent of age, sex, depth of primary lesion, and location of SLN biopsy. The etiology and significance of larger SLNs warrant further analysis.

Breast Cancer Risk Reduction, Version 2.2015.

Breast cancer is the most frequently diagnosed malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. To assist women who are at increased risk of developing breast cancer and their physicians in the application of individualized strategies to reduce breast cancer risk, NCCN has developed these guidelines for breast cancer risk reduction.

Analysis of melanoma recurrence following a negative sentinel lymph node biopsy.

Little attention has been paid to the characteristics and outcomes of patients who experience distant, local or regional recurrence of melanoma following a negative sentinel lymph node biopsy. This article aims to review the published literature on the topic and presents some general summaries regarding this patient population. Patients who experience a disease recurrence following a negative sentinel lymph node biopsy have a worse overall survival compared with patients with a positive sentinel lymph node biopsy. The implications and possible explanations for these findings are discussed in order to both underscore the need for in-depth investigation of local, regional or distant melanoma recurrence among patients following a true negative sentinel lymph node biopsy, as well as increased efforts to minimize the rate of false negative sentinel lymph node biopsies.

Metabotropic glutamate receptor-1 contributes to progression in triple negative breast cancer.

TNBC is an aggressive breast cancer subtype that does not express hormone receptors (estrogen and progesterone receptors, ER and PR) or amplified human epidermal growth factor receptor type 2 (HER2), and there currently exist no targeted therapies effective against it. Consequently, finding new molecular targets in triple negative breast cancer (TNBC) is critical to improving patient outcomes. Previously, we have detected the expression of metabotropic glutamate receptor-1 (gene: GRM1; protein: mGluR1) in TNBC and observed that targeting glutamatergic signaling inhibits TNBC growth both in vitro and in vivo. In this study, we explored how mGluR1 contributes to TNBC progression, using the isogenic MCF10 progression series, which models breast carcinogenesis from nontransformed epithelium to malignant basal-like breast cancer. We observed that mGluR1 is expressed in human breast cancer and that in MCF10A cells, which model nontransformed mammary epithelium, but not in MCF10AT1 cells, which model atypical ductal hyperplasia, mGluR1 overexpression results in increased proliferation, anchorage-independent growth, and invasiveness. In contrast, mGluR1 knockdown results in a decrease in these activities in malignant MCF10CA1d cells. Similarly, pharmacologic inhibition of glutamatergic signaling in MCF10CA1d cells results in a decrease in proliferation and anchorage-independent growth. Finally, transduction of MCF10AT1 cells, which express c-Ha-ras, using a lentiviral construct expressing GRM1 results in transformation to carcinoma in 90% of resultant xenografts. We conclude that mGluR1 cooperates with other factors in hyperplastic mammary epithelium to contribute to TNBC progression and therefore propose that glutamatergic signaling represents a promising new molecular target for TNBC therapy.