A Comprehensive Assessment of Radial Scars on Core Needle Biopsy in Patients with or without Breast Cancer: Upgrade Rate and Implications on Management.

BACKGROUND: Radial scars/radial sclerosing lesions (RS) are benign breast lesions identified on core needle biopsy (CNB) which can upgrade to malignancy at excision. There is limited data on RS detection and upgrade rates with more sensitive imaging such as magnetic resonance imaging (MRI) and none during their detection for breast cancer workup and its implication on patient treatment decisions. METHODS: A retrospective institutional study of RS diagnosed on CNB between January 2008 and December 2017 was conducted. Clinicopathologic and radiologic features of RS, patient treatment decisions, upgrade rates and long-term follow-up were examined. RESULTS: We identified 133 patients with RS on CNB, of whom 106 opted for surgery for an upgrade rate to malignancy of 1.9%, 2 patients. Radial scar was diagnosed on mammogram in 60%, MRI in 25% and ultrasound in 15% of patients. In this cohort, 32 patients had their RS detected during breast cancer workup (coexistent group) and they were more likely to have their radial scar detected by MRI (60% vs. 14%, P < .001) and undergo more extensive surgery (94% vs. 75%, P = .02). Among the 27 patients electing observation of their RS, only one (3.7%) developed breast cancer. CONCLUSIONS: Our results show an extremely low upgrade rate to malignancy of RS, regardless if there is coexisting breast cancer elsewhere. Despite this, RS still prompted more extensive surgical excisions. The findings do not support excision of RS even among breast cancer patients when identified at a separate site from their cancer.

Lymphatic Microsurgical Preventive Healing Approach for the Primary Prevention of Lymphedema: A 4-Year Follow-Up.

BACKGROUND: Axillary lymph node dissection (ALND) remains the leading cause of lymphedema nationally, and there is still no cure for the disease. The lymphatic microsurgical preventive healing approach (LYMPHA) is a promising option for lymphedema prophylaxis in patients undergoing ALND, but long-term outcomes of the LYMPHA are not well established. METHODS: The authors conducted a retrospective review of patients undergoing ALND at their center from November of 2012 to November of 2016 and assembled two cohorts, those who received the LYMPHA and those who did not (non-LYMPHA). Patient data were collected to evaluate lymphedema risk and long-term lymphedema incidence of each group. RESULTS: Forty-five women were included in both our LYMPHA and non-LYMPHA cohorts. Mean body mass index (27.7 kg/m2 versus 29.9 kg/m2; P = 0.15) and radiation therapy rates (60.0% versus 68.9%; P = 0.51) did not differ between groups. Non-LYMPHA patients underwent complete mastectomy more frequently than LYMPHA patients (97.8% versus 77.8%; P = 0.007), but had a similar number of nodes removed during ALND (14.4 versus 15.8; P = 0.32). Median follow-up time was greater than 4 years for both LYMPHA and non-LYMPHA groups (57.0 months versus 63.0 months; P = 0.07). Overall, lymphedema incidence was 31.1% in the LYMPHA group and 33.3% in the non-LYMPHA group (P > 0.99). No significant differences in lymphedema incidences were observed between the LYMPHA and non-LYMPHA groups for patients with obesity, patients who received radiation therapy, or patients with obesity who also received radiation therapy (P > 0.05 for all subgroups). CONCLUSIONS: The LYMPHA may not prevent lymphedema long-term in patients who undergo ALND. More long-term studies are needed to determine the true potential of the procedure. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Optical coherence tomography holds promise to transform the diagnostic anatomic pathology gross evaluation process.

SIGNIFICANCE: Real-time histology can close a variety of gaps in tissue diagnostics. Currently, gross pathology analysis of excised tissue is dependent upon visual inspection and palpation to identify regions of interest for histopathological processing. Such analysis is limited by the variable correlation between macroscopic and microscopic findings. The current standard of care is costly, burdensome, and inefficient. AIM: We are the first to address this gap by introducing optical coherence tomography (OCT) to be integrated in real-time during the pathology grossing process. APPROACH: This is achieved by our high-resolution, ultrahigh-speed, large field-of-view OCT device designed for this clinical application. RESULTS: We demonstrate the feasibility of imaging tissue sections from multiple human organs (breast, prostate, lung, and pancreas) in a clinical gross pathology setting without interrupting standard workflows. CONCLUSIONS: OCT-based real-time histology evaluation holds promise for addressing a gap that has been present for >100 years.

Risk factors for breast cancer-related lymphedema in patients undergoing 3 years of prospective surveillance with intervention.

BACKGROUND: To evaluate risk factors (treatment-related, comorbidities, and lifestyle) for breast cancer-related lymphedema (BCRL) within the context of a Prospective Surveillance and Early Intervention (PSEI) model of care for subclinical BCRL. METHODS: The parent randomized clinical trial assigned patients newly diagnosed with breast cancer to PSEI with either bioimpedance spectroscopy (BIS) or tape measurement (TM). Surgical, systemic and radiation treatments, comorbidities, and lifestyle factors were recorded. Detection of subclinical BCRL (change from baseline of either BIS L-Dex ≥6.5 or tape volume ≥ 5% and < 10%) triggered an intervention with compression therapy. Volume change from baseline ≥10% indicated progression to chronic lymphedema and need for complex decongestive physiotherapy. In this secondary analysis, multinomial logistic regressions including main and interaction effects of the study group and risk factors were used to test for factor associations with outcomes (no lymphedema, subclinical lymphedema, progression to chronic lymphedema after intervention, progression to chronic lymphedema without intervention). Post hoc tests of significant interaction effects were conducted using Bonferroni-corrected alphas of .008; otherwise, an alpha of .05 was used for statistical significance. RESULTS: The sample (n = 918; TM = 457; BIS = 461) was female with a median age of 58.4 years. Factors associated with BCRL risk included axillary lymph node dissection (ALND) (p < .001), taxane-based chemotherapy (p < .001), regional nodal irradiation (RNI) (p ≤ .001), body mass index >30 (p = .002), and rurality (p = .037). Mastectomy, age, hypertension, diabetes, seroma, smoking, and air travel were not associated with BCRL risk. CONCLUSIONS: Within the context of 3 years of PSEI for subclinical lymphedema, variables of ALND, taxane-based chemotherapy, RNI, body mass index >30, and rurality increased risk.

Efficacy of a password-protected, pill-dispensing device with mail return capacity to enhance disposal of unused opioids after cancer surgery.

BACKGROUND: Opioid misuse is a public health crisis, and unused postoperative opioids are an important source. Although 70% of pills prescribed go unused, only 9% are discarded. This study evaluated whether an inexpensive pill-dispensing device with mail return capacity could enhance disposal of unused opioids after cancer surgery. METHODS: A prospective pilot study was conducted among adult patients who underwent major cancer-related surgery. Patients received opioid prescriptions in a mechanical device (Addinex) linked to a smartphone application (app). The app provided passwords on a prescriber-defined schedule. Patients could enter a password into the device and receive a pill if the prescribed time had elapsed. Patients were instructed to return the device and any unused pills in a disposal mailer. The primary end point was feasibility of device return, defined as ≥50% of patients returning the device within 6 weeks of surgery. Also explored was total pill use and return as well as patient satisfaction. RESULTS: Among 30 patients enrolled, the majority (n = 24, 80%) returned the device, and 17 (57%) returned it within 6 weeks of surgery. In total, 567 opioid pills were prescribed and 170 (30%) were used. Of 397 excess pills, 332 (84% of unused pills, 59% of all pills prescribed) were disposed of by mail. Among 19 patients who obtained opioids from the device, most (n = 14, 74%) felt the benefits of the device justified the added steps involved. CONCLUSIONS: Use of an inexpensive pill-dispensing device with mail return capacity is a feasible strategy to enhance disposal of unused postoperative opioids.

Shaves off the Cavity or Specimen in Lumpectomy for Breast Cancer.

INTRODUCTION: Re-excision for positive margins (margins where tumor is positive) after breast conserving surgery (BCS) is common and burdensome for breast cancer patients. Routine shave margins can reduce positive margins and re-excision rates. Cavity shaving margin (CSM) removes margins from the lumpectomy cavity edges, whereas specimen shave margin (SSM) requires ex vivo removal of margins from the resected specimen. METHODS: We assessed breast cancer patients undergoing BCS who received CSM or SSM procedures from 2017 to 2019. CSM and SSM techniques were compared by analyzing positive rates of primary and final shaved margins, re-excision rates, and tissue volumes removed. RESULTS: Of 116 patients included in this study, 57 underwent CSM and 59 underwent SSM. Primary margins were positive or close in 19 CSM patients and 21 SSM patients (33% versus 36%; P = 0.798). Seventeen CSM patients had a tumor in shaved margin specimens, compared to four patients for SSM (30% versus 7%; P < 0.001); however, final shave margins were similar (5% versus 5%; P = 0.983). Volumes of shave specimens were higher with SSM (40.7 versus 13.4 cm3; P < 0.001), but there was no significant difference in the total volume removed (146.8 versus 134.4 cm3; P = 0.540). For tumors 2 cm or larger, the total volume removed (140 versus 206 cm3; P = 0.432) and rates of final margin positivity (7.5% versus 0%; P = 0.684) were similar for both techniques. CONCLUSIONS: CSM and SSM are effective techniques for achieving low re-excision rates. Our findings suggest that surgeons performing either CSM or SSM may maintain operative preferences and achieve similar results.

When the clipped node goes missing, CT guided SAVI SCOUT placement: A novel approach for localizing soft tissue targets.

Axillary staging in breast cancer is performed with physical exam and axillary imaging. Suspicious lymph nodes are biopsied and clipped prior to surgery to identify the previously biopsied node during surgery. Conventional mapping techniques of blue dye and radioisotope do not always accurately identify the clipped lymph node and therefore many techniques have been described to improve the identification of the clipped lymph node. Most of these techniques rely on axillary ultrasound to identify the previously biopsied lymph node or previously placed clip. A marker such as a fiducial reflector is then placed percutaneously. In this case report we describe a novel technique of Computed tomography (CT) identification of a previously clipped lymph node with CT guided placement of a fiducial reflector (SAVI SCOUT). The SAVI SCOUT was then identified and successfully excised with the previously biopsied lymph node. A PRECIS: CT guided placement of SAVI SCOUT is a novel technique for the identification and retrieval of a previously biopsied axillary lymph node in breast cancer patients.

An Open-Label, Randomized, Multi-Center Study Comparing the Sequence of High Dose Aldesleukin (Interleukin-2) and Ipilimumab (Yervoy) in Patients with Metastatic Melanoma.

Combination immunotherapy with sequential administration may enhance metastatic melanoma (MM) patients with long-term disease control. High Dose Aldesleukin/Recombinant Interleukin-2 (HD rIL-2) and ipilimumab (IPI) offer complementary mechanisms against MM. This phase IV study assessed the sequenced use of HD rIL-2 and IPI in MM patients. Eligible Stage IV MM patients were randomized to treatment with either two courses of HD rIL-2(600,000 IU/kg) followed by four doses of IPI 3 mg/kg or vice-versa. The primary objective was to compare one-year overall survival (OS) with historical control (46%, Hodi et al., NEJM 2010). Secondary objectives were 1-year progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) profile. Evaluable Population (EP) included patients who received at least 50% of planned treatment with each drug. Thirteen and 16 patients were randomized to receive HD rIL-2 first, and IPI first, respectively. One-year OS rate was 75% for intention to treat population. Eighteen patients were included in EP, 8 in HD rIL-2, 10 in IPI first arm. In EP, 1-year OS, PFS and ORR rates were 87%, 68%, and 50%, respectively. The frequency of AEs was similar in both arms with 13 patients experiencing Grade 3 or higher AEs, 3 resulting in the end of study participation. There was one HD rIL-2-related death, from cerebral hemorrhage due to thrombocytopenia. In this study with small sample size, HD rIL-2 and IPI were safe to administer sequentially in MM patients and showed more than additive effects. 1-year OS was superior to that of IPI alone from historical studies.

Complication Rates After Intraoperative Radiation Therapy: Do Applicator Size and Distance to Skin Matter?

BACKGROUND: Intraoperative radiation therapy (IORT) has gained popularity for early stage breast cancer treatment. Few studies have examined the relationship between complications and both demographic and technical factors. The objective of the current study was to determine if applicator size or distances to the skin were significant risk factors for complications. METHODS: Data was prospectively collected on patients who underwent lumpectomy followed by IORT from November 1, 2013 to August 31, 2018. Exclusion criteria included any prior radiation exposure or personal history of breast cancer. Comorbid conditions such as body mass index, diabetes, and smoking as well as technical specifications such as applicator size and distances to the skin were included for investigation. Student's t-test, Fisher's exact test, and odds ratios were utilized for statistical analysis. RESULTS: The study was comprised of 219 patients. None developed Clavien-Dindo grade 2 or above complications. Of 21.0% (n = 46) had minor complications. The most common complication was a palpable breast seroma (n = 37). Diabetes was the only comorbid condition with increased risk for complications (OR 3.2; 95% CI1.3-7.5; P = 0.008). The applicator sizes and average skin distances were similar between groups. Surprisingly, the closest skin distance was not a significant risk factor for post-operative complications (1.4 +/- 1.6 versus 1.4 +/- 1.9 cm; P = 1.0). CONCLUSION: Neither applicator size nor the closest skin distance were associated with increased complications. Traditionally described risk factors such as BMI and smoking were not predictive. This data provides support for potentially expanding the utilization for IORT without increasing complications.

Automated digital TIL analysis (ADTA) adds prognostic value to standard assessment of depth and ulceration in primary melanoma.

Accurate prognostic biomarkers in early-stage melanoma are urgently needed to stratify patients for clinical trials of adjuvant therapy. We applied a previously developed open source deep learning algorithm to detect tumor-infiltrating lymphocytes (TILs) in hematoxylin and eosin (H&E) images of early-stage melanomas. We tested whether automated digital (TIL) analysis (ADTA) improved accuracy of prediction of disease specific survival (DSS) based on current pathology standards. ADTA was applied to a training cohort (n = 80) and a cutoff value was defined based on a Receiver Operating Curve. ADTA was then applied to a validation cohort (n = 145) and the previously determined cutoff value was used to stratify high and low risk patients, as demonstrated by Kaplan-Meier analysis (p ≤ 0.001). Multivariable Cox proportional hazards analysis was performed using ADTA, depth, and ulceration as co-variables and showed that ADTA contributed to DSS prediction (HR: 4.18, CI 1.51-11.58, p = 0.006). ADTA provides an effective and attainable assessment of TILs and should be further evaluated in larger studies for inclusion in staging algorithms.

Case of Merkel cell carcinoma in a patient with pre-existing ILD.

Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin with high rates of local recurrence and distant metastases despite treatment with traditional cytotoxic chemotherapies. The recent advances in immunotherapy, including the use of immune checkpoint blockade (ICB) has revolutionized treatment for this disease and resulted in durable responses for some patients. However, many patients, due to underlying conditions, have been insufficiently evaluated for potential use of immunotherapy. Here we present a case of ICB treatment with Programmed cell death protein 1 (PD-1) inhibition in a patient with underlying interstitial lung disease (ILD) and a new diagnosis of MCC. Through a multidisciplinary approach, we were able to maintain close monitoring with serial clinical and radiographical follow-up. The patient achieved a complete response though unrelated medical issues resulting in a treatment hold. At the last follow-up, the patient continued to experience a durable response without evidence of recurrence. This case describes the use of pembrolizumab, a PD-1 inhibitor, for the treatment of MCC in a patient with underlying ILD. The use of active surveillance with a multidisciplinary approach resulted in successful treatment of MCC without exacerbation of the underlying ILD.

Harmonic motion imaging of human breast masses: an in vivo clinical feasibility.

Non-invasive diagnosis of breast cancer is still challenging due to the low specificity of the imaging modalities that calls for unnecessary biopsies. The diagnostic accuracy can be improved by assessing the breast tissue mechanical properties associated with pathological changes. Harmonic motion imaging (HMI) is an elasticity imaging technique that uses acoustic radiation force to evaluate the localized mechanical properties of the underlying tissue. Herein, we studied the in vivo feasibility of a clinical HMI system to differentiate breast tumors based on their relative HMI displacements, in human subjects. We performed HMI scans in 10 female subjects with breast masses: five benign and five malignant masses. Results revealed that both benign and malignant masses were stiffer than the surrounding tissues. However, malignant tumors underwent lower mean HMI displacement (1.1 ± 0.5 µm) compared to benign tumors (3.6 ± 1.5 µm) and the adjacent non-cancerous tissue (6.4 ± 2.5 µm), which allowed to differentiate between tumor types. Additionally, the excised breast specimens of the same patients (n = 5) were imaged post-surgically, where there was an excellent agreement between the in vivo and ex vivo findings, confirmed with histology. Higher displacement contrast between cancerous and non-cancerous tissue was found ex vivo, potentially due to the lower nonlinearity in the elastic properties of ex vivo tissue. This preliminary study lays the foundation for the potential complementary application of HMI in clinical practice in conjunction with the B-mode to classify suspicious breast masses.

Presenting for Duty: Lessons From A Specialty Surgery Division at the Pandemic Epicenter.

MINI-ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic has had catastrophic repercussions across the world and here in the United States. The healthcare system in New York City, the epicenter, has faced significant disruptions due to the sheer volume of cases and critical care needs of severely ill patients. For surgical specialty services, the postponement of all elective surgeries, redeployment of faculty and staff, and cancellation of outpatient clinics became a rapid reality. These circumstances required a nimble restructuring of services and communications to facilitate continued support of academic and clinical missions. Throughout the course of the pandemic, significant adjustments were made in regards to duties, patient services, and communication. The frameworks and techniques utilized are described along with the relevant outcomes. Immediate restructuring of tumor boards, a focused multidisciplinary approach to management that incorporated the barriers presented by the pandemic, optimization of telehealth services, inclusive communication, and a service-oriented approach to redeployment were critical to sustaining the Division of Breast, Melanoma, and Soft Tissue surgery.

Fully Automated Postlumpectomy Breast Margin Assessment Utilizing Convolutional Neural Network Based Optical Coherence Tomography Image Classification Method.

BACKGROUND: The purpose of this study was to develop a deep learning classification approach to distinguish cancerous from noncancerous regions within optical coherence tomography (OCT) images of breast tissue for potential use in an intraoperative setting for margin assessment. METHODS: A custom ultrahigh-resolution OCT (UHR-OCT) system with an axial resolution of 2.7 µm and a lateral resolution of 5.5 µm was used in this study. The algorithm used an A-scan-based classification scheme and the convolutional neural network (CNN) was implemented using an 11-layer architecture consisting of serial 3 × 3 convolution kernels. Four tissue types were classified, including adipose, stroma, ductal carcinoma in situ, and invasive ductal carcinoma. RESULTS: The binary classification of cancer versus noncancer with the proposed CNN achieved 94% accuracy, 96% sensitivity, and 92% specificity. The mean five-fold validation F1 score was highest for invasive ductal carcinoma (mean standard deviation, 0.89 ± 0.09) and adipose (0.79 ± 0.17), followed by stroma (0.74 ± 0.18), and ductal carcinoma in situ (0.65 ± 0.15). CONCLUSION: It is feasible to use CNN based algorithm to accurately distinguish cancerous regions in OCT images. This fully automated method can overcome limitations of manual interpretation including interobserver variability and speed of interpretation and may enable real-time intraoperative margin assessment.

A Randomized Trial Evaluating Bioimpedance Spectroscopy Versus Tape Measurement for the Prevention of Lymphedema Following Treatment for Breast Cancer: Interim Analysis.

BACKGROUND: Breast cancer-related lymphedema (BCRL) represents a major source of morbidity among breast cancer survivors. Increasing data support early detection of subclinical BCRL followed by early intervention. A randomized controlled trial is being conducted comparing lymphedema progression rates using volume measurements calculated from the circumference using a tape measure (TM) or bioimpedance spectroscopy (BIS). METHODS: Patients were enrolled and randomized to either TM or BIS surveillance. Patients requiring early intervention were prescribed a compression sleeve and gauntlet for 4 weeks and then re-evaluated. The primary endpoint of the trial was the rate of progression to clinical lymphedema requiring complex decongestive physiotherapy (CDP), with progression defined as a TM volume change in the at-risk arm ≥ 10% above the presurgical baseline. This prespecified interim analysis was performed when at least 500 trial participants had ≥ 12 months of follow-up. RESULTS: A total of 508 patients were included in this analysis, with 109 (21.9%) patients triggering prethreshold interventions. Compared with TM, BIS had a lower rate of trigger (15.8% vs. 28.5%, p < 0.001) and longer times to trigger (9.5 vs. 2.8 months, p = 0.002). Twelve triggering patients progressed to CDP (10 in the TM group [14.7%] and 2 in the BIS group [4.9%]), representing a 67% relative reduction and a 9.8% absolute reduction (p = 0.130). CONCLUSIONS: Interim results demonstrated that post-treatment surveillance with BIS reduced the absolute rates of progression of BCRL requiring CDP by approximately 10%, a clinically meaningful improvement. These results support the concept of post-treatment surveillance with BIS to detect subclinical BCRL and initiate early intervention.

A Single-Institution Experience in the Preoperative Selection of DCIS Patients for IORT using the ASTRO Consensus Guidelines.

PURPOSE: Intraoperative radiation therapy (IORT) as a form of accelerated partial breast irradiation (APBI) is controversial given the limited evidence to support its efficacy. However, it remains an attractive option for low-risk patients with ductal carcinoma in situ (DCIS), who derive a small absolute benefit in local control with standard whole breast irradiation (WBI). We examine how the American Society for Therapeutic Radiation Oncology (ASTRO) APBI consensus guidelines (CG) may be applied to the preoperative selection of patients with DCIS for IORT and determine treatment outcomes by CG group. METHODS AND MATERIALS: We identified patients with biopsy-proven pure DCIS enrolled in an institutional prospective registry IORT database using the Zeiss Intrabeam® device between September 2013 and February 2017. Based on available preoperative clinicopathologic information, patients were deemed suitable, cautionary, or unsuitable for IORT according to the ASTRO CG. Change in CG group based on final pathologic diagnosis was determined, and additional therapy was recommended for unsuitable patients. Outcome in terms of ipsilateral breast tumor recurrence was determined. RESULTS: A total of 61 DCIS lesions in 60 patients were treated with IORT. Preoperatively, 21 patients (35%) were suitable and 36 (59%) were cautionary. Four (6%) were unsuitable because of lesion size but declined WBI. Final pathologic diagnosis changed the CG grouping of 10 patients (16%) because of either occult high-grade disease in 2 (3%) or close/positive margins in 8 (13%). Ultimately 12 patients total were considered unsuitable, of whom 8 (66%) accepted additional WBI after IORT. At a median follow-up of 2.2 years, ipsilateral breast tumor recurrence was identified among 2 suitable, 1 cautionary, and no unsuitable patients. CONCLUSION: Further investigation is necessary to refine selection of patients with DCIS who may be optimally treated with IORT alone. High acceptance of additional therapy among unsuitable patients resulted in excellent outcomes. The use of biomarkers in addition to traditional clinical and pathologic factors may help to better select patients for IORT.

Erratum: Author Correction: Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint.

[This corrects the article DOI: 10.1038/s41523-018-0074-6.].

Validation of Melanoma Immune Profile (MIP), a Prognostic Immune Gene Prediction Score for Stage II-III Melanoma.

PURPOSE: Biomarkers are needed to stratify patients with stage II-III melanoma for clinical trials of adjuvant therapy because, while immunotherapy is protective, it also confers the risk of severe toxicity. We previously defined and validated a 53-immune gene melanoma immune profile (MIP) predictive both of distant metastatic recurrence and of disease-specific survival (DSS). Here, we test MIP on a third independent population. EXPERIMENTAL DESIGN: A retrospective cohort of 78 patients with stage II-III primary melanoma was analyzed using the NanoString assay to measure expression of 53 target genes, and MIP score was calculated. Statistical analysis correlating MIP with DSS, overall survival, distant metastatic recurrence, and distant metastasis-free interval was performed using ROC curves, Kaplan-Meier curves, and standard univariable and multivariable Cox proportional hazards models. RESULTS: MIP significantly distinguished patients with distant metastatic recurrence from those without distant metastatic recurrence using ROC curve analysis (AUC = 0.695; P = 0.008). We defined high- and low-risk groups based on the cutoff defined by this ROC curve and find that MIP correlates with both DSS and overall survival by ROC curve analysis (AUC = 0.719; P = 0.004 and AUC = 0.698; P = 0.004, respectively). Univariable Cox regression reveals that a high-risk MIP score correlates with DSS (P = 0.015; HR = 3.2). CONCLUSIONS: MIP identifies patients with low risk of death from melanoma and may constitute a clinical tool to stratify patients with stage II-III melanoma for enrollment in clinical trials.