Hieken, Tina J

AbstractIntroductionMelanoma guidelines stem largely from data on non‐Hispanic White (NHW) patients. We aimed to identify features of melanoma within non‐Hispanic Black (NHB) patients to inform strategies for earlier detection and treatment.MethodsFrom 2004 to 2019 Surveillance, Epidemiology, and End Results (SEER) data, we identified nonmetastatic melanoma patients with known TN category and race. Kaplan–Meier cancer‐specific survival (CSS) estimates and multivariable Cox proportional hazard modeling analyses were performed.ResultsOf 492 597 patients, 1499 (0.3%) were NHB, who were younger (21% vs. 17% age <50) and more commonly female (54% vs. 41%) than NHW, both p < 0.0005. For NHBs, lower extremity was the most common site (52% vs. 15% for NHWs, p < 0.0001), T category was higher (55% Tis–T1 vs. 82%; 27% T3–T4 vs. 8%, p < 0.0001) and stage at presentation was higher (19% Stage III, vs. 6%, p < 0.0001). Within the NHB cohort, males were older, and more often node‐positive than females. Five‐year Stage III CSS was 42% for NHB males versus 71% for females, adjusting for age and clinical nodal status (hazard ratio 2.48).ConclusionsNHB melanoma patients presented with distinct tumor characteristics. NHB males with Stage III disease had inferior CSS. Focus on this high‐risk patient cohort to promote earlier detection and treatment may improve outcomes.

AbstractBackground and ObjectivesCurrent NCCN guidelines discourage repeat sentinel lymph node (SLN) surgery in patients with local recurrence (LR) of breast cancer following prior mastectomy. This study addresses the feasibility and therapeutic impact of this approach.MethodsWe identified 73 patients managed with repeat SLN surgery for post−mastectomy isolated LR. Lymphatic mapping was performed using radioisotope with or without lymphoscintigraphy and/or blue dye. Successful SLN surgery was defined as retrieval of ≥1 SLN.ResultsSLN surgery was successful in 65/73 (89%), identifying a median of 2 (range 1–4) SLNs, with 10/65 (15%) SLN‐positive. Among these, 5/10 (50%) proceeded to ALND. In unsuccessful cases, 1/8 (13%) proceeded to ALND. Seven of 10 SLN‐positive patients and 50/55 SLN‐negative patients received adjuvant radiotherapy. Chemotherapy was administered in 31 (42%) and endocrine therapy in 50 of 57 HR+ patients (88%). After 28 months median follow‐up, eight patients relapsed with the first site local in two, distant in five, and synchronous local/distant in one. No nodal recurrences were observed.ConclusionsSLN surgery for patients with LR post−mastectomy is feasible and informative. This approach appears oncologically sound, decreases axillary dissection rates and may be used to tailor adjuvant radiation target volumes and systemic therapies.

AbstractAnorectal melanoma is an aggressive mucosal melanoma subtype with a poor prognosis. Although recent advancements have been seen for cutaneous melanoma, the optimal treatment paradigm for management of anorectal melanoma is evolving. In this review, we highlight differences in the pathogenesis of mucosal versus cutaneous melanoma, new concepts of staging for mucosal melanoma, updates to surgical management of anorectal melanoma, and current data for adjuvant radiation and systemic therapy in this unique patient population.

Abstract Purpose: To evaluate the impact of trimodality treatment versus monotherapy or dual therapy for radiation-associated angiosarcoma of the breast (RAASB) after prior breast cancer treatment. Experimental Design: With Institutional Review Board approval, we identified patients diagnosed with RAASB and abstracted data on disease presentation, treatment, and oncologic outcomes. Trimodality therapy included (i) taxane induction, (ii) concurrent taxane/radiation, and then (iii) surgical resection with wide margins. Results: A total of 38 patients (median age 69 years) met inclusion criteria. Sixteen received trimodality therapy and 22 monotherapy/dual therapy. Skin involvement and disease extent were similar in both groups. All trimodality patients required reconstructive procedures for wound closure/coverage, compared with 48% of monotherapy/dual therapy patients (P &lt; 0.001). Twelve of 16 (75%) patients receiving trimodality therapy had a pathologic complete response (pCR). With median follow-up of 5.6 years, none had local recurrence, 1 patient (6%) had distant recurrence, and no patients died. Among 22 patients in the monotherapy/dual therapy group, 10 (45%) had local recurrence, 8 (36%) had distant recurrence, and 7 (32%) died of disease. Trimodality therapy demonstrated significantly better 5-year recurrence-free survival [RFS; 93.8% vs. 42.9%; P = 0.004; HR, 7.6 (95% confidence interval, CI: 1.3–44.2)]. Combining all patients with RAASB regardless of treatment, local recurrence was associated with subsequent distant recurrence (HR, 9.0; P = 0.002); distant recurrence developed in 3 of 28 (11%) patients without local recurrence compared with 6 of 10 (60%) with local recurrence. The trimodality group had more surgical complications that required reoperation or prolonged healing. Conclusions: Trimodality therapy for RAASB was more toxic but is promising, with a high rate of pCR, durable local control, and improved RFS.

Abstract Purpose: Mucosal melanoma is a rare, aggressive form of melanoma with extremely high recurrence rates despite definitive surgical resection with curative intent. Currently there is no consensus on adjuvant therapy. Data on checkpoint inhibitors for adjuvant therapy are lacking. Patients and Methods: We performed a single-arm, multicenter clinical trial using “flip dose” ipilimumab (1 mg/kg q3w × 4 cycles), and nivolumab (3 mg/kg q3w × 4 cycles), then nivolumab 480 mg q4w × 11 cycles to complete a year of adjuvant therapy. Participants must have had R0/R1 resection ≤90 days before registration, no prior systemic therapy (adjuvant radiotherapy allowed), ECOG 0/1, and no uncontrolled autoimmune disease or other invasive cancer. Patients were recruited through the Midwest Melanoma Partnership/Hoosier Oncology Network. Results: From September 2017 to August 2021, 35 patients were enrolled. Of these, 29 (83%) had R0 resections, and 7 (20%) received adjuvant radiotherapy. Median age was 67 years, 21 (60.0%) female. Recurrence-free survival (RFS) rates at 1 and 2 years were 50% [95% confidence interval (CI), 31%–66%] and 37% (95% CI, 19%–55%), respectively. Overall survival rates at 1 and 2 years were 87% (95% CI, 68%–95%) and 68% (95% CI, 46%–83%), respectively. Median RFS was 10.3 months (95% CI, 5.7–25.8). Most common grade 3 toxicities were diarrhea (14%), hypertension (14%), and hyponatremia (11%), with no grade 4/5 toxicities. Conclusions: Flip-dose ipilimumab and nivolumab after resection of mucosal melanoma is associated with outcomes improved over that of surgical resection alone. Long-term follow-up, subgroup analyses and correlative studies are ongoing.

AbstractBackground and objectivesPrevious studies have identified racial‐ethnic differences in the diagnostic patterns and recurrence outcomes of women with phyllodes tumors (PT). However, these studies are generally limited in size and generalizability. We therefore sought to explore racial‐ethnic differences in age, tumor size, subtype, and recurrence in a large US cohort of women with PT.MethodsWe performed an 11‐institution retrospective review of women with PT from 2007 to 2017. Differences in age at diagnosis, tumor size and subtype, and recurrence‐free survival according to race‐ethnicity.ResultsWomen of non‐White race or Hispanic ethnicity were younger at the time of diagnosis with phyllodes tumor. Non‐Hispanic Other women had a larger proportion of malignant PT. There were no differences in recurrence‐free survival in our cohort.ConclusionsDifferences in age, tumor size, and subtype were small. Therefore, the workup of young women with breast masses and the treatment of women with PT should not differ according to race‐ethnicity. These conclusions are supported by our finding that there were no differences in recurrence‐free survival.

AbstractBackgroundMerkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy that usually occurs in the head/neck or extremities. However, there are reports of MCC developing in the lymph nodes or parotid gland without evidence of a primary cutaneous lesion.MethodsWe reviewed 415 patients with biopsy‐proven MCC. Patients with MCC of unknown primary (n = 37, 9%, MCCUP) made up the study cohort. The primary endpoints of the study were rate of recurrence, disease‐free survival, and overall survival.ResultsPatients with MCCUP presented with tumors in lymph nodes (n = 34) or parotid gland (n = 3). Nodal disease was most commonly detected in the inguinal/external iliac (n = 15) or axillary (n = 14) regions. The mean age at diagnosis was 70 years and 24% were female. Patients presented with distant metastases in 24.3% of cases. Patients with stage IIIA disease treated with regional lymph node dissection (RLND) had a lower risk of disease recurrence (hazard ratio 0.26, p = 0.046). Recurrence‐free survival was 59.3% at 5 years. Disease‐specific survival was 63.3% at 5 years.ConclusionPatients with MCCUP have a high risk of recurrence and mortality. The optimal treatment for MCCUP has yet to be elucidated, although therapeutic RLND appears beneficial for these patients.

AbstractBackground and ObjectivesOf clinically node‐negative (cN0) cutaneous melanoma patients with sentinel lymph node (SLN) metastasis, between 10% and 30% harbor additional metastases in non‐sentinel lymph nodes (NSLNs). Approximately 80% of SLN‐positive patients have a single positive SLN.MethodsTo assess whether state‐of‐the‐art clinicopathologic models predicting NSLN metastasis had adequate performance, we studied a single‐institution cohort of 143 patients with cN0 SLN‐positive primary melanoma who underwent subsequent completion lymph node dissection. We used sensitivity (SE) and positive predictive value (PPV) to characterize the ability of the models to identify patients at high risk for NSLN disease.ResultsAcross Stage III patients, all clinicopathologic models tested had comparable performances. The best performing model identified 52% of NSLN‐positive patients (SE = 52%, PPV = 37%). However, for the single SLN‐positive subgroup (78% of cohort), none of the models identified high‐risk patients (SE > 20%, PPV > 20%) irrespective of the chosen probability threshold used to define the binary risk labels. Thus, we designed a new model to identify high‐risk patients with a single positive SLN, which achieved a sensitivity of 49% (PPV = 26%).ConclusionFor the largest SLN‐positive subgroup, those with a single positive SLN, current model performance is inadequate. New approaches are needed to better estimate nodal disease burden of these patients.

BackgroundFor patients with sentinel lymph node (SLN)‐positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease‐specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown.MethodsIn a retrospective cohort of SLN‐positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all‐site recurrence‐free survival (RFS), isolated nodal RFS, distant metastasis‐free survival (DMFS), and DSS using Kaplan‐Meier curves and Cox proportional hazard models.ResultsAmong 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty‐nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti–PD‐1 immunotherapy. After a median follow‐up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty‐eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk‐adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15‐0.88), but not all‐site RFS (HR, 0.68; 95% CI, 0.45‐1.02). Adjuvant therapy improved all‐site RFS (HR, 0.52; 95% CI, 0.47‐0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment.ConclusionsActive surveillance has been adopted for most SLN‐positive patients. At initial assessment, real‐world outcomes align with randomized trial findings, including in adjuvant therapy recipients.Lay Summary For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real‐world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up‐front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma.

Abstract Background Although inflammatory breast cancer (IBC) is postulated to be a distinct biological entity, practice guidelines and previous data suggest that treatment and outcomes are influenced by standard approximated biological subtype. The aim of this study was validation in a large recent National Cancer Database (NCDB) patient cohort. Methods Patients with non-metastatic IBC treated in 2010–2015 with neoadjuvant systemic therapy and surgery were identified from the NCDB. Approximated biological subtypes were categorized as oestrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−), ER−/HER2− and HER2+. Total pathological complete response (pCR) was defined as ypT0/ypTis, ypN0. χ2 tests were used to compare pCR rates, and Kaplan–Meier curves and Cox proportional hazards regression to analyse overall survival. Results Among 4068 patients with IBC (median age 56 years), the approximated biological subtype was ER+/HER2− in 1575 (38·7 per cent), HER2+ in 1323 (32·5 per cent) and ER−/HER2− in 1170 (28·8 per cent). A total of 3351 patients (84·0 per cent) were cN+ at presentation, with no differences across subtypes. Total pCR rates varied significantly by subtype: ER+/HER2− (6·2 per cent), HER2+ (38·8 per cent), ER−/HER2− (19·1 per cent) (P &lt; 0·001), as did breast pCR rates (10·4, 44·5 and 25·2 per cent respectively) and nodal pCR rates (16·9, 56·9 and 33·1 per cent). The 5-year overall survival rate varied significantly across subtypes (ER+/HER2− 64·9 per cent, HER2+ 74·0 per cent, ER−/HER2− 44·0 per cent; P &lt; 0·001) and by pCR within subtypes (all P &lt; 0·001). In multivariable analysis, ER−/HER2− subtype (hazard ratio 2·89 versus HER2+ as reference; P &lt; 0·001) and absence of total pCR (hazard ratio 3·23; P &lt; 0·001) predicted worse survival. Conclusion Both treatment response and survival in patients with IBC varied with approximated biological subtype, as among other invasive breast cancers. These data support continued tailoring of systemic treatment to approximated biological subtype and highlight the recent improved outcomes in patients with HER2+ disease.