Interdisciplinary Implementation of a Synoptic Reporting Template for Melanoma Nodal Surveillance Ultrasound.

BACKGROUND: With nodal surveillance increasingly used for sentinel lymph node-positive (SLN+) melanoma following the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II), high-quality nodal ultrasonography (U/S) has become a critical need. Previous work has demonstrated low utilization of MSLT-II U/S criteria to define abnormal lymph nodes requiring intervention or biopsy. To address this gap, an evidence-based synoptic template was designed and implemented in this single-center study. METHODS: Sentinel lymph node-positive patients undergoing nodal surveillance at a tertiary cancer center from July 2017 to June 2023 were identified retrospectively. Ultrasound reporting language was analyzed for MSLT-II criteria reported and clinically actionable recommendations (e.g., normal, abnormal with recommendation for biopsy). Following a multidisciplinary design process, the synoptic template was implemented in January 2023. Postimplementation outcomes were evaluated by using U/S reports and provider surveys. RESULTS: A total of 337 U/S studies were performed on 94 SLN+ patients, with a median of 3 U/S per patient (range 1-12). Among 42 synoptic-eligible U/S performed postimplementation, 32 U/S (76.0%) were reported synoptically. Significant increases were seen in the number of MSLT-II criteria reported (Pre 0.5 ± 0.8 vs. Post 2.5 ± 1.0, p < 0.001), and clinically actionable recommendations for abnormal findings (Pre 64.0% vs. Post 93.0%, p = 0.04). Nearly all surgeon and radiologist survey respondents were "very" or "completely" satisfied with the clinical utility of the synoptic template (90.0%). CONCLUSIONS: Following implementation of a synoptic template, U/S reports were significantly more likely to document MSLT-II criteria and provide an actionable recommendation, increasing usefulness to providers. Efforts to disseminate this synoptic template to other centers are ongoing.

International Center-Level Variation in Utilization of Completion Lymph Node Dissection and Adjuvant Systemic Therapy for Sentinel Lymph Node-Positive Melanoma at Major Referral Centers.

OBJECTIVE: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma. SUMMARY BACKGROUND DATA: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization. METHODS: We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics. RESULTS: Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients. CONCLUSIONS: There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation.

Recurrence Patterns for Regionally Metastatic Melanoma Treated in the Era of Adjuvant Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: The purpose of this systematic review was to examine the timing and patterns of recurrence for patients with regionally metastatic melanoma on the basis of nodal management and receipt of adjuvant therapy. METHODS: We identified randomized controlled trials and non-randomized studies published between 2010 and 2020 that reported timing and/or patterns of recurrence. We evaluated recurrence-free survival (RFS), location of recurrence, and surveillance strategy on the basis of receipt of adjuvant systemic therapy and nodal management with observation versus completion dissection. We compared differences in patterns of recurrence across studies using RevMan. RFS was evaluated graphically using point estimates and confidence intervals. RESULTS: Among the 19 publications, there was wide variation in study populations, imaging surveillance regimens, and format of recurrence reporting. Patterns of disease recurrence did not differ between adjuvant and placebo/observation groups. A total of 11 studies reported RFS at variable time intervals, which ranged in adjuvant therapy groups (38-88% at 1 year, 29-67% at 2 years, 33-58% at 3 years, and 34-53% at 5 years) and placebo/observation groups (47-63% at 1 year, 39-47% at 2 years, 33-68% at 3 years, and 57% at 5 years). Anti-PD-1 immune therapy and BRAF/MEK inhibitor therapy were superior to placebo at year 1. DISCUSSION: We found that adjuvant treatment improved RFS but did not alter the patterns of disease recurrence compared with patients managed without adjuvant systemic treatment. Future studies should separately report sites of disease recurrence on the basis of specific adjuvant systemic treatment and surveillance practices to better advise patients about their patterns and risk of recurrence.

Real-World Adherence to Nodal Surveillance for Sentinel Lymph Node-Positive Melanoma.

BACKGROUND: Patients with sentinel lymph node-positive (SLN+) melanoma are increasingly undergoing active nodal surveillance over completion lymph node dissection (CLND) since the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II). Adherence to nodal surveillance in real-world practice remains unknown. METHODS: In a retrospective cohort of SLN+ melanoma patients who underwent nodal surveillance at a single institution from July 2017 through April 2021, this study evaluated adherence to nodal surveillance ultrasound (US). Adherence to nodal US was compared with adherence to other surveillance methods based on receipt of adjuvant therapy. Early recurrence data were reported using descriptive statistics. RESULTS: Among 109 SLN+ patients, 37 (34%) received US surveillance at recommended intervals. Of the 72 (66%) non-adherent patients, 16 were lost to follow-up, and 33 had planned follow-up at an outside institution without available records. More patients had a minimum of bi-annual clinic visits (83%) and cross-sectional imaging (53%) compared to those who were adherent with nodal US. The patients who received adjuvant therapy (60%) had fewer ultrasounds (p < 0.01) but more exams (p < 0.01) and a trend toward more cross-sectional imaging (p = 0.06). Of the overall cohort, 26 patients (24%) experienced recurrence at a median follow-up period of 15 months. Of these recurrences, 10 were limited to the SLN basin, and all of these isolated nodal recurrences were resectable. CONCLUSIONS: Pragmatic challenges to real-world delivery of nodal surveillance remain after MSLT-II, and adjuvant therapy appears to be associated with a decreased likelihood of US adherence. Understanding US utility alongside cross-sectional imaging will be critical as increasingly more patients undergo nodal surveillance and adjuvant therapy.

Surveillance of Sentinel Node-Positive Melanoma Patients Who Receive Adjuvant Therapy Without Undergoing Completion Lymph Node Dissection.

INTRODUCTION: Adjuvant therapy trials required completion lymph node dissection (CLND) for sentinel lymph node (SLN)-positive melanoma prior to systemic treatment, but nodal surveillance without CLND is now common. For patients receiving adjuvant therapy without CLND, patterns of recurrence are unknown and the value of regional nodal ultrasound alongside cross-sectional imaging is not well-defined. METHODS: In a retrospective cohort of SLN-positive melanoma patients managed with nodal surveillance from June 2014 to June 2019, we evaluated the association between adjuvant treatment and location of first recurrence (locoregional, nodal, distant, or multisite) using Chi-square tests. We compared methods of recurrence detection and cost by surveillance intensity using Chi-square and Dunn's tests. RESULTS: Among 177 nodal surveillance patients, 66 (37%) received adjuvant therapy. Median follow-up was 24 months, during which 48 patients (27%) recurred. Adjuvant treatment did not alter patterns of initial recurrence (p = 0.76). Adjuvant therapy recipients more often had both nodal ultrasound and cross-sectional imaging surveillance (p < 0.01). Among 13 isolated nodal recurrences, 85% were within the first year and 85% were detected by examination and/or ultrasound. Increasing surveillance intensity was not associated with recurrence detection rates but increased overall cost and cost per detected recurrence. CONCLUSION: Regardless of adjuvant treatment, most nodal recurrences occurred in the first year and were initially detected clinically or by ultrasound. Findings support continued use of examination and nodal basin ultrasound in addition to any planned cross-sectional imaging surveillance.

TARGIT-R (Retrospective): 5-Year Follow-Up Evaluation of Intraoperative Radiation Therapy (IORT) for Breast Cancer Performed in North America.

BACKGROUND: Intraoperative radiation therapy (IORT) has been investigated for patients with low-risk, early-stage breast cancer. The The North American experience was evaluated by TARGIT-R (retrospective) to provide outcomes for patients treated in "real-world" clinical practice with breast IORT. This analysis presents a 5-year follow-up assessment. METHODS: TARGIT-R is a multi-institutional retrospective registry of patients who underwent lumpectomy and IORT between the years 2007 and 2013. The primary outcome of the evaluation was ipsilateral breast tumor recurrence (IBTR). RESULTS: The evaluation included 667 patients with a median follow-up period of 5.1 years. Primary IORT (IORT at the time of lumpectomy) was performed for 72%, delayed IORT (after lumpectomy) for 3%, intended boost for 8%, and unintended boost (primary IORT followed by whole-breast radiation) for 17% of the patients. At 5 years, IBTR was 6.6% for all the patients, with 8% for the primary IORT cohort and 1.7% for the unintended-boost cohort. No recurrences were identified in the delayed IORT or intended-boost cohorts. Noncompliance with endocrine therapy (ET) was associated with higher IBTR risk (hazard ratio [HR], 3.67). Patients treated with primary IORT who were complaint with ET had a 5-year IBTR rate of 3.9%. CONCLUSION: The local recurrence rates in this series differ slightly from recent results of randomized IORT trials and are notably higher than in previous published studies using whole-breast radiotherapy for similar patients with early-stage breast cancer. Understanding differences in this retrospective series and the prospective trials will be critical to optimizing patient selection and outcomes going forward.

Surgeon decision-making for management of positive sentinel lymph nodes in the post-Multicenter Selective Lymphadenectomy Trial II era: A survey study.

BACKGROUND AND OBJECTIVES: Completion lymph node dissection (CLND) did not improve melanoma-specific survival for patients with sentinel lymph node (SLN)-positive melanoma in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II). We assessed surgeons' awareness of MSLT-II and its impact on CLND recommendations. METHODS: An anonymous online cross-sectional survey of the Society of Surgical Oncology membership evaluated surgeon thresholds in offering CLND using patient scenarios and clinicopathologic characteristics ranking. RESULTS: Of the 2881 e-mails delivered, 146 surgeons (5.1%) completed all seven scenarios. Most (129 of 131, 98%) were aware of MSLT-II and 125 (95%) found it practice-changing. Specifically, 52% (65 of 125) always, 40% usually, 6% rarely, and 3% never offered CLND before MSLT-II. Meanwhile, 4% always, 9% usually, 78% rarely, and 8% never offer CLND now, after MSLT-II (p < .0001). The most important clinicopathologic factors in determining CLND recommendations were extracapsular extension, number of positive SLN, and SLN tumor deposit size, while primary tumor mitotic index and nodal basin location were the least important. Surgical oncology fellowship training, melanoma patient volume, and academic center practice also influenced CLND recommendations. CONCLUSIONS: Most surgeon respondents are aware of MSLT-II, but its application in practice varies according to several clinicopathologic and surgeon factors.

Sidedness of Colorectal Cancer Impacts Risk of Second Primary Gastrointestinal Malignancy.

INTRODUCTION: A history of colorectal cancer (CRC) increases the risk of subsequent gastrointestinal (GI) cancer. Cancers of the right colon, left colon, and rectum differ according to molecular profiles, responses to treatment, and outcomes. OBJECTIVE: The purpose of this study was to determine if CRC location is associated with differential risk for secondary primary GI malignancy. METHODS: A retrospective cohort of adults with CRC was compiled using the Surveillance, Epidemiology, and End Results database (1973-2015). Standardized incidence ratios (SIRs) for second primary GI malignancies were compared based on location of the index CRC (right colon, left colon, or rectum). RESULTS: The cohort included 281,413 adults with CRC (30.3% right, 35.3% left, 34.3% rectum). With a median 4.9-year follow-up, 12,064 (4.3%) patients developed a second primary GI malignancy (64% CRC, 36% non-CRC). Those with CRC at any location had higher than expected incidences of small intestine, bile duct, and other CRCs, and lower incidences of liver and gallbladder cancer. The SIR for small intestinal cancer was higher after right colon cancer than after left colon or rectal cancer. The esophageal cancer SIR was higher after left colon cancer. Pancreas cancer was higher than expected for right colon cancer, but lower for left colon and rectal cancer. CONCLUSION: The location of CRC leads to differences in the incidence and location of second primary GI malignancies and may be related to similarities in the associated carcinogenesis and molecular pathways or response to treatment. CRC location not only impacts treatment response and outcomes, but should also be considered during subsequent surveillance.

Contemporary trends in extent of surgery for differentiated thyroid cancer with extrathyroidal extension.

OBJECTIVE: Although lobectomy is acceptable for patients with small, low-risk differentiated thyroid cancer (DTC), gross extrathyroidal extension (ETE) remains an indication for total thyroidectomy (TT). Here we investigate evolving trends in extent of surgery for â€‹+ â€‹ETE DTC. METHODS: Patients with +ETE DTC who underwent resection from 2010 to 2020 were identified using the National Cancer Database. The primary outcome was performance of TT versus lobectomy. RESULTS: Among 5851 patients, most were female (79.7%), white (80.0%), and had minimal ETE (91.8%). Ninety-two percent of patients received TT. Year of treatment was influential (p â€‹< â€‹0.001), with increasing lobectomy rates in later years. On multivariable analyses, a decreased likelihood of TT was seen in years 2015 through 2020. CONCLUSIONS: Most patients with +ETE DTC underwent guideline-concordant TT, but lobectomy rates doubled over the study period. These findings may reflect increased preference for lobectomy in low-risk DTC, but could undertreat patients with high-risk features.

Quality of breast surgery care at a comprehensive cancer center and its rural affiliate hospital.

BACKGROUND: Cancer centers are increasingly affiliating with rural hospitals to perform surgery. Perioperative and oncologic outcomes for cancer center surgeons operating at rural hospitals are understudied. METHODS: For patients with non-metastatic breast cancer from a rural catchment area who had oncologic surgery at an NCI-designated comprehensive cancer center (CC) or its rural affiliate (RA) from 2017 to 2022, we compared perioperative outcomes (composite of surgical site infection, seroma requiring drainage, and reoperation for margins) and receipt of guideline-concordant care (if patient received all applicable treatments) using descriptive statistics and chi-squared tests. RESULTS: Among 168 patients, 99 had surgery at RA, 60 CC. RA patients were older, higher stage, and more often had lumpectomy. There were no differences in perioperative outcomes (CC 10%, RA 14%, p â€‹= â€‹0.445) or guideline concordant care (RA 76%, CC 78%, p â€‹= â€‹0.846). CONCLUSIONS: Cancer center surgeons operating at a rural affiliate had comparable perioperative outcomes and guideline-concordant care.

Racial and ethnic variation in presentation and outcomes of high-grade soft tissue sarcoma at a Southeastern United States comprehensive cancer center.

BACKGROUND: High-grade soft tissue sarcoma is rare and associated with poor prognosis. This study examines racial and ethnic variation in presentation and outcomes at a Southeastern US cancer center. METHODS: Among an institutional cohort of patients seen between January 2016-December 2021, racial and ethnic differences were evaluated using chi-squared tests, Kaplan Meier curves, and Cox proportional hazards models. RESULTS: There were 295 patients (71 â€‹% Non-Hispanic White, 24 â€‹% Black, 3 â€‹% Hispanic White, 2 â€‹% Other). Black representation was greater than national cohorts (24 â€‹% vs. 12 â€‹%). Histological subtype varied by race/ethnicity (p â€‹= â€‹0.007). Adjusting for histology and stage, survival was worse for Black vs. White patients (HR 1.71, 95 â€‹% CI 1.07-2.76) and those with metastatic disease (5.47, 3.54-8.44). In non-metastatic patients, survival differences for Black vs. White patients were attenuated by receipt of multi-modal treatment (1.53, 0.82-2.88). CONCLUSION: Observed racial disparities in survival of high-grade sarcoma may be addressed by early, multidisciplinary management.

Health System Integration and Cancer Center Access for Rural Hospitals.

BACKGROUND: Cancer centers provide superior care but are less accessible to rural populations. Health systems that integrate a cancer center may provide broader access to quality surgical care, but penetration to rural hospitals is unknown. METHODS: Cancer center data were linked to health system data to describe health systems based on whether they included at least one accredited cancer center. Health systems with and without cancer centers were compared based on rural hospital presence. Bivariate tests and multivariable logistic regression were used with results reported as P-values and odds ratios (OR) with 95% confidence intervals (CIs). RESULTS: Ninety percent of cancer centers are in a health system, and 72% of health systems (434/607) have a cancer center. Larger health systems (P = .03) with more trainees (P = .03) more often have cancer centers but are no more likely to include rural hospitals (11% vs 6%, P = .43; adjusted OR .69, 95% CI .28-1.70). The minority of cancer centers not in health systems (N = 95) more often serve low complexity patient populations (P = .02) in non-metropolitan areas (P = .03). DISCUSSION: Health systems with rural hospitals are no more likely to have a cancer center. Ongoing health system integration will not necessarily expand rural patients' access to surgical care under existing health policy infrastructure and incentives.

Evolving variation in the extent of surgery for low-risk papillary thyroid cancer in the United States.

BACKGROUND: The continued debate over total thyroidectomy versus lobectomy and declining favor for prophylactic central neck dissection for patients with clinically node-negative papillary thyroid cancer ≤4 cm is ongoing after the 2015 guideline updates from the American Thyroid Association. This study aimed to evaluate contemporary trends in the extent of surgery in this low-risk cohort. METHODS: Retrospective data from the National Cancer Database were used to identify adult patients with clinically node-negative papillary thyroid cancer ≤4 cm who underwent resection from 2012 to 2020. The primary outcome was the extent of surgery (lobectomy or total thyroidectomy, with or without prophylactic central neck dissection). Multivariable regression was performed to identify characteristics associated with variation in the extent of surgery. RESULTS: Of 83,464 included patients, 79.3% were female patients with a median age of 51 years. The majority underwent total thyroidectomy either with prophylactic central neck dissection (39.1%) or without (37.5%) versus lobectomy with prophylactic central neck dissection (7.2%) or without (16.2%). Lobectomy rates increased from 18.3% in 2012 to 29.9% in 2020. Prophylactic central neck dissection rates also increased (42.9% to 52.1%). Patients who were male sex, Asian American, had smaller tumors or were treated at community cancer programs had a decreased likelihood of total thyroidectomy. Patients who were older, male sex, Black race, with smaller tumors, or were treated at community cancer programs or mid- or low-volume facilities had decreased likelihood of prophylactic central neck dissection. CONCLUSION: Proportional use rates of operative approaches for low-risk, clinically node-negative papillary thyroid cancer have changed in recent years after the American Thyroid Association guideline changes, including increasing overall rates of lobectomy as well as prophylactic central neck dissection, with differences noted based on patient- and facility-level factors.

Implementation of melanoma guidelines in the multidisciplinary setting: A qualitative analysis.

BACKGROUND: Data suggest variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy (AT) for sentinel lymph node-positive melanoma. We aimed to explore how clinicians consider multidisciplinary treatment options. METHODS: We conducted semi-structured interviews of surgical oncologists, medical oncologists, and otolaryngologists to produce a thematic analysis. RESULTS: Participants (n = 26) described melanoma care as inherently "multidisciplinary," noting the importance of conversations facilitated by shared clinic days or space. Despite believing that their practice mirrored other clinicians, participants revealed diverging perspectives on CLND and AT. Multidisciplinary care presented challenges for surveillance as surgeons expressed desire to retain ownership of patients but did not feel comfortable overseeing AT needs. Participants questioned the fidelity of nodal ultrasounds, noted redundancy in their roles, and described a "surveillance burden" for patients. CONCLUSION: Opportunities exist to improve multidisciplinary melanoma care through broader consensus of how to translate emerging data into patient care and delineating surveillance roles.

Evidence and implementation gaps in management of sentinel node-positive melanoma in the United States.

BACKGROUND: Melanoma clinical trials demonstrated that completion lymph node dissection is low value for most sentinel lymph node-positive patients. Contemporaneous trials of adjuvant systemic immunotherapy and BRAF/MEK targeted therapy showed improved recurrence-free survival in high-risk sentinel lymph node-positive patients. To better understand how oncologic evidence is incorporated into practice (implementation), we evaluated factors associated with discontinuation of completion lymph node dissection and adoption of systemic treatment at United States Commission on Cancer-accredited centers. METHODS: In a retrospective cohort study of adults with sentinel lymph node-positive melanoma treated from 2012 to 2017 using the National Cancer Database, we evaluated use of completion lymph node dissection and adjuvant systemic treatment using mixed-effects logistic regression, reporting results as odds ratios with 95% confidence intervals. RESULTS: Among 10,240 sentinel lymph node-positive melanoma patients, performance of completion lymph node dissection declined from 60% to 27%. Adjuvant systemic treatment increased from 29% to 43% (37% in stage IIIA patients, 46% in IIIB-C). Completion lymph node dissection was less common with lower extremity tumors (odds ratio = 0.53, 95% confidence interval = 0.44-0.64) and more common with multiple positive sentinel lymph nodes (odds ratio = 2.36, 95% confidence interval = 2.08-2.67), treatment at a high- or moderate-volume center (odds ratiohigh = 1.49, 95% confidence interval = 1.05-2.12; odds ratiomoderate = 1.32, 95% confidence interval = 1.05-1.64), and receipt of systemic therapy (odds ratio = 1.44, 95% confidence interval = 1.27-1.63). The increased likelihood of completion lymph node dissection in patients receiving adjuvant systemic treatment persisted in the most recent study years and in patients with a single positive sentinel lymph node. CONCLUSION: At a population level, completion lymph node dissection declined and adjuvant systemic treatment increased, reflecting evidence-responsive care. Variation in persistent use of completion lymph node dissection and in provision of adjuvant treatment for lower risk patients highlights residual gaps in both evidence and implementation.

Outcomes with adjuvant anti-PD-1 therapy in patients with sentinel lymph node-positive melanoma without completion lymph node dissection.

Until recently, most patients with sentinel lymph node-positive (SLN+) melanoma underwent a completion lymph node dissection (CLND), as mandated in published trials of adjuvant systemic therapies. Following multicenter selective lymphadenectomy trial-II, most patients with SLN+ melanoma no longer undergo a CLND prior to adjuvant systemic therapy. A retrospective analysis of clinical outcomes in SLN+ melanoma patients treated with adjuvant systemic therapy after July 2017 was performed in 21 international cancer centers. Of 462 patients who received systemic adjuvant therapy, 326 patients received adjuvant anti-PD-1 without prior immediate (IM) CLND, while 60 underwent IM CLND. With median follow-up of 21 months, 24-month relapse-free survival (RFS) was 67% (95% CI 62% to 73%) in the 326 patients. When the patient subgroups who would have been eligible for the two adjuvant anti-PD-1 clinical trials mandating IM CLND were analyzed separately, 24-month RFS rates were 64%, very similar to the RFS rates from those studies. Of these no-CLND patients, those with SLN tumor deposit >1 mm, stage IIIC/D and ulcerated primary had worse RFS. Of the patients who relapsed on adjuvant anti-PD-1, those without IM CLND had a higher rate of relapse in the regional nodal basin than those with IM CLND (46% vs 11%). Therefore, 55% of patients who relapsed without prior CLND underwent surgery including therapeutic lymph node dissection (TLND), with 30% relapsing a second time; there was no difference in subsequent relapse between patients who received observation vs secondary adjuvant therapy. Despite the increased frequency of nodal relapses, adjuvant anti-PD-1 therapy may be as effective in SLN+ pts who forego IM CLND and salvage surgery with TLND at relapse may be a viable option for these patients.