Suppression of Ca2+ signaling enhances melanoma progression.

The role of store-operated Ca2+ entry (SOCE) in melanoma metastasis is highly controversial. To address this, we here examined UV-dependent metastasis, revealing a critical role for SOCE suppression in melanoma progression. UV-induced cholesterol biosynthesis was critical for UV-induced SOCE suppression and subsequent metastasis, although SOCE suppression alone was both necessary and sufficient for metastasis to occur. Further, SOCE suppression was responsible for UV-dependent differences in gene expression associated with both increased invasion and reduced glucose metabolism. Functional analyses further established that increased glucose uptake leads to a metabolic shift towards biosynthetic pathways critical for melanoma metastasis. Finally, examination of fresh surgically isolated human melanoma explants revealed cholesterol biosynthesis-dependent reduced SOCE. Invasiveness could be reversed with either cholesterol biosynthesis inhibitors or pharmacological SOCE potentiation. Collectively, we provide evidence that, contrary to current thinking, Ca2+ signals can block invasive behavior, and suppression of these signals promotes invasion and metastasis.

Preoperative Treatment of Locally Advanced Rectal Cancer.

BACKGROUND: Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain. METHODS: We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects. RESULTS: From June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P = 0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy. CONCLUSIONS: In patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.).

Novel MIR143HG::PLAG1 gene fusion identified in a rectal myxoid leiomyosarcoma.

Myxoid leiomyosarcoma (MLS) is a rare but well-documented tumor that often portends a poor prognosis compared to the conventional leiomyosarcoma. This rare sarcoma has been reported in the uterus, external female genitalia, soft tissue, and other locations. However, a definite rectal MLS has not been reported. Recently five cases of MLS were reported to harbor PLAG1 fusions (TRPS1::PLAG1, RAD51B::PLAG1, and TRIM13::PLAG1). In this report, we present a case of rectal MLS with a novel MIR143HG::PLAG1 fusion detected by RNA next-generation sequencing.

Current patterns of care and outcomes for dermatofibrosarcoma protuberans: An international multi-institutional collaborative.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with an infiltrative growth pattern that makes it challenging to clear margins. High quality data regarding DFSP natural history, management, and outcomes are limited. METHODS: Data were retrospectively collected for adult DFSP patients who underwent resection at 10 institutions in eight countries. Demographics, tumor characteristics, treatment strategies, and outcomes were analyzed. RESULTS: Analysis included 347 patients consisting of young (median, 42 years), White (76.2%), males (54.2%) with truncal lesions (57.3%). The majority (76.8%) were symptomatic at presentation. Preoperative imaging was used in 55.9% of cases. Diagnosis was established with excisional biopsy in 50.9% versus incisional biopsy in 25.0% of cases. Despite planned margins of >1.0 cm in 67.4% of cases, only 69.0% of patients achieved R0 resection. Twenty-two percent of patients underwent at least one re-excision. R0 resection was achieved at a second procedure in 80.2% and a third procedure in 86.2%. Ultimately, R0 resection was feasible in 89.5% of all patients. Fibrosarcomatous transformation (FST) was observed in 12.6%. In total, 6.6% (N = 23) recurred (17 local, six distant). Of the six distant recurrences, 50.0% had FST. With a median follow-up of 47.0 months, disease-specific survival rate was 98.8%. In multivariable analysis, R0 margins at index resection were associated with wider circumferential margins and non-FST histology. CONCLUSIONS: In this international, multicenter collaborative, DFSP practice patterns were heterogeneous but achieved favorable recurrence rates and survival. Multiple excisions to clear margins remain commonplace and can inform future efforts to optimize margin selection.

A Randomized, Controlled Trial Evaluating Perioperative Risk-Stratification and Risk-Based, Protocol-Driven Management After Elective Major Cancer Surgery.

OBJECTIVE: We evaluated the efficacy of risk-based, protocol-driven management versus (vs) usual management after elective major cancer surgery to reduce 30-day rates of postoperative death or serious complications (DSC) . SUMMARY BACKGROUND DATA: Major cancer surgery is associated with significant perioperative risks which result in worse long-term outcomes. METHODS: Adults scheduled for elective major cancer surgery were stratified/randomized to risk-based escalating levels of care, monitoring, and co-management vs usual management. The primary study outcome was 30-day rate of DSC. Additional outcomes included complications, adverse events, health care utilization, health-related quality of life (HRQOL), and disease-free and overall survival (DFS and OS). RESULTS: Between August 2014 and June 2020, 1529 patients were enrolled and randomly allocated to the study arms; 738 patients in the Intervention Arm and 732 patients in the Control Arm were eligible for analysis. 30-day rate of DSC with the intervention was 15.0% (95% CI, 12.5-17.6%) vs 14.1%, (95% CI, 11.6-16.6%) with usual management (P=0.65). There were no differences in 30-day rates of complications or adverse events (including return to the operating room); postoperative length of stay; rate of discharge to home; or 30, 60, or 90-day HRQOL or rates of hospital readmission or receipt of anti-neoplastic therapy between the study arms. At median follow-up of 48 months, OS (P=0.57) and DFS (P=0.91) were similar. CONCLUSIONS: Risk-based, protocol-driven management did not reduce 30-day rate of DSC after elective major cancer surgery compared to usual management, nor improve postoperative health care utilization, HRQOL, or cancer outcomes. Trials are needed to identify cost-effective, tailored perioperative strategies to optimize outcomes after major cancer surgery.

Perceptions of Readiness for Practice After Complex General Surgical Oncology Fellowship: A Survey Study.

BACKGROUND: Surgical subspecialty training aims to meet the needs of practicing surgeons and their communities. This study investigates career preparedness of Complex General Surgical Oncology (CGSO) fellowship graduates, identifies factors associated with practice readiness, and explores potential opportunities to improve the current training model. METHODS: The Society of Surgical Oncology partnered with the National Cancer Institute to conduct a 36-question survey of CGSO fellowship graduates from 2012 to 2022. RESULTS: The overall survey response rate was 38% (221/582) with a slight male predominance (63%). Forty-six percent of respondents completed their fellowship after 2019. Factors influencing fellowship program selection include breadth of cancer case exposure (82%), mentor influence (66%), and research opportunities (38%). Overall, graduates reported preparedness for practice; however, some reported unpreparedness in research (18%) and in specific clinical areas: thoracic (43%), hyperthermic intraperitoneal chemotherapy (HIPEC) (15%), and hepato-pancreato-biliary (15%) surgery. Regarding technical preparedness, 70% reported being "very prepared". Respondents indicated lack of preparedness in robotic (63%) and laparoscopic (33%) surgery approaches. Suggestions for training improvement included increased autonomy and case volumes, program development, and research infrastructure. Current practice patterns by graduates demonstrated discrepancies between ideal contracts and actual practice breakdowns, particularly related to the practice of general surgery. CONCLUSIONS: This study of CGSO fellowship graduates demonstrates potential gaps between trainee expectations and the realities of surgical oncology practice. Although CGSO fellowship appears to prepare surgeons for careers in surgical oncology, there may be opportunities to refine the training model to better align with the needs of practicing surgical oncologists.

NCCN Guidelines® Insights: Merkel Cell Carcinoma, Version 1.2024.

The NCCN Guidelines for Merkel Cell Carcinoma (MCC) provide recommendations for diagnostic workup, clinical stage, and treatment options for patients. The panel meets annually to discuss updates to the guidelines based on comments from expert review from panel members, institutional review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new page for locally advanced disease in the setting of clinical node negative status, entitled "Clinical N0 Disease, Locally Advanced MCC." This new algorithm page addresses locally advanced disease, and the panel clarifies the meaning behind the term "nonsurgical" by further defining locally advanced disease. In addition, the guideline includes the management of in-transit disease and updates to the systemic therapy options.

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.

Retrospective Analysis of Retroperitoneal-Abdominal-Pelvic Ganglioneuromas: An International Study by the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).

OBJECTIVE: The Transatlantic Australasian Retroperitoneal Sarcoma Working Group conducted a retrospective study on the disease course and clinical management of ganglioneuromas. BACKGROUND: Ganglioneuromas are rare tumors derived from neural crest cells. Data on these tumors remain limited to case reports and single-institution case series. METHODS: Patients of all ages with pathologically confirmed primary retroperitoneal, intra-abdominal, and pelvic ganglioneuromas between January 1, 2000, and January 1, 2020, were included. We examined demographic, clinicopathologic, and radiologic characteristics, as well as clinical management. RESULTS: Overall, 328 patients from 29 institutions were included. The median age at diagnosis was 37 years with 59.1% of patients being female. Symptomatic presentation comprised 40.9% of cases, and tumors were often located in the extra-adrenal retroperitoneum (67.1%). At baseline, the median maximum tumor diameter was 7.2 cm. One hundred sixteen (35.4%) patients underwent active surveillance, whereas 212 (64.6%) patients underwent resection with 74.5% of operative cases achieving an R0/R1 resection. Serial tumor evaluations showed that malignant transformation to neuroblastoma was rare (0.9%, N=3). Tumors undergoing surveillance had a median follow-up of 1.9 years, with 92.2% of ganglioneuromas stable in size. With a median follow-up of 3.0 years for resected tumors, 84.4% of patients were disease free after resections, whereas recurrences were observed in 4 (1.9%) patients. CONCLUSIONS: Most ganglioneuromas have indolent disease courses and rarely transform to neuroblastoma. Thus, active surveillance may be appropriate for benign and asymptomatic tumors particularly when the risks of surgery outweigh the benefits. For symptomatic or growing tumors, resection may be curative.

Basal Cell Skin Cancer, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States. Due to the high frequency, BCC occurrences are not typically recorded, and annual rates of incidence can only be estimated. Current estimated rates are 2 million Americans affected annually, and this continues to rise. Exposure to radiation, from either sunlight or previous medical therapy, is a key player in BCC development. BCC is not as aggressive as other skin cancers because it is less likely to metastasize. However, surgery and radiation are prevalent treatment options, therefore disfigurement and limitation of function are significant considerations. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline an updated risk stratification and treatment options available for BCC.

COVID-19 is Affecting the Presentation and Treatment of Melanoma Patients in the Northeastern United States.

BACKGROUND: Covid-19 significantly affected healthcare delivery over the past year, with a shift in focus away from nonurgent care. Emerging data are showing that screening for breast and colon cancer has dramatically decreased. It is unknown whether the same trend has affected patients with melanoma. METHODS: This is a retrospective cohort study of melanoma patients at two large-volume cancer centers. Patients were compared for 8 months before and after the lockdown. Outcomes focused on delay in treatment and possible resultant upstaging of melanoma. RESULTS: A total of 375 patients were treated pre-lockdown and 313 patients were treated post-lockdown (17% decrease). Fewer patients presented with in situ disease post-lockdown (15.3% vs. 17.9%), and a higher proportion presented with stage III-IV melanoma (11.2% vs. 9.9%). Comparing patients presenting 2 months before versus 2 months after the lockdown, there was an even more significant increase in Stage III-IV melanoma from 7.1% to 27.5% (p < 0.0001). Finally, in Stage IIIB-IIID patients, there was a decrease in patients receiving adjuvant therapy in the post lockdown period (20.0% vs. 15.2%). CONCLUSIONS: As a result of the recent pandemic, it appears there has been a shift away from melanoma in situ and toward more advanced disease, which may have significant downstream effects on prognosis and could be due to a delay in screening. Significantly patients have presented after the lockdown, and fewer patients are undergoing the recommended adjuvant therapies. Patient outreach efforts are essential to ensure that patients continue to receive preventative medical care and screening as the pandemic continues.

National Trends in Treatment for Retroperitoneal Soft Tissue Sarcoma: A Modern Appraisal of Variability in Therapeutic Strategies.

BACKGROUND: Little level 1 evidence exists to guide multimodality treatment in retroperitoneal soft tissue sarcoma (RPS), which may lead to significant variation in therapeutic approaches. This analysis aimed to describe national RPS treatment trends and explore potential variability among low-/high-volume hospitals (LVH/HVHs). PATIENTS AND METHODS: In total, 5992 patients who underwent resection for primary RPS were retrospectively identified in the National Cancer Database (2004-2017). Time trend analyses examined rates of multivisceral resection (MVR), radiation, and chemotherapy use. LVHs were defined as those carrying out fewer than ten resections per year (N = 5433), whereas HVHs were defined as those carrying out ten or more (N = 559). Descriptive statistics and logistic regression models compared trends between groups. RESULTS: MVR was more frequent at HVHs (63.7% versus 43.5%, p < 0.001). Use of radiation varied widely by hospital volume. HVHs more frequently employed preoperative radiation as compared with LVHs (14.7% versus 8.1%, p < 0.001). Throughout the study period, LVHs increased utilization of preoperative radiation (2.6% to 12.0%, p < 0.001) whereas rates at HVHs remained stable. Overall, LVHs utilized postoperative radiation significantly more frequently as compared with HVHs (14.7% versus 2.7%, respectively, p < 0.001). Postoperative radiation at LVHs remained stable until 2013 and sharply declined thereafter (16.7% to 6.9%, p < 0.001). Rates of postoperative radiation use at HVHs remained lower than those at LVHs at all time points. CONCLUSIONS: Strategies for resection and radiation use at LVHs have trended towards those of HVHs. Current national implementation of preoperative radiation, MVR, and chemotherapy remains heterogeneous. These findings inform future trial design and support standardization of care.

Oncologic Outcomes of Multi-Institutional Minimally Invasive Inguinal Lymph Node Dissection for Melanoma Compared with Open Inguinal Dissection in the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II).

BACKGROUND: Minimally invasive inguinal lymphadenectomy (MILND) is safe and feasible, but limited data exist regarding oncologic outcomes. METHODS: This study performed a multi-institutional retrospective cohort analysis of consecutive MILND performed for melanoma between January 2009 and June 2016. The open ILND (OILND) comparative cohort comprised patients enrolled in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II) between December 2004 and March 2014.The pre-defined primary end point was the same-basin regional nodal recurrence, calculated using properties of binomial distribution. Time to events was calculated using the Kaplan-Meier method. The secondary end points were overall survival, progression-free survival, melanoma-specific survival (MSS), and distant metastasis-free survival (DMFS). RESULTS: For all the patients undergoing MILND, the same-basin regional recurrence rate was 4.4 % (10/228; 95 % confidence interval [CI], 2.1-7.9 %): 8.2 % (4/49) for clinical nodal disease and 3.4 % (6/179) for patients with a positive sentinel lymph node (SLN) as the indication. For the 288 patients enrolled in MSLT-II who underwent OILND for a positive SLN, 17 (5.9 %) had regional node recurrence as their first event. After controlling for ulceration, positive LN count and positive non-SLNs at the time of lymphadenectomy, no difference in OS, PFS, MSS or DMFS was observed for patients with a positive SLN who underwent MILND versus OILND. CONCLUSION: This large multi-institutional experience supports the oncologic safety of MILND for melanoma. The outcomes in this large multi-institutional experience of MILND compared favorably with those for an OILND population during similar periods, supporting the oncologic safety of MILND for melanoma.

Management of Locally Recurrent Retroperitoneal Sarcoma in the Adult: An Updated Consensus Approach from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: Surgery is the mainstay of treatment for retroperitoneal sarcoma (RPS), but local recurrence is common. Biologic behavior and recurrence patterns differ significantly among histologic types of RPS, with implications for management. The Transatlantic Australasian RPS Working Group (TARPSWG) published a consensus approach to primary RPS, and to complement this, one for recurrent RPS in 2016. Since then, additional studies have been published, and collaborative discussion is ongoing to address the clinical challenges of local recurrence in RPS. METHODS: An extensive literature search was performed, and the previous consensus statements for recurrent RPS were updated after review by TARPSWG members. The search included the most common RPS histologic types: liposarcoma, leiomyosarcoma, solitary fibrous tumor, undifferentiated pleomorphic sarcoma, and malignant peripheral nerve sheath tumor. RESULTS: Recurrent RPS management was evaluated from diagnosis to follow-up evaluation. For appropriately selected patients, resection is safe. Nomograms currently are available to help predict outcome after resection. These and other new findings have been combined with expert recommendations to provide 36 statements, each of which is attributed a level of evidence and grade of recommendation. In this updated document, more emphasis is placed on histologic type and clarification of the intent for surgical treatment, either curative or palliative. Overall, the fundamental tenet of optimal care for patients with recurrent RPS remains individualized treatment after multidisciplinary discussion by an experienced team with expertise in RPS. CONCLUSIONS: Updated consensus recommendations are provided to help guide decision-making for treatment of locally recurrent RPS and better selection of patients who would potentially benefit from surgery.

A Virtual Tumor Board Platform: A Way to Enhance Decision-Making for Complex Malignancies.

INTRODUCTION: Multidisciplinary tumor boards (TBs) are crucial for decision-making and management of patients diagnosed with complex malignancies. The social distancing conditions imposed by coronavirus disease 2019 presented an opportunity to compare virtual versus in-person TBs. METHODS: A retrospective analysis of attendance data from an National Cancer Institute-designated cancer center's gastrointestinal (GI) TB participant data from September 2019 to October 2020. In addition, an online survey assessing the virtual TB experience was sent to participants of all TBs. Interrupted time series analyses were performed to evaluate preintervention and postintervention GI TB attendance only. RESULTS: The overall mean attendance for GI TB was 30 participants; turnout was higher for virtual format compared to in-person (32 versus 23 attendees, P < 0.001). This increase was seen across all participant categories: attending physicians (15 versus 11 attendees, P < 0.001), trainees (11 versus 8, P < 0.001), and support staff (6 versus 3, P < 0.001). There was no significant difference in the mean number of cases discussed between TB formats. The majority of the 141 survey respondents (across all TB) were attending physicians with >20-year experience. Most supported a permanent virtual or hybrid TB format, 72.5% found this format to be more time efficient and with similar productivity, and 85.8% found it easier to attend. The majority (89.9%) felt confident that the decision-making process was not affected by virtual interactions. CONCLUSIONS: A virtual platform for multispecialty TBs allows for greater attendance without sacrificing the decision-making process. This survey supports continuing with a virtual or hybrid format, which may increase attendance and facilitate access to multidisciplinary discussions leading to improved patient care.

Defining the role of neoadjuvant systemic therapy in high-risk retroperitoneal sarcoma: A multi-institutional study from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: In patients with retroperitoneal sarcoma (RPS), the incidence of recurrence after surgery remains high. Novel treatment approaches are needed. This retrospective study evaluated patients with primary, high-risk RPS who received neoadjuvant systemic therapy followed by surgery to 1) determine the frequency and potential predictors of radiologic tumor responses and 2) assess clinical outcomes. METHODS: Clinicopathologic data were collected for eligible patients treated at 13 sarcoma referral centers from 2008 to 2018. Univariable and multivariable logistic models were performed to assess the association between clinical predictors and response. Overall survival (OS) and crude cumulative incidences of local recurrence and distant metastasis were compared. RESULTS: Data on 158 patients were analyzed. A median of 3 cycles of neoadjuvant systemic therapy (interquartile range, 2-4 cycles) were given. The regimens were mostly anthracycline based; however, there was significant heterogeneity. No patients demonstrated a complete response, 37 (23%) demonstrated a partial response (PR), 88 (56%) demonstrated stable disease, and 33 (21%) demonstrated progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Only a higher number of cycles given was positively associated with PR (P = .005). All patients underwent complete resection, regardless of the tumor response. Overall, patients whose tumors demonstrated PD before surgery showed markedly worse OS (P = .005). An indication of a better clinical outcome was seen in specific regimens given for grade 3 dedifferentiated liposarcoma and leiomyosarcoma. CONCLUSIONS: In patients with high-risk RPS, the response to neoadjuvant systemic therapy is fair overall. Disease progression on therapy may be used to predict survival after surgery. Subtype-specific regimens should be further validated.

Active surveillance of patients who have sentinel node positive melanoma: An international, multi-institution evaluation of adoption and early outcomes after the Multicenter Selective Lymphadenectomy Trial II (MSLT-2).

BACKGROUND: For 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. METHODS: In 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. RESULTS: Among 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. CONCLUSIONS: Active 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.

Treatment at an Academic Cancer Center Confers Better Survival by Stage for Signet-Ring Cell and Non-signet-Ring Cell Gastric Cancer.

BACKGROUND: The literature lacks large-scale population studies comparing survival outcomes between signet-ring cell gastric carcinoma (SRGC) and non-SRGC (NSRGC) when treatment is delivered at academic versus community cancer centers. METHODS: The National Cancer Database (NCDB) from 2004 to 2016 was queried to examine the association between treatment facility category and overall survival of patients who underwent gastrectomy for resectable gastric adenocarcinoma (GAC). RESULTS: The study investigated 22,871 patients. Upstaging of resectable GAC to pathologic stage 4 was more evident at community centers (3.5%) than at academic centers (2.8%) for the NSRGC variant (p = 0.211), whereas it was comparable between the two facility categories for the SRGC variant (5.9% vs 6%, respectively). Patients with pathologic stage 1 or 3 NSRGC who underwent gastrectomy at academic programs had better overall survival (OS) (hazard ratio [HR], 0.68; p < 0.0001) than those who underwent gastrectomy at community centers (HR, 0.79; p < 0.0065). Similarly, patients with stage 2 SRGC had better OS when treated at academic versus community centers (HR, 0.54; p = 0.0019). No statistically significant improvement in OS was observed between patients with stage 2 NSRGC (HR, 0.84; p = 0.083) and those with stage 3 SRGC (HR, 0.78; p = 0.054) who were treated at academic centers. No survival benefit was demonstrated for stage 1 SRGC when academic and community centers were compared (p = 0.56). CONCLUSIONS: This is the first study based on a large-scale database in the Western population that addressed the overall survival-by-stage of two distinct GAC histologic variants. Treatment at academic centers was associated with significant improvements in OS.

Gastrostomy Tube for Nutrition and Malignant Bowel Obstruction in Patients With Cancer.

BACKGROUND: Gastrostomy tubes (G-tubes) are invaluable clinical tools that play a role in palliation and nutrition in patients with cancer. This study aimed to better understand the risks and benefits associated with the placement and maintenance of G-tubes. METHODS: Patients who underwent placement of a G-tube for cancer from January 2013 through December 2017 at a tertiary care center were considered for inclusion. Clinical data were retrospectively collected from medical records. RESULTS: A total of 242 patients with cancer, whose average age at diagnosis was 61 years (range, 21-94 years), underwent G-tube placement for nutrition (76.4%), decompression (22.7%), or both (0.8%). Successful insertion was achieved in 96.8%, but 8 patients required >1 attempted method of insertion. In the decompression group, minor postplacement complications were less common (23.6% vs 53.5%; P<.001) and survival was shorter (P<.001) compared with the nutrition group. For those with decompressive G-tubes, 45.5% had a palliative care consult; 56.4% were seen by social workers; and 46.3% went to hospice. The frequency of hospice discharge was higher in patients who had consults (53.7% vs 23.1%; P=.01). CONCLUSIONS: Half of the patients who received decompressive G-tubes presented with stage IV disease and died within 1 month of placement. Those with >1 consult were more likely to be discharged to hospice. Patients with G-tubes for nutrition saw no change in functionality, complication rate, or survival, regardless of adjunct chemotherapy status. These findings illustrate the need for a tool to allow a better multidisciplinary approach and interventional decision-making for patients with cancer.

NCCN Guidelines® Insights: Squamous Cell Skin Cancer, Version 1.2022.

The NCCN Guidelines for Squamous Cell Skin Cancer provide recommendations for diagnostic workup, clinical stage, and treatment options for patients with cutaneous squamous cell carcinoma. The NCCN panel meets annually to discuss updates to the guidelines based on comments from panel members and the Institutional Review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new surgical recommendation terminology (peripheral and deep en face margin assessment), as well as recent updates on topical prophylaxis, immunotherapy for regional and metastatic disease, and radiation therapy.