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Effectiveness and Safety of Extended Treatment Apixaban Versus Low-Molecular-Weight Heparin in Cancer-Associated Venous Thromboembolism

Alexander T. Cohen, Amol D. Dhamane, Xuejun Liu, Risho Singh, Stella Han, Robert Stellhorn, Jane Wang, and Xuemei Luo

Background: Limited real-world evidence is available comparing the safety and effectiveness of apixaban and low-molecular-weight heparins (LMWHs) for preventing recurrent venous thromboembolism (VTE) in patients with active cancer receiving anticoagulation in an extended treatment setting. This study evaluated the risk of bleeding and recurrent VTE in patients with cancer-associated VTE who were prescribed apixaban or LMWH for ≥3 months. Methods: A US commercial claims database was used to identify adult patients with VTE and active cancer who initiated apixaban or LMWH 30 days following the first VTE diagnosis and had ≥3 months of continuous enrollment and 3 months of primary anticoagulation treatment. Patients were followed from the day after the end of primary anticoagulation treatment until the earliest of: date of disenrollment, discontinuation of index anticoagulant, switch to another anticoagulant, or end of the study period. Inverse-probability treatment weighting (IPTW) was used to balance treatment cohorts. Incidence rates (IRs) for the outcomes were calculated per 100 person-years (PY). Cox proportional hazard models were used to evaluate the adjusted risk of recurrent VTE, major bleeding (MB), and clinically relevant nonmajor bleeding (CRNMB). Results: A total of 13,564 apixaban- and 2,808 LMWH-treated patients were analyzed. Post-IPTW, the treatment cohorts were balanced. Patients receiving apixaban had lower adjusted IRs for recurrent VTE (4.1 vs 9.6 per 100 PY), MB (6.3 vs 12.6), and CRNMB (26.1 vs 36.0) versus LMWH (P<.0001 for all comparisons) during the follow-up period. Patients on apixaban had a lower adjusted risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.34–0.53), MB (HR, 0.50; 95% CI, 0.41–0.61), and CRNMB (HR, 0.76; 95% CI, 0.68–0.85) versus LMWH. Conclusions: Extended anticoagulation treatment of ≥3 months with apixaban was associated with lower rates of recurrent VTE, MB, and CRNMB compared with LMWH in adults with cancer-associated VTE.

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Erratum

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Highlights of the NCCN Oncology Research Program

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NCCN Guidelines® Insights: Rectal Cancer, Version 3.2024

Featured Updates to the NCCN Guidelines

Al B. Benson III, Alan P. Venook, Mohamed Adam, George Chang, Yi-Jen Chen, Kristen K. Ciombor, Stacey A. Cohen, Harry S. Cooper, Dustin Deming, Ignacio Garrido-Laguna, Jean L. Grem, Paul Haste, J. Randolph Hecht, Sarah Hoffe, Steven Hunt, Hisham Hussan, Kimberly L. Johung, Nora Joseph, Natalie Kirilcuk, Smitha Krishnamurthi, Midhun Malla, Jennifer K. Maratt, Wells A. Messersmith, Jeffrey Meyerhardt, Eric D. Miller, Mary F. Mulcahy, Steven Nurkin, Aparna Parikh, Hitendra Patel, Katrina Pedersen, Leonard Saltz, Charles Schneider, David Shibata, Benjamin Shogan, John M. Skibber, Constantinos T. Sofocleous, Anna Tavakkoli, Christopher G. Willett, Christina Wu, Frankie Jones, and Lisa Gurski

The determination of an optimal treatment plan for an individual patient with rectal cancer is a complex process. In addition to decisions relating to the intent of rectal cancer surgery (ie, curative or palliative), consideration must also be given to the likely functional results of treatment, including the probability of maintaining or restoring normal bowel function/anal continence and preserving genitourinary functions. Particularly for patients with distal rectal cancer, finding a balance between curative-intent therapy while having minimal impact on quality of life can be challenging. Furthermore, the risk of pelvic recurrence is higher in patients with rectal cancer compared with those with colon cancer, and locally recurrent rectal cancer is associated with a poor prognosis. Careful patient selection and the use of sequenced multimodality therapy following a multidisciplinary approach is recommended. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Rectal Cancer, including the addition of endoscopic submucosal dissection as an option for early-stage rectal cancer, updates to the total neoadjuvant therapy approach based on the results of recent clinical trials, and the addition of a “watch-and-wait” nonoperative management approach for clinical complete responders to neoadjuvant therapy.

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NCCN News

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Neuroblastoma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology

Rochelle Bagatell, Julie R. Park, Sahaja Acharya, Jennifer Aldrink, Jenna Allison, Elizabeth Alva, Carola Arndt, Daniel Benedetti, Erin Brown, Steve Cho, Alanna Church, Andrew Davidoff, Ami V. Desai, Steven DuBois, Douglas Fair, Joaquim Farinhas, Douglas Harrison, Frederick Huang, Paul Iskander, Susan Kreissman, Margaret Macy, Brian Na, Farzana Pashankar, Praveen Pendyala, Navin Pinto, Stephanie Polites, Raja Rabah, Hiroyuki Shimada, Leonora Slatnick, Elizabeth Sokol, Clare Twist, Kieuhoa Vo, Tanya Watt, Suzanne Wolden, Peter Zage, Ryan Schonfeld, and Lisa Hang

Neuroblastoma is the most common extracranial solid tumor diagnosed in children. This inaugural version of the NCCN Guidelines for Neuroblastoma provides recommendations for the diagnosis, risk classification, and treatment of neuroblastoma. The information in these guidelines was developed by the NCCN Neuroblastoma Panel, a multidisciplinary group of representatives with expertise in neuroblastoma, consisting of pediatric oncologists, radiologists, pathologists, surgeons, and radiation oncologists from NCCN Member Institutions. The evidence-based and consensus recommendations contained in the NCCN Guidelines are intended to guide clinicians in selecting the most appropriate treatments for their patients with this clinically heterogeneous disease.

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Care Patterns and Barriers to Outpatient Care for Adults With AML Following Intensive Chemotherapy at NCCN Member Institutions

Anna B. Halpern, Jessica M. Sugalski, Lindsey Bandini, Megan Othus, F. Marc Stewart, and Roland B. Walter

Background: Prolonged hospitalization following intensive (re)induction chemotherapy for acute myeloid leukemia (AML), while standard, is costly and resource intense, limits inpatient bed capacity, and negatively impacts quality of life. Early hospital discharge (EHD) following completion of chemotherapy has proven safe as an alternative at select institutions, but is not widely implemented. Patients and Methods: From February 2023 through May 2023, the NCCN Best Practices Committee conducted a survey evaluating AML hospitalization patterns, care models, and barriers to EHD at its 33 member institutions. Results: A total of 30 (91%) institutions completed the survey; two-thirds treat >100 patients with AML annually and 45% treat more than half of these with intensive chemotherapy. In the (re)induction setting, 80% of institutions keep patients hospitalized until blood count recovery, whereas 20% aim to discharge patients after completion of chemotherapy if medically stable and logistically feasible. The predominant reasons for the perceived need for ongoing hospitalization were high risk of infection, treatment toxicities, and lack of nearby/accessible housing. There was no significant association between ability to practice EHD and annual AML volume or treatment intensity patterns (P=.60 and P=.11, respectively). In contrast, in the postremission setting, 87% of centers support patients following chemotherapy in the outpatient setting unless toxicities arise requiring readmission. Survey responses showed that 80% of centers were interested in exploring EHD after (re)induction but noted significant barriers, including accessible housing (71%), transportation (50%), high toxicity/infection rate (50%), high transfusion burden (50%), and limited bed availability for rehospitalization (50%). Conclusions: Hospitalization and care patterns following intensive AML therapy vary widely across major US cancer institutions. Although only 20% of surveyed centers practice EHD following intensive (re)induction chemotherapy, 87% do so following postremission therapy. Given the interest in exploring the EHD approach given potential advantages of EHD for both patients and health care systems, strategies to address identified medical and logistical barriers should be explored.

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Establishing Consensus for Mohs Micrographic Surgical Techniques in the Treatment of Melanoma in Situ for Future Clinical Trials: A Modified Delphi Study

Kristen K. Curtis, Nathan J. Fakult, Jennifer L. Strunck, Sumaira Z. Aasi, Christine S. Ahn, Murad Alam, Anna A. Bar, Ramona Behshad, Christopher K. Bichakjian, Diana Bolotin, Susan L. Boone, Jeremy S. Bordeaux, Jerry D. Brewer, David R. Carr, John A. Carucci, Jason R. Castillo, Sean R. Christensen, Melanie A. Clark, Lindsey K. Collins, Addison M. Demer, Daniel B. Eisen, Hao Feng, Bahar F. Firoz, Roy C. Grekin, Jason M. Hirshburg, Todd E. Holmes, Conway C. Huang, Thomas A. Jennings, Shang I. Brian Jiang, Sailesh Konda, Justin J. Leitenberger, Jesse M. Lewin, Ian A. Maher, Elise Ng, Ida F. Orengo, Faramarz H. Samie, Drew K. Saylor, Victoria Rose Sharon, Teo Soleymani, Susan M. Swetter, Jesalyn A. Tate, Marta J. Van Beek, Nahid Y. Vidal, Alok Vij, Ashley Wysong, Yaohui Gloria Xu, Bryan T. Carroll, and Wesley Y. Yu

Background : Mohs micrographic surgery (MMS) is a promising treatment modality for melanoma in situ (MIS). However, variations in surgical technique limit the generalizability of existing data and may impede future study of MMS in clinical trials. Methods: A modified Delphi method was selected to establish consensus on optimal MMS techniques for treating MIS in future clinical trials. The Delphi method was selected due to the limited current data, the wide range of techniques used in the field, and the intention to establish a standardized technique for future clinical trials. A literature review and interviews with experienced MMS surgeons were performed to identify dimensions of the MMS technique for MIS that (1) likely impacted costs or outcomes of the procedure, and (2) showed significant variability between surgeons. A total of 8 dimensions of technical variation were selected. The Delphi process consisted of 2 rounds of voting and commentary, during which 44 expert Mohs surgeons across the United States rated their agreement with specific recommendations using a Likert scale. Results: Five of eight recommendations achieved consensus in Round 1. All 3 of the remaining recommendations achieved consensus in Round 2. Techniques achieving consensus in Round 1 included the use of a starting peripheral margin of ≤5 mm, application of immunohistochemistry, frozen tissue processing, and resecting to the depth of subcutaneous fat. Consensus on the use of Wood’s lamp, dermatoscope, and negative tissue controls was established in Round 2. Conclusions: This study generated 8 consensus recommendations intended to offer guidance for Mohs surgeons treating MIS. The adoption of these recommendations will promote standardization to facilitate comparisons of aggregate data in multicenter clinical trials.

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The Impact of Adjuvant Chemotherapy on the Long-Term Prognosis of Breast Malignant Phyllodes Tumors: A Propensity Score–Matched Study

Zilin Zhuang, Ailifeire Yilihamu, Zhihua Li, Rong Lei, Xun Li, Mengjia Han, Wei Wei, Guangxin Li, Zhen Ma, Yulu Zhang, Hui Hu, Xiaoyun Xiao, and Yan Nie

Background: Malignant phyllodes tumors (MPTs) are rare breast tumors with high risks of local recurrence and distant metastasis. Surgical intervention is the primary treatment, but the effectiveness of adjuvant therapies is uncertain. This study was designed to analyze the prognostic risk factors associated with MPTs and evaluate the efficacy of postoperative adjuvant chemotherapy. Patients and Methods: Patients who were first diagnosed with MPT without distant metastasis and received R0 resection surgery between 1999 and 2023 were included in the present study and stratified into 2 groups: chemotherapy and nonchemotherapy groups. Propensity score matching (PSM) was used to balance baseline characteristics between groups. Kaplan-Meier curves were used to estimate local recurrence–free survival (LRFS) and overall survival (OS). Cox proportional hazards analyses (univariate and multivariate) were conducted to identify prognostic risk factors. Results: We conducted a study involving 145 patients, 31 of whom underwent a total of 12 different chemotherapy regimens following initial surgical resection. Most patients received chemotherapy regimens primarily consisting of anthracyclines, including anthracycline + ifosfamide (AI) or anthracycline + cyclophosphamide/docetaxel (AC-T) regimens. After a median follow-up of 54.5 months, 37 (25.5%) patients experienced local recurrence and 24 (16.6%) experienced distant metastasis. No significant difference was detected in the rates of local recurrence or distant metastasis between the 2 groups. Axillary lymph node positivity was the only risk factor for LRFS, whereas older age, larger tumors, axillary lymph node positivity, local recurrence, and distant metastasis were significantly associated with worse OS. Chemotherapy did not emerge as a protective factor for LRFS (P=.501) or OS (P=.854). After PSM, patients in the chemotherapy group did not exhibit better 5-year LRFS (P=.934) or 5-year OS (P=.328). Conclusions: According to our retrospective evaluation, postoperative adjuvant chemotherapy was not associated with improved survival in patients with MPTs without distant metastasis.

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Increasing Colorectal Screening Uptake in Spouses of Patients With Colorectal Cancer Using a Randomized Behavioral Trial

Jerrald Lau, Lina Choe, Daphne Hui Juan Lee, Athena Ming-Gui Khoo, Wei-Ling Koh, Cherie Peh, Alyssa Ng, Tian-Zhi Lim, Bettina Lieske, Kuok-Chung Lee, Choon-Seng Chong, Choon-Sheong Seow, Christopher H.L. Keh, Jing-Yu Ng, and Ker-Kan Tan

Background: Colorectal cancer (CRC) is one of the few cancers for which screening has been associated with better survival and morbidity, but screening uptake has been underexplored in spouses of existing patients with CRC. The objective of this study was to evaluate whether a brief, structured behavioral intervention delivered to spouses of patients with CRC in a colorectal clinical setting could increase fecal immunochemical test (FIT) uptake within 3 months of the study period. Methods: This study was designed as a block randomized, unblinded, parallel trial conducted in the colorectal outpatient clinics of 2 public tertiary hospitals in Singapore from December 2017 to February 2023. The intervention group received a structured informational pamphlet on CRC screening by the Singapore Ministry of Health and a printed guide with instructions on how to properly use a FIT kit. Results: No significant differences in baseline characteristics were observed between the 2 groups. There was a statistically significant difference (P<.001) in FIT screening uptake between spouses in each group, with 86.2% (n=25) in the intervention group and 38.7% (n=12) in the control group. Conclusions: Our study demonstrated that a brief, structured behavioral intervention offered to spouses accompanying patients with CRC while they wait for the clinic appointment is useful in increasing FIT screening uptake rates. Colorectal clinics can consider setting aside 10 to 15 minutes to educate accompanying spouses in the future as a complementary avenue to holistically promote CRC prevention, subjected to the resources available in each clinic.

ClinicalTrials.gov identifier: NCT04544852