NCCN Guidelines Insights: Soft Tissue Sarcoma, Version 1.2021

Featured Updates to the NCCN Guidelines

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  • 1 Fox Chase Cancer Center;
  • | 2 Roswell Park Comprehensive Cancer Center;
  • | 3 Moffitt Cancer Center;
  • | 4 Massachusetts General Hospital Cancer Center;
  • | 5 The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute;
  • | 6 UCLA Jonsson Comprehensive Cancer Center;
  • | 7 Stanford Cancer Institute;
  • | 8 Dana-Farber/Brigham and Women’s Cancer Center;
  • | 9 O'Neal Comprehensive Cancer Center at UAB;
  • | 10 UT Southwestern Simmons Comprehensive Cancer Center;
  • | 11 Vanderbilt-Ingram Cancer Center;
  • | 12 Memorial Sloan Kettering Cancer Center;
  • | 13 Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance;
  • | 14 University of Colorado Cancer Center;
  • | 15 Fred & Pamela Buffett Cancer Center;
  • | 16 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins;
  • | 17 St. Jude Children’s Research Hospital/The University of Tennessee Health Science Center;
  • | 18 University of Wisconsin Carbone Cancer Center;
  • | 19 City of Hope National Medical Center;
  • | 20 Mayo Clinic Cancer Center;
  • | 21 Huntsman Cancer Institute at the University of Utah;
  • | 22 Duke Cancer Institute;
  • | 23 Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute;
  • | 24 University of Michigan Rogel Cancer Center;
  • | 25 Abramson Cancer Center at the University of Pennsylvania;
  • | 26 UC San Diego Moores Cancer Center;
  • | 27 Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine;
  • | 28 UCSF Helen Diller Family Comprehensive Cancer Center; and
  • | 29 National Comprehensive Cancer Network.

The NCCN Guidelines for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with soft tissue sarcomas. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including the development of a separate and distinct guideline for gastrointestinal stromal tumors (GISTs); reconception of the management of desmoid tumors; inclusion of further recommendations for the diagnosis and management of extremity/body wall, head/neck sarcomas, and retroperitoneal sarcomas; modification and addition of systemic therapy regimens for sarcoma subtypes; and revision of the principles of radiation therapy for soft tissue sarcomas.

NCCN: Continuing Education

Target Audience: This activity is designed to meet the educational needs of oncologists, nurses, pharmacists, and other healthcare professionals who manage patients with cancer.

Accreditation Statements

In support of improving patient care, National Comprehensive Cancer Network (NCCN) is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Medicine (ACCME): NCCN designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Nursing (ANCC): NCCN designates this educational activity for a maximum of 1.0 contact hour.

Pharmacy (ACPE): NCCN designates this knowledge-based continuing education activity for 1.0 contact hour (0.1 CEUs) of continuing education credit. UAN: JA4008196-0000-20-013-H01-P

All clinicians completing this activity will be issued a certificate of participation. To participate in this journal CE activity: (1) review the educational content; (2) take the posttest with a 66% minimum passing score and complete the evaluation at https://education.nccn.org/node/89065; and (3) view/print certificate.

Pharmacists: You must complete the posttest and evaluation within 30 days of the activity. Continuing pharmacy education credit is reported to the CPE Monitor once you have completed the posttest and evaluation and claimed your credits. Before completing these requirements, be sure your NCCN profile has been updated with your NAPB e-profile ID and date of birth. Your credit cannot be reported without this information. If you have any questions, please e-mail education@nccn.org.

Release date: December 10, 2020; Expiration date: December 10, 2021

Learning Objectives:

Upon completion of this activity, participants will be able to:

  • Integrate into professional practice the updates to the NCCN Guidelines for Soft Tissue Sarcoma
  • Describe the rationale behind the decision-making process for developing the NCCN Guidelines for Soft Tissue Sarcoma

Disclosure of Relevant Financial Relationships

The NCCN staff listed below discloses no relevant financial relationships:

Kerrin M. Rosenthal, MA; Kimberly Callan, MS; Genevieve Emberger Hartzman, MA; Erin Hesler; Kristina M. Gregory, RN, MSN, OCN; Rashmi Kumar, PhD; Karen Kanefield; and Kathy Smith.

Individuals Who Provided Content Development and/or Authorship Assistance:

Margaret von Mehren, MD, Panel Chair, has disclosed that she receives grant/research support from Blueprint Medicines, Deciphera Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Arog, Gradalis, and Spring Works Therapeutics.

John M. Kane III, MD, Panel Vice Chair, has disclosed that he has no relevant financial relationships.

Kristen N. Ganjoo, MD, Panel Member, has disclosed that she is a scientific advisor for Foundation Medicine.

Edward Kim, MD, Panel Member, has disclosed that he has no relevant financial relationships.

David Liebner, MD, Panel Member, has disclosed that he is a scientific advisor for Foundation Medicine, Blueprint Medicines, and Epizyme.

Martin McCarter, MD, Panel Member, has disclosed that he has no relevant financial relationships.

Alberto S. Pappo, MD, Panel Member, has disclosed that he has received consulting fees from Bayer Healthcare, Iqvia, and UpToDate.

Amanda M. Parkes, MD, Panel Member, has disclosed that she has received consulting fees from Daiichi-Sankyo Co. and Deciphera Pharmaceuticals, Inc.

Matthew Poppe, MD, Panel Member, has disclosed that he has equity interest/stock options in AstraZeneca Pharmaceuticals LP, Johnson & Johnson, Merck & Co., Inc., Inovio Pharmaceuticals, Inc., Moderna, Inc., PEEL Therapeutics, Inc., and sanofi-aventis U.S.

Richard F. Riedel, MD, Panel Member, has disclosed that he receives grant/research support from AADi, AROG, Blueprint Medicines, Daiichi-Sankyo, Decipherma Pharmaceuticals, GlaxoSmithKline, Immune Design, Karyopharm Therapeutics, NanoCarier, Oncternal, Philogen, Plexxikon, Roche Laboratories, Springworks, and TRACON Pharmaceuticals; and that he is a scientific advisor for Bayer HealthCare, Blueprint Medicines, Daiichi-Sankyo, Deciphera Pharmaceuticals, and NanoCarrier.

Brian Rubin, MD, PhD, Panel Member, has disclosed that he receives consulting fees from Eli Lilly and Company, is a scientific advisor for Avalon Healthcare Solutions and PathAI, receives other financial benefit from Blueprint Medicines.

Mary Anne Bergman, Guidelines Coordinator, NCCN, has disclosed that she has no relevant financial relationships.

Giby V. George, MD, Oncology Scientist/Medical Writer, NCCN, has disclosed that she has no relevant financial relationships.

To view all of the conflicts of interest for the NCCN Guidelines panel, go to NCCN.org/disclosures/guidelinepanellisting.aspx.

This activity is supported by educational grants from AstraZeneca; Celgene Corporation; Coherus BioSciences; Genentech, a member of the Roche Group; and TESARO, a GSK Company. This activity is supported in part by an educational grant from Bayer Healthcare Pharmaceuticals. This activity is supported by an independent medical education grant from Bristol-Myers Squibb. This activity is supported by a medical education grant from Exelixis, Inc. This activity is supported by an independent educational grant from Merck & Co., Inc.

Overview

Collectively, sarcomas are a heterogenous group of solid tumors of mesenchymal origin. They can be divided broadly into sarcomas arising from soft tissues (such as fat, muscle, blood vessels, nerve/nerve sheath, and other connective tissues) and those arising from bone. Although bone sarcomas are covered in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bone Cancer, and Gastrointestinal Stromal Tumors (GISTs) are now detailed in their own separate NCCN Guidelines, the NCCN Guidelines for Soft Tissue Sarcoma address in depth the following soft tissue sarcoma (STS) subtypes: STS of extremity/body wall, head/neck, retroperitoneal and intraabdominal STS, desmoid tumors (aggressive fibromatosis), and rhabdomyosarcoma (RMS).

Sarcomas are relatively rare, accounting for only 1% of all adult malignancies and 15% of childhood malignancies.1 It is estimated that in 2020, 13,130 people in the United States will be diagnosed with STS, with approximately 5,350 deaths.2 There are estimated to be >50 different histologic subtypes of STS with varying clinical and biologic characteristics.3

Characterized by local infiltration rather than distant metastasis, desmoid tumors (DTs), or aggressive fibromatosis (AF), are a unique soft tissue tumor subtype.4 They are rare, thought to affect only 1 to 2 per 500,000 individuals worldwide, with approximately 900 to 1,500 new cases diagnosed annually within the United States.5 Peak incidence occurs among individuals aged 25 to 35 years.4 They most often occur sporadically (>90%)6 and in postpartum females, or may be diagnosed in association with familial adenomatous polyposis (FAP) or its variant, Gardner syndrome.5

Although reports of fatality outside of individuals with FAP are infrequent, DTs may cause significant morbidity, including chronic pain, functional impairment, disfigurement, and numerous psychological ramifications (eg, depression and anxiety). Therefore, an optimal treatment plan determined by a multidisciplinary team of providers with experience and expertise in the management of sarcomas is recommended. Due to the possibility of spontaneous regression, an initial period of observation, or active surveillance, has now been adopted as the first-line approach for many patients. In the event of disease progression, a short course of observation may again be considered if the patient is minimally symptomatic or the anatomic location is not critical. For patients who exhibit ongoing progression with potential morbidity and significant symptoms, intervention is recommended. Treatment options include surgery (if resectable), systemic therapy, definitive radiation therapy (RT), ablation procedures, or surgery with RT. Choice of therapy is dependent upon the anatomic location (ie, abdominal wall, intra-abdominal/retroperitoneal/pelvic, truncal/extremity, or head/neck/intrathoracic) and institutional expertise.

The NCCN Guidelines for STS provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with soft tissue sarcomas. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including the development of a separate and distinct guideline for GISTs; reconception of the management of DTs; inclusion of further recommendations for the diagnosis and management of extremity/body wall, head/neck sarcomas, and retroperitoneal sarcomas; modification and addition of systemic therapy regimens for sarcoma subtypes; and revision of the principles of RT for STS.

Genetics and Risk Factors

Grossly, DTs are locally invasive with infiltration into surrounding tissues. Microscopically, they are characterized by fascicles of low-grade appearing fibroblasts and myofibroblasts.7 As mentioned earlier, DTs can occur either sporadically or in association with FAP or Gardner syndrome. Inherited in an autosomal dominant manner, FAP is characterized by mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. Individuals with FAP are predisposed to the development of >100 adenomatous polyps, most commonly in the colon and rectum, as well as the occurrence of DTs.8 DTs are reported to occur in 7.5% to 16% of patients with FAP,9,10 and more commonly arise in the intra-abdominal region in these individuals.8,11 Research suggests that previous surgery (especially open as opposed to laparoscopic procedures) in individuals with FAP is a risk factor for desmoid formation.8 In individuals with FAP who have undergone surgery, intra-abdominal DTs are reported to be among the leading causes of mortality (due to bowl obstruction or ulceration).12,13 Other risk factors for sporadic DTs include a positive family history for DTs, hormonal exposure (estrogens), trauma, and previous pregnancy or abdominal surgery.10,14 Gardner syndrome is a subtype of FAP characterized by a triad of colonic polyposis, osteomas, and soft tissue tumors (epidermoids and desmoids).15,16

Although mutations in the APC gene are responsible for hereditary DTs, mutations in the CTNNB1 gene encoding β-catenin have been implicated in sporadic desmoids.17 The APC and CTNNB1 mutations are mutually exclusive; hence, recognition of a somatic CTNNB1 mutation excludes syndromic origin.18 Three distinct mutations in the CTNNB1 gene have been identified: T41A, S45F, and S45P.19 Several studies have reported an increased risk of recurrence associated with the S45F mutation.20,21 Although further research is required to confirm the prognostic significance of genotyping, DTs are characterized ultimately by aberrant Wnt signaling.19 Diagnosis of DT requires a thorough patient history and physical examination (with evaluation for FAP/Gardner syndrome) followed by imaging of the primary site (using either CT or MRI) and a biopsy for confirmation.

Observation: An Initial Management Approach

The treatment paradigm of AF has shifted in recent years from active intervention to initial observation in the absence of progressive, morbid, or symptomatic disease. Although historically surgery (ie, wide local excision) has been the primary modality of treatment of DTs, given that spontaneous regression has been reported in 20% of cases,6 an initial period of observation is permissible in many patients with newly diagnosed DTs. In an institutional analysis involving 213 patients with pathologically confirmed DTs that were either sporadic (48%), associated with pregnancy (14%), or affiliated with FAP (38%), individuals were divided into 3 groups: A (untreated patients), B (patients with desmoids that were resected elsewhere), and C (patients with recurrent tumors). It was reported that of the 176 individuals in group A, 109 underwent initial observation. Of this subset, 51 individuals required intervention, whereas 93% of the remaining 58 patients who underwent observation demonstrated spontaneous regression or stable disease.22

In a more recent study, active surveillance was used for the initial management of 168 patients with primary DTs. A total of 36% of patients displayed progressive disease radiographically, whereas 36% exhibited stable disease and 27% showed regression. Progression was more often noted in patients aged <50 years. Overall, 46% of patients required treatment following a median initial surveillance period of 31 months. The most common indications for treatment included pain (32%), progression (31%), or both. It was concluded that although nearly 50% of patients with desmoids may eventually require treatment, an initial period of active surveillance may be appropriate for many patients given the rate of spontaneous regression and stabilization.23

The Desmoid Tumor Working Group, as published in their 2020 global consensus paper, also supports an initial active surveillance approach as the first step in the management of DTs.18 The group cites a comparative study conducted by Penel et al24 in which event-free survival (EFS) rates showed little difference between patients managed with initial observation (58%) and those managed with surgery (53%). They found that for favorable anatomic locations (eg, abdominal wall, lower limb), 2-year EFS was comparable in individuals treated surgically (70%) and conservatively (63%); whereas for unfavorable anatomic locations (eg, head/neck, chest wall), 2-year EFS was superior in those managed conservatively (52% vs 25%).24 Several other studies also support an initial period of active surveillance for asymptomatic or nonprogressive disease.

Given the evidence for a conservative approach, the NCCN panel now recommends that patients confirmed to have a DT undergo an initial period of observation in the absence of progressive, morbid, or symptomatic disease. In the case of progressive disease, a short course of observation may again be considered if the patient is minimally symptomatic or the anatomic location is not critical. Intervention is recommended for patients who exhibit ongoing progression with potential morbidity and significant symptoms.

Active Therapy for Progressive, Morbid, or Symptomatic Disease

Choice of therapy for progressive, morbid, or symptomatic disease depends upon the site of origin (eg, abdominal wall, intra-abdominal/retroperitoneal/pelvic, truncal/extremity, or head/neck/intrathoracic) and institutional expertise. For patients with DTs arising from the abdominal wall, treatment consists of either surgery (if resectable), systemic therapy, ablation procedures, or definitive RT. For DTs originating from an intra-abdominal, retroperitoneal, or pelvic region, the NCCN panel recommends systemic therapy or surgery (if resectable). RT and ablation procedures should be avoided in such sites. Systemic therapy, surgery (if resectable), ablation procedures, or definitive RT may be considered for DTs arising from the trunk or extremity. Finally, for head, neck, or intrathoracic DTs, the panel recommends treatment in the form of systemic therapy, ablation procedures, definitive RT, or surgery with adjuvant RT.

Although upfront surgery was formerly the mainstay of treatment of DTs, the postoperative recurrence rate was found to be unacceptably high (>40%).6 Risk factors associated with recurrence included larger tumor size, younger age, and the presence of a CTNNB1 S45F mutation.13 Similar rates of recurrence were found following R0 and R1 resections, and therefore the significance of margin status is debated.4 Regardless, surgery may be considered a treatment option for progressive, morbid, or symptomatic disease that is resectable. Although the goal of surgery in such cases is a complete microscopic resection, if an R0 resection would lead to undue morbidity, an R1 resection may be acceptable. Following an R1 resection, observation or further treatment in the form of reresection or adjuvant RT may be considered. Treatment options following an R2 resection include definitive RT, systemic therapy, radical surgery, ablation procedures, or observation.

RT may be administered definitively or in the adjuvant setting (following an R1/R2 resection). The NCCN panel has included definitive RT as a treatment option for progressive DTs, except for those arising from an intra-abdominal, retroperitoneal, or pelvic site. Previous studies have reported good long-term local control rates with RT (70%–93%).25 In a study of patients with AF treated with RT, overall survival (98% at 5 years) and local control (82% at 5 years) were reported to be exceptional. However, it was found that younger patients (aged <20 years) demonstrated significantly poorer 5-year local control than older patients (72% vs 97%, respectively).26 Similarly, in a review of 209 patients with DT treated with either RT alone or with surgery, it was found that among both treatment arms, individuals aged ≤30 years and those who had larger tumor size (>10 cm) exhibited poorer local control.27 Thus, although RT may be an effective local control modality for DTs, caution must be exercised with its use in younger patients given their unique tumor biology and associated radioresistance and future risk for radiation-induced malignancies.

The panel has included ablation procedures as a treatment option for desmoids. A retrospective study of 23 patients with extra-abdominal DTs who received either initial or salvage CT-guided percutaneous cryoablation reported a 90% clinical response rate. The average tumor volume reduction at 12 months was 81%, and 71% of individuals exhibited complete response or partial response (based on modified RECIST criteria).11 Other studies have also published favorable outcomes for percutaneous image-guided cryoablation, although its use is not advisable in larger tumors or in desmoids abutting critical structures.28,29 Several studies have also reported good local control with radiofrequency ablation (RFA).3032 In one study of 4 patients treated with RFA and followed for a mean duration of 30 months, no recurrence was reported and complications included skin ulceration and cellulitis.30 High-intensity focused ultrasound (HIFU) is another emerging treatment alternative for progressive or symptomatic desmoids. In a multicenter study of 15 patients with DTs treated with MR-guided focused ultrasound, median viable targeted tumor volume was reduced to 63% after treatment, with significant improvement in pain.33 Similar outcomes with minimal complications (eg, superficial burns) have also been reported by others supporting the use of HIFU in the treatment of extra-abdominal desmoids.3437 Thus, ablative therapies offer novel treatment approaches and may be considered as an alternative to RT; however, data supporting the safety and efficacy are still limited at this time.

The panel has organized the systemic therapy regimens for desmoids according to treatment urgency: “time to response more critical” and “time to response less critical.” The regimens have been preference-stratified according to the NCCN Categories of Preference. Preferred agents under “time to response more critical” include sorafenib, imatinib, liposomal doxorubicin, doxorubicin ± dacarbazine, and finally, pazopanib. Hormonal (antiestrogen) agents have been removed by the NCCN panel due to lack of meaningful response, unpleasant side effects (eg, hot flashes), and the potential risk for thrombotic events or uterine malignancies. Preferred regimens under “time to response less critical”’ include methotrexate/vinblastine and methotrexate/vinorelbine. Nonsteroidal anti-inflammatory drugs, including sulindac and celecoxib, have been included under “useful in certain circumstances” for patients experiencing pain.

Pazopanib was added to the NCCN Guidelines following the noncomparative, randomized, open-label, multicenter phase II DESMOPAZ study, in which patients were randomized to receive either pazopanib or methotrexate/vinblastine. The primary endpoint was the proportion of patients with no progression after 6 months who completed 1 cycle or 2 incomplete cycles of pazopanib or methotrexate/vinblastine. Among the first 43 patients in the pazopanib treatment arm, 83.7% (95% CI, 69.3%–93.2%) showed no progression at 6 months, whereas only 45% (95% CI, 23.1%–68.5%) of those in the methotrexate/vinblastine treatment arm exhibited no progression at 6 months. Based on its efficacy and tolerable safety profile (most common grade 3/4 adverse effects were hypertension and diarrhea), pazopanib has been included as a treatment option for progressive, symptomatic, or morbid desmoids with an NCCN category 2A recommendation.38

Following treatment, follow-up should include history and physical examination accompanied by imaging (CT or MRI) every 3 to 6 months for 2 to 3 years, and then every 6 to 12 months thereafter to assess for recurrence. Ultrasound may be an alternative imaging modality for select locations (eg, abdominal wall).

Summary

Given the rate of spontaneous regression and high postoperative recurrence rate, the NCCN panel has adopted a treatment strategy of initial observation for patients with asymptomatic and nonprogressive desmoids. This preference for a first-line active surveillance approach obviates unnecessary surgery and any associated complications. In the event of progressive, morbid, or symptomatic disease, the panel has delineated treatment options according to the disease site. Treatment options include surgery (if resectable), systemic therapy, definitive RT, ablation procedures, or surgery with RT. Finally, pazopanib has been added to the systemic therapy options for DTs, which have since been reorganized according to treatment urgency and preference-stratified according to the NCCN Categories of Preference.

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    • PubMed
    • Search Google Scholar
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NCCN CATEGORIES OF EVIDENCE AND CONSENSUS

Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.

Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.

All recommendations are category 2A unless otherwise noted.

Clinical trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

PLEASE NOTE

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment. The NCCN Guidelines Insights highlight important changes in the NCCN Guidelines recommendations from previous versions. Colored markings in the algorithm show changes and the discussion aims to further the understanding of these changes by summarizing salient portions of the panel's discussion, including the literature reviewed.

The NCCN Guidelines Insights do not represent the full NCCN Guidelines; further, the National Comprehensive Cancer Network® (NCCN®) makes no representations or warranties of any kind regarding their content, use, or application of the NCCN Guidelines and NCCN Guidelines Insights and disclaims any responsibility for their application or use in any way.

The complete and most recent version of these guidelines is available free of charge at NCCN.org.

© National Comprehensive Cancer Network, Inc. 2019. All rights reserved. The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN.

NCCN CATEGORIES OF EVIDENCE AND CONSENSUS

Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.

Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.

All recommendations are category 2A unless otherwise noted.

Clinical trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

PLEASE NOTE

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment. The NCCN Guidelines Insights highlight important changes in the NCCN Guidelines recommendations from previous versions. Colored markings in the algorithm show changes and the discussion aims to further the understanding of these changes by summarizing salient portions of the panel's discussion, including the literature reviewed.

The NCCN Guidelines Insights do not represent the full NCCN Guidelines; further, the National Comprehensive Cancer Network® (NCCN®) makes no representations or warranties of any kind regarding their content, use, or application of the NCCN Guidelines and NCCN Guidelines Insights and disclaims any responsibility for their application or use in any way.

The complete and most recent version of these guidelines is available free of charge at NCCN.org.

© National Comprehensive Cancer Network, Inc. 2020. All rights reserved. The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN.

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