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NCCN Flash Updates: NCCN Guidelines Updated for Mesothelioma: Pleural and more

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) and the NCCN Drugs and Biologics Compendium (NCCN Compendium^®) for Mesothelioma: Pleural. These NCCN Guidelines^® are currently available as Version 1.2024.

Link directly to the Updates section of the NCCN Guidelines: Mesothelioma: Pleural

 

PM-3

• Adjuvant Treatment
  • Chemotherapy clarified as pemetrexed and cisplatin (or carboplatin).

PM-B 1 of 2

• Footnote f modified: Consider rechallenge with pemetrexed-based therapy, if good response to front-line pemetrexed-based treatment.

PM-B 2 of 2

• Reference 16 added: Popat S, Curioni-Fontecedro A, Dafni U, et al. A multicentre randomised phase III trial comparing pembrolizumab versus single-agent chemotherapy for advanced pre-treated malignant pleural mesothelioma: the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial. Ann Oncol 2020;31:1734-1745.

 

 

NCCN has published updates to the NCCN Guidelines, and the NCCN Drugs and Biologics Compendium (NCCN Compendium^®) for Mesothelioma: Peritoneal. These NCCN Guidelines are currently available as Version 1.2024.

Link directly to the Updates section of the NCCN Guidelines: Mesothelioma: Peritoneal

 

PEM-1

• Initial Evaluation
  • Bullet 2 added: Consider FDG-PET/CT scan

PEM-2 (previous version) removed

• Pathologic subtype removed: Peritoneal inclusion cyst or well-differentiated papillary mesothelial tumor (includes removal of PEM-5 [previous version])
• Diffuse peritoneal mesothelioma changed to Peritoneal mesothelioma

PEM-2

• Footnote removed: Adjuvant intraperitoneal (IP) chemotherapy may be considered for patients who do not receive HIPEC.

PEM-3

• Biphasic/sarcomatoid histology
  • Treatment options expanded after initial systemic therapy
    • Medically operable and complete cytoreduction achievable
      • CRS + HIPEC
        • Imaging Surveillance

PEM-A 3 of 8

• Markers to confirm a mesothelial malignant proliferation
  • Bullet 2; sub-bullet 5 added: CDKN2A FISH and MTAP IHC are less useful for the diagnosis of peritoneal mesotheliomas because the prevalence of CDKN2A deletions is 8%–26% and MTAP loss is 14%–16% in peritoneal mesotheliomas.

PEM-A 7 of 8

• References 40-44 added.
  • 40 Dagogo-Jack I, Madison RW, Lennerz JK, et al. Molecular characterization of mesothelioma: Impact of histologic type and site of origin on molecular landscape. JCO Precis Oncol 2022;6:e2100422.
  • 41 Hiltbrunner S, Fleischmann Z, Sokol E, et al. Genomic landscape of pleural and peritoneal mesothelioma tumors. Br J Cancer 2022;127:1997-2005.
  • 42 Joseph NM, Chen Y-Y, Nasr A, et al. Genomic profiling of malignant peritoneal mesothelioma reveals recurrent alterations in epigenetic regulatory genes BAP1, SETD2 and DDX3X. Mod Pathol 2017;30:246-254.
  • 43 Hung YP, Dong F, Torre M, et al. Molecular characterization of diffuse malignant peritoneal mesothelioma. Mod Pathol 2020;33:2269-2279.
  • 44 Offin M, Yang S-R, Egger J, et al. Molecular characterization of peritoneal mesotheliomas. J Thorac Oncol 2022;17:455-460.

 

PEM-B 1 of 3

• Bullet 7 added: Resectable epithelioid mesothelioma should undergo upfront CRS and HIPEC. If there are no high-risk features identified (positive lymph node [LN], incomplete cytoreduction, or high Ki-67 >9%) then surveillance is sufficient. If high-risk features are identified then consideration for adjuvant therapy is recommended.
• Bullet 8 added: For patients with biphasic, sarcomatoid, clinically positive LN, or high PCI >17; neoadjuvant therapy is strongly encouraged followed by re-evaluation for complete CRS and HIPEC.
• Bullet 9 added: For patients with bicavitary disease and minimal disease burden in the thorax, systemic therapy is recommended. Surgery can be considered in select cases.
• Bullet 10 added: If a bevacizumab-containing regimen is administered, there should be at least a 6-week interval between the last dose and CRS.
• Bullet 12 added: Early postoperative or prolonged adjuvant IP therapy have been investigated with some success and limited toxicity, but there remains insufficient evidence to recommend their use outside of a clinical trial.
• Bullet 13 added: Patients who recur in the peritoneum after CRS and HIPEC should be re-evaluated for repeat CRS and HIPEC, as studies show this can be done safely and with good outcomes in appropriately selected patients
• Bullets removed
  • The presence of bicavitary mesothelioma is a relative contraindication to surgery. In selected situations, bicavitary surgery with resection of the diaphragm and bicavitary chemoperfusion or staged approaches may be considered. Neoadjuvant chemotherapy is also a strong consideration in this borderline group.
  • Long-term survival is achievable in select patients with low-volume biphasic mesothelioma if complete cytoreduction (CC-0) can be achieved. Neoadjuvant systemic chemotherapy is a strong consideration in this histologic subtype.
  • Perioperative systemic therapy should be considered for high-risk features such as: Ki-67 >9%, nodal metastasis, high tumor burden (PCI >17), CC score >1, biphasic disease, or bicavitary disease. Patients with favorable prognostic profile (ie, complete cytoreduction, epithelioid subtype, no lymph node involvement, Ki-67 ≤9%, PCI ≤17) could be followed in surveillance as the benefit of adjuvant therapy is unknown.

PEM-B 3 of 3

• References 6–8,11–14 added.
  • 6 Ripley RT, Holmes HM, Whitlock RS, et al. Pleurectomy and decortication are associated with better survival for bicavitary cytoreductive surgery for mesothelioma compared with extrapleural pneumonectomy. J Thorac Cardiovasc Surg. 2023;165:1722-1730.
  • 7 Petrillo M, Nero C, Carbone V, et al. Systematic review of cytoreductive surgery and bevacizumab-containing chemotherapy in advanced ovarian cancer: focus on safety. Ann Surg Oncol. 2018;25:247-254.
  • 8 King BH, Baumgartner JM, Kelly KJ, et al. Preoperative bevacizumab does not increase complications following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. PLoS One. 2020;15:e0243252.
  • 11 Sugarbaker PH, Chang D. Long-term regional chemotherapy for patients with epithelial malignant peritoneal mesothelioma results in improved survival. Eur J Surg Oncol 2017;43:1228-1235.
  • 12 Bijelic L, Stuart OA, Sugarbaker PH. Adjuvant bidirectional chemotherapy with intraperitoneal pemetrexed combined with intravenous Cisplatin for diffuse malignant peritoneal mesothelioma. Gastroenterol Res Pract 2012;2012:890450.
  • 13 Pasqual EM, Londero AP, Robella M, et al. Repeated cytoreduction combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in selected patients affected by peritoneal metastases: Italian PSM Oncoteam Evidence. Cancers (Basel) 2023;15:607.
  • 14 Wong J, Koch AL, Deneve JL, et al. Repeat cytoreductive surgery and heated intraperitoneal chemotherapy may offer survival benefit for intraperitoneal mesothelioma: a single institution experience. Ann Surg Oncol 2014;21:1480-1486.

PEM-C 1 of 2

• Footnote removed: The combination regimens of pemetrexed/cisplatin/bevacizumab, pemetrexed/carboplatin/bevacizumab, and nivolumab/ipilimumab are only for unresectable disease.

 

NCCN has published updates to the NCCN Guidelines, NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™), and the NCCN Drugs and Biologics Compendium (NCCN Compendium^®) for Thymomas and Thymic Carcinomas. These NCCN Guidelines are currently available as Version 1.2024.

Link directly to the Updates section of the NCCN Guidelines: Thymomas and Thymic Carcinomas

 

THYM-1

• Initial Evaluation
  • Bullet 4 modified: FDG-PET/CT scan (whole-body or skull base to mid-thigh), as clinically indicated
  • Bullet 6 modified: Chest MRI with and without contrast, as clinically indicated
• Footnote a added: Patients with thymoma should be evaluated clinically for signs of myasthenia gravis and other paraneoplastic syndromes with appropriate workup and treatment. (also applies to THYM-3 and THYM-4)

THYM-2

• Footnote e added: If R0 resection considered uncertain, preoperative systemic therapy should be considered. See Principles of Systemic Therapy (THYM-C).

THYM-3

• Postoperative Evaluation; R0 resection
  • Thymoma or thymic carcinoma, no capsular invasion or thymic carcinoma, Masaoka-Koga stage I
    • Surveillance
      • Surveillance for recurrence with Chest CT with contrast every 6–12 mo for 2 y, then annually foruntil 5 y for thymic carcinoma and until 10 y for thymoma
• Postoperative Evaluation
  • R0 resection, Thymoma or thymic carcinoma, capsular invasion present, Masaoka-Koga stages II–IV; R1 resection; R2 resection
    • Surveillance for recurrence with Chest CT with contrast every 3–6 mo for thymic carcinoma and every 6 mo for thymoma for 2 y, then annually foruntil 5 y for thymic carcinoma and until 10 y for thymoma
      (also applies to THYM-4)

THYM-4

• Medically inoperable/unresectable:
  • Consider observation added as an option.
• Footnote o modified: FDG-PET/CT includes whole-body or skull-base to mid-thigh.

THYM-A 1 of 2

• Bullet 5 added: If an R0 resection appears unlikely, patient should be considered for neoadjuvant systemic therapy. Debulking tumors is discouraged.

THYM-A 2 of 2

• References 11–14 added
  Hwang SK, Lee GD, Kang CH, et al. Long-term outcome of minimally invasive thymectomy versus open thymectomy for locally advanced cases. Eur J Cardiothorac Surg 2022;62:ezac238.
  Yang C-F, Hurd J, Shah SA, et al. A national analysis of open versus minimally invasive thymectomy for stage I to III thymoma. J Thorac Cardiovasc Surg 2020;160:555-567.
  Hurd J, Haridas C, Potter A, et al. A national analysis of open versus minimally invasive thymectomy for stage I–III thymic carcinoma. Eur J Cardiothorac Surg 2020;62:ezac159.
  Gu Z, Chen C, Wang Y, et al. Video-assisted thoracoscopic surgery versus open surgery for Stage I thymic epithelial tumours: a propensity score-matched study. Eur J Cardiothorac Surg 2018;54:1037-1044.

 

THYM-C 1 of 3

• Footnote b added: Regimens can be used with RT, as definitive concurrent chemoradiation.

THYM-C 2 of 3

• Thymoma
  • Octreotide
    • Clarification added: if octreotide scan or dotatate PET/CT positive
• Thymic Carcinoma
  • The following regimens moved from other recommended to preferred
    • Pembrolizumab
    • Sunitinib
    • Lenvatinib
    • Gemcitabine ± capecitabine
• Footnote c modified: Nuclear medicine scan (octreotide scan or dotatate PET/CT [dotatate PET/CT preferred if available]) to assess for octreotide-avid disease.

THYM-C 3 of 3

• Reference removed: Johnson DH, Greco FA, Strupp J, et al. Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial. J Clin Oncol 1990;8:1613-1617.

THYM-D 1 of 2

• Footnote a modified: For thymoma composed of two or more subtypes, are termed “thymoma,” with listing of the components should be listed in 10% increments.
• Footnote d modified: Microscopic thymoma; sclerosing thymoma, Lipofibroadenoma.

THYM-D 2 of 2

• The following subtypes added:
  • Neuroendocrine tumors (NCCN Guidelines for Neuroendocrine and Adrenal Tumors)
    • Carcinoid tumor, NOS/neuroendocrine tumor, NOS
    • Typical carcinoid/neuroendocrine tumor, grade 1
    • Atypical carcinoid/neuroendocrine tumor, grade 2
  • Neuroendocrine carcinomas
    • Small cell carcinoma
    • Combined small cell carcinoma
    • Large cell neuroendocrine carcinoma

 

 

For the complete updated versions of the NCCN Guidelines, NCCN Guidelines with NCCN Evidence Blocks™, the NCCN Drugs & Biologics Compendium (NCCN Compendium^®), the NCCN Biomarkers Compendium^®, the NCCN Chemotherapy Order Templates (NCCN Templates^®), the NCCN Radiation Therapy Compendium™, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™), please visit NCCN.org.

To view the NCCN Guidelines for Patients^®, please visit NCCN.org/patientguidelines.

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