Chordoma Guidelines

Guidelines for the management of chordoma have been published by the following organizations:

• National Comprehensive Cancer Network (NCCN) ^{[38, 39]}
• European Society for Medical Oncology (ESMO) ^{[40, 41]}

NCCN Guidelines

NCCN recommendations for treatment of chordoma are as follows ^{[38, 39]} :

• Enrollment in a clinical trial should be considered when available; in addition, when possible, patients should be referred to a tertiary care center with expertise in sarcoma, for treatment by a multidisciplinary team.
• Wide excision with or without radiation therapy should be provided for tumors of the sacrum and mobile spine.
• Intralesional excision with or without radiation therapy may be the best feasible treatment for resectable skull base tumors when wide excision is not possible; re-resection can be considered with positive surgical margins; postoperative radiation can improve local control.
• Adjuvant radiation therapy can be considered for large tumors or for positive surgical margins after resection.
• Radiation therapy is the primary treatment for unresectable tumors regardless of location.
• Dedifferentiated chordomas are treated according to soft tissue sarcoma management guidelines; chemotherapy can be provided when clinically indicated.
• For local recurrence, surgical excision should be performed with or without radiation therapy and/or chemotherapy.
• For metastatic disease, options include chemotherapy and/or surgical excision and/or radiation therapy and/or best supportive care.

Conventional or Chondroid Chordoma

National Comprehensive Cancer Network (NCCN) guidelines (2020) recommend that all patients with conventional or chondroid chordoma should be evaluated and treated by a multidisciplinary team of doctors who are experts in the management of chordoma. They should undergo the following tests before treatment is begun ^[38] :

• Medical history and physical exam
• Imaging of primary site that might include x-ray, computed tomography (CT) and/or magnetic resonance imaging (MRI), as well as screening MRI of the spine
• Chest/abdominal/pelvic CT with contrast
• Positron emission tomography (PET)/CT (skull base to midthigh)
• Bone scan (should be considered)

Treatment options may include surgical excision and/or radiation therapy and/or systemic therapy, along with best supportive care.

Systemic therapy options may include use of imatinib, dasatinib, sunitinib, cisplatin or sirolimus, erlotinib, lapatinib (for epidermal growth factor receptor [EGFR]-positive chordoma), and sorafenib, given alone or in combination.

The finding of other lesions indicates a non-bone primary tumor. If no other lesions are found, the patient should be referred to an orthopedic oncologist for biopsy.

Poorly Differentiated or Dedifferentiated Chordoma

For those with poorly differentiated or dedifferentiated chordoma, practitioners can refer to the NCCN Guidelines for Soft Tissue Sarcoma (2020), which recommend the following ^[39] :

General health testing

• Medical  history
• Family history
• Physical exam

Imaging tests

• MRI
• CT
• PET scan
• X-ray
• Ultrasonography
• Angiography

Tissue testing

• Fine-needle aspiration
• Core needle biopsy
• Incisional biopsy

Genetic testing (should be considered)

Cancer staging

• Tumor-node-metastasis (TNM) scores
• Cancer grade
• Disease stage

Treatment options may include surgery, radiation therapy, and other local treatments.

Systemic therapy options may include chemotherapy, targeted therapy, and immunotherapy.

ESMO Guidelines

ESMO guidelines are in general agreement with NCCN guidelines. ^{[38, 39, 40, 41]}

Over many years, experts had not reached consensus regarding appropriate clinical management of chordoma, resulting in inconsistent care and suboptimal outcomes for many patients. To address this shortcoming, the European Society of Medical Oncology (ESMO) and the Chordoma Foundation (CF)—the global chordoma patient advocacy group—convened a multidisciplinary group of chordoma specialists to define by consensus evidence-based best practices for the optimal approach to chordoma. In January 2015, the first recommendations of this group were published. In November 2015, ESMO and CF convened a second consensus group, including specialists from Europe, the United States, and Japan with expertise in treatment of patients with chordoma. ^{[40, 41]}

ESMO best practices for management of local-regional recurrent chordoma recommend follow-up of an abnormal radiograph with contrast-enhanced magnetic resonance imaging (MRI) of the whole compartment with adjacent joints. In addition, restaging with total body computed tomography (CT) and whole spine MRI and a thorough clinical examination should complement locoregional assessment to rule out distant metastases and/or subarachnoid spread. ^{[40, 41]}

Surgical and radiation therapy (RT) strategies should be guided by the nature and extent of the previous procedure, the location of the recurrence, tumor resectability, deliverability of RT, and the expected morbidity of each procedure. Other relevant factors include age, comorbidity, performance status, and status of surrounding tissues including the skin.

Retrospective data suggest that cryoablation and radiofrequency ablation (RFA) can be safe and useful palliative treatments in recurrent chordoma, providing pain control benefit. Stereotactic body radiation therapy (SBRT) has been suggested as a palliative treatment option, but prospective confirmatory data are needed. In principle, other local therapies such as local microwave hyperthermia and high-intensity focused ultrasound (HIFU) may offer benefit in a palliative setting; however, no published data are available to support their use.

Medical therapy options are limited, and no drugs are approved for treatment of advanced chordoma. Several targeted therapies have shown modest activity in patients with recurrent disease. Imatinib and sorafenib are the agents with greatest evidence of efficacy in advanced chordoma and represent reasonable palliative treatment options to slow disease progression or alleviate symptoms.

Cytotoxic chemotherapy is generally inactive, and evidence is insufficient to recommend it. No predictors of response to targeted agents have been identified, but one potentially relevant biomarker is loss of INI1, which has been reported in dedifferentiated chordoma and may confer sensitivity to EZH2 inhibitors.

Worsening of somatic and neuropathic pain and/or worsening neurologic symptoms can be the first sign of disease relapse/progression, even when this cannot be detected radiologically.

First-line analgesic therapy should be provided according to available guidelines.

In the terminal phase, the patient’s preferred setting of care should be identified. Hospice and home care are valid options.

Palliative care should be considered as part of the active management of all patients and should include pain and symptom control, discussion about a patient’s concerns and wishes, conversation about advanced directives, and evaluation of patient and family psychosocial needs.

Guidelines summary

Both NCCN and ESMO guidelines state that biopsy is required to confirm the diagnosis prior to any surgical procedure and should be performed at a specialized center that will provide definitive treatment. ^{[38, 39, 40, 41]}

For patients with unsuccessful surgery and RT, there remains an urgent unmet need for new therapeutic options. To facilitate patient participation in clinical trials, the Chordoma Foundation maintains an up-to-date list of trials open to chordoma patients (www.chordomafoundation.org/clinical-trials/) and a target dashboard (www.chordomafoundation.org/targets/) summarizing published data about therapeutically relevant targets.