Steven H. Lin and Michelle Alonso-Basanta
What are chordomas?
Chordomas are rare, slow-growing, locally aggressive neoplasms of bone arising from embryonic remnants of the notochord.
Where do chordomas most commonly arise?
Chordomas most commonly arise in 3 locations in the axial skeleton:
1. Spheno-occipital region of the skull base (35%)
2. Sacrococcygeal region (50%)
3. Vertebral column (15%)
In craniocervical chordomas, the most common sites are the dorsum sellae, clivus, and nasopharynx.
What are the most common histologic subtypes seen for chordomas?
Most common histologic subtypes of chordoma:
1. Conventional: most common, no cartilaginous or mesenchymal components
2. Chondroid: 5%–15%, contains cartilaginous components but is distinct from chondrosarcoma
3. Dedifferentiated or sarcomatous transformation: 2%–8%, aneuploid tumors interspersed in areas of conventional chordomas, poorer survival
What features characterize conventional chordomas?
Gelatinous, pink or gray masses with solid or cystic areas. Microscopically, characteristic physaliphorous cells are present.
What histologic types of chordomas are most commonly found in the skull base?
Conventional is still the most common, though the chondroid type has a predilection for the cranial region (one third of cranial chordomas are chondroid).
What tumor antigens are commonly found on chordomas?
Epithelial membrane antigen (EMA) and cytokeratin are commonly found on chordomas.
What % of chordoma pts have metastatic Dz, and what distant sites are most commonly involved?
~25% of chordoma pts have metastatic Dz, with lungs, liver, and bones being most commonly involved.
How do pts with chordomas present clinically?
Depends on the site of origin, but pts with base of skull chordomas present with intermittent diplopia, HA, neck pain, or other lower CN findings. Invasion of the cavernous sinus produces diplopia and facial numbness.
What is important in the workup for skull base tumors?
Skull base tumor imaging workup: MRI/CT (to assess local bone destruction) and Bx
What are the T1-T2 MRI features of chordomas?
T1-T2 MRI features of chordomas:
1. T1: intermediate to low signal intensity, with marked but heterogeneous enhancement with gadolinium
2. T2: very high signal intensity
Besides chordomas, what must be on the DDx of tumors arising in the axial skeleton?
Mets, chondrosarcoma, mucinous adenocarcinoma, myxopapillary ependymoma, meningiomas, neuromas, glomus jugulare tumors, cholesteatoma, nasopharyngeal carcinoma, and other soft tissue sarcomas −(rhabomyosarcoma in children)
What immunostains distinguish chordomas from chondrosarcomas?
Chondrosarcomas do not express cytokeratin or EMA and chordomas do not express vimentin, but both express S100 antigen. Neither express glial fibrillary acidic protein (but myxopapillary ependymoma does).
Why is it important to distinguish chordomas from chondrosarcomas?
Chondrosarcomas have a better prognosis.
What staging system is used for chordomas?
Per the AJCC, chordoma is staged as a primary bone tumor.
What is the mainstay of Tx for chordomas?
Surgery is the mainstay of Tx of chordomas, with max surgical resection being optimal to improve outcomes.
What Tx is most commonly employed after surgical resection?
Since most chordomas are not fully resectable, postop radiotherapy is often employed.
Is aggressive management of chordomas at initial presentation (surgery + adj RT) important to improve outcomes compared to the same Tx at the time of recurrence (salvage RT)?
Yes. Adj RT may improve outcomes compared to a strategy of observation, reserving RT for salvage.
A retrospective series from France (Carpentier A et al., J Neurosurg 2002) found that pts managed aggressively at initial presentation (surgery + RT) compared to those treated aggressively at the time of recurrence (after initial surgery) had improved outcomes (5- and 10-yr survival: 80% and 65% for aggressive vs. 50% and 0% for salvage). These strategies have not been prospectively evaluated.
Is conventional fractionated RT an effective Tx for chordomas?
Yes. Conventional fractionated RT is effective for −palliating chordomas. Retrospective series of skull base chordomas demonstrated that with 50 Gy (photons only), 85% of pts achieved useful and prolonged pain palliation. However, LC was ~27%, 5-yr PFS was ~23%, and MS was ~62 mos (Catton C et al., −Radiother Oncol 1996). Larger total doses are not achievable with conventional fractionated RT without causing undue toxicities.
What RT modality is preferred for the management of skull base chordomas?
Charged-particle RT (protons or carbon ions) allows high doses of RT to be delivered while limiting the dose to surrounding normal structures. Doses of 70–80 Gy can be achieved. In the largest series of 195 pts with chordomas treated at the Massachusetts −General Hospital from 1974–1995, with a mean dose of 67.8 cobalt Gray equivalents (CGE; 63–79.2 CGE), the 5- and 10-yr PFS was 70% and 45%, respectively. (Debus J et al., IJROBP 1997)
What factor determines the risk for recurrence after Tx with proton beam therapy?
The volume of residual Dz after surgical resection determines the risk of recurrence after Tx with proton beam therapy.
In a series from Loma Linda (Hug EB et al., J Neurosurg 1999), for residual tumors abutting the brain stem or >25 cc, the control rate was about 50% in the follow-up period (mean, 33 mos); those not −abutting the brain stem or <25 cc residual Dz did not have recurrence.
What is the pattern of recurrence of chordomas after Tx?
LR is most common (95%), while 10%–20% of the pts who recur also develop nodal or distant Dz. The most common sites of distant Dz are lung and bone. (Fagundes MA et al., IJROBP 1995)
What is the typical LC and OS for chordomas compared to chondrosarcomas after 70 CGE of proton beam therapy?
In the Loma Linda series of 58 pts (33 chordomas and 25 chondrosarcomas), with a mean follow-up of 33 mos, LC was 76% for chordoma and 92% for chondrosarcoma. The 5-yr OS rates were 79% for chordoma and 100% for chondrosarcoma. (Hug EB et al., J Neurosurg 1999)
What is the role of SRS in the management of chordomas?
FSR and SRS are feasible options but with less of a track record compared with charged-particle therapy. The LC and survival rates are promising.
In 1 series using FSR (Debus J et al., IJROBP 2000), achieving a median dose of 66.6 Gy at the isocenter, the 2- and 5-yr LC rates were 82% and 50%, and the 2- and 5-yr OS were 97% and 82%, respectively.
In a series from Pittsburgh using SRS to 16 Gy × 1 fx (in mainly recurrent chordoma), the 5-yr LC was 63%. (Martin JJ et al., J Neurosurg 1987)
What is the role of brachytherapy in the management of chordomas?
Small series have shown that recurrent chordomas of the skull base and spine can be successfully managed with interstitial iodine-125 in select cases. (Gutin PH et al., J Neurosurg 1987; Kumar PP et al. J Neurosurg 1988)
What is the role of chemo or molecularly targeted agents in the management of chordomas?
In chordomas, cytotoxic chemo has not shown −clinically significant activity. Imatinib (Gleevac) is −currently being evaluated in the phase II setting. In addition, preclinical work suggests potential for the inhibition of PI3K/MTOR pathways (Schwab J et al., Anticancer Res 2009).
What is the survival of pts with recurrent Dz who rcv salvage Tx compared to supportive care?
The outcomes after recurrence are generally poor, but salvage Tx (surgery + RT) can be used after recurrence, with 2-yr survival of 63% vs. 21% with supportive care. However, most pts die even with therapy, with 5-yr survival only 6% after recurrence. (Fagundes MA et al., IJROBP 1995).
Definitive proton beam can salvage some pts, with a 2-yr actuarial LC rate of 33%. (Berson AM et al., IJROBP 1988)
What are 5 poor prognostic factors for chordomas?
Poor prognostic factors for chordoma:
1. Recurrent Dz
2. Base of skull tumors
3. Female sex
4. Presence of tumor necrosis in pre-Tx Bx
5. Large tumors (>70 cc in 1 series)
What are some common late toxicities that manifest after the Tx of skull base chordomas?
~26% of skull base chordoma pts develop endocrine abnormalities, while 5%–10% of pts develop vision loss, brainstem injury, or temporal lobe injury in 2–5 yrs. (Berson AM et al., IJROBP 1988; Santoni R et al., IJROBP 1998)