gms | German Medical Science

Chordomas are rare tumors that origin from embryonic remnants of the primitive notochord (Batsakis, 1979). Their incidence is around 0,05/100000/year. They account less than 1% of central nervous system tumors (Weber et al., 1995) and they account for <5% of all bone tumors. The most common locations are the sacrococcygeal region (45%–49%), the base of the skull (36%–39%), and the spinal axis (8%–15%) (Harrison and Lund, 1993). No racial predilection for chordomas has been reported, male-to-female ratio is generally reported to be 2:1. (Perzin and Pushparaj, 1986; Weber et al., 1995). Every age can be involved with predominance for the third and fourth decades for intracranial localization (Perzin and Pushparaj, 1986; Weber et al., 1995). Chordoma has no known association with irradiation or any other environmental factors. A small percentage of cases have a familial pattern of inheritance (Dalprà L, 1999).

Chordomas lie in the bone, so they initially grow extradurally with bone destruction and secondary extension into the adjacent soft tissues (Oikawa et al., 2001); they have common characteristics of a malignant tumor, with local invasiveness, tendency for recurrence, and the potential to metastatize. In 1973 Heffelfinger first described the chondroid chordoma, a histologic variant of chordoma. Dedifferentiated or sarcomatoid chordomas are high-grade neoplasms, but account for only 5% of cases.

Clinically they are slow-growing diseases. Tumor spread mainly occurs locally. Symptoms manifest late, even after years, and therefore the local extent of disease is often huge at diagnosis. Pain and neurological symptoms from local compression are the main subjective patient’s complaints. They obviously depend on tumor location. Headache and diplopia are the most common symptoms (among the oculomotor nerves the abducens is the most frequently involved) related to chordoma of the clivus and base of the skull (Volpe et al., 1993).

Given the natural history and histological characteristics of the disease, treatment is based on local modalities. Surgery is the treatment of choice. The aggressiveness of local resection has been correlated to patient’s outcome, in terms of both local control and survival.

Postoperative radiotherapy can provide better control of the disease. (Rosenberg et al., 1999; Hug et al., 1999; Crockard et al., 2001). Chemiotherapy has been resorted to, but only anedoctal reports of activity of chemotherapeutic agents or regimens are available.

A series of 32 patients with clival chordomas operated on at the Department of Neurosurgery of the San Raffaele Scientific Institute in Milan, between 1990 and 2005 was reviewed; we report data and statistical analysis on 29 cases.

The age range was 4 to 69 years with an average age of 46,7 years; 17 patients were male (58,6%) and 12 were female (41,4%). The length of follow-up ranged from 1 to 177 months, with an average of 57,4 months. Nine patients underwent previous treatments: 6 cases were biopsied, 2 underwent partial surgery and one was treated with radiosurgery. The three most frequent presenting symptoms were diplopia (55,1%), headache (24,1%) and ptosis (17,3%); the pre-operative neurological exam showed cranial nerve impairments in 72,4%: the most frequent cranial nerve involved was the abducent (48,3%), the oculomotor in 24,1% of cases and the optic nerve in 24,1%. In the 6,9% of Others presentig signs were para or tetraparesis in 6,9% of patients, hemiparesis in 6,9% of patients and cerebellar signs in 3,4% of cases.

Concerning the tumor location, we have considered the Sekhar classification of 1993, in which he distinguished upper, middle and lower clival chordomas. In our series, in 3,4% of cases the tumor involved the upper clivus, in 37,9% the upper and middle clivus, in 24,1% only the middle clivus, in 24,1% middle and lower clivus, and in 10,3% the chordoma spread along all the clivus; in 15 cases the development of the tumor was only extradural (51,7%), while in 14 cases was transdural (48,3%). The clivus neighbour structures more frequently involved by the tumor were the sphenoidal sinus in 44,8% of cases, cavernous sinus in 34,5% and sella turcica in 27,6% of cases.

Fourty-four surgical procedures were carried out; in 7 cases a staged operation was planned in two or threee procedures. To approach extradural tumors, the anterior routes were preferred to the lateral ones; the transsphenoidal approach was used in 16 cases (36,4%), in 11 cases (25%) a transmaxillary approach (Le Fort I osteotomy in 8 cases, open door maxillotomy in the other 3 cases) was used; in 7 cases (15,9%) the extended subfrontal approach was used; 6 cases (13,6%) were operated on through a fronto-temporal or fronto-orbito-zygomatic approach; in only 2 cases (4,5%) a total petrosectomy was performed; other appoaches were used in the last 2 cases.

The surgical removal was gross-total in 11 cases (37,9%), subtotal (>90%) in 12 cases (41,4%), partial (<90%) in 4 cases (13,8%) and 2 cases underwent only a biopsy (6,9%).

The histology was classic chordoma in 18 cases (62%) and chondroid chordoma in 11 cases (37,9%).

Eleven patients died, 10 for progression of disease and one for surgical complications (cerebral infarction) one month after surgery. Post-operative complications occurred in 4 patients; we recorded one case of cerebellar infarction, one of cerebral-spinal-fluid leak, one of severe hyponatremia and one of sinusitis. Twenty-four patients underwent adjuvant therapies: 15 (51,7%) patients were treated with proton beam, 6 (20,7%) with conventional radiotherapy, 3 patients (10,3%) underwent radiosurgery with gamma-knife; 5 patients (17,2%) didn’t receive any form of adjuvant therapy.

Among the 18 alive patients we have compared the pre-operative Karnofsky Performance Status (KPS) score to the KPS score recorded at last follow-up clinical examination; in 9 patients the score was unchanged, in 6 patients was improved, and in 3 cases was worsened. The mean of pre-operative KPS score was 92,2 (SD=7,33) and the mean of KPS at last clinical examination was 92,8 (SD=13,2). In the other two publicated series (Gay et al., 1995, Pamir et al., 2004) in which the KPS has been considered, the mean of post-operative KPS score was worse than the mean of pre-operative KPS score.

The overall survival and the progression-free survival were estimated using the Kaplan-Meier survivorship method; the overall survival was 67% at 5 years and 46% at 10 years; the progression-free survival was 48% at 5 years and 40% at 10 years. The overall survival at 5 and 10 years of patients tretaed with radiation therapy after sutgery – respectively 78% and 50% (P<0.001) – was better then the overall survival of patients who didn’t undergo any form of adjuvant therapy (all of these patients died before 5 years after surgery).

Figure 1 [Fig. 1]