Demographics

• Proliferative ability of chordoma was found to be related to increased age, clinical status and nuclear pleomorphism in patients with both skull based chordomas (SBC) and nonskull based chordomas (NSBC). The prognosis for NSBC patients with nuclear pleomorphism was found to be significantly poorer than for those without . [1]
• An age of greater than 53 years-old, tumor relapse after surgical resection, tumor diameters greater than 45 mm, tumor volumes greater than 23 square-cm, and irradiation of less than 90% of the gross tumor volume were found to be associated with poorer prognosis among 100 chordoma patients treated with combination photon-proton therapy. [2]
• Among 19 patients with skull base chordoma, there was a statistically significant difference between the ages of patients with a fast-growing tumor (mean = 47.7 years) and those with a slow-growing tumor (mean = 26.2 years). [3]
• Among 41 chordoma patients, those aged younger than 40 (n = 18) had a statistically significant higher probability of survival than those aged 40 or older (n = 23). [4]

Tumor Anatomy and Surgery

• Twenty-six intraosseous benign notochordal cell tumours were found in the vertebra and clival bones from from 20 of 100 autopsy cases. There were 7 in the clival region and 19 in the vertebral column: 5 in the coccyx, 4 in the C2, 2 each in S3 and S4 and one each in C5, L3, L4, S1, S2, and S5. The results, according to anatomical segments, showed that 11.5% of the clivus, 5.0% of the cervical vertebrae, 0% of the thoracic vertebrae, 2.0% of the lumbar vertebrae, and 12.0% of the sacro-coccygeal vertebrae were affected. [5]
• 15 of 61 patients (24.6%) in whom both vertebral column and clival portions were examined had benign notochordal cell tumours. [5]
• A resected chordoma demonstrated a small intraosseous benign notochordal lesion in the coccyx, which was adjacent to the classic chordoma. [6]
• Predictors of low probability for overall survival among 37 chordoma patients with cervical or sacral spine tumors were inadequate surgical margin without radiotherapy, involvement of multiple contiguous vertebral levels, and cervical spine location. [7]
• Predictors of local recurrence among 37 chordoma patients with cervical or sacral spine tumors were inadequate surgical margin at initial surgery and involvement of multiple contiguous vertebral levels (independent factors). [7]
• Predictors of tumor-related death among 37 chordoma patients with cervical or sacral spine tumors were upper cervical spine location and involvement of multiple contiguous vertebral levels because of inadequate surgical margins. [7]
• Initial surgery margin was not statistically predictive for chordoma prognosis among 37 chordoma patients with cervical or sacral spine tumors. [7]
• Retrospective review of 56 patients with sacral spine chordoma treated with surgical resection found wide surgical margins to be associated with increased survivorship to local recurrence. [8]
• Retrospective review of 56 patients with sacral spine chordoma treated with surgical resection found no difference in survivorship to local recurrence between wide and wide-contaminated surgical margins. [8]
• Retrospective review of 56 patients with sacral spine chordoma treated with surgical resection found previous intralesional surgery to be associated with an increased local recurrence rate. [8]
• Retrospective review of 56 patients with sacral spine chordoma treated with surgical resection found no relationship between a lower level of resection and survivorship to local recurrence. [8]
• 12 of 19 (63.2%) patients with classic, surgically resected, skull base chordoma experienced recurrence between 5 and 80 months post-operatively. Among these patients, those with wider surgical margins at initial operation tended to experience recurrence at a later time. [9]
• Among 15 chordoma patients with surgically resected skull base tumors, the tumor doubling time tended to be directly associated with surgical margin at initial operation. [9]

Tumor Histology

• In patients with NSBC, prognosis was found to be significantly poorer in cases with nuclear pleomorphism than in those without (P = 0.027). [1]
• Cases consisted of 6 clival chordomas, 1 lumbosacral chordoma, and 1 chordoma arising from the sphenoid bone. In 8 pediatric chordomas, there was a correlation between higher MIB-1 LI and tumor recurrence (p = 0.007) and MIB-1 LI and low survival rate (p = 0.007). [10]
• The presence of mitosis was detected in 14 of 28 (50%) skull base chordoma samples. Mitotic presence was positively correlated with tumor doubling time, with greater presence suggestive of a worse prognosis. [3]
• Ki-67 staining of classic chordoma samples from 19 patients surgically resected skull base chordoma revealed non-homogeneous staining and an average proliferative index of 3.6 ± 2.0% among primary tumor samples and 5.0 ± 2.1% among recurrent tumor samples. Tumor doubling time was seen to be negatively associated with the proliferative index. [9]
• The average Ki-67 labeling index, by immunohistochemistry, among 28 tumor samples from 19 patients with skull base chordoma was 5.1%. Ki-67 labeling index of greater than 6% was negatively correlated with tumor doubling time, with higher labeling suggestive of a worse prognosis. [3]

Chemotherapy and Radiation

• 2 patients (2 years-old and 15 years-old) were diagnosed with clival chordoma and received subtotal tumor resection. Both developed severe post-operative complications. One of those two patients (2 year-old) underwent intensity modulated radiation therapy followed by chemotherapy with ifosfamide and etoposide after relapse, while the other patient (15 year-old) refused adjunct therapy. The patient who underwent adjunct therapy was still alive with stable, residual tumor 13 years following diagnosis, while the patient who refused therapy died of progressive disease 1.5 years post-diagnosis. [11]
• 4 patients (median age = 6 years) were diagnosed with clival chordoma and received partial tumor resection. None of the patients developed serious post-operative complications. 2 patients underwent chemotherapy with ifosfamide and etoposide after initial resection. One of the two developed tumor relapse, which was treated by partial resection. Both of these patients were alive with stable, residual tumor 9 years following diagnosis. After initial resection, 1 patient underwent proton beam radiation therapy followed by chemotherapy with ifosfamide and etoposide and adherence to Celebrex and Gleevec. This patient was alive with stable, residual tumor at 6 years post-diagnosis. The final patient underwent intensity modulated radiation therapy alongside oral etoposide following initial resection. At relapse, the patient received a partial tumor resection followed by adherence to chemotherapy (ifosfamide and liposomal doxorubicin) and adjunct treatment with Celebrex and Gleevec. This patient died 3.25 months post-diagnosis of intracranial bleeding after developing acute myeloid leukemia subsequent to the second tumor resection. [11]
• Combination photon-proton therapy on 100 chordoma patients resulted in 94.3% 2-year survival, 89.6% 4-year survival, and 80.5% 5-year survival. [2]
• 28 of 100 (28%) chordoma patients treated with combination photon-proton therapy experienced tumor relapse at a median of 26 months following the end of radiotherapy. [2]
• The 2-year local tumor control rate was 86.3% while the 4-year rate was 53.8% among 100 chordoma patients treated with combination photon-proton therapy. [2]
• Local tumor control rate in 100 chordoma patients treated with combination photon-proton therapy was negatively associated with minimum photon-proton dose delivery to the tumor (<56 CGE) and dose delivery to 90% or 95% of the gross tumor volume at <95% prescribed dose. [2]

Cytogenetics

• The odds ratio for recurrence in lesions with an abnormal versus a normal karyotype was 12. [12]
• Aberrations in chromosomes 3, 4, 12, 13, and 14 were associated with frequent recurrence and decreased survival time. [12]
• In de novo cases, 31 of 42 lesions (74%) had a normal karyotype, while among recurrent cases only 6 of 22 (27%) had a normal karyotype. There were significantly more cases of chromosomal aberrations in recurrent chordomas than in de novo lesions.[12]
• 7 of 37 chordomas with a normal karyotype (1 de novo and 6 recurrent lesions) and 20 of 27 lesions with an abnormal karyotype (5 de novo and 15 recurrent cases) had progression or recurrence noted at follow-up. The 5-year recurrence-free survival rate was 81% in 37 patients with chordomas of normal karyotypes, and 34% in 27 patients with chordomas of an abnormal karyotype. [12]
• 95% of cases with progression involved chromosome 3 and/or 13 abberations. The median survival time was 4 months when both of these chromosomes had aberrations. [12]

General Protein Expression

• No correlations between sex steroid hormone receptor expression and disease-free survival were observed . [13]
• E-cadherin expression correlated with disease-free survival, tumor recurrence, and low survival rate; MIB-1 labeling index correlated with tumor recurrence and low survival rate; CD44 expression did not correlate with recurrence or survival rate [10]
• The 5-year survival rate among 40 patients was 38.9% for patients with p53 overexpression and 79.4% for patients without p53 overexpression. Anatomic site, age, gender, aberrations in other proteins (MDM2, cyclin D1, pRb, and p27Kip1) and mdm2 amplification did not correlate to clinical outcome [14]
• Extensive expression (>50% tissue stained) of N-cadherin correlates with a diminished recurrence-free survival rate, and a 3.28 fold increase in probability of recurrence. Minimal or sparse expression (<50% tissue stained) of E-cadherin correlated with increased probabilities of death, and a 10.98 fold increase in probability of death. These results suggest that changes in the relative expression of the cadherin–catenin complex reflect chordoma aggressiveness; and that decreased expression of E-cadherin and increased expression of N-cadherin may underlie the transition from a less to a more aggressive tumor phenotype. [15]
• Higher MMP-9 expression was correlated with poorer outcome. [16]
• The expression of E-cadherin correlated with disease-free survival (P = 0.009), tumor recurrence (P > 0.0007), and low survival rate (P > 0.0007). [10]
• There was no correlation between percentage of expression of CD44 and recurrence (p = 0.056) or survival rate (p = 0.056). [10]
• Patients with higher expression of both MMP-1 and uPA showed worse prognosis compared with the others. [17]
• Predictors of low probability for disease-free survival among 37 chordoma patients with cervical or sacral spine tumors were inadequate surgical margin at initial surgery, performance of the primary surgical procedure outside a specialized center, involvement of contiguous vertebral levels, and overexpression of ENO1 or PKM2. [7]
• Overexpression of ENO1, PKM2, and gp96 were not prognostic for chordoma among 37 chordoma patients with cervical or sacral spine tumors. [7]
• High MMP-9 expression was found to be a statistically significant negative predictor of disease-free survival among 11 patients with skull base chordoma. [16]
• A higher ratio between MMP-9 and RECK (reversion-inducing cysteine-rich protein with Kazal motifs) expression was found to be a statistically significant negative predictor of disease-free survival among 11 patients with skull base chordoma. [16]
• Immunohistochemistry on 8 recurrent tumor samples from patients with skull base chordoma followed by statistical analysis found a statistically significant smaller difference in the change in p53 expression between the primary versus recurrent tumor sample in patients who were alive at the time of the study compared to patients who were dead. [18]
• Immunohistochemistry on 8 recurrent tumor samples from patients with skull base chordoma followed by statistical analysis found a statistically significant lower level of both Ki-67 and p53 expression in samples from patients with disease-free survival at the time of the study compared to samples from patients with ongoing disease. [18]
• Continuous disease-free survival time was greater among 22 patients with sacral chordoma when the tumor was located below S3, when PCNA and bFGF expression were low in the primary tumor sample, when the tumor was initially excised by radical resection. [19]
• 16 of 29 (55.2%) classic, skull base chordoma samples showed mutation of p53 protein by IHC. These p53-positive chordomas tended to have a shorter tumor recurrence interval, shorter tumor doubling time, decreased recurrence-free probability, and higher proliferative index than p53-negative chordomas. [9]
• Expression of human telomerase reverse transcriptase (hTERT) mRNA was observed by ISH in 14 of 29 (48.3%) classic, skull base chordoma samples. Chordomas expressing hTERT mRNA tended to have a shorter tumor recurrence interval, shorter tumor doubling time, decreased recurrence-free probability, and higher proliferative index than hTERT mRNA-negative chordomas. [9]

Brachyury (T) Expression

• Among 181 chordoma patients, no correlation was found between copy number gain of T and display of metastatic disease, tumor recurrence, tumor size, and age at presentation of tumor. [20]

Cytokine Receptor Expression

• High (>75% of tumor nuclei ) pStat3 immunohistochemical staining was associated with significantly worse prognosis than low pStat3 (<10% of tumor nuclei ) staining. [21]
• Recurrent tumors expressed greater level of pStat3 than primary tumors, and pStat3 expression intensity was higher in tumors with metastasis compared with the primary tumors without metastasis. [21]

Receptor Tyrosine Kinase Expression

• The staining patterns of PDGFR-B, EGFR, p-EGFR, KIT, HER2, p-MAPK, p-Akt, and p-stat3 did not correlate with disease-free survival or site of origin . [22]
• The 5-year survival rate was 79.9% in patients with c-MET expression, and was 44.4% in those without c-MET expression; there was a significant difference noted with regard to their survival rate. [23]

References