Base of skull chordomas in children and adolescents: a clinicopathologic study of 73 cases

Chordomas in children and adolescents comprise <5% of all chordomas and most frequently develop in the skull base. These tumors are believed to behave more aggressively than chordomas in adults and may have unusual morphology. This study examines a large series of pediatric skull base chordomas treated with a standardized protocol to characterize the behavior and morphology of these tumors. There were 31 males and 42 females ranging from 1 to 18 (mean 9.7) years. Forty-two cases (58%) were conventional chordomas, some of which had unusual histopathologic features. Chondroid chordomas comprised 23% of cases. Fourteen tumors (19%) were highly cellular and had a solid growth pattern with no myxoid matrix or lobular architecture. Eight of these had cytologic features of conventional chordoma cells including physaliferous cells (cellular chordoma). The remaining cellular tumors were composed of poorly differentiated epithelioid cells set in a fibrous stroma and lacked physaliferous cells (poorly differentiated chordoma). All variants studied by immunohistochemistry showed positive staining for cytokeratin, epithelial membrane antigen, S100 protein, and vimentin. Mitoses and necrosis were seen in all variants. Follow-up data were available for all patients and ranged from 1 to 21 (mean 7.25) years. The survival rate was 81%. All but 1 patient with poorly differentiated chordoma died of disease. Overall, base of skull chordomas in children and adolescents treated with proton beam radiation have better survival than chordomas in adults. However, poorly differentiated chordomas are highly aggressive tumors

Base of skull chordoma. A correlative study of histologic and clinical features of 62 cases

Background. Chordomas are uncommon primary malignant tumors of bone that typically occur in the axial skeleton including the sacrum, vertebrae, and skull base. The base of skull tumors usually are not amenable to complete surgical resection, and most require postoperative radiotherapy. The natural history of skull base chordoma is typified by slow locally invasive tumor progression and eventual death, although few parameters are known that allow stratification of patients into prognostic groups. Methods. Sixty‐two patients with skull base chordomas treated at the Massachusetts General Hospital by proton beam irradiation therapy with at least 2 years of follow‐up information were reviewed in an attempt to identify clinical and pathologic parameters that predicted outcome. Results. Female sex, tumor necrosis in preradiation treatment biopsy, and tumor volume in excess of 70 ml were each independent predictors of shortened overall survival after radiation therapy for skull base chordoma. Conclusions. Stratification of patients with skull base chordoma into poor and good outcome groups can be performed using the three parameters identified in our study. In addition, the striking difference in survival between the sexes suggests that further investigations of these tumors should include determination of their hormonal receptor status and consideration of hormonal manipulation in their management

Accuracy of proton beam range verification using post-treatment positron emission tomography/computed tomography as function of treatment site

PURPOSE: For 23 patients, an off-line positron emission tomography scan and a computed tomography scan after proton radiotherapy was performed at the Massachusetts General Hospital to assess in vivo treatment verification. A well-balanced population of patients was investigated to assess the effect of the tumor location on the accuracy of the technique. METHODS AND MATERIALS: Range verification was achieved by comparing the measured positron emission tomography activity distributions with the corresponding Monte Carlo-simulated distributions. Observed differences in the distal end of the activity distributions were analyzed as potential indicators for the range differences between the actual delivered and planned dose. RESULTS: The average spatial agreement between the measured and simulated activity distribution was within ±3 mm, and the corresponding average absolute agreement was within ±45% (derived from gamma index analysis). The mean absolute range deviation at 93 randomly chosen positions in 17 treatment fields delivered to 11 patients was 3.6 mm. Characteristic differences in the agreement of the measured and simulated activity distribution for the different tumor/target sites were found. This resulted from the different effect of factors such as biologic washout effects, motion, or limitations in the Monte Carlo-simulated activity patterns. CONCLUSION: We found that intracranial and cervical spine patients can greatly benefit from off-line positron emission tomography and computed tomography range verification. However, for the successful application of the method to patients with abdominopelvic tumors, major technological and methodologic improvements are needed. Among the intracranial and cervical spine target sites, patients with arteriovenous malformations or metal implants represent groups that could especially benefit from the approach

Sacral chordomas: Impact of high-dose proton/photon-beam radiation therapy combined with or without surgery for primary versus recurrent tumor

Purpose: To assess the efficacy of definitive treatment of sacral chordoma by high-dose proton/photon-beam radiation therapy alone or combined with surgery. Methods and Materials: The records of 16 primary and 11 recurrent sacral chordoma patients treated from November 1982 to November 2002 by proton/photon radiation therapy alone (6 patients) or combined with surgery (21 patients) have been analyzed for local control, survival, and treatment-related morbidity. The outcome analysis is based on follow-up information as of 2005. Results: Outcome results show a large difference in local failure rate between patients treated for primary and recurrent chordomas. Local control results by surgery and radiation were 12/14 vs. 1/7 for primary and recurrent lesions. For margin-positive patients, local control results were 10 of 11 and 0 of 5 in the primary and recurrent groups, respectively; the mean follow-up on these locally controlled patients was 8.8 years (4 at 10.3, 12.8, 17, and 21 years). Radiation alone was used in 6 patients, 4 of whom received ≥73.0 Gy (E); local control was observed in 3 of these 4 patients for 2.9, 4.9, and 7.6 years. Conclusion: These data indicate a high local control rate for surgical and radiation treatment of primary (12 of 14) as distinct from recurrent (1 of 7) sacral chordomas. Three of 4 chordomas treated by ≥73.0 Gy (E) of radiation alone had local control; 1 is at 91 months. This indicates that high-dose proton/photon therapy offers an effective treatment option

Updated Outcome and Analysis of Tumor Response in Mobile Spine and Sacral Chordoma Treated With Definitive High-Dose Photon/Proton Radiation Therapy

Treatment of spine and sacral chordoma generally involves surgical resection, usually in conjunction with radiation therapy. In certain circumstances where resection may result in significant neurologic or organ dysfunction, patients can be treated definitively with radiation therapy alone. Herein, we report the outcome and the assessment of tumor response to definitive radiation therapy. A retrospective analysis was performed on 40 patients with unresected chordoma treated with photon/proton radiation therapy. Nineteen patients had complete sets of imaging scans. The soft tissue and bone compartments of the tumor were defined separately. Tumor response was evaluated by the modified Response Evaluation Criteria in Solid Tumors (RECIST) and volumetric analysis. With a median follow-up time of 50.3 months, the rates of 5-year local control, overall survival, disease-specific survival, and distant failure were 85.4%, 81.9%, 89.4%, and 20.2%, respectively. Eighty-four computed tomographic and magnetic resonance imaging scans were reviewed. Among the 19 patients, only 4 local failures occurred, and the median tumor dose was 77.4 GyRBE. Analysis at a median follow-up time of 18 months showed significant volumetric reduction of the total target volume (TTV) and the soft tissue target volume (STTV) within the first 24 months after treatment initiation, followed by further gradual reduction throughout the rest of the follow-up period. The median maximum percentage volumetric regressions of TTV and STTV were 43.2% and 70.4%, respectively. There was only a small reduction in bone target volume over time. In comparison with the modified RECIST, volumetric analysis was more reliable, more reproducible, and could help in measuring minimal changes in the tumor volume. These results continue to support the use of high-dose definitive radiation therapy for selected patients with unresected spine and sacral chordomas. Assessment of tumor response to radiation therapy by volumetric analysis is superior to modified RECIST in chordoma patients. Evaluating the soft tissue target volume is an excellent indicator of tumor response

Ectopic Recurrence of Skull Base Chordoma after Proton Therapy

BACKGROUND: Chordoma are rare tumors of the axial skeleton. The treatment gold standard is surgery, followed by particle radiotherapy. Total resection is usually not achievable in skull base chordoma (SBC) and high recurrence rates are reported. Ectopic recurrence as a first sign of treatment failure is considered rare. Favorable sites of these ectopic recurrences remain unknown. METHODS: Five out of 16 SBC patients treated with proton therapy and surgical resection developed ectopic recurrence as a first sign of treatment failure were critically analyzed regarding prior surgery, radiotherapy, and recurrences at follow-up imaging. RESULTS: Eighteen recurrences were defined in five patients. A total of 31 surgeries were performed for primary tumors and recurrences. Seventeen out of eighteen (94%) ectopic recurrences could be related to prior surgical tracts, outside the therapeutic radiation dose. Follow-up imaging showed that tumor recurrence was difficult to distinguish from radiation necrosis and anatomical changes due to surgery. CONCLUSIONS: In our cohort, we found uncommon ectopic recurrences in the surgical tract. Our theory is that these recurrences are due to microscopic tumor spill during surgery. These cells did not receive a therapeutic radiation dose. Advances in surgical possibilities and adjusted radiotherapy target volumes might improve local control and survival

Patient study of in vivo verification of beam delivery and range, using positron emission tomography and computed tomography imaging after proton therapy

PURPOSE: To investigate the feasibility and value of positron emission tomography and computed tomography (PET/CT) for treatment verification after proton radiotherapy. METHODS AND MATERIALS: This study included 9 patients with tumors in the cranial base, spine, orbit, and eye. Total doses of 1.8-3 GyE and 10 GyE (for an ocular melanoma) per fraction were delivered in 1 or 2 fields. Imaging was performed with a commercial PET/CT scanner for 30 min, starting within 20 min after treatment. The same treatment immobilization device was used during imaging for all but 2 patients. Measured PET/CT images were coregistered to the planning CT and compared with the corresponding PET expectation, obtained from CT-based Monte Carlo calculations complemented by functional information. For the ocular case, treatment position was approximately replicated, and spatial correlation was deduced from reference clips visible in both the planning radiographs and imaging CT. Here, the expected PET image was obtained from an analytical model. RESULTS: Good spatial correlation and quantitative agreement within 30% were found between the measured and expected activity. For head-and-neck patients, the beam range could be verified with an accuracy of 1-2 mm in well-coregistered bony structures. Low spine and eye sites indicated the need for better fixation and coregistration methods. An analysis of activity decay revealed as tissue-effective half-lives of 800-1,150 s. CONCLUSIONS: This study demonstrates the feasibility of postradiation PET/CT for in vivo treatment verification. It also indicates some technological and methodological improvements needed for optimal clinical application

High-dose proton-based radiation therapy in the management of spine chordomas: outcomes and clinicopathological prognostic factors

Spinal chordomas can have high local recurrence rates after surgery with or without conventional dose radiation therapy (RT). Treatment outcomes and prognostic factors after high-dose proton-based RT with or without surgery were assessed. The authors conducted a retrospective review of 126 treated patients (127 lesions) categorized according to disease status (primary vs recurrent), resection (en bloc vs intralesional), margin status, and RT timing. Seventy-one sacrococcygeal, 40 lumbar, and 16 thoracic chordomas were analyzed. Mean RT dose was 72.4 GyRBE (relative biological effectiveness). With median follow-up of 41 months, the 5-year overall survival (OS), local control (LC), locoregional control (LRC), and distant control (DC) for the entire cohort were 81%, 62%, 60%, and 77%, respectively. LC for primary chordoma was 68% versus 49% for recurrent lesions (p = 0.058). LC if treated with a component of preoperative RT was 72% versus 54% without this treatment (p = 0.113). Among primary tumors, LC and LRC were higher with preoperative RT, 85% (p = 0.019) and 79% (0.034), respectively, versus 56% and 56% if no preoperative RT was provided. Overall LC was significantly improved with en bloc versus intralesional resection (72% vs 55%, p = 0.016), as was LRC (70% vs 53%, p = 0.035). A trend was noted toward improved LC and LRC for R0/R1 margins and the absence of intralesional procedures. High-dose proton-based RT in the management of spinal chordomas can be effective treatment. In patients undergoing surgery, those with primary chordomas undergoing preoperative RT, en bloc resection, and postoperative RT boost have the highest rate of local tumor control; among 28 patients with primary chordomas who underwent preoperative RT and en bloc resection, no local recurrences were seen. Intralesional and incomplete resections are associated with higher local failure rates and are to be avoided