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ORIGINAL ARTICLE
Ahead of print publication  

Chordoma: Retrospective analysis of patients treated with radiotherapy at a single institution


 Department of Radiation Oncology, The Gujarat Cancer and Research Institute, M.P.Shah Cancer Hospital, New Civil Hospital Campus, Asarwa, Ahmedabad, Gujarat, India

Date of Submission05-Mar-2022
Date of Decision19-Apr-2022
Date of Acceptance12-May-2022
Date of Web Publication24-Aug-2022

Correspondence Address:
Maitrik Mehta,
Department of Radiation Oncology, The Gujarat Cancer and Research Institute, M.P.Shah Cancer Hospital, New Civil Hospital Campus, Asarwa, Ahmedabad, Gujarat
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jrcr.jrcr_18_22

  Abstract 

Introduction: Chordoma is a low-grade notochordal tumor of the skull base, mobile spine, and sacrum, which is locally invasive and tends to present late in the disease course and confers a poor prognosis. They usually recur locally and surgery is the mainstay of treatment. Radiotherapy (RT) is often given postoperatively to reduce local recurrence. The purpose of this study is to assess RT treatment given at our center for chordoma patients. Materials and Methods: In this retrospective analysis, 25 patients with chordoma treated with RT between 2013 and 2020 at a single institution were reviewed. Eleven patients had sacrococcygeal tumors, three had clival tumors, two had lumbar, one had sphenoid tumors, one had nasal cavity tumors, two had cervical spine tumors, and two had sellar/suprasellar tumors. Out of 25 patients, 19 patients underwent surgical excision (partial/complete) and in 6 patients only a biopsy was done. Two patients underwent recurrent surgical excision. All patients received RT either postoperative or in recurrent settings or after biopsy only. The median RT dose was 30 Grey (Gy) (range, 16–60 Gy). Results: On analysis, seven patients were lost to follow-up. Three patients were on follow-up till 56, 53, and 41 months and were included in a 4-year survival analysis. Eighteen patients follow-up were available. Out of 18 patients, 8 patients had died and 10 patients were alive. With the median follow-up of 37.5 months, the 4-year overall survival rate was 61.9% in 21 patients. With the median follow-up of 39 months, the 5-year overall survival rate was 55.6% in 18 patients. Conclusions: RT in the postoperative setup may improve the overall survival in chordoma patients. Further detailed analysis is necessary for RT dose and/or higher techniques need to be used for local control of the disease.

Keywords: Chordoma, overall survival, radiotherapy



How to cite this URL:
Mehta M, Patel M, Parikh A, Suryanarayan U, Singh J, Thimmarayappa A, Pandya A. Chordoma: Retrospective analysis of patients treated with radiotherapy at a single institution. J Radiat Cancer Res [Epub ahead of print] [cited 2022 Dec 4]. Available from: https://www.journalrcr.org/preprintarticle.asp?id=354438


  Introduction Top


Chordomas are slowly growing but locally invasive and tend to destroy bone and infiltrate soft tissues. They arise from remnants of the primitive notochord and 50% arise in the sacrococcygeal area, 35% intracranial where they typically involve the clivus, and the remaining 15% in the midline along the path of the notochord, primarily involving the cervical vertebrae.[1] The general management of the patient is dictated by the anatomic location of the tumor and the direction and extent of spread. Complete surgical resection is usually unusual.[2] As chordomas have a high incidence of local recurrence, surgical excision followed by local radiotherapy (RT) is highly recommended.[2],[3],[4],[5],[6],[7],[8] With advances in RT treatment such as conformal techniques, proton, and heavy-ion therapy have been used to improve local control and functional outcomes.[9],[10],[11] Moreover, modern RT plays a role mainly as an adjunct to surgical resection usually when given early in the course.[11],[12],[13],[14],[15] We reviewed RT treatment results of chordoma patients involving different sites.


  Materials and Methods Top


We assessed patients with chordoma registered in our institute between July 2013 and June 2020 in this retrospective analysis. We retrieved files from the medical record department with permission. A total of 52 patients with chordoma were registered during this period. Out of 52, 25 patients had received RT and were assessed for the stated objective. All patients were followed till December 2021 and who did not come to follow up, we called them to ask for their current status.

We have retrieved data for all cases of chordoma such as clinical presentation, computed tomography scan or magnetic resonance imaging findings, biopsy, surgical excision, and RT treatment delivered with follow-up details.

Site-wise presentation is as follows: 13 patients had sacrococcygeal tumors, 3 had clival tumors, 2 had lumbar, 1 had a sphenoid tumor, 1 had skull base tumor followed by recurrence in nasal cavity tumor, 3 had cervical spine tumor, and 2 had sellar/suprasellar tumors.

All patients were treated with RT with the median dose of 30 Grey (Gy) (range, 16 Gy–60 Gy). The RT dose fractionation regimen was dependent on the consultant's decision. Usually, in postoperative near-complete excision or minimum residual disease, the dose of 50 Gy/54 Gy/60 Gy was used. However, in the case of large residual or patients with metastatic disease, the dose of 30 Gy/10# was used.

RT was delivered either by conventional portals (clival tumors – bilateral portal, sacral tumors – single posterior field or anteroposterior/posteroanterior field in case of large tumors, lumbar tumors – posterior field, cervical spine tumors – bilateral portal, and seller/suprasellar tumors – bilateral portal) or conformal treatment (three-dimensional conformal RT-3DCRT or intensity-modulated RT) depending on site.

[Table 1] and [Table 2] show site-wise presentation, surgical and RT details of patients stated above.
Table 1: Age, site-wise presentation, and postoperative radiotherapy details of patients with chordoma treated at a single center

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Table 2: Age, site-wise presentation, and radiotherapy (after biopsy only) details of patients of chordoma treated at a single center

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Out of 25 patients, 7 patients were lost to follow-up. One patient received 16 Gy of radiation then did not take further treatment and one patient received 30 Gy of radiation and lost to follow-up, rest five patients were on follow-up till 56, 10, 53, 41, and 4 months, respectively. Patients who had follow-ups of 56, 53, and 41 months, we included in the study and as per the statistical analysis, we calculated median 4-year overall survival. Eighteen patients' status is well known till December 2021, so, we enroll them in 5-year survival analysis.

The primary endpoint of the study was to assess the survival rate in patients who had received RT (postoperative or after biopsy only) in our institute.

The primary aim of this study was to assess the survival rate in patients who had received RT (postoperative or after biopsy only) in our institute. Hence, we calculated overall survival for patients who received RT and followed till December 2021 (18 patients), and 4-year overall survival for 21 patients (three patients had longer follow-up and as per statistician advice). Overall survival was calculated from the date of diagnosis to the event (death). Survival functions were calculated according to the Kaplan–Meier method,[16] with differences compared (between postoperative RT and RT after biopsy only patients) using the log-rank test.[17]

Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) software version 21 (IBM SPSS Statistics for Windows, Armonk, New York, USA; IBM Corp.). The continuous variables were reported as median with standard deviation and categorical variables as percentages. The association between categorical variables was evaluated for significance, the period of diagnosis to death was calculated in each risk group, and Student's t-test was applied to study the relationship between survival rates of postoperative RT and RT after biopsy only patients The test was considered significant if the P < 0.05.


  Results Top


A total of 52 patients with chordoma were registered between July 2013 and June 2020. Out of 52, 25 patients were treated with RT. Fifteen patients were male and ten patients were female. The median age of presentation was 41 (range, 22–70) years. Nineteen patients had undergone debulking surgery/complete excision followed by postoperative radiation and six patients had undergone biopsy only followed by RT.

On evaluation, seven patients were lost to follow-up. Out of the rest 18 patients, 8 patients had died and 10 patients were alive. Four out of 18 patients were put on palliative imatinib after the completion of RT, out of which 3 patients died and 1 patient is still on follow-up.

Out of seven lost to follow-up patients, two patients were put on palliative imatinib, but we could not be able to contact them.

Out of 13 sacrococcygeal tumors, in 6 patients, only a biopsy was done, in 7 patients, surgery was done either in the form of laminectomy or wide local excision with secrectomy. One patient underwent surgery two times, RT was given for recurrent disease a third time, and eventually patient developed metastasis.

Three patients had clival region tumors, and all three lesions were surgically resected.

One patient had a lesion in the skull base, and surgery was done followed by a recurrent lesion in the nasal cavity and again surgery was done for the same. RT was given after the first surgery.

For two patients with lumbar region lesions, in one patient, surgery was done three times. In the patient in whom surgery was done three times, RT was given after the second surgery.

One patient had sphenoid region disease and surgical excision was done.

Three patients had a disease in cervical spine. Out of three patients, in two patients, laminectomy and fixation were done.

In two patients with suprasellar/parasellar tumors, both patients undergo endoscopic surgical resection.

In three patients (skull base, lumbar, and sacral lesion), repeated surgery was done for recurrent lesions.

Four patients develop metastasis (one with cerebral-cerebellar metastasis, one with lung metastasis, one with liver and bone metastasis, and one with acetabular metastasis).

[Table 1] and [Table 2] show the follow-up period and current status of all patients. Of the eight patients who had died at the time of analysis, five died of local recurrence and three died from distant metastasis. Out of ten patients who are alive, one patient had local recurrence after RT treatment and is on palliative imatinib, one patient had advanced disease and was given palliative RT and is now on palliative imatinib, and the rest eight patients are disease-free.

The median follow-up was 37.5 months for 21 patients in 4-year survival analysis, and the median follow-up was 39 months for 18 patients for actuarial 5-year survival analysis.

The actuarial overall survival rates were 61.9% (21 patients) and 55.6% (18 patients) at 4 and 5 years, respectively. Analysis of actuarial survival rates by the method of treatment showed significantly better survival times for patients treated by surgery with RT versus those patients treated with RT alone.

Four-year survival rates (21 patients) were 70.6% and 25% for surgery plus RT and RT alone, respectively (P = 0.003). Five-year survival rates (18 patients) were 64.3% and 25% for surgery plus RT and RT alone, respectively (P = 0.009).

[Figure 1] shows a 5-year survival analysis for 18 patients treated with surgery followed by RT versus RT alone. The solid line shows patients treated with biopsy only followed by RT, and the dotted line shows patients treated with surgery followed by RT.
Figure 1: Five-year survival analysis

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It can be seen that range of radiation doses was narrow and the number of patients were small, but, looking at the rarity of chordoma tumors, these results are also encouraging.


  Discussion Top


Due to the local aggressiveness of the disease, the usual biological behavior of chordoma is local recurrence/progression and death. Surgery plays a mainstay role and combined with local radiation longer follow-ups can be achieved. However, in certain inaccessible sites for surgery such as clivus and also due to the radioresistant nature of the disease, usually, local control rates are low and also overall survival.

This analysis shows details regarding overall survival and recurrence pattern for chordoma patients treated at our institute.

In a study from M. D. Anderson Cancer Center,[5] overall 5-year disease-free survival rate was <10%–20% of 19 patients treated definitively. In a study by Fuller and Bloom, of 25 patients treated with radiation, overall actuarial survival rates were 44% and 17% at 5 and 10 years, respectively.

Catton et al.[18] analyzed the long-term results of chordoma with the sacrum, base of skull, and mobile spine treated with postoperative RT. In 20 base of skull lesions with conventional fractionated treatment with the median RT dose of 50 Gy in 25 fractions for 5 weeks (range, 25 Gy–50 Gy), median survival was 62 months (range 4–240 months) from diagnosis. Furthermore, there was no survival advantage with radiation doses >50 Gy to <50 Gy.

In a study by Forsyth et al.,[19] 51 patients with intracranial chordomas were treated with surgery and 39 patients received postoperative irradiation. Overall 5- and 10-year survival rates were 51 and 35%, respectively. Patients with postoperative RT had longer disease-free survival times.

In a study by Keisch et al.,[20] 21 patients (five clival, two nasopharyngeal, and one lumbar) were treated with surgery, and 8 had a subtotal resection and postoperative RT, and 4 received RT after biopsy. Five- and 10-year actuarial survival was better in patients treated with surgery alone or surgery and irradiation than RT alone 52%, 32%, 0%.

Our analysis of patients also showed that in patients in whom surgery has been performed either in the form of debulking or complete excision, long-term follow-up has been achieved with postoperative RT. Four-year overall survival was 70.6% and 25% in patients with surgery plus RT versus RT alone, respectively, for 21 patients. Moreover, 5-year overall survival was 64.3% and 25% in patients with surgery plus RT versus RT alone, respectively, for 18 patients. In both of the scenarios, even the P value is significant at 0.03% and 0.09%, respectively, for 4-year and 5-year overall survival. Our results look comparable to international studies published. In our study, with 18 patients treated with RT (after surgery or after biopsy), combined overall survival is 55.6% and overall survival is 64.3% and 25% in patients with postoperative RT and biopsy alone, respectively, which is comparable to international studies. In four patients, imatinib chemotherapy was also used, but, its real benefit is doubtful. We can assess from the study that patients who had received postoperative radiation had longer follow up than those patients who had RT following biopsy only. Interesting to see that, only the biopsy was done mainly in the sacral region tumor and for the rest of other sites' surgery (complete or partial was done). Cummings et al.,[4] re-examined the dose-time analysis, adding more patients and excluding those treated with orthovoltage irradiation; they came to the conclusion that total doses >40–55 Gy were not more likely to provide a longer disease-free interval.

Debus et al.[21] analyzed 45 patients, treated with postoperative 3D stereotactic radiation therapy. Local control at 5 years was 50% and survival was 82%. Hence, higher conformal techniques may improve overall disease-free survival and overall survival also which needs to be tested subsequently.


  Conclusions Top


Based on our experience and review of the literature, there appears to be an improvement in overall survival times in patients with chordoma treated primarily by surgery followed by postoperative RT. The dose–response data are inconclusive. Our current recommendations for treating patients with chordoma are surgery with maximum debulking and postoperative RT.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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Fuller DB, Bloom JG. Radiotherapy for chordoma. Int J Radiat Oncol Biol Phys 1988;15:331-9.  Back to cited text no. 5
    
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9.
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Rotondo RL, Folkert W, Liebsch NJ, Chen YL, Pedlow FX, Schwab JH, et al. High-dose proton-based radiation therapy in the management of spine chordomas: Outcomes and clinicopathological prognostic factors. J Neurosurg Spine 2015;23:788-97.  Back to cited text no. 13
    
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Moojen WA, Vleggeert-Lankamp CL, Krol AD, Dijkstra SP. Long-term results: Adjuvant radiotherapy in en bloc resection of sacrococcygeal chordoma is advisable. Spine (Phila Pa 1976) 2011;36:E656-61.  Back to cited text no. 14
    
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Kano H, Iqbal FO, Sheehan J, Mathieu D, Seymour ZA, Niranjan A, et al. Stereotactic radiosurgery for chordoma: A report from the North American Gamma Knife Consortium. Neurosurgery 2011;68:379-89.  Back to cited text no. 15
    
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Keisch ME, Garcia DM, Shibuya RB. Retrospective long-term follow-up analysis in 21 patients with chordomas of various sites treated at a single institution. J Neurosurg 1991;75:374-7.  Back to cited text no. 20
    
21.
Debus J, Schulz-Ertner D, Schad L, Essig M, Rhein B, Thillmann CO, et al. Stereotactic fractionated radiotherapy for chordomas and chondrosarcomas of the skull base. Int J Radiat Oncol Biol Phys 2000;47:591-6.  Back to cited text no. 21
    


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