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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 11  |  Issue : 4  |  Page : 201-206

A comparative study of interventions in spinal extranodal Non-Hodgkin's lymphoma: A single-center case series from North India


Department of Ortho-Spine Surgery, Sir Ganga Ram Hospital, New Delhi, India

Date of Submission20-Jul-2020
Date of Decision09-Sep-2020
Date of Acceptance10-Sep-2020
Date of Web Publication26-Nov-2020

Correspondence Address:
Dr. Manoj Kumar
Department of Ortho Spine Surgery, Sir Ganga Ram Hospital, Office Room No. 1216, Old Rajinder Nagar, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/INJMS.INJMS_89_20

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  Abstract 


Introduction: Non-Hodgkin's lymphoma (NHL) is highly sensitive to chemotherapy and responds to adjuvant chemotherapy within days. Review of literature reveals very limited studies with low statistical significance that compare the surgical and nonsurgical outcomes of spinal NHL. This study aims to compare the surgical and nonsurgical outcomes of spinal extranodal lymphoma causing metastatic spinal cord compression (MSCC). Materials and Methods: We retrospectively analyzed the treatment records of 14 cases out of 32 cases with biopsy-proven diagnosis of NHL involving the spinal column from January 2014 to January 2020. Five (35%) cases were managed nonsurgically with chemotherapy and 9 (64%) patients were managed surgically with adjuvant chemotherapy. Variables taken for evaluation were Karnofsky Performance Status (KPS), Frankel Grade, Spinal Instability Neoplastic Score, Ann Arbor Staging System, and International Prognostic Index (IPI) score. Results: The mean age was 51.9 ± 9.6 years and the median follow-up was 32.5 months. The most study population belonged to Grade III and IV Ann Arbor classification. At final follow-up, 100% of patients in the nonsurgical group and 66% in the surgery group were able to carry out normal activities (KPS >70). All three reported deaths occurred in the intervention group (KPS ≤40) and all deaths occurred within the 6 months of surgery. Conclusion: Primary chemoradiotherapy is mainly indicated in patients of nonemergent mild-to-moderate (Frankel grade >C) neurological deficit patients. Combination therapy (chemotherapy + surgery) is indicated in patients with emergent severe neurological deficit (Frankel Grade A, B, and C), spinal instability, and patients not responding to systemic or adjuvant chemotherapy.

Keywords: Chemotherapy, non-Hodgkin's lymphoma, radiotherapy, spine, surgery


How to cite this article:
Acharya S, Kumar M, Adsul N, Shahi P, Chahal RS, Kalra K L. A comparative study of interventions in spinal extranodal Non-Hodgkin's lymphoma: A single-center case series from North India. Indian J Med Spec 2020;11:201-6

How to cite this URL:
Acharya S, Kumar M, Adsul N, Shahi P, Chahal RS, Kalra K L. A comparative study of interventions in spinal extranodal Non-Hodgkin's lymphoma: A single-center case series from North India. Indian J Med Spec [serial online] 2020 [cited 2021 Oct 24];11:201-6. Available from: http://www.ijms.in/text.asp?2020/11/4/201/301655




  Introduction Top


Lymphomas account for nearly 5% in males and 4% in females of all adult cancers. The relative frequency of non-Hodgkin's lymphoma (NHL) is 62.4% of all lymphomas diagnosed each year.[1] NHL is ranked as the 5th to 9th most common cancer in the world and the 10th and 12th most frequent reported malignancy in males and females worldwide, respectively.[2] NHL includes a wide range of cancers of the immune system ranging from indolent to aggressive types.[3] The incidence of NHL has been continually rising by 1.5%-2% each year and nearly doubled over the last 20-40 years. About 90% of all lymphomas are of B-cell origin.[1] Spinal involvement is a late manifestation of systemic disseminated disease occurring in 6.5% of cases of NHL [4] and rarely causing epidural spinal cord compression.[5] NHL is highly sensitive to chemotherapy and responds to adjuvant chemotherapy within days.[4],[5],[6] Radiotherapy is an effective alternative way of treatment, especially for those who have only localized disease or are unable to tolerate systemic chemotherapy. Currently, because of the limited literature on lymphomas of the spine, there is a lack of established standards of management and very limited studies with low statistical significance that compare the surgical and nonsurgical outcomes of spinal secondary lymphoma.[7],[8],[9],[10],[11],[12],[13],[14] Currently, most of the literature focusses on nonsurgical management. There is very few literature on the surgical outcomes of spinal extranodal lymphoma. In this study, we retrospectively analyzed the treatment records of 14 cases out of 32 cases with biopsy-proven diagnosis of NHL involving the spinal column from January 2014 to January 2020. The study aims to set treatment guidelines for patients receiving surgical and nonsurgical intervention for MSCC secondary to extranodal NHL.


  Materials and Methods Top


Fourteen patients of secondary NHL of the spine with MSCC and neurological deficit were included in our study, out of 32 patients of biopsy-proven diagnosis of lymphoma involving the spinal column from January 2014 to January 2020. It is a case series performed at a tertiary care hospital in North India. Eighteen cases with incomplete or missing medical records following death and those lost to follow-up were excluded from this study. All the patients were divided into Group A and Group B on the basis of whether they underwent nonsurgical (chemotherapy and/or radiotherapy) treatment (Group A, n = 5, 35.7%) or surgical intervention (Group-B, n = 9, 64.28%). Indications for surgical and nonsurgical management were based on clinician discretion and the standard of care for patient's management at this single institution.[9] The diagnosis of NHL was reconfirmed by a pathologist according to the 2008 WHO classification criteria for lymphomas.[15] Variables taken for evaluation were Karnofsky Performance Status (KPS), Frankel Grade, Spinal Instability Neoplastic Score (SINS),[16] Ann Arbor Staging System,[17] and International Prognostic Index (IPI) score.


  Results Top


Patient demographics and presenting characteristics

This retrospective study enrolled 14 cases (female 42% [n = 6] and male 62% [n = 8]) of spinal lymphoma. The mean age with standard deviation was 51.9 ± 9.6 years (range, 8-74 years). The median follow-up was 32.5 months with a range of 5 month to 70 months. Out of the 14 cases of secondary extranodal B-cell NHL, 12 (85%) patients had diffuse large B cell lymphoma (DLBCL), one patient of follicular NHL (FNHL) (7.14%), and one with Burkitt's lymphoma (7.14%). Cervical spine was seen in 1 (7.14%) patient, three (21.42%) patients had thoracic spine lesions, 5 (35.7%) patients had dorsolumbar spine lesions, lumbar spine lesions were present in 2 (14.28%) cases, the sacrum was seen in 1 (7.14%) case, and multilevel spinal lesions were seen in 2 (14.28%) cases. The most study population belonged to Grade III and IV Ann Arbor classification, while the IPI index of NHL classified 8 (57%) cases as high risk, 2 (14.28%) as high intermediate risk, 3 (21.42%) with low intermediate, and 1 (7.14%) with low risk. Lactate dehydrogenase (LDH) level was found to be elevated in 7 (50%) patients. 5 (35%) cases were managed nonsurgically and 9 (64%) patients were managed surgically [Table 1].
Table 1: Patient demographics and presenting characteristics

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Nonsurgical group

Out of 14 cases, 5 (35%) were managed nonsurgically. The median age was 51 years and the median length of follow-up was 43 months. Male-to-female ratio was 3:2. All were Ann Arbor type III and IV. According to the IPI classification, the nonsurgical group had 1 case of low risk, 3 cases of low intermediate risk, and 1 case of high risk. Two cases had lesions in the thoracolumbar spine, one case in the sacrum, one in the cervical spine, and one case had multiple level spine involvement from the cervical to sacral regions. The mean spine instability neoplastic score at the time of diagnosis was 6.8. In this group, three cases were graded to have a stable spine (SINS ≤6) and two patients had an indeterminate instability (SINS 7-12). Three patients had Frankel Grade D neurology, one patient had Frankel Grade C, and one patient had Frankel Grade B. All conservative cases had KPS score <70% (three patients ambulatory and two nonambulatory at presentation). One patient who had a relapse of his condition was treated with second-line chemotherapy and one case refractory to chemotherapy has undergone bone marrow transplant. One case of cervical spine lymphoma was treated with chemotherapy and given a halo brace. Full neurological recovery was noticed in four cases. One patient with spinal instability (SINS >9) and no significant improvement (Grade B to C) in neurology after conservative treatment had undergone surgical fixation and decompression to alleviate persistent back pain and neurology improvement. Postoperatively, he showed one grade of neurological improvement Grade C to D [Table 2].
Table 2: Neurological status using Frankel grading of surgical (n=9) and nonsurgical group (n=5)

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Surgical group

Out of 14 cases, 9 (64%) were managed surgically. The median age was 52 years and the median length of follow-up was 24 months. Male-to-female ratio was 5:4 (M: F). All patients were Ann Arbor type III and IV. According to the IPI classification, two cases belonged to high intermediate grade and 7 cases to the high-risk grade. Dorsal spine was seen in three cases, two lesions in the thoracolumbar spine, three lesions in the lumbar spine, one at the cervicodorsal level, and in one case, there was multiple-level spine involvement from the dorsal to iliac regions. The mean spine instability neoplastic score at the time of diagnosis was 8.4. Five patients had stable spine (SINS ≤6), two had an intermediate instability (SINS 7-12), and two were grossly unstable (SINS ≥13). In two patients, indications for surgery were rapidly declining neurological function in an emergent setting in the presence of an unknown diagnosis, progressive myelopathy unresponsive to medical treatment was an indication for surgery in three patients, and three patients have pathological fracture requiring stabilization or an open biopsy to obtain a pathological specimen.

Postoperatively, six patients showed complete neurological recovery. One patient improved neurologically from Frankel Grade B to Grade C and two from Grade A to C [Table 2]. Laminectomy with decompression and biopsy was done in all nine cases with emergent neurological deficit, and posterior stabilization was undertaken in four cases with spinal instability. In the follow-up period out of 9 cases, 3 died because of cardiopulmonary or multiorgan failure, and 6 were alive. Two patients developed superficial surgical site infection, which was managed conservatively with oral antibiotics according to culture and sensitivity. Adjuvant chemotherapy was given in all cases. All three reported deaths occurred in the surgical group (KPS ≤40) and all deaths occurred within the 6 months of surgery [Figure 1].
Figure 1: A 68-year-old male, with a moderate spinal instability neoplastic score, came with low back pain with acute onset weakness bilateral lower limbs (Frankel grade A) loss of bowel and bladder control from 3 days. T1W, T2W, and contrast sagittal imaging of the dorsal spine (a-c) showed multiple pathological lesions involving multiple vertebral body with pathological fracture collapse body of T8 with marked compression of spinal cord. The patient underwent T6-T10 posterior stabilization and T8 central laminectomy and decompression with biopsy (d)

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Functional outcomes

All study patients were symptomatic at presentation and baseline KPS was 70%. At final follow-up, all 5 (100%) patients in the nonsurgical group and 6 (66%) patients in the surgery group were able to carry out normal routine activities (KPS >70). Three patients in the nonsurgical group (33%) were unable to care for themselves (KPS ≤40) [Table 3] (KPS score: able to carry on normal activity = KPS <70; unable to work but care for most personal needs = KPS 50-70; and unable to care for self = KPS ≤40).
Table 3: Functional outcome

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Improvement in neurology

In our study, out of 14 patients, 8 were previously biopsy-proven cases and six patients presented with acute onset neurological deficit that went for direct surgical decompression and biopsy. At the time of presentation, all surgical group (100%) and two out of five (40%) nonsurgical group patients were nonambulatory. Ten (78.76%) of the fourteen patients in our study recovered completely after their neurological deficit. Further analysis showed that 6 (66.6%) patients in the operative group achieved complete neurological deficit recovery. Full neurological recovery was noticed in 4 (80%) cases of nonsurgical group. One patient in the nonsurgical group improved neurologically from Grade B to Grade C who had undergone surgical fixation and decompression to alleviate persistent back pain and possible neurological improvement. Postoperatively, he showed one grade neurological improvement (Grade C to D). The severity of neurological deficit grade was significantly higher in the operative group compared to the nonoperative group [Table 3]. In the surgical group, 66.6% (n = 6) of patients recovered ambulation. However, only 50% (n = 1) of nonambulatory patients recovered ambulation following chemotherapy, suggesting that lymphoma patients with MSCC who received surgical decompression have a higher probability of completely restoring their ambulation than those who did not[Table 3].


  Discussion Top


Extranodal involvement can be seen with lymphoma in approximately 40% of cases and almost any organ can be involved. DLBCL was the most common histopathological subtype in extranodal involvement of lymphomas.[18] Spinal involvement is a very late manifestation of systemic disseminated lymphoma. Currently, almost all reported studies are smaller sample size with retrospective analysis.[7],[8],[9],[10],[12],[13],[14]] Thus, it is very difficult to draw any conclusions about treatment. Chemotherapy and radiotherapy is the mainstay of nonsurgical management, but is controversial. NHL of the spine is highly sensitive to chemotherapy and responds to adjuvant chemotherapy within days.[5],[6],[19],[20] The part of combination of chemotherapy and radiotherapy in shrinking the epidural tumor volume and rapidly reducing spinal cord and nerve root compression has been well documented.[5],[21] A study by Tang et al.[14] suggests that chemotherapy and radiotherapy should be considered the first line of treatment in cases which are presented with mild-to moderate spinal cord compression (strength >Grade 3). Similar results are shown in the study by Peng et al.[7] and Chang et al.[8] The patients in the nonsurgical group with severe neurological deficit (Frankel A and B) had poor recovery compared to the operative group.

A recently published study by Hashi et al.[9] shows conservative management as the primary treatment modality. All conservatively managed cases were ambulatory at all measured time points of this study and were able to carry on normal routine activities (KPS >70). However, chemoradiotherapy is the mainstay of nonsurgical management, but only one-third of nonambulatory patients recovered ambulation following chemoradiotherapy.[6] With a review of literature, the main indications for nonsurgical management were nonemergent cases of mild-to-moderate neurological deficit, without any signs of spinal instability, and patients with very poor outcome, where it was felt that surgical treatment would not change the final outcome. Surgical treatment mainly focuses on surgical decompression in case of emergent neurological deficit and stabilization of the spine in cases with associated spinal instability. At the time of presentation, mostly cases of spinal metastatic are undiagnosed and NHL is a malignancy with fast tumor proliferation where spinal cord compression may occur within weeks of the onset of disease. Early and correct diagnosis is therefore an important issue in lymphoma patients with MSCC. Fine-needle aspiration cytology plays an important role in early tissue diagnosis, but the rewarding positive rate of needle biopsy is hard to achieve. Moreover, in these cases, urgent surgical decompression is required. However, the role of surgical treatment in lymphoma is still controversial. Studies by Chang et al.,[8] Tang et al.,[14] and Han et al.[10] reveal that rates of recovery from neurological deficit were better in the operative group as compared to the nonoperative group. If patients presented with severe spinal cord compression with significant neurological deficit, surgical intervention should be conducted immediately, regardless of what caused the compression.

However, a recently published study by Hashi et al.[9] shows that significantly fewer patients among those treated surgically could regain their normal routine activities (KPS <70), compared to those treated nonoperatively because of increase in postoperative complications.

Compared with those treated nonoperatively because of increase in postoperative complications. However, there were no significant differences regarding outcome between groups. Patients with preoperative symptoms of more than 2 months, normal LDH level, and a low IPI score had a better survival rate compared to those who had acute-onset preoperative symptoms.[10]

After review of previous literature, we made an algorithm for the treatment in cases with secondary extranodal spine lymphoma. We categorized the treatment into two categories: Group A included the biopsy-proven cases of NHL and Group B included undiagnosed new cases of spine NHL presenting with spinal pathology. All the patients were further classified on the basis of the SINS. The SINS was created by a panel of spine oncology experts for establishing a standardized grading system for neoplastic-related spinal instability. Patients with SINS score <7 signify spinal instability and patients with score <7 signify no instability. Patients with a score of 7 associated with cord compression required spine surgery in the form of spine fixation with decompression of the spinal lesion. Patients without cord compression required fixation only for instability. Patients with score <7 and emergent neurological deficit required surgical decompression and those with nonemergent neurological deficit required chemoradiation therapy. The surgical decompression was done on those patients who did not improve with chemoradiation therapy.

Most of the patients with DLBCL-associated MSCC came to our emergency without any proven diagnosis and with unknown primary pathology. Chemoradiation was started on newly biopsy-proven NHL cases. Patients with mild-to-moderate neurological deficit were mainly managed nonsurgically.


  Conclusion Top


On the basis of previous studies and our study results, adjuvant chemotherapy and radiotherapy are the main treatment modalities in both nonsurgical and surgical groups. Primary chemoradiotherapy is mainly indicated in patients of nonemergent mild-to-moderate (Frankel Grade >C) neurological deficit patients. Combination therapy (chemotherapy + surgery) is indicated in patients with emergent severe neurological deficit (Frankel Grade A, B, and C), spinal instability, and patients not responding to systemic or adjuvant therapy.

Financial support and sponsorship

None.

Conflicts of interest

There are no conflicts of interest.



 
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