Strategy for the Practice of Spine Oncological Surgery During the Covid-19 Pandemic

Pedro Berjano, MD, PhD; Daniele Vanni, MD; Laura Fariselli, MD; Riccardo Cecchinato, MD; Stefano Boriani, MD

Disclosures

Spine. 2020;45(19):1386-1394. 

In This Article

Results

Indications and Timing on Diagnosis: Importance of Diagnosis Under Covid-19 Pandemic (Grade of Recommendations B, Level of Evidence II)

Obtaining an accurate diagnosis before treatment is a golden rule of spinal oncology in standard health care situations. Surgical treatment before the diagnosis has been completed might appear as equally appropriate. The case reported in Figure 1 illustrates how misleading such approach can be. A patient presents with a large lytic tumor eroding the anterior arch of C1 and extending in both articular masses. The Spine Instability Neoplastic Score[9] (SINS) is suggesting the opportunity to perform a surgical occipitocervical fusion. A diagnosis of myeloma was obtained by a computed tomography (CT) scan-guided trocar biopsy. The patient did not present other lesions, the laboratory tests were negative. Considering limited availability of ICU and the high radiosensitivity of the disease, the choice was made to protect the craniocervical joint with an orthosis and refer the patient to the radiation oncologist. Ossification of the lesion can be expected after radiotherapy, resulting in local stability. Although in standard health care situations some advantage of surgery can be advocated (ie, prompt resolution of instability), in the current pandemic, nonoperative treatment shows clear advantage. CT-guided biopsy and radiation therapy could be provided without hospital stay, reducing the risk of postoperative Covid-19 pneumonia. A second reason for underlining the importance of diagnosis before treatment is distinguishing primary bone tumors from metastases. Bone metastases are more frequent than primary tumors in the spine[10] (300:1 ratio) and the treatment is deeply different. Spine metastases are often found incidentally during follow-up, but sometimes their clinical onset is increasing pain, pathologic fracture, and/or neurological symptoms. Patients with these symptoms may present spontaneously at the emergency care unit, and the primary tumor is not always known. Conversely, few primary spinal tumors have acute onset. A misdiagnosis bringing to treat a primary tumor as it was a metastasis, negatively affects prognosis.[7] Biopsy must therefore be performed in all cases in which no other diagnostic element exists. It is advisable that diagnosis and treatment are performed in the same center:[11,12] referral to an oncology spine center should be a rule.[13] Even during Covid-19 pandemic a CT scan trocar biopsy can be performed in E.R., thus reducing person to person interactions and risk of Covid-19 transmission.

Figure 1.

Male, 42 years' old. Increasing neck pain. Wide erosive changes invading the anterior arch of C1 and extending to both articular masses. SINS 14. Computed tomographyscan-guided biopsy under local anesthesia allowing the diagnosis of Myeloma.

Indications and Timing in Spinal Metastases: Risk of Fracture (Grade of Recommendation B, Level of Evidence II and III)

Function preservation is the major target in the treatment strategy of bone metastases of the spine. Recently Fisher et al[9] proposed a scoring system for spine neoplastic instability, (the SINS) which has been subsequently validated[14–16] and is now widely accepted. According to SINS, metastatic lesions scoring <7 do not need surgical treatment and can be considered for immediate radiation treatment. Cases scoring ≥13 require surgical fixation before radiotherapy to avoid complete collapse with potential neurological sequelae due to cord secondary compression. Cases scoring 8 to 12 have an intermediate risk of fracture and they require individual analysis and multidisciplinary discussion of the indication. To reduce hospital stay and surgery during the Covid-19 pandemic, cases of mid-thoracic vertebrae with SINS 8 to 12 might be better considered for cement augmentation on ambulatory basis. For metastases in other locations with intermediate SINS, our suggestion is to protect the patient with a rigid orthosis, reduction of weight bearing, standing and spinal flexion, and prompt referral to radiation therapy in a hypofractionated schedule. Careful clinical and imaging follow-up will be performed at shorter periods. Surgery could be considered later on if instability will occur. In selected cases, percutaneous fixation, under spinal anesthesia (to avoid intubation) can be considered. Only cases with SINS >12 should therefore be considered for surgery, selecting whenever possible minimally invasive techniques and ambulatory setting.

Indications and Timing in Spinal Metastases: Risk of Neurological Impairment (Grade of Recommendation B, Level of Evidence II)

Bilsky et al[17] proposed a staging system to define the epidural tumor extension and canal encroachment, aiming to recommend "separation surgery," before radiation for treatment of metastases,[18] to increase the distance between the spinal cord and the tumor, enhancing the dose of radiation without causing neural damage. This scoring system allows a better exchange of opinions between surgeons and radiotherapists. Bilsky grade 3 cases (spinal cord compression with no cerebrospinal fluid visible in the axial scan at the level of compression) are mostly severely symptomatic and should be submitted to decompression surgery, even in emergency. For Bilsky grade 2 cases, an individualized decision should be made after discussion with the radiation oncologist. Whenever a safe treatment plan can be made, surgery should be avoided or postponed. Highly selective modalities of radiation therapy are stereotactic radiotherapy, three-dimensional comformal radiation therapy, intensity-modulation radiation therapy. Bilsky grade 1 cases are not associated to immediate neurological risk and radiation therapy when applicable should be the preferred treatment.

Indications and Timing in Spinal Metastases: Metastatic Disease Case Studies (Grade of Recommendation B, Level of Evidence II)

Two are the most frequent situations to be faced even during Covid-19 pandemic for patients spontaneously presenting at the emergency department. The finding of a SINS intermediate pattern in a mid-thoracic vertebral body, associated with severe pain, and a MR image of cancellous edema, in a patient with already diagnosed metastatic disease or multiple myeloma. In these cases, a vertebroplasty (easily performed in local anesthesia, without bed occupancy and therefore well tolerated even in Covid-19 pandemic) can resolve immediately the pain, confirm diagnosis, and prevent a kyphotic deformity (Figure 2A and B), which would require a very complex surgery. The second frequent occurrence is a rapidly evolving paraplegia in a patient under medical oncology treatment, due to the epidural extension of a previously unknown spine metastasis (Figure 3A and B). In this case, even during Covid-19 pandemic, emergency decompression and fixation are mandatory, since complete neoplastic paraplegia is constantly associated to poor outcome.[19] When possible, minimally invasive fixation and decompression are to be preferred, reducing debilitation of the patient and hospital stay. Preoperative selective embolization in highly vascularized metastases such as the case of renal cell carcinoma, significantly reduce intraoperative bleeding[20] More aggressive approaches to bone metastases of the spine[5] (which would cause excess of ICU usage) are nowadays less frequently adopted due to the progresses of medical oncology[21]

Figure 2.

Male, 54 years T6 Myeloma localization. At onset severe orthostatic pain. SINS 11. No local treatment. Orthosis and medical oncology protocol. 1 year later. chronic back pain, significant increase of thoracic kyphosis.

Figure 3.

Male, 78 years. Renal Cell ca under Sutinib treatment since 2 years. He was referred at the emergency room with incomplete, rapidly progressing paraplegia. (A) Previously undiscovered T12 metastatic deposit. MRI T2-weighted showing a posteriorly located huge tumor compressing and dislocating the dural sac. Bilky 3, SINS 9. Therefore, it is a potentially unstable lesion, provoking a severe cord compression. Surgical indication to decompression and fixation. (B) Postoperative results, with wide decompression.

Indications and Timing in Primary Spine Bone Tumors (Grade of Recommendation B, Level of Evidence II)

Primary spine tumors are much less frequent than metastases and very rarely present with acute onset. Treatment must be based on oncological staging and is first targeted to be curative.[6,7] Disease-free survival takes priority over functional preservation. These concepts make treatment of primary tumors as conceptually opposite compared to metastases. Two rules help reduce negative consequences on patient's prognosis: suspect a primary tumor whenever no other diagnostic element per metastases exist; in primary tumors a first-biopsy approach (without hospital admission), instead of treatment in emergency, can be the life-saving procedure. Once diagnosis and staging are completed, the treatment strategy is consequential based on the Enneking's staging system[6] and the possible effect by Covid-19 pandemic can be considered to evaluate the impact.

Indications and Timing in Primary Spine Bone Tumors: Benign Primitive Tumors (Grade of Recommendation B, Level of Evidence II)

Stage 1 tumors are latent[6] and do not require oncological treatment, except for pathological fractures or slow-evolving cord compression in hemangiomas. If symptoms are rapidly evolving, minimally invasive fixation and/or cord decompression (reducing bed occupancy) can be a reasonable option during Covid-19 pandemic, otherwise the treatment can be delayed. Stage 2, so-called "active,"[6] tumors like osteoid osteoma and small osteoblastomas can be reasonably managed delaying surgery for some weeks and treated at the end of the pandemic. In some instances, thermal ablation (an outpatient percutaneous procedure) can be the treatment of election.[22,23] Stage 3 benign tumors are defined "aggressive"[6] as sometimes their growth is fast, resulting in pathologic fracture or neurological compression. In case of stage 3 osteoblastomas, during the pandemic, surgery should be reserved to cases at is risk of imminent fracture or when neural compression is presenting (specially of the spinal cord). If enbloc resection is feasible with low morbidity, this should find a place to be done even during Covid-19 pandemic, if the tumor is rapidly growing. When stage 3 osteoblastomas are huge and enbloc resection would require important functional losses, the best option is to perform a gross total excision and a reconstruction with metal-free implants[24] to allow accelerated particle radiotherapy. This is a less morbid surgery as compared to enbloc resection, particularly if performed after selective arterial embolization to reduce the blood loss. In this perspective (less blood unit need, no intensive care) this option could be particularly valid during Covid-19 pandemic. Surgical treatment of giant cell-rich stage 3 benign tumors like giant cell tumor or aneurysmal bone cyst can be delayed until past the peak of the pandemic with the use of denosumab (on GCT and ABC) or selective arterial embolization (ABC). Denosumab is a human monoclonal antibody to RANKL, a cytokine expressed from osteoblasts, which can bind to osteoclast precursors, activating to mature osteoclasts. RANKL can be blocked by osteoprotegerin (OPG), thus inhibiting osteoclasts activity. Denosumab mimics OPG activity. The first clinical trial yielded promising results with clinical response in >85% of the patients at 6 months[25] of that same cohort, and a marked reduction of the multinucleated giant cells being observed (>90%) on histopathological analysis.[26] In 2016, the AO Spine Knowledge Forum Tumor recommended denosumab either as a stand-alone for treatment of inoperable GCT or as an adjuvant before surgical resection.[27] Later on, several studies reported positive results by using denosumab in the treatment of ABC.[28–30] Open surgical treatment of ABC is actually mostly neglected, first due to favorable reports with selective arterial embolization[31] which is now less considered due to presumptive high patient exposition to radiation. A number of image-guided, minimally invasive techniques have recently gained popularity, including injection of bone marrow centrifugate to stimulate bone reaction,[32,33] or injection of doxycycline.[34] Doxycycline is an antibiotic that has shown, on culture, antitumoral proprieties with inhibition of matrix metalloproteinase (MMP), osteoclastic function, and induction of osteoclast apoptosis. It has been recently demonstrated that ABC expresses high level of MM and bony destruction is associated with upregulation of MMP. It is obvious that all these techniques, either embolization or local injection, can play a central role during the Covid-19 pandemic.

Indications and Timing in Primary Spine Bone Tumors: Malignant Primitive Tumors (Grade of Recommendation B, Level of Evidence II)

Low Grade. In low-grade malignant tumors (like chordoma and chondrosarcoma), enbloc resection[35,36] is the treatment of choice, when feasible.[37] Enbloc resection is a complex and morbid surgery, associated to a complication rate from 13% to 74% and mortality rate of 0 to 8% in the adult series.[38,39] These procedures have high risk for blood loss, which in children and adolescent, may be another limiting factor due to lower circulating volume than adults, long operating room occupancy, and some days of ICU stay. However, chordoma and chondrosarcoma have a low growth rate and a delay of some weeks can be tolerated during the pandemic as not severely impacting on prognosis. If the decision of delaying surgery is made, careful clinical and imaging follow-up needs to be performed to monitor the tumor local growth and switch to immediate treatment, in case of risk of functional permanent damage or loose possibility to perform appropriate oncological surgery. A recent literature review[40] demonstrated that surgery (either Enneking appropriate or inappropriate), when combined with radiation therapy, will likely result in higher local control rates, than surgical resection alone. Therefore, enbloc resection planned during the Covid-19 pandemic may be delayed after an appropriate course of radiation therapy is completed. Chordoma and chondrosarcoma may respond to high doses of radiation, which can be delivered with better spatial specificity with accelerated particles such as proton therapy or carbon-ion radiation. Radiation therapy of at least 60 to 65 Gy equivalents, with proton therapy when available, is recommended as an adjuvant treatment for chordoma and chondrosarcoma of the spine when there has been incomplete resection or an intralesional margin.[41] When en-bloc resection cannot be safely delayed, particularly for patients with comorbidities that might darken their prognosis in case of Covid-19 infection, an alternative strategy consisting of intralesional resection and reconstruction with metal-free implants followed by particle radiation therapy can be considered. In case of recurrent tumors, excision should be associated with composite carbon fiber construct to combine with accelerated particle therapy (Figure 4A and B).

Figure 4.

Man, ageing 67, submitted in August '12 to gross total excision of a gr.2 Chondrosarcoma arising from T2 to T4 posterior elements, followed by titanium fixation T1 to T7. Periodical followup control in January 20. Asymptomatic. STIR_long TE sagittal MR image. A round image posteriorly located at T1-T2 level, presumably related to local recurrence. Increased kyphotic thoracic curve due to initial distal junctional kyphosis. T2W-TSE transverse MR image. A round image with the same features can be found posteriorly to the thecal sac, in close contact with the dura, slightly dislocating without any compression on the spinal cord.

High Grade. In the treatment of high-grade malignancies, neoadjuvant therapy can be a time buyer, but can also become a constraint (in case it is already completed and the window of efficacy is small, surgery might be needed in a narrow time window). The accepted protocols of treatment of high-grade malignancy usually include some preoperative course of chemotherapy. In the treatment strategy of osteogenic sarcoma (OGS), en bloc resection is mandatory.[42,43] En bloc resection should be performed after four courses of chemotherapy. The pathologist's analysis of the surgical piece regarding the necrosis rate is a valid guide for selecting the best postoperative course of chemotherapy. In consideration of the complexity of the neoadjuvant chemotherapy, a window open for surgery during the Covid-19 pandemic cannot reasonably be neglected. These cases be provided with time, resources, and ICU space available to permit diligent oncological surgery, thus preventing a negative impact of delay on prognosis. Conversely surgery does not seem so relevant in the treatment strategy of Ewing sarcoma (ES), at least from the point of view of timing. ES is the most common primary high-grade malignancy of the spinal column.[44] Differently from OGS, in the strategy of ES the role of surgery is less relevant,[45] whereas radiotherapy is mandatory in the treatment strategy.[46] Acute paraplegia is reported as a common onset symptom[47] and in contrast with the oncological paradigm of sequential chemotherapy/surgery or radiotherapy/chemotherapy, the first treatment of many instances of ES turns out to be a decompressive laminectomy performed in a community hospital for neurological involvement. Studies have suggested that this decompression (intralesional) surgery, resulting in an excisional biopsy, negatively affect the prognosis[48] due to local dissemination of the tumor. In a retrospective study on 1011 primary bone tumors of the spine, based on the Nations Cancer Database, radiation therapy was associated with improved survival in EWS, and decreased 5-year survival for OGS.[44] The traditional treatment of ES consists of neoadjuvant chemotherapy followed by local between radiation therapy or surgery (Figure 5A–C). Once radiotherapy is decided after the first courses of chemotherapy, surgery could be considered at the end of the full course. During the Covid-19 pandemic, it would be reasonable to delay enbloc resection surgery.

Figure 5.

Male, 17 years T1 Ewing sarcoma, submitted elsewhere to open biopsy. MR image at the onset. Huge tumor mass arising from the T1 vertebral body, fully infiltrated and expanding in the epidural space. Bilsky 3. A protocol including chemotherapy courses, that decision between surgery and radiotherapy, further chemotherapy and surgery, if not performed before, followed by radiotherapy, if not performed before MR image after full protocol of Chemotherapy and Radiotherapy. No evidence of soft tissue tumor invasion. Enbloc resection with reconstruction by composite/PEEK carbonfiber implants as posterior fixation and anterior vertebral body reconstruction. In case of further re-irradiation needed, a fully titanium-free construct will allow proton therapy.

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