Spinal metastasis of bronchopulmonary cancer: Interest of a Spine surgery and prognostic scales value

doi:10.21203/rs.3.rs-404730/v1

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Spinal metastasis of bronchopulmonary cancer: Interest of a Spine surgery and prognostic scales value

https://doi.org/10.21203/rs.3.rs-404730/v1

This work is licensed under a CC BY 4.0 License

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posted 12 Apr, 2021

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Background

lung cancer is the first mortality cause by cancer around the world. Bones metastasis occurrence is a common eventuality in case of lung cancer (40% at the diagnosis). In order to evaluate the indications and measure the effectiveness of surgery in the management of PBC spinal metastases, we report a series of 52 patients.

Methods

During 6 years, from January 2009 to December 2014 at the Neurosurgery Unit of Marseille North Hospital (France), we studied retrospectively 52 patients records, who underwent a surgery for spinal metastasis of lung cancer. The study was only about patients which metastases were surgically treated. We used Stata software for the computation, and concerning the linear regression, all values under 0.1 were considered significant.

Results

the average age was 63.6 years (39–80 years) with a sex ratio of 3. Non-small cell lung cancer was the most common, ie 36 cases (69.2%). Rachialgia associated to vertebral fracture with medullar compression was the most common clinical presentation (31 cases or 59.6%). SINS score (spinal instability neoplastic score) was equal or above 7 in 41 cases (78.9%). The general condition (Karnofski) was medium in 35 cases (67.4%). Survival prediction beyond 12 months was null according to Tokuhashi Index. The surgical indication was essentially palliative. Evolution was characterised by painful symptomatology regression in 44 cases (84.6%), stabilization of initially unstable lesion and motor deficit improvement in 48.3 % of cases. The average survival time following the surgery was 16 months.

Conclusion

Our results show the interest of surgery for pain relief and spinal stabilization in patient with spinal metastasis of lung cancer, and the relativity of predictive survival score.

Neurosurgery

Neurology

cancer

bronchopulmonary

metastasis

spine

Bronchopulmonary cancer (PBC) is one of the most common cancers in men, and the first mortality cause by cancer around the world [1, 5]. Almost half of non-small cell bronchopulmonary cancers and 2/3 of small cell cancers are from the outset metastatic at the diagnosis [4, 26]. Bones metastasis is a common eventuality in case of bronchopulmonary cancer. Almost 40% of patients present bones metastasis at the diagnosis or during the lung cancer evolution, and 40% of them are spinal metastases [21]. Spinal metastasis commonly occurs in dorsal spine (20%) or lumbar spine (15%). Cervical locations are more unusual (5%) [19]. The evolution of the spinal lesions was characterized in 50% of cases by osseous events as pain, fracture, hypercalcemia of malignancy and/ or medullar compression. Medullar compression is the most significant event, threatening the functional prognosis [2]. Those elements encourage to an early and optimal care of the vertebral bones lesions in order to prevent the medullar compression [15].

In this work, we report a series of 52 patients operated on for spinal metastases of PBC with the aim of evaluating the indications and measuring the effectiveness of spinal surgery in the management of these lesions.

We realized a retrospective study in a period of 6 years with 52 patients records. They were operated for spinal metastasis of bronchopulmonary cancer between January 2009 and December 2014 in the Neurosurgery department of North Hospital of Marseille (France).

The studied parameters were age, sex, histologic type of the BPC, TNM classification, spinal topography of the metastasis, number of spinal metastasis, type of osseous events (rachialgia, fracture and medullar compression), pain assessment by the Visual Analog Scale (VAS): pain was considered mild when the VAS is less than 4, moderate when the VAS is between 4 and 6, and severe when the VAS is greater than 6, extra spinal metastasis, Karnofski scale, Tokuashi scale, Tomita scale, surgical indication, type of surgery (open surgery: laminectomy, osteosynthesis, anterior corpectomy + prosthesis, minimal invasive surgery or mini open: kyphoplasty or associated surgery: open + mini open surgery), postoperative complications, evolution and survival after surgery.

Our study essentially concerned patients which spinal metastasis was surgically treated. We used Stata software for the computation, and concerning the linear regression, all values under 0.1 were considered significant.

Among the 52 selected patients, the average age was 63.6 years (extremes: 39–80 years) with a sex ratio of 3 (39 males/13 females). The most frequent histological type was adenocarcinoma non-small cell bronchial cancers (NSCLC) [36 cases or 69.2%], followed by squamous cell carcinomas [9 cases or 17.3%], small cell bronchopulmonary cancers (SCBC) [5 cases or 9.6%], spindle cell squamous cell carcinomas (SpsCC) and large cell carcinomas (LCC) [1 case each or 1.9%]. Molecular genotyping by Next Generation Sequencing (NGS) was performed in 21 patients, revealing a mutation in 4 cases (3 cases of KRAS mutation and 1 case of EGFR mutation).

The principal spinal topography was at the thoracic level, 16 cases (30%). Spinal metastasis topography is showed in Table 1.

In 36.5% of cases, it was 1 or 2 metastasis and in 63.5% cases more than 2 metastasis. Metastasis was synchronous in 82.7% of cases and metachronous in 17.3% of cases.

All patients had rachialgia, which was isolated in 6 cases (11.5%), associated in 15 cases (28.9%) with a vertebral fracture without nerve compression and in 31 cases with spinal cord compression (59.6%) with complete deficit (Frankel A-B) in 11 patients and incomplete deficit (Frankel C-D) in 20 patients. The average VAS was 6.9 with extremes ranging from 6 to 10. This pain was moderate in 30 cases (57.6%) and severe in 22 cases (42.4%).

The SINS score (spinal instability neoplasic score) was equal to or above 7 in 41 cases (78.9%) and under 7 in 11 cases (21.1%).

Table 1

Spinal Topography
Spinal Topography	Number	Percentage
Cervical Cervico-dorsal Cervico- dorsolumbar Dorsal Dorso-lumbar Dorso-lumbosacral Dorsosacral Lumbar	2 6 12 16 10 1 1 4	3,8 12 23 30 19,2 2 2 8

Extra-spinal metastases were detected in 30 cases (57.6%), including 28 cases of bone metastases, 3 pleural cases, 13 cases of contralateral lung, 8 hepatic cases, 8 cerebral cases, 2 renal cases, 11 adrenal cases, 8 lymph node cases, 1 peritoneal case and 1 muscular case.

Stage IV of TNM classification was the most common [46 patients (88,6%)], followed by stages IIIB, IIIA, and IA, [2 cases each (3,8%)].

The general condition was good in 15 cases (28.8%), moderate in 35 cases (67.4%) and poor in 2 cases (3.8%). Tokuhashi scale is summarized in Table 2 and Tomita scale in Table 3.

Table 2

Tokuhashi scale
Scale		Survival	Number
Group A (0–8) Group B (9–11) Group C (12–15)		< 6 months 6-12 months > 12 months	48 4 0

Table 3

Tomita scale
Scale		Survival	Number
Group A (2–3) Group B (4–5) Group C (6–7) Group D (8–10)		> 24 months 12–24 months 6–12 months < 3 months	0 7 15 30

The surgical indication was essentially palliative. There were 31 cases of open surgery, 6 cases of mini open surgery and 15 cases of associated surgery (open and mini open). At the time of surgery 20 patients were undergoing chemotherapy (1st line: paclitaxel and cisplatin in 15 cases, 2nd line: docetaxel, gemcitabine and vinorelbine in 5 cases, and associated in 1 case with molecular therapy targeted by Gefitinib) combined with adjuvant treatments (corticosteroid therapy 17 cases, bisphosphonate: ZOMETA 2 cases and anti RANKL: XGEVA 4 cases) and postoperatively 25 patients had received conventional fractionated adjuvant radiotherapy on the spine (an irradiation of 30 Gy in ten fractions and a single dose of 8 Gy). In 68% of cases, this radiotherapy was combined with chemotherapy.

Evolution was characterised by the regression of painful symptomatology in 44 cases (84.6%), with an average postoperative VAS of 2.9, the stabilization of the lesions initially unstable and the improvement of the motor deficit in 48.3%.

Postoperative complications were noted in 15 cases (28.8%) including 9 cases of pneumopathy, 1 case of compression of the iliac vein with cement, 1 case of extra pedicular screw, 1 case of deep venous thrombosis of the left lower limb, 1 case of parietal infection, 1 case of pulmonary embolism and 1 case of isolated fever. Post-surgery survival was less than 6 months for 36 patients, 6–12 months for 8 patients, and more than 12 months for 8 patients. Survival as a function of the Tokuhashi score is summarized in Fig. 1 and the parameters that influenced it are summarized in Table 4.

Table 4

Parameters that influenced the survival after surgery
Parameters	Values (P)
1.Complementary treatments (RT, CT)^a	0.072*
2.Histology ^bEC ^cADK ^dSCC ^eSCLC ^fCEGC	0.068* 0.287 0.396 0.827 0.407
3.Karnofsky 10–40% 50–70% 80–100%	0.119 0.287 0.097*
4.Age < 55 years > 55 years	0.103 0.907
5.Number of metastasis > 2 1	0.506 0.327 0.201
6.Complications Respiratory Other complications	0.037* 0.773

^a(RT radiotherapy; CT chemotherapy); ^bEC : epidermoid carcinoma; ^cADK : adenocarcinoma; ^dSCC: spindle cell carcinoma; ^eSCLC: small cell lung cancer; ^fCEGC: Giant cell carcinoma

* p < 0.1: all value 0.1 was considered as statistically significant

Spinal metastases are frequently observed complications in the malignant disease at terminal stage [20]. At least 30 to 90% of patients who died of cancer had spinal metastasis in cadaveric studies [3, 8, 38]. The average age of our series was 63.6 years. Indeed, spinal metastasis has a high incidence in people aged 40 to 65 years, that match with the period where the risk of cancer is at the highest [25]. Men are most susceptible to develop spinal metastasis, thus probably reflecting the men’s slight higher prevalence of developing spinal metastasis of lung cancer and of prostate cancer against symptomatic breast cancer [25]. This man predominance is considerably observed in our series (39 men/13 women).

The NSCLC of adenocarcinoma type was the most common in our series (69.2%). Histological type varies according to the studies. Sun & Al [32], in 2011, reported an incidence of 23% of osseous metastasis in a retrospective series of 1166 NSCLC.

Predominance of dorsal localization (30 %) is also reported by Patricia & Al in their series (49 %) [24]. In 36.5% of cases, it was 1 or 2 metastasis and in 63.5% of cases, more than 2 metastases. Metastasis was synchronous in 82.7% of cases and metachronous in 17.3 % of cases. Sioutos and Col [31] noticed that ambulatory patients in preoperative, and whose metastasis only concerned one vertebra, had statistically survived more than non-ambulatory patients whose metastasis concerned several vertebral levels.

Depending on the extent and the localization, they cause variable symptoms from pain to neurological deficit (complete or partial) [19]. Those osseous spinal metastases occur most often at the posterior part of vertebral body [20]. When they extend to the epidural space and are compressing the spinal cord, they are presented as a medullar compression of neoplastic origin [7]. In our series, pain was the main symptom associated in 59.6% to a medullar compression presentation. The preoperative SINS (spinal instability neoplastic score) was evaluated in all patients as previously described [11]. A score under 7 means stability, between 7 and 12 corresponds to an indeterminate or upcoming instability and a score from 13 to 18 suggests instability. This score can be used as a guide for making the surgical decision, because unstable lesions are most susceptible to require stabilization for a long-term management of metastatic diseases of the vertebral column [24].

In our series 41 patients (78.9%) had a score equal or above 7 and 11 patients (21.1%) under 7.

Extra spinal metastasis was present in 57.6 % of cases in our series. Tumorous extension was evaluated by TNM classification, the stage 4 was the most common with 88.6% of cases. Functional consequences were appreciated by Karnofsky Index, which has an important part in our decision making. In our series, it was good in 28 % of cases (80–100), moderate in 67.4% (50–70) and poor in 3.8% (10–40%). It was equal or above 70% in 33 patients and under 70% in 9 patients for Patricia and Al’s series [24].

Survival was evaluated by Tokuhashi Index, some authors covered the topics of survival after a surgery for spinal metastasis [35, 36]. Indeed, Tokuhashi and Col [34] have studied the results of 64 patients who underwent surgery for spinal metastasis. They included all primary diagnosis and surgery performed for diverse indications including pain and paralysis. Based on this, they formulate specific parameters including general condition, number of osseous extra spinal metastasis, vertebral metastasis number, presence of lesions in other internal organs, primary lesion localization, spinal cord lesion severity.

A score of 9 or above was predictive of at least 12 months of survival, a score of 8 or weaker indicate survival of less than 12 months and a score of 5 and under predicted 3 month or less of survival. Based on those data, it appears that the Tokuhashi system can be a precious tool in preoperative discussions and the decision making; its values were confirmed by other authors. Enkaoua, & al. [9] found it predictive of survival after surgery for most of patients presenting spinal metastasis. Although Tomita's scale [35] should not be overlooked, it still can be used to predict survival (Table 4). In our series, 48 patients had survival prediction of less than 6 months (Tokuhashi 0–8) and 4 patients a prediction of 6 to 12 months (9–11). There was no patient with a survival prediction above 12 months; as a matter of fact, the nature of the vertebral ailment which is secondary to a lung cancer is a bad prognosis element [13, 34, 35]. Thus, the Van der Linden team [36] found a median survival of 2.9 months for the patients suffering from spinal metastasis of lung cancer unlike our series where we found a median survival of 16 months. In our series, Tokuhashi's group C (12–15) and Tomita's group A (2–3), which correspond to good prognosis groups, were not found because of the high severity and mortality of bronchopulmonary cancers at the time of diagnosis. This partly proves the inadequacy and relativity of the classic prognosis scores (Tokuhashi and Tomita) in PBCs. The non-representation of good prognosis groups in PBC should lead us to set up a specific prognostic classification of PBC spinal metastases considering all groups of patients.

Surgery was essentially palliative in our series; the main objective was to relieve pain and restore the stability. The palliative surgery allowed pain control, vertebral column stabilization, dural sheath release in case of medullar or root compression [2]. There is a lot of technics and surgical approaches which can be chosen depending on the area to treat, the medullar compression severity, the risk of instability and the patient general condition [2]. Vertebroplasty is indicated for spinal mechanical pain before or after surgery and provides a rapid relief in less than 12 hours [22]. The other consolidation technics are kyphoplasty (Fig. 2) and stentoplasty or percutaneous osteosynthesis when we doubt of the sufficiency of cementoplasty alone or with stent to stabilize the spine [2]. Other surgical options are corpectomy associated to a reconstruction by vertebral prosthesis (Fig. 3), laminectomy and stabilization by osteosynthesis (Fig. 4) and vertebrectomy [10, 18]. The surgical treatment has allowed the regression of the painful symptomatology in 84.6% of patients of our series, and allowed to stabilize the spine for all patients.

The after-surgery pain relief rate for metastatic tumors was generally high. Weigel and al. [37] noticed a moderate relief of pain in 89 % of patients after they underwent decompressive anterior surgery and stabilization. Likewise, Rompe & al [27] and Hussein & al. [14] have documented a pain relief in almost 90 % of their cases, while Shimizu & al [30] Cahill and Kumar [6] noticed a pain relief of 100% after posterior approach surgery. The motor deficit was improved in 48.3% of our patients with a gain of at least one grade of Frankel. Similar rates of neurological improvement were reported by King and al. [16] with a rate of 50% of improvement of at least one grade of Frankel in 20 patients after an anterior decompression combined with posterior stabilization without laminectomy. Also, a meta-analysis published in 2005 [17] resuming the results of 28 studies including 1542 patients with medullar metastases, found 1.3 times more important rates of ambulatory patients in case of surgery compared to radiotherapy alone (capacity to walk for 85% of operated patients versus 64% of irradiated patients)

In our series, postoperative complications were present in 28.8% of cases. They were essentially pulmonary complications. Panayiotis & al. [23] report that 17 % of postoperative complications were dominated by pulmonary complications in their series, covering 109 cases of solid cancer thoracic spine metastasis. Survival prediction above 12 months was null in our study and there were only 4 patients between 6 and 12 months. However, after surgery, 8 patients had a survival above 12 months and 8 others between 6 and 12 months. Factors which influenced this survival in our series were complementary treatments: RT/CT (p = 0.072), the histological type essentially the epidermoid carcinoma (p = 0.068) and preoperative Karnofsky 80–100% (p = 0.097). A possible explanation of this prediction can be the enhanced availability of adjuvant therapy. Indeed, new therapies have been introduced to improve patients affected by lung cancer survival [12, 29]. The median survival of patients with advanced lung cancer improved from 6 to 12 months with introduction of new treatment diagram combined with monoclonal antibodies, which proceed as angiogenesis inhibitor [28, 29]. Immunotherapy, which efficiency in improving the survival of bone metastases was first demonstrated by the retrospective analysis of Tamiya et al [33].

Our results show evidence of the interest of surgery in pain relief and spine stabilization for patients carrying spine metastasis of lung cancer. Survival predictive scores for patients with spinal metastases

(Tokuhashi, Tomita) are of limited applicability to PBC cancer metastasis due to the lack of good prognosis groups. Nevertheless, given the high morbidity and mortality of bronchopulmonary cancers, it would be necessary to implement a specific classification for PBC spinal metastases centered on the patient (personalized medicine) for a better assessment of the survival prediction for these patients.

Ethical approval

Approval was obtained from the ethics committee of the Marseille North Hospital in France. The procedures used in this study adhere to the tenets of the Declaration of Helsinki. For this type of study formal consent is not required.

This article does not contain any studies with human participants or animals performed by any of the authors.

Consent for publication

Not applicable.

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests

Funding

No funding was received for this research.

Authors’ contributions

FM, BLF and KJM collaborated to complete the conception and design of the study, acquisition, analysis and interpretation of the data. BLF completed the draft of the article and FM critically revised the article. SECN and DM participated in the design, statistical collection and analysis, performed the procedure, and provided technical support. RPH conceived of the study, participated in its design, performed the operations, and reviewed submitted version of the manuscript. All authors read and approved the final manuscript.

Acknowledgements

Not applicable.

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Spinal metastasis of bronchopulmonary cancer: Interest of a Spine surgery and prognostic scales value

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Abstract

Figures

1. Introduction

2. Materials And Methods

3. Results

4. Discussion

Conclusion

Declarations

References

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