Is there an optimal timing between radiotherapy and surgery to reduce wound complications in metastatic spine disease? A systematic review

Abstract

Purpose

Surgery with radiation therapy (RT) is more effective in treating spinal metastases, than RT alone. However, RT when administered in close proximity to surgery may predispose to wound complications. There exist limited guidelines on the optimal timing between RT and surgery. The purpose of this systematic review is to: (1) address whether pre-operative RT (preop-RT) and/or post-operative RT (postop-RT) is associated with wound complications and (2) define the safe interval between RT and surgery or vice versa.

Methods

PubMed, Embase and Scopus databases were systematically searched for articles dealing with spinal metastases, treated with surgery and RT, and discussing wound status.

Results

We obtained 2332 articles from all databases, and after applying exclusion criteria, removing duplicates and reading the full text, we identified 27 relevant articles. Fourteen additional articles were identified by hand-search, leading to a total of 41 articles. All 41 mentioned wound complications/healing. Sixteen articles discussed preop-RT, 8 postop-RT, 15 both, and 2 mentioned intraoperative-RT with additional pre/postop-RT. Twenty studies mentioned surgery-RT time interval; one concluded that wound complications were higher when RT-surgery interval was ≤ 7 days. Seven studies reported significant association between preop-RT and wound complications.

Conclusions

Evidence is insufficient to draw definitive conclusion about optimal RT-surgery interval. However, based on published literature and expert opinions, we conclude that an interval of 2 weeks, the minimum being 7 days, is optimum between RT-surgery or vice versa; this can be reduced further by postop-stereotactic body RT. If RT-surgery window is > 12 months, wound-complications rise. Postop-RT has fewer wound complications versus preop-RT.

Appendices

Appendix 1: Search strategies used to search PubMed, Scopus and Embase databases

PubMed search strategy

(((((("spine"[MeSH Terms] OR "spine"[All Fields]) OR "Spinal"[All Fields]) OR "Vertebra*"[All Fields]) AND ((((((("neoplasms"[MeSH Terms] OR "neoplasms"[All Fields]) OR ("neoplasm metastasis"[MeSH Terms] OR ("neoplasm"[All Fields] AND "metastasis"[All Fields]) OR "neoplasm metastasis"[All Fields])) OR "Cancer"[All Fields]) OR "Malignan*"[All Fields]) OR "Metastases"[All Fields]) OR "Metastasis"[All Fields]) OR "Metastatic"[All Fields])) AND (((("laminectomy"[MeSH Terms] OR "laminectomy"[All Fields]) OR ("surgery"[Subheading] OR "surgery"[All Fields] OR "surgical procedures, operative"[MeSH Terms] OR ("surgical"[All Fields] AND "procedures"[All Fields] AND "operative"[All Fields]) OR "operative surgical procedures"[All Fields] OR "surgery"[All Fields] OR "general surgery"[MeSH Terms] OR ("general"[All Fields] AND "surgery"[All Fields]) OR "general surgery"[All Fields])) OR "Vertebrectomy"[All Fields]) OR "Corpectomy"[All Fields])) AND (((("radiotherapy"[Subheading] OR "radiotherapy"[All Fields] OR "radiotherapy"[MeSH Terms]) OR "Radiation therapy"[All Fields]) OR "Irradiation"[All Fields]) OR "Stereotactic"[All Fields])) AND (((((((("wounds and injuries"[MeSH Terms] OR ("wounds"[All Fields] AND "injuries"[All Fields]) OR "wounds and injuries"[All Fields]) OR ("wound healing"[MeSH Terms] OR ("wound"[All Fields] AND "healing"[All Fields]) OR "wound healing"[All Fields])) OR ("wound infection"[MeSH Terms] OR ("wound"[All Fields] AND "infection"[All Fields]) OR "wound infection"[All Fields])) OR "Wound problem"[All Fields]) OR "Wound complication"[All Fields]) OR "Wound dehiscence"[All Fields]) OR "Major wound complication"[All Fields]) OR "Wound breakdown"[All Fields]) AND (has abstract[text] AND "humans"[MeSH Terms] AND English[lang] AND ("adolescent"[MeSH Terms] OR "adult"[MeSH Terms]))

Scopus search strategy

(TITLE-ABS-KEY (spine OR "Spinal" OR "Vertebra*")) AND (TITLE-ABS-KEY (neoplasms OR neoplasm AND metastasis OR "Cancer" OR "Malignan*" OR "Metastases" OR "Metastasis" OR "Metastatic")) AND (TITLE-ABS-KEY (laminectomy OR surgery OR "Vertebrectomy" OR "Corpectomy")) AND (TITLE-ABS-KEY (radiotherapy OR "Radiation therapy" OR "Irradiation" OR "Stereotactic")) AND (TITLE-ABS-KEY (wounds AND injuries OR wound AND healing OR wound AND infection OR "Wound problem" OR "Wound complication" OR "Wound dehiscence" OR "Major wound complication" OR "Wound breakdown")) AND (LIMIT-TO (PUBYEAR, 2019) OR LIMIT-TO (PUBYEAR, 2018) OR LIMIT-TO (PUBYEAR, 2017) OR LIMIT-TO (PUBYEAR, 2016) OR LIMIT-TO (PUBYEAR, 2015) OR LIMIT-TO (PUBYEAR, 2014) OR LIMIT-TO (PUBYEAR, 2013) OR LIMIT-TO (PUBYEAR, 2012) OR LIMIT-TO (PUBYEAR, 2011) OR LIMIT-TO (PUBYEAR, 2010) OR LIMIT-TO (PUBYEAR, 2009) OR LIMIT-TO (PUBYEAR, 2008) OR LIMIT-TO (PUBYEAR, 2007) OR LIMIT-TO (PUBYEAR, 2006) OR LIMIT-TO (PUBYEAR, 2005) OR LIMIT-TO (PUBYEAR, 2004) OR LIMIT-TO (PUBYEAR, 2003) OR LIMIT-TO (PUBYEAR, 2002) OR LIMIT-TO (PUBYEAR, 2001) OR LIMIT-TO (PUBYEAR, 1999) OR LIMIT-TO (PUBYEAR, 1998) OR LIMIT-TO (PUBYEAR, 1997) OR LIMIT-TO (PUBYEAR, 1996) OR LIMIT-TO (PUBYEAR, 1991) OR LIMIT-TO (PUBYEAR, 1989) OR LIMIT-TO (PUBYEAR, 1986) OR LIMIT-TO (PUBYEAR, 1984) OR LIMIT-TO (PUBYEAR, 1982) OR LIMIT-TO (PUBYEAR, 1971)) AND (LIMIT-TO (LANGUAGE, "English")).

Embase search strategy

('spine'/exp OR 'spine':ab,kw,ti OR spinal:ab,kw,ti OR vertebra*:ab,kw,ti) AND (neoplasms:ab,kw,ti OR (neoplasm AND metastasis:ab,kw,ti) OR cancer:ab,kw,ti OR malignancy:ab,kw,ti OR metastases:ab,kw,ti OR metastasis:ab,kw,ti OR metastatic:ab,kw,ti OR 'neoplasm'/exp OR 'neoplasm metastasis'/exp) AND (laminectomy:ab,kw,ti OR surgery:ab,kw,ti OR vertebrectomy:ab,kw,ti OR corpectomy:ab,kw,ti OR 'laminectomy'/exp OR 'surgery'/exp) AND ('radiotherapy'/exp OR radiotherapy:ab,kw,ti OR (radiation AND therapy:ab,kw,ti) OR irradiation:ab,kw,ti OR stereotactic:ab,kw,ti) AND ('wounds and injuries'/exp OR 'wound healing'/exp OR 'wound infection'/exp OR (wounds AND injuries:ab,kw,ti) OR (wound AND healing:ab,kw,ti) OR (wound AND infection:ab,kw,ti) OR (wound AND problem:ab,kw,ti) OR (wound AND complication:ab,kw,ti) OR (wound AND dehiscence:ab,kw,ti) OR (major AND wound AND complication:ab,kw,ti) OR (wound AND breakdown:ab,kw,ti)) AND ([adult]/lim OR [young adult]/lim) AND ('clinical article'/de OR 'clinical trial'/de OR 'human'/de) AND (1969:py OR 1978:py OR 1983:py OR 1984:py OR 1985:py OR 1986:py OR 1988:py OR 1989:py OR 1990:py OR 1991:py OR 1992:py OR 1993:py OR 1994:py OR 1995:py OR 1996:py OR 1997:py OR 1998:py OR 1999:py OR 2000:py OR 2001:py OR 2002:py OR 2003:py OR 2004:py OR 2005:py OR 2006:py OR 2007:py OR 2008:py OR 2009:py OR 2010:py OR 2011:py OR 2012:py OR 2013:py OR 2014:py OR 2015:py OR 2016:py OR 2017:py OR 2018:py OR 2019:py

Appendix 2: Description of the articles from the systematic literature review considered for data extraction

First author, year	Study design	No. of patients (included in final analysis); Gender (N) (M/F)	Age (years)	Treatment sequence (RT to MSTS or MSTS to RT) and type of surgery (N)	Interval between RT and MSTS or vice versa	Results related to wound complications	Conclusion/s
Redmond KJ, 2020 [53]	Phase II, prospective study	35 (M/F: 22/13)	Median: 63 (21–75)	Surgical resection prior to SBRT treatment	Surgical resection not more than 16 weeks prior to SBRT	No incidence of wound dehiscence/complications	Post-operative SBRT demonstrates excellent local control with low toxicity compared to historical post-operative conventional RT. No information on association between post-operative SBRT and wound complications
Barzilai O, 2019 [62]	Retrospective chart and imaging review	88 (M/F: 44/44)	Mean: 61 (27–84)	Open posterolateral decompression and stabilisation (67): Post-operative RT (63) (SBRT [63%]; conventional EBRT [33%]); surgery on previously irradiated lesions (20) Percutaneous minimally invasive surgery (21): Post-operative RT (11)	Not mentioned	3 wound infections or dehiscence requiring additional surgical intervention at 17, 22, and 29 months after initial surgery	Hybrid therapy with separation surgery and post-operative SBRT provides durable local control. Delayed complications include local and marginal tumour recurrence/progression, hardware failure, and wound complications. No information was reported on the correlation between pre- and/or post-operative RT and wound complications.
Tsagozis P, 2019 [69]	Retrospective review of prospective database	50 (M/F: 31/19)	Median: 65 (31–85)	Instrumentation (29) Posterior decompression only (21) Overall pre- or post-operative RT (33)	Post-operative RT was given 3–6 weeks after wound healing.	5 wound infections and dehiscence; 2 required extraction of the implant combined with antibiotic therapy; 2 needed debridement and flap reconstruction.	Early surgical decompression is associated with good neurological outcome in patients with cord compression from radiosensitive haematological neoplasia. A significant association was reported between RT and post-operative complications, with no mention of any specific connection of RT to wound complications.
Szczerba P, 2019 [24]	Retrospective analysis	723 (M/F: 260/463)	Mean age of women: 64 (28–85) Mean age of men: 69 (34–83)	Minimally invasive procedure (vertebroplasty, kyphoplasty, percutaneous stabilisation) (138) Posterior approach (417); anterior approach (137); combined approach (31) Prior RT (n = 151; 21%)	Not mentioned	42 wound healing problems and infections. Wound-healing disorders and infections were noted more frequently in patients with prior RT (n = 30; 19% of previous RT group).	Previous systemic (radiation) therapy may have a significant impact on the risk of wound-healing complications. No information on the influence of RT pre- or post-surgery on the risk of wound complications
Roser S, 2019 [70]	Retrospective review	137 (M/F: 80/57) (141 vertebrectomies)	Mean: 61 (25–83)	Vertebrectomy with anterior reconstruction and posterior fixation Thoracic (104); Lumbar (2); and Cervical (14) Pre-operative RT details were collected, but not reported.	Not mentioned	7 wound infections or dehiscence requiring operative revision. Out of these, 4 underwent pre-operative RT.	Vertebrectomy is a safe and effective means of providing circumferential neural decompression and stabilisation with an acceptable complication rate in patients with vertebral metastases. No information has been reported on the association between RT and wound complications.
Paulino Pereira NR, 2019 [49]	Retrospective cohort study	647 (M/F: 375/272)	Median: 60 (52–68)	Corpectomy with stabilisation (313); decompression with stabilisation (230); decompression alone (84); stabilisation alone (20) Prior RT (221)	Not mentioned	Wound infections and dehiscence were noted in 42 and 28 patients, respectively resulting in reoperation. Prior RT was significantly associated with reoperation.	Prior RT to the spinal tumour was independently associated with reoperation. Information regarding association between RT and wound complications has not been reported.
Pielkenrood B, 2018 [36]	Prospective cohort study	142 (M/F: not mentioned)	Not mentioned	Surgical stabilisation Pre-operative RT (91) Post-operative RT (51)	Interval between: Pre-operative RT and surgery: 0–280 days; surgery and post-operative RT: 8–69 days	10 wound complications; 3 in pre-operative RT group, and 7 in post-operative RT group	There was no significant difference in the complication rates, including wound complications between pre- and post-operative RT groups for spinal metastases.
Carl HM, 2018 [41]	Retrospective review	159 (M/F: 85/74)	Average: 59.6 ± 11.7	Resection of metastatic spine lesions: Anterior approach (41); Posterior approach (105); Combined approach (13) Pre-operative RT (63) Post-operative RT (75): Conventional EBRT (70); SRS (5)	Not mentioned	22 wound complications (6 wound dehiscence and 16 wound infections requiring surgery): 12 had pre-operative RT and 6 had post-operative conventional EBRT, but no significant association was detected.	Patients who undergo metastatic spine tumour resection are at an inherently high risk for wound-related reoperations due to high rates of adjuvant radiation. No information on association between RT and/or interval between surgery and RT and wound complications was reported.
Iida K, 2018 [71]	Retrospective analysis	34 (M/F: 17/17)	Mean: 64 (45–87)	Laminectomy of the compressed spinal cord and posterior instrument stabilisation; with or without RT All patients who underwent surgery + RT had post-operative RT	Not mentioned	3 wound complications	Surgical decompression and stabilisation may be required to improve the neurological function in patients with metastatic spinal cord compression presenting with myelopathy. High rate of complications associated with surgery should be considered. No information was reported on the association between RT and wound complications.
Versteeg AL, 2018 [23]	Prospective cohort	13 (M/F: Not mentioned)	Range: 41–85	SBRT followed by surgical stabilisation within 24 h Surgery: Percutaneous pedicle screw fixation (11); open procedure including decompression (2)	Median time between SBRT and surgery was 17 h (IQR 5–19 h) with four patients receiving both treatments on the same day.	None of the patients experienced disturbed wound healing or wound infection.	This study demonstrates the safety and feasibility of SBRT followed by surgery within 24 h for the treatment of spinal metastases with no patients demonstrating wound complications.
Abu-Bonsrah N, 2017 [63]	Retrospective analysis	159 (M/F: 85/74)	Mean: 59.6 ± 11.7	Surgical resection of metastatic spine tumour: Anterior approach (41); Posterior approach (105); Combined approach (13) Prior RT (62)	Not mentioned	76 (47.8%) had at least one peri-operative complication, of which 10 (6.3%) had wound complications.	Prior RT was independently associated with an increased risk for readmissions, but no information on association between prior RT and readmissions due to wound complications.
Roesch J, 2017 [54]	Retrospective study	30 (M/F: 13/17)	Median: 59 (27–84)	Open surgical decompression (24) and/or pedicle screw stabilisation (18) Vertebroplasty or balloon kyphoplasty only (10) (5 patients had a combined approach with decompression and placement of spinal instrumentation) Previous SBRT in all patients (conventional RT in 17 patients prior to SBRT)	Median interval between SBRT and surgical salvage therapy: 6 months (1–39 months)	2 cases of delayed wound healing	Prior spine SBRT does not significantly increase the risk of intra- and post-surgical complications. No information on the association between prior RT and wound complications has been reported.
Chen K, 2017 [55]	Retrospective cohort study	40 (M/F: 18/22)	Mean: 47.3 (28–67)	32 patients (42 vertebrae) had percutaneous puncture IORT + Cement; 8 patients (10 vertebrae) had open decompression + IORT All patients received IORT and 8 patients received post-operative EBRT.	Not mentioned	No wound complications	Surgery combined with tumour conformal IORT for thoracolumbar metastases has good short-term effects with no apparent wound complications.
Berriochoa CA, 2016 [51]	Retrospective review	63 (M/F: Not mentioned)	Not mentioned	Surgical decompression (corpectomy or separation surgery) followed by palliative RT Post-operative SBRT (37); post-operative EBRT (26) Instrumentation was performed in all 37 SBRT, and 18/26 EBRT patients.	RT was performed within 3 months of surgery.	2 wound complications in SBRT group and 1 in EBRT group. One-year projected cumulative incidence of wound complications in the SBRT and EBRT groups: 2.8% and 6.3%, respectively	Both post-operative SBRT and EBRT are safe for spinal metastases. No information on association between post-operative RT and wound complications was reported.
Harel R, 2016 [64]	Retrospective cohort study	Total N = 22; Response to therapy was evaluated in 17 patients (M/F: 11/6).	Mean: 57 (7–85)	Conventional approach and post-operative single-session SRS (22) Combined ventral and dorsal approach (5); ventral (13); dorsal (4) Decompression only (6); un-instrumented fusion (1); Decompression + instrumented fusion (15)	SRS done within 2 months following surgery	2 superficial wound infections; pre-SRS, no prior RT. No cases of new/persistent wound infection or dehiscence post SRS	Spine surgery with adjuvant SRS appears to be beneficial in reducing potential wound complications.
Sugita S, 2016 [26]	Retrospective cohort study	279 (M/F: 118/161)	Median: 63 (56–70)	All patients received IORT and surgery (post fusion surgery [with or without decompression]); in addition, 137 received pre-operative RT.	Not mentioned	27 of 137 who received pre-op RT had wound infection.	Pre-operative RT was found to be independently associated with occurrence of SSI in patients who underwent surgery with IORT for spinal metastases.
Park HY, 2015 [72]	Retrospective chart review	23 (M/F: 17/6)	Mean: 54.72 (35–73)	Simple decompression with laminectomy for tumour involved posterior column, laminectomy plus trans-pedicular anterior decompression for tumour located vertebral body and total spondylectomy. For anterior column support, corpectomy followed by inserting titanium mesh cage or cement bloc. All procedures were combined with instrumentation Pre-operative RT (6); Post-operative RT (10); Pre- and post-operative RT (3)	Not mentioned	3 wound infections or dehiscence (one had pre- and one had post-operative RT); two required re-operation	Surgical procedures including posterior approach, debulking surgery, and stabilisation under neurophysiologic monitoring with adjuvant radiation therapy are an important part of the treatment of metastatic spinal tumours located on cervicothoracic junction. No information on the association between pre- or post-operative RT and wound complications has been reported.
Yokogawa N, 2014 [61]	Retrospective cohort study	50 (M/F: 27/23)	Mean: 57.8 (24–75)	Surgical approach: TES Pre-operative RT (18)	< 12 months in 8 patients, > 12 months in 10 patients	No wound complications	Perioperative complication rate associated with TES for spinal metastasis is significantly higher in pre-operative RT group than in no RT group.
Keam J, 2014 [31]	Retrospective cohort study	165 (165 surgical wounds) (M/F: 90/75)	Median: XRT: 62 (26–84); IGRT: 60 (43–82)	Single-stage surgery with decompression and spinal fixation Pre-operative XRT (130) Pre-op hypo fractionated IGRT (35)	Mean: XRT: 410 ± 658 days; IGRT: 345 ± 389 days	24 wound complications: 22 were after XRT, and 2 were after hypo fractionated IGRT	No significant difference in wound complication rates in patients receiving conventionally fractionated or high dose hypo fractionated radiation before surgery.
Nemelc RM, 2014 [35]	Retrospective cohort study	Total, N = 86 (Survival analysis done on 81 patients) (M/F: 37/44)	59 (24–87)	Anterior approach (11); posterior approach (67); Combined approach (8) Details of RT: Not mentioned	Not mentioned	4 cases of deep surgical wound infection, out of which 2 received RT prior to surgery and 1 patient received adjuvant RT	Pre-operative RT had no influence on the risk for post-operative surgical wound infections.
Kumar S, 2015 [32]	Retrospective cohort study	95 (M/F: 51/44)	19–87	Combined anterior–posterior surgical approach; reconstruction (6) No patients underwent RT in the immediate pre or post-operative period.	Post-operative RT was commenced once the surgical wound was completely healed.	All the patients with wound infection had it in their post-spinal wounds. No wound infection was noted after the onset of post-operative RT.	≥ 7 vertebral levels of surgery increase the risk of infection significantly. No correlation was observed between RT and wound infection.
Massicotte E, 2012 [65]	Retrospective cohort study	10 (M/F: Not mentioned)	Not Mentioned	All patients treated with MASS + adjuvant post-operative SBRT Pre-operative RT (1)	Median time to SBRT planning: 6.5 days (1–18) and treatment ensued on average 7 days following planning	No wound complications	MASS avoids the risks of surgical morbidity and the potential delays in receiving post-operative RT/chemo associated with invasive surgery.
Omeis IA, 2011 [28]	Retrospective, case–control	678 patients (M/F: 364/314) (895 procedures)	Mean: 47.2	Treatment sequence not mentioned Surgery: 82% patients were treated by posterior approach.	Not mentioned	65 patients developed SSI.	Having a previous surgery or RT to the operative area was a significant risk for wound infection. No significant difference was noted  in wound infections based on surgical approach (anterior vs. posterior).
Moulding HD, 2010 [34]	Retrospective cohort study	21 (M/F: 15/6)	Median: 53.2 (28.7–78.4); mean: 52.9 ± 12.1	Posterolateral decompression and instrumentation with local autologous bone graft in all patients Adjuvant post-operative single-fraction high-dose SRS	Mean duration from surgery to SRS: 43.9 (26–63) days	No wound complications	High-dose single-fraction radiation (24 Gy) provides durable tumour control that is histology independent. No correlation was observed between RT and wound infection.
Harel R, 2010 [66]	Retrospective cohort study	15 (M/F: 10/5)	Mean: 53 (24–79)	Surgery + post-operative RT with XRT or SRS Combined anterior and posterior approach (4); single approach (anterior or posterior) (11)	Surgery to post-operative RT: Within 2 months (median time from surgery to SRS was 38 days)	One patient in the XRT group had a deep wound infection.	SRS is a feasible adjuvant treatment to spine surgery with high rates of tumour control and low associated complications.
Demura Sa, 2009 [29]	Retrospective cohort study/prospective cohort study	110 (M/F: 65/45) (113 surgeries)	Median: 56 (32–72)	En bloc surgery (38); Debulking (43); Palliative (29) Pre-operative RT (22)	(Mean ± SD): Without PGE1: 12.1 ± 9.1 months; With PGE1: 15.1 ± 14.5 months	SSI incidence: 7.1% (8/113 surgeries); rate of SSI with irradiation: 31.8% (7/22 cases) and without irradiation (1.1%, 1/91 cases)	Prior irradiation was associated with a higher incidence of SSI by univariate analysis and multivariate logistic regression.
Chaichana KL, 2008 [73]	Retrospective review	78 (M/F: 46/32)	Mean: 56 ± 13	Anterior approach (28); Posterior approach (43); Anteroposterior approach (7) Post-operative RT (21); no details on pre-operative RT	Not mentioned	4 wound dehiscence	Pre- and post-operative RT were associated with a lower and higher likelihood of regaining ambulatory function at follow-up, respectively. No information on association between RT and wound complications was reported.
Street J, 2007 [37]	Prospective cohort study	66 (SPLV group of 42) (M/F: 23/19)	Mean: 56.04 (19–76)	SPLV group (42): Simultaneous 360° tumour resection and immediate spinal column reconstruction. 14 patients had pre-operative RT/ SPLV for disease of the lumbar spine, combined with bilateral costotransversectomies in the thoracic spine. Comparison group (24): thoracic or lumbar tumour decompression and spinal stabilisation	RT to surgery interval > 7 days	10 patients with major wound complications, of which 3 had had pre-operative RT	Pre-operative RT did not adversely affect the rate of complications in either population of patients.
Holman PJ, 2005 [30]	Retrospective cohort study	139 (M/F: 85/54) (166 procedures)	Median: 55 (12–83)	89 patients received some form of treatment for spinal disease at outside institutions. RT (14); surgical decompression (4); RT + surgery (8); RT + Chemo + Surgery (9). 80 patients required post-operative adjuvant therapy including RT alone and RT and chemo Surgical approach: Thoracoabdominal (27); retroperitoneal (47); transperitoneal (1); transpedicular (23)	Not mentioned	7 wound infections, majority of which (6/7) were in posterior surgeries	No significant association between pre-operative RT and wound infection. Whenever surgical intervention is contemplated, RT involving the operative field should be delayed, if possible.
Wang JC, 2004 [38]	Retrospective cohort study	140 (M/F: 105/35)	Median: 60.3(20.5–85.9)	Single-stage posterolateral transpedicular approach Pre-operative RT (84); patients with radioresistant tumours (14) had surgery within 30 days of pre-operative RT for tumour progression Post-operative EBRT (24): Operation + failed EBRT—underwent repeated IMRT (2); no pre-operative RT but had post-operative IMRT (5)	Mean time between failed RT and surgery: 4.2 months	Most prevalent complication: Wound dehiscence and/or infection—16 patients (11.4%)	No statistical difference was noted in risk rates in patients undergoing pre-operative RT or de novo surgery (p = 0.21), including patients who had pre-operative RT within 6 weeks of surgery (p = 0.29).
Sundaresan N, 2002 [25]	Retrospective cohort study	80 (M/F: 44/36)	Mean: 56; median: 55(22–81)	Surgical approach: anterior (32); strictly posterior or posterolateral (8); anteroposterior (40); en bloc resection (6) Previous RT (40); all had failed RT Remaining 40 patients—surgery because of clinical symptoms and the solitary nature of the tumour	Not mentioned	1/40 de-novo surgery had wound infection. 10/40 previous RT had wound breakdowns. All wound complications requiring revision surgery were noted in irradiated patients.	Wound infection was observed mainly in patients who received pre-operative RT. Statistically significant (p < 0.03) difference was noted in complication rates between irradiated and non-irradiated patients.
Ghogawala Z, 2001 [22]	Retrospective case series	85 (M/F: Not mentioned)	Mean: XRT = 55 XRT/ Surgery = 63 Surgery/XRT = 62	Single-stage posterolateral decompression and stabilisation RT Only (23); pre-operative RT (28); post-operative RT (34)	Pre-operative RT ≤ 7 days in 13 patients; Pre-operative RT > 7 days in 15 patients	13 major wound complications; pre-operative RT ≤ 7 days: 46% wound complications; pre-operative RT > 7 days: 20% wound complications	Wound complication rate was higher when surgery was performed ≤ 7 days of RT, as compared to > 7 days after RT.
Fourney DR, 2001 [67]	Retrospective cohort study	95 patients (M/F: 55/40) (100 procedures)	Median: 54 (14–79)	Surgical approach: post tumour resection and stabilisation (48); anterior approach + posterior reconstruction (51); others (1) Pre-operative RT only (9); chemo only (34); RT and chemo (34); Neither (18) Post-operative RT only (7); chemo only (23); RT and chemo (20); Neither (35)	Not mentioned	9 wound infections	Pre-operative RT (p = 0.002) was associated with post-operative complications. The study findings emphasize the importance of avoiding pre-operative RT in patients who are candidates for surgery as a first-line therapy.
Wise JJ, 1999 [48]	Retrospective cohort study	80 (M/F: 38/42) (88 procedures)	Median: 55.6 (20–84)	Surgical approach: Anterior, posterior or combined decompression and stabilisation Pre-operative RT (41) (45 procedures); no pre-operative RT (39) (43 procedures)	Not mentioned	Superficial wound infection (2); deep wound infection (6); all these patients had undergone pre-operative RT	Wound infection was observed mainly in patients who received pre-operative RT.
Pascal-Mousellard H, 1998 [27]	Retrospective cohort study	145	Not Mentioned	Treatment sequence not mentioned Surgical approach: Cervical corpectomy (48); thoracic laminectomy (109)	Not mentioned	Post-operative wound infection (6): 4 had pre-operative RT; wound dehiscence (8): 7 had pre-operative RT; delayed healing (6): 4 had pre-operative RT	Wound infection rate in pre-operative RT patients was higher than those with post-operative RT (statistically significant). Vertebral metastases should be primarily treated by surgery before RT in order to significantly prevent surgical complications.
McPhee B, 1998 [33]	Retrospective review	53 (75 wounds) (M/F: 31/22)	Mean: patients with wound infection/dehiscence: 54 ± 13; patients with healed wounds: 53 ± 17	Anterior surgery (23); posterior surgery (52) Perioperative RT was administered in 10 wounds that broke down and 32 wounds that healed	1 month before or 1 month after surgery	Of the 75 wounds, 60 healed and 15 broke as a result of infection or dehiscence.	There was no statistically significant correlation between perioperative RT and wound infections.
Akeyson EW, 1996 [40]	Retrospective case series	25 (M/F: 13/12)	Mean: 53.8 ± 2.6	Single-stage operation combining a near complete (90%) single- or multi-level spondylectomy, vertebral body replacement using methyl methacrylate (MMA), and posterior fixation Pre-operative RT (20); post-operative RT (3) after allowing enough time for wound healing	Not mentioned	3 non-healing wounds (1 infection and dehiscence; 1 dehiscence without infection; 1 infection). 2 out of these 3 patients received pre-operative RT leading to wound-healing problems. No deep wound infections	Wound infection was observed mainly in patients who received pre-operative RT.
Sundaresan N, 1995 [74]	Retrospective study	110 (M/F: 57/53)	Median: 58 (28–85)	Staged anterior–posterior resection and instrumentation (53); anterior resection with instrumentation (33); anterior resection only (18); posterior resection and instrumentation (6) Previous RT (47); post-operative RT (20)	Not mentioned	18 wound breakdown and 13 infections	Anterior–posterior resection of neoplastic compression from epidural metastasis is effective, with majority requiring instrumentation. No information on association between prior or post RT and wound complications was reported.
Johnston FG, 1989 [68]	Retrospective cohort study	34 (M/F: 17/17)	Mean: 61 (18–78)	Single-stage anterior decompression and debulking, with posterior stabilisation Pre-operative RT failed to maintain neurological status (14)	Not mentioned	Wound infection and dehiscence in 5/34 (15%) patients; all 5 had pre-operative RT	Wound infection was observed mainly in patients who received pre-operative RT.
Harrington KD, 1988 [75]	Retrospective cohort study	77 (92 operations)	Not mentioned	Anterior decompression alone (76); anterior decompression + second-stage posterior decompression and stabilisation (3–10 days after first surgery) (5) Pre-operative RT (58); post-operative RT (4)	Post-op RT 3 weeks after surgery (in 4 patients who were not previously irradiated)	1 deep infection in 83 anterior stabilisation procedures. 3 wound dehiscence in 6 patients with posterior stabilisation after pre-operative RT. All 3 had secondary wound infection.	Wound infection was observed mainly in patients who received pre-operative RT.
Young RF, 1980 [39]	Randomised controlled trial	29 (M/F: not mentioned)	Mean: Group I: 53.8 (19–70) Group II: 63.8 (34–83)	Decompressive laminectomy + post-operative RT (group I) (16); RT alone (group II) (13)	Group I: post-operative RT: 7 days after surgery	No wound infection/dehiscence following surgery	No statistical difference between surgery + RT vs RT alone in treatment of spinal epidural metastasis. No wound complications were noted following surgery or related to RT

1. Chemo chemotherapy, EBRT external beam radiation therapy, IGRT image-guided radiation therapy, IORT intraoperative radiotherapy, MASS minimal access spine surgery, MSTS metastatic spine tumour surgery, PGE1 prostaglandin E1, RT radiotherapy, SBRT stereotactic body radiotherapy, SPLV single-stage posterolateral vertebrectomy, SRS stereotactic radiosurgery, SSI surgical site infection, TES total en bloc spondylectomy, XRT fractionated radiation therapy
2. ^aStudy comprised of 2 phases: Phase 1 was retrospective and phase 2 was prospective clinical study