Patient-Reported Outcomes After Intramedullary Nailing of Oncologic Impending or Pathologic Fractures With Carbon Fiber or Titanium Implant.

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Bone metastases are a common occurrence in patients with breast, prostate, kidney, or lung cancer, and approximately 20 to 25% of patients with metastatic bone disease experience impending or pathologic fractures. 1 In this population, pathologic fractures are associated with a notable decrease in quality of life and overall survival and, as such, often treated surgically. 2 Intramedullary nailing (IMN) is an effective procedure to prophylactically or therapeutically stabilize the bone and prevent additional fracture. 3 Owing to the limited life expectancy of these patients, the goal of this surgical procedure was to improve the patient's quality of life by reducing pain and increasing functional mobility.

Patient-reported outcomes (PROs) have had a notable effect on the care of orthopaedic patients in various subspecialties, such as hand, foot and ankle, and spine. 4 - 6 In musculoskeletal oncology, the Toronto Extremity Salvage Score is the most commonly used PRO measure for patients undergoing surgery for extremity tumors. 7 , 8 The Patient-Reported Outcomes Measurement Information System (PROMIS) is a set of patient-reported outcome (PRO) questionnaires developed by the National Institutes of Health, which have also been extensively studied in the orthopaedic population. 9 In orthopaedic oncology, studies have reported that PROMIS Pain Interference and Physical Function scores correlate with Toronto Extremity Salvage Scores. 9 Despite the increasing use of PROs, there is limited literature on oncologic patients undergoing pathologic fracture fixation with IMN.

In recent years, the mechanical and biocompatible properties of carbon fiber (CF) have led to its increasing utilization in orthopaedic implants, such as intramedullary nails. 10 , 11 Among their several benefits, CF nails stand out for being radiolucent and may provide better visualization of fracture reduction and tumor recurrence after bone stabilization. Despite available literature on the biomechanical properties and clinical outcomes of patients treated with carbon fiber polyetheretherketone nails, 12 , 13 no studies have compared postoperative PROs between CF and titanium implants. This remains critically important because the lack of data on PROs after CF IMN might limit the adoption of this technique among physicians. Therefore, we focused our study strictly on the PROs after IMN with either CF or titanium implants. Other areas of comparison such as clinical outcomes are not covered because previous multicenter studies spearheaded by our group have demonstrated similarity between implant types. 13 - 15

In patients treated with intramedullary nailing for impending or pathologic fractures due to bone metastases, our study sought to assess the following: (1) What are the PROs for physical function, mental function, and pain visual analog scale (VAS) after IMN? (2) Are postoperative PROs for physical function, mental function, and pain VAS different between patients treated with CF or titanium nails?

Materials and Methods

Study Design and Setting

We obtained Institutional Review Board approval before the beginning of the study. A retrospective review of the electronic medical records of patients treated at a large tertiary care academic center was conducted.

Participants

Inclusion criteria for our study were the following: (1) surgical treatment of an impending or pathologic fracture of the femur, humerus, or tibia with intramedullary nailing, (2) metastatic bone disease as the cause of the impending or complete fracture, (3) surgery performed between 2016 and 2022, and (4) completion of at least one postoperative PROMIS assessment at the 1-month, 3-month, 6-month, or 1-year time points. Because PROMIS questionnaires through the electronic health record portal only became available in 2016 at our institution, we restricted our analysis to patients treated from 2016 onward.

Patients undergoing IMN with a CF implant received any of the following implants: CarboFix Trochanteric Nailing System, CarboFix Tibial Nail, and CarboFix Humeral Nail. All CF implants were manufactured by CarboFix Orthopaedics. In the group treated with titanium nails, the following implants were used: Cannulated Trochanteric Fixation Nail (DePuy Synthes Inc), Cannulated Tibial Nail (DePuy Synthes Inc), and Cannulated Humeral Nails (DePuy Synthes Inc). All cephalomedullary nails were combined with a lag screw. Surgeons had the option to choose between CF or titanium implants, with CF being preferred for aggressive tumors with a high chance of recurrence or when visualizing the response to radiation therapy was essential.

Variables and Outcomes of Interest

The following demographic and clinical parameters were obtained from each patient chart: age, sex, American Society of Anesthesiologists (ASA) class, body mass index, age-adjusted Charlson comorbidity index (CCI), type of primary tumor, type of fracture (impending or complete), type of lesion (lytic, sclerotic, or mixed), type of nail (CF or titanium), nail location, bone region, length of stay in days, and follow-up in months.

Outcomes of interest were postoperative PROs, measured using the PROMIS questionnaires and pain VAS. Regarding PROMIS, scores from three questionnaires were assessed: Global Health Short Form (SF) Mental (SF Mental), Global Health SF Physical (SF Physical), and Physical Function SF 10a (SF 10a). When available, preoperative scores for each of the included outcome measures were extracted. Only assessments filled within 120 days before surgery were considered. When multiple preoperative values existed, the closest to the date of surgery was selected.

Patient-reported outcomes were assessed after surgery at the 1-month, 3-month, 6-month, and 1-year time points. A margin of error of ± 10 days was allowed for the 1-month mark; as such, assessments completed between postoperative days 20 and 40 could be included as 1-month scores. Margins of error of ± 20, ± 30, and ± 60 days were used for the 3-month, 6-month, and 1-year marks, respectively. When multiple scores were available within a certain period, the value closest to the exact mark (30, 90, 180, and 365 days) was used. This strategy was implemented because completion of questionnaires depended on patients accessing the electronic health record portal and filling the forms online.

Absolute and differential scores at each of the time points of interest were assessed. Differential scores were calculated by subtracting preoperative scores for each assessment from their respective absolute scores at each time point. Because calculation of differential scores required availability of both postoperative and preoperative PROMIS scores, the number of analyzable events was lower than the number of absolute scores (Supplementary Table 1, http://links.lww.com/JG9/A347 ). Improvement in differential postoperative scores was seen as a positive value in the case of PROMIS SF Physical, SF Mental, and SF 10a scores and a negative value in the case of pain VAS score.

Patient Population

A total of 321 patients treated with IMN for pathologic or impending fractures were eligible for inclusion. A different distribution of covariables between patients treated with CF or titanium nails was seen in the unmatched cohort (Table 1 ). After propensity score matching, 207 patients were included in the final analysis (Figure 1 ). Fifty-one patients (24.6%) were treated with CF nails and 156 (75.4%) with titanium nails (Table 1 ). The median age was 68 and 67 years for the CF and titanium groups, respectively. No differences in sex, ASA class, body mass index, age-adjusted CCI, and primary tumor type were seen between groups. Impending fractures were found in 76.5% and 72.4% of patients treated with CF or titanium nails, respectively ( P = 0.57). Lytic lesions were present in 76.9% and 85.6% of patients treated with CF or titanium nails, respectively ( P = 0.35). The femur was the most common location for IMN in both groups, most lesions were located in the diaphyseal region of the bone in both groups, and the median length of stay was 3 days for both groups. Furthermore, we found similar overall survival between groups (Figure 2 ).

The median preoperative PROMIS SF Physical score was 36.2 in the CF group and 37.4 in the titanium one ( P = 0.80) (Table 2 ). No differences were seen in preoperative PROMIS SF Mental ( P = 0.43) and SF 10a ( P = 0.79) scores between groups. Patients treated with CF nails had a higher preoperative pain VAS score than those treated with titanium nails ( P = 0.03).

Statistical Analysis

Demographic, clinical, and PROMIS variables were displayed using descriptive characteristics. The Shapiro-Wilk test was used to check for normal distribution of data. Because data were non-normally distributed ( P < 0.05 on Shapiro-Wilk test), median values and interquartile ranges were used for continuous variables. Differences between groups were compared using the Mann-Whitney U test (nonparametric) for continuous variables and chi-square for categorical ones. To reduce the effect of potential confounding between CF and titanium IMN, patients were matched using propensity scores. Propensity score matching was conducted using a three-to-one nearest neighbor matching without replacement and a caliper fixed at 0.1. The propensity scores were calculated using a logit model including the following variables: age-adjusted CCI, type of primary tumor, ASA class, type of fracture, and location of the nail. A P value ≤ 0.05 was considered statistically significant. All statistical analyses were conducted using Stata (StataCorp, USA).

Results

What Are the Patient-Reported Outcomes for Physical Function, Mental Function, and Pain Visual Analog Scale After Intramedullary Nailing?

One month postoperatively, the overall mean PROMIS SF Physical score was 37.4 while SF Mental and SF 10a scores were 45.8 and 31.8, respectively (Table 3 ). The median pain VAS score was three during that period. One-month differential scores showed a one-point decrease in the pain VAS score while PROMIS SF Physical, SF Mental, and SF 10a still did not present improvement. Three months postoperatively, the median reported pain VAS scores decreased by two points and there was a 3.85-point, 1.25-point, and three-point improvement in median PROMIS SF Physical, SF Mental, and SF 10a scores, respectively. At 6 months and one year postoperatively, the median PROMIS SF Physical, SF Mental, and SF 10a scores were higher than preoperative scores. Pain VAS scores decreased by a median of one and three points at the 6-month and 1-year postoperative marks, respectively.

Are Postoperative Patient-Reported Outcomes for Physical Function, Mental Function, and Pain Visual Analog Scale Different Between Patients Treated With Carbon Fiber or Titanium Intramedullary Nailing?

At 1 month postoperatively, no differences in PROMIS SF Physical, SF Mental, and SF 10a scores were seen between groups (Table 4 and Figure 3 ). The median pain VAS score was higher in patients treated with CF nails ( P = 0.001). No differences in absolute scores were seen in PROMIS SF Physical, SF Mental, SF 10a, or pain VAS scores between groups at the 3-month, 6-month, and 1-year marks (Table 4 ).

No difference in differential scores were seen at the 1-month postoperative mark (Table 5 ). No differences in pain VAS, PROMIS SF Physical, SF Mental, and SF 10a scores were seen between groups. At 6 months postoperatively, both groups displayed higher physical function scores (PROMIS SF Physical and SF 10a) than preoperative scores. One year after surgery, both groups achieved similar levels of pain reduction and physical and mental function.

Discussion

Use of PROMIS assessments has steadily increased in the past decade, and their values are increasingly being used for both clinical research and healthcare value assessment. 16 Despite the growing popularity of PROMIS, analysis of these scores in orthopaedic oncology is challenging because of the higher disease burden of most patients. 9 In metastatic disease, although IMN provides short-term pain relief and partial restoration of physical function, it is not a curative procedure, and patients may still have disseminated disease. While previous research has compared the clinical outcomes of CF and titanium implants, we solely focused on PROs. Our study found that patients reported notable pain relief at the 1-month postoperative mark while mental health and physical function scores began to improve at the 3-month to 6-month marks. In addition, PROs were similar between patients treated with CF or titanium intramedullary nails. To our knowledge, our study is the largest cohort to analyze PROs in patients undergoing surgery for impending or pathologic fractures due to metastatic bone disease.

Our study presented several limitations. First, this was a retrospective study and, as such, no cause-effect relationships could be assessed, only associations. Second, owing to the retrospective nature of our study, our analyses of PROs were restricted to patients that were alive at a certain time point and actually filled out the surveys. We found different response rates between groups, and patients who filled one survey did not necessarily fill all other surveys at the established time points. Although patient survival was similar between patients treated with CF and titanium nails (Figure 2 ), differences in questionnaire response rates were seen between groups in multiple categories (Supplementary Table 1, http://links.lww.com/JG9/A347 ). Most differences in response rates were seen in preoperative and differential PROMIS scores, with the latter requiring both absolute values at a certain time point and preoperative scores. We consider that this is explained by the progressive adoption of CF nails at our institution from 2016 onward. Patients recently treated were more likely to receive a CF nail, and because PROMIS assessments only became available in 2016, they were more likely to have access to preoperative PROMIS. Instead, patients treated around 2016 were mainly treated with titanium nails because CF nails were just starting to be introduced at our center. These patients often did not have access to preoperative PROMIS. Response bias could also have contributed to this difference, with patients with more advanced disease or worse health status being less prone to fill the questionnaires online. We approached this by running a propensity score match between study groups. Although no differences were found in demographic and clinical characteristics, additional confounders might be present. Third, our study was restricted to the period between 2016 and 2022 because of unavailable PROMIS data before 2016. Although this might limit the generalizability of our findings, we do not consider this to be the case because the surgical approach for IMN has been fairly consistent during the past two decades. In addition, CF nails only began to be used in our center in 2016 and, therefore, time restriction is rather beneficial because both groups were treated in the same period. Fourth, differences in implant length, perioperative techniques, and anatomy of the involved segment between groups (titanium and CF) could have altered PROs. Fifth, additional patient factors such as the body habitus, bone quality, and preoperative function may have affected the quality of bone fixation. Inadequate fixation could affect PROs, resulting in different outcomes between populations. Finally, there was notable heterogeneity in terms of type of primary tumor and lesion characteristics that may affect the generalizability of our findings.

Our study showed improvement in pain relief at the 1-month postoperative mark. Conversely, patient-reposted physical function showed improvement 3 months after surgery and mental function only after 6 months. Early improvements in pain scores, as soon as 2 weeks after surgery, have been reported by multiple studies and underscore the effectiveness of IMN for pain relief after pathologic fractures. 17 , 18 Regarding functional status, existing literature has focused on using the TESS and Musculoskeletal Tumor Society questionnaires to assess postoperative function. 18 - 22 To our knowledge, a study by Blank et al. 23 was the only one to use PROMIS questionnaires for postoperative PRO assessment in metastatic bone disease. In a prospective cohort of nine patients, they found that average physical function already began to improve by 2 weeks after surgery. Despite its prospective nature, the study had a limited sample size. Although a select group of patients may report early improvement in functional patient-reported measures, this is usually not the standard, and previous research suggests that notable improvement in this realm occurs at the 6-week to 12-week postoperative mark. 18 Finally, the delayed improvement in mental function highlights how recovery of preoperative mental health does not necessarily go hand-in-hand with pain relief and restoration of physical function, and additional support in this field is needed.

Our study further compared postoperative PROMIS and pain VAS scores in patients undergoing IMN with either CF or titanium implants. Comparing both materials is essential because CF implants exhibit decreased rigidity compared with titanium. 24 , 25 Theoretically, the similar elastic modulus of CF implants to bone helps to lessen stress concentration at the bone-implant interface. 25 , 26 However, literature supporting these findings focuses on osteoporotic bone and may not be applicable to pathologic fractures due to neoplastic processes. Therefore, additional research is required to determine whether CF mechanical properties result in improved healing potential or instead translate into insufficient stiffness for healing.

In addition, CF facilitates the transfer of stress and enables an even distribution of forces throughout the bone, potentially extending the implant's lifespan. In our study, we found no differences in both absolute and differential pain VAS scores between groups. Our findings complement previous research by our group showing similar postoperative outcomes and surgical types between CF and titanium nails 13 , 25 and demonstrate that CF nails are comparable to their titanium counterparts from a PRO standpoint.

Conclusions

Intramedullary nailing of pathologic fractures due to bone metastases or primary bone and soft tissue was associated with notable improvement in postoperative PROMIS scores. In our cohort, early pain relief was followed by improvement in physical and mental function. The type of implant (CF or titanium) did not affect postoperative PROMIS. Given the similar PROs after CF IMN and the added benefits of this material, physicians should consider these implants as a viable alternative to stabilize or treat bone metastases. However, additional research is required to determine how these implants compare in terms of fracture fixation. Future prospective studies should also focus on identifying risk factors of delayed improvement in mental function and understanding which factors contribute the most to patient quality of life.

Supplementary Material

Footnotes

Dr. Lozano-Calderon or an immediate family member is a member of a speakers’ bureau or has made paid presentations on behalf of CarboFix Orthopedics (Ocean Isle Beach, NC 28469). None of the following authors or any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this article: Ms. Xu, Ms. Sodhi, Mr. Fang, Ms. Kim, Mr. Groot, Dr. Schwab, Dr. Gonzalez.

Institutional Review Board approval was obtained before the start of the study. A copy of the approval letter is present in our submission file.

This investigation was performed at the Massachusetts General Hospital, Boston, MA.

Contributor Information

Marcos R. Gonzalez, Email: mgonzalez52@mgh.harvard.edu.

Raylin F. Xu, Email: rfxu@mgh.harvard.edu.

Alisha Sodhi, Email: asodhi1@mgh.harvard.edu.

Vincent Fang, Email: vincentfang2000@gmail.com.

Chaewon Kim, Email: chaewonskim@gmail.com.

Tom M. de Groot, Email: tgroot@mgh.harvard.edu.

Joseph H. Schwab, Email: jhschwab@mgh.harvard.edu.

References

1. Willeumier JJ, van der Linden YM, van de Sande MAJ, Dijkstra PDS: Treatment of pathological fractures of the long bones. EFORT Open Rev 2016;1:136-145.

2. Narazaki DK, de Alverga Neto CC, Baptista AM, Caiero MT, De Camargo OP: Prognostic factors in pathologic fractures secondary to metastatic tumors. Clinics 2006;61:313-320.

3. Kirkinis MN, Lyne CJ, Wilson MD, Choong PFM: Metastatic bone disease: A review of survival, prognostic factors and outcomes following surgical treatment of the appendicular skeleton. Eur J Surg Oncol 2016;42:1787-1797.

4. Beckmann JT, Hung M, Voss MW, Crum AB, Bounsanga J, Tyser AR: Evaluation of the patient-reported outcomes measurement information System upper extremity computer adaptive test. J Hand Surg Am 2016;41:739-744.e4.

5. Hung M, Baumhauer JF, Latt LD, Saltzman CL, SooHoo NF, Hunt KJ, National Orthopaedic Foot & Ankle Outcomes Research Network: National orthopaedic foot & ankle outcomes research network: Validation of PROMIS ® physical function computerized adaptive tests for orthopaedic foot and ankle outcome research. Clin Orthop Relat Res 2013;471:3466-3474.

6. Purvis TE, Andreou E, Neuman BJ, Riley LH, Skolasky RL: Concurrent validity and responsiveness of PROMIS health domains among patients presenting for anterior cervical spine surgery. Spine 2017;42:E1357-E1365.

7. Davis AM, Devlin M, Griffin AM, Wunder JS, Bell RS: Functional outcome in amputation versus limb sparing of patients with lower extremity sarcoma: A matched case-control study. Arch Phys Med Rehabil 1999;80:615-618.

8. Davis AM, Wright JG, Williams JI, Bombardier C, Griffin A, Bell RS: Development of a measure of physical function for patients with bone and soft tissue sarcoma. Qual Life Res 1996;5:508-516.

9. Ploetze KL, Dalton JF, Calfee RP, McDonald DJ, O’Keefe RJ, Cipriano CA: Patient-reported outcomes measurement information System physical function correlates with Toronto extremity salvage score in an orthopaedic oncology population. J Orthop Trans 2019;19:143-150.

10. Kurtz SM, Devine JN: PEEK biomaterials in trauma, orthopedic, and spinal implants. Biomaterials 2007;28:4845-4869.

11. Chua CYX, Liu HC, Di Trani N, et al. : Carbon fiber reinforced polymers for implantable medical devices. Biomaterials 2021;271:120719.

12. Piccioli A, Piana R, Lisanti M, et al. , Italian Orthopaedic Society SIOT Bone Metastasis Study Group: Carbon-fiber reinforced intramedullary nailing in musculoskeletal tumor surgery: A national multicentric experience of the Italian orthopaedic society (SIOT) bone metastasis study group. Injury 2017;48suppl 3:S55-S59.

13. Yeung CM, Bhashyam AR, Groot OQ, et al. : Comparison of carbon fibre and titanium intramedullary nails in orthopaedic oncology. Bone Joint Open 2022;3:648-655.

14. Carbon-Fiber International Collaboration Initiative Research Group: Complications of patients with bone tumors treated with carbon-fiber plates: An international multicenter study. Sci Rep 2022;12:18969.

15. Lozano-Calderon SA, Rijs Z, Groot OQ, et al. : Outcomes of long bones treated with carbon-fiber nails for oncologic indications: International multi-institutional study. J Am Acad Orthop Surg 2024;32:e134-e145.

16. Agarwal A, Pain T, Levesque J-F, et al. , HSRAANZ PROMs Special Interest Group: Patient-reported outcome measures (PROMs) to guide clinical care: Recommendations and challenges. Med J Aust 2022;216:9-11.

17. Nooh A, Goulding K, Isler MH, et al. : Early improvement in pain and functional outcome but not quality of life after surgery for metastatic long bone disease. Clin Orthop Relat Res 2018;476:535-545.

18. Talbot M, Turcotte RE, Isler M, Normandin D, Iannuzzi D, Downer P: Function and health status in surgically treated bone metastases. Clin Orthop Relat Res 2005;438:215-220.

19. Bickels J, Kollender Y, Wittig JC, Meller I, Malawer MM: Function after resection of humeral metastases: Analysis of 59 consecutive patients. Clin Orthop Relat Res 2005;437:201-208.

20. Selek H, Başarir K, Yildiz Y, Sağlik Y: Cemented endoprosthetic replacement for metastatic bone disease in the proximal femur. J Arthroplasty 2008;23:112-117.

21. Potter BK, Chow VE, Adams SC, Letson GD, Temple HT: Endoprosthetic proximal femur replacement: Metastatic versus primary tumors. Surg Oncol 2009;18:343-349.

22. Piccioli A, MacCauro G, Rossi B, Scaramuzzo L, Frenos F, Capanna R: Surgical treatment of pathologic fractures of humerus. Injury 2010;41:1112-1116.

23. Blank AT, Lerman DM, Shaw S, et al. : PROMIS ® scores in operative metastatic bone disease patients: A multicenter, prospective study. J Surg Oncol 2018;118:532-535.

24. Clunk MJ, Gonzalez MR, Denwood HM, et al. : A peek into carbon fiber: A practical guide for high performance composite polymeric implants for orthopaedic oncology. J Orthop 2023;45:13-18, doi.

25. Yeung CM, Bhashyam AR, Patel SS, Ortiz-Cruz E, Lozano-Calderón SA: Carbon fiber implants in orthopaedic oncology. J Clin Med 2022;11:4959.

26. Sha M, Guo Z, Fu J, et al. : The effects of nail rigidity on fracture healing in rats with osteoporosis. Acta Orthop 2009;80:135-138.