1 Introduction

Limb-sparing surgery has gained prominence in bone tumor reconstruction due to its comparable survival rates and superior functional outcomes compared to amputation.¹ Post tumor resection, surgeons have multiple reconstructive options including tumor prostheses, osteoarticular allografts, and composite biological reconstructions.^2,3 Each method presents distinct short- and long-term trade-offs.⁴

Endoprosthetic reconstruction allows for early mobilization and immediate weight-bearing, expediting recovery and rehabilitation. However, this approach carries risks of prosthesis loosening and infection, alongside significant financial implications. Additionally, prosthesis survival rates vary with type and tumor location, complicated by soft tissue attachment challenges and long-term mechanical issues.^5–8

Vascularized autografts are beneficial for large pediatric defects, but pose technical challenges and donor site morbidity.⁹ Osteoarticular allografts also carry risks of osteoarthritis, infection, fracture, and non-union,¹⁰ and are often scarce with high complication rates, necessitating careful patient selection and management.

Composite biological reconstruction combines the benefits of metallic prostheses and biological methods, offering a promising solution for complex cases. Among composite biologic reconstruction methods, the recycled autograft technique stands out, particularly when allograft resources are scarce. Various techniques are employed to recycle autografts, including extracorporeal radiation,^11,12 pasteurization,^13,14 and freezing.¹⁵ The advantages of recycling autografts are numerous, including abundant availability, eliminating reliance on bone banks, facilitating biological reconstruction, minimizing disease transmission risk, reducing immunological responses, allowing soft tissue and ligament attachment, and providing a substantial bone stock reservoir.¹⁶

The use of recycled autograft techniques in bone sarcoma reconstruction is a promising area, but one that is hindered by a scarcity of robust evidence. While initial reports suggest potential benefits, the limited number of studies and variability in techniques and outcomes underscore the need for further investigation.

This study aimed to evaluate the oncological, radiological, and functional outcomes of osteo-articular reconstruction using sterilized autograft-prosthetic composites in complex peri-acetabular and extremity bone sarcoma resections at a tertiary cancer center in India. By doing so, this research seeks to inform the standardization of protocols and promote the adoption of this technique, ultimately enhancing the management of bone sarcomas.

2 Materials and methods

A retrospective analysis (2017–2022) of our primary bone sarcoma database identified 50 patients who underwent osteoarticular reconstruction using sterilized autograft-prosthetic complexes. These patients were divided into two groups: Group A (pelvic resection) and Group B (extremity resection). Collected data included patient demographics, Enneking staging, pathological diagnosis, tumor location, sterilization method, implant type, intraoperative blood loss, time to union, implant failure, oncological outcomes, and follow-up duration.

Patients with high-grade sarcomas received preoperative chemotherapy based on histology, followed by wide excision and anatomically tailored reconstruction after neoadjuvant chemotherapy.

Intraoperatively, patients were selected for sterilization methods based on tumor characteristics. Those with osteoblastic tumors or minimal cortical destruction (<1/3) underwent cryo-sterilization, while those with predominantly lytic tumors or extensive cortical destruction (≥1/3) underwent Extra Corporeal Radiation Therapy (ECRT) sterilization.

3 Statistical analyses

Functional results were assessed at final follow-up visits using the Musculoskeletal Tumor Society (MSTS) system. Analyses were performed using SPSS version 13.0 (SPSS Inc., Chicago, IL, USA), and p values of <0.05 were considered significant. The Kaplan–Meier method estimated overall survival (OS), and progression free survival (PFS). Survival times were measured from treatment initiation to the event or last follow-up. Events were defined as follows: OS as death from any cause and PFS as progression despite treatment. Calculations included all incidents until censoring.

4 Results

The patient demographics and tumor characteristics were evaluated for both groups (Table 1). The cohort's pathological diagnoses consisted of various sarcoma subtypes, including chondrosarcoma (20 cases), osteosarcoma (17 cases), primary leiomyosarcoma of bone (5 cases), and Ewing's sarcoma (8 cases). In Group A (pelvic resection), the mean age was 42 years, with a female predominance (55 %). The mean resection tumor size was 12 cm, and chondrosarcoma was the most frequent histology, accounting for 60 % of cases. In contrast, Group B (extremity resection) had a mean age of 33 years, with a slightly lower female representation (45 %). The mean resection tumor size was 7 cm, and osteosarcoma was the most common histology, occurring in 46 % of patients. There were 12 cases of proximal femur tumors, 7 of distal femur, 5 of proximal tibia and 6 of humerus. The follow-up periods also differed between the groups, with a mean of 3 years (range: 1–5 years) for Group A and a mean of 4 years (range: 3–5 years) for Group B.

The perioperative details showed significant differences between the two groups. In Group A, the mean duration of surgery was 8 hours, accompanied by a substantial mean blood loss of 2000ml. In contrast, Group B had a notably shorter mean duration of surgery, lasting 4 hours, and a significantly lower mean blood loss of 800ml. These findings highlight the more extensive and complex nature of pelvic resection surgeries compared to extremity resections. In terms of reconstruction methods, Group B patients primarily received cemented, long-stemmed prosthesis. In contrast, Group A patients who underwent pelvic resection were reconstructed using conventional total hip replacement (THR) with a constrained liner and double plate augmentation in 16 out of 20 cases. The remaining 4 patients in Group An underwent bipolar hemiarthroplasty, with 2 cases utilizing pelvic screw augmentation and the other 2 using double-plating fixation.

Post operatively, radiological union was achieved in 16 out of 20 patients in Group A, with a mean time to osteotomy union of 13.5 months. In contrast, Group B demonstrated a higher rate of radiological union, with 26 patients achieving complete union, and a shorter mean osteotomy union time of 7 months. Furthermore, the ISOLS (International Society of Limb Salvage) radiographic scores differed significantly between the groups, with Group B having a mean score of 82.8 %, indicating better bone healing and incorporation, compared to Group A's mean score of 66.9 %. The 5-year graft survival rates were estimated using Kaplan-Meier analysis, revealing an 80 % survival rate in Group A and an 86 % survival rate in Group B. These findings suggest that extremity resection patients tend to have faster and more effective bone healing compared to pelvic resection patients (see Figs. 1-2).

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Fig. 1 Pedical cryo sterilised autograft prosthetic complex A) Plain radiograph suggesting osteosclerotic lesion proximal tibia B) mri suggestive of enhancing lesion proximal tibia C) Pedical freezing proximal tibia lesion D) Long stemmed cemented implant anterior view E) Long stemed cemented implant medial view F) Immediate post op radiograph G) 4 Year post op radiograph.

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Fig. 2 Ecrt sterilised autograft prosthetic complex A) Mri pelvis - suggestive of enhancing lesion left periacetabular region B) Resected specimen C) Ecrt sterilised autograft preparation before implantation D) Sterilised autograft prosthetic complex osteosynthesis E) 1 Month post op radiograph F) 4 Years post op radiograph G) Functional outcome H) Functional outcome.

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Revision surgery was necessary in 6 out of 20 patients (30 %) in the pelvic resection group, with 2 patients requiring debridement and flap revision in the immediate postoperative period. Implant failure occurred in 4 patients (20 %), with 3 undergoing graft removal due to deep infection and subsequent mesh-plasty, and 1 undergoing graft removal due to screw failure and dislocation. In contrast, the extremity resection group had a lower revision rate of 13 %. The reasons for revision included resorption of sterilized bone and implant loosening in 2 patients, and deep infection in 2 patients. All 4 patients underwent revision to conventional mega-prosthesis (see Figs. 3-4).

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Fig. 3 Implant failure pelvic resection group A) Mri pelvis- suggestive of enhancing lesion left periacetabular region B) Resected specimen C) Ecrt treated autograft preparation before implantation D) Immediate post op E) Screw failure with dislocation F) Graft removal with meshplasty.

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Fig. 4 Implant failure extremity resection group A) Mri suggestive of enhancing lesion proximal tibia B) Resected specimen C) Liquid nitrogen treated autograft D) Long stemed cemented implant anterior view E) Clinical deep infection immediate post op period F) Graft removal and conversion to megaprosthesis with free flap c.overage.

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5 Oncological outcomes analysis

At the final follow-up, Group A had a 5-year overall survival (OS) rate of 80 %, with 16 patients alive. 5 year graft survival was 80 % (Graph 1). One patient developed local recurrence, which was treated with external hemipelvectomy, and remained disease-free at the final follow-up. Additionally, one patient experienced local and distant recurrence, while three patients had distant recurrence alone. All four patients received palliative chemotherapy and eventually succumbed to the disease, with a mean progression-free survival (PFS) of 3 months Table 2.

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Graph 1 5 yr graft survival of Group A.

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In contrast, Group B had a 5-year OS rate of 83 %. 5 year graft survival was 86 % (Graph 2). Two patients experienced local recurrence, both located in the proximal tibia, and were treated with above-knee amputation. At the final follow-up, one patient was disease-free, while the other progressed to distant recurrence. Distant recurrence occurred in six patients, all of whom received systemic treatment. At the final follow-up, one patient was alive with disease, while five succumbed to the disease, with a mean PFS of 5 months.

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Graph 2 5 yr graft survival of group B.

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6 Discussion

Recent studies on sterilized autograft prosthetic osteo-articular complex reconstruction following bone tumor resection have focused on various methods of biological reconstruction, particularly the use of liquid nitrogen and extracorporeal irradiation for sterilizing autografts. These techniques aim to address the challenges of reconstructing large bone defects after tumor resection while minimizing complications.

Our study's reconstruction methods are consistent with existing literature. Hindeskere et al.¹⁷ reported that 55 % (48 of 88) of patients undergoing biological reconstruction used liquid nitrogen-sterilized autograft (90 %, 43 of 48), extracorporeal irradiation-sterilized autograft (4 %, 2 of 48), or allograft (6 %, 3 of 48). Another study¹⁸ compared three bone graft methods in 90 patients with primary malignant bone tumors of the extremities: nonvascularized autograft (n = 27), allograft (n = 34), and recycled frozen autograft (n = 29). Our cohort of 50 patients, comprising 20 pelvic resection and 30 extremity resection cases, is comparable to these studies in terms of reconstruction methods and patient demographics.

The mean tumor size in the Hindiskere study liquid nitrogen group¹⁷ was 8.5 cm, while the mean size in the extracorporeal radiation therapy (ECRT) group was 10 cm. This is consistent with the reported range of tumor sizes in various studies, which typically span from 5 cm to over 20 cm in size, depending on the stage of diagnosis and disease extent.^19,20 Notably, our study's mean tumor sizes were comparable, with pelvic tumors averaging 12 cm and extremity tumors averaging 7 cm. This similarity in tumor size demographics suggests that our findings may be generalizable to other patient populations with similar characteristics.

Our study's perioperative blood loss is comparable to that of similar studies, with some notable differences. The studies by Hindeskere et al.¹⁷ and Gundavda MK et al.²¹ reported mean blood losses of 750 ml and 600 ml, respectively, with a higher proportion of extremity tumors. Similarly, our extremity tumor group had a mean blood loss of 600 ml. However, our pelvic tumor group experienced a significantly higher mean blood loss of 2000 ml, suggesting that pelvic tumor resections may be associated with greater blood loss compared to extremity tumor resections. This discrepancy highlights the importance of considering anatomical location in perioperative blood loss estimates.

The surgical duration in our study is consistent with that reported by Hindeskere et al.,¹⁷ who observed a median duration of 280 minutes (range: 210–510 minutes) in 41 patients undergoing liquid nitrogen sterilization of autografts. Our study's median surgical durations were 240 minutes for extremity tumors and 480 minutes for pelvic tumors, demonstrating a similar range. The longer surgical duration for pelvic tumors likely reflects the complexity and technical challenges associated with pelvic resections.

Our study's follow-up duration surpasses that of comparable studies. For instance, a study assessing functional outcomes and joint status after reconstruction with extracorporeal irradiation-treated autografts had a mean follow-up of 24 months.²¹ Similarly, a study involving 88 patients also reported a mean follow-up of 24 months.¹⁷ In contrast, our study has a mean follow-up of 36 months for the pelvic resection group and 48 months for the extremity resection group. This extended follow-up duration enhances the reliability and validity of our findings, allowing for a more comprehensive understanding of long-term outcomes.

The primary benefit of sterilized autograft prosthetic complexes lies in their potential to enhance reconstruction longevity by restoring host bone stock. However, two significant challenges exist. High rates of delayed or non-union at junctional sites increase the risk of stem loosening or stem fracture, compromising the reconstruction's integrity.

Additionally, time-dependent resorption or fracture of the treated autograft accelerates loosening or implant fracture, further jeopardizing the reconstruction's success. To address these challenges, we propose two strategies to improve junctional healing. Utilizing compressive screws across osteotomy sites can enhance stability and promote union.

Furthermore, planning an oblong osteotomy can increase the surface area for future union, facilitating more robust bone healing. By implementing these strategies, we aim to mitigate the risks associated with sterilized autograft prosthetic complexes and optimize reconstruction outcomes.

The authors of this study have previously demonstrated, in their study on vascularized fibula with and without extracorporeal radiotherapy for limb salvage surgery in Indian patients,²² that the combination of extracorporeal radiotherapy and reimplantation with vascularized fibula yields better outcomes than vascularized fibula alone. Specifically, they observed a shorter time to union (9.6 months vs 12.2 months) and a lower rate of graft-related complications (14.2 % vs 62.5 %). Based on these findings, the authors recommend augmenting vascularized fibula grafts whenever feasible.

However, the authors advise against using artificial bone graft substitutes, as they may increase the risk of secondary infection at the surgical site. This is supported by Joerg Friesenbichler et al.'s study,²³ which concluded that bone substitutes should not be used in the treatment of bony defects due to their potential to cause soft tissue inflammation and pain.

Furthermore, the authors believe that augmenting non-vascularized cortical strut grafts is not beneficial, as treated autografts already serve as a scaffold for future union. The union time of recycled autografts is likely to outlive the survival or incorporation of non-vascularized autografts.

The advent of 3-D printing and augmented reality has led to the development of innovative 3-D-printed pelvic prostheses. These prostheses feature an internal structure similar to natural bone, facilitating osseointegration and soft tissue reattachment.²⁴ While these advancements hold promise, they also come with limitations, including prolonged lead times, cost-effectiveness concerns, and resource availability issues, particularly in developing nations.

Bone sarcoma patients have various reconstruction options available, all of which offer acceptable oncological and functional outcomes. As each method has its unique limitations, treating surgeons must tailor the treatment plan to individual patients' needs. We acknowledge our selection bias, as we selected small volume pelvic tumors for sterilization techniques, which may have contributed to better functional scores and fewer complications. This bias highlights the importance of careful patient selection and personalized treatment approaches in achieving optimal outcomes.

We acknowledge several limitations in our study. Firstly, our research was conducted at a single institute, with a retrospective study design, a small sample size, and a limited follow-up period of only 5 years. Secondly, we lacked a control group for comparative analysis of outcomes. Thirdly, the heterogeneity in histological diagnoses and varied chemotherapy regimens within each group may have influenced survival rates and functional outcomes. To address these limitations, a randomized, multicentric, prospective study is needed. Such a study would provide a more comprehensive understanding by comparing functional outcomes and survival rates of various reconstruction methods over an extended follow-up period.

CRediT authorship contribution statement

Himanshu Rohela: Conceptualization, Methodology, Investigation. Anupam Lahiri: Data curation, Writing – original draft. Irfan Ahmed: Software, Visualization. Kundan Singh Chufal: Writing – review & editing. Kripa Mishra: Writing – review & editing. Rajan Arora: Validation, Supervision.

Consent

The authors declare that proper consent was taken from the patients for using and dissemination of data collected during the study. The patients understood that their identity will not be revealed.

Ethical committee approval

The study has been performed in accordance with the ethical standards in the 1964 Declaration of Helsinki.

The study has been carried out in accordance with US Health Insurance Portability and Accountability Act (HIPAA).

Status of Approval by Ethical Committee for conduction of the study titled ‘TERTIARY CANCER CENTER RESULTS OF STERILIZED AUTO-GRAFT PROSTHETIC OSTEO-ARTICULAR COMPLEX RECONSTRUCTION FOLLOWING BONE TUMOR RESECTION’ - Approved.

Declaration of generative AI and AI-assisted technologies in the writing process

During the preparation of this work the authors used Meta AI in order to make the text more readable and maintain the flow of the text. After using this tool, the authors reviewed and edited the content as needed and took full responsibility for the content of the published article.

Funding Statement

The authors declare that no funding was received for the conduction of this study.