General Principles of Intralesional Treatment of Bone Tumors

James P. Norris, MD, FAAOS

Dr. Norris or an immediate family member serves as a paid consultant to or is an employee of Adaptimmune.

ABSTRACT

Intralesional resection of bone lesions is characterized by entering a bone lesion through an osseous defect and removing the entirety of the lesion internally. This approach is suitable in cases of aggressive benign lesions, low-grade malignant lesions, and metastatic lesions. In comparison with the wide excision required of more aggressive malignancies, intralesional resection attempts to preserve function at the expense of local control in lesions for which recurrence does not carry a significant risk of morbidity or mortality. Commonly studied lesions include aneurysmal bone cysts, giant cell tumors of bone, chondroblastomas, and atypical cartilaginous tumors; however, the same principles can be applied to any bone lesion for which this is suitable. Local adjuvants, including mechanical (high-speed burr), chemical (hydrogen peroxide, ethanol), and thermal (argon beam, polymethyl methacrylate) strategies, have been shown to decrease local recurrence rates to varying degrees and in various combinations. Percutaneous intralesional therapies such as embolization for aneurysmal bone cysts and radiofrequency ablation for osteoid osteomas have also proved to be effective. Structural augmentation with void fillers or internal fixation implants is not universally used and is dictated by the demands of the given case.

INTRODUCTION

Although various techniques exist, intralesional resection of bone tumors—be they aggressive benign lesions, certain low-grade malignant lesions, or metastatic lesions—is generally characterized by accessing the bone through a surgically created cortical window, a preexisting fenestration created by the lesion itself or a pathologic fracture. This is followed by mechanical extraction of lesional tissue from within the tumor itself to remove gross disease. In distinction to the negative margin achieved by wide resection, the margin status of an intralesional resection is intentionally irrelevant and by definition contaminated. It is important to discuss the indications for this type of resection and explore the various techniques used to increase effectiveness and decrease complications, along with oncologic and functional outcomes as available.

INDICATIONS

The contaminated margins of an intralesional resection are appropriate only in lesions for which this strategy does not incur significant oncologic risk. First is the case of aggressive benign bone tumors that threaten the structural integrity of host bone. Aneurysmal bone cysts (ABC),¹^,²^,³^,⁴^,⁵ unicameral bone cysts (UBCs),⁶^,⁷ giant cell tumors (GCT) of bone,⁸^,⁹^,¹⁰^,¹¹^,¹²^,¹³^,¹⁴^,¹⁵^,¹⁶^,¹⁷^,¹⁸^,¹⁹ and chondroblastomas²⁰^,²¹^,²²^,²³^,²⁴^,²⁵ are well-studied aggressive benign bone tumors commonly managed with intralesional resection. Similar principles can be applied to osteoblastomas,²⁶ fibrous dysplasia,²⁷ chondromyxoid fibromas, and destabilizing nonossifying fibromas, among others. Although GCTs have a low metastatic potential, the minimal mortality risk does not warrant a wide resection. In addition, the consequences of local recurrence are manageable and can be successfully treated with revision surgery. Even self-limiting lesions such as nonossifying fibromas can warrant intralesional treatment if the bone is significantly destabilized (Figure 1). The second case in which intralesional resection is used is that of low-grade malignancies, most successfully grade I chondrosarcomas (recently reclassified as atypical cartilaginous tumor in the appendicular skeleton by the World Health Organization).²⁸^,²⁹^,³⁰^,³¹ The metastatic potential and mortality risk are low and are unaffected by local control strategies. Therefore, intralesional strategies are typically favored in this setting because of their decreased complication rate and better functional outcomes. In addition, local recurrences can be managed with either revision surgery or conversion to wide excision and reconstruction. The third case is bony metastatic lesions. Given the palliative goal of managing metastatic bony lesions, intralesional treatment can decrease disease burden and provide immediate bony stability. Neither a contaminated resection nor disease progression will affect the patient’s overall mortality in this particular setting.

FIGURE 1 Radiographs from a 12-year-old girl with a large nonossifying fibroma of the radius. The bone had been fractured several times (A). Because of the persistent fractures, the patient underwent curettage, allograft bone placement, and flexible intramedullary nail placement (B). The nail was subsequently removed, and the lesion healed completely (C and D). Aggressive, extended intralesional treatment was not used in an effort to preserve local biology in the setting of a typically self-limiting lesion.

LOCAL ADJUVANTS

During intralesional resection, curets are typically used to remove visible lesional tissue before the planned reconstruction necessary for the defect. In addition, many studied techniques have been characterized by so-called extended curettage, which uses local adjuvant treatments to further remove or kill tumor cells. The goal of these strategies is to further decrease the risk of recurrence. The point must be made that the literature is rife with variability and retrospective review, making it difficult to determine the exact contributions of any one specific element. To highlight this variability, two retrospective reviews published 4 years apart in the same journal drew opposite conclusions about the effect on local control of a secondary ABC within a GCT managed with intralesional resection. A review of 60 patients found a significant increase in local recurrence on univariate and multivariate analysis, whereas a similar 2023 review of 36 patients found no difference on multivariate analysis.³²^,³³ Despite these limitations, obvious trends are noted throughout the literature and are summarized in the following section.

Mechanical Adjuvants

Curettage is a mechanical process to physically remove lesional cells from the tumor cavity. However, the zone of transition varies from lesion to lesion. Sometimes there is a sclerotic border and narrow zone of transition, such as in a UBC or ABC, and other times the lesions percolate into the surrounding cancellous bone as in metastatic lesions. Thus, a high-speed burr has become a widely
used tool to remove a narrow rim of bone surrounding the lesion cavity. The theory is that microscopic and macroscopic disease can be harbored in small irregularities or pits in the periphery of the tumor cavity and surrounding cancellous bone. By burring away several millimeters of bone circumferentially around the tumor, tumor cells are more completely removed, thus lowering local recurrence.

Curettage was popularized by a study that reported a 12% local recurrence rate in 34 ABCs when curettage was used with the additional use of a high-speed burr; this technique has become commonplace in the intralesional treatment of patients with bone tumors.² Similar success has been seen in subsequent studies of ABCs,⁵ GCTs,⁸^,¹⁰ chondroblastomas,²²^,²³^,²⁴ and low-grade chondrosarcomas or atypical cartilaginous tumors.²⁸ A systematic review of 387 GCTs managed with curettage and burring with or without the use of chemical or thermal adjuvants suggested no additional benefit when chemical and thermal means were used.⁸ Another review of 214 GCTs suggested a cumulative effect of high-speed burring, peroxide, and polymethyl methacrylate (PMMA), with both burring and PMMA being successful in isolation to decrease the rate of local recurrence⁹ (Figure 2). Regardless of the effect size and use of additional adjuvants, the literature supports the meticulous removal of tumor cells with the use of a high-speed burr.

FIGURE 2 Radiograph (A) and magnetic resonance image (B) of a lytic, expansile lesion of the left proximal tibial epiphysis and metaphysis histologically confirmed to be a giant cell tumor of bone. C, Radiograph shows the defect left after curettage and high-speed burring, highlighted with a radiopaque dye. The lesion was treated with hydrogen peroxide and filled with polymethyl methacrylate. Plate augmentation was used to further support the articular surface because of the size of the lesion and proximity to the joint. D, Radiograph shows no local recurrence at 15 months postoperatively.

Thermal Adjuvants

Thermal adjuvants have taken several forms over the past several decades. If the temperature of the surrounding bone can be brought above or below that at which living cells can survive, the zone of tumor treatment can be extended past the visible tumor cavity. Liquid nitrogen—an early thermal adjuvant—was found to have a wide zone of histologic necrosis within cancellous bone of up to 12 mm.³⁴ Although effective at treating tumor cells, this practice has fallen out of favor because of the high rate of complications, namely pathologic fracture and local tissue necrosis.³⁵^,³⁶

PMMA is commonly used after curettage to increase structural stability, but the exothermic reaction of PMMA curing provides an additional thermal treatment to the surrounding bone. Although small boluses of cement do not create temperatures high enough to cause significant tumor necrosis, larger boluses have been modeled to cause a zone of necrosis as wide as 6 mm.³⁴^,³⁷ Retrospective studies have suggested increased local control when PMMA is used after curettage. This has been well established in the treatment of GCTs.⁹^,¹¹^,¹⁴^,¹⁹ A review of 330 patients treated with curettage, burr, and pulse lavage with or without cement found that the local recurrence rate was decreased by half with the addition of PMMA.¹¹ Similarly, a systematic review of 1,293 patients across 6 studies found a twofold increase in the rate of local recurrence when bone graft was used compared with PMMA, regardless of the addition of other local adjuvants.¹⁹ This is somewhat tempered by the results in the distal radius from another study, which suggest no additional benefit to PMMA use, but this may be explained by the smaller cement bolus that would be used in the relatively smaller radius.³⁸ Cement has other key benefits. First, it provides immediate structural stability. Second, the bone-cement interface is radiographically stark, which aids in the assessment of new lucency that might signal a local recurrence (Figure 3). Bone graft or void fillers resorb over time; when used, it can be difficult to determine if similar lucencies represent tumor recurrence or simply graft resorption.

FIGURE 3 Radiograph (A) and magnetic resonance image (B) of a right tibial aneurysmal bone cyst in a 16-year-old girl. C, Radiograph shows that the patient underwent curettage, high-speed burring, polymethyl methacrylate (PMMA) packing, and plate fixation. She continued to have pain postoperatively, and repeat radiograph (D) revealed a new lytic lesion at the proximal aspect of the cement mantle (arrow). These images highlight one additional benefit of PMMA: its relative radio-opacity allows for easy identification of new lucency. If a similar lucency had occurred after use of bone graft or other resorptive void filler, it would be more difficult to determine if the lucency was caused by graft resorption or disease recurrence. The patient required revision intralesional treatment and additional PMMA packing.

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