Limb-sparing resection in pelvic sarcoma: where are we?
The treatment of pelvic sarcoma is one of the most difficult in the orthopaedic oncology world. In other areas of oncology, the development of limb-sparing techniques with megaprosthesis, vascularized autograft, or allograft has transformed the functional outcomes with similar overall and disease-free survival rates to amputation. However, it is not entirely clear where the orthopaedic literature stands regarding treatment of pelvic sarcoma and the role, if there is any, of limb-sparing surgery. This systematic review from Nashville, Tennessee (USA) sets out to establish more accurately the non-oncological complication and reoperation rates, as well as the functional outcomes, for patients after pelvic sarcoma resection and reconstruction.1 The authors did a sterling job of trawling the literature, identifying 2350 potential studies, all of which were reviewed. The inclusion criteria yielded 22 Level-IV studies with a total of 801 patients. A wide range of reconstructive techniques were used across these studies, including allografts, allograft-prosthesis composites, saddle prostheses, custom endoprostheses, and irradiated autografts. Pooled means were calculated for five-year patient survival (55%), non-oncological complication rate (49%), non-oncological reoperation rate (37%), and Musculoskeletal Tumor Society score (65%). The authors concluded that the non-oncological complication and reoperation rates for pelvic reconstruction are high, whilst five-year survival is poor. Although functional outcomes were found to be satisfactory, they may not be better than a resection without reconstruction. The authors recommend that forgoing pelvic reconstruction should be considered, especially in patients with poor overall prognosis.
Paediatric soft-tissue sarcoma: changing practice and outcomes
The role of adjuvant therapies in surgical oncology has grown as understanding of tumour mechanics, optimization of outcomes and more accurate imaging, and effective chemotherapy and radiotherapy techniques have become available. In the domain of soft-tissue sarcoma, radiotherapy is now universally accepted to be an essential component for obtaining adequate local control, especially in the setting of organ- and function-preserving surgery. However, radiotherapy in children with maturing tissues of low-radiation tolerance has undesirable late effects, both in terms of local complications and tumour neogenesis. Over the past few decades, the refinement and development of techniques that reduce the volume of normal tissues being irradiated have made radiotherapy a more accessible treatment to the paediatric population. This study from Mumbai (India) aimed to evaluate long-term clinical outcomes, adverse effects, and the practice of interstitial brachytherapy for paediatric soft-tissue sarcomas.2 In brachytherapy, the radiation is delivered locally, rather than via external beam radiation, and is often combined with either external beam radiotherapy (as in soft-tissue sarcoma) or chemotherapy. In this study, 105 children (with a median age of ten years) were treated with brachytherapy for their soft-tissue sarcoma. The treatment strategy in all cases included wide local excision and brachytherapy with or without external beam radiotherapy. Most patients reported here (n = 85, 81%) received brachytherapy alone. Local control (83%), disease-free survival (66%), and overall survival (73%) rates all looked very promising at ten years (median follow-up, 65 months). The important take-home messages from this series are that children receiving brachytherapy alone had comparable reported local control to those in whom it was combined with external beam radiotherapy (84% vs 80%). The complications observed were: wound complications (6%), subcutaneous fibrosis (25%), limb oedema (6%), and secondary skeletal abnormalities (3%). One child went on to develop a second malignancy after seven years. The authors therefore concluded, based on their series, that interstitial brachytherapy with or without external beam radiotherapy leads to very good long-term outcomes. When used judiciously, they reported that radical brachytherapy alone resulted in excellent local control and function with minimal treatment-related morbidity.
The role of surgical margins in chondrosarcoma
The authors of this novel study from Birmingham (UK) sought to iron out some of the uncertainties surrounding surgical margin status in chondrosarcoma surgery.3 They investigated the relationship between surgical excision margins and local recurrence-free survival, and the role of local recurrence in disease-specific survival in chondrosarcoma of the limb and pelvis. Their series was based on 341 pelvic and limb chondrosarcomas that were treated over a 12-year period and included in the study on a retrospective basis. During the study itself, local recurrence developed in just under a quarter (23%) of cases. After an initial univariate analysis, pelvic location, pathological fracture, margin, and grade were deemed to be significant factors for local recurrence. Subsequent multivariate analysis revealed surgical margin and pelvic location to be positive factors for local recurrence. As would be expected, grade 1 and grade 2 chondrosarcomas were found to be negative prognostic factors for local recurrence. Univariate analysis for disease-free survival showed that the presence of pathological fracture, central versus peripheral location, grade of the tumour, and development of local recurrence were all significant factors. An unusual but welcome addition, given the high numbers of dichotomous outcomes, was the addition of competing risk analysis, in which local recurrence was statistically significant for disease-free survival in grade 2 and grade 3 tumours. The authors therefore concluded that surgical margins determine local recurrence rates in all chondrosarcoma grades, but that local recurrence is only a determinant of disease-free survival in grade 2 and grade 3 tumours. They recommended that, whilst narrow resection margins are acceptable in grade 1 tumours, a minimum 4 mm margin should be the aim in all cases due to the unreliability of biopsy in predicting the final grade.
Neoadjuvant chemotherapy in non-metastatic high-grade pelvic osteosarcoma?
For patients with high-grade osteosarcoma, the most common treatment strategy is neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy. With this in mind, the authors of this retrospective study from Beijing (China) aimed to address three questions.4 First, does neoadjuvant chemotherapy followed by delayed surgery offer a survival benefit to patients with non-metastatic, high-grade pelvic osteosarcoma compared with immediate surgery and adjuvant chemotherapy? Second, is the timing of chemotherapy and surgery associated with a difference in the survivorship free from local recurrence and the risk of complications? Finally, is the threshold of 90% necrosis after neoadjuvant chemotherapy appropriate to distinguish responders from non-responders in patients with pelvic osteosarcoma? Their work was based on their own reported series of 112 patients with non-metastatic, high-grade primary pelvic osteosarcoma. Of these patients, 93 underwent tumour resection with chemotherapy and so were potentially eligible. Four patients were lost to follow-up and the remaining 89 were included. Patients were allocated into two groups, depending on the timing of their surgery and chemotherapy: neoadjuvant chemotherapy followed by delayed surgery and adjuvant chemotherapy (n = 56); and immediate surgery followed by adjuvant chemotherapy (n = 33). The total duration, dosing regimen, and agents used for chemotherapy were similar in both groups. There was no survival benefit found in the patients treated with neoadjuvant chemotherapy followed by delayed surgery. The likelihood of successful limb salvage was comparable for the two groups, at 89% in the neoadjuvant chemotherapy group versus 91% in the immediate surgery group. Similar five-year local recurrence-free survival rates were also similar for the two groups (68% vs 67%), and there was no apparent difference in survival between patients whose tumours demonstrated more than 90% necrosis. It should be noted, however, that only four of 56 patients in the neoadjuvant chemotherapy group demonstrated 90% necrosis. This finding should therefore be interpreted with caution. The authors concluded that, whilst the treatment allocation in this series was not randomized, the authors did administer a standard multidrug chemotherapy regimen. They were unable to demonstrate a survival advantage with chemotherapy before delayed surgery compared with immediate surgery in patients with non-metastatic high-grade pelvic osteosarcoma, and suggest that the decision on chemotherapy timing should be made for reasons other than survival. Such factors include the ability to assess necrosis, considerations of anticipated margin status, and whether there is sufficient time to plan resection and reconstruction options with the patient. They recommend that a prospective trial is needed to confirm this conclusion.
Osteosarcoma and age: the Japan experience
The authors of this simple study from Tokyo (Japan) aimed to establish the effect of patient age on the clinical features, prognosis, and prognostic factors of patients presenting with osteosarcoma.5 Their series consisted of 1043 osteosarcoma patients, who were identified using the Bone and Soft Tissue Tumor Registry in Japan. These patients were categorized into three age brackets: those younger than 40 years old (n = 760), those aged between 41 and 64 years (n = 173), and those older than 65 years (n = 110). There was a differing pattern of presentation and outcomes within the groups, with patients older than 65 years showing a significantly higher proportion of tumours arising in the trunk and with metastasis at diagnosis. The five-year disease-specific survival was significantly worse for patients older than 65 years with metastasis (33%) versus without metastasis (39%) present at diagnosis. Adjuvant chemotherapy did not significantly improve disease-specific survival in the two older groups of patients (41 to 64 years, 65+ years), although it did lead to significantly better survival in patients younger than 40 years. Clearly there is some food for thought here, with little benefit seen in adjuvant chemotherapy in the older population of osteosarcoma. This is useful information to know, whether discussing risks in a multidisciplinary team (MDT) setting or, indeed, with the patients themselves.
Reconstructing diaphyseal tumours using radiated (50 Gy) autogenous tumour bone graft
Whilst a well-established technique, there has been little published in recent years on autogenous irradiated bone graft reconstruction. Generally speaking, the thoughts of orthopaedic oncologists have tended to linger instead on megaprosthesis reconstruction options in recent years. However, in diaphysis tumours where it is possible to preserve the adjoining joints after intercalary resection, the use of irradiated autogenous bone remains a potentially attractive one. The advantage of a biological reconstruction is that, if uncomplicated, it may provide a more durable alternative to megaprosthesis. From a surgical perspective, reimplanting the patient’s own sterilized tumour bone is one of the more appealing biological reconstructions, as it circumvents the logistical issues involved in obtaining size-matched strut allografts. The risk of disease transmission and rejection – which, although rare, is nevertheless a possibility in bulk bone grafting – is also obviated. In their series of 70 non-metastatic patients, these authors from Mumbai (India) evaluated their surgical outcomes with a focus on the complications associated with bulk allografting.6 All patients had high-grade tumours of the limb, with diagnoses of both osteosarcoma (n = 38) and Ewing’s sarcoma (n = 32). The minimum follow-up was three years. Patients underwent reconstruction with intercalary extracorporeal radiotherapy (ECRT) grafts, which were sterilized with 50 Gy and reimplanted back into the original position in the diaphyseal region. The outcomes reported focused on graft survival and union at the two osteotomy sites. A higher proportion of metaphyseal osteotomies (91%) united without additional intervention compared with diaphyseal osteotomies (71%). The addition of a small plate at diaphyseal osteotomy appeared to reduce the incidence of nonunion (17% vs 31% for metaphyseal osteotomy). There was no evidence, however, that the addition of morsellized allograft improved the likelihood of bony union. At final follow-up, 19 patients had died and two were lost to follow up. The cohort suffered seven (10%) local recurrences, all in the soft tissues, and a quarter (25%) of patients needed removal of the graft during the period of the study. Overall five-year survival for the ECRT graft was 79%, or 84% excluding removal for local recurrence. The authors therefore concluded that reimplanting sterilized tumour bone using 50 Gy for tumour ablation was an easily applicable, oncologically safe biological reconstruction option for primary diaphyseal tumours of the limb.
Fibular epiphyseal transfer in primary sarcoma of bone
The difficulties of treating epiphyseal tumours in children are readily apparent. We were interested to see this paper from Birmingham (UK), in which the authors describe the outcomes following proximal humeral reconstruction using a technique involving vascularized fibular epiphyseal transfer.7 All of the children in this study had diagnoses of primary bone sarcomas. In this small ‘proof of concept’ study, the authors retrospectively reported 11 patients: six with a diagnosis of Ewing’s sarcoma and five with osteosarcoma. The age at the time of surgery ranged from two to eight years. The mean age at the time of surgery was five years, with a mean follow-up of 5.2 years. At both five and ten years, the overall reported survival rate was 91%, and all but one of the patients were alive at the time of the final review. There were, however, multiple complications: seven fractures, four transient nerve palsies, and two instances of patients developing avascular necrosis of the graft. The fractures all presented within one year following surgery, and all seven united with conservative management. Hypertrophy and axial growth were observed in the nine patients who did not have avascular necrosis of the graft. At final follow-up, the mean modified functional Musculoskeletal Tumour Society score was 77% and the mean Toronto Extremity Salvage Score (TESS) was 84%. The authors reported, based on this study, that vascularized fibular epiphyseal transfer preserves function and growth in young children following excision of the proximal humerus for a malignant bone tumour. Although function is favourable when compared with other limb-salvage procedures in children, here at 360, we agree with the authors’ conclusion that longer-term analysis is required to determine if this technique proves to be durable into adulthood.
References
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