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10.1245/ASO.2005.06.002
Annals of Surgical Oncology 12:322-331 (2005)
© 2005 Society of Surgical Oncology
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Original Article

Osteosarcoma of the Hand and Forearm: Experience of the Cooperative Osteosarcoma Study Group

Wolfgang Daecke, MD1, Stefan Bielack, MD3, Abdul-Kader Martini, MD1, Volker Ewerbeck, MD2, Heribert Jürgens, MD3, Rainer Kotz, MD4, Winfried Winkelmann, MD5, Hartmut Kabisch, MD6, Matthias Kevric3 and Ludger Bernd, MD2

1 Department of Hand Surgery, University of Heidelberg, Schlierbacher Landstrasse 200, 69118 Heidelberg, Germany
2 Department of Orthopedic Surgery, University of Heidelberg, Schlierbacher Landstrasse 200, 69118 Heidelberg, Germany
3 Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany
4 Department of Orthopedic Surgery, University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
5 Department of Orthopedic Surgery, University of Münster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany
6 University Children’s Hospital, Martinistrasse 52, 20246 Hamburg, Germany

Correspondence: Address correspondence and reprint requests to: Wolfgang Daecke, MD, Cooperative Osteosarkomstudiengruppe, Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie, Albert-Schweitzer-Strasse 33, D-48149, Münster, Germany; E-mail: coss{at}uni-muenster.de.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Osteosarcoma is extremely rare in the hand and forearm. Therefore, only limited data are available for planning treatment or predicting the outcome and prognosis of osteosarcoma in the peripheral upper extremity.

Methods: Epidemiological, clinical, and histopathologic data were analyzed in 39 patients with osteosarcoma of the forearm or hand who were enrolled in studies of the Cooperative German-Austrian-Swiss Osteosarcoma Study Group from 1977 to December 2000. In patients with high-grade osteosarcoma, the treatment entailed surgical resection in combination with chemotherapy, whereas patients with low-grade osteosarcoma underwent only surgery.

Results: The 5-year overall survival rate among the 33 patients with high-grade central osteosarcoma of the distal upper extremity was 86.2% ± 6.4% . The 5-year event-free survival rate was 65.4% ± 9.6% . Five of the eight patients with secondary metastases were in remission at the time of analysis. Four patients died of their disease, and two patients died of chemotherapy-related complications. The mean overall survival rate was 88.0% ± 6.5% in patients treated by wide or radical tumor resection and was 75.0% ± 21.7% in patients with nonwide margins of resection. Whether amputation or local resection was performed had no significant influence on the prognosis. All six patients whose osteosarcoma was not classified as high-grade central osteosarcoma were in remission at the time of analysis.

Conclusions: The results demonstrate a remarkably high survival rate for patients with high-grade osteosarcoma of the hand and forearm and confirm that multiagent chemotherapy in combination with wide excision is a highly effective treatment for this malignant tumor.

Key Words: Osteosarcoma • Hand • Forearm • Surgery • Chemotherapy


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The addition of chemotherapy to the treatment of osteosarcoma has substantially improved the survival rate of this generally high-grade malignant bone tumor.1 Osteosarcoma is divided into clinical/radiological subgroups (central, juxtacortical [parosteal and periosteal], and extraosseous) and histological variants (osteoblastic, chondroblastic, fibroblastic, and telangiectatic). Furthermore, tumor grading has important implications for the type and outcome of therapy. Among these subgroups, high-grade central osteosarcoma is predominant. Even though osteosarcoma is the most common primary tumor of bone, it is extremely rare in the hand and forearm.1,2 Therefore, only limited data are available for planning treatment or predicting the outcome and prognosis of osteosarcoma in the peripheral upper extremity. For patients with osteosarcoma of the hand, previous studies led to recommendations of surgical resection with wide margins.3 There is some controversy about the role of chemotherapy in the therapeutic strategy for osteosarcoma of the hand.3,4 For a better understanding of this condition, prospectively collected data obtained from the multi-center interdisciplinary Cooperative Osteosarcoma Study Group (COSS) were analyzed.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
This report includes all patients with osteosarcoma of the forearm or hand who were enrolled in studies conducted by COSS from 1977 to December 2000.5,6 Histologically confirmed primary osteosarcoma of the forearm or hand was the inclusion criterion; exclusion criteria were previous treatment such as chemotherapy and radiation. Patients were divided into two groups. All high-grade central osteosarcomas were defined as such; all other osteosarcoma variants, such as low-grade osteosarcoma (parosteal or central) and atypical high-grade osteosarcoma (periosteal or extraosseous) were defined as unconventional osteosarcoma, and patients with these tumors were analyzed separately.

Epidemiological data (sex and age) were documented. Further recorded data were the date and results of biopsy; the duration of symptoms before definitive biopsy; localization/extension of tumor; occurrence of metastases at the time of diagnosis; date and nature of any operation related to the tumor and histological features of the resected specimen (analysis of the pathology reports); and duration of follow-up. Procedures used to define the extension of the primary tumor included conventional radiography in all patients, whereas other methods (computed tomography and magnetic resonance imaging) varied over time as they became available. The minimum requirements for exclusion of primary metastases were a negative chest radiograph and a negative 99mTc-methylene diphosphonate bone scan. As of 1991, computed tomography of the chest was also mandatory. All primary metastases were to be removed surgically whenever feasible.

The recommended treatment of patients with high-grade central osteosarcoma and atypical high-grade osteosarcoma was a combination of chemotherapy and surgery. Preoperative and/or postoperative (in the COSS-77 study [the given treatment protocol], only postoperative) chemotherapy was recommended to all patients with high-grade osteosarcoma according to the COSS protocol active at the time of enrollment. All protocols included high-dose methotrexate with leucovorin rescue. In addition, doxorubicin, cisplatin, and ifosfamide with or without bleomycin, cyclophosphamide, and dactinomycin were used in varying combinations. The scheduled duration of chemotherapy ranged from 24 to 38 weeks. Definitive surgery was scheduled to take place before chemotherapy in the COSS-77 study, between protocol weeks 9 and 18 in the COSS-80 study, and between weeks 9 and 11 in all other protocols.6 The type of surgery was specified as local resection (alone or in combination with autologous or allogeneic intercalate bone grafting and vascularized bone transplantation) or amputation (above or below the elbow). It was stated that complete removal of the tumor should be attempted. All surgical margins were classified according to Enneking.7 The surgical specimens were examined histologically, and the response to chemotherapy was categorized according to the Salzer-Kuntschik criteria.8 Tumor cell destruction of >90% (Salzer-Kuntschik grades 1–3, corresponding to Huvos grades 3 and 4) was defined as a good response.9 For patients with low-grade osteosarcoma, surgical resection was the only therapy.

All studies were approved by the local ethics committee, the protocol review committee of the German Ministry for Science and Technology, or both. Before the initiation of treatment, informed consent was obtained from all patients or their legal guardians.

During follow-up, radiograms of the chest and the primary tumor were repeated at regular intervals specified in the appropriate treatment protocols. Secondary operations related to relapse, complications, or functional improvement were documented.

All patients with high-grade central osteosarcoma were evaluated on an intention-to-treat basis. Chi-square analysis and Student’s t-test were used to compare unrelated samples. Survival was calculated together with standard errors by using the Kaplan-Meier method.10 Overall survival was calculated from the date of the diagnostic biopsy until death from any cause, and event-free survival was calculated until relapse or death, whichever came first. Patients who never achieved a complete surgical remission were assumed to have experienced an event on day 1. In patients who underwent intralesional resection as their primary surgery and complete resection in a secondary definitive operation, the surgery was defined as a wide or radical resection. The log-rank test (±SD) was used to compare survival curves with reference to sex, age, extension of tumor, type of surgery, margins of resection, and response to chemotherapy.11 No statistical analyses were performed in the unconventional osteosarcoma group because the patients were few in number and inhomogeneous in their characteristics. The median age of patients including range was recorded.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Epidemiological and Clinical Data and Tumor-Related Variables
In this study, data on 39 patients with high-grade central and unconventional osteosarcoma of forearm or hand were assessed. Thirty-three patients with histologically confirmed primary high-grade central osteosarcoma were included in the analysis. In addition, six patients with unconventional osteosarcoma histologically confirmed as low-grade osteosarcoma (parosteal, n = 1; central, n = 1) or atypical high-grade osteosarcoma (periosteal, n = 3; extra-osseous, n = 1) were also evaluated.

Altogether, there were 21 females and 18 males with a median age of 15.5 years (range, 5–59 years). In the group of patients with high-grade central osteosarcoma, 16 were male and 17 female. The age ranged from 5 to 47 years, with a median age of 14 years. The median age of the four female and two male patients with unconventional osteosarcoma was 22 years (range, 8–59 years).

Of all tumors, 34 were located at the forearm (median age, 14 years; range, 5–47 years), and 5 were located at the hand (median age, 23 years; range, 11–59 years). Most high-grade central osteosarcomas were located at the distal radius (n = 20), distal ulna (n = 6), and hand (n = 3). There was no predominant site in the six unconventional osteosarcoma patients. The exact distribution of osteosarcoma is shown in Fig. 1Go.



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  		FIG. 1. Distribution of high-grade central and unconventional osteosarcomas.

 
In relation to bone diameter, 34 osteosarcomas were located centrally (33 high-grade osteosarcomas and 1 low-grade osteosarcoma), 4 juxtacortically (3 periosteal atypical high-grade osteosarcomas and 1 parosteal low-grade osteosarcoma), and 1 extraosseously (atypical high-grade osteosarcoma). The tumor extended into more than one third of the involved bone in 13 patients with high-grade central osteosarcoma. In 20 patients, extension of tumor was less than one third. For patients with a juxta-cortical or extraosseous tumor location, the extension of tumor in relation to bone diameter was not defined.

Histological assessment of specimens was performed by a local pathologist in every case and additionally assessed by a second pathologist in 4 cases or by a member of the COSS pathology panel in 24 cases. The predominant histological features are shown in Fig. 2Go. In our patients, 86% were assessed as having high-grade central and 14% as having unconventional osteosarcoma. The osteoblastic osteosarcoma was the most frequent subtype among the high-grade central osteosarcomas. Other subtypes, such as chondroblastic and fibroblastic osteosarcoma, were less frequent. Juxtacortical osteosarcoma was the predominant unconventional tumor. A total of 37 tumors were graded as high-grade osteosarcoma (33 high-grade central, 3 atypical high-grade juxtacortical, and 1 atypical high-grade extraosseous), and 2 were graded as low-grade osteosarcoma (1 low-grade juxtacortical and 1 low-grade central).



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  		FIG. 2. Predominant histomorphological subtypes of osteosarcomas.

 
The time lapse between symptoms (swelling, pain, and so on) and diagnosis ranged from 0 to 20 months. In six cases, a pathologic fracture led to the diagnosis. Staging at diagnosis revealed primary metastases in two patients with high-grade central osteosarcoma. One had multiple metastases. The second patient had a skip lesion at the adjacent bone (from proximal ulna to distal humerus).

Osteosarcoma Treatment
Twenty-four patients with high-grade central osteosarcoma completed a neoadjuvant chemotherapy regimen that included high-dose methotrexate ± doxorubicin ± cisplatin ± ifosfamide ± bleomycin, cyclophosphamide, and actinomycin D according to the COSS protocols.5,6 For these patients, the response to chemotherapy was analyzed according to the Salzer-Kuntschik criteria.8 Two other patients with high-grade central osteosarcoma died of chemotherapy-related complications during treatment. In seven cases with high-grade central osteosarcoma, chemotherapy was not performed as prescribed by the COSS protocols, and the tumor response to chemotherapy according to the Salzer-Kuntschik criteria was not evaluated. Six of these patients underwent surgery before chemotherapy because an osteosarcoma was not suspected. Two received the complete neoadjuvant regimen according to the COSS protocols after surgery. A modified COSS protocol with a varying combination of ifosfamide and doxorubicin was applied in a further three patients and was personalized additionally by carboplatin in one of them. The sixth patient, who underwent amputation despite an unknown tumor type, received no chemotherapy. Another was treated according to a different regimen. In the group of cases with unconventional osteosarcoma, four patients with atypical high-grade tumors received chemotherapy according to COSS protocols. The tumor response was not evaluated because of the limited number of cases in this group. The two patients with low-grade osteosarcoma did not receive chemotherapy.

In all 39 patients, surgery involved 27 local resections, 7 of which included autologous or allogeneic intercalate bone grafts. In eight cases (all after 1992), vascularized bone transplants (fibula in six cases and iliac crest and toe in one case) were applied. Twelve patients were treated only with local resection without skeletal reconstruction. A further 10 patients underwent primary amputation, most of them (80% ) before 1993. There were two above-elbow and eight below-elbow amputations.

The type of surgery was influenced by the anatomical region. All patients (n = 3) with osteosarcoma of the proximal radius underwent forearm exarticulation or above-elbow amputation. Patients with tumor occurrence at the proximal ulna (n = 3) were treated by resection and skeletal reconstruction. In one case, an elbow alloarthroplasty was implanted. At the distal radius (n = 21), various procedures were performed in accordance with the degree of soft tissue involvement. Surgical therapy consisted of local resection without skeletal reconstruction (n = 6), resection with nonvascularized or vascularized bone grafts (n = 7), and below-elbow (n = 5) and above-elbow (n = 1) amputation. In three patients, the wrist was stabilized by radiocarpal or ulnocarpal arthrodesis. In four of six patients with osteosarcoma of the distal ulna, skeletal reconstruction was performed. Phalanx amputation or ray amputation was the procedure for all osteosarcomas of the hand. In one case, a toe transplantation was added.

In patients with high-grade central osteosarcoma, surgery usually involved amputation (9 cases) or local resection with or without bone grafting (22 cases). In one case, the surgical report was not available for evaluation. Another patient who already had multiple metastases at the time of diagnosis did not undergo surgery at all. In six cases, the initial operation was inadequate because of the presence of a malignant bone tumor that was not suspected at the time of operation. These patients received chemotherapy immediately after confirmation of a high-grade osteosarcoma and underwent a second operation according to the study protocol. Five patients with high-grade central osteosarcoma had local resection with or without bone grafting, and an additional patient underwent below-elbow amputation.

Six patients with high-grade central or unconventional osteosarcoma underwent at least one further operation to achieve functional improvement. In two cases with unconventional osteosarcoma, secondary amputations were performed for local or systemic relapse.

Histological Response to Chemotherapy
Of the 24 appropriately treated tumors, 13 demonstrated a good response to chemotherapy (>90% necrosis) according to the Salzer-Kuntschik criteria.8 The response to chemotherapy was not assessed in the patients with high-grade central osteosarcoma who died of chemotherapy-related complications, in those who received chemotherapy divergent from COSS protocols (e.g., operation before chemotherapy), or in the cases of atypical high-grade osteosarcoma.

Surgical Remission
In 28 patients with high-grade central osteosarcoma, the margins of resection were radical or wide. In four cases with primary intralesional surgery and complete resection in an immediate secondary operation, the surgery was defined as a wide or radical resection as stated previously. Five patients with wide or radical resection developed systemic relapse at some time during their disease course. One patient with lung metastases died of the disease 12 months after diagnosis, and another with osseous metastases died 16 months after diagnosis. The other three patients with systemic relapse (lung or bone metastases) were in second complete remission at the time of analysis (8–19 years after diagnosis of osteosarcoma). Two patients died of chemotherapy-related complications during treatment. In five patients with high-grade central osteosarcoma, resection was marginal, intralesional, or not performed at all. One of the four patients with marginal or intralesional resection was the patient with the missing surgical report, but histological assessment was available. He was lost to follow-up soon after surgery. Three of the patients with nonwide resection experienced secondary lung metastases at some time during their disease course. One of them died of disease 5 years after diagnosis. The other two patients underwent segmental pulmonary resection, chemotherapy, or both, being standard for all patients with secondary lung metastases, and are still alive at the time of this writing (6–9 years after diagnosis of osteosarcoma). No local relapse was noted for the last three patients. The fifth patient did not undergo operation because of the presence of multiple metastases at the time of diagnosis and died 8 months later. None of the six patients whose primary operation was inadequate because a malignant bone tumor was not suspected at the time of the surgery and who achieved clear margins only in a second operation developed local relapse. However, two of them were among the eight cases with secondary metastases (lung), and a third patient was one of those who died of chemotherapy-related complications.

In the group of six patients with unconventional osteosarcoma, the surgical margins were wide or radical in five cases. One patient with marginal resection of a periosteal osteosarcoma developed a local relapse 10 months after the first operation. Above-elbow amputation was performed, and he is in second remission. A further patient with periosteal osteosarcoma who received primary below-elbow amputation obtained a secondary interthoracic shoulder amputation because of lymph node relapse. Wide resection was achieved in the third case. The three patients with periosteal osteosarcoma are alive in first or second remission at the time of this writing (6–8 years after biopsy). In the patient with extra-osseous atypical high-grade osteosarcoma, wide resection was performed, and he is in first remission 27 months after diagnosis. One patient with low-grade central osteosarcoma and another with parosteal (low-grade juxtacortical) osteosarcoma underwent local resection with wide margins. Both are in first remission (4 and 6 years after diagnosis).

Overall and Event-Free Survival
The median follow-up period of all surviving patients was 6.2 years (range, .7–18.8 years). The overall 5-year survival rate of the 33 patients with high-grade central osteosarcoma of the distal upper extremity was 86.2% ± 6.4% . Five of these patients died. Three patients experienced secondary metastases (two in lung and one in bone), and another experienced progressive primary metastases. Two more patients died of chemotherapy-related complications. Death was due to doxorubicin-induced cardiomyopathy in the first case and to methotrexate-related leukopenic septic shock in the second patient. In the group of patients with unconventional osteosarcoma, no tumor-related death occurred.

The 5-year event-free survival rate for high-grade central osteosarcoma was 65.4% ± 9.6% . In the group with high-grade central osteosarcoma, two primary events, two chemotherapy-related deaths, and eight secondary systemic relapses were noted. Five of the eight patients with secondary metastases were in second remission at the time of this writing, and three died. Of the five patients with secondary lung metastases, three are still in remission. Two patients with secondary metastases (lung) died. Two of three patients with secondary osseous metastases are still alive, and one died.

In the group of cases with unconventional osteosarcoma, four of six patients remained event free. One local and one systemic relapse (lymph node) occurred.

Analysis of Prognostic Factors
Because of the limited number of cases with unconventional osteosarcoma and the numerous histomorphological subtypes, prognostic factors were determined only for patients with high-grade central osteosarcoma (Table 1Go). No significant influence of sex or age on survival rate could be detected.


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  		TABLE 1. Five-year overall and event-free survival of 33 patients with high-grade central osteosarcoma
 
Because of the small number of cases with proximal tumor occurrence, a correlation between tumor location and survival could not be evaluated. Thus, out of four cases with a proximal tumor location, only two patients survived ≥5 years after diagnosis. In contrast, 25 of 29 subjects with osteosarcoma in the hand or distal forearm were alive at least 5 years after biopsy.

No significant correlation of tumor size with prognosis was noted. However, patients with limited tumor extension had an increased overall survival rate and a remarkably higher event-free survival rate in comparison with patients who had extended tumors.

Only one of two subjects with primary metastases survived ≥5 years after diagnosis. In comparison, 26 of 31 patients without primary metastases at the time of diagnosis survived at least 5 years after biopsy. Whether amputation or local resection was performed had no significant influence on the overall outcome.

The mean overall survival rate of patients with wide or radical tumor resection in the definitive operation (see Patients and Methods) was 88.0% ± 6.5% and 75.0% ± 21.7% , respectively, for patients in whom the margins of resection were less than wide (nonwide or no resection at all). Two of four deaths in the group with wide or radical resection were due to chemotherapy-related complications and were not caused by the tumor. Therefore, a significant influence of margins of resection on the overall survival rate could not be proven.

None of the 13 patients with a good response to chemotherapy according to the Salzer-Kuntschik criteria8 died as a result of the tumor. Death occurred due to chemotherapy-related complications in only one case. Of 11 patients with a poor response to chemotherapy, 3 died as a result of the tumor. However, no significant difference in survival rate with respect to the response to chemotherapy could be detected.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Osteosarcoma in the hand or forearm is rare. To our knowledge, reports on only 42 patients with osteosarcoma of the hand have been published worldwide.3,12–33 No thorough evaluation of osteosarcoma in the forearm is available. Because the COSS group follows up on most osteosarcoma patients treated during the chemotherapy era in Germany, Austria, and Switzerland, it was possible to include 5 tumors of the hand and 34 osteosarcomas of the forearm in this analysis. In comparison with our data for all investigated osteosarcomas in the trunk and extremities,6 in this study, the ratio of high-grade central osteosarcoma to unconventional osteosarcoma (6:1) was notably shifted toward unconventional osteosarcoma. This alteration was mainly a result of the high percentage of unconventional tumors in the hand (Fig. 2Go). In keeping with other authors’ results, osteosarcoma in the hand had a greater preference than osteosarcoma in other locations for arising from the surface of the bone.3

The analysis of clinical outcome revealed a 5-year overall survival rate of 86.2% ± 6.4% and a 5-year event-free survival rate of 65.4% ± 9.6% for patients with high-grade central osteosarcoma. Events in the entire follow-up period consisted of secondary metastases (lung and bone) in 24% . All patients with unconventional osteosarcoma survived, although local or systemic relapse occurred in two of six.

The survival-related parameters were remarkably high in this study (Fig. 3Go), thus confirming the effectiveness of the multidisciplinary treatment approach. Therapy consisted of (neo)adjuvant chemotherapy combined with surgical resection in 36 patients with high-grade central (or atypical high-grade) osteosarcoma and resection only in 2 subjects with low-grade osteosarcoma.



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  		FIG. 3. Kaplan-Meier curves of overall (solid line) and event-free (dashed line) survival for all 33 patients with high-grade central osteosarcoma of the forearm and hand.

 
The value of chemotherapy as an important component of multimodal treatment for high-grade osteosarcoma has been shown in the past. With chemotherapy, the overall survival rate improved from 5%–23% (4-year) to 70% –80% (3-year).1 In this study, 54% of patients in whom a response to chemotherapy was investigated demonstrated a good response to chemotherapy. None of these patients died of causes connected with the tumor. Furthermore, a large number of remissions (five of all eight) were seen in all secondary metastases. The other patients (three of eight) who died of secondary metastases were among the 46% of cases with a poor response to the initial chemotherapy. Response to chemotherapy therefore seems to be a useful prognostic factor and a predictor for outcome. However, because of the limited number of events, no significant difference in the survival rate with respect to the response to chemotherapy could be detected.

On the basis of an analysis of 1702 patients, our group recently confirmed that failure to achieve complete surgical remission is the strongest negative prognostic factor in osteosarcoma.6 In this study, the mean overall survival rate in patients with wide or radical tumor resection seemed higher (88.0% ± 6.5% ) than in patients in whom the margins of resection were less than wide (75.0% ± 21.7% ). A significant influence of the margins of resection on overall survival rate could not be proven, probably because 50% of the deaths in the group with wide or radical resection were due to chemotherapy-related complications and were not caused by the tumor.

Achieving wide tumor resection at the distal forearm is highly demanding because of the small size of the muscle and expandable soft tissue. This could be an explanation for the high number of amputations at this site. In osteosarcoma of the proximal radius, there is a potential role for limb salvage with either allografts or endoprostheses for reconstruction of bone defects. However, similarly to the situation in the distal radius, osteosarcoma of the proximal radius leads to early infiltration of vital neurovascular structures. This necessitated amputation in every patient with osteosarcoma at the proximal radius in our study.

Moreover, surgical techniques have changed substantially over time. Because of the improvements in diagnosis and microsurgical techniques, the rate of amputations has decreased notably. In our study, 80% of the amputations were performed before 1993. In contrast, all vascularized bone transplantations were performed after 1992, and this technique is now the state-of-the-art treatment for extensive bone defects.4 Fortunately, limb salvage has not resulted in a worsening of prognosis in terms of survival, as is confirmed by our results. Thus, thorough preoperative planning and experience in hand and oncological surgery, such as is available in specialized centers, are essential to achieve a reliable surgical remission and optimal functional results for patients with osteosarcoma of the peripheral upper extremity.

For osteosarcoma of the hand, Okada et al.3 recommended only wide resection, without chemotherapy. Reviewing the files of the Mayo Clinic between 1918 and 1987, Okada et al. reported 12 cases of osteosarcoma in the hand. Because >50% of their patients had been treated before 1973 (the beginning of the chemotherapy era), data on patients who received chemotherapy are limited, and the follow-up period was <5 years for most cases. In the literature,3,15,21,24,26,28–30,33 several cases (8 of 42) of tumor-related deaths due to osteosarcoma of the hand are documented, thus demonstrating the systemic nature of this disease. Therefore, in addition to wide resection, chemotherapy comparable to the COSS protocols is a fundamental component of the treatment for high-grade osteosarcoma of the hand.

Tumor location is known to be an important factor for prognosis in patients with osteosarcoma.34 An increase in the survival rate with decreasing proximity to the trunk was detected.6 Because of the small number of cases with proximal tumor occurrence, a significant effect of tumor location on survival could not be verified for our patients. Nevertheless, the overall survival rate for patients with osteosarcoma of forearm and hand in this study was higher than the average survival rate for all osteosarcomas in the COSS study.6

The timing of tumor occurrence was linked to the growth period in life.1 Thus, in accordance with other studies, high-grade central osteosarcoma of the forearm was found to be chiefly an affliction of the young, even though cases have also been documented in all other age groups. In contrast, patients with osteosarcoma of the hand seem to be older than those with involvement of the forearm. Because patients with osteosarcoma of the bone surface are known to be older than those with central osteosarcoma, the difference in age between patients with osteosarcoma of the hand (23 years; range, 11–59 years) and of the forearm (14 years; range, 5–47 years) was due to the high percentage of unconventional osteosarcomas in the hand in our study. Because of the many secondary osteosarcomas (6 of 42 cases), the median age among all published cases of osteosarcoma in the hand is, at 37 years, even higher.3,15,21,24,26,28–30,33

The 5-year overall survival rate (86.2% ± 6.4% ) and the event-free survival rate (65.4% ± 9.6% ) in patients with high-grade central osteosarcoma of the distal upper extremity were remarkably high in this study, thus confirming the effectiveness of the multidisciplinary treatment approach. These results compare favorably to the survival in the cohorts of patients with osteosarcoma of the extremities recently presented by COSS and other groups.1,2,6 Thus, multiagent chemotherapy in combination with wide excision of the tumor has proven to be a highly effective treatment for high-grade central osteosarcoma of the forearm and hand. Operative resection of the tumor without chemotherapy should be performed only in the case of low-grade osteosarcoma.


   ACKNOWLEDGMENTS
 
The patients included in this report were registered by the pediatric oncology units of the University Hospitals Berlin (n = 1), Dresden (n = 1), Erlangen (n = 1), Frankfurt (n = 2), Giessen (n = 1), Graz (n = 1), Hamburg (n = 5), Jena (n = 1), Magdeburg (n = 1), Munich (n = 1), and Münster (n = 6); the Pediatric Hospitals Bayreuth (n = 1), Johanniter Kinderklinik St. Augustin (n = 1), Olgahospital Stuttgart (n = 1), and St. Anna Kinderspital Vienna (n = 1); the medical oncology units of the University Hospitals Cologne (n = 1), Hamburg (n = 1), Technische Universität Munich (n = 1), Münster (n = 1), and Tübingen (n = 2); the Städtische Kliniken Dortmund (n = 1), Kassel (n = 1), Lübeck-Süd (n = 1), and Mannheim (n = 1); and the Orthopaedic University Hospitals Vienna (n = 2), Heidelberg (n = 1), and Zurique (n = 1) (Germany, Austria, and Switzerland). Histological assessment of specimens was performed at the pathology units of the University Hospitals Hamburg* (n = 19), Münster* (n = 10), Vienna* (n = 3), Freiburg (n = 3), Basel* (n = 1), Zurich* (n = 1), Munich (n = 1), and Ulm (n = 1) (*member of the COSS pathology panel). Supported by a grant from the Alexander von Humbolt Foundation. The Cooperative Osteosarcoma Study Group studies are supported by Deutsche Krebshilfe.

Received for publication June 1, 2004. Accepted for publication November 24, 2004.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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