Prognostic factors in the treatment of Ewing's sarcoma. The Ewing's Sarcoma Study Group of the German Society of Paediatric Oncology CESS 81

From 1981 up to February 1985, a total of 93 protocol patients entered the study CESS 81. The protocol recommended an initial 18-week period of polychemotherapy (VACA) followed by local therapy and two additional cycles of chemotherapy. Local therapy consisted either of radical surgery or of incomplete resection plus postoperative irradiation with 36 Gy or of radiotherapy alone (46 and 60 Gy). Centrally located lesions were always irradiated with 60 Gy. This article summarizes the data after 5 years. Data of 93 patients were analysed in October 1986 after a median follow-up of 37 months. The projected 5-year survival is 50%. The relapse rate was 42%, distant relapses occurred in 19%, local (plus distant) relapses in 23%. Most of the relapses occurred during the first 3 years of observation. Failure rate was high in patients undergoing irradiation alone (44%). Initial tumour mass (greater than 100 ml) and histopathologic response to initial chemotherapy were identified as major prognostic factors. Tumour site and type of local therapy were not significant if patients were categorised by tumour volume. In small lesions, surgery and radiotherapy were equally effective. In large lesions greater than 100 ml volume, a trend towards a better prognosis in surgically treated patients was observed. The results of CESS 81 emphasize the importance of permanent local control in Ewing's sarcoma even in the presence of systemic control by an effective multi-drug chemotherapy.     

Ewing's sarcoma of the ribs. A report from the Cooperative Ewing's Sarcoma Study

31 patients with primary Ewing's sarcoma of the ribs were treated according to the protocols of CESS 81, CESS 86P and CESS 86. The results of treatment were reviewed and analysed. 24 patients presented with localised disease and 7 with regional disease. 20 of 24 localised cases and 6 of 7 regional cases underwent tumour resection. All but 2 localised cases received irradiation. The cumulative relapse-free survival (RFS) rate of 31 patients was 61% at 12.8 years. Patients with poor prognosis had tumour of the upper ribs (P = 0.0338), the posterior component of the ribs (P = 0.0597), or regional disease (P = 0.0001). Tumour size, existence of pleural effusion, type of the surgical margin and response to chemotherapy were not significant prognostic factors. Most of the localised cases could be controlled by combined treatment, but in regional cases prognosis remained poor.     

Local therapy in localized Ewing tumors: results of 1058 patients treated in the CESS 81, CESS 86, and EICESS 92 trials

PURPOSE: The impact of different local therapy approaches on local control, event-free survival, and secondary malignancies in the CESS 81, CESS 86, and EICESS 92 trials was investigated. METHODS AND MATERIALS: The data of 1058 patients with localized Ewing tumors were analyzed. Wherever feasible, a surgical local therapy approach was used. In patients with a poor histologic response or with intralesional and marginal resections, this was to be followed by radiotherapy (RT). In EICESS 92, preoperative RT was introduced for patients with expected close resection margins. Definitive RT was used in cases in which surgical resection seemed impossible. In CESS 81, vincristine, adriamycin, cyclophosphamide, and actinomycin D was used. In CESS 86, vincristine, adriamycin, ifosfamide, and actinomycin D was introduced for patients with central tumors or primaries >100 cm(3). In CESS 92, etoposide, vincristine, adriamycin, ifosfamide, and actinomycin D was randomized against vincristine, adriamycin, ifosfamide, and actinomycin D in patients with primaries >100 cm(3). RESULTS: The rate of local failure was 7.5% after surgery with or without postoperative RT, and was 5.3% after preoperative and 26.3% after definitive RT (p = 0.001). Event-free survival was reduced after definitive RT (p = 0.0001). Irradiated patients represented a negatively selected population with unfavorable tumor sites. Definitive RT showed comparable local control to that of postoperative RT after intralesional resections. Patients with postoperative RT had improved local control after intralesional resections and in tumors with wide resection and poor histologic response compared with patients receiving surgery alone. Patients with marginal resections with or without postoperative radiotherapy showed comparable local control, yet the number of patients with good histologic response was higher in the latter treatment group (72.2% vs. 38.5%). CONCLUSION: Patients with resectable tumors after initial chemotherapy had a low local failure rate. With preoperative RT, local control was comparable. RT is indicated to avoid intralesional resections. After intralesional or marginal resections and after a poor histologic response and wide resection, postoperative RT may improve local control.     

A long-term review of the treatment of patients with Ewing's sarcoma in one institution.

AIMS: The treatment of patients suffering from Ewing's sarcoma has changed over the last three decades. We report the analyses, significant prognostic factors, interdisciplinary approach and development of therapy in one institution in Austria. METHODS: One hundred and forty-two patients treated for Ewing's sarcoma between 1949 and 1994 were reviewed. Median follow-up was 8.5 years. Fifty-six patients were treated between 1949 and 1980 (group 1), and 86 patients between 1981 and 1994 (group 2). Patients in group 1 were treated with polychemotherapy. Patients in group 2 were treated with a neoadjuvant CESS (Cooperative Ewing's Sarcoma Study) regimen. In group 1, 24 patients underwent biopsy only, 32 patients had a definitive operation, 48 patients received either radiation therapy only or additional radiation therapy compared with in group 2: 6, 80 and 44 cases, respectively. RESULTS: Five-year overall survival (OS) increased from 27% to 57%. Significant prognostic factors for OS were pre-operative metastases (P=0.0001), tumour location (P=0.0048), type of chemotherapy (P=0.002) and response to chemotherapy (P=0.0004). Chemotherapy (P=0.037), tumour location (P=0.0017) and metastases at diagnosis (P=0.0025) were significant. CONCLUSION: The most effective treatment of Ewing's sarcoma is chemotherapy.     

Radiotherapy in Ewing tumors of the vertebrae: treatment results and local relapse analysis of the CESS 81/86 and EICESS 92 trials

PURPOSE: Treatment results in patients with Ewing tumors of the vertebrae enrolled in the Cooperative Ewing's Sarcoma Study (CESS) 81, 86, and the European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) 92 trials were analyzed with special emphasis on radiation-associated factors. PATIENTS AND METHODS: A retrospective analysis was performed on 116 patients with primary tumors of the cervical, thoracic, or lumbar vertebrae treated between 1981 and 1999. Furthermore, a relapse analysis was done on those patients who underwent radiotherapy and subsequently had a local recurrence. RESULTS: A total of 64.6% of the patients received definitive radiotherapy; 27.5% of patients had surgery and radiotherapy. Only 4 patients (3.4%) underwent definitive surgery. Twenty-seven patients presented with metastases at diagnosis. 22.4% of the total group developed a local relapse. Among the subgroup with definitive radiotherapy, local recurrence was seen in 17 of 75 patients (22.6%). Event-free survival and survival at 5 years were 47% and 58%, respectively. Of the 14 evaluable patients with a local relapse after radiotherapy, 13 were in-field. No correlation between radiation dose and local control could be found. CONCLUSION: Surgery with wide resection margins is rarely possible. The results after definitive radiotherapy in vertebral tumors are comparable to those of other tumor sites when definitive radiotherapy is given. Nearly all local relapses after radiotherapy are in-field.     

Localized Ewing tumor of bone: final results of the cooperative Ewing's Sarcoma Study CESS 86.

PURPOSE: Cooperative Ewing's Sarcoma Study (CESS) 86 aimed at improving event-free survival (EFS) in patients with high-risk localized Ewing tumor of bone. PATIENTS AND METHODS: We analyzed 301 patients recruited from January 1986 to July 1991 (60% male; median age 15 years). Tumors of volume >100 mL and/or at central-axis sites qualified patients for "high risk" (HR, n = 241), and small extremity lesions for "standard risk" (SR, n = 52). Standard-risk patients received 12 courses of vincristine, cyclophosphamide, and doxorubicin alternating with actinomycin D (VACA); HR patients received ifosfamide instead of cyclophosphamide (VAIA). Tumor sites were pelvis (27%), other central axis (28%), femur (19%), or other extremity (26%). The initial tumor volume was <100 mL in 33% of cases and > or =100 mL in 67%. Local therapy was surgery (23%), surgery plus radiotherapy (49%), or radiotherapy alone (28%). Event-free survival rates were estimated by Kaplan-Meier analyses, comparisons were done by log-rank test, and risk factors were analyzed by Cox models. RESULTS: On May 1, 1999 (median time under study, 133 months), the 10-year EFS was 0.52. Event-free survival did not differ between SR-VACA (0.52) and HR-VAIA (0.51, P =.92). Tumor volume of >200 mL (EFS, 0.36 v 0.63 for smaller tumors; P =.0001) and poor histologic response (EFS, 0.38 v 0.64 for good responders; P =.0007) had negative impacts on EFS. In multivariate analyses, small tumor volumes of <200 mL, good histologic response, and VAIA chemotherapy augured for fair outcome. Six of 301 patients (2%) died under treatment, and four patients (1.3%) developed second malignancies. CONCLUSION: Fifty-two percent of CESS 86 patients survived after risk-adapted therapy. High-risk patients seem to have benefited from intensified treatment that incorporated ifosfamide.     

Radiotherapy in ewing’s sarcoma and PNET of the chest wall: results of the trials cess 81, cess 86 and eicess 92

Purpose: Treatment results and the pattern of relapse were evaluated in the multimodal treatment of Ewing’s sarcomas of the chest wall.

Methods and Materials: In a retrospective analysis, 114 patients with non-metastatic Ewing’s sarcoma of the chest wall were evaluated. They were treated in the CESS 81, CESS 86, or EICESS 92 studies between January 1981 and December 1993. The treatment consisted of polychemotherapy (VACA, VAIA, or EVAIA) and local therapy, either surgery alone (14 patients), radiotherapy alone (28 patients) or a combination of both (71 patients). The median follow-up was 46.6 months (range 5–170). A relapse analysis for all patients with local or combined relapses was performed.

Results: Overall survival was 60% after 5 years, event-free survival was 50%. Thirty-seven patients had a systemic relapse (32.4%), 11 patients had a local relapse alone (9.6%), and 3 patients had a combined local and systemic relapse (2.6%). The risk to relapse locally after 5 years was 0% after surgery alone, 19% after radiation alone, and 19% after postoperative irradiation. None of the 8 patients with preoperative irradiation have failed locally so far. With the introduction of central radiotherapy planning in CESS 86, local control of irradiated patients improved. Ten of 14 patients with local failure could be evaluated in the relapse analysis: 3 patients had an in-field relapse, 4 patients had a marginal relapse, 2 patients had a relapse outside the radiation fields, and 1 patient failed with pleural dissemination. Six treatment deviations were observed.

Conclusion: Local control was best after surgery alone in a positively selected group of patients. Local control after radiation or combined radiation and surgery was good. With diligent performance of radiotherapy, it will be possible to further improve the results in the radiotherapy group.     

Local and distant control in non-metastatic pelvic Ewing's sarcoma patients

BACKGROUND AND OBJECTIVES: Due to possible complication and loss of function, surgery is not often indicated in pelvic Ewing's sarcoma (ES). The purpose of this study was to review our experience and evaluate the role of different local treatment in non-metastatic pelvic ES patients. METHODS: One hundred twenty-nine patients with pelvic ES were treated at our institution between 1975 and 1999. We excluded patients presenting metastases, patients who had died of other causes, or those with incomplete clinical documentation. Among the 73 eligible patients, 17 (23%) with progression of tumor growth during induction chemotherapy eventually died. The analysis was focused on the remaining 56 patients with good or stable clinical response to the chemotherapy. RESULTS: Patients treated with surgery, with or without radiation therapy, had a better local control (82.6% vs. 66.7%) and a significantly higher rate of 5-year EFS (73.9% vs. 30.3%, P = 0.036) than those who were only treated with local radiation therapy. CONCLUSION: Chemotherapy is the key factor in the treatment of pelvic ES. In our series, surgical treatment was associated with good prognosis for pelvic ES. The use of radiotherapy alone was less effective and should be only used in non-operable patients. Radiotherapy after surgery as a rescue method might not act effectively, while preoperative radiotherapy was associated with good clinical response and should be recommended.     

Multidisciplinary treatment of primary Ewing's sarcoma of bone. A 6-year experience of a European Cooperative Trial

The German Society of Pediatric Oncology in 1981 initiated the Cooperative Ewing's Sarcoma Study (CESS 81) using a four-drug combination of chemotherapy prior to definitive local control with surgery and/or radiation. From January 1, 1981 until February 28, 1985, 93 patients were registered at the trial office from 54 participating institutions in West Germany, Austria, Switzerland, and the Netherlands. On February 1, 1987, 54 of 93 patients were disease-free. Using the Kaplan-Meier life table analysis, the estimated disease-free survival (DFS) rate was 60% at 36 months and 55% at 69 months. The median period of observation was 29 months, ranging from 22 months to 69 months. Twenty-one of 93 patients (23%) had local failure, 18 of 93 patients (19%) developed systemic metastases. The local failure rate was particularly high in patients treated with radiation and was reduced when radiation planning was centralized within the study based upon the extent of disease at diagnosis. Cox regression analysis of prognostic factors showed that tumor volume was a significant factor influencing prognosis. The estimated 3-year DFS rate was 80% for patients with small tumors (volume less than 100 ml) compared to 31% for patients with large tumors (volume greater than or equal to 100 ml). In patients who had surgery for local control, the histologic response to chemotherapy was analyzed on the surgical specimen and had a strong influence on survival: 79% DFS at 3 years for patients with less than 10% viable tumor (good responders) compared to 31% DFS for patients with more than 10% viable tumor (poor responders). Tumor load and responsiveness to chemotherapy are the two major factors influencing prognosis in patients with primary Ewing's sarcoma of bone.     

Long-term results in 144 localized Ewing's sarcoma patients treated with combined therapy

The results of 144 previously untreated cases of primary Ewing's sarcoma of bone are reported with a minimum follow-up of 5 years. This series was treated between 1972 and 1982 at Istituto Ortopedico Rizzoli with a combined therapy. The local control of the disease consisted of amputation (ten cases), resection followed by radiation therapy (35-45 Gy) (48 cases) and radiation therapy alone (40-60 Gy) (86 cases). Adjuvant chemotherapy, rigorously standardized, was performed according two different protocols: the first (85 cases treated in the period 1972-1978) consisted of vincristine (VCR) Adriamycin (doxorubicin) (ADM), and cyclophosphamide (EDX); the second (59 cases treated in the period 1979-1982) of VCR, ADM, EDX and dactinomycin (DACT). At a follow-up of 5 to 16 years (median, 9), 59 patients (41%) are continuously disease-free (CDF), 81 (56%) developed metastatic disease and/or local recurrence, and four (3%) had a second malignancy. Three factors seem to be correlated to prognosis: the site of the initial lesion (only 23% of the pelvic lesions are represented in the CDF group versus 46% of the other locations); the chemotherapy protocol (32% of the cases in the first protocol are CDF versus 54% in the second); the type of local treatment (60% of the patients treated with amputation or resection plus radiotherapy versus 28% of those treated with radiation therapy alone are CDF). A local recurrence was observed in 24% of the patients (8% in the group locally treated with surgery or surgery plus radiation therapy versus 36% in the group treated with radiation therapy alone). These data suggest that even though adjuvant chemotherapy can improve the long-term results in localized Ewing's sarcoma patients, this disease still represents, in a high percentage of cases, a lethal process whose final prognosis widely depends on the local control of the lesion. Due to the questionable effect of the radiation therapy alone in controlling the primary lesion and its important side effects, the role of surgery in treating Ewing's sarcoma of bone should be extended.     

Curability of Ewing's sarcoma and considerations for future therapeutic trials

Twenty previously untreated children with primary Ewing's sarcoma and 8 children with primary tumor and metastatic disease were treated with surgery or radiation therapy (6,000-7,000 rads) for their primary tumor and T-2 chemotherapy. Of the 20 children with primary Ewing's sarcoma treated with T-2 "adjuvant" chemotherapy, 15 had no evidence of recurrent disease for from 31+-82+ months (median 46+ months) from the start of treatment. The actuarial 5-year disease-free survival rate for this group of patients was 75%. Eight patients presenting with metastatic disease had complete responses to T-2 chemotherapy, but 7/8 with metastatic disease eventually had tumor recurrence. Examination of the treatment failures, both those patients relapsing after adjuvant chemotherapy for primary Ewing's sarcoma (5), and those relapsing after having a complete response of metastatic disease (7) to T-2 chemotherapy, revealed that all relapses occurred at the end of the second year of T-2 chemotherapy or after chemotherapy was stopped. In addition, of 23 patients receiving "curative" radiation therapy to their primary tumor, 5 had local recurrence (22%) and 6 (26%) had severe functional debility secondary to combined radiation therapy and T-2 chemotherapy. The conclusions drawn from this experience have led us to consider a new approach to the treatment of Ewing's sarcoma, namely: 1) more aggressive initial or "induction" chemotherapy with subsequent T-2 "maintenance" chemotherapy to eradicate more completely all metastatic microfoci of disease presumed to be present in patients with primary tumor at the time of diagnosis, and ostensively present in patients with metastatic disease; 2) the use of surgery alone or in combination with moderate doses of radiation therapy in those patients in whom we can predict a high frequency of local recurrence (pelvic lesions) or a high percentage of "functional failures" (young children with lower extremity lesions). Preliminary results with this latter approach are encouraging with 11/13 patients with primary Ewing's sarcoma free of disease at 12+-26+ months. A longer follow-up of this more aggressive treatment is needed to determine the superiority of this approach for both increased survival and improved late physical rehabilitation.     

Cutaneous and subcutaneous Ewing's sarcoma: an indolent disease

PURPOSE: The occurrence of extraosseous Ewing's sarcoma (ES) in deep soft tissues has been well described, but cases in which this tumor occurs in a primary cutaneous or subcutaneous site have rarely been reported. The superficial variant may be less aggressive than are the more common bony and deep soft tissue counterparts with an apparently favorable outcome. A retrospective review of patients with cutaneous or subcutaneous ES was conducted to analyze outcome and patterns of failure. METHODS AND MATERIALS: Between July 1985 and March 1997, 14 patients with cutaneous or subcutaneous ES were treated at St. Jude Children's Research Hospital. The median age at presentation was 16 years (range 7-21 years). Anatomic locations included trunk and pelvis (7), upper or lower extremity (4), and head and neck (3). The median size of the lesion was 3 cm (range, 1-12 cm). Thirteen had definitive surgical resections, and one had biopsy of the mass at the time of referral. They were enrolled on institutional (12) or cooperative group (2) protocols. All patients received chemotherapy, composed of vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide, and dactinomycin. Patients on institutional protocols received radiation (36 Gy) to the operative bed (150-180 cGy/fraction/day). Postoperative radiotherapy was omitted for 2 patients who had complete resection on the cooperative group study. RESULTS: No patients had metastatic disease at presentation. Thirteen patients had wide local excision of the primary tumors prior to enrollment on chemotherapy; surgical margins were negative (10), microscopically positive (2), and indeterminate (1). Eleven patients received radiotherapy to the tumor bed; 2 with clear surgical margins were treated without irradiation. The patient who had biopsy only received induction chemotherapy followed by definitive surgical resection and postoperative radiotherapy. The median follow-up was 77 months (range 17-111 months). None of the patients has developed local recurrence or distant metastasis. Several of the patients developed treatment-related sequelae, including veno-occlusive disease of the lung and hemorrhagic cystitis (1), myelodysplastic syndrome (1), chemotherapy-induced ovarian failure (1), moist desquamation (1), and dermatofibroma within the radiotherapy volumes (1). CONCLUSIONS: Cutaneous and subcutaneous ES are associated with an indolent course and a favorable prognosis when treated with combined modality therapy. Elimination of radiation therapy following complete resection has been tested in the POG 9354 trial. The high rate of local control, low rate of metastatic disease, and excellent overall outcome may suggest a role for less intensive chemotherapy, as well as tailoring to diminish or avoid radiation therapy in completely resected cases, with a goal to minimize toxicity while maintaining a high cure rate.     

Ewing's sarcoma: surgical resection as a prognostic factor

A retrospective review of 46 cases of Ewing's (43) and extraosseous Ewing's (3) sarcoma was performed to examine for prognostic factors. Follow-up ranged from 27 to 135 months with a mean of 77.6 months, 86% greater than 36 months. Nine (20%) patients presented with distant metastases, 98% received multiagent chemotherapy, and 98% received radiation therapy. Overall actuarial survival and local control at 5 years were .52 +/- .08 and .78 +/- .07, respectively. The freedom from relapse or treatment related mortality at 5 years was .46 +/- .08. In 12 (26%) patients, surgical resection of the involved bone or soft tissue was part of the initial treatment plan. Ninety-two percent (11/12) of these patients also received radiation therapy. In addition to surgical resection, tumor size (less than 500 cc vs. greater than or equal to 500 cc), primary site (central vs. other), and stage were also analyzed for prognostic significance, and where appropriate, were included in Cox multivariate analyses. Considering all patients, the 5-year actuarial survival was .92 +/- .08 vs. .37 +/- .09 for patients receiving and not receiving surgical resection, respectively (p = .001 by logrank, p = .02 by Cox). To make the groups more comparable, 8 patients with local failure and 5 patients with non-evaluable primary sites were excluded. After these exclusions, the presence or absence of surgical resection had decreased significance: .92 +/- .08 vs. .59 +/- .11, respectively; p = .01 by logrank, p = .07 by Cox. Only primary site remained statistically significant: .86 +/- .08 for noncentral sites vs. .38 +/- .16 for central sites, p less than .0002 by logrank, p = .0004 by Cox. Surgical resection when added to local irradiation has prognostic significance in this retrospective review. The reason for this is not clear, but may be related to a decrease in local failure after resection.     

根治性放疗同步化疗治疗局部晚期尤文氏肉瘤家族肿瘤的临床效果#br#

目的评价根治性放疗同步化疗治疗局部晚期尤文氏肉瘤家族肿瘤的临床效果。方法回顾性分析2012年6月至2015年12月新疆医科大学附属肿瘤医院收治的24例局部晚期尤文氏肉瘤家族肿瘤行根治性放疗同步化疗患者的临床资料,男15例,女9例;骨病变12例,骨外病变12例;腰椎3例,骶骨3例,小腿6例,上臂3例,肩胛骨3例,锁骨3例,腰大肌3例;24例均无法广泛切除。先行4周期化疗,方案：长春新碱+阿霉素+环磷酰胺/异环磷酰胺+依托泊苷（VAC/IE）交替方案各2周期,每3周重复1次,再行调强放疗,处方剂量：56 Gy/28f,2 Gy/次,5次/周,6周完成;放疗过程中原方案同步化疗2周期,再按原方案化疗10个周期;治疗过程中,每2周期化疗后根据实体肿瘤疗效评价标准（RECIST）评估原发病灶局部情况;治疗结束后,通过定期复查进行随访。结果同步放化疗后,全组24例患者中6例完全缓解（CR）,12例部分缓解（PR）,6例疾病稳定（SD）;总有效率（CR+PR+SD）为100%。5年无进展生存率（RFS）为58.3%,5年总生存率（OS）为62.5%。放化疗后发生Ⅰ～Ⅱ度骨髓抑制15例,Ⅲ～Ⅳ度骨髓抑制9例;Ⅰ～Ⅱ度胃肠道反应24例,1～2级急性放射性皮炎24例。结论根治性放疗同步化疗治疗局部晚期尤文氏肉瘤家族肿瘤的效果确切,耐受性良好,对于不能手术保肢或肿瘤不可切除的患者可选择该治疗方案。     

Extremity preservation by combined modality therapy in sarcomas of the hand and foot: an analysis of local control, disease free survival and functional result

A primary tumor arising in the hand or foot represents an uncommon presentation for patients with Ewing's sarcoma (ES) or soft tissue sarcoma (STS). While there exists considerable literature on the treatment of extremity sarcomas, very little deals specifically with lesions of the hand or foot. It remains controversial whether these lesions can be successfully treated with combined modality therapy which preserves the extremity and maintains function. From 1972 to 1979, 10 patients with sarcomas arising in the hand or foot were treated with combined modality therapy at the National Cancer Institute. Seven patients with ES of bone received local irradiation to 5000 rad and combination chemotherapy following an incisional biopsy. Three patients with STS received a gross tumor excision and local irradiation to 6000 rad. One STS patient also received combination chemotherapy. Local control was achieved in nine patients (90%) with a follow-up of 30-119 months (median 56 months). These patients have complete or almost complete function of the treated extremity. Nine patients are alive with five patients remaining disease-free following the initial combined modality treatment. Two patients with Ewing's sarcoma relapsed (1 patient with both local and distant failure) at 26 and 58 months and were again rendered disease-free with surgery, total body irradiation and further chemotherapy. One patient relapsed for a second time, being disease-free from the first relapse for 30 months. We conclude that for selected patients with sarcomas arising in the hand or foot, combined modality therapy which leaves the extremity intact results in excellent local tumor control and preserves function. Careful treatment planning is an essential aspect of successful radiation therapy of a hand or foot primary. Our treatment recommendations are outlined. This approach is a viable alternative to amputation in these patients.     

Surgery for lung metastases in Ewing's sarcoma of bone.

The addition of chemotherapy and radiotherapy to local treatment for Ewing's sarcoma of bone (ES) significantly bettered its prognosis. Nonetheless, although with no signs of local recurrence some patients still relapse with lung metastases. These patients are generally treated with non-surgical procedures. The few reports in literature on surgical resection of metachronous pulmonary metastases do not allow any conclusions. This study aims to report the results achieved in 24 Ewing's sarcoma patients who relapsed only with lung metastases, and no local recurrence, treated with surgery at the authors' institution.     

Ewing's sarcoma: local tumor control and patterns of failure following limited-volume radiation therapy

Sixty children with localized osseous Ewing's sarcoma were treated between 1978 and 1988 with induction chemotherapy (cyclophosphamide, adriamycin), irradiation and/or surgery, and 10 months of maintenance chemotherapy (cyclophosphamide, adriamycin, dactinomycin, vincristine). Following induction chemotherapy, 43 patients received primary radiation therapy to limited radiation volumes defined by post-chemotherapy residual soft tissue tumor extension and initial osseous tumor extent. Irradiation was defined as low dose at 30-36 Gy (median 35 Gy) for 31 cases with objective response to induction chemotherapy and high dose at 50-60 Gy (median 50.4 Gy) for 12 patients with poor response to induction chemotherapy or with tumors greater than or equal to 8 cm. Overall event-free survival at 5 years is 59% and local tumor control is 68%. Initial failures have been local (12), simultaneous local and distant failures (7), and distant (6). In the surgical resection group, 14 patients had complete resection without radiation therapy, and 3 patients had microscopic residual plus 35-41 Gy; 100% local control has been maintained. In 43 patients with primary radiation therapy group, local tumor control is 58% (p = .004). Despite limited radiation volume, 18/19 local failures occurred centrally within the bone, well within the radiation volume. Imaging response to induction chemotherapy predicted local tumor control in the radiation therapy group: 62% with complete response/partial response versus 17% with no response/progressive disease (p less than 0.01). Local tumor control related strongly to primary tumor size in the radiation therapy group; among 31 cases receiving 35 Gy, local tumor control is 90% for lesions less than 8 cm versus 52% for tumors greater than or equal to 8 cm (p = .054). The central pattern of local failure in this experience suggests the effectiveness of limited radiation volume. The overall local tumor control rate following the tested dose level of 35 Gy appears to be inadequate, although results in selected cases with tumors less than 8 cm in greatest tumor dimension indicate potential efficacy in a yet limited experience.     

Therapy for primary non-Hodgkin's lymphoma of bone and a comparison of results with Ewing's sarcoma. Ten years' experience at the Istituto Ortopedico Rizzoli

The authors report on the results obtained in 30 consecutive cases of primary non-Hodgkin's lymphoma of bone (PNHLB) treated at the Istituto Ortopedico Rizzoli between 1972 and 1982. Four patients were treated with radiotherapy only and 26 were treated with radiotherapy plus adjuvant chemotherapy. At a median follow-up of 86 months (range, 30-160), among the 26 patients treated with chemotherapy also there were 3 relapses (2 had meningeal involvement and 1 had recurrence in another bone). Relapse (local recurrence plus multiple new localizations) was observed in one of the four patients treated with radiotherapy only. These results are compared with the results of 68 patients with Ewing's sarcoma who were treated during the same period with radiation therapy and adjuvant chemotherapy and reported in a previous study. In this group, the disease-free survival rate was only 32% (20/68) with a much higher incidence of local recurrence (31%). The necessity of making a clear distinction between PNHLB and Ewing's sarcoma is discussed.     

Multimodal therapy for the management of localized Ewing's sarcoma of pelvic and sacral bones: a report from the second intergroup study

A total of 59 eligible patients with localized Ewing's sarcoma of the pelvic and sacral bones were entered into a multimodal Intergroup Ewing's Sarcoma Study (IESS-II) (1978 to 1982) and compared with a historical control series of 68 patients entered into an earlier multimodal Intergroup Ewing's Sarcoma Study (IESS-I) (1973 to 1978). High-dose intermittent multiagent chemotherapy (vincristine, cyclophosphamide, Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH], and dactinomycin) was given to all patients for 6 weeks before and for 70 weeks following local therapy. All patients who had a tumor biopsy or incomplete resection performed received a dose of 55 Gy to the tumor bed. With a median follow-up time of 5.5 years, two of 59 patients (3%) had a local recurrence, five patients (8%) had a local recurrence and metastases, and 17 patients (29%) developed metastases only. There was significant statistical evidence of an advantage in relapse-free survival (RFS) and survival (S) for patients on IESS-II versus IESS-I, P = .006 and P = .002, respectively. At 5 years, the comparison between IESS-II versus IESS-I was 55% versus 23% for RFS and 63% versus 35% for S.     

Ewing's sarcoma: a trial of adjuvant chemotherapy and sequential half-body irradiation

The results of a pilot study using adjuvant chemotherapy and sequential half-body irradiation (HBI) for nonmetastatic Ewing's sarcoma are presented. Seventeen patients received Cyclophosphamide, Vincristine, and Adriamycin (8 cycles), followed by sequential radiation treatment of the upper (500 cGy) and lower (600 cGy) half body. Survival at 3 years was 49%. These results are contrasted with those for 18 concurrently treated patients who received standard adjuvant therapy. Overall 5-year survival and relapse-free survival for these 35 consecutive patients was 61 and 53%. The pilot protocol was given on an out-patient basis with limited and acceptable acute toxicology. Further study is necessary to determine the value of the pilot protocol.