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.     

Pseudo‐Kaposi’s sarcoma: The association of arterio‐venous malformations with skin lesions resembling Kaposi’s sarcoma

A patient is described with skin lesions resembling Kaposi’s sarcoma (KS). Arteriography revealed multiple arteriovenous malformations in the affected limb. This condition has been termed pseudo‐Kaposi’s sarcoma. Although reports of this condition have appeared in dermatological journals, as yet we are unaware of any account in the radiological literature. This paper presents a case and reviews the literature. In suspected cases of KS in which the history or clinical features are atypical, this unusual condition should be considered and a search made for the diagnostic vascular lesions.     

Primary spinal epidural extraosseous Ewing’s sarcoma: Report of five cases and literature review

Ewing’s sarcoma is the most common malignant bone tumour occurring in children and adolescents and exists in two different clinicopathological entities: osseous Ewing’s sarcoma (OES) and extraosseous Ewing’s sarcoma (EES). Five cases of primary epidural EES are described, which presented with non‐specific symptoms leading to a long diagnostic delay. The median age at diagnosis was 22 years (range 13–36 years). The median diagnostic delay was 3 months. All patients had one or more neurological deficits. All underwent surgical exploration with a laminectomy and partial resection followed by adjuvant radiotherapy to a dose of 46–50 Gy and chemotherapy with VAC (vincristine, adriamycin and cyclophosphamide) alternating with ICE (ifosphamide, cisplatin and etoposide) for at least six cycles. The mean follow‐up period is 21.2 months (range 11–32 months). Four of the five patients achieved a complete remission and are disease free at the time of writing this report. Two patients have a residual neurological deficit – both having presented with long history of neurological deficit. Primary spinal epidural EES should be suspected whenever young patients present with back pain and/or radicular pain, have abnormal neurology and an extradural mass is demonstrated on MRI. Surgical excision followed by adjuvant radiotherapy (50 Gy) and combination chemotherapy (VAC alternating with ICE) achieved local and systemic control in these patients. A greater number of patients and longer follow up are required to evolve a generally accepted treatment policy for this aggressive but potentially curable malignancy.     

92例初治尤文氏肉瘤家族肿瘤综合治疗疗效和生存分析

背景和目的：尤文氏肉瘤家族肿瘤（Ewing’ssarcomafamilyoftumor,ESFF）恶性度高、进展快,其最佳治疗方法目前仍在探讨中。本研究旨在分析ESFF的临床特点和探讨其治疗方法。方法：回顾性分析1995年1月至2008年4月中山大学肿瘤防治中心收治的92例初治ESFF。结果：骨尤文氏肉瘤（Ewing’ssarcomaofbone,ETB）23例,骨外尤文氏肉瘤（extraosseousEwing’Ssarcoma,EOE）21例,外周性原始神经外胚叶瘤（peripheralprimitiveBeuroectodermaltumor,PNET）43例,Askin瘤5例。中位随访时间31．5个月（10～137个月）。局限期综合治疗38例,单一治疗19例,两组3年生存（overallsurvival,OS）率分别为63％、20％,3年无事件生存（events．freesurvival,EFS）率分别为46％、18％,两组问生存差异具有统计学意义（P均〈0．001）。局限期综合治疗患者在全身化疗的基础上加用手术加或不加放疗组远期生存均优于化疗＋放疗组（x2=7．591、9．212,P=0．006、0．002）。CAV／IE交替方案对局限期接受综合治疗患者延长了无事件生存期,但其总生存时间差异无统计学意义（X2=6．950、3．530,P=0．008、0．06）。多因素生存分析显示治疗模式以及疗效是独立的预后因素。结论：综合治疗能明显改善局限期ESFT患者疗效和生存．手术加化疗加或不加放疗的治疗模式在疗效和生存方面优于化疗加放疗治疗模式。治疗模式和近期疗效是独立的预后因素。     

Ewing’s sarcoma of the pelvis: changes over 25 years in treatment and results

The pelvic localisations of Ewing’s sarcoma have the worst prognosis due to large size at diagnosis, frequent distant metastases, radiosensitive organs next to the tumour and difficult surgery. The purpose of the present study was to analyse treatment results over a period of 25 years and to investigate the impact of newer chemotherapy schedules, improved radiotherapy techniques and newer surgical methods on the prognosis. 35 children and young adults were identified from 1967 to 1994 for whom diagnosis, presentation, performed treatment and outcome were available. Tumour size, as measured from CT scans, response to chemotherapy and radiotherapy target volume, could be reviewed in the later years. Actuarial 5-year survival for the whole group was 31% and for the 24 non-metastatic patients 40%, with a disease-free interval of 19%. Tumour size could be measured in 27 patients and ranged from 36 to 1540 cm³. There were 12 local recurrences, 1 in the 4 patients treated with surgery. After 1983, 9 out of 17 irradiated patients developed local failure. 3 patients had adequate fields and one a close field which did not cover completely the prechemotherapy extent and 3 of these recurred. All 4 patients with stable disease after neoadjuvant CT failed locally, not withstanding high-dose radiotherapy. The mean length of neoadjuvant CT tended to be shorter in patients without local relapse. There was no significant difference in survival before and after 1983.     

Radiotherapy to improve local control regardless of surgical margin and malignancy grade in extremity and trunk wall soft tissue sarcoma: a Scandinavian sarcoma group study

PURPOSE: Adjuvant radiotherapy has during the past decades become increasingly used in the treatment of localized soft tissue sarcoma. We evaluated the effect of radiotherapy (RT) on local recurrence rates (LRRs) in Scandinavia between 1986 and 2005. METHODS AND MATERIALS: A total of 1,093 adult patients with extremity or trunk wall soft tissue sarcoma treated at four Scandinavian sarcoma centers were stratified according to the treatment period (1986-1991, 1992-1997, and 1998-2005). The use of adjuvant RT, quality of the surgical margin, interval between surgery and RT, and LRR were analyzed. The median follow-up was 5 years. RESULTS: The use of RT (77% treated postoperatively) increased from 28% to 53%, and the 5-year LRR decreased from 27% to 15%. The rate of wide surgical margins did not increase. The risk factors for local recurrence were histologic high-grade malignancy (hazard ratio [HR], 5), an intralesional (HR, 6) or marginal (HR, 3) surgical margin, and no RT (HR, 3). The effect of RT on the LRR was also significant after a wide margin resection and in low-grade malignant tumors. The LRR was the same after preoperative and postoperative RT. The median interval from surgery to the start of RT was 7 weeks, and 98% started RT within 4 months. The LRR was the same in patients who started treatment before and after 7 weeks. CONCLUSION: The results of our study have shown that adjuvant RT effectively prevents local recurrence in soft tissue sarcoma, irrespective of the tumor depth, malignancy grade, and surgical margin status. The effect was most pronounced in deep-seated, high-grade tumors, even when removed with a wide surgical margin.     

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.     

Disseminated intraosseous Kaposi’s sarcoma: A rare manifestation of HIV/AIDS

Kaposi Sarcoma (KS), a mucocutaneous cancer that most frequently occurs in the context of Acquired Immunodeficiency Syndrome (AIDS) secondary to Human Immunodeficiency Virus (HIV), is a relatively benign condition, acting more as a marker of immunodeficiency than directly causing harm itself. However, it has been known to spread both locally and in a metastatic fashion, with reports of KS affecting almost all organ systems. One of the most rarely reported areas of involvement is the musculoskeletal system, with secondary osseous spread representing an even smaller subset of these. We report a case of biopsy proven disseminated intraosseous KS involving the entire imaged skeleton that occurred with HIV/AIDS, despite maximal treatment and normal imaging 8 months prior.     

Soft tissue sarcomas of the head and neck: outcome and prognostic factors

Background. Soft tissue sarcomas of the head and neck are uncommon malignant tumors. Up till now, their treatment has not been standardized. We retrospectively reviewed the records of adult patients with soft tissue sarcomas of the head and neck to identify prognostic factors affecting local control and survival. Methods. The records of 48 adult patients with soft tissue sarcoma of the head and neck region treated between 1987 and 1997 were reviewed. The data were analyzed for the impact of potential prognostic factors on local control, disease-free survival, and overall survival. Factors evaluated were age, sex, tumor grade, T-stage, bone invasion, site, surgical margin, treatment modality, and radiation dose. Results. The 5-year actuarial local control rate of the entire group was 40%. Tumor size was the only predictor for local control on multivariate analysis. Combined surgery and radiotherapy appeared to yield superior local control compared with surgery alone (46% vs 35%); however, the difference was not significant (P < 0.06). The 5-year actuarial overall and disease-free survivals were 48% and 34%, respectively. On multivariate analysis, tumor size was a significant factor for local control and for overall and disease-free survivals, while histological grade was a significant predictor only for disease-free survival. Conclusion. Tumor size was a significant predictor factor for local control and for overall and disease-free survivals. Histological grade was another significant predictor, affecting only disease-free survival. There was a trend for better local control with the addition of postoperative radiotherapy, although the difference did not reach significance, because of probable selection bias among the patients who were indicated for radiotherapy. Received: December 14, 1998 / Accepted: May 24, 2000     

Local Recurrence of Low-Grade Myofibroblastic Sarcoma of the Chest Wall： Report of a Case and Literatures Review

Myofibroblastic sarcoma, composed primarily of myofibroblast, is a rare malignant tumor. Low-grade myofibroblastic sarcoma （LGMS） has been defined properly as a distinct entity in the 2002 WHO classification of soft tissue tumors. Primary sarcoma of the chest wall is also a rare disease. This article describes a case of locally recurrent LGMS of the chest wall.     

Radiotherapy and surgery-an indispensable duo in the treatment of retroperitoneal sarcoma

The authors undertook a systematic review to designate the role that radiotherapy (RT) might play in the treatment of retroperitoneal sarcomas. Correlating with recent literature, the objective of this review was to evaluate whether there was enough evidence for the authors to develop an institutional treatment protocol concerning the use of RT in the treatment of retroperitoneal sarcoma. Furthermore, this was a call for surgeons to talk to radiation oncologists before performing surgery. The 2 objectives of this review were: 1) to determine the benefit of RT in terms of local control and/or survival in the treatment of retroperitoneal sarcomas and 2) to discover the optimal timing of RT in the treatment sequence. A computerized literature search was performed in the PubMed database, the Cochrane Library database, and reference lists; and journals also were searched by hand to identify all retrospective and prospective reports published since 1998 relating to RT treatment of adult retroperitoneal sarcoma. Mainly, analyses were sought that were based on a 5-year local control rate (LCR), 5-year disease-free survival, and 5-year overall survival (OS). If only 2 years follow-up were available, then the authors also noted this outcome. Toxicity data were collected and analyzed separately. The synthesis of the literature was based on 9 prospectively nonrandomized studies and 10 retrospective studies that, together, reviewed a total of 1426 patients. The 5-year LCR varied from 27% to 62%, and the results from other reports fell in between those values. The 5-year OS rate ranged from 12% to 90%, and complete resection and tumor grade were the most important prognostic factors in most studies. This review resulted in 7 recommendations concerning the use of RT in the treatment of retroperitoneal sarcoma. The authors concluded that there is good evidence from multiple single-institutions studies that RT improves the LCR in patients with retroperitoneal sarcoma. Until now, there has not been a translation of this approach into survival benefit. The current results indicated that preoperative external-beam RT followed by radical surgery seems to be the preferred sequence, and adding intraoperative RT is a safe procedure for dose escalation in the upper abdomen.     

Ewing’s sarcoma family tumors of the humerus: Outcome of patients treated with radiotherapy, surgery or surgery and adjuvant radiotherapy

Background and purpose

Local treatment for non-metastatic Ewing’s sarcoma family tumors (ESFTs) is controversial. Results achieved in a single institution in patients with ESFT of the humerus are presented.

Materials and methods

Patients treated between 1983 and 2000 for ESFT of the humerus were included. The impact of local treatment (surgery, radiotherapy or both) on outcome was assessed.

Results

55 patients: 34 males (62%); 21 females (38%); mean age: 17.9 (range: 3-40). Local treatment: surgery in 27 patients (49%), radiotherapy in 17 (31%) and surgery followed by radiotherapy in 11 (20%). After a mean follow-up of 15 years (range: 7-25 years), 27 patients (49%) remained continuously disease free, 27 (49%) relapsed and one died of chemotherapy toxicity. The local recurrence rate was 13% overall: 18% (3/17) after radiotherapy, 7% (2/27) after surgery and 19% (2/11) after surgery followed by adjuvant radiotherapy (p = ns). On the contrary, the 10-year EFS resulted significantly higher after surgery (64%) than radiotherapy (18%, p < 0.01). The 10-year EFS after surgery followed by radiotherapy was 45%, non-significantly different from EFS of surgery or radiotherapy alone. The 3 treatment groups had a similar distribution of the most important prognostic variables for ESFT, except for the tumor-bone ratio, which was higher for patients who underwent radiotherapy, and surgical margins, more frequently inadequate in patients treated with a combination of radiotherapy and surgery compared to those managed by surgery alone.

Conclusions

In conclusion this study shows that in EFST of the humerus surgery is the best treatment for small tumors. Large tumors are probably best treated with surgery too, as long as good functional results and quality of life can be expected, and adequate surgical margins are achievable. Postoperative radiotherapy is mandatory when margins are inadequate. A high local control rate, of more than 80%, can be obtained also by means of radiotherapy alone.     

Localized aggressive non-Hodgkin’s lymphoma of the nasal cavity: a survey by the Japan Lymphoma Radiation Therapy Group

Purpose: To clarify the role of radiotherapy and chemotherapy in the treatment of patients with localized aggressive non-Hodgkin’s lymphomas (NHL) originating in the nasal cavity.

Methods and Materials: The survey, administered at 25 Japanese institutes in 1998, enabled us to collect the clinical data for 787 patients with localized aggressive NHL who were treated between 1988 and 1992.

Results: There were 42 patients (5%) with nasal lymphomas. Twelve of these patients received radiotherapy alone, and 30 were treated with a combination of radiotherapy and chemotherapy. The median radiation dose was 47 Gy (22–66). Twelve patients were reviewed histopathologically according to REAL (Revised European-American Classification of Lymphoid neoplasms) classification. T-cell or natural killer (NK) cell lymphomas were detected in 9 patients (75%), and diffuse large B-cell lymphomas in 3 (25%). The 5-year overall and disease-free survival (DFS) rates of all patients were 57% and 59%, respectively. The 5-year DFS rate for the 30 patients treated with the combined therapy was 64% and that for the 12 patients treated with radiotherapy alone was 46% (p = 0.021). For the 34 patients with stage-modified International Prognostic Index (m-IPI) 0–1, the 5-year DFS rates of those treated with the combined therapy and radiotherapy alone were 68% and 45%, respectively (p = 0.020), but there was no difference in DFS rate among the two groups of patients with m-IPI 2–3. The 5-year local control rates of the patients who received >46 Gy (n = 22) and ≤46 Gy (n = 20) were 95% and 76% (p = 0.087), respectively. There was no significant difference among the 5-year DFS rates (62% vs. 67%) and local control rates (87% vs. 100%) of the patients with T-cell or NK-cell lymphoma and diffuse large B-cell lymphoma.

Conclusions: Patients with nasal lymphomas (m-IPI 0–1) should be treated with combined therapy. For the patients with high risk (m-IPI 2–3), the effectiveness of combined therapy was not clarified because of the small number of the patients. A high radiation dose >46 Gy may need to be used to achieve good local control.     

Subdiaphragmatic stage I & II Hodgkin’s disease: long-term follow-up and prognostic factors

Purpose: To report long-term follow-up results and to analyze prognostic factors for overall and disease-free survival in patients with subdiaphragmatic Stage I & II Hodgkin’s disease.

Methods and Materials: From September 1962 to April 1995, 109 patients presented at the M. D. Anderson Cancer Center with subdiaphragmatic Hodgkin’s disease. The medical records of these patients were retrospectively reviewed; 22 patients who received no treatment at the M. D. Anderson Cancer Center or who had radiation therapy at other institutions were excluded. The remaining 87 patients formed the basis of this study. The median age of our group was 33 years with a male: female ratio of 3.3:1. The histological subtypes were nodular sclerosis in 21 (24.1%) patients, mixed cellularity in 31 (35.6%), lymphocyte predominance in 33 (37.9%), lymphocyte depletion in 1 (1.1%) and unclassified histology in 1 (1.1%). Of the patients, 32 (36.8%) underwent laparotomy for diagnosis or staging purpose, 74 (85.1%) had lymphangiography, and 35 (40.2%) had computerized tomography of the abdomen and pelvis. Among the patients, 22 (25%) had more than three sites of nodal involvement at presentation, 56 (64.4%) had pelvic or abdominal disease, and 14 (18.4%) had bulky disease that was defined as disease with the largest dimension ≥ 7 cm. Stage distribution was IA in 33.3%, IIA in 39.1%, and IIB in 27.6%. Treatment was radiotherapy alone in 60 (69%) patients, chemotherapy and radiation in 23 (26.4%), and chemotherapy alone in 4 (4.6%).

Results: The 10- and 20-year actuarial overall survival rates for all patients were 74.6% and 55.3%, and the corresponding disease-free survival rates were 72.4% and 67.5%, respectively. On univariate analysis, age > 40 years, B symptoms, nodular sclerosis or mixed cellularity histology, and decreased albumin or hemoglobin levels were statistically significant adverse pretreatment factors for overall survival. B symptoms, decreased albumin level, more than 3 sites of disease at presentation, and Stage II were statistically significant negative pretreatment prognostic factors for disease-free survival. Only B symptoms and decreased albumin level predicted worse outcome in both overall and disease-free survivals. On multivariate analysis, age > 40 years, nodular sclerosis and mixed cellularity histology, and decreased hemoglobin levels were three independent risk factors for overall survival. An analysis of the pattern of failure revealed that the majority of the patients with central Stage II disease who did not receive mantle radiation failed in the supradiaphragmatic area. Late complications of radiation were infrequent.

Conclusions: Long-term follow-up of this group of patients revealed similar overall and disease-free long-term survival, as would be expected from supradiaphragmatic Hodgkin’s disease. For patients with central Stage II disease, it is anticipated that supradiaphragmatic radiation therapy would improve the disease-free survival.     

Synovial sarcoma of children and adolescents: the prognostic role of axial sites

BackgroundThe outcome of patients with non-extremity synovial sarcoma (SS) is generally worse than that of patients with limb tumours.MethodsThe present study analysed a series of 115 consecutive SS patients treated in Italian paediatric protocols (period 1979–2005), mainly focusing on the 30 cases arising from ‘axial’ sites (16 head–neck, 8 trunk, 4 lung-pleura and 2 retroperitoneum).ResultsInitial gross resection was achieved in 40% of axial cases and in 80% of limb SS (p < 0.0001). Five-year EFS and overall survival (OS) were, respectively, 43.3% and 55.1% for axial SS, and 69.6% (p = 0.0068) and 84.0% (p = 0.0004) for extremity SS. Local progression/recurrence was the cause of treatment failure in 75% of relapsing patients axial disease.ConclusionsOur findings emphasise that children and adolescents with SS originating at non-extremity locations have a worse prognosis than those with limb SS. Tumour site should be considered when defining a risk-adapted treatment strategy for SS.     

The prognostic role of the preoperative systemic immune-inflammation index and high-sensitivity modified Glasgow prognostic score in patients after radical operation for soft tissue sarcoma

IntroductionThe prognostic values of nutritional and immune-inflammatory indicators in non-metastatic soft tissue sarcoma (STS) patients are not clear. We investigated the utility of systemic immune-inflammation index (SII) and the high-sensitivity modified Glasgow prognostic score (Hs-mGPS) in the prediction of STS patient's prognosis.Materials and methodsPatients admitted between January 2000 and December 2016, who underwent R0 resection for STS at SYSUCC were carefully retrospectively reviewed, and 454 patients were enrolled. The laboratory data and clinical data were collected from the patient's record. ROC analysis is used to determine the optimal cutoff value. Survival curves were analysed by Kaplan-Meier method. Cox proportional hazard model was used to find out prognostic variables.ResultsIncreased SII and Hs-mGPS values were significantly related to larger tumour size, deep tumour location, higher tumour grade and more advanced American Joint Committee on Cancer (AJCC) stage. Patients with an elevated SII had a shorter median survival time and a lower 5-year OS rate than those with a low SII. And patients with low Hs-mGPS had longer median OS and DFS. Multivariate analysis revealed that both the SII and the Hs-mGPS were independent predictive indicators for OS. And a joint model containing both the Hsm-GPS and the SII appeared to have the strongest predictive ability.ConclusionOur findings indicated that malnutrition and systemic inflammation are risk factors for the survival of STS patients after operation, and early recognition and intervention of malnutrition and systemic inflammation may help to improve the survival of the patients.