Gemcitabine Concurrent with Thoracic Radiotherapy after Induction Chemotherapy with Gemcitabine/Vinorelbine in Locally Advanced Non-Small Cell Lung Cancer

PURPOSE: To determine the maximum tolerated dose (MTD) of gemcitabine every 2 weeks to a concurrent radiotherapy administered during an aggressive program of sequential and simultaneous radio-/chemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Ten patients with histologically confirmed NSCLC were observed and treated in accordance with a combined radio-/chemotherapy protocol. This included two cycles of induction chemotherapy with gemcitabine (1,200 mg/m(2)) and vinorelbine (30 mg/m(2)) at days 1, 8 and 22, 29, followed by concurrent radiotherapy including [(18)F] fluorodeoxyglucose positron emission tomography-(FDG-PET-)based target volume definition (2.0 Gy/d; total dose 66.0 Gy) and chemotherapy with gemcitabine every 2 weeks at days 43, 57, and 71. The initial dose was 300 mg/m(2). The dose of gemcitabine was increased by 100 mg/m(2) until the MTD was realized. Three patients were enrolled for each dose level. RESULTS: Dose-limiting toxicity (DLT) was identified for the patient group receiving gemcitabine 500 mg/m(2), due to grade 2 esophagitis (next to grade 3) in all patients. 6 weeks after the completion of radio-/chemotherapy, most patients still presented treatment-induced esophagitis. In accordance with expected complications, such as esophagitis, dysphagia and odynophagia, the MTD was defined at this dose level, although no DLT grade 3 was reached. CONCLUSION: After induction chemotherapy, the MTD and frequency of gemcitabine in locally advanced NSCLC is 500 mg/m(2) every 2 weeks during a maximum of 7 weeks of thoracic radiotherapy.     

Three-Times-Daily Radiotherapy with Induction Chemotherapy in Locally Advanced Non-Small Cell Lung Cancer Feasibility and Toxicity Study

Purpose:   

To evaluate the feasibility and toxicity of three-times-daily radiotherapy (3tdRT), preceded by induction chemotherapy (iCT), in stage IIIA–IIIB non-small cell lung cancer (NSCLC).     

Intraindividual Comparison of Conventional Three-Dimensional Radiotherapy and Intensity Modulated Radiotherapy in the Therapy of Locally Advanced Non-Small Cell Lung Cancer

BACKGROUND: Local failure is the one of the most frequent cause of tumor related death in locally advanced non-small cell lung cancer (LAD-NSCLC). Dose escalation has the promise of increased loco-regional tumor control but is limited by the tolerances of critical organs. PATIENTS AND METHODS: To evaluate the potential of IMRT in comparison to conventional three-dimensional conformal planning (3DCRT) dose constraints were defined: Maximum dose (D(max)) to spinal cord < 48 Gy, mean lung dose 70 Gy in not more than 5 cm of the total length. For ten patients two plans were compared: (1) 3DCRT with 5 weekly fractions (SD) of 2 Gy to a total dose (TD) of 50 Gy to the planning target volume of second order (PTV2). If the tolerance of the critical organs was not exceeded, patients get a boost plan with a higher TD to the PTV1. (2) IMRT: concomitant boost with 5 weekly SD of 2 Gy (PTV1) and 1.5 Gy to a partial (p)PTV (pPTV=PTV2 profile of a line PTV1) to a TD of 51 Gy to the pPTV and 68 Gy to the PTV1. If possible, patients get a boost plan to the PTV1 with 5 weekly SD of 2 Gy to the highest possibly TD. RESULTS: Using 3DCRT, 3/10 patients could not be treated with TD > 50 Gy, but 9/10 patients get higher TD by IMRT. TD to the PTV1 could be escalated by 16% on average. The use of non-coplanar fields in IMRT lead to a reduction of the irradiated lung volume. There is a strong correlation between physical and biological mean lung doses. CONCLUSION: IMRT gives the possibility of further dose escalation without an increasing mean lung dose especially in patients with large tumors.     

Microwave Ablation in Combination with Chemotherapy for the Treatment of Advanced Non-Small Cell Lung Cancer

Purpose

To verify whether microwave ablation (MWA) used as a local control treatment had an improved outcome regarding advanced non-small cell lung cancer (NSCLC) when combined with chemotherapy.

Methods

Thirty-nine patients with histologically verified advanced NSCLC and at least one measurable site other than the ablative sites were enrolled. Primary tumors underwent MWA followed by platinum-based doublet chemotherapy. Modified response evaluation criteria in solid tumors (mRECIST) and RECIST were used to evaluate therapeutic response. Complications were assessed using the National Cancer Institute Common Toxicity Criteria (version 3.0).

Results

MWA was administered to 39 tumors in 39 patients. The mean and median diameters of the primary tumor were 3.84 cm and 3.30 cm, respectively, with a range of 1.00–9.00 cm. Thirty-three (84.6 %) patients achieved a partial response. No correlation was found between MWA efficacy and clinicopathologic characteristics. For chemotherapy, 11 patients (28.2 %) achieved a partial response, 18 (46.2 %) showed stable disease, and 10 (25.6 %) had progressive disease. The overall objective response rate and disease control rate were 28.2 and 74.4 %, respectively. The median progression-free survival time was 8.7 months (95 % CI 5.5–11.9). The median overall survival time was 21.3 months (95 % CI 17.0–25.4). Complications were observed in 22 (56.4 %) patients, and grade 3 adverse events were observed in 3 (7.9 %) patients.

Conclusions

Patients with advanced NSCLC could benefit from MWA in combination with chemotherapy. Complications associated with MWA were common but tolerable.

     

Hyperfractionated Radiotherapy in Locally Advanced Nasopharyngeal Cancer

BACKGROUND: Despite numerous randomized trials suggesting a benefit of unconventional fractionation in locally advanced head and neck cancer, the role of this approach in nasopharyngeal carcinoma is debatable. Based on the current clinical experience, the authors introduced hyperfractionated irradiation in the treatment of locally advanced head and neck cancer, including nasopharyngeal tumors. The preliminary results of this treatment approach in nasopharyngeal cancer patients are presented, with special focus on the pattern of failure and toxicity. PATIENTS AND METHODS: 43 patients with nasopharyngeal cancer (stage II-IV, TNM 1997) underwent hyperfractionated irradiation. In 34 cases, radiotherapy was preceded by a median of three cycles of cisplatin-based induction chemotherapy. Irradiation was delivered using a shrinking-field technique up to a total dose of 74.4 Gy in 62 fractions of 1.2 Gy twice daily (minimum 6-h interval)/5 days/week. RESULTS: Acute toxicity of hyperfractionated radiotherapy was significant but tolerable. Mucositis proved the most common side effect (grade 3: 24 patients, grade 4: three patients). Severe late toxicity was not observed. 30 of 34 patients (88%) responded to induction chemotherapy. At 6 weeks after completion of radiotherapy, complete response was seen in 35 patients (81%), partial response in five (12%), stable disease in one, and progressive disease in two. After a median follow-up of 32 months, 18 patients (41%) developed progressive disease. Primary tumor progression was observed in three patients, and seven patients each showed regional lymph node progression and distant metastases. In one case both regional lymph node progression and distant metastases were diagnosed. The 2-year progression-free survival and overall survival rates were 58% and 84%, respectively. CONCLUSION: Hyperfractionated radiotherapy seems a feasible and active regimen in locally advanced nasopharyngeal carcinoma. Accompanying acute and late toxicity is acceptable and does not compromise delivery of the planned irradiation dose. This regimen is associated with a high local control rate; relatively high nodal and distant failure, however, call for further treatment modifications, e. g., optimization of irradiation technique and/or dose escalation as well as improved systemic therapies.     

Ablation Therapy for Advanced Stage Non-Small Cell Lung Cancer: A National Cancer Database Study

PurposeTo compare overall survival (OS) of ablation with no treatment for patients with advanced stage non-small cell lung cancer.MethodsPatients with clinical stage IIIB (T_1–4N₃M₀, T₄N₂M₀) and stage IV (T_1–4N_0–3M₁) non-small cell lung cancer, in accordance with the American Joint Committee on Cancer, 7th edition, who did not receive treatment or who received ablation as their sole primary treatment besides chemotherapy from 2004 to 2014, were identified from the National Cancer Data Base. OS was estimated using the Kaplan-Meier method and evaluated by log-rank test, univariate and multivariate Cox proportional hazard regression, and propensity score-matched analysis. Relative survival analyses comparing age- and sex-matched United States populations were performed.ResultsA total of 140,819 patients were included. The 1-, 2-, 3- and 5-year survival rates relative to age- and sex-matched United States population were 28%, 18%, 12%, and 10%, respectively, for ablation (n = 249); and 30%, 15%, 9%, and 5%, respectively for no treatment (n = 140,570). Propensity score matching resulted in 249 patients in the ablation group versus 498 patients in the no-treatment group. After matching, ablation was associated with longer OS than that in the no-treatment group (median, 5.9 vs 4.7 months, respectively; hazard ratio, 0.844; 95% confidence interval, 0.719–0.990; P = .037). These results persisted in patients with an initial tumor size of ≤3 cm.ConclusionsPreliminary results suggest ablation may be associated with longer OS in patients with late-stage non-small cell lung cancer than survival in those who received no treatment.     

Surgery and Chemotherapy for Small Cell Lung Cancer in Stages I–II with or without Radiotherapy

PURPOSE: To analyze the effectiveness of surgery and chemotherapy with or without radiotherapy in the management of limited small cell lung cancer (LSCLC) in stages I and II. PATIENTS AND METHODS: 39 patients (median age 62 years) with LSCLC in stages pT1 or pT2 and pN0 or pN1 (stages IA-IIB) who had a tumor resection and systematic lymph node dissection were reviewed retrospectively. The median follow-up period was 29 months. 35 patients (90%) received a median of four cycles of a platinum-containing chemotherapy postoperatively. 16 patients (41%) received an adjuvant thoracic radiotherapy (TRT, median 50 Gy); 21 patients (54%) received a prophylactic cranial irradiation (PCI, median 30 Gy). RESULTS: The median overall survival for all patients was 47 months, resulting in actuarial 1-, 3-, and 5-year survival rates of 97%, 58%, and 49%, respectively. Distant metastases were found in 13 patients (33%) after a median of 16 months. Patients who received an adjuvant TRT showed a trend toward improved thoracic recurrence-free survival (p = 0.06) and improved overall survival (p = 0.07) compared to those treated with surgery and chemotherapy only. Brain metastasis-free survival (p = 0.01) and overall survival (p = 0.01) were improved significantly in patients who received a PCI. CONCLUSION: Surgical tumor resection may be considered for carefully selected patients. Adjuvant chemotherapy and PCI are recommended for all patients. Adjuvant TRT is currently used in patients with positive lymph nodes (pN1), because the probability of a subclinical involvement of the mediastinal lymphatic system appears to be increased in these patients.     

Intraindividual Comparison of Conventional Three-Dimensional Radiotherapy and Intensity Modulated Radiotherapy in the Therapy of Locally Advanced Non-Small Cell Lung Cancer A Planning Study

Background: Local failure is the one of the most frequent cause of tumor related death in locally advanced non-small cell lung cancer (LAD-NSCLC). Dose escalation has the promise of increased loco-regional tumor control but is limited by the tolerances of critical organs. Patients and Methods: To evaluate the potential of IMRT in comparison to conventional three-dimensional conformal planning (3DCRT) dose constraints were defined: Maximum dose (D_max) to spinal cord < 48 Gy, mean lung dose h 24 Gy, D_max esophagus > 70 Gy in not more than 5 cm of the total length. For ten patients two plans were compared: (1) 3DCRT with 5 weekly fractions (SD) of 2 Gy to a total dose (TD) of 50 Gy to the planning target volume of second order (PTV2). If the tolerance of the critical organs was not exceeded, patients get a boost plan with a higher TD to the PTV1. (2) IMRT: concomitant boost with 5 weekly SD of 2 Gy (PTV1) and 1.5 Gy to a partial (p)PTV (pPTV=PTV2 š PTV1) to a TD of 51 Gy to the pPTV and 68 Gy to the PTV1. If possible, patients get a boost plan to the PTV1 with 5 weekly SD of 2 Gy to the highest possibly TD. Results: Using 3DCRT, 3/10 patients could not be treated with TD > 50 Gy, but 9/10 patients get higher TD by IMRT. TD to the PTV1 could be escalated by 16% on average. The use of non-coplanar fields in IMRT lead to a reduction of the irradiated lung volume. There is a strong correlation between physical and biological mean lung doses. Conclusion: IMRT gives the possibility of further dose escalation without an increasing mean lung dose especially in patients with large tumors. Hintergrund: Lokale Rezidive sind eine häufige Todesursache bei Patienten mit lokal fortgeschrittenen nichtkleinzelligen Bronchialkarzinomen (LAD-NSCLC). Dosiseskalation verspricht hier eine Verbesserung der lokalen Kontrolle, ist aber limitiert durch die Toleranz der Nachbarstrukturen. Patienten und Methoden: Um das Potential der IMRT im Vergleich zur konventionellen 3-D-Planung herauszuarbeiten, wurden folgende Dosis-Volumen-Vorgaben definiert: Maximale Dosis (D_max) des Myelons < 48 Gy, mittlere Lungendosis (MLD) h 24 Gy, D_max des Ösophagus > 70 Gy in h 5 cm der Gesamtlänge. Für zehn Patienten mit LAD-NSCLC wurden verglichen: 1. 3DCRT mit fünf wöchentlichen Einzeldosen (ED) von 2 Gy bis zu einer Gesamtdosis (GD) von 50 Gy für das Planungszielvolumen zweiter Ordnung (PTV2). Wenn die Toleranz der umliegenden Gewebe dies zuließ, erhielten die Patienten einen Boostplan für das PTV1. 2. IMRT: Concomitant Boost mit fünf söchentlichen ED von 2 Gy für das PTV1 und 1,5 Gy für das partielle PTV (pPTV=PTV2 š PTV1) bis zu einer GD von 51 Gy im pPTV und 68 Gy im PTV1. Falls die Belastung des Normalgewebes dies erlaubte, erfolgte ein Boostplan für das PTV1 mit fünf wöchentlichen ED von 2 Gy bis zur höchstmöglichen GD. Ergebnisse: Konventionell konnten 3/10 Patienten mit GD > 50 Gy behandelt werden - mittels IMRT konnten bei 9/10 Patienten höhere Dosen appliziert werden. Im PTV1 konnte im Mittel eine Dosiseskalation von 16% erreicht werden. Besonders Patienten mit großen Tumoren profitierten von der IMRT. Die Verwendung nonkoplanarer Techniken führte zur Verringerung der Dosis innerhalb des kritischen Lungenvolumens. Die physikalischen mittleren Lungendosen waren hoch korreliert mit den biologisch gewichteten mittleren Lungendosen. Schlussfolgerung: Im Vergleich zur 3DCRT ermöglicht die IMRT eine Dosiseskalation in der Behandlung von LAD-NSCLC ohne Erhöhung der mittleren Lungendosis. Von der Technik profitieren insbesondere Patienten mit größeren Tumoren.     

非小细胞肺癌放疗结合介入化疗或静脉化疗的对照研究

目的:评价放射治疗结合介入化疗或静脉化疗治疗晚期非小细胞肺癌(NSCLC)的疗效.方法:58例晚期中央型非小细胞肺癌随机分为2组,介入化疗加放疗组(A组):31例患者经支气管动脉灌注(BAI)(DDP 40mg,5-FU 1000mg,MMC 8mg);静脉化疗加放疗组(B组):27例经静脉点滴MFP方案(MMC 10mg一次性静脉灌注,DDP 30mg及5-FU 1000mg静滴5周),两组均化疗3～7d后,对肺部病灶及纵隔淋巴结引流区进行放射治疗,总量60Gy、5次/周.结果:A组总有效率(CR+PR)为80.6%, B组总有效率(CR+PR)为77.8%,两组总有效率差异没有显著性意义(χ2=0.072,P=0.0788).A、B两组患者1年及3年生存率分别为58.1%、48.1%和29.1%、7.4%,两组差异有显著性意义(P<0.05).结论:综合治疗是晚期肺癌主导方向;介入化疗加放疗治疗晚期NSCLC的远期有效率优于静脉化疗加放疗方案,因此更值得临床推广应用.     

Early Morbidity after Radiotherapy with or without Chemotherapy in Advanced Head and Neck Cancer

BACKGROUND: Data on early treatment-related morbidity after radiotherapy alone (RT; 217 patients) or combined with chemotherapy (RT + CT; 182 patients) of head and neck squamous cell carcinoma are analyzed. PATIENTS AND METHODS: The patients were treated between November 1985 and November 1996 in four Swiss centers that independently introduced combined-modality therapy in selected cases of head and neck cancer. RT schedules varied among the four centers, but within each institution all patients received the same dose-fractionation schedule irrespective of whether they had CT or not. The following early morbidity items were evaluated: skin, mucosa, larynx, salivary glands, dysphagia, weight loss, and toxic death. Toxicity was scored using the EORTC/RTOG scale. RESULTS: Although considerable variation was noted among the treatment schedules/centers, the main findings are as follows: (1) early morbidity was significantly enhanced after all five RT + CT schedules compared with RT alone; (2) typically, a third of the patients lost > 10% of their body weight during concurrent RT + CT as compared with 10% of the patients receiving RT alone; (3) at 12 weeks, the prevalence of grade 2 morbidity was 25-60% after RT + CT as compared with 4-20% after RT alone. CONCLUSION: A number of early morbidity items were found to be more prevalent and/or more severe after RT + CT than after RT alone.     

99Tcm-HL91乏氧显像预测局部晚期非小细胞肺癌放疗敏感性

目的 探讨99Tcm-4,9-二氮-3,3,10,10-四甲基十二烷-2,11-二酮肟(HL91)乏氧显像预测局部晚期非小细胞肺癌(locally advanced non-small cell lung cancer,LANSCLC)对放疗敏感性的临床价值.方法 对29例LANSCLC患者静脉注射99Tcm-HL91 1110MBq 后进行1 h(早期)及4 h(延迟)SPECT断层显像,根据显像进行目测和半定量分析(T/N值),并按延迟显像T/N值将患者分为低摄取组及高摄取组.所有患者均接受常规分割放射治疗, 对2组放疗近期疗效进行比较.结果 99Tcm -HL91早期和延迟显像对LANSCLC患者乏氧诊断的灵敏度分别为75.9%(22/29)、100%(29/29),二者相比有显著差异(P=0.010).半定量分析结果T/N值与不同病理类型、临床分期、病灶大小无明显关系(P＞0.05).低摄取组(T/N＜2.15,n=17)放疗近期有效率76.5%(13/17)高于高摄取组(T/N≥2.15,n=12)的33.3%(4/12),比较有显著性差异(P=0.029).结论 99Tcm -HL91显像对LANSCLC乏氧诊断具有较高的灵敏度,并在预测其放疗近期效果方面具有一定的临床价值.     

放疗结合介入法化疗治疗中、晚期食管癌

目的探讨放射治疗结合动脉灌注化疗治疗中、晚期食管癌的临床应用价值。方法对38例中、晚期食管癌患者随机分组为单纯放疗组和放射治疗加化疗综合治疗组并随访3～24个月,观察临床及放射学改善情况,评价治疗效果。结果治疗后大部分患者临床指标及X线片表现明显改善,综合治疗组X线Ⅰ级片率明显高于单纯放疗组。结论放射治疗结合经导管直接向肿瘤供血动脉灌注化疗药物,能增加局部的药物浓度和药物效应,减轻全身毒性反应,有效缩小局部肿块。因此,采用放射治疗结合超选择性食管供血动脉灌注化疗是一种行之有效的综合治疗中、晚期食管癌的方法。     

DWI对局部进展期乳腺癌新辅助化疗疗效评价的初步研究

目的:探讨磁共振扩散加权成像(DWI)对局部进展期乳腺癌新辅助化疗疗效评价以及作为预测因子的可行性.方法:根据10例乳腺癌化疗后退缩情况将肿瘤分成缓解和进展两组,比较两组化疗前后ADC值和DWI信号强度的变化,并评价治疗前ADC值与化疗结束肿瘤退缩变化的相关性.结果:无论是治疗前还是治疗后,ADC值和DWI信号强度在缓解组和进展组间差异均无显著性意义(P＞0.05),但缓解组治疗后ADC值升高,而进展组则降低,尤其在b=1000和2000 s/mm2时明显.b=1000 s/mm2时,肿瘤高活性区和低活性区对治疗反应比较显示,肿瘤高活性区ADC值较低,治疗后ADC值升高(1.195±0.230和1.371±0.295);而肿瘤低活性区ADC值较高,治疗后ADC值反而下降(1.632±0.241和1.312±0.297);与病理对照显示,治疗后肿瘤细胞蜕变,并伴有明显的胶元和纤维化形成.治疗前ADC值与治疗后肿瘤退缩呈负相关,当b取1000和2000 s/mm2时相关更明显,前者为r= -0.802,P=0.005,后者的r = -0.745,P=0.013.结论:DWI可以对局部进展期乳腺癌新辅助化疗疗效作评价,并能对治疗疗效作出预测.     

吉西他滨联合多西紫杉醇新辅助化疗方案在局部晚期肺癌的疗效观察

目的：观察吉西他滨联合多西紫杉醇用于Ⅲ期非小细胞肺癌（NSCLC）新辅助化疗的效果及耐受性。方法：67例Ⅲ期NSCLC手术患者,术前接受新辅助化疗。其中,GT组32例,接受gemcitabine＋docetaxel方案,与同期接受长春瑞滨（NVB）＋DDP方案（NP组）35例作比较。结果：GT组,CR1例,PR14例,总有效率46．88％;NP组,CR2侧,PR16例,总有效率51．43％,两组有效率无显著性差异（P〉0．05）;化疗后肿瘤分期下降两组分别为：GT组43．75％（14／32）,NP组45．71％（16／35）,两组比较无显著性差异（P〉0．05）。结论：吉西他滨联合多西紫杉醇用于NSCLC术前新辅助化疗效果肯定,该方案可作为NSCLC术前新辅助化疗的可选择方案。     

MRI对局部进展期乳腺癌新辅助化疗早期疗效评价

目的 采用磁共振扩散加权成像(DWI)表观扩散系数(ADC)评价局部进展期乳腺癌(LABC)新辅助化疗(NCT)的早期疗效.资料与方法 32例LABC患者采用多西紫杉醇联合表柔比星(75mg/m2静脉推注,第1天给药,3周方案)进行NCT治疗.每21d为1个周期,至肿瘤缩小到可手术或保乳手术可行时停止化疗.于化疗前、化疗1个周期后和手术前行DWI扫描,分析肿瘤体积、ADC值变化及其相关性.结果 20例(62.5％,95％ CI 45.7％～79.3％)患者行2个周期化疗后出现整体有效(OR),临床完全缓解(cCR)率及病理完全缓解(pCR)率分别为156％ (5/32)和9.4％ (3/32):疾病稳定(cSD)率为34.4％ (11/32),疾病进展(cPD)率为3.1％ (1/32);第1个NCT后,cCR+部分缓解(cPR)组AD)C值显著增加[化疗前ADC值为(0.98±0.16)×103mm2/s,化疗后为( 1.22±026)×103mm2/s] (P＜ 0.001).化疗前cCR+cPR组初始ADC值显著低于cSD+cPD组[(1.13±0.06)×10-3mm2/s](P＜0.001).初始ADC值与化疗后肿瘤体积变化呈负相关(r=-0.58,P=0.02);化疗后肿瘤ADC值与肿瘤体积变化呈正相关(r=096,P＜0.001).结论 乳腺癌病灶初始ADC值及NCT后早期ADC值变化可以作为预测乳腺癌对NCT敏感性和化疗早期评价乳腺癌敏感性的指标.     

Radiotherapy and High-Dose Chemotherapy in Advanced Ewing's Tumors

BACKGROUND: Ewing's tumors are sensitive to radio- and chemotherapy. Patients with multifocal disease suffer a poor prognosis. Patients presenting primary bone marrow involvement or bone metastases at diagnosis herald a 3-year disease-free survival below 15%. The European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) has established the following indications for high-dose therapy in advanced Ewing's tumors: Patients with primary multifocal bone disease, patients with early (< 2 years after diagnosis) or multifocal relapse. PATIENTS AND METHOD: As of 1987, 83 patients have been treated in the EICESS group, 39 of them at the transplant center in Düsseldorf, who have been analyzed here. All individuals received 4 courses of induction chemotherapy with EVAJA and stem cell collection after course 3 and 4. Consolidation radiotherapy of the involved bone compartments was administered in a hyperfractionated regimen 2 times 1.6 Gy per day, up to 22.4 Gy simultaneously to course 5 and 22.4 Gy to course 6 of chemotherapy. The myeloablative chemotherapy consisted of melphalan and etoposide (ME) in combination with 12 Gy TBI (Hyper-ME) or Double-ME with whole lung irradiation up to 18 Gy (without TBI). RESULTS: The survival probability at 40 months was 31% (44% DOD; 15% DOC). Pelvic infiltration did not reach prognostic relevance in this cohort. Radiotherapy encompassed 75% of the bone marrow at maximum (average 20%). Engraftment was not affected by radiotherapy. CONCLUSION: High-dose chemotherapy can improve outcome in poor prognostic advanced Ewing's tumors. The disease itself remains the main problem. The expected engraftment problems after intensive radiotherapy in large volumes of bone marrow can be overcome by stem cell reinfusion.