High-dose therapy for patients with primary multifocal and early relapsed Ewing's tumors: results of two consecutive regimens assessing the role of total-body irradiation.

PURPOSE: Risk stratification of metastatic and relapsed Ewing's tumors (ETs) has been a matter of debate during the last decade. Patients with bone or bone marrow metastases or early or multiple relapses constitute the worst risk group in ET and have a poorer prognosis than patients with primary lung metastases or late relapses. In this article, the results of the present Meta European Intergroup Cooperative Ewing Sarcoma Study (MetaEICESS) (tandem melphalan/etoposide [TandemME]) were compared with the result of the previous study (hyper melphalan/etoposide [HyperME]), both at 5 years, in a patient population within the same high-risk stratum to determine toxicity. PATIENTS AND METHODS: Among 54 eligible patients, 26 were treated according to the HyperME protocol, and 28 were treated according to TandemME protocol. Patients received six cycles of the Cooperative Ewing Sarcoma Study treatment in HyperME and six cycles of the EICESS treatment in TandemME as induction chemotherapy. Patients also received involved-compartment irradiation for local intensification and myeloablative systemic intensification consolidation with hyperfractionated total-body irradiation (TBI) combined with melphalan/etoposide in HyperME or two times the melphalan/etoposide in TandemME followed by autologous stem-cell transplantation. RESULTS: The event-free survival (EFS) rate +/- SD in HyperME and TandemME was 22% +/- 8% and 29% +/- 9%, respectively. The dead of complication rate was 23% in HyperME and 4% in TandemME. CONCLUSION: TandemME offers a decent, albeit still not satisfactory, rate of long-term remissions in most advanced ETs (AETs), with short-term treatment and acceptable toxicity. TBI was not required to maintain EFS level in this setting but was associated with a high rate of toxic death. Future prospective studies in unselected patients are warranted to evaluate high-dose therapy in an unselected group of patients with AET.     

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.     

Intra-thoracic failure pattern and survival status following 3D conformal radiotherapy for non-small cell lung cancer: a preliminary report

BACKGROUND: To study the intra-thoracic failure pattern, clinical target volume (CTV) and survival status following 3D conformal radiotherapy (3DCRT) boost for non-small cell lung cancer (NSCLC). METHODS: From May 1994 through June 1998, 33 patients (26 male, seven female) with NSCLC were treated with a complete course of radiotherapy (RT) in our institute. Group A included 10 patients receiving radical operation and adjuvant postoperative RT. The other 23 patients (groups B and C) received definitive radiotherapy as local treatment. Among them there were seven cases as group B (stage I-II) and 16 cases as group C (stage III). Fifteen (15/33) patients received chemotherapy. The radiotherapy strategy constituted conventional AP/PA radiotherapy (RT) 19.8-45 Gy (median 39.6 Gy) plus 3DCRT boost 6-34.2 Gy (median 20 Gy). The median total tumor dose was 59.6 Gy (ranging from 39.8 to 64.8 Gy). Patients were followed up regularly (6/33) or until their death (27/33). Nineteen patients received follow-up chest computed tomography (CT). The relationship between intra-thoracic failure found by chest CT and the initial RT and boost RT fields was analyzed. Local failure was defined as one of the following: clinical disease progression, CXR progression or relapse noted by CT. The overall survival (OS) and local failure free survival (LFF) were obtained using the Kaplan-Meier method. RESULTS: Sixteen intra-thoracic failures were noted in 15 follow-up chest CT examinations, which included nine in-field relapses, three partial in-field relapses and four out-field relapses. The 2-year OS and LFF for groups A, B and C were 78.8/59.2, 14.2/16.7 and 6.2/7.1% respectively. RTOG grade III/IV complications included one pneumothorax (RTOG grade III). CONCLUSION: Our retrospective study showed that selective omission of contralateral mediastinal lymph node station irradiation may be appropriate in RT for NSCLC. Chest wall and pleural relapses may not be a negligible cause of intra-thoracic failure after RT for NSCLC.     

Multi-institutional review of repeat irradiation of chest wall and breast for recurrent breast cancer

PURPOSE: To review the toxicity and clinical outcomes for patients who underwent repeat chest wall or breast irradiation (RT) after local recurrence. METHODS AND MATERIALS: Between 1993 and 2005, 81 patients underwent repeat RT of the breast or chest wall for locally recurrent breast cancer at eight institutions. The median dose of the first course of RT was 60 Gy and was 48 Gy for the second course. The median total radiation dose was 106 Gy (range, 74.4-137.5 Gy). At the second RT course, 20% received twice-daily RT, 54% were treated with concurrent hyperthermia, and 54% received concurrent chemotherapy. RESULTS: The median follow-up from the second RT course was 12 months (range, 1-144 months). Four patients developed late Grade 3 or 4 toxicity. However, 25 patients had follow-up >20 months, and no late Grade 3 or 4 toxicities were noted. No treatment-related deaths occurred. The development of Grade 3 or 4 late toxicity was not associated with any repeat RT variables. The overall complete response rate was 57%. No repeat RT parameters were associated with an improved complete response rate, although a trend was noted for an improved complete response with the addition of hyperthermia that was close to reaching statistical significance (67% vs. 39%, p = 0.08). The 1-year local disease-free survival rate for patients with gross disease was 53% compared with 100% for those without gross disease (p < 0.0001). CONCLUSIONS: The results of our study have shown that repeat RT of the chest wall for patients with locally recurrent breast cancer is feasible, because it is associated with acceptable acute and late morbidity and encouraging local response rates.     

Treatment of orbital rhabdomyosarcoma: survival and late effects of treatment--results of an international workshop.

PURPOSE: Orbital rhabdomyosarcoma (RMS) historically has been associated with an excellent survival rate. The majority of patients are cured with the use of both chemotherapy and radiation therapy, but a significant number experience important late sequelae of treatment. In an attempt to determine optimal therapy in relation both to cure and to sequelae, the experience of the four international collaborative groups (Intergroup Rhabdomyosarcoma Study Group [IRSG], International Society of Paediatric Oncology [SIOP] Sarcoma Committee, German Collaborative Soft Tissue Sarcoma Group [CWS], and Italian Cooperative Soft Tissue Sarcoma Group [ICG] studies) was shared at an international workshop. PATIENTS AND METHODS: A total of 306 eligible patients were identified from group records (186 from IRS, 43 from SIOP MMT, 40 from CWS, and 37 from ICG). Median age was 6.8 years, and median follow-up was 6.5 years. Eighty percent of patients received radiation therapy (RT) as part of primary therapy, but there were significant differences in the use of RT between the individual groups (93% in IRSG, 76% in ICG, and 70% in CWS, but only 37% in the SIOP MMT group). RESULTS: At 10 years, event-free and overall survival for the whole cohort were 77% (range, 71% to 81%) and 87% (range, 82% to 92%), respectively. There was no difference in overall survival between the collaborative groups regardless of differences in the use of initial RT. In total, 34 (12%) of 273 survivors had not received RT, although this varied between the different groups (41% in the SIOP MMT group, 20% in CWS, 7% in ICG, and 6% in IRSG). There was no difference in overall survival for the whole cohort regardless of whether radiotherapy was used as part of initial therapy (86% at 10 years for both). CONCLUSION: These data suggest that a subset of patients with orbital RMS can be cured without systematic local therapy, although the total burden of treatment (primary therapy and treatment for relapse) must be taken into account when assessing the implications for late sequelae.     

Prognostic factors in Ewing's tumor of bone: analysis of 975 patients from the European Intergroup Cooperative Ewing's Sarcoma Study Group.

PURPOSE: To further elaborate on prognostic factors for Ewing's sarcoma of bone and to document improvements in relapse-free survival (RFS) and trends in local therapy over the study period (1977 to 1993). PATIENTS AND METHODS: A retrospective analysis was performed on a combined Gesellschaft Für P?diatrische Onkologie und H?matologie/Cooperative Ewing Sarcoma Study and United Kingdom Children's Cancer Study Group/Medical Research Council data set of 975 patients registered with the respective trial offices before the current collaborative European Intergroup Cooperative Ewing's Sarcoma Study trial. Both groups independently undertook studies with similar chemotherapy during the period. RESULTS: The key adverse prognostic factor is metastases at diagnosis (5-year RFS, 22% of patients with metastases at diagnosis v 55% of patients without metastases at diagnosis; P: <.0001). For the group with metastases, there was a trend for better survival for those with lung involvement compared with those with bone metastases or a combination of lung and bone metastases (P: <.0001). In the group of patients with no metastases at diagnosis, multivariate analysis demonstrated that site (axial v other), age-group (< 15 v > or = 15 years), and period of diagnosis had significant influence on RFS (all P: <.005). RFS was superior in the period after 1985 compared with the period before 1985 for nonmetastatic patients (45% v 60%, respectively; P: <.0001) and for metastatic patients (16% v 30%, respectively; P: =.016). Patients who relapsed within 2 years of diagnosis had a less favorable prognosis than patients who relapsed later (5-year survival after relapse, 4% v 23%, respectively; P: <. 0001). There were other changes over the period; in particular, radiotherapy or amputation were more common in the period before 1986, whereas endoprosthetic surgery was widely used in the later period. CONCLUSION: Survival and RFS improved over the period. Prognostic factors are metastases at diagnosis, primary site, and age.     

Primary metastatic (stage IV) Ewing tumor: Survival analysis of 171 patients from the EICESS studies

Background: In the multicenter European Intergroup Cooperative Ewing's Sarcoma Studies, localized Ewing tumors of bone were treated by combination chemotherapy with surgery and/or radiotherapy. Patients with primary metastases (pm-pts) were treated in high risk protocols.Patients and methods: One hundred seventy-seven pm-pts were registered from January 1990 to December 1995, 171 were evaluable for survival analyses. Thirty-six pm-pts received myeloablative megatherapy with stem cell rescue following conventional treatment. Bilateral whole lung irradiation (WLI) was administered in 57 pm-pts with pulmonary involvement. Event-free survival (EFS) rates were estimated by Kaplan–Meier analysis. Prognostic factors were identified by log-rank statistics, Cox procedures and logistic regression.Results: Eighty-nine deaths were recorded by 1 February 1997, EFS four years after diagnosis for all 171 pm-pts was 0.27. EFS for isolated lung metastases was 0.34, for bone/bone marrow (BM) metastases, 0.28, and for combined lung plus bone/BM metastases, 0.14 (P < 0.005). WLI improved outcome in case of isolated pulmonary involvement (0.40 vs. 0.19, P < 0.05). In pm-pts with combined pulmonary/skeletal metastases, intensification by megatherapy and/or WLI improved EFS from 0.00 to 0.27 (P = 0.0001).Conclusions: EFS four years after diagnosis in patients with disseminated Ewing tumors is 0.27. Whole lung irradiation and megatherapy improve outcome in subgroups of patients with disseminated Ewing disease.     

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.     

Impact of local management on long-term outcomes in Ewing tumors of the pelvis and sacral bones: the University of Florida experience

PURPOSE: This retrospective analysis describes our 35-year experience with respect to disease control and functional status. PATIENTS AND METHODS: Thirty-five patients with localized Ewing tumors of the pelvis and sacral bones were treated from 1970 to 2005. Twenty-six patients were treated with definitive radiotherapy (RT), and 9 patients were treated with combined local therapy in the form of surgery + RT. The median RT dose was 55.2 Gy. The patients who received RT alone were more likely to be older men with larger tumors exhibiting soft-tissue extension. Patients in the definitive RT group were more likely to receive etoposide and ifosfamide or undergo bone marrow transplant. Median potential follow-up was 19.4 years. RESULTS: The 15-year actuarial cause-specific survival, freedom from relapse rate, and local control rates were 26% vs. 76% (p = 0.016), 28% vs. 78% (p = 0.015), and 64% vs. 100% (p = 0.087), respectively, for patients treated with definitive RT and combined therapy. Overall, tumors <8 cm had significantly better cause-specific survival, but this was unrelated to local control. The median Toronto Extremity Salvage Score for the definitive RT and combined therapy groups were 99 and 94, respectively (p = 0.19). Seven definitive RT patients (27%) had serious complications. CONCLUSION: Combined modality local therapy should be considered if pelvic Ewing tumors are resectable. However, because of the extent of local disease, most patients have unresectable or partially resectable tumors and therefore require RT in some capacity. For this reason, innovative RT strategies are needed to improve long-term disease outcomes and minimize side effects while maintaining an acceptable functional result.     

Hemithoracic radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma

PURPOSE: To evaluate pleurectomy/decortication (P/D) and adjuvant radiotherapy (RT) in the treatment of malignant pleural mesothelioma (MPM). METHODS AND MATERIALS: In a retrospective review, we included MPM patients treated with P/D and adjuvant RT at Memorial Sloan-Kettering Cancer Center from 1974 to 2003. When indicated, patients received intraoperative brachytherapy to residual tumor. RESULTS: All 123 patients received external beam RT (median dose, 42.5 Gy; range, 7.2-67.8 Gy) to the ipsilateral hemithorax postoperatively. Fifty-four patients underwent brachytherapy (matched peripheral dose, 160 Gy). The median and 2-year overall survival for all patients was 13.5 months (range, 1-199 months) and 23%, respectively. One-year actuarial local control for all patients was 42%. Multivariate analysis for overall survival revealed radiation dose <40 Gy (p = 0.001), nonepithelioid histology (p = 0.002), left-sided disease (p = 0.01), and the use of an implant (p = 0.02) to be unfavorable. Two patients (1.6%) died from Grade 5 toxicity within 1 month of treatment. CONCLUSIONS: Pleurectomy/decortication with adjuvant radiotherapy is not an effective treatment option for patients with MPM. Our results imply that residual disease cannot be eradicated with external RT with or without brachytherapy and that a more extensive surgery followed by external RT might be required to improve local control and overall survival.     

Efficacy of irradiation and external hyperthermia in locally advanced, hormone-refractory or radiation recurrent prostate cancer: a preliminary report

PURPOSE: To present a preliminary report on the feasibility, efficacy, and toxicity of irradiation (RT) and hyperthermia (HT) in patients with locally advanced, hormone-refractory prostate cancer (LAHRPC) who may or may not have received prior RT. METHODS AND MATERIALS: Between 1997 and 2002, 13 consecutive patients with LAHRPC or RT-recurrent prostate cancer were treated with RT and HT on a Phase I-II protocol. Eight patients had RT-recurrent LAHRPC (Group A) and 5 had LAHRPC without prior RT (Group B). All patients had large and clinically symptomatic tumors. The median RT dose was 39.6 Gy and 66.6 Gy in Groups A and B, respectively. External deep HT was delivered using a BSD-2000 Sigma-60 applicator. The median number of HT treatments was 8 in group A and 10 in group B. RESULTS: The median follow-up was 14 and 13 months for Groups A and B, respectively. All patients achieved a complete or partial response (CR/PR) and complete palliation of symptoms. Eleven patients had follow-up CT scans that demonstrated a CR in six and a PR in five. Two patients, who died of metastasis, did not have CT scans and had a PR on digital rectal examination. Two patients demonstrated a biochemical CR. The median duration of the CR/PR among Group A patients was 12 months after therapy. Three patients in Group A developed tumor recurrence at 9, 17, and 27 months after repeat RT to doses of 39.6, 36, and 50 Gy, respectively. At last follow-up, no Group B patient developed local recurrence. Grade 1-2 rectal bleeding was noted in 3 patients. RT and HT were generally well tolerated by all patients who had not previously undergone RT. Of the 8 patients who had, 6 (75%) tolerated retreatment well with minimal or no complications. Two patients in the repeat RT group had severe complications. One patient with lymphoma and factor XI deficiency developed Grade 4 hemorrhagic cystitis. Another previously irradiated patient developed a rectovesical fistula 4 months after retreatment, after disappearance of a large, invasive, and necrotic tumor. CONCLUSION: This preliminary report demonstrates the feasibility and efficacy of RT and HT in patients with LAHRPC, who may or may not have received prior RT. Presently, such patients who have undergone previous RT have no effective treatment options. RT and HT were generally well tolerated by patients who were not previously undergone RT. Of those who had been, most (6 of 8) tolerated retreatment well with minimal or no complications. The high-risk factors for treatment- and tumor regression-related side effects include the presence of large necrotic tumors, previous RT with a large dose/fraction, and the presence of bleeding disorders. Despite the size of these large tumors, RT and HT resulted in significant tumor shrinkage, rapid serum prostate-specific antigen decline, durable treatment responses, and durable palliation of symptoms. Additional clinical studies are warranted.     

Factors influencing the outcome of radiotherapy in malignant mesothelioma of the pleura--a single-institution experience with 189 patients

PURPOSE: To determine the factors influencing the response to palliative radiotherapy (RT) in malignant mesothelioma of the pleura (MM). METHODS AND MATERIALS: A retrospective review was conducted of the records of all patients with mesothelioma who were referred to our institution between 1979 and 1996. A total of 227 RT series were administered to 189 patients with MM. Of these, 21 patients with chest wall nodules also received concomitant local hyperthermia. RESULTS: The median survival was 5 months from the start of RT and only 17% of patients were alive at 1 year after treatment. Chest pain and painful chest wall metastases were the main indications for RT. A higher local response rate was seen for patients treated with a 4-Gy per fraction scheme, vs. those receiving fractions of less than 4 Gy (50% vs. 39%). Pain recurrence occurred predominantly within the previous RT field, and pain recurred after a median of 69 days (range 32-363) in the group treated using 4-Gy fractions. When compared with a matched group, patients treated with combined RT and hyperthermia had higher response rates and fewer in-field recurrences. CONCLUSIONS: RT provides local palliation in at least 50% of patients with MM who were treated using a 4-Gy/fraction scheme to a median dose of 36 Gy. The low response rates with RT alone suggest that combined RT and local hyperthermia should be further evaluated in MM.     

High dose endobronchial irradiation in recurrent bronchogenic carcinoma.

Between November 1988 and March 1990, 24 patients with endobronchial tumors that had recurred after external beam radiation therapy were treated with high dose rate intraluminal irradiation. A remote afterloading high dose rate unit was used, and most patients received two endobronchial treatments, separated by a two week interval. All patients were given the same dose and dose specification to assess the feasibility and complications of the therapy. At each treatment, 15 Gy were delivered with dose specified at a radius of 6 mm from the center of the source, which corresponds to a dose of 9 Gy at a radius of 1 cm. Overall, 21 of 24 patients (88%) showed good symptomatic improvement. Of 18 patients whose chest x-ray showed evidence of collapse or atelectasis caused by tumor obstruction, 15 (83%) had evidence of reaeration. The median duration of palliation, marked by symptoms or a chest x-ray that worsened, was 26 weeks, the range varying from seven to 40 weeks. No patient died as a result of therapy and only one had a complication, bronchospasm, which responded well to bronchodilators. One patient died of hemoptysis approximately three months after treatment. Five additional patients, who were treated off protocol because they had an Eastern Cooperative Oncology Group performance status of greater than two, also received endobronchial irradiation. All five died within one month from worsening pulmonary disease, and we do not recommend endobronchial irradiation for patients with an Eastern Cooperative Oncology Group performance status of greater than two. We conclude that high dose rate endobronchial brachytherapy effectively relieves the symptoms of endobronchial obstruction due to recurrent lung cancer and can be given safely as an outpatient procedure. As the complications were minimal in this series treated with a uniform dose of 15 Gy per treatment, future studies should aim at determining the maximum tolerated dose. This technique may also be helpful as a boost after maximal external beam irradiation or to open up areas of atelectasis prior to external beam irradiation.     

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.     

Efficacy of radiotherapy for ovarian ablation: results of a breast intergroup study

BACKGROUND: In 1994, the Eastern Cooperative Oncology Group (ECOG) initiated for the Breast Intergroup a randomized clinical trial (E3193) in premenopausal patients with early-stage breast carcinoma (lymph node-negative and receptor-positive, with tumors measuring < or = 3 cm) comparing tamoxifen as adjuvant systemic therapy with tamoxifen and ovarian ablation by one of three different methods. Ovarian ablation could be accomplished either via radiotherapy (RT) (20 Gray [Gy]/10 fractions to a modified pelvic volume), surgical oophorectomy, or goserelin/leuprolide injections as per patient/physician choice. In the current study, we report the efficacy of pelvic RT with this dose-fractionation scheme in the induction of ovarian ablation. METHODS: Twenty-two of 174 patients (13%) who were randomized to treatment with tamoxifen and ovarian ablation received RT for ovarian ablation. RT quality assurance was performed. Of the 22 patients, 19 were treated per protocol, 1 patient had a minor violation (20 elapsed days for 10 RT fractions), and 2 patients had major violations (1 patient who was treated with RT as per protocol but who was treated at a non-Intergroup center, and 1 patient who was treated at a dose of 15 Gy/5 fractions). RESULTS: No acute Grade 3 or 4 (according to the Common Toxicity Criteria of the National Cancer Institute) toxicities were reported during RT. Of the 22 patients receiving RT, evaluable follow-up data were available for 20 patients. Based on postmenopausal levels of estradiol or follicle-stimulating hormone at varying intervals after the completion of RT, 15 of 20 patients (75%) achieved successful ovarian ablation with RT. At a median follow-up of 54 months (range, 21-66 months), no Grade 3 or 4 complications from RT were observed. CONCLUSIONS: Ovarian ablation by RT as performed in the current trial (given at a dose of 20 Gy in 10 fractions to a modified pelvic treatment volume) was found to be effective for ovarian ablation in the majority of patients, but may take some months to be complete. Consequently, patients should be evaluated to ascertain that ablation has been accomplished.     

Clear cell sarcoma of tendons and aponeuroses in pediatric patients: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group

BACKGROUND: Clear cell sarcoma (CCS) of tendons and aponeuroses is extremely rare in childhood and little information is available on its clinical management. Originally believed to be a type of melanoma of soft tissue origin, CCS is now considered a distinct clinicopathologic entity that behaves like a high-grade soft tissue sarcoma. We report on a series of 28 pediatric patients treated from 1980 to 2000 by the Soft Tissue Sarcoma Italian Cooperative Group and the German Cooperative Group. METHODS: Patients were treated with a multimodality therapeutic approach. Surgical resection was complete in 17 patients (mutilating in 3), radiotherapy was administered to 8 patients, and 20 patients received chemotherapy. RESULTS: After a median follow-up of 102 months (range, 19-238 months), the 5-year and event-free survival rates were 66.4% and 63.3%, respectively. Seventeen patients were alive in first remission, two were alive in second remission, and nine had died of disease. The response to chemotherapy in the 7 evaluable patients included one partial remission, one minor response, and five no responses. Radiotherapy contributed to achieving local control in four of six Intergroup Rhabdomyosarcoma Study (IRS) Group II patients. Statistically significant differences in outcome were evident according to IRS group, tumor size, and site. CONCLUSIONS: Our study confirms the aggressive behavior of CCS. Complete surgical resection represents the mainstay of treatment, and even the only treatment for patients with small tumors. Radiotherapy may control microscopic residual disease after surgery. Chemotherapy is ineffective and the prognosis is unfavorable for patients with unresectable and large tumors.     

诱导性同步放化疗治疗侵袭性肺上沟瘤

目的分析同步放化疗(CRT)在NSCLC外科治疗的地位.方法回顾性总结1987～1996年外科手术的30例累及胸顶部的NSCLC,单纯手术组10例,手术+放疗组(RT)9例,含铂方案化疗+放疗组(CRT)11例.结果单纯手术组2、4年生存率分别为30%和20%, RT组为22% 和11%,CRT组为73% 和53%.单因素分析根治性(是与否比较,P=0.027)和诱导性治疗(单纯手术和RT与CRT比较,P=0.0173)是有意义的预后因素.多因素分析仅诱导性治疗,P=0.023 8,是有意义的预后因素.结论与诱导性放疗和单纯手术相比,CRT可提高累及胸顶部的NSCLC患者的生存率.     

Recurrence-free survival rates after external-beam radiotherapy for patients with clinical T1-T3 prostate carcinoma in the prostate-specific antigen era: what should we expect?

BACKGROUND: The objective of the current study was to report biochemical recurrence-free survival (bRFS) rates among men with T1-T3 prostate carcinoma who were treated with external-beam radiotherapy (RT) at the Cleveland Clinic Foundation (Cleveland, OH). METHODS: In total, 1352 patients were identified between 1987 and 2000 with a minimum follow-up of 1 year (median follow-up, 55 months; range, 12-189 months). The median radiation dose was 74.0 grays (Gy) (range, 63.0-83.0 Gy). The median radiation doses for patients who received < 68.0 Gy (n = 201), 68.0-72.0 Gy (n = 373), and > or = 72.0 Gy (n = 778) were 66.6 Gy, 70.0 Gy, and 78.0 Gy, respectively. The RT techniques used were standard RT in 41% of patients, 3-dimensional conformal RT in 34% of patients, and intensity-modulated RT in 25% of patients. Androgen-deprivation (AD) therapy lasting < or = 6 months was administered to 34% of patients. RESULTS: The 5-year and 7-year bRFS rates were 63% and 59%, respectively. On multivariate analysis, T classification (P < 0.001), pretreatment prostate-specific antigen level (P < 0.001), biopsy Gleason score (P = 0.001), radiation dose (P < 0.001), and year of therapy (P < 0.001) were independent predictors of biochemical failure. Age, race, AD therapy, and RT technique did not predict for biochemical failure. For patients with low-risk tumors, the 5-year bRFS rates for those who received RT doses of < or = 68.0 Gy, 68.0-72.0 Gy, and > or = 72.0 Gy were 52%, 82%, and 93%, respectively (P < 0.001); for patients with intermediate-risk tumors, the respective 5-year bRFS rates were 27%, 51%, and 83% (P < 0.001); and for patients with high-risk tumors, the respective 5-year bRFS rates were 21%, 29%, and 71%, respectively (P < 0.001). CONCLUSIONS: The most significant therapeutic factor affecting bRFS rates after RT was radiation dose, rather than AD therapy use or radiation technique.     

Her2/neu-positive disease does not increase risk of locoregional recurrence for patients treated with neoadjuvant doxorubicin-based chemotherapy, mastectomy, and radiotherapy

PURPOSE: Preclinical data suggest that overexpression of Her2/neu confers cellular radioresistance. We retrospectively studied whether Her2/neu-positive disease was associated with locoregional recurrence (LRR) after postmastectomy radiotherapy (RT) for breast cancer. METHODS AND MATERIALS: Data from 337 patients treated in four institutional prospective clinical trials neoadjuvant doxorubicin-based chemotherapy, mastectomy, and RT were reviewed. The trials were conducted between 1989 and 2000. Of the 337 patients, 108 (32%) had tumors that were tested for Her2/neu, with positivity defined by 3+ immunohistochemistry staining or gene amplification detected by fluorescence in situ hybridization. RT was delivered to the chest wall and draining lymphatics (median dose, 50 Gy) followed by a chest wall boost (median dose, 10 Gy). RESULTS: Thirty-two patients had Her2/neu-positive disease and 76 patients had Her2/neu-negative disease. The Her2/neu-positive tumors were associated with a greater rate of estrogen receptor-negative disease (p = 0.03), the presence of supraclavicular disease at diagnosis (p = 0.027), and a greater number of positive lymph nodes after chemotherapy (p = 0.026). Despite these adverse features, the actuarial overall LRR rate was roughly equivalent for the patients with Her2/neu-positive tumors vs. those with Her2/neu-negative tumors (5-year rate 17.5% vs. 13.9%, respectively; 10-year rate 17.5% vs. 18.9%, respectively; p = 0.757). On Cox regression analysis of LRR adjusted for N stage and estrogen receptor status, the hazard ratio for Her2/neu positivity was 0.89 (95% confidence interval, 0.31-2.59; p = 0.83). CONCLUSION: Her2/neu overexpression does not appear to predispose to LRR after neoadjuvant doxorubicin-based chemotherapy, mastectomy, and RT.     

乳腺癌改良根治术后常规放疗剂量学分析

目的 分析乳腺癌改良根治术后常规二维放疗模式下胸壁及锁骨上区剂量分布和内乳区非计划性受量。方法 回顾分析2015-2016年间20例改良根治术后放疗的女性乳腺癌患者资料,左右乳腺癌各10例。放疗范围为患侧胸壁和锁骨上下区,处方剂量43.5Gy (2.9 Gy/次)。胸壁采用单前野电子线照射,锁骨上下野予以6MV X线单前野照射。同时比较锁骨上下采用前后对穿野照射时的剂量分布。结果 锁骨上单前野照射中85%患者接受了D90≥90%处方剂量,前后对穿野中所有患者均达到了D90≥90%处方剂量(39.15Gy, EQD2≥45Gy),胸壁单前电子线野D90中位数为35.38Gy。非计划性内乳区域照射的平均剂量中位数为13.65Gy。体重指数小患者锁骨上、胸壁的D90更高(P=0.039、0.347)。结论 锁骨上下单前X线野能满足绝大多数受量≥90%的处方剂量照射,而前后对穿野在满足所有人受量需求时不增加正常组织受量。单前电子线野胸壁剂量分布不佳,内乳区有一定的非计划性照射,但剂量有限。体重指数是影响剂量分布的因素。