Adjuvant chemotherapy with doxorubicin in high-grade soft tissue sarcoma: a randomized trial of the Scandinavian Sarcoma Group

From January 1981 to February 1986, a total of 240 patients with primary, malignancy-grade III or IV soft tissue sarcoma were entered into an adjuvant chemotherapy multicenter trial conducted by the Scandinavian Sarcoma Group (SSG). Of these patients, 181 were evaluable. The tumor was located in the extremities in 155 patients. After radical surgery (wide and compartmental) the patients were randomized to treatment with single-agent doxorubicin 60 mg/m2 administered as an intravenous (IV) bolus once a month for 9 months (group 1, n = 77) or to control (group 2, n = 77). If the surgical procedure was marginal, the patients initially received postoperative radiotherapy, followed by doxorubicin (group 3, n = 16) or control (group 4, n = 11). The control groups did not receive any adjuvant chemotherapy. Adjuvant therapy was initiated within 6 weeks of surgery (group 1) or within 10 weeks of surgery for patients receiving postoperative radiotherapy (group 3). With a median follow-up of 40 months, there was no significant difference between the four treatment groups in overall survival (group 1, 75%; group 2, 70%; group 3, 69%; group 4, 73%), disease-free survival (group 1, 62%; group 2, 56%; group 3, 62%; group 4, 64%), or local tumor control (group 1, 92%; group 2, 92%; group 3, 87%; group 4, 90%). The conclusions were the same whether the total group or evaluable patients only were included in the analysis. The local recurrence rate for patients undergoing radical surgery was 8% and for patients undergoing marginal surgery followed by radiotherapy was 12%. This study indicates that the use of single-agent doxorubicin as postoperative adjuvant chemotherapy has no significant clinical benefit in patients with high-grade soft tissue sarcoma.     

Treatment and local control of primary extremity soft tissue sarcomas.

BACKGROUND AND OBJECTIVES: Modern series of adult extremity soft tissue sarcomas utilize combinations of modalities in all patients. Remaining questions: 1) is it necessary to strive for wide margins in the multimodality era; 2) to use adjuvant therapy in every high-grade sarcoma? 3) Does previous partial or marginal resection seriously interfere with the definitive resection? METHODS: In a retrospective review of 194 extremity soft tissue sarcomas (1977-1994), limb preservation was possible in 181/194 (93%) of cases. Patients with narrow margins received adjuvant radiation. Some patients were referred after partial (n = 39) or "complete" (n = 63) excision. RESULTS: Local recurrence was observed in 181/141 (13%) of patients treated with wide or compartmental resection, and in 10 of 42 (24%) of those treated with conservative resection plus radiation (P = 0.14). The 5-year survival rate for grade III, >/=5-cm sarcomas was not significantly different (P = 0.82) with adjuvant (46%) or without (48%) adjuvant systemic chemotherapy. Five-year survival varied (P = 0.0001) according to grade. Patients referred with partial, or "complete" (63%, 38/63, had residual tumor at reoperation) excision had a local recurrence rate of 8% and 6%, and 5-year survival rates of 75% and 84%, respectively. CONCLUSIONS: 1) It is important to strive for wide margins even when adjuvant radiation is intended. 2) When a wide margin is possible, adjuvant radiation may not be necessary. 3) Adjuvant systemic chemotherapy may be considered for high-grade tumors, preferably within a prospective protocol. 4) A partial or "complete" excision of the tumor before referral to a tertiary center does not appear to compromise the limb preservation, local control, or survival rates of these patients.     

Pattern of Recurrence following Local Chemotherapy with Biodegradable Carmustine (BCNU) Implants in Patients with Glioblastoma

OBJECTIVE: Recently a randomized placebo-controlled phase III trial of biodegradable polymers containing carmustine has demonstrated a significant survival benefit for patients treated with local chemotherapy. A local chemotherapy applied directly to the resection cavity may act directly on residual tumor cells in adjacent brain possibly leading to a local control of the tumor and increased survival. METHODS: We have analyzed the pattern of recurrence using serial MRI studies of 24 patients treated with GLIADEL Wafers or placebo wafers following resection of glioblastomas. RESULTS: Of 24 patients 11 received carmustine wafers and 13 placebo. The age distribution and Karnowsky performance scores of the two populations were not different. However, the median survival (14.7 versus 9.5 months; P = 0.007) and the time to neurological deterioration (12.9 +/- 4.85 vs. 9.4 +/- 2.73 months; P = 0.035) was significantly longer in the treatment group versus the placebo treated control. Preoperative and follow up MRI studies were evaluated in a blinded fashion. Out of 24 patients that entered the analysis 11 showed clearance of all contrast enhancement following resection of glioblastomas. Seventeen tumors progressed locally and 7 showed different patterns of distant failure. Within the carmustine treated group 8 patients showed a local treatment failure with recurrent tumors immediately adjacent to the resection cavity or progression form a residual tumor. Three patients showed a multifocal distant and local pattern of failure after complete or subtotal removal. In no case the local chemotherapy resulted in a distant recurrence only. However, the time to radiographic progression was 165.1 +/- 80.75 days for the GLIADEL Wafer group and 101.9 +/- 43.06 days for the placebo group (P = 0.023). CONCLUSION: In this subgroup analysis of a phase III trial population both the clinical progression and radiological progression were significantly delayed in patients treated with local chemotherapy, resulting in an increased survival time. Local chemotherapy with carmustine containing wafer implants did not result in an altered pattern of recurrence and did not promote multifocal patterns of recurrence.     

Results of surgery and multimodal therapy for patients with soft tissue sarcoma invading to vascular structures

BACKGROUND: The aim of this study was to analyze the impact of resection and reconstruction of major vessels on the limb salvage rate, local disease free survival, and overall survival for patients with soft tissue sarcomas invading to neurovascular bundles. METHODS: Twenty patients were treated in a 7-year period by one surgical team. Preoperative therapy consisted of isolated limb perfusion (n = 6), systemic chemotherapy (n = 4), systemic chemotherapy combined with regional hyperthermia (n = 2), and external beam irradiation (n = 1). All patients underwent resection of the sarcoma monobloc together with the neurovascular bundle invaded. Vessels were replaced by an autologous vein transplant or an allograft, and, in six patients, a myocutaneous flap or skin graft had to be used for soft tissue coverage. RESULTS: Histologic examination revealed negative histologic margins (R0-resection) and infiltration of the neurovascular bundle in all patients. In four patients, a local recurrence was observed, and, in three of them, reresection with negative margins was achieved. The mean local recurrence free survival was 54 months (confidence interval [CI], 42-66 months), and the mean overall survival was 48 months (CI, 32-57 months). Limb salvage was achieved in 19 of 20 patients. Eleven patients developed distant metastases after a mean survival time of 30 months. CONCLUSIONS: Extended sarcoma resection, including vessel replacement after preoperative multimodal therapy, provides long term local control and limb salvage. Amputation of extremity sarcoma can hardly be justified, even in cases of tumor invasion to neurovascular bundles. However, efforts to achieve better control over systemic spread are required for long term disease free survival.     

Completely resected anaplastic thyroid carcinoma combined with adjuvant chemotherapy and irradiation is associated with prolonged survival.

BACKGROUND: The prognosis of anaplastic thyroid carcinoma (ATC) has been dismal. The objective of this study was to identify prognostic factors in patients who had prolonged survival. METHODS: Patients with ATC were identified from a computer database at a tertiary referral center. Univariate and multivariate analyses for survival differences were performed using the Kaplan-Meier log-rank statistic and the Cox proportional hazards model, respectively. RESULTS: Of the 33 evaluable patients, median survival was 3.8 months. Median age was 69 years. Prior goiter was present in 6 patients (18%), and 6 (18%) had prior thyroid carcinoma. Median tumor size was 6 cm, and 12 (36%) had adjacent well-differentiated carcinoma. Of the 26 patients who underwent neck exploration, 8 patients were potentially cured and received postoperative chemotherapy and irradiation; 4 (50%) were surgically macroscopically free of disease, and 4 (50%) patients had minimal residual disease after total thyroidectomy and resection of tumor adherent to adjacent structures. Four of these 8 patients survived longer than 2 years; their 5-year survival estimate was 50%. Eighteen patients underwent palliative resection of neck disease, leaving macroscopic residual disease or distant metastases; postoperative adjuvant chemotherapy and irradiation were administered in 16 of these 18 patients. Seven patients were treated with only chemotherapy and irradiation. In patients treated with potentially curative resection, median survival was 43 months compared with 3 months with palliative resection (P =0.002); the median survival of 3.3 months with only chemotherapy and irradiation was no different than palliative resection (P =0.63). No association was found between survival and age, prior goiter, prior thyroid carcinoma, adjacent differentiated carcinoma, or tumor size. CONCLUSIONS: Although the prognosis of most patients with ATC continues to be poor, complete resection of ATC combined with postoperative adjuvant chemotherapy and irradiation resulted in long-term survival, even with persistent minimal disease that remained on vital structures. An aggressive attempt at maximal tumor debulking followed by adjuvant therapy was found to be warranted in patients with localized ATC.     

Impact of ductal resection margin status on long-term survival in patients undergoing resection for extrahepatic cholangiocarcinoma

BACKGROUND: The current study was performed to clarify whether the presence of residual carcinoma in situ at ductal resection margins differs prognostically from residual invasive ductal lesions in patients undergoing surgical resection for extrahepatic cholangiocarcinoma. METHODS: A retrospective analysis of 84 patients with extrahepatic cholangiocarcinoma who underwent surgical resection was conducted. The ductal resection margin status was classified as negative (n = 64 patients), positive with carcinoma in situ (n = 11 patients), or positive with invasive carcinoma (n = 9 patients). The median follow-up period was 105 months. RESULTS: Ductal margin status was found to be a strong independent prognostic factor by both univariate (P = 0.0002) and multivariate (P = 0.0039) analyses. The outcome after surgical resection was comparable between patients with negative ductal margins (median survival time of 45 months; cumulative 10-year survival rate of 40%) and those with positive ductal margins with carcinoma in situ (median survival time of 99 months; cumulative 10-year survival rate of 23%; P = 0.4742). In patients with positive ductal margins, the outcome was found to be significantly better in patients with residual carcinoma in situ than in those with residual invasive carcinoma (median survival time of 21 months; cumulative 5-year survival rate of 0%; P = 0.0003). Of 11 patients with residual carcinoma in situ, 4 died of tumor recurrence and the initial site of the disease recurrence was local. All 9 patients with residual invasive carcinoma died of disease recurrence (local recurrence with or without distant metastases) within 40 months after surgical resection. CONCLUSIONS: After surgical resection for extrahepatic cholangiocarcinoma, invasive carcinoma at ductal resection margins appears to have a strong adverse effect on patient survival, whereas residual carcinoma in situ does not.     

Uterine Sarcoma: Clinical Presentation,Treatment and Survival Outcomes in Thailand

Background: Uterine sarcoma is a group of rare gynecologic tumors with various natures, and different lines of treatment. Most have a poor treatment outcome. This study targeted clinical characteristics, treatment, overall survival (OS), progression-free survival (PFS), and prognostic factors in uterine sarcoma patients in one tertiary center for cancer care. Materials and Methods: Uterine sarcoma patients who were treated at the Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital between January 1994 and December 2014 were identified. Clinico-pathological data were analyzed. Prognostic outcomes were examined by Kaplan-Meier curves and Cox regression analysis. Results: We identified 46 uterine sarcoma patients: 25 carcinosarcoma (CS) (54.3%), 15 leiomyosarcoma (LMS) (32.6%), and 6 undifferentiated uterine sarcoma (UUS) (13.1%) cases. Mean age was 54.011.9 years (range 25-82 years). Abnormal uterine bleeding was the most common presenting symptom (63.0%). Among 33 patients (71.7%) who had pre-operative tissue collected, diagnosis of malignancy was correct in 29 (87.9%). All patients received primary surgery and retroperitoneal lymph nodes were resected in 34 (73.9%). After surgery, 5 (10.9%) had gross residual tumors. Stage I disease was most commonly found (56.5%). Adjuvant treatment was given to 27 (58.7%), most commonly chemotherapy. After a median follow-up of 16.0 months (range 0.8-187.4 months), recurrence was encountered in 22 patients (47.8%). Median time to recurrence was 5.8 months (range1.0-105.5 months). Distant metastasis was more common than local or loco- regional failure. The 2-year PFS was 45.2% (95% confidence interval [CI], 30.6%-59.7%) and the 2-year OS was 48.3% (95% CI, 33.3%-60.7%). Multivariable analyses found residual disease after surgery as a significant factor only for PFS. Conclusions: Uterine sarcoma is a rare tumor entity. Even with multimodalities of treatment, the prognosis is still poor. Successful cytoreductive surgery is a key factor for a good survival outcome.     

A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group Study

After hysterectomy, 156 evaluable patients with stage I (limited to the corpus) or stage II (limited to the corpus and cervix) uterine sarcomas were randomly assigned to adjuvant chemotherapy with Adriamycin (Adria Laboratories, Columbus, Ohio) for six months or to no further treatment. Pelvic irradiation (external or intracavitary) was optional before randomization. Of 75 patients receiving Adriamycin, 31 have suffered recurrences compared with 43 of 81 receiving no adjuvant chemotherapy. This difference is not statistically significant. Moreover, there is no difference in progression-free interval or survival. The optional radiotherapy did not influence the outcome although there was a suggestion that vaginal recurrence was decreased by pelvic radiotherapy. The recurrence rates in specific cell types (leiomyosarcoma, homologous mixed mesodermal sarcoma, or heterologous mixed mesodermal sarcoma) were not significantly different although the pattern of recurrence differed, with pulmonary metastases being more common in leiomyosarcoma and extrapulmonary recurrence being more common in mixed mesodermal sarcoma. The outcome with respect to chemotherapy was not altered even after adjusting for maldistribution of cases. Thus, we could not show a benefit for this dose schedule of Adriamycin as adjuvant treatment for uterine sarcomas.     

Alternating hepatic arterial infusion and systemic chemotherapy for stage IV colorectal cancer with synchronous liver metastasis

Among 41 patients with synchronous liver metastases of colorectal cancer, 15 patients underwent synchronous resection of their liver metastases and achieved a median survival time (MST) of 1,441 days (versus 748 days for the 26 patients without resection, p=0.038), a median relapse-free survival time of 652 days (MST not reached), and a recurrence rate in the residual liver of 20% (3/15 patients). The alternating hepatic arterial infusion and systemic chemotherapy showed partial response (PR) in 6 cases, stable disease (SD) in 8 cases, and progressive disease (PD) in 1 case (n=15/26). They had an objective response rate of 40% (6/15), tumor control rate (>/= SD) of 93.3% (14/15), one-year progression-free survival rate of 35.7%, 50% time to progression of 270 days, one-year survival rate of 76.2%, and two-year survival rate of 50.8% (MST not reached). Grade 3 leucopenia was observed in 2/15 patients (13.3%). These results suggest that the present alternating therapy may become a standard regimen for patients in whom synchronous resection of liver metastases is impossible and patients who have stage IV colorectal cancer with a risk of recurrence in the remnant liver and/or at extrahepatic sites such as the lungs.     

Therapy for localized Ewing's sarcoma of bone

Fifty-two previously untreated patients with localized Ewing's sarcoma of bone were treated with nonintensive chemotherapy in combination with surgery or radiation therapy (RT). RT was delivered to limited volumes in a dose dependent on the initial response to induction chemotherapy (30 to 35 Gy v 50 to 55 Gy). Fifty of the 52 patients achieved complete or partial responses with induction chemotherapy, with one nonresponding patient rendered free of tumor with surgery. Fifty patients were evaluable for local control of tumor and overall response to protocol therapy. Seventeen relapses have occurred; three metastatic, four local plus metastatic, and ten local. Two factors predicted worse disease-free survival: high WBC count (P = .03) and size of primary tumor (P = .05). Of the 14 local recurrences, 12 occurred in 28 patients who presented with primary tumors greater than 8 cm in size while only two of 22 patients with lesions less than 8 cm had local recurrence. The Kaplan-Meier estimate of disease-free survival at 3 years is 82% for those with small lesions and 64% for those with larger lesions. Site of primary was of no prognostic value (P = .27). The 5-year survival estimate for all patients is 80% (median time on study, 3.3 years).     

72例标危型髓母细胞瘤放疗剂量对生存的影响

目的 回顾分析标危型髓母细胞瘤采用全脑全脊髓放疗剂量≤24 Gy和>24 Gy对预后的影响。方法 标危型髓母细胞瘤定义为年龄>3岁、未发生转移、肿瘤全切或近全切(残留≤1.5 cm³)。2003—2013年共入组72例初治儿童、青少年标危型髓母细胞瘤患者。患者术后接受全脑全脊髓+局部瘤床放疗和8个疗程辅助化疗,化疗方案为顺铂、司莫司汀或卡莫司汀联合长春新碱。按放疗剂量≤24 Gy和>24 Gy分为A、B组(20、52例),比较两组患者复发率和生存率。Kaplan-Meier法计算复发率和生存率并Logrank法检验组间差异。结果 A组接受全脑全脊髓放疗19.2~24.0 Gy,B组接受全脑全脊髓放疗24.1~30.6 Gy。放疗后66例(92%)患者完成全部辅助化疗。共11例患者复发。随访满3年患者48例,其中复发11例,死亡7例。全组3年EFS率为83%,3年OS率为86%。A组和B组患者3年EFS率分别为84%和83%(P=0.609), 3年OS率分别为85%和87%(P=0.963)。结论 标危型髓母细胞瘤经规范综合治疗效果较好,其中全脑全脊髓放疗剂量减少至19.2~24.0 Gy未影响疗效。     

Prognostic factors and treatment modalities in uterine sarcoma

The aim of this study was to identify the impact of various prognostic factors in the management of uterine sarcoma. Fifty-nine patients with uterine sarcoma were treated at King Faisal Specialist Hospital and Research Center between 1980 and 1997. Forty-three patients (73%) were treated by total abdominal hysterectomy and bilateral salpingo-oophorectomy, 7 (12%) total abdominal hysterectomy and bilateral salpingo-oophorectomy with sampling of pelvic lymph nodes, and 9 (15%) had biopsy only. Nine patients received adjuvant treatment; five had radiation therapy (XRT), two had chemotherapy, one had combined XRT and chemotherapy, and one received hormonal treatment. Leiomyosarcoma cases accounted for 42% of all the uterine sarcomas, carcinosarcoma cases for 34%, and endometrial stromal sarcoma (ESS) for 24%. Fifty (85%) patients had pathologic grade II and III tumor, with only 9 patients grade I. Twenty-seven patients (46%) were classified surgically as stage I, 7 (12%) as stage II, 17 (29%) as stage III, and 8 (13%) had stage IV tumor. Recurrences developed in 34 patients (71%). The 5- and 10-year overall actuarial survival for all patients was 42%, and the corresponding relapse-free survivals for those who achieved complete response after primary treatment (48 patients) were 27% and 20%. On the univariate analysis, grade I tumors (p = 0.04), ESS (p = 0.02), nonmetastatic stage (p = 0.05), and negative peritoneal cytology (p = 0.04) were associated with better overall survival. Factors associated     

Prognostic factors and outcome in women with uterine sarcoma.

OBJECTIVES: A retrospective analysis of patients with uterine sarcoma was undertaken to assess prognostic factors and treatment related outcomes. PATIENTS AND METHODS: Ninety-four patients (median age: 60years, range: 20-93years) with a histologically verified uterine sarcoma treated at the McGill University Health Centre (MUHC) between 1989 and 2004 were identified from the tumor registry and pathology database. RESULTS: Twenty-eight patients had an endometrial stromal sarcoma (ESS), 30 had a leiomyosarcoma (LMS), and 36 had mixed muellerian tumors (MMT). According to FIGO classification, Stage I, II, III, and IV tumors were identified in 49, 7, 20, and 18 patients, respectively. At the time of analysis, 55.5% of patients (52/94) were dead due to progressive sarcoma disease; 8.5% of the patients (8/94) were alive with disease recurrence, and 36.2% (34/94) were alive without disease recurrence, with a median survival of 35months. Univariate analysis demonstrated a statistically significant association between overall survival and histology in favor of patients with ESS (p<0.001). Analyzing each of the histological subtypes separately, adjuvant treatment with chemotherapy and/or hormonal treatment had no demonstrable impact on overall survival. In multivariate analysis age and advanced stage, remained a significant predictor for overall survival in patients with LMS and MMT, but not in patients with ESS. Regarding adjuvant treatment, radiotherapy had a significant impact on overall survival only in patients with MMT (p=0.002). CONCLUSIONS: In patients with uterine sarcoma, in comparison to LMS and MMT, ESS tends to present as a less aggressive disease with a favorable outcome. Furthermore, reflected by an improved overall survival after radiotherapy only in patients with MMT, it seems to be mandatory to differentiate between these histological subtypes.     

Oral trofosfamide and etoposide in pediatric patients with glioblastoma multiforme

BACKGROUND: Glioblastoma multiforme in childhood is rare, and the prognosis for patients with the disease is poor. The Pediatric Oncology Society of the Germanic language group (GPOH) enrolls patients in a series of pilot trials, the first of which is reported here (HIT-GBM-A). METHODS: Twenty-two patients with glioblastoma multiforme, World Health Organization Grade 4, between the ages of 3-15 years (45% male) were enrolled during the period 1995-1997. There were 13 supratentorial tumors, 8 brainstem tumors, and 1 cerebellar tumor. The patients underwent the following procedures: stereotactic biopsy (n = 3 patients), open biopsy (n = 1 patient), partial resection (n = 6 patients), subtotal resection (n = 4 patients), and macroscopic total resection (n = 8 patients). Adjuvant treatment consisted of oral chemotherapy with trofosfamide, 100 mg/m(2), and etoposide, 25 mg/m(2), daily or for 21-day cycles interrupted by 1-week rests. Standard fractionated radiation (54 grays) was started concurrently with the first cycle. RESULTS: The chemotherapy was well tolerated, with no treatment-related deaths and only minor side effects. The responses in 12 evaluable patients after two cycles were as follows: 1 complete response, 1 partial response, 3 patients with stable disease, and 7 patients with progressive disease. The median overall survival was 12 months. The 1-year, 2-year, and 4-year overall survival rates were 52%, 26%, and 22%, respectively, and the event free survival rates were 26%, 22%, and 4%, respectively. None of the four surviving patients (3.2 years, 3.4 years, 4.0 years, and 4.2 years after diagnosis) is event free. Two patients are alive after tumor progression: One patient was diagnosed with a medulloblastoma, and one patient was diagnosed with an osteosarcoma as second malignancies. A control group extracted from the Surveillance, Epidemiology, and End Results data had lower survival rates: the difference between the groups was not statistically significant (P = 0.26). CONCLUSIONS: This chemotherapy will not be used in a randomized trial of patients with glioblastoma; however, it may be evaluated for patients with tumors that have more chemoresponsive histologies.     

Preradiation chemotherapy for pediatric patients with high-grade glioma

BACKGROUND: To evaluate the feasibility and efficacy of intensive chemotherapy given prior to irradiation in pediatric patients with malignant glioma, the Society of Pediatric Oncology in Germany started a randomized trial in 1991. The high-grade glioma strata had to be closed because of insufficient patient accrual. The follow-up data from these patients are reported. METHODS: Fifty-two patients with World Health Organization (WHO) Grade 4 malignant glioma (n = 27 patients) or with WHO Grade 3 anaplastic astrocytoma (n = 25 patients) between the ages of 3 years and 17 years were available for analysis. The tumor locations were supratentorial in 42 patients, the cerebellum in 8 patients, and the spinal cord in 2 patients (the brainstem was excluded). Tumor surgeries were biopsy in 10 patients, partial resection in 5 patients, subtotal resection in 10 patients, and macroscopic total resection in 21 patients. Patients received either 54 grays of irradiation (n = 22 patients) followed by chemotherapy with lomustine, vincristine, and cisplatin (maintenance chemotherapy) or sandwich chemotherapy (n = 30 patients), which consisted of ifosfamide, etoposide, methotrexate, cisplatin, and cytosine arabinoside followed by irradiation. RESULTS: The extent of resection was the most important prognostic factor. The median survival was 5.2 years for patients who underwent tumor resection of > or = 90% compared with 1.3 years for patients who underwent less than complete resection (P < 0.0005). After undergoing macroscopic total resection, sandwich chemotherapy (n = 15 patients) resulted in better overall survival (median, 5.2 years) compared with the maintenance protocol (n = 16 patients; median survival, 1.9 years; P = 0.015). A Cox multivariate regression analysis showed better survival for female patients (P = 0.025), WHO Grade 3 disease (P = 0.016), tumor resection of > or = 90% (P = 0.003), irradiation with > or = 54 grays (P = 0.003), and sandwich chemotherapy (P = 0.006). CONCLUSIONS: These data suggest that early, intensive chemotherapy increases survival rates in patients with malignant glioma who undergo complete resection.     

Undifferentiated sarcoma of the liver in childhood: a curable disease

BACKGROUND: Undifferentiated (embryonal) sarcoma of the liver (UESL) is a rare childhood hepatic tumor, and it is generally considered an aggressive neoplasm with an unfavorable prognosis. METHODS: The Soft Tissue Sarcoma Italian and German Cooperative Groups enrolled 17 children with UESL in studies conducted between 1979 and 1995. They were treated using the same multimodal approach as for patients with sarcomas including conservative surgery at diagnosis, multiagent chemotherapy, and second-look operation in cases of residual disease. Radiotherapy was occasionally used (2 of 17 patients). RESULTS: Twelve patients are alive with follow-up ranging from 2.4 to 20 years. Eight underwent complete tumor resection either at diagnosis or after preoperative chemotherapy, and all are currently alive. After initial chemotherapy tumor reduction was evident in six of nine evaluable cases. Overall three patients died of disease and one of a surgical complication. One child died in second complete remission for a non-disease-related cause. CONCLUSIONS: The current prognosis of UESL no longer should be regarded as poor. Modern multimodal treatment and supportive therapy have improved survival.     

Preoperative diagnosis and treatment results in 106 patients with uterine sarcoma in Hokkaido, Japan

OBJECTIVE: The aim of this study was to evaluate the clinicopathological features of uterine sarcoma in Hokkaido, Japan, between 1990 and 1999, and to identify prognostic factors of patients with such malignancies in this area and period. METHODS: One hundred and six patients with histologically proven uterine sarcoma were evaluated retrospectively. RESULTS: 93.5% of the patients with carcinosarcoma (CS) were diagnosed as having malignant disease preoperatively, while 65% of those with leiomyosarcoma (LMS) and 75% of those with endometrial stromal sarcoma (ESS) were preoperatively diagnosed as benign leiomyoma. When patients had no residual disease postoperatively, 5-year survival rates in patients with CS and LMS were 78.8 and 73.0%, respectively. ESS cases had a better prognosis (94.7% for stage I cases). In patients with early-stage sarcoma, pelvic lymphadenectomy and adjuvant chemotherapy, with or without cis-diamminedichloroplatinum, failed to show a survival benefit in both CS and LMS cases. Distant metastasis, myometrial invasion, and no residual disease at surgery were significantly associated with risk of death or recurrence in CS and LMS cases. CONCLUSION: Accurate preoperative diagnosis of uterine sarcoma was difficult, and no residual disease at surgery was the most important prognostic factor in patients with this disease. Postoperative adjuvant therapy had little effect on survival, especially in early-stage disease.     

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.     

Undifferentiated embryonal sarcoma of the liver in adults

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL), a rare tumor that predominantly affects children, generally has been considered an aggressive neoplasm with an unfavorable prognosis. More recent reports have indicated that modern multimodal treatment and supportive care improve the survival of children with UESL. Data regarding the treatment and survival of adults have not been reviewed comprehensively, and only a few adult patients with UESL have been reported in the literature. METHODS: The authors analyzed demographics, treatment, and actuarial survival of all reported cases of UESL in patients aged >or=15 years (n = 67 patients). In addition, 1 case is presented of a patient with UESL who was treated successfully at the authors' institution. RESULTS: The median survival of all patients with UESL who were analyzed was 29 months. Patients who underwent complete tumor resection followed by adjuvant chemotherapy survived over a median follow-up of 28.5 months and had significantly better survival compared with patients who underwent surgical treatment alone. Patients who underwent an incomplete tumor resection had a tendency toward poorer outcomes. CONCLUSIONS: To the authors' knowledge, this is the first report to demonstrate a significant effect on survival for adjuvant chemotherapy after complete surgical resection of UESL in adults. The role of neoadjuvant chemotherapy was not evaluated in this study. In the case study presented herein, combined therapy with surgery and chemotherapy led to a complete, sustained remission that has lasted for >6 years to date.     

Localized unresectable non-rhabdo soft tissue sarcomas of the extremities in pediatric age: results from the Italian studies

BACKGROUND: Treatment of initially unresectable nonrhabdo soft tissue sarcomas (NRSTS) in pediatric age is debated, due to their different chemosensitivity. The authors objective was to evaluate clinical features and treatment results observed in a series of Italian patients over a 24-year period. METHODS: Fifty-two patients age 8-18 years (median 8 years) were observed (1979-2002). Primary sites were on the lower limbs in 41 and on the upper limbs in 11 cases. Clinical TNM and surgical Intergroup Rhabdomyosarcoma Staging systems were adopted. Therapeutic guidelines recommended an initial biopsy plus neoadjuvant chemotherapy. Aggressive delayed surgery of residual disease, including compartmental resections, was recommended. Radiotherapy was suggested only for patients age > 3 years when surgery was incomplete or not feasible. RESULTS: The evaluation was performed dividing the patients into two categories according to their chemosensitivity. Chemosensitive (CTs) sarcomas, 21: synovial sarcoma, 11; extraosseous Ewing sarcomas, 5; primitive peripheral neuroectodermic tumors, 5. Nonchemosensitive (CTns) sarcomas, 31: fibrosarcoma, 11; malignant peripheral nerve sheet tumors, 10; liposarcoma, 2; hemangiopericitoma adult type, 2; epithelioid sarcoma, 2; and alveolar soft part sarcoma, leiomyosarcoma, clear cell sarcoma, and sarcoma NOS, each 1. Nineteen of 21 patients with CTs-NRSTS were alive without disease: the 5-year overall survival (OS) and progression-free survival (PFS) were 94.4% and 79.3%, respectively; 23 of 31 patients with CTns-NRSTS were alive without disease: 5-year OS and PFS were 75.3% and 68.3%, respectively. Response to neoadjuvant chemotherapy was complete or partial in 10 of 20 evaluable CTs and in 8 of 26 evaluable CTns tumors. The achievement of complete delayed resection was particularly important for CTns-NRSTS. Tumor size < 5 cm, distal site, and tumor grading for CTns sarcomas were often linked to a favorable outcome; no conclusive results were detected concerning age of the patients or T status of the tumor. CONCLUSIONS: Multidisciplinary treatment without mutilating procedures allowed the cure of most patients with CTs and CTns-NRSTS. Relapses were cured in several cases of CTs tumors, whereas almost all patients with relapsed CTns tumors died due to the high rate of metastatic spread.