A European treatment protocol for bone sarcoma in patients older than 40 years

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10516-10516 ◽  
Author(s):  
S. Ferrari ◽  
S. Smeland ◽  
S. Bielack ◽  
A. Comandone ◽  
P. Dileo ◽  
...  
Keyword(s):  
Complete Remission ◽  
Treatment Protocol ◽  
International Study ◽  
Bone Sarcoma ◽  
Poor Responders ◽  
High Grade ◽  
Dedifferentiated Chondrosarcoma ◽  
Peripheral Neurotoxicity ◽  
Central Location ◽  
Synchronous Metastases

10516 Background: EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) is the first prospective multicenter international study for patients 41 - 65 years old with high-grade bone sarcoma. Methods: Patients with HG Osteosarcoma (OS), HG sarcoma NOS (S), Fibrosarcoma, MFH, Leiomyosarcoma, Dedifferentiated Chondrosarcoma (DCh) were included. Chemotherapy: Combinations of cisplatin/doxorubicin (CDP 100mg/m2/ADM 60mg/m2), ifosfamide/CDP(IFO 6g/m2/CDP 100mg/m2) and IFO/ADM (IFO 6g/m2/ADM 60mg/m2) were repeated three times (9 cycles). Surgery was planned after 3 cycles. Methotrexate (8g/m2) was postoperatively added in poor responders. Immediate surgery was allowed and 9 cycles with CDP, ADM, IFO were postoperatively given. Results: In December 2007, 140 patients were registered (median age 51 years). OS (51%), S (16%), and DCh (11%) were the more frequent histotypes. Synchronous metastases in 30 (21%) patients, central location of tumor in 45 (32%). Surgical complete remission (SCR) was achieved in 84% of patients, (localized 91%, metastatic 37%) without difference among the histology groups. One surgical-related and one chemotherapy-related death were reported. Grade 4 WBC and PLT incidence was 55% and 17%.Renal toxicity and peripheral neurotoxicity were reported in 16% and 20% of patients. With a median follow-up of 25 months (4–68) 3 year OS was 58% (95%CI 48–68%) [7% (95%CI 0–19%) without SCR]. In patients with SCR, 3 year OS and EFS were 46% (95%CI 9–83%) and 0% in case of synchronous metastases and 69% (95%CI58–80%) and 45% (95%CI33–57%) for localized patients; 50% (95%CI 29–71%) and 40% (95%CI 20–59%) for patients with central tumor, 73% (95%CI61–85%) and 44% (95%CI31–57%) for those with extremity tumor; 68% (95%CI 52–83%) and 46% (95%CI 32–54%) for OS, 64% (95%CI 42–85%) and 48% (95%CI 25–71%) for S, 48% (95%CI 13–82%) and 27% (95%CI 1–54%) for DCh. Conclusions: The protocol is feasible, but the chemotherapy-related toxicity is remarkable. Surgical complete remission is the main factor influencing survival. Central location and synchronous metastases are negative prognostic factors, but 50% 3-year OS can be achieved with aggressive local and systemic treatment. Osteosarcoma and high-grade sarcoma NOS benefit from chemotherapy more than patients with dedifferentiated chondrosarcoma. No significant financial relationships to disclose.

EURO-B.O.S.S.: A European study on chemotherapy in bone-sarcoma patients aged over 40: Outcome in primary high-grade osteosarcoma

2018 ◽  
Vol 104 (1) ◽  
pp. 30-36 ◽  
Author(s):  
Stefano Ferrari ◽  
Stefan S. Bielack ◽  
Sigbjørn Smeland ◽  
Alessandra Longhi ◽  
Gerlinde Egerer ◽  
...  
Keyword(s):  
Present Report ◽  
International Study ◽  
Bone Sarcoma ◽  
Hematological Toxicity ◽  
High Grade ◽  
Aggressive Approach ◽  
Younger Patients ◽  
Probability Of Survival ◽  
Localized Disease ◽  
High Grade Osteosarcoma

Introduction: The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international study for patients 41-65 years old with high-grade bone sarcoma treated with an intensive chemotherapy regimen derived from protocols for younger patients with high-grade skeletal osteosarcoma. Methods: Chemotherapy based on doxorubicin, cisplatin, ifosfamide, and methotrexate was suggested, but patients treated with other regimens at the investigators’ choice were also eligible for the study. Results: The present report focuses on the subgroup of 218 patients with primary high-grade osteosarcoma. With a median follow-up of 47 months, the 5-year probability of overall survival (OS) was 66% in patients with localized disease and 22% in case of synchronous metastases. The 5-year OS in patients with localized disease was 29% in pelvic tumors, and 70% and 73% for extremity or craniofacial locations, respectively. In primary chemotherapy, tumor necrosis ≥90% was reported in 21% of the patients. There were no toxic deaths; however, hematological toxicity was considerable with 32% of patients experiencing 1 or more episodes of neutropenic fever. The incidence of nephrotoxicity and neurotoxicity (mainly peripheral) was 28% and 24%, respectively. After methotrexate, 23% of patients experienced delayed excretion, in 4 cases with nephrotoxicity. Conclusions: In patients over 40 years of age with primary high-grade osteosarcoma, an aggressive approach with chemotherapy and surgery can offer the probability of survival similar to that achieved in younger patients. Chemotherapy-related toxicity is significant and generally higher than that reported in younger cohorts of osteosarcoma patients treated with more intensive regimens.

scholarly journals Patients presenting with metastases: stage IV uveal melanoma, an international study

2021 ◽  
pp. bjophthalmol-2020-317949
Author(s):  
Gaurav Garg ◽  
Paul T Finger ◽  
Tero T Kivelä ◽  
E Rand Simpson ◽  
Brenda L Gallie ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Ciliary Body ◽  
Regional Lymph Node ◽  
Subcutaneous Tissue ◽  
Primary Tumour ◽  
Stage Iv ◽  
International Study ◽  
Whole Body ◽  
Retrospective Data Analysis ◽  
Synchronous Metastases

ObjectiveTo analyse ocular and systemic findings of patients presenting with systemic metastasis.Methods and analysisIt is an international, multicentre, internet-enabled, registry-based retrospective data analysis. Patients were diagnosed between 2001 and 2011. Data included: primary tumour dimensions, extrascleral extension, ciliary body involvement, American Joint Committee on Cancer (AJCC)-tumour, node, metastasis staging, characteristics of metastases.ResultsOf 3610 patients with uveal melanoma, 69 (1.9%; 95% CI 1.5 to 2.4) presented with clinical metastasis (stage IV). These melanomas originated in the iris, ciliary body and choroid in 4%, 16% and 80% of eyes, respectively. Using eighth edition AJCC, 8 (11%), 20 (29%), 24 (35%), and 17 (25%) belonged to AJCC T-categories T1–T4. Risk of synchronous metastases increased from 0.7% (T1) to 1.5% (T2), 2.6% (T3) and 7.9% (T4). Regional lymph node metastases (N1a) were detected in 9 (13%) patients of whom 6 (67%) had extrascleral extension. Stage of systemic metastases (known for 40 (59%) stage IV patients) revealed 14 (35%), 25 (63%) and 1 (2%) had small (M1a), medium-sized (M1b) and large-sized (M1c) metastases, respectively. Location of metastases in stage IV patients were liver (91%), lung (16%), bone (9%), brain (6%), subcutaneous tissue (4%) and others (5%). Multiple sites of metastases were noted in 24%. Compared with the 98.1% of patients who did not present with metastases, those with synchronous metastases had larger intraocular tumours, more frequent extrascleral extension, ciliary body involvement and thus a higher AJCC T-category.ConclusionsThough higher AJCC T-stage was associated with risk for metastases at diagnosis, even small T1 tumours were stage IV at initial presentation. The liver was the most common site of metastases; however, frequent multiorgan involvement supports initial whole-body staging.

Clinical significance of chronic endometritis in poor responder`s patients underg art programs

2018 ◽  
pp. 92-97
Author(s):  
G.V. Strelko ◽  
◽  
V.V. Ulanova ◽  
Keyword(s):  
Risk Factors ◽  
Diagnostic Criteria ◽  
Pathological Condition ◽  
Treatment Protocol ◽  
Ovarian Response ◽  
Laboratory Research ◽  
Control Group ◽  
Poor Responders ◽  
Chronic Endometritis ◽  
Tract Infections

The objective: determination of the frequency of detection, risk factors, diagnostic criteria for chronic endometritis in poor responders patients in ART cycles with the study of the effectiveness of the proposed regimens for the treatment of this pathological condition. Materials and methods. A clinical study of the diagnosis of chronic endometritis in in poor responders patients have been conducted to develop individual approaches to overcoming infertility in a given cohort of women, taking into account not only the ovarian reserve, but also the endometrial status, assessed by clinical, instrumental and laboratory research methods, for achievement of successful implantation and ongoing pregnancy. The control group of women included 93 patients with infertility, a normal ovarian response to stimulation and lack of criteria for bad defendants. Results. As a result of a study conducted in poor responders patients, there is a significant percentage of the presence of chronic endometritis, which greatly complicates the overcoming of infertility. Risk factors for the occurrence of this pathological condition are genital tract infections, surgical intervention, intrauterine manipulations. Diagnostic criteria for chronic endometritis in women with infertility are micropolips, stomach edema, local and diffuse congestion of the endometrium during hysteroscopic examination and high expression of the imunohistochemical marker CD-138. Conclusion. The treatment protocol of the first line of chronic endometritis – docxicillin 100 mg 2 times a day 14 days, neomycin sulfate 35 000 MU, polymyxin B sulfate 35 000 MU, nystatin 100 000 MU for 1 suppositirium 1 time per day for 10 days and diclofenac 100 mg rectally for 5 days – is effective in 67.5% of cases . In patients who are resistant to previous antibiotic therapy, the second line treatment regimen is – сefotaxime 2.0 i /v 1 time per day, gentamycin 80 mg 3 times a day in / m, metronidazol 100 ml per day i / v, and diclofenac 100 mg rectally once daily for 7 days – the effectiveness of the treatment of chronic endometritis reached 79.1% of the cases. Key words: chronic endometritis, infertility, poor responders, ART.

Radiotherapy after High-Dose Chemotherapy Followed by Autologous Bone Marrow Transplantation in Patients with Intermediate or High-Grade Non-Hodgkin's Lymphoma

1996 ◽  
Vol 82 (4) ◽  
pp. 335-338
Author(s):  
Salvina Barra ◽  
Almalina Bacigalupo ◽  
Renzo Corvò ◽  
Marina Guenzi ◽  
Tindaro Scolaro ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Complete Remission ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
High Grade ◽  
Bulky Disease ◽  
Autologous Bone

Patients with intermediate or high-grade non-Hodgkin's lymphoma are rarely cured of their disease after the failure of conventional therapy. Autologous bone marrow transplantation (ABMT) offers such patients a new possibility of cure. Our purpose was to evaluate the usefulness of radiotherapy in these patients who did not achieve complete remission of disease after high-dose chemotherapy (HDCT) followed by ABMT or who had previous bulky disease. In this study we examined 10 patients: after HDCT+ABMT, 9 patients had persistent disease and 1 patient with previous bulky disease was in complete remission. All patients underwent involved-field radiotherapy administered by a 6-18 MV linear accelerator, total mean dose 4000 cGy (range, 3200-5000 cGy). At the end of radiotherapy we observed 6 complete responses and 4 progressions of disease outside the radiotherapy field. No serious side effects were observed. To date, of the 6 complete responses 2 have relapsed (after 9 and 11 months) and 4 are alive and disease free at 24 months (range, 8-39 months) after radiotherapy. In our opinion, radiotherapy is an effective treatment after HDCT+ABMT and may have a role in a prospective multidisciplinary approach.

Chemotherapy in the Management of Osteosarcoma and Ewing's Sarcoma

2007 ◽  
Vol 5 (4) ◽  
pp. 449-455 ◽  
Author(s):  
Scott M. Schuetze
Keyword(s):  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Disease Patient ◽  
Bone Sarcoma ◽  
The United States ◽  
High Grade ◽  
Medical Oncologists ◽  
Bone Sarcomas ◽  
Localized Disease ◽  
Relapsed Disease

Sarcomas of bone are rare malignancies diagnosed in fewer than 3000 individuals yearly in the United States. Ewing's sarcoma and most osteosarcoma are high-grade neoplasms and account for approximately one half of bone sarcoma cases. Fewer than 20% of patients presenting with localized Ewing's sarcoma or osteosarcoma are cured with surgery alone. Current management typically involves collaboration among orthopedic oncologists, medical oncologists, musculoskeletal radiologists, sarcoma pathologists, and radiation oncologists. Modern multidisciplinary management of Ewing's sarcoma and osteosarcoma has improved the cure rate of patients with localized disease to more than 50%. Primary chemotherapy for high-grade bone sarcomas often involves intensive, multiagent regimens, and few secondary chemotherapy options are available to treat refractory or relapsed disease. Patient participation in clinical trials of novel therapies for Ewing's sarcoma and osteosarcoma should be strongly encouraged.

Experience of a Brazilian Institution with Adult Acute Lymphoblastic Leukemia: Clinical, Laboratory and Prognosis in 102 Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4447-4447
Author(s):  
Edilson D. Pinheiro-júnior ◽  
Elvira R.P. Velloso ◽  
Beatriz Beitler ◽  
Gracia A. Martinez ◽  
Monika Conchon ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Complete Remission ◽  
Clinical Laboratory ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Treatment Protocol ◽  
Rank Test ◽  
Induction Treatment ◽  
Induction Phase ◽  
Adverse Factor

Abstract ALL is an aggressive bone marrow neoplasm, mainly associated with a poor outcome in adult patients. The aim of this study is to describe clinical, laboratory and prognostic factors in 102 patients treated in one institutional department from 1990 to 2005, retrospectively. Adult ALL subtype L3 (FAB) or B-IV (EGIL) was excluded. Statistical analysis was done by SPSS 10.0.The association of features and prognosis was assessed by Pearson’s chi-square. OS and DFS curves were constructed by Kaplan-Meier method and the differences were analyzed by the log-rank test. Mean age was 30,6 (12 to 82) years and 55,9% was male. Clinical findings, at diagnosis, were fatigue (55,9%), splenomegaly (56,9%), hepatomegaly (54,6%), lymphadenopathy (52,6%), fever (38,8%), bone pain (28,6%), bleeding (27,5%) and headache (15,3%). Involvement of CNS was detected in 11(10,8%) patients and testicular involvement was observed in one patient. Cutaneous infiltration occurred in one patient immunophenotyping T-IV(group b). Kidney and pulmonary infiltration, documented by biopsy, was found in 2 and 1 patients respectively. At diagnosis; mean blood values were 8,5g/dl, 84.341/mm3 and 76.275/mm3 for hemoglobin, leukocytes and platelets respectively. 98,7% of the patients presented with lymphoblasts in peripheral blood. FAB classification was L1 and L2, 50% each. B and T-ALL was observed in 69,7% and 30,2% respectively. One case was identified as biphenotypic B and T leukemia. Karyotype analysis was performed in 40 cases, Ph chromosome was identified in 20% (8/40) of the cases. Others abnormalities were hyperdiploid karyotype (6/40); t(4;11) in 2 cases; t (1;19) and t(10;11) each one with 1 case. Patients were treated with different protocols: BFM 86 modified (BFM 86M) in 47,1% (48/102) of the patients, OPAL86 and OPAL87 protocols (Linker e cols) in 45,1% (46/102) and CHOP in 7,8% (8/102). Ten patients died in early induction phase and 70,6% (65/92) were in complete remission after induction treatment. Age less than 35 years (p=0.021), CNS not infiltrated (p= 0.022) and immunophenotyping B1 and B3 (p=0.018) were associated with a better induction response in a univariated analysis. The first two parameters were associated with a high probability of complete response (p=0.041 and 0.034, respectively) in a multivariate analysis. In a median follow up of 49 months, we have observed a four-years OS of 30,4% (median 19 months). Univariate analysis of OS showed that age less than 35 and mainly less than 18 years (p=0.01), absent bleeding and hepatomegaly at diagnosis (p=0.0022; p=0.029), early time to complete remission (p=0.0001) and treatment protocol BFM 86M (p=0.0034) were associated with better survival. In a multivariate analysis age >35y, presence of hepatomegaly or bleeding at diagnosis were associated with poor OS, and were used to created a prognosis score. Patients with none to one adverse factor have a significantly better survival than patients with more than one (p=0.0001). We have observed in our population a DFS of 27% in 4 years with a median DFS of 18,9 months. Only fever, at diagnosis, was an adverse factor related to DFS in univariate analysis (p=0.0057).

Influence of Race and Nutritional Status on the Long Term Event Free Survival in Childhood Acute Lymphoblastic Leukemia (ALL): A 14-year Follow-up with a Reduced BFM-Based Treatment Protocol (GBTLI ALL-93)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 13-13
Author(s):  
Silvia Regina Brandalise ◽  
Maria Pombo-de-Oliveira ◽  
Vitoria Régia Pereira Pinheiro ◽  
Maria Jose Mastellaro ◽  
Waldir Veiga Pereira ◽  
...  
Keyword(s):  
High Risk ◽  
Complete Remission ◽  
Nutritional Status ◽  
Risk Group ◽  
Treatment Protocol ◽  
Low Risk ◽  
Event Free Survival ◽  
Free Survival ◽  
All Treatment

Abstract Background: Different event-free survival rates (EFS) of childhood ALL treatment regarding race, were published in the literature. However, a better consensus exists considering the bad prognosis of undernutrition. Taking into account the social economic reality of a low-income country such as Brazil, the systematic evaluation of these variables is of utmost importance, while inserted in a modern ALL treatment protocol. Objective: To compare, prospectively, the long-term EFS rates of previously untreated children with ALL, according to race and nutritional status at diagnosis. Methods: Patients were classified as Low Risk and High Risk according to NCI Criteria. Treatment schedule: Low Risk group: Remission induction therapy with DEXA 6mg/m2/d × 28 days, VCR 1.5 mg/m2/wk × 4, Daunomycin 25 mg/m2/wk × 4, L-ASP 10.000 U/m2/dose × 8, Ara-C 75mg/m2/dose × 8 and TIT therapy (day 0,28 and 42). Intensification therapy with MTX 2g/m2/wk × 4, 24 h continuous infusion with LCV rescue 15mg/m2/dose × 4, 6MP-50mg/m2 d × 21days and TIT therapy (x 4). Re-induction therapy: Dexa 6mg/m2 d × 21days, VCR 1.5mg/m2/wk × 4, L-ASP 10.000 U/m2/d × 4, 6-MP 50mg/m2/d × 14days, Ara-C 75 mg/m2/d × 4 and TIT therapy (x3). Central randomization was done for maintenance therapy duration (130 vs 103 wk). Maintenance: 6-MP 50mg/m2/d, MTX 25mg/m2/wk and TIT therapy every 8 weeks during all treatment. No CNS radiation was done. For High Risk patients, an induction intensification with intermediate dose of AraC (750 mg/m2/d × 6) was introduced, as well as, a rotational maintenance therapy with different pair of drugs were proposed (AraC 750mg/m2 × 4/Asp 6 000 U; Dexa/VCR/wk × 3 and 6-MP 75 mg/m2/d × 21 days/MTX 40 mg/m2/wk × 3). Prophylatic CNS radiation(18Gy) was done at wks 19–21 of therapy. Statistical analysis: EFS is defined as the time from diagnosis till any failure, relapse, death, or the development of a second malignancy. Continuous complete remission duration (CCR) is defined as EFS, contingent upon induction of a complete remission. EFS and CCR rates have been estimated by Kaplan and Meier’s method. Results: From October 1993 to September 1999, 867 patients were consecutively enrolled in the protocol GBTLI ALL-93. Fourteen pts were excluded (1.5%), due to wrong diagnosis or previous corticosteroid treatment. 853 pts were evaluated in this study. 447 pts were classified as Low Risk group (52%) and 406(48%) as High Risk. According to race, 226 pts (26.5%)were classified as black and 627 (73.5%) as white. Overall undernutrition was diagnosed among 7.0 % of the patients. In the black population 10.4% were undernourished, comparing with 5.7% in the white group. The 14yrs-EFS for all the study patients is 80% ± 2% and 55% ± 2.5% for the Low Risk and High Risk pts, respectively. Concerning race, the 14yrs-EFS is of 71.7% ± 4.5% for the black children, comparatively to 83% ± 2.1% for the white ones (p=0.01). According to the nutritional status, the EFS is of 70.2%± 1.7% and 53.0%± 6.8% for the nourished and undernourished children, respectively. Malnutrition had the worst desfavorable impact among the High Risk pts, with a 14yrs-EFS of 40.1% ± 8.7%, compared to those without malnutrition of 57.8% ± 2.7% (p = 0.05). Social and economical issues directly involved with treatment, were provided by means of free medical attention and drugs supplies. Treatment abandon was < 1%. Conclusion: The black race and undernutrition had significant adverse effect on the long-term EFS among the patients of this study.

Array-CGH Identifies Regions, Including the FOXP1 Locus, Associated with Different Clinical Outcome in Diffuse Large B-Cell Lymphomas (DLBCL) Treated with R-CHOP

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 478-478
Author(s):  
Marta Scandurra ◽  
Paola M.V. Rancoita ◽  
Timothy C. Greiner ◽  
Wing C. Chan ◽  
Julie M. Vose ◽  
...  
Keyword(s):  
Complete Remission ◽  
B Cell ◽  
De Novo ◽  
B Cell Lymphoma ◽  
Response To Therapy ◽  
Poor Responders ◽  
Score Distribution ◽  
Genomic Aberrations ◽  
Large B Cell

Abstract Background. Diffuse large B-cell lymphoma (DLBCL) consists of a heterogeneous group of tumors. More than 30% of cases are not cured with R-CHOP chemotherapy. Aim. To identify genomic aberrations that could affect the response to therapy, we performed an arrayCGH study on uniformly treated DLBCL patients. Materials and Methods. Tumor samples were analyzed with Affymetrix Human Mapping 250K SNP arrays. Eligibility criteria were diagnosis of de novo DLBCL, first line treatment with R-CHOP or R-CHOP-like regimens, availability of frozen biopsy and of clinical baseline and follow-up data. Exclusion criteria were: primary mediastinal DLBCL, primary central nervous system DLBCL, HIV-positivity. Material has been collected according to the local IRB guidelines. Results. Genomic tumor profiles have been obtained in 163 samples from 10 Institutions; 23/163 cases were excluded from this analysis because the information on response was not available; 140/163 cases fulfilled the study requirements. The clinical parameters of the patients reflected the normal DLBLC population, as shown by the IPI score distribution (0–1 in 30%, 2 in 37%, 3 in 23% and 4–5 in 10%). The median follow-up was 23 months (range 1–1251). Complete remission was observed in 108/140 (77%) patients, partial response in 21 (15%), stable disease in 6 (4%) and progression in 5 (2%). Genomic differences were observed between complete responders (108 cases) and the remaining patients, grouped together as poor responders (32 cases). The latter group had more gains of 3p14.1 (FOXP1 locus), 3q29, 11q24.3, and losses of 2p11.2-p13.3, 8p23.1- pter, 10p12.31-p13, 15q11.2-q14, 15q21.1 and copy neutral LOH of chromosome 9p. On the converse, 1q gains were more common among patients achieving complete remission. No differences were observed for other common region of gains (7, 12, 18q/BCL2) or losses (1p, 6q, 17p/TP53). Conclusions. Specific genomic aberrations are associated with the response to R-CHOP in patients with DLBCL. In particular, the gain of the 3p14.1 (FOXP1 locus), which is associated with a lack of response to R-CHOP, suggests that the role of FOXP1 should be further investigated in DLBCL.

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