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D Maraninchi

Publications and source records attributed to D Maraninchi.

At least 19 recordsLinked to original sources

A phase II trial of rituximab as adjuvant to intensive sequential chemotherapy in patients under 60 years with untreated poor-prognosis diffuse large B-cell lymphoma.

The potential benefit of rituximab as adjuvant to high-dose therapy (HDT) has been investigated in patients under 60 years with poor-risk (age-adjusted international prognostic index at 2-3) CD20+ diffuse large B-cell lymphoma (DLBCL). The treatment consisted of four cycles of high-dose CEOP (cyclophosphamide, epirubicin, vincristine, prednisone), plus etoposide and cisplatin during the two last cycles. Peripheral blood stem cells were collected after cycle 1, and reinfused after cycles 3 and 4. Four weekly rituximab infusions were subsequently delivered. Among the 36 patients included, 30 could complete chemotherapy schedule, and 24/36 received rituximab. A complete response occured in 26/36 patients (72%). With a median follow-up of 30 months, the estimated 5-year overall survival (OS) and event-free survival (EFS) rates (mean +/- s.d.) were 65 +/- 16 and 63 +/- 15%, respectively. For the 24 patients who received both chemotherapy and rituximab, the estimated 5-year OS and EFS rates were 86 +/- 14 and 82 +/- 15%. These data suggest that rituximab after HDT is feasible. Both complete remission rate and survival curves compare favorably with the poor outcome usually observed in high-risk DLBCL patients managed with HDT without rituximab.

Adult↗

Postoperative serum proteomic profiles may predict metastatic relapse in high-risk primary breast cancer patients receiving adjuvant chemotherapy.

A total of 30-50% of early breast cancer (EBC) patients considered as high risk using standard prognostic factors develop metastatic recurrence despite standard adjuvant systemic treatment. A means to better predict clinical outcome is needed to optimize and individualize therapeutic decisions. To identify a protein signature correlating with metastatic relapse, we performed surface-enhanced laser desorption/ionization-time of flight mass spectrometry profiling of early postoperative serum from 81 high-risk EBC patients. Denatured and fractionated serum samples were incubated with IMAC30 and CM10 ProteinChip arrays. Several protein peaks were differentially expressed according to clinical outcome. By combining partial least squares and logistic regression methods, we built a multiprotein model that correctly predicted outcome in 83% of patients. The 5-year metastasis-free survival in 'good prognosis' and 'poor prognosis' patients as defined using the multiprotein index were strikingly different (83 and 22%, respectively; P<0.0001, log-rank test). In a multivariate Cox regression including conventional pathological factors and multiprotein index, the latter retained the strongest independent prognostic significance for metastatic relapse. Major components of the multiprotein index included haptoglobin, C3a complement fraction, transferrin, apolipoprotein C1 and apolipoprotein A1. Therefore, postoperative serum protein pattern may have an important prognostic value in high-risk EBC.

Adult↗

Detailed analysis of a randomized phase III trial: can the tolerability of capecitabine plus docetaxel be improved without compromising its survival advantage?

BACKGROUND: In a phase III trial, 3-weekly capecitabine (1250 mg/m(2) twice daily days 1-14) plus docetaxel (75 mg/m(2) day 1) demonstrated significantly superior overall survival to 3-weekly docetaxel (100 mg/m(2) day 1). We report a retrospective analysis of the impact of capecitabine/docetaxel dose reduction on safety and efficacy. PATIENTS AND METHODS: Safety and efficacy data were analyzed retrospectively according to the actual doses of capecitabine and docetaxel administered. RESULTS: More patients receiving capecitabine/docetaxel (65%) had dose reductions for adverse events than docetaxel alone (35%). In most patients requiring dose reduction with the combination (80%), capecitabine and docetaxel were simultaneously reduced to 950 mg/m(2) and 55 mg/m(2), respectively. Subsequently, there were fewer cycles (17%) with grade 3/4 adverse events than with the full doses (34%). Time to progression and overall survival appeared to be similar in patients starting the second cycle with reduced doses of capecitabine/docetaxel and those who continued to receive full doses of capecitabine/docetaxel for at least the first four cycles. CONCLUSIONS: Capecitabine/docetaxel dosing flexibility allows management of side-effects without compromising efficacy. This retrospective analysis, as well as multiple phase II studies of taxanes with reduced-dose capecitabine, shows that reducing the starting dose of capecitabine with docetaxel is a reasonable strategy for the treatment of patients with metastatic breast cancer. In addition, reducing the dose of both agents may be appropriate.

Adult↗

Early administration of recombinant erythropoietin improves hemoglobin recovery after reduced intensity conditioned allogeneic stem cell transplantation.

The use of recombinant human erythropoietin (rHuEPO) has been controversial after myeloablative allogeneic Stem cell transplantation (allo-SCT). Reduced intensity conditioning regimens (RIC) offer a novel approach that might translate into a different profile of erythropoietic recovery. We treated 20 consecutive patients with rHuEPO early after matched sibling RIC allo-SCT. Conditioning included fludarabine, busulfan and antithymocyte globulin. EPO treatment was analyzed in terms of toxicity, impact on the frequency of Red blood cell transfusions (RBCT) and kinetics of Hemoglobin recovery within the 60 days post-allo-SCT. Results were compared with 27 matched patients who did not receive rHuEPO. In the first 2 months after allo-SCT all patients receiving rHuEPO (100%) achieved an Hb level > 11 g/dl at a median of 30 (15-35) days post-allo-SCT, as compared to only 63% of the patients not receiving rHuEPO (P = 0.007) at a median of 35 (20-55) days (P = 0.03). A total of 70% (95% CI, 50-90) of rHuEPO patients maintained an Hb over 11 g/dl in the second month as compared to only 19% (95% CI, 4-34) in the other group (P = 0.0004). For patients receiving RBCT, the use of rHuEPO was associated with a trend towards reduced RBCT requirements. This pilot study suggests a potential benefit of early administration of rHuEPO after RIC allo-SCT on early erythropoietic recovery.

Adult↗

[Molecular alterations in breast cancer: clinical implications and new analytical tools].

PURPOSE: Breast cancer is a complex and heterogeneous disease resulting from various molecular alterations, the identification of which should have profound impact on the management of patients. CURRENT KNOWLEDGE AND KEY POINTS: The discovery of germline mutations within breast cancer susceptibility genes, such as BRCA1 and BRCA2, which are associated with a major risk of breast cancer during lifetime, has improved the assessment of the individual risk toward the disease, allowing appropriate strategies of screening and prevention. The identification of key molecular actors in the mammary oncogenesis may help to better assess the prognosis of the disease, while providing new therapeutic targets. Large-scale molecular technologies, which allow simultaneous assessment of a high number of molecular parameters in a single assay, should provide new tools to tackle complexity and heterogeneity of breast cancer. Hence, by examining transcriptional profiles of breast cancer using DNA microarrays, it was possible to reveal new prognostic tumor subgroups, previously indistinguishable. Further improvements are awaited with the recent development of high throughput and large-scale technologies investigating the tumor proteome. PROSPECTS AND PROJECTS: Precise knowledge of molecular alterations involved in each individual breast cancer will allow more effective and less toxic, tailored therapies.

Breast Neoplasms↗

Autologous stem cell transplantation for acute myelogenous leukemia in first complete remission: a 6-year follow-up study of 101 patients from a single institution.

The objective of the study was to assess the long-term outcome and impact of stem cell source in patients with acute myelogenous leukemia (AML) who received ASCT in first complete remission (CR). A total of 101 patients (median age 46 years) were included in the study. Cytogenetic categories distribution was: favorable: 18%, intermediate: 42%, and unfavorable: 7%. More than one induction course was needed for CR in 21% of patients. In all, 78% of patients had received at least one course of high-dose ara-C before autologous stem cell transplantation (ASCT). Bone marrow (n=58) or peripheral blood stem cells (PBSC) (n=43) transplantation was performed at a median of 3.5 months from CR. Hematologic recovery and hospitalization duration were significantly reduced in the PBSC group. No toxic death was recorded in this group. The median follow-up of survivors is 67 months (range: 15-183). The 6-year survival, disease-free survival (DFS), and relapse probabilities are 44%, 38%, and 54%, respectively. The presence of a favorable karyotype and the use of PBSC are independently associated to better survival, and DFS by multivariate analysis. Our results confirm that long-term DFS can be achieved with high-dose chemotherapy and ASCT in patients with AML. They show that use of PBSC is associated to very low mortality rate and acceptable morbidity and contributes to an improvement of autotransplant results.

Adolescent↗

Multivariate analysis of survival in inflammatory breast cancer: impact of intensity of chemotherapy in multimodality treatment.

The prognosis of inflammatory breast cancer (IBC) is poor. We evaluated clinical and biopathological characteristics that could affect survival in 74 women with nonmetastatic IBC consecutively treated in our institution between 1976 and 2000. Patients received primary anthracycline-based chemotherapy at conventional doses (n=20) or high-dose chemotherapy (HDC) with haematopoietic stem cell support (HSCS) (n=54). After chemotherapy, 84% of patients underwent mastectomy, 95% were given radiotherapy and 55% tamoxifen. Immunohistochemistry data (ER, PR, ERBB2, P53) on pre-chemotherapy specimens suggested strong differences between IBC and non-IBC. The rate of pathological complete response to chemotherapy was 26% (27% with HDC and 17% with conventional doses, not significant). No single factor was found predictive of response. With a median follow-up of 48 months after diagnosis, the 5-year projected disease-free survival (DFS) was 24% and overall survival (OS) 41%. In multivariate analysis, the strongest independent prognostic factor was the delivery of HDC. The 5-year DFS and OS of patients were respectively 28 and 50% with HDC and 15 and 18% with conventional chemotherapy. These results and comparisons with other series of patients suggest a role for HDC with HSCS as part of the therapeutic approach in IBC. Further prospective studies are required to confirm it.

Adult↗

Graft-versus-myeloma effect following antithymocyte globulin-based reduced intensity conditioning allogeneic stem cell transplantation.

In all, 41 multiple myeloma (MM) patients received an antithymocyte globulin (ATG), fludarabine, and busulfan-based reduced intensity conditioning (RIC) for allogeneic stem cell transplantation (allo-SCT) from HLA-identical siblings. In total, 29 patients (70%) were in partial remission, one patient in complete remission, and 11 (27%) with progressive disease at the time of allo-SCT. Median time between diagnosis and allo-SCT was 24 months. The cumulative incidences of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) were 36% (95% CI, 21-51%) and 7% (95% CI, 2-20%), respectively. Overall, 10 patients developed limited chronic GVHD, whereas seven developed an extensive form (cumulative incidence, 41% (95% CI, 26-56%) at 2 years). With a median follow-up of 389 days, the overall cumulative incidence of transplant-related mortality (TRM) was 17% (95% CI, 6-28%). In all, 11 patients (27%) are in continuous complete remission, and the Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) at 2 years were 62% (95% CI, 47-76%) and 41% (95% CI, 23-62%), respectively. PFS and OS were significantly higher in patients with chronic GVHD as compared to patients without chronic GVHD (P=0.006 for PFS and P=0.01 for OS). Collectively, these data demonstrate that RIC allo-SCT can mediate a potentially curative graft-versus-myeloma effect with an acceptable incidence of toxicity and TRM.

Adult↗

Decreased RBCTs after reduced intensity conditioning allogeneic stem cell transplantation: predictive value of prior Hb level.

BACKGROUND: RBCT (RBCT) requirements of stem cell transplant (SCT) recipients are often substantial and may be related to transplant type. STUDY DESIGN AND METHODS: An analysis was done of RBCT requirements and Hb recovery kinetic in the first 60 days after HLA-identical sibling allogeneic SCT in a series of 110 consecutive patients treated for various malignant diagnoses. Patients were prepared with either an antithymocyte globulin (ATG) and reduced intensity chemotherapy-based conditioning (RIC) (n=64) or a myeloablative conditioning regimens (MAC; n=46). Patients received marrow (n=64) or PBPCs (n=46). RESULTS: Overall, intensity of conditioning regimen (RIC vs. MAC; p=0.0005) and graft source (PBPC vs. marrow; p<0.0001) independently predicted RBCT requirements. Hb recovery was accelerated after RIC when compared to MAC allo-SCT (p=0.02). In RIC patients, RBCTs were inversely correlated to Hb level before conditioning (p<0.0001) and the dose of ATG (p=0.009). Moreover, Hb level before allo-SCT significantly influenced Hb recovery kinetic after RIC but had no impact on RBCT requirements and Hb recovery after MAC. CONCLUSION: Thus, RIC conditioning creates a different pattern of erythropoiesis recovery as compared to a MAC regimen and suggest a need for studies aimed at further reducing RBCT and accelerating Hb recovery.

Adolescent↗

Occult tumor cell contamination in patients with stage II/III breast cancer receiving sequential high-dose chemotherapy.

The purpose of this study was to evaluate the presence of micrometastatic cells in the apheresis products from patients with breast cancer, and also to determine if repeated infusion of contaminated products had any clinical impact. A total of 94 patients with high-risk breast cancer were enrolled in a prospective single center study to evaluate the use of dose-intensified chemotherapy (doxorubicine 75 mg/m(2) and cyclophosphamide 3000 or 6000 mg/m(2) for four cycles) with repeated (x 2) stem cell reinfusion. All women were monitored for the presence of metastatic cells in aphereses, collected after first course of intensive chemotherapy, and following additional mobilization with rhG-CSF. Epithelial cells were screened with monoclonal antibodies directed to cytokeratin. Eight of the 94 patients had detectable tumor cells in one or several aphereses collected after intensive chemotherapy; this was unrelated to other tumor characteristics, including size, histology, Scarff Bloom and Richardson (SBR) grading (presence or absence of hormone receptors). Hemato-poietic reconstitution was similar in the cells from these eight patients, and in the total patient population. Three of these eight patients relapsed. This study has confirmed that contamination of apheresis products remains a rare event, which does not seem to affect clinical evolution, even when reinfused into the patient.

Adult↗

Higher doses of CD34+ peripheral blood stem cells are associated with increased mortality from chronic graft-versus-host disease after allogeneic HLA-identical sibling transplantation.

Allogeneic peripheral blood stem cell transplantation (PBSCT) has emerged as an alternative to bone marrow transplantation. PBSCT can be associated with a higher incidence of chronic graft-versus-host disease (cGVHD). In this study, we investigated whether there was a correlation between the composition of PBSC grafts (CD34+ and CD3+ cells) and hematological recovery, GVHD, relapse, and relapse-free survival (RFS) after myeloablative HLA-identical sibling PBSCT. The evolution of 100 acute or chronic leukemia patients was analyzed. Neither hematological recovery, acute or cGVHD, nor relapse, was significantly associated with CD3+ cell dose. Increasing CD34+ stem cells was associated with faster neutrophil (P=0.03) and platelet (P=0.007) recovery. Moreover, 47 of the 78 patients evaluable for cGVHD (60%; 95% CI, 49-71%) developed extensive cGVHD. The probability of extensive cGVHD at 4 years was 34% (95% CI, 21-47%) in patients receiving a 'low' CD34+ cell dose (<8.3 x 10(6)/kg), as compared to 62% (95% CI, 48-76%) in patients receiving a 'high' CD34+ cell dose (>8.3 x 10(6)/kg) (P=0.01). At a median follow-up of 59 months, this has not translated into a difference in relapse. In patients evaluable for cGVHD, RFS was significantly higher in patients receiving a 'low' CD34+ cell dose as compared to those receiving a 'high' CD34+ cell dose (P=0.04). This difference was mainly because of a significantly higher cGVHD-associated mortality (P=0.01). Efforts to accelerate engraftment by increasing CD34+ cell dose must be counterbalanced with the risk of detrimental cGVHD.

Acute Disease↗

Infectious complications following allogeneic HLA-identical sibling transplantation with antithymocyte globulin-based reduced intensity preparative regimen.

In the setting of reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT), the epidemiology of transplant-related infections is still poorly defined. In 101 high-risk patients who received an HLA-identical sibling allo-SCT after RIC, including fludarabine, busulfan and antithymocyte globulin (ATG), we report during the first 6 months a cumulative incidence of positive CMV antigenemia of 42% (95% CI 32-52%), developing at a median of 37 (range 7-116) days without evidence of CMV disease (median follow-up, 434 days). The cumulative incidence of bacteremia was 25% (95% CI 17-33%), occurring at a median of 67 (range 7-172) days, while patients had recovered a full neutrophil count. In all, 65% of the bacteremia (95% CI 49-81%) were gram negative. The cumulative incidence of fungal infections was 8% (95% CI 3-13%), with a median onset of 89 (range 7-170) days. In multivariate analysis, stem cell source (bone marrow; P=0.0002) was significantly associated with the risk of positive CMV antigenemia, while higher doses of prednisone (>2 mg/kg) represented the major risk factor for bacteremia (P=0.0001). Infectious-related mortality was 5% (95% CI 1-9%), with aspergillosis being the principal cause. Collectively, these results suggest that prospective efforts are warranted to develop optimal antimicrobial preventive strategies after RIC allo-SCT.

ABO Blood-Group System↗

Docetaxel and radiotherapy and pancreatic cancer.

PURPOSE: We conducted a phase 1 trial to determine the maximum tolerated dose (MTD) of weekly docetaxel delivered concurrently with radiation therapy for the treatment of locally advanced adenocarcinoma of the pancreas. PATIENTS AND METHODS: Thirteen patients with histologically proven locally non-resectable advanced adenocarcinoma of the pancreas were enrolled in this study. Patients received 4 weekly doses of docetaxel by 1-hour intravenous (IV) infusion with 40 Gy of external beam radiation therapy during 4 weeks. Patients who were stabilized or in response, received 2 additional cycles of docetaxel with a 10 Gy boost of radiotherapy. Doses were escalated at 10 mg/m2 increments in successive cohorts of 3 new patients until MTD was observed. RESULTS: Four patients received docetaxel at 20 mg/m2/week, 3 at 25 mg/m2/week, 3 at 30 mg/m2/week, and 3 at 35 mg/m2/week. All patients, except 2, were given the treatment in its integrity. The most common toxicities were nausea, vomiting, asthenia, and abdominal pains. Except for 1 patient, all toxicity was reversible and did not exceed grade 3. Hematologic toxicity was mild and has not required treatment interruption. 28% of the patients had to be rehospitalized. A total of 73 cycles was administered with a mean of 4 cycles per patient (2-6). CONCLUSION: Even the MTD was not reached, dose escalation was stopped at 35 mg/m2/week. This dose is comparable to the ones previously published using docetaxel in combination with radiotherapy in other tumors. Three patients achieved stable disease and 1 patient an objective response. This combination of weekly docetaxel and radiotherapy shows a feasible and well-tolerated regimen, with, nonetheless, a significant rate of rehospitalization, for patients with locally advanced pancreatic cancer.

Adenocarcinoma↗

Randomized, controlled, dose-range study of Ro 25-8315 given before and after a high-dose combination chemotherapy regimen in patients with metastatic or recurrent breast cancer patients.

PURPOSE: To evaluate the safety, pharmacokinetics, and efficacy of three different dose levels of pegylated granulocyte colony-stimulating factor (Ro 25-8315) on progenitor cell mobilization and hematologic recovery in cancer patients. PATIENTS AND METHODS: Breast cancer patients (n = 36) were randomly assigned to receive before (part I) and after (part II) chemotherapy either a single-dose injection of Ro 25-8315 (20 microg/kg, n = 9; 60 microg/kg, n = 9; 100 microg/kg, n = 10) or a standard daily dose of filgrastim (part I, 10 microg/kg/d; part II, 5 microg/kg/d) (control group, n = 8). RESULTS: Overall, Ro 25-8315 was well tolerated. In part I, more progenitor cell mobilization was observed with Ro 25-8315 100 microg/kg. The peak of circulating CD34(+) cells was obtained at day +5 in the four groups, and the absolute neutrophil count (ANC) returned to less than 20 x 10(9)/L by day +15. In part II, high levels of circulating CD34(+) cells (> 20 cells/microL) were obtained in all four groups. The chemotherapy-induced neutropenia (< 1 x 10(9)/L) was similar in the four groups. Ro 25-8315 100 microg/kg was more effective than filgrastim in reducing the number of patients with an ANC less than 0.5 x 10(9)/L on day +12 after chemotherapy. CONCLUSION: A single injection of Ro 25-8315 100 microg/kg might be the optimal dose for steady-state peripheral-blood progenitor cell mobilization. A single injection of 20, 60, or 100 microg/kg could be as efficient as daily administration of filgrastim to correct chemotherapy-induced cytopenia. The optimal dose of Ro 25-8315 should be determined according to the planned chemotherapy regimen.

Adult↗

Overexpression of erb B2 remains a major risk factor in non-metastatic breast cancers treated with high-dose alkylating agents and autologous stem cell transplantation.

The importance of dose intensity has been strongly emphasized in high-risk breast cancer. Overexpression of erb B2 is clearly correlated with an overall poor prognosis which could be limited in patients receiving intensive chemotherapy with alkylating agents and autologous stem cell transplants (SST). Thirty-five patients with high-risk non-metastatic breast cancer (>4 involved lymph nodes), treated with high-dose chemotherapy (HDC) followed by SST were analyzed. All were previously treated by four cycles of standard-dose anthracycline or anthracene dione. Nine had erb B2 overexpression. Minimum follow-up duration was 41 months (median 68 months). At 5 years, the actuarial relapse-free survival is 57.4% and actuarial overall survival 67.4%. Patients with overexpression of erb B2 had significantly lower disease-free survivals (P: 0.021) and overall survivals (P: 0.001). On multivariate analysis, erb B2 overexpression appeared to be the single independent poor prognosis factor for relapse (RR 3.25, range 1.12 to 9.45) and overall (RR 5.28, range 1.74 to 16.03) survival. These results suggest that poor prognosis of erb B2 overexpression is unchanged after HDC with alkylating agents but a possible benefit may exist in these patients with the additional monoclonal antibody, herceptin.

Antineoplastic Agents, Alkylating↗

Modulations of dose intensity of doxorubicin and cyclophosphamide in association with G-CSF and peripheral blood stem cells in adjuvant chemotherapy for breast cancer: comparative evaluation of completion and safety of three intensive regimens.

The aim of this study was to evaluate and to compare in terms of toxicity the modulations of dose intensity of cyclophosphamide and doxorubicin in adjuvant chemotherapy for high-risk breast cancer. Four cycles of sequential high-dose chemotherapy with doxorubicin and cyclophosphamide (AC), supported with G-CSF and peripheral blood stem cells (PBSC) were administered to 81 women. Three successive cohorts were studied: doxorubicin (75 mg/m(2)) + cyclophosphamide (3000 mg/m(2)) every 21 days (group 1), doxorubicin (75 mg/m(2)) + cyclophosphamide (3000 mg/m(2)) every 15 days (group 2), and doxorubicin (75 mg/m(2)) + cyclophosphamide (6000 mg/m(2)) every 21 days (group 3). Seventy-five patients received four cycles of treatment with a total of 310 cycles administered. The received dose intensity of doxorubicin was higher in group 2 and that of cyclophosphamide was lower in group 1 than in the other two groups. Hematological and extra-hematological toxicities, as well as the number and duration of hospitalizations for toxicity, were significantly higher in group 3. We conclude that the group 3 regimen is associated with toxicities comparable to autologous transplantation. Increasing dose intensity of doxorubicin and cyclophosphamide is feasible in an outpatient setting and safe in groups 1 and 2 with the support of hematopoietic factor and PBSC.

Adult↗

Intensive sequential dose dense chemotherapy with stem cell support as first-line treatment in advanced ovarian carcinoma: a phase II study.

From August 1995 to December 1997, 15 patients with stage III-IV ovarian cancer were treated with outpatient intensive chemotherapy with G-CSF and stem cell support. The first cycle consisted of cyclophophamide IV 6 g/m(2); second, third, fourth and fifth paclitaxel 250 mg/m(2) and the sixth and seventh carboplatin AUC 18. CD34(+) cells were collected after the first cycle and reinfused after completion of cycles 6 and 7. Fourteen patients had stage IIIc and one patient had stage IV disease with liver metastases. All patients underwent laparotomy to maximize tumor debulking. This was optimal in eight patients and suboptimal in seven patients. Second-look surgery was performed in 14 patients. All patients had macroscopic complete responses and 10 patients had complete histologic response. Median follow-up was 48 months (range, 20 to 62). Twelve patients had further progression at a median of 27 months (range, 9 to 42) and nine are alive, three without evidence of disease progression. This pilot study shows that dose-dense chemotherapy with paclitaxel and carboplatin is associated with low toxicity and may improve the outcome of patients with poor prognosis ovarian cancer.

Adult↗