Gastrointestinal metastases in renal cell carcinoma: A retrospective multicenter GETUG (Groupe d'Étude des Tumeurs Uro-Génitales) study.

BACKGROUND: Among patients with renal cell carcinoma (RCC), bone and visceral metastases have a poor prognosis, while endocrine gland metastases have a more favorable prognosis. Gastrointestinal metastases (GIMs) are rare, and their prognosis is still poorly understood. OBJECTIVES: To report clinical presentations, patient characteristics, therapeutic strategies, and prognosis of GIMs from RCC. METHODS: We retrospectively collected data from RCC patients presenting GIMs, in 10 French GETUG centers, between 2000 and 2021. RESULTS: We identified 74 patients with 87 GIMs, mostly gastric or duodenal. The median age at GIM diagnosis was 69 years and 76% of patients already had other metastases. GIMs occurred after a median duration of 5.4 years (IC95%=[4.2-7.1]) and 1.9 years (IC95%=[1.2-3.8]) from RCC diagnosis and first metastasis, respectively. GIMs were symptomatic in 52 patients (70%), with anemia in 41 patients (55%) and/or gastrointestinal bleeding in 31 patients (42%). Only 22 asymptomatic patients (30%) were fortuitously diagnosed. GIM management consisted of systemic treatment only in 29 GIMs (33%), local treatment only in 23 GIMs (26%), and both local and systemic treatment in 18 GIMs (21%). For 17 GIMs (20%), there was no therapeutic modification. After diagnosis of GIM, median overall survival was 19 months. CONCLUSION: We report the largest retrospective cohort of GIMs in RCC patients. They should be suspected in case of anemia or gastrointestinal bleeding in any patient with a history of RCC. Their management varies widely depending on their location in the digestive tract and whether or not they are symptomatic.

Patterns of relapse in poor-prognosis germ-cell tumours in the GETUG 13 trial: Implications for assessment of brain metastases.

BACKGROUND: The GETUG 13 phase III trial tested personalised chemotherapy based on tumour marker decline in patients with poor-prognosis germ-cell tumour (GCT) and demonstrated that a dose-dense regimen improves progression-free survival in patients with an unfavourable decline. We investigated the pattern of relapse for patients included in GETUG 13. METHODS: We conducted an analysis of relapse events in patients from GETUG 13. Baseline procedures before inclusion in the trial comprised a thoraco-abdomino-pelvic computed tomography scan and a magnetic resonance imaging of the brain. RESULTS: With a median follow-up of 4.1 years (0.3; 8.8 years), a progression event was observed in 109/254 patients (43%). First event consisted in a marker progression only in 47 patients (43%), a radiographic progression only in 35 patients (32%), a mix progression on both markers and imaging in 12 patients (11%) and death in 15 patients (14%). In patients with radiographic progression only, brain was the predominant site (n = 19/35, 54%). Among patients with unfavourable decline who experienced a radiographic progression (as first and subsequent progression event, n = 58), brain was a site of progression in 28 patients (48%): 12/30 (40%) in patients treated with cisplatin, bleomycin and etoposide and 16/28 (57%) in those treated with dose-dense chemotherapy. CONCLUSIONS: Brain metastases develop often, early and frequently as the only site of relapse in the course of poor-prognosis GCT. This raises the question of early detection and optimal treatment of brain metastases in these patients, e.g. by integrating a systematic brain MRI after 2-3 months of chemotherapy.

Management and prognosis of malignant peripheral nerve sheath tumors: The experience of the French Sarcoma Group (GSF-GETO).

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are a rare subtype of soft tissue sarcoma. They can arise in irradiated fields, in patients with type 1 neurofibromatosis (NF1), or sporadically. MPNST exhibit an aggressive behaviour, and their optimal management remains controversial. An unsolved issue is whether NF1-related and sporadic forms of MPNST have a different prognosis, and should be managed differently. MATERIAL AND METHODS: Adult and paediatric patients with histologically confirmed MPNST treated between 1990 and 2013 in French cancer centres of the GSF/GETO network, were included in this retrospective study. RESULTS: A total of 353 patients (37% with NF1 and 59% with sporadic tumours) were analysed. Median age at diagnosis was 42 years (range 1-94). The majority of tumours developed in the limbs, were deep-seated and of high grade. Two hundreds and ninety four patients underwent a curative intent surgery. Among them, 60 patients (21%) had neoadjuvant treatment (mainly chemotherapy), and 173 (59%) had adjuvant treatment (mainly radiotherapy). For operated patients, median progression free and overall survival (OS) were 26.3 months and 95.8 months, respectively. In multivariate analysis, poor-prognosis factors for OS were high grade, deep location, locally advanced stage at diagnosis, and macroscopically incomplete resection (R2). NF1 status was not negatively prognostic, except in the recurrence or metastatic setting, where NF1-related MPNST patients treated with palliative chemotherapy showed worse survival than patients with sporadic forms. CONCLUSION: To our knowledge, our series is the largest study of patients with MPNST reported to date. For operated patients, we showed a worse prognosis for NF1-related MPNST, due to different clinical features at diagnosis, more than NF1 status itself. The French sarcoma group is now conducting correlative analyses on these patients, using the latest molecular tools.

UNICANCER-PEGASE 07 study: a randomized phase III trial evaluating postoperative docetaxel-5FU regimen after neoadjuvant dose-intense chemotherapy for treatment of inflammatory breast cancer.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and aggressive disease requiring a multimodal treatment. We evaluated the benefit of adding docetaxel-5-fluorouracil (D-5FU) regimen after preoperative dose-intense (DI) epirubicin-cyclophosphamide (EC) and locoregional treatment in IBC patients. PATIENTS AND METHODS: PEGASE 07 was a national randomized phase III open-label study involving 14 hospitals in France. Women with nonmetastatic IBC were eligible and randomly assigned to receive either four cycles of DI EC (E 150 mg/m(2) and C 4000 mg/m(2) every 3 weeks with repeated hematopoietic stem cell support), then mastectomy with axillary lymph node dissection, and radiotherapy (arm A) or the same treatment followed by four cycles of D-5FU (D 85 mg/m(2), day 1 and 5FU 750 mg/m(2)/day continuous infusion, days 1-5 every 3 weeks) administered postradiotherapy (arm B). Patients with hormone receptor-positive tumors received hormonal therapy. Disease-free survival (DFS) was the primary end point. Secondary end points included tolerance, pathological complete response (pCR) rate, and overall survival (OS). RESULTS: Between January 2001 and May 2005, 174 patients were enrolled and treated (87 in each arm). Median follow-up was similar in both arms: 59.6 months [95% confidence interval (CI) 58.4-60.3] in arm A and 60.5 months (95% CI 58.3-61.4) in arm B. The estimated 5-year DFS rates were not different: 55% (95% CI 43.9-64.7) in arm A and 55.5% (95% CI 44.3-65.3) in arm B [hazard ratio (HR) = 0.94 (0.61-1.48); P = 0.81]. Identical results were observed for 5-year OS: 70.2% (95% CI 59.1-78.8) in arm A and 70% (95% CI 58.8-78.7) in arm B [HR = 0.93 (0.55-1.60); P = 0.814]. Following DI EC induction, in-breast and global (breast plus nodes) pCR were 28.9% and 20.1%, respectively. Estrogen receptor and pCR status were independently associated with survival. CONCLUSION: The addition of D-5FU after preoperative DI EC and standard local therapy did not improve DFS in IBC. CLINICAL TRIAL NUMBER: ClinicalTrials.gov identifier: NCT02324088.

Outcomes from second-line therapy in long-term responders to first-line tyrosine kinase inhibitor in clear-cell metastatic renal cell carcinoma.

BACKGROUND: Although sequential targeted therapy is standard in patients with metastatic clear-cell renal cell carcinoma (m-ccRCC), the choice of drugs and optimal administration sequence have yet to be established. The objective of this study was to explore whether it is preferable to rechallenge a long-term responder to a first-line tyrosine kinase inhibitor (TKI) with a TKI or whether to switch to a mammalian target of rapamycin inhibitor (mTORi); to determine whether second-line treatment response depends on duration of first-line response (TD1). PATIENTS AND METHODS: Retrospective multicenter study (2004-2011) of 241 consecutive mRCC patients (clear-cell histology) who received a first-line TKI for ≥6 months followed by a second-line TKI (n = 118) or mTORi (n = 123). END POINTS: Progression-free survival (PFS) and time-to-treatment failure (TTF) on second-line therapy. Multivariable full-model: second-line drug, TD1, ECOG-PS before first- and second-line, best objective response (first-line), Fuhrman grade, number of metastatic sites, and presence of bone metastases. Adjustment covariable: International mRCC Database Consortium (IMDC) risk score. Multiple propensity score and missing data methods were used. Any correlation between first-line and second-line PFS was investigated using censored quantile regression models (CQRM). RESULTS: Sequence effect in the overall cohort was in favor of the TKI-TKI sequence over the TKI-mTORi sequence on using TD1 as continuous covariable (HR ≈ 0.75 for PFS and TTF). TKI-TKI superiority was attributed in large part to the 11-22 month (TD1) subgroup of patients which displayed significantly better outcomes [HR ≈ 0.5; median PFS (months): 9.4 (5.9-12.2) versus 3.9 (3.0-5.5), P = 0.003; TTF(months): 8.0 (5.5-11.0) versus 3.6 (3.0-4.6), P = 0.009]. Upon full CQRM, long-term second-line responders were more likely to have received a second TKI than an mTORi and to have been long-term responders to first-line TKI. CONCLUSIONS: m-ccRCC patients who remained on first-line TKI between 11 and 22 months benefited from a TKI rechallenge rather than from second-line mTORi.

Adjuvant radiotherapy for extremity and trunk wall atypical lipomatous tumor/well-differentiated LPS (ALT/WD-LPS): a French Sarcoma Group (GSF-GETO) study.

BACKGROUND: The role of adjuvant radiotherapy (RT) in the management of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WD-LPS) remains controversial. METHODS: Two hundred eighty-three patients with operable ALT/WD-LPS, no history of previous cancer, chemotherapy (CT) or RT, treated between 1984 and 2011 registered in the Conticabase database were included and described. Overall (OS), progression-free survival (PFS) and time to local relapse (TTLR) were evaluated from the time of first treatment. RESULTS: Three of 20 centers enrolled 58% of the patients. Median age at diagnosis was 61 (range 25-94) years, 147 patients (52%) were males, 222 (78%) patients had their primary tumor located in an extremity while 36 (13%) and 25 (9%) had tumors involving the girdle and the trunk wall, respectively. The median size of primary tumors was 17 cm (range 2-48 cm). Adjuvant RT was given to 132 patients (47%). Patients who received adjuvant RT had larger tumors (P = 0.005), involving more often the distal limbs (P < 0.001). Use of adjuvant RT varied across centers and along the study period. Other characteristics were balanced between the two groups. Median follow-up was 61.7 months. None of the patients developed metastasis during follow-up. The 5-year local relapse-free survival rates were 98.3% versus 80.3% with and without adjuvant RT, respectively (P < 0.001). Once stratified on time period (before/after 2003), adjuvant RT, tumor site and margin status (R0 versus other) were independently associated with TTLR. No OS difference was observed (P = 0.105). CONCLUSION: In this study, adjuvant RT following resection of ALT/WD-LPS was associated with a reduction of LR risk.

Single-nucleotide polymorphisms associated with outcome in metastatic renal cell carcinoma treated with sunitinib.

BACKGROUND: There are no validated markers that predict response in metastatic renal cell cancer (RCC) patients treated with sunitinib. We aim to study the impact of single-nucleotide polymorphisms (SNPs) that have recently been proposed as predictors of outcome to anti-VEGF-targeted therapy in metastatic RCC in an independent cohort of patients. METHODS: We genotyped 16 key SNPs in 10 genes involved in sunitinib pharmacokinetics, pharmacodynamics and VEGF-independent angiogenesis in patients with metastatic clear-cell RCC treated with sunitinib as the first-line targeted therapy. Association between SNPs, progression-free survival (PFS) and overall survival (OS) were studied by multivariate Cox regression using relevant clinical factors associated with PFS and OS as covariates. RESULTS: In a series of 88 patients, both PFS and OS were associated significantly with SNP rs1128503 in ABCB1 (P=0.027 and P=0.025), rs4073054 in NR1/3 (P=0.025 and P=0.035) and rs307821 in VEGFR3 (P=0.032 and P=0.011). Progression-free survival alone was associated with rs2981582 in FGFR2 (P=0.031) and rs2276707 in NR1/2 (P=0.047), whereas OS alone was associated with rs2307424 in NR1/3 (P=0.048) and rs307826 in VEGFR3 (P=0.013). CONCLUSION: Our results confirm former communications regarding the association between SNPs in ABCB1, NR1/2, NR1/3 and VEGFR3 and sunitinib outcome in clear-cell RCC. Prospective validation of these SNPs is now required.

The role of imaging in staging and monitoring testicular cancer.

The prognosis for testicular cancer is excellent, with a 5-year survival rate greater than 95%. Patients affected can therefore expect to be cured after treatment. Successful treatment requires assessment of the condition at the various stages of its management. Imaging plays a major role in initial analysis of the lymphatic extension and in looking for metastases. It is essential for evaluating the response to treatment and during follow-up after treatment. CT is the most commonly used imaging method in this context, but the role of PET is currently developing. The purpose of this paper is to review the role of the imaging methods commonly used in the management of testicular cancer.

Maximising the duration of disease control in metastatic renal cell carcinoma with targeted agents: an expert agreement.

With six targeted agents approved (sorafenib, sunitinib, temsirolimus, bevacizumab [+interferon], everolimus and pazopanib), many patients with metastatic renal cell carcinoma (mRCC) will receive multiple therapies. However, the optimum sequencing approach has not been defined. A group of European experts reviewed available data and shared their clinical experience to compile an expert agreement on the sequential use of targeted agents in mRCC. To date, there are few prospective studies of sequential therapy. The mammalian target of rapamycin (mTOR) inhibitor everolimus was approved for use in patients who failed treatment with inhibitors of vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) based on the results from a Phase III placebo-controlled study; however, until then, the only licensed agents across the spectrum of mRCC were VEGF(R) inhibitors (sorafenib, sunitinib and bevacizumab + interferon), and as such, a large body of evidence has accumulated regarding their use in sequence. Data show that sequential use of VEGF(R) inhibitors may be an effective treatment strategy to achieve prolonged clinical benefit. The optimal place of each targeted agent in the treatment sequence is still unclear, and data from large prospective studies are needed. The Phase III AXIS study of second-line sorafenib vs. axitinib (including post-VEGF(R) inhibitors) has completed, but the data are not yet published; other ongoing studies include the Phase III SWITCH study of sorafenib-sunitinib vs. sunitinib-sorafenib (NCT00732914); the Phase III 404 study of temsirolimus vs. sorafenib post-sunitinib (NCT00474786) and the Phase II RECORD 3 study of sunitinib-everolimus vs. everolimus-sunitinib (NCT00903175). Until additional data are available, consideration of patient response and tolerability to treatment may facilitate current decision-making regarding when to switch and which treatment to switch to in real-life clinical practice.

Novel method of doxorubicin-SPION reversible association for magnetic drug targeting.

A new method of reversible association of doxorubicin (DOX) to superparamagnetic iron oxide nanoparticles (SPION) is developed for magnetically targeted chemotherapy. The efficacy of this approach is evaluated in terms of drug loading, delivery kinetics and cytotoxicity in vitro. Aqueous suspensions of SPION (ferrofluids) were prepared by coprecipitation of ferric and ferrous chlorides in alkaline medium followed by surface oxidation by ferric nitrate and surface treatment with citrate ions. The ferrofluids were loaded with DOX using a pre-formed DOX-Fe(2+) complex. The resulting drug loading was as high as 14% (w/w). This value exceeds the maximal loading known from literature up today. The release of DOX from the nanoparticles is strongly pH-dependent: at pH 7.4 the amount of drug released attains a plateau of approximately 85% after 1h, whereas at pH 4.0 the release is almost immediate. At both pH, the released drug is iron-free. The in vitro cytotoxicity of the DOX-loaded SPION on the MCF-7 breast cancer cell line is similar to that of DOX in solution or even higher, at low-drug concentrations. The present study demonstrates the potential of the novel method of pH-sensitive DOX-SPION association to design novel magnetic nanovectors for chemotherapy.

High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group.

The optimum treatment of primary CNS lymphoma (PCNSL) is not yet determined. The objective of this study was to assess the safety and efficacy of initial methotrexate-based chemotherapy followed by high-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) in patients with newly diagnosed PCNSL. Twenty-five patients received two courses of initial chemotherapy combining methotrexate, etoposide, carmustine and methylprednisolone, and one course of ifosfamide-cytarabine followed by peripheral stem cell collection. Seventeen responsive patients then received HDT using carmustine, etoposide, cytarabine and melphalan with autologous stem cell rescue. After ASCT for responding patients or after salvage therapy for non-responders, whole brain radiation therapy at a dose of 30 Gy was delivered. The objective response rate to the induction chemotherapy was 84%. Four of the 21 responding patients did not have ASCT because of toxicity or refusal. With a median follow-up time of 34 months, the projected event free survival rate is 46% at 4 years. Projected overall survival is 64% at 4 years. Sixteen patients are actually in continuous complete response. No evidence of late treatment-related toxicity was observed. This treatment approach appears feasible in newly diagnosed PCNSL with encouraging results.

Post-operative sequential high-dose chemotherapy with haematopoietic stem cell support as front-line treatment in advanced ovarian cancer: a phase II multicentre study.

In spite of multimodal management including aggressive surgery and chemotherapy, the prognosis of advanced ovarian cancer (AOC) remains poor. Multicycle high-dose chemotherapy (HDC) with haematopoietic stem cell (HSC) support has been shown to be a promising procedure in various cancers including AOC. We conducted a phase II multicentre study to evaluate feasibility, toxicity and efficacy of post-operative front-line sequential HDC with HSC support in AOC. Thirty four patients with stage IIIC/IV received a post-operative sequential combination of high-dose cyclophosphamide/epirubicin (D1, D21) with HSC harvesting, high-dose carboplatin (D42, D98) followed by HSC infusion, and dose-dense paclitaxel (D63, D77, D119, D133). Rh-G-CSF (filgrastim) was administered following all cycles. Primary endpoint was pathological complete response rate (pCR). Thirty patients received at least 7 of the scheduled 8 cycles. Haematological toxicity was significant but manageable. Grade 3/4 extra-haematopoietic toxicities were relatively uncommon and reversible. No toxicity-related death was observed. The observed pCR was 37% and did not reach the initial endpoint. Post-operative front-line sequential HDC in AOC is feasible and safe in a multicentre setting. The observed pCR does not support a clear advantage over conventional treatment. This approach remains an experimental strategy to further optimise and validate.

[Agranular CD4+ CD56+ CD123+ hematodermic neoplasm (blastic NK-cell lymphoma) revealed by cutaneous localization: 2 cases]. / Localisations cutanées révélatrices d'une hématodermie CD4+ CD56+ CD123+: 2 cas.

BACKGROUND: Agranular CD4+ CD56+ hematodermic neoplasm (blastic NK-cell lymphoma) has been recently described. The skin is often the first organ involved. OBSERVATIONS: Two old men of respectively 70 and 77 years consulted for infiltrated cutaneous lesions. Preliminary histological examination of cutaneous biopsy taken in both patients showed a malignant proliferation suggesting a cutaneous lymphoma, and the patients were referred. Histological examination of new biopsies showed a very similar proliferation in the 2 cases of monotonous medium-sized mononuclear cells without expression of the common antigens CD3 and CD20 and the expression of CD4, CD56, and CD123. No rearrangement of the T-cell receptor gene or the immunoglobulin heavy chain gene were evidenced. No extracutaneous involvement was initially detected in the first patient. Thrombocytopenia associated with the abnormal presence of 15 p. 100 of circulating CD4+ CD56+ cells was initially found in the second patient. The first patient was treated with chemotherapy, with complete remission. A cutaneous relapse promptly occurred, followed by bone and cerebral localizations. The patient died one year after the diagnosis of the disease, in spite of intensification of the treatment. Treatment is still ongoing in the second patient. COMMENTS: The histological presentation of these two patients was very similar with an unusual phenotype of tumor cells expressing CD4, CD56, CD123, but not expressing CD3 and CD20. Some cases have been published under the "term of blastic NK lymphoma" which is the actual term for the disease in the WHO classification. However, the tumor cells derive from the dendritic plasmacytoid cells, also called type 2 dendritic cells, and perhaps from a common precursor to lymphocyte T and dendritic plasmacytoid cells. In spite of complete cutaneous response in the 2 cases presented, as in other reports, extra-cutaneous involvement occurs quickly. Overall survival is usually poor since nearly all the patients died in less than 3 years. This justifies attempting aggressive protocols, with bone marrow allograft in the younger patients.

A phase II study with 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX-4 regimen) in patients with metastatic renal cell carcinoma.

PURPOSE: To investigate the efficacy and safety of the FOLFOX-4 regimen for patients with metastatic renal cell carcinoma (MRCC). PATIENTS AND METHODS: Fifty-nine patients (median age 59 years) pre-treated or not by cytokines (29 vs. 30) received the FOLFOX-4 regimen every 2 weeks. RESULTS: Three minor responses, and no complete or partial responses were obtained. The median progression-free survival was 3 months (95% CI: 2.6-3.4), the median survival 10.6 months (95% CI: 8.7-12.4), with no difference between pre-treated patients and others. Treatment was well tolerated. CONCLUSION: The FOLFOX-4 regimen is ineffective in patients with MRCC. We believe that oxaliplatin should no longer be explored in renal carcinoma.

[Role of high-dose chemotherapy with hemopoietic stem-cell support in the treatment of adult patients with high-grade glioma]. / Place de la chimiothérapie intensive avec autogreffe de cellules souches hématopoïétiques dans le traitement des tumeurs gliales de haut grade chez l'adulte.

Despite surgery, post-operative irradiation and adjuvant conventional chemotherapy, prognosis of high-grade gliomas remains poor. Carmustine (BCNU) has been shown to have limited activity at conventional dosage but is still the standard chemotherapy. Activity of chemotherapy is limited by the blood-brain barrier impermeability and high levels of expression of multidrug resistance proteins on tumor and/or endothelial cells. Despite high response rates, development of intra-arterial chemotherapy remains limited because of frequent acute brain toxicity related to drug administration. High-dose intravenous chemotherapy rescued by autologous hemopoietic stem cell transplantation is an alternative that might increase drug delivery through the blood-brain barrier and tumor control. Several phase I-II trials using high-dose BCNU were published. The maximum tolerated dose seems to be 800 mg/m2 and interstitial pneumonitis and hepatitis are dose-limiting toxicities. Few phase I-II trials of high-dose therapy were published using drug combinations. High response rates in patients with progressive tumor were observed and in adjuvant setting, encouraging results in terms of median survival time and long survivors were published. No phase III trial was reported to date. Future investigations should include randomized trials comparing high-dose and conventional-dose chemotherapy and development of new high-dose regimens that incorporate new drugs such as temozolomide.

Multiple myeloma in elderly patients: presenting features and outcome.

Few studies have been performed regarding multiple myeloma (MM) in elderly patients. We report a retrospective series of 130 unselected patients with MM aged 75 yr or more at diagnosis. Presenting features were identical to those reported in younger patients, except for a higher rate of infection. Heavy comorbidity was characteristic of unselected geriatric patients. Ninety-four patients received conventional chemotherapy. The response rate was 62%. Treatment toxicity was mild. Median survival was 22 months. Durie-Salmon (DS) clinical stages II and III MM were severe and often led to death, while significantly more patients with DS stage I MM died from unrelated causes (p<0.0001). Univariate analysis showed that age > or = 85 yr, performance status > or = 2, creatinine level > or = 120 micromol/l, beta 2 microglobulin level > 4 mg/l, C-reactive protein level > 6 mg/l, platelet count < 100 x 10(9)/l, presence of infection and lack of response to chemotherapy were adverse prognostic factors for survival. In Cox multivariate regression analysis, age > or = 85 yr (p<0.0001), performance status > or = 2 (p<0.0001) and creatinine level > or = 120 micromol/l (p<0.0001) were independent factors in predicting short survival. This study provides evidence that in patients with symptomatic MM age should not be considered as a major obstacle to active treatment. Prospective clinical trials are needed in this population of patients and should include an assessment of quality of life.

[Malt lymphoma of the thyroid and Graves'disease]. / Lymphome thyroïdien de type MALT et maladie de Basedow.

Maltoma of the thyroid associated to Graves'disease is not such a frequently described association. We report a case of Maltoma of the thyroid gland in a patient with Grave's disease. The diagnosis was established by histological examination after total thyroidectomy. Slow enlargement of the thyroid gland despite a clinically successful antithyroid drug therapy could be considered as an advocating clinical manifestation. Associated anti-neoplastic chemotherapy and cervical irradiation resulted in good outcome with six years follow-up. A review is presented on treatment and prognosis of these tumors.

Early secondary acute myelogenous leukemia in breast cancer patients after treatment with mitoxantrone, cyclophosphamide, fluorouracil and radiation therapy.

BACKGROUND: The topoisomerase II-targeted drugs, epipodophyllotoxins and anthracyclines, have been shown to induce therapy-related AML (t-AML) characterized by a short latency period after chemotherapy, the absence of prior myelodysplastic syndrome and stereotyped chromosome aberrations. Few reports have been published on patients treated with the anthracenedione mitoxantrone which also targets topoisomerase II. We observed 10 cases of such t-AML over a 7-year-period in breast cancer patients treated with mitoxantrone combined with fluorouracil, cyclophosphamide and regional radiotherapy, and in three cases with vindesine. PATIENTS AND METHODS: We retrospectively analyzed patients referred to our hospital for AML with a past history of polychemotherapy for breast cancer, including mitoxantrone, either as adjuvant (8 patients)/neoadjuvant (1 patient) therapy or for metastatic disease (1 patient). We studied the probability of developing t-AML in a prospective series of 350 patients treated with an adjuvant FNC regimen (mitoxantrone, fluorouracil, cyclophosphamide) and radiation therapy. RESULTS: The median age was 45 years (range 35-67). t-AML developed 13-36 months (median 16) after beginning chemotherapy for breast cancer, and 4-28 months (median 10.5) after ending treatment. As described in t-AML following treatment with epipodophyllotoxins or anthracyclines, we found a majority of FAB M4, M5 and M3 phenotypes (7 of 10), and characteristic karyotype abnormalities that also can be found in de novo AML: breakpoint on chromosome 11q23 (3 patients), inv(16)(p13q22) (2 patients), t(15;17)(q22;q11) (1 patient), t(8;21)(q22;q22) (1 patient) and del(20q)(q11) (1 patient). The prognosis was poor. All patients died of AML shortly after diagnosis. Since two patients had been enrolled in a prospective trial for the treatment of breast cancer which included 350 patients, the probability of developing t-AML was calculated to be 0.7% from 25-40 months, using the Kaplan-Meier method (95%, confidence interval (95% CI): 0.1-4.5). CONCLUSIONS: The combination of mitoxantrone with cyclophosphamide, fluorouracil, and radiation therapy can induce t-AML, as with other topoisomerase II-targeted drugs. Despite a low incidence, the prognosis appears to be poor.

[Microbial infection documented on admission to the intensive care unit for post-chemotherapy neutropenia after empiric antibiotic therapy]. / Infections microbiologiquement documentées à l'admission en réanimation pour neutropénie post-chimiothérapie après antibiothérapie probabiliste.

OBJECTIVE: The purpose of this study was to determine whether a systematic strategy of multiple microbiological samples for all adult patients with neutropenia admitted to an intensive care unit could document sepsis despite prior empiric antibiotic therapy. PATIENTS AND METHODS: All adults admitted to the intensive care unit with chemotherapy-induced neutropenia (WBC < 500/mm3) were included in the study. Microbiological samples were systematically obtained in all patients: 6 blood, 1 stool, 1 urine, 1 nasal swab. Data were analyzed for 54 consecutive patients: 22 men, 32 women, 42 with hematology diseases and 12 with solid tumors, mean age 46.6 +/- 14.4 years. Assessment of disease severity showed: simplified gravity index = 256 +/- 17; organ system failure score on day 1 = 2.42 +/- 1.1; 26 cases of septic shock among 47 cases of sepsis. Mortality was 50%. Within 48 h, bronchioalveolar lavage samples were obtained in 48 patients, and there were 12 spinal taps, 3 laparotomies, 3 skin biopsies and 6 sinus punctures. RESULTS: A microorganism was isolated in 39 patients (70%): 12 Gram negative, 12 Gram positive, 11 mycoses, 3 cases of herpes. Positive cultures were found for 31 blood, 1 bronchioalveolar lavage, 2 surgical, 5 serous and 22 oral or digestive tract samples. Documented microbial infection did not have prognostic value. Septic shock at admission was predictive of poor outcome. DISCUSSION: Despite prior antibiotic therapy in 46 patients, with a theoretically active drug in 37 cases, a systematic strategy of multiple deep samples increased the number of documented cases of infection in neutropenic patients. Oral and digestive tract infections predominated despite selective decontamination of the digestive tract.